Precigen Inc Aktie

Good afternoon, ladies and gentlemen, and welcome to the President's Second Quarter 2026 Financial Results and Business Updates Conference Call. At this time, online are in lesson only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Tuesday, August 4, 2026. And I would now like to turn the conference over to Steve Harasim. Please go ahead.

Thank you, Operator, and thank you to everyone joining us for Prestigen's second quarter 2026 update call. We are pleased to be speaking with you today as we continue to see strong momentum across the commercial launch of PEPs and MEOs. Joining me on today's call are Helen Salbzavary, our President and Chief Executive Officer, Phil Tennant, our Chief Commercial Officer, Harry Tomasian, our Chief Financial Officer, and Ritul Shah, our Chief Operating Officer. Helen will begin with an overview of the launch and key strategic updates. Phil will provide a additional details on the commercial execution. Harry will review our financial results, and Ritul will be available for the Q&A section. Before we begin our prepared remarks, I remind everyone that we will be making various forward-looking statements.

These statements are based on our current expectations and beliefs. We encourage you to review the slide in this presentation and our SEC filings, which include risks and uncertainties that could cause actual results to differ materially from today's forward-looking statements. With that, I will now turn the call over to Dr. Sabzavari.

Thank you, Steve, and thank you to everyone joining us for our G2 2026 Business Update Call. As we approach the one-year anniversary of TAPSIMIUS approval in August 2025, it is worth reflecting on what a meaningful milestone this has been for adults with RRP. Maximius brought the first and only approved therapy and the new first line standard of care to the RRP community. Nearly one year after approval, we continue to see a strong commercial momentum with broadening patient access, growing physician adoption, and increasing utilization across both major medical centers and community practices. I'll begin with a high-level overview of what we are seeing across the launch before turning the call over to Phil for additional commercial details. Q2 represented exceptional growth from Q1. I'm proud to state that we generated $53.1 million in Paximius revenue compared to $21.6 million in Q1. presenting more than 145% revenue growth and marks a significant financial milestone for President.

Topsimus Revenue in Q2 propelled the company to a quarterly net profit. even before we reach the first anniversary of FDA approval. These results reinforce the significant enthusiasm we continue to see among patients, physicians, and institutions. What is particularly encouraging as we move through Q2 and continuing to Q3 is that momentum is building across several dimensions of the launch at the same time. We believe we now have the commercial foundation for durable, multi-purpose, and sustainable. growth for papzimias. We are seeing a strong demand, broader access, expanding use across care settings, and continued physician adoption. These indicators give us increased confidence in the breadth and durability of PAP-CMEA's early commercial trajectory. We are seeing the benefit of launching with full approval and a broad FDA label translate into a real-world prescribing behavior.

Importantly, the label does not impose a minimum number of prior surgeries before a patient can be treated with Pepsimia. As a result, physicians are able to consider papzimius based on the individual patient's clinical need. We are seeing use across a broad range of RRP patients, not just the severe cases. This supports our view that toxemius is being embedded earlier in the treatment paradigm. The clinical profile continues to resonate strongly with physicians and patients at the new standard of care. Tapsy-MERS is not another intervention in a cycle of repeated surgical interventions. It is designed to address the underlying HPV6 or 11 driver of the disease through a targeted immune response.

Papsinius durability data continues to strengthen as the long-term follow-up matures. As we presented at ASCO, as of the April 30th cutoff, the ongoing durability of complete responses continues to increase with 83% of patients in ongoing complete response beyond three years, with the number of beyond 40 years of being surgery-free. I would like to emphasize that these durable, complete responders have not received any treatment for RRP after receiving PAP-SIMIUS. We believe this combination of transformative efficacy, durability, and ongoing responses, and a favorable safety profile remains highly differentiated. Finally, the FDA granted topsyneus seven-year market exclusivity for adult RRP patients. This exclusivity... to August 2032 adds an important layer of protection against prospective competition, and supports the value of the commercial opportunity as we continue to expand access and adoption. Collectively, these factors have helped build a strong commercial foundation, leading to a strong performance in Q2 and momentum for what we anticipate to be a continued growth.

As we have said before, we believe the RRP indication has a blockbuster potential. With that, I will now turn the call over to Phil for more details on our commercial launch. Phil?.

Thank you, Helen, and welcome to everyone joining us today. I'm pleased to provide an update on the continued progress of our commercial launch. Two represented a meaningful acceleration across the business with strong demand, expanding patient access, and increasing engagement from physicians and institutions as Pabst-Zimmias continues to establish itself as the new standard of care for adults with RRP. Importantly, the commercial indicators we are seeing support the view that this is the beginning of a durable growth story. As Helen mentioned in Q2, Papsimeus generated $53.1 million in revenue, compared with $21.6 million in Q1, reflecting continued strong launch performance since the first full quarter of sales in Q1. Launch to date PAP-SMEOS revenue exceeded $78 million at the end of Q2, underscoring the continued strong momentum we are seeing across all aspects of our launch effort. As per my commentary in previous quarters, there are a number of factors and leading indicators continuing to support the impressive launch performance.

Patient engagement through the Precision Hub continues to grow. As of today, the total hub number is well over 500 patients. This reflects steady patient identification and continued interest from both major academic centers and community settings. Importantly, Presagen Hub data did not capture all patients, so the meaningful proportion of treated patients are coming through non-Hub using institutions. sites are becoming increasingly confident in their own processes for securing patient access, which could mean more patients in the future receiving pap simios without necessarily requiring precision hub intervention. We believe the current picture reinforces the breadth of demand for the brand, irrespective of our hub utilization. Payer coverage remains exceptional and continues to provide a strong foundation for access. With the addition of approximately 18 million covered lives in Q2, total commercial and government coverage is now approximately 315 million lives, representing nearly all potential covered lives. lives in the U.S. market.

In my experience, this compares extremely favorably to the typical speed and breadth of coverage for newly approved treatments in the U.S. As expected, we also continue to see activation across both major medical centers and community practices. We feel the permanent J-code, which became effective April 1st, has been particularly important as accounts move from initial engagement to routine use. It provides a standard pathway for reimbursement, it helps institutions process claims more efficiently, and it reduces uncertainty for sites that are still building Pepsimius into their workflows. Together with our field reimbursement support and favorable payer coverage, this has helped bring forward additional accounts and supported continued adoption across both academic centers and community practices. Taken together, the Q2 numbers show clear and continued acceleration across leading indicators, including hub registrations, new patient starts, payer coverage and account activation, on top of the FDA-granted market exclusivity and robust quarter-over-quarter revenue growth. We are extremely pleased with the launch performance to date and believe these trends provide a strong foundation for continued growth.

The key point is that Absymious remains early in its launch curve with a substantial continued opportunity in RRP. I'll now turn the call over to Harry for an overview of our Q2 financials. Harry.

Thank you, Phil, and good afternoon to all of you participating in our call today. You've heard Helen and Phil talk about the exciting second quarter of Pepsimios revenue that we've reported today. That revenue has propelled Precision to profitability for both the quarter and the six months ended June 30th. This is a significant milestone and somewhat rare for a company to have achieved this prior to the first anniversary of an FDA-approved drug. With that said, let me provide some further color on our overall financial results for the quarter. Total revenues were $55 million, which included $53.1 million related to PEP-SIMEOs. Our Second quarter PEP CMEOS revenue grew from the first quarter by $31.5 million as we saw demand for PEP CMEOS continue to build as the second quarter progressed.

Cost of products and services for the second quarter totaled $2.8 million, resulting in a gross margin of $52.2 million, or 95%. After the sale of our remaining pre-launch inventory, which we anticipate to be in the third quarter of this year, we expect gross margins related to PAP-SIMEOs to stabilize between the high 80 percentages and low 90 percentages. The research and development cost for the quarter was $7.3 million, which compared to the prior year second quarter decreased by $4.2 million. The majority of this change is explained by the fact that Pepsimios manufacturing costs were expensed as R&D costs prior to the FDA approval, amount was $5.7 million in the prior year quarter. We expect that R&D expenses will increase as the year progresses and we continue to advance our pipeline. Selling, general, and administrative expenses for the quarter were $22.2 million, having increased by $6.1 million from the prior year's second quarter. This increase was significantly driven by increased commercial activities related to PAP-CMEDOS.

Moving down the statement of... operations, operating income for the quarter was $22.6 million. Other expense net totaled $2.6 million for the second quarter, representing interest expense of $3 million on our $100 million outstanding debt offset by interest income on investments of approximately $4 million. $400,000. Net income for the quarter was $20.1 million, or $0.05 per diluted share. Turning to the balance sheet, we ended the quarter with $38.7 million in cash, cash equivalents, and investments. Q2 represented the first quarter where we saw cash proceeds from the collection of accounts receivable related to Patsy Meos. We ended the quarter with $71.9 million in trade accounts receivable on the balance sheet, which based on customer payment terms we expect to collect over the four following the quarter end. We continue to reiterate that based on our current financial forecast, our cash, cash equivalents and investments, along with the collection of Pepsimio's receivables, will fund operations through cash flow breakeven by the end of 2026.

Thank you again for participating in today's call. I'd like to now turn it back to Helen for some closing remarks. Helen?.

Thank you, Harry. I will now provide an update on our broader portfolio beginning with pap smear's clinical and regulatory progress in the U.S. and abroad. Papsimeus has the potential for redosing, supported by its mechanism of action and favorable safety profile. We are currently evaluating this in an ongoing clinical trial, which is actively enrolling patients. We remain on track to initiate a pediatric clinical trial of Capsinius this year. In addition, our marketing authorization application for Papsimeus is under review by the EMA. had been granted orphan drug designation from the European Commission. Now turning to PRGN 2009, which uses the same adenovirus platform backbone as our approved therapy, PAP-C-MEF. and underscores the broader potential of this technology. GRGN 2009 is an investigational immunotherapy designed to train the immune system to recognize and eliminate tumor cells associated with HPV 16 and HPV 18, which are the underlying drivers of several major related cancers, including certain head and neck and cervical cancers.

Together, HPV-related malignancies represent nearly 5% of all cancer cases worldwide. CRGN 2009 is currently advancing in multiple phase two clinical trials in combination with PEMBRO in both head and neck cancer and cervical cancer. We remain very enthusiastic about the potential of this program. particularly given the scale of HPV-related cancers globally. We look forward to providing updated data on head and neck cancer later this year. More broadly, the success of Papzinius and the progress of PRG in 2009 has established proof of principle for the Ad Universe platform. As commercial and clinical evidence continues to build, we believe the platform has a strategic value across various indications, and we are extremely excited to advance the platform to maximize its potential. We expect to continue evaluating opportunities to advance this. platform.

With that, I will now turn the call over to the operator for Q&A. Operator.

Thank you. Ladies and gentlemen, we will now begin the question and answer session. If you have a question, please press star four by the one on your telephone keypad. You will hear a prompt that your hand has been raised. And should you wish to cancel your request, please press star four by the two. I would like to advise everyone to have a limit of one question and one follow-up. If anyone have an additional question, you can put yourself back in the queue by pressing star 1. If you are using a speakerphone, please lift the handset before pressing any keys.

One moment please for your first question. Thank you. And your first question comes from the line of Jason Butler from Citizens.

Hi, thanks for taking the questions and congrats on an exceptional quarter. obvious first question, can you give us any color into, you know, or insight into the growth rate we should expect from 2Q to 3Q? Can you maintain the growth rate you saw from 1Q to 2Q or at least just in broad level help us understand the trajectory we should expect here? And then the follow up is, can you give a sense of the number of physicians and institutions that have used the drug so far, and if the majority of patients are coming from your hub or outside of the hub. Thank you.

Hey Jason, thank you for the question. It's Phil here. Let me address the first one first. Obviously the growth rate is critical. We definitely have a very exciting growth story on our hands and as you've seen we've grown significantly from Q1 into Q2. The growth story will continue, the level at which we continue to grow will be determined when we get to the end of Q3. But all of the things that we've spoken about in terms of the leading indicators, the payer coverage, the account activation, the patients that are coming into play, the permanent J code, all of these things are leading to a continued growth story. Now, mathematically, obviously, when you launch, the growth rate tends to diminish over time, but it's still a growth story, and we're very encouraged by what we're seeing as we head into Q3.

And physicians and so on. We're seeing activations of accounts consistently, so it's a high proportion of our targeted accounts and others that are actually using. And importantly, that's both at the IDN level and in the community setting. we expect that to continue to grow as we go forward.

And maybe, Jason, this is Helen, and thank you for your question. Maybe we can also add further. Obviously, a tremendous growth rate from Q1 to Q2, which we expect to continue. As Phil mentioned, I think the pre-work that was done by the commercial group in establishing all the fundamentals that is needed to sustain the growth and promote this as we go forward has paid off and continues to pay off. We are really looking forward as we move. with 27,000 patients at hand in the United States alone. And as you are seeing with the continuous increase in the number of the patients in our hub and also ex-precision hubs, clearly this speaks to the uptake of of Pepsimus as a standard of care by physicians, the request of the patient, and what we are seeing, which is also extremely exciting, it's not just on a severe patient population. We see this across a broad label that we have, and all of that are indicators for us that we are looking at really a very very exciting trajectory.

Thank you, Helen. Thanks for taking questions.

Thanks, Chase. Thank you. And your next question comes from the line of Suayam Pakula from Ramakant from RainRide. Please go ahead. Thank you. Good afternoon, team. Excellent.

Congratulations from my end as well. So Pap Simios is... is a four injection course over 12 weeks. So what portion of the second quarter revenues these later cycle doses in these patients who initiated in the first quarter. How should we think about that as a tailwind as we go into third quarter? That's the first question. I have a couple more. Can I go one by one?.

Sure. Okay. Hi. Thank you for the question. So in regard to the patients that we have up to this point had We have treated more than 200 patients, at least have received one dose of pap smear. And as you are seeing the number of the patients in the hubs, it continues to grow as well as in ex-hubs and patients that are coming in from a community center. So this is quite an increase. As far as the number of the patients that have completed, there are over 100 patients have gone through all the tests basically for treatment. And obviously, new patients are joining the hubs as we go. So we are very excited about this and fairly...

Yes, okay, you're right, though. There is a sort of a mini annuity, right, with these patients, depending upon when they start during the quarter.

And, you know, some of those doses are carried over into the following quarter. But I would say that certainly for the next few quarters, the bulk of the revenue that we will win is going to be new demand. There's definitely a carryover factor, quarter over quarter, but it's new demand that is driving the business. Thank you.

Okay. The couple more questions that I have is, one is of the $53.1 million that you recorded in the second quarter, is there any true up from prior period revenue reserves? And the third question is on the gross margin, You recorded 95%, obviously quite a bit of that is from your pre-approval manufacturing costs, but this got expensed through the R&D line. What could be the real steady-state COGS once that inventory is consumed? Okay.

Hey, RK. It's Harry. How are you? The first question, remind me again the first question.

So the order of that $53.1 million that you recorded in the second quarter, is there any true-up from the prior quarter? Yes.

Any true-up that would have been recorded as part of reserves would have been very insignificant, so the answer is no.

Okay. And then on the COGS, you know, what could be the steady-state COGS once you, you know, once you use up all your pre-approval manufacturing reserves?.

We've guided that we anticipate the gross margin will be in the high 80% to low 90%, so in the 10% range for COGS.

Perfect. Thank you very much, folks. Thanks. Thanks, Hakeem. Thank you. And your next question comes from the line of Brian Chang from JPMorgan Chase. Please go ahead.

Hey guys, thanks for taking our questions this afternoon. Maybe just two from us. First, can you talk about the trajectory that we're seeing here just based on the patients at your own patient hub? Are you seeing more patients onboarding from the Center of Excellence versus your own patient hub in the recent quarter? And then second question is, you're just looking into the update later this year. What will you be looking for from the head and neck and cervical updates?.

Thank you. Hey Brian, Phil here. I'll take the first question. So, you know, I think the revenue speaks to a very exciting trajectory in terms of patient identification and treatment, regardless of whether it's patients in our hub or patients that have come from outside of our hub. And there's a significant contribution of treated patients from institutions who don't use our hub who haven't used our hub so I think what we're seeing and you can you know we've reported the hub numbers which are now well over 500 you see that steady and ongoing patient identification but that is not the only source of patient identification and we're excited by both trends.

Yes, hi, Brian. In regard to PRGN 2009 and head and neck, as we had mentioned previously, our head and neck trial is open-labeled trial. So clearly, we have the, we are seeing the data as we move, and we will be presenting not only all of the science-based data that will be there, but also the clinical efficacy as well as safety. And especially it's quite interesting as obviously the arms of the trial are continuing and we are following those, but definitely the clinical efficacy. data as well as the scientific data of the mechanism of action and everything else will be presented. We are very excited about this in the coming weeks. coming very near future by the end of the year, we will be presenting. Great. And maybe just a quick follow-up here.

Can you talk about just the cadence of patients are incoming? I mean, you've seen your permanent JCO in place in April. Has that changed in a meaningful way in terms of patients that are onboarding? Just curious if you can provide a little bit more color since the J code is in place. Thank you.

Yes, thanks, Brian. I mean, we've seen from other launch analogs that the J-code can have an impact. And I think it's safe to say that it definitely has helped us since April 1. You know, tangibly, we've seen some institutions that we knew were holding back and waiting for the permanent J-code. And as you would imagine, they've now come on board and are starting to identify patients. And just in general, across the board, this J-code, which does give more certainty for providers of being reimbursed by payers, is quite an important factor. And I think across the board, that has sort of lifted all boats in terms of identification of patients and their treatments. So, yes, the momentum is definitely with us, particularly after the J-code.

Thank you, guys. Thank you. And your next question comes from the line of Michael DeFior from Evercore ISI. Please go ahead.

Hi, guys. Thanks so much for taking my question, and congrats on the Stellar quarter. You frequently referenced that the prevalent patient pool in the U.S. is 27,000. So I guess my question is how many of those patients are actively managed, identifiable, and realistically adjustable by the your commercial infrastructure at this point and have a follow-up.

No, great question. Thanks for that. You know, yes, there are a lot of patients out there, 27,000. And in any one year, you would expect, you know, a number of several thousand of those are actually very evident to the healthcare system because they're They have multiple surgeries and they're using a lot of resources of the healthcare system. So there are thousands of what you might call severe patients, but then beyond that, particularly as you then go into the community setting, there are many patients who are earlier in their journey. So the good thing from our perspective is that we have a very broad label, and patients right from the beginning of that journey and be treated with pap simius, and that's obviously our goal. We are seeing patients across all severities, as Helen mentioned, starting to be treated. But as we also said, we feel we're at the beginning of our journey, and there are a lot more patients, and there's a lot more runway ahead for us.

Yes.

Thank you. Michael, go ahead. I'm sorry. Go ahead. No, no, no. I was going to say, I'm sorry. Go ahead.

I'm sorry. I was going to say a related question is regarding if there's any any bolus or pent-up demand slash warehouse patients? How big is that? And how long might it take you to work through? Thank you.

Yes, well I'd refer you to my previous answer really because there are several thousand, you know, in any one year, and that's just, just say a count over the past 12 months, but in any one year you're going to have, from our perspective, our numbers, several thousand patients who fall into that more severe category, which is an obvious place to start for some physicians as they get experience with the drug. But, you know, we haven't worked our way through that. And there are many more patients consistent with our broad label. So, again, we reiterate there's an ongoing growth story here.

Maybe I can also add, Michael, from a perspective of the patient population for the RRP, unfortunately patients that are diagnosed with RRP or they have been diagnosed over the years, the tendency of this disease is just it becomes worse. As we have mentioned, these patients just by doing a surgery, this disease does not go away because surgeries never address the underlying issues, which is infection by HPV, basically 611, whereas pap smear does that. and addresses exactly the underlying issue. So for that reason, as Phil mentioned, not only we have these severe patient populations that exist, we have a patient population that they unfortunately, they are infected and start and then eventually as they the year go by, it becomes worse. But also what it's very... for us is very important and what we are seeing across is the uptake of pap smear by physicians and also patients that because the physician at this point based on the broad label, the safety, the efficacy, and especially the durability that we see and we reported ASCO, that now we have not only passed three years on some of our patients, in four years, post-receiving pap simios have not required any treatment for RRP. This has added to the excitement for treating the patients as early as possible so they do not receive irreversible damages. So as you can see, not only we have the thousands of patients that are at the severe position, but also patients that are in their journey with RRP with the less severe, and definitely the physicians do not want them to become more severe and therefore prescribing the PAP-C-MIS. Okay.

Very helpful. Thank you. Thank you. And your last question comes from the line of Yuwen Zai from B-Riley. Please go ahead.

Thank you for taking our questions and congrats, Maurice Brown-Walter. Since you had in-person engagement with initial target accounts, can you remind us how many accounts were on the initial list and how many have actually ordered your drug so far? And then maybe a quick follow-up there. what is the second wave expansion plan now you have 500 registration in the hub. Thank you.

Thanks for the question. So just going back to the initial footprint and target. number of institutions we identified. There were about 500 institutions that we identified that looked at over 90% or covered 90% of the patient population. And within that, it was about 100 large hospital systems that were responsible for over 80%. Obviously, we've targeted accordingly, but as I also mentioned before, we've seen the community come on board quickly and so we've embraced the community side of things into our targeting as well. I won't give a specific number on the number that are using, but as you can see from our revenue and all of the leading indicators that we've spoken about, we're making great progress on activating those accounts. accounts that are activated are becoming repeat users. So in terms of the outlook, I mean, all of the things that we've spoken about, the continued account activation with the support of the permanent J-code, our broad label, the continued durability results that we have, the safety profile of the drug, and the early experience of treating patients with pap simios and the user friendliness of that experience is all going to drive the continued wave of growth that we expect.

Got it. Thank you for taking our questions. Thank you. And that concludes our question and answer session. I want to hand the call back to Helen Sabsevari for any closing remarks.

Thank you, operator, and thank you to everyone who joined us today. We are very pleased with the strong results we delivered in the second quarter, particularly the continued momentum behind Papdenius and the important foundation we are building for long-term growth. As we approach the one-year anniversary of approval, we remain focused on expanding access, supporting adoption, advancing our clinical and regulatory priorities, and continuing to execute across the business. On behalf of the entire Precision team, thank you for joining us today and for your continued support. We look forward to keeping you updated as the year progresses.

That concludes our call for today. Thank you for participating. You may all disconnect.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Great. So first, welcome to the 47th Annual Goldman Sachs Healthcare Conference. Very pleased to be joined by Helen and Phil from Precigen. So first, welcome.

Maybe to start things for those who maybe might be a little bit less familiar with Precigen and overall story as it stands today. Maybe, Helen, if you could give a brief overview of the company.

Sure. First of all, thank you for having us here. Precigen is a cell and gene therapy company. It works on a really innovative, differentiated platform with combining it really for fit our technology to the right indication with the right regulatory pathways. And this is very important from the very beginning because it allows the focus and allows us to move very rapidly, which is a good example of this, we have a portfolio of 2 technology platform. One is our AdenoVerse platform, which is a very unique and differentiated basically delivery platform that allows that you can repeat dose patients with very specific adenovirus vectors that are not similar to what you have seen in the field.

And the reason for that it has a large capacity and it allows for continuous repeat dosing and without very little or no neutralizing antibodies. And the good part of that is that you can repeat dose as many times, which we have shown in our clinical trial. And the front runner of that using this platform is our PAPZIMEOS drug that has been now approved in the rare disease space for recurrent respiratory papillomatosis, RRP, which for the past 100 years have not had any kind of approved treatment. And these patients basically as a result of HPV infection with either HPV 6 or 11, they develop these tumors, benign tumors in the throat or on the vocal cord.

And as a result of that, they continuously -- the only thing that physicians could offer them up to the last year was continuous surgery. Some of our patients have had over 300 surgery. Some of them have to receive a surgery every practically month. And this disease can be basically established either as a child by child passing through the birth canal or and getting infected from the mother or in adult [indiscernible] transmission. It's a devastating disease. And for the first time, in a very, very -- a very exciting data that we are able now to treat 51% of these patients go to a complete response, not requiring any basically surgery or any other treatment, which is unheard of in this field.

So on the back of the same platform we have our PRGN-2009, which we are very excited. And again, it's applies to the cancers, HPV-related cancers such as head and neck and cervical cancer, which we will be actually looking forward to sharing data in early Q4 of this year on the head and neck cancer. And then we also have our cellular therapy, which is our UltraCAR-T cells, which is -- this is truly an overnight with the manufacturing directly in patient. And with that, we have finished our basically Phase Ib, and we are moving now to setting up the pivotal for a Phase II.

And so as a result of having this platform, it allows the Precigen to come up with very innovative treatments for the patient, which not only has a very good safety profile, but also have a very unique efficacy and a durability of response that we will be touching based on that, for instance, in regard to PAPZIMEOS, which is now well over into the 40-year post treatment.

Great. You mentioned upcoming data, but maybe near- and medium-term catalysts that investors should keep in mind in the coming quarters?

Absolutely. First of all, our PAPZIMEOS is, as we mentioned, we received under accelerated top from FDA last year in August, full approval actually, it became a full approval and currently, as Phil will be speaking, we are very excited about the commercial revenues and the path that is coming in. But at the same token, we have started the redosing the trials for this, which becomes very important as we mentioned, not only we had the 51% complete response in this patient population that they never had any treatment before, but we have an 86% overall response.

And based on that, actually, FDA was very interested and safety that we showed that those partial responders that should also be redosed. And they perhaps will benefit from this. So we have started those studies of redosing. We also will be -- start studies in a pediatric population. Again, because of the safety and efficacy and durability of response that we see with PAPZIMEOS, this was highly encouraged by the FDA. We are extremely excited because this is a unique platform that it will lend itself to the pediatric trials.

At the same token, we have already submitted for the approval for European in EMA. So we will be waiting in the upcoming quarters to communicate in regard to that. And our application is under review from the PAPZIMEOS side. And also one of the other aspects is that currently, our PRGN-2009, which I mentioned, is the drug that is on the same backbone of the viral vector with PAPZIMEOS. It's in the clinic on Phase II for head and neck and cervical cancer. And we are very, very excited about the trial reporting on a trial in fall, probably by Q4, early Q4.

The result of the head and neck. As you know, this is actually 2-arm trial in the patients that they have head and neck. The response rate of the patients in these settings are between 15% to 18%, even with all the checkpoint inhibitor. And in the Phase I, what we show was the objective responses of 30%. And currently, obviously, this is an open trial that we have a view to the data, and we are very excited to be sharing that in Q4 of this year. And I think this will be very relevant for the investors.

Great. You recently got orphan drug exclusivity. Can you talk about the importance of that to the company and overall?

Absolutely. So we had originally received the orphan drug designation when we submitted our application. And as part of that, if you receive approval, then you become qualified for the orphan drug market exclusivity. It doesn't mean that every company will receive that. It's just that they will be qualified, especially in rare diseases. This is a special program that FDA has basically put forward for the innovative treatment. And what they have done is to encourage the companies to work on the rare diseases.

Now with receiving the orphan drug market exclusivity, we have 7 years of market exclusivity that basically similar type of drugs are not going to be approved by FDA. So you can imagine and Phil will speak to this more that this now allows PAPZIMEOS and Precigen have the full 7 years of basically having the marketing of the PAPZIMEOS and the drug for RRP. And it's very, very important because similar drugs cannot be receiving approval from FDA and also they have to meet the same efficacy as well as durability as well as basically the safety. So it puts the bar very, very high for 7 and allows us to move very rapidly. So that's quite exciting for us.

Great. Maybe turning to the commercial side and maybe Phil. Obviously, early innings still. I'm not going to pin you down on Q2. But how is the launch going so far? And any update you can give investors there?

Sure. Well, we've covered a lot of the dynamics that are leading to our excitement about the launch. You're right. We won't go into Q2 in any great detail, but we look forward to sharing Q2 results in August. But a lot of the building blocks of launch have exceeded expectations. We had a rapid increase in payer coverage to well over 200 commercial lives within 6, 8 months of launch. When you include Medicare, Medicaid and the others, we've got over 90% of insured lives covered. And as you can imagine, for any rare disease launch, without that, launch is going to be in trouble.

So to get the payer coverage has been phenomenal. Our prelaunch work told us that there was a concentration of patients in the academic centers. So we estimate there were 27,000 in the U.S. with this condition. And most of those, because of the cyclical nature of surgery, they were concentrated in the academic centers, the IDNs. And that is indeed the case. But one of the things that we're also seeing through launch is the community interest in the drug and community uptake.

And that makes sense for a number of reasons. It's closer to home for the patient. And we've put in place simple low-cost solutions because our drug is ultra cold chain, but freezer release programs and just-in-time shipping mean that basically we can ship the drug and the patient can get treated anyway.

So that community uptake has been very important. We had a paper published under the auspices of the foundation in January, where 16 thought leaders basically put their name to the fact that PAPZIMEOS is the standard of care for all adult patients with RRP irrespective of surgical burden. And then in April, we got the permanent J-code, which is an important piece of the jigsaw puzzle as you're launching a drug. That just takes a lot of the drama out of old patient journey to access. And we were aware of certain institutions that were waiting for the permanent J-code, and now we've got the permanent J-code. So as in other rare disease launches that we've looked at, we expect that to help with our acceleration and [indiscernible].

And maybe I can just add to what Phil mentioned. In regard to our label from FDA, we have a very broad label that covers all patients -- adult patients with RRP. And that becomes -- has become very important because now we see that patients across the spectrum are being treated. And one of the reasons for the community centers is because they are the first line and when patients actually start their journey with this disease, they go first to their community doctors. And we are seeing the uptake not only just in severe patient population, but as early as just being diagnosed, the patients now started receiving this, which is excellent for the patient because this is a kind of a disease that by fifth surgery, these patients have irreversible damage. And the sooner that you get to them, the better.

Great. In terms of real-world usage, what are you seeing from a compliance standpoint in the initial audience?

Yes. Pretty much what we saw in our registrational studies where all 4 patients -- all 35 patients took all 4 doses of the treatment. We are seeing very good observance of that regimen in practice, which reflects the safety and the promise of durability that we've seen in the data and we continue to see in the extended follow-up. So yes, we're very pleased. We're not seeing anything untoward in the real-world use of the drug.

Great. Phil, you mentioned a little bit ago academic versus community centers, especially on the other side of J-code, maybe a little bit more detail in terms of how you're seeing usage patterns and how that may inform things going forward?

Yes. So we have -- we've talked a lot about hub, our manufacturers hub. So this is a site where basically patients can register and physicians can register patients with the intent of getting them on to drug. That's one source of the top of the funnel as it were. Some institutions are very well versed in their own patient support services, and they don't use our hub. So it's only part of the story. But 25% of the patients registered in our hub are from the community, which gives you an idea of what I talked about earlier in terms of the community uptake of PAPZIMEOS. So both sides of that coin, the academic and the community centers are embracing the drug and basically treating patients.

To Helen's point, early on in launch, you would expect at the academic institutions, the severe patients, those who have multiple surgeries, those have highest unmet need to be treated. But now with the community and even at the IDNs, we're seeing that now expand into less severe patients, which is important for the long-term growth -- continued growth of [indiscernible].

Great. Helen, you mentioned earlier the -- your recent ASCO data. Can you give a little bit more detail in terms of the updated durability data you gave and especially how that's going to inform the product?

No, absolutely. I think this is the most -- one of the most important indicator for this drug is not only the safety and efficacy that we saw in the pivotal trial, which was looking at a very robust endpoint of not having any surgery or requiring any treatment for the first year. But now we have gone well over that. The median of the patients have passed 36 months, and we have -- at ASCO, we showed the number of patients that they have passed 40 years. And these were the most severe patient population, imagining a patients that they required the surgery practically some of them every month and to go now more than 40 years, not requiring -- not only any surgery, no treatment at all.

This is quite with what some of our investigators and the physicians say out there is really outstanding. They have never seen anything like this and with the safety that it has. So -- and as I mentioned, the total response rate is 86% in this patient population. And this has put a standard now for the treatment that is really outstanding as the standard of care for that.

And Rob, I mentioned that we're in a great position with payers. But as you can imagine, this increasing durability just adds to that confidence that a lot of patients are going to be treated with this drug and have a great durable response and payers like that sort of thing.

Certainly helps with the health economics. That is for sure. Maybe back to kind of the practicalities of commercial launch. Can you walk us through the steps involved from getting scripts to treatments? And maybe along similar lines, any characteristics of treated patients in terms of [indiscernible].

We operate in a complex -- talk about site activation internally, and there are a number of things that have to happen. But basically, when a doctor registers the patient, that's an intention to prescribe. That's a prescription. They may or may not be within our hub, as I mentioned earlier. But that triggers if they are in our manufacturers hub benefit verification process to make sure the patient has the insurance and coverage and everything else. Once that is done, it's really up to the institution then to help get the prior authorization through dialogue with the payer. And then the patient is ready. When those 3 things come together, you get the treatment. And that should take a matter of weeks, that entire process once those things are in place.

So we have put dedicated resources in field to help the institutions get through that prior authorization step because a lot of these ENT sites, they've never had to do this before. So we have the expertise now, and we dedicated that resource to make sure that those patients are accelerating through to treatment.

In terms of the characteristics of the patients, we talked earlier, initially, as you would expect, the more severe patients, but we have a broad label, and it's important now to stress that we are seeing the use beyond those severities and that needs to continue and our marketing programs are designed to make sure that every single patient that is conditioned has a conversation about PAPZIMEOS with the treating physicians. That has to be our goal.

Excellent. On the label, I guess, how are you seeing things regarding the label and potential for an opportunity for redosing?

So from the label, as we mentioned, when we received the full approval from FDA and very -- also we received a broad label, which meant that regardless of severity of the disease, the patients are qualified to receive this treatment. And also based on the original discussions with FDA, it was very clear based on the safety and efficacy that we were seeing that -- and the immunological data that we showed that the patients that also had reduced their number of surgeries, but have not gone to 0, they perhaps can benefit from redosing.

And so as part of that, we have already started our redosing and actually patients are enrolling in that program currently. So we very rapidly move with that concept. At the same token, our label is not really restricted in the -- already in the redosing. So it's at the discretion of the physicians. But obviously, we are generating also further data on a redosing. This will be very important because it adds the 36% or 35% of the patients that they have been partial responders that have benefit, and we showed that data as well that they reduced their number of surgery. And as the patient, they say, even reduction with one surgery for them is very relevant. So we would be moving very rapidly with that.

That's great. Especially early in the launch, things can be lumpy and not always the easiest to track. I guess from an investor standpoint, what's the best way to think about tracking the launch going forward?

Well, revenue, is quite the indicator of -- we shared -- yes, all road lead to revenue, right? We shared our Q1 revenue, which I think got favorable responses, which is an indicator of all the work that we've done on the platform that we've set in Q4 into Q1. And as I said, we're very excited about sharing. We still got a best part of a month to go of the second quarter, but we're already looking forward to sharing that information. So I'd say revenue is a pretty big clue.

But we'll continue to share information on patient hub numbers because that represents the intention to prescribe both in our hub and from elsewhere. We talked about payer numbers, which are very healthy. So there's not going to be too much more to say on that because we're in such a great position, but we'll continue to reinforce that. And we'll continue to talk about the community and the IDN sort of split. And I think that the community side of the business, and we would expect that to be a more prominent part as we go forward of our overall business opportunity, and we'll continue to share that.

Makes sense. We've talked about the patient hub a few times. Can you give us a sense of the conversion you're seeing and also a sense of how you think that might evolve?

Yes. Well, first and foremost, our ambition is to make sure that all of those patients in our manufacturers hub get on to treatment, and we have the resources in place to help with that conversion. The revenue that we shared in Q1 obviously gives a big clue as to how we're doing in terms of that conversion. And now we have the permanent J-code as of April, I think that will help provide a little bit more momentum. So we expect that conversion to continue to even accelerate and to be represented in the revenues that we'll share in Q2.

Yes. And maybe I can just add to what Phil mentioned. In regard to the -- our hub, as we have seen from last year to this year, continuous increase in the number of hundreds in the hub, just our hub. And this, as Phil mentioned, is not really talking about the patients that are in the other hubs of the institute.

But also, I think one of the things that I'm going to address more is really how fast this treatment has been picked up by the payers. both Phil and I, we have quite a long experience in the drug development. And this is one of the fastest pace that we have seen, especially for rare diseases, which are [indiscernible] necessarily very low pay and for the payers and insurers, but to be able to approve it and approve it so rapidly and get to more than 90% of the payers agreeing with the label and also agreeing with the payment. This has helped tremendously, and it would get reflected as has been reflected in the revenue.

Great. Switching gears to the Europe side. So you filed last year -- late last year. Can you give an update on regulatory [indiscernible]?

So we have already submitted the application. Our application is under review in -- by EMA. And we are looking forward, obviously, to the results from there. And this is a similar application that we have submitted to the FDA. And I think we have also communicated we are looking in the path for the commercialization, which a major part of that is with the partnerships in Europe and to -- perhaps as soon as we hopefully get approval, then within the right strategy, we also will start the treatment in Europe.

And one of the things that our team has done over the years, again, looking in the numbers of the patients in Europe and very interestingly, Europe and Japan probably have similar or more of their patients than the United States. So it's quite a large market there as well. And of course, China is even a much bigger market, which we will be paying our attention.

Great. Makes sense. We talked a little bit about the expansion opportunities for redosing. Can you talk a little bit about pediatric opportunity?

Absolutely. I think pediatric opportunity, as I mentioned, some of the patients -- actually, a lot of adult patients, they come -- they are infected as a child. And as early as age of 1, we have had a patient at 1 year old was infected. And can you imagine basically taking a 1 year old to OR every month or every other month. So there is a continuous population, some are estimated by FDA that between 1,000 to 1,500 cases per year. And unfortunately, with -- I think without taking the vaccine, preventive vaccine that this might become even larger population.

For children, the safety of the drug, it becomes the side effects is extremely important, as you can imagine, because the threshold of the tolerance of adults is different than a child, and it becomes very important. And FDA, based on the results that we have shown, they have been extremely excited. And so as we -- to take this to the pediatric population end of this year in Q4, we will be basically opening our trial for the pediatric. And we look forward to having a similar at least or even hopefully more in pediatric because we are now intervening at a much earlier stage even of the disease. And so we look forward to that. And I think PAPZIMEOS is the only drug that has the ability to go very rapidly in the pediatric.

We talked a little bit about it earlier, but you have a similar same platform in the clinic for HPV-associated head and neck as well as cervical. Can you talk in a little bit more detail in terms of when we would expect to readout and expectations going into it in terms of what you might see?

Absolutely. So PRGN-2009 is our basically a second molecule that is exactly on the backbone of the vector that has PAPZIMEOS is built on. So first of all, as you can imagine, it's very important under also the new guidances from FDA. We are going towards applying for the platform designation. This platform designation allows now all of the -- basically the next drugs that are comes with the same platform with the same vector, they receive and they will have the same safety and manufacturing, which from a regulatory perspective, it makes it much easier and faster to move.

So PRGN-2009, [indiscernible] of cervical cancer and head and neck. These are in patients that they have failed practically -- well, on the cervical cancer, everything. On a head and neck, we have gone to various stages of head and neck, not only Stage 4 in our Phase I, but also now in Phase II, we have gone to even earlier stages. These -- just to give you a perspective, checkpoint inhibitor in these settings they have had between 15% to 20%. And when they -- in a head and neck, when they combine the checkpoint inhibitors with the standard of care in the early stages of head and cancer, there was no benefit whatsoever.

What we have done now is in conjunction with pembro, we have gone in both cervical cancer and head and neck. And we showed that actually quite a substantial increase to 30% objective responses, complete responder, partial responders that they went well over, for instance, complete responders over 2 years, and some of them continue. And now in head and neck, we will be reporting on the data in early Q1, which is going to be very exciting in the different stages in conjunction with pembro. And in that space, really the standard of care has been really harsh. You have surgeries followed by extensive chemo radiation, which really the patients become devastated as a result of that. And we are looking forward to show that data. I think it will be -- in my opinion, it will change the paradigm.

Great. Such high unmet need in both patient populations. Maybe in closing, in the last couple of minutes, what do you think is the most underappreciated aspect of Precigen that you want investors to take away?

Absolutely. I think I have heard from a lot of investors that they have certain [indiscernible] Helen, we missed this and Precigen, we missed Precigen. It was under the radar. And first of all, to say that still there is a huge potential for Precigen as it's going up, and this is just the tip of the iceberg for us. So we are looking forward to this portfolio and the next molecules.

As we have shown, Precigen, really, we started the company in 2020. And if you can imagine, in the middle of a pandemic and then the global market crashing. What we have done, our PAPZIMEOS drug entered to a Phase I in 2021. By end of 2021, we had finished the Phase I. We started the Phase II in 2022. We received a full approval in 2025. This is unprecedented for drug development, even by the biggest pharma left alone by a small biotech. We have been very focused from basically financially and strategically, we position our assets with our technology and regulatory path, not just basically hoping and wishing for a miracle. This is not our style. We are very focused on that.

And I think people, they really didn't understand that differentiated the technology at the beginning. And also, I think the discipline that we have shown over the years on our portfolio and advancement and having a team that -- a management team that is well versed not only in discovery and development, but also in commercial. And at various stages, there has been always question, especially going in a rare disease, that there was, well, what is the market value of this and basically how fast can you get approval? Would the payers pay for this? All those questions were all along. And I think that has led to underappreciation. But I think one by one, we have taken this obstacle, and we have answered them, and we have moved the assets forward and the portfolio.

So I think hopefully, the investors see the evolution of our company. And also, as I mentioned, this is just the tip of the iceberg for us. We are looking forward in the upcoming quarters, not only from our PAPZIMEOS commercialization, but also the next generation of the molecules in the oncology indication.

Wonderful. Well, that is a great place to close. Thank you, Helen and Phil, for joining us.

Thank you very much for having us.

Good afternoon, ladies and gentlemen, and welcome to the Precigen First Quarter 2026 Financial Results and Business Update Conference Call.

[Operator Instructions] This call is being recorded on Wednesday, May 13, 2026.

And I would now like to turn the conference over to Mr. Steven Harasym. Please go ahead, sir.

Thank you, operator, and thank you for all those joining us today for our Q1 2026 update call.

Joining me today are Dr. Helen Sabzevari, our President and CEO; Phil Tennant, our Chief Commercial Officer; Harry Thomasian, our CFO; and Raul Shah, our COO.

Before we begin our prepared remarks, I remind everyone that we will be making certain forward-looking statements during this call. These statements are based on our current expectations and beliefs. We encourage you to review the slide in this presentation as well as our SEC filings, which include risks and uncertainties that could cause actual results to differ materially from today's forward-looking statements.

With that, I will now turn the call over to Dr. Sabzevari.

Thank you, Steve, and thank you to all those joining us for our Q1 update call.

The approval of PAPZIMEOS in August of 2025 has brought a novel first-line standard of care treatment for adults with RRP. In nine short months, we have witnessed tremendous progress with the first commercial therapeutic launch in the disease's history.

Since last reporting in March, the launch has continued to show accelerating momentum. The early success and trajectory continues to build on this landmark achievement for the patients, families, health care providers, the RRP Foundation and all of those impacted by this devastating disease.

I will begin by providing you with some general color around what we are seeing and then turn the call over to Phil, who will provide more specifics around commercialization.

The accelerating trajectory we are seeing in revenue growth is robust. As reported in our quarterly report, PAPZIMEOS' net product revenue for Q1 2026, the first full quarter of availability was $21.6 million as compared to $3.4 million in Q4 2025.

Prescribers continue to add PAPZIMEOS to their practices at both major medical centers and community practices alike, which has been a strong tailwind as we are seeing this increasing momentum continue into Q2. This is a clear signal of the high level of enthusiasm among patients and physicians resulting in significant uptake of the therapy.

Why we believe we are seeing such a significant launch trajectory. First, the full approval and broad label from the FDA. There are no restrictions on the number of surgeries a patient must undergo prior to treatment with PAPZIMEOS. We are seeing this as patients are being dosed across all severities and in the extensive payer coverage we have secured.

Second, the transformative clinical data based on significant efficacy, durable and ongoing responses with a median duration of follow-up of three years. Importantly, we look forward to updating the ongoing durability data at ASCO next month.

Third, the ease of administration of the drug has enabled broad and rapid uptake at not just the major medical institution, but increasingly at community practices. Specifically, the ease of dosing as well as the efficient distribution infrastructure we have in place across the country allow rapid and effective integration into routine clinical practices.

Finally, the power of this therapy is strongly supported by a landmark expert position paper released earlier this year. The paper is sponsored by the RRP Foundation and authored by 16 leading U.S. physicians specializing in RRP was published in the laryngoscope, the premier peer-reviewed journal in otolaryngology. The paper recommends PAPZIMEOS as the new standard of care and the preferred first-line therapy.

Collectively, these factors mean that PAPZIMEOS has set a new benchmark for this space, prioritizing medical therapy over repeated surgical interventions to improve patients' outcome. As a reminder, this therapy directly addresses the root cause of RRP by eliciting a targeted immune response against HPV-6,11.

PAPZIMEOS also offers the potential for redosing due to its mechanism of action and favorable safety profile. We are evaluating this in an ongoing clinical trial, which is enrolling patients as we speak.

I will now turn the call over to Phil for details around our commercial launch. Phil?

Thank you, Helen, and a warm welcome to all those listening.

I'm delighted to share the most recent progress of our launch efforts with details around the completion of Q1 and the sharp momentum we continue to see with PAPZIMEOS launch in Q2 of this year.

As seen in our filings, we showed strong quarter-over-quarter product revenue growth in Q1 2026, clearly demonstrating the expected acceleration of product uptake from $3.4 million to $21.6 million. As we report today, we continue to see comprehensive payer coverage and further activation of accounts across the country.

I will now present some of the leading indicators we are observing as of today, translating to the launch acceleration. Registrations in the PAPZIMEOS patient hub continue to grow. As of today, we have approximately 400 patients registered, of which 25% are in the community setting, underscoring the broad reach of PAPZIMEOS beyond academic and major centers and reinforcing that PAPZIMEOS can be effectively integrated into routine clinical practice beyond major centers.

As previously mentioned, this does not account for non-hub patients directly enrolled by institutions. This continues to support the fact that there is expected pent-up demand for the new standard of care for adults with RRP.

Payer coverage has been exceptional and provides a solid platform for patient access to PAPZIMEOS. Total lives covered through commercial Medicare and Medicaid stands at an estimated 297 million. All inclusive, this equates to more than 90% of insured lives covered in the U.S.

As expected, we continue to see activation of accounts who are prescribing and ordering PAPZIMEOS across both major medical centers and community practices. We are seeing this trend continue into Q2, further fueled by the permanent J-code and a dedicated field reimbursement resources we have implemented.

As Helen mentioned earlier, the expert position paper continues to solidify PAPZIMEOS as the first choice for adult patients and treating physicians. We continue to have a significant presence at major scientific congresses in the U.S. and beyond, both through publications and presentations and interactions with thought leaders and the broader treatment community. This again reinforces the strong receptivity to PAPZIMEOS that we are seeing from the market. These congresses will continue to be a significant part of our commercial and scientific strategy moving forward.

The assignment of the permanent J-code on April 1, coupled with the durability of response that we are seeing in patients is helping this impetus continue. The permanent J-code designation will further simplify claims processing and facilitate broader patient access through both medical centers and community practices.

The significant quarter-over-quarter revenue growth is a clear sign that the health care community is embracing PAPZIMEOS. We are thrilled with launch performance in Q1 and expect these positive trends to continue into Q2 and beyond. I look forward to sharing those Q2 results in August.

I'll now turn the call over to Harry for an overview of our Q1 financials. Harry?

Thank you, Phil, and good afternoon to all of the participants on today's call.

As you've already heard, we are extremely pleased with our top line financial results for the first quarter. I also want to add that not only do we surpass $21 million in PAPZIMEOS revenue, but our operating loss for the quarter was only $6 million. Let me provide some further color on our overall financial results for the quarter.

Total revenue was $23.3 million, which included $21.6 million related to PAPZIMEOS sales. We saw demand for PAPZIMEOS continue to build as the first quarter progressed, and we're continuing to see that demand increase as we enter the second quarter.

Research and development costs for the quarter were $5.6 million, which compared to the prior year first quarter decreased by $4.8 million. The majority of this change is explained by the fact that PAPZIMEOS manufacturing costs were expensed prior to the FDA approval. As we look forward, we anticipate R&D expense will increase as the year progresses.

Selling, general and administrative expenses for the quarter were $21 million, having increased by $8.7 million from the prior year's first quarter. The increase was significantly driven by increased commercial activities related to PAPZIMEOS. Moving down the statement of operations. As I noted earlier, our operating loss for the quarter was $6 million. Our net loss for the quarter was $7.9 million or $0.02 per basic and diluted share.

Turning to the balance sheet. We ended the quarter with $56.7 million in cash, cash equivalents and investments. I do want to point out that our cash used in operations for the quarter was $43.8 million and included $13 million of cash outflows that we do not expect to recur in future quarters this year. The first quarter cash used also did not include any cash receipts from PAPZIMEOS sales based on customer payment terms. With that said, we expect cash used in operations in the second quarter to be significantly lower than what we saw in Q1.

We continue to reiterate that based on our current financial forecast, our cash, cash equivalents and investments, along with the collection of PAPZIMEOS receivables will fund operations through cash flow breakeven by the end of 2026, and we currently do not see a need to access capital markets for additional funding.

I'd like to now turn it back to Helen for some closing remarks. Helen?

Thank you, Harry.

I will now provide updates on the portfolio, starting with PAPZIMEOS clinical and regulatory updates. We intend on initiating a pediatric trial in PAPZIMEOS in Q4 of this year, as previously mentioned. In addition, our marketing authorization application continues under the review path by EMA for PAPZIMEOS.

We are also pleased to announce our sponsorship of a third annual RRP Awareness Day in June. This event provides another excellent platform to raise global awareness of RRP and the new standard of care for its treatment in the U.S.

Now turning to PRGN-2009. This is the same backbone as our approved therapy PAPZIMEOS, expanding the proven AdenoVerse platform. Our PRGN-2009 immunotherapy is designed to train the immune system to recognize and eliminate tumor cells infected with HPV-16 and HPV-18, the root cause of major HPV-driven cancers such as head and neck and cervical cancers. These malignancies together represents nearly 5% of all cancer cases worldwide.

PRGN-2009 is advancing in multiple Phase II clinical trials in combination with pembro in both head and neck and cervical cancers. I am very enthusiastic about the prospects of this program. We plan to provide updates on the program later in the year.

With that, I will now turn the call over to the operator for Q&A. Operator?

[Operator Instructions] And your first question comes from the line of Jason Butler from Citizens.

Congrats on the quarter and the progress with PAPZIMEOS. A couple for me. First of all, can you speak to the number of patients that have now received at least the first dose -- and if you're now also seeing patients complete the full course of therapy.

Second question, on the redosing trial, can you just maybe hit a couple of the design highlights for the trial and when we may see initial cuts of data? And then last one for me on PRGN-2009. So the update that you'll give later this year, can we expect to see any results from the ongoing Phase II trials in that update?

Thank you, Jason, for the question. So in regards to the first question, I'm going to hand it over to Phil, and then I will take the last two questions.

Jason, thanks for the question. Yes, we're not commenting on the specific number of patients who have actually been initiated on treatment. But as you can see from the revenue number, we're obviously making some very good progress there. And yes, given that we started our dosing in November and it's a 12-week regimen, then yes, absolutely, we are starting to see patients who have completed treatment.

Yes. And maybe I can also add that very clearly, as patients are being dosed and finishing all of the patients have received their doses. So, this is, again, going back to the original data that we have presented on the safety and efficacy and durability of PAPZIMEOS, which again points to that factor and ease of administration.

In regards to the second question on redosing, we have currently started the redosing of the patients, especially the patients that -- they had a partial responses in our previous treatment, in our previous trials, in [Tivicay] trial, and we are -- have started with that. And clearly, our patients in that are being dosed right now commercially, obviously, we are very much excited.

And from what we are hearing from the field, the physicians are extremely excited about some of the results that are seeing currently. So, for now, we are focusing on the partial responders that were in our original trials, and we are gathering the information on that, and we will be reporting from that perspective.

In regards to the PRGN-2009, the answer is absolutely. We will be reporting data. And actually, we are looking forward to that. This is -- as we have mentioned in our Phase II trials, both in -- especially on the head and neck that is in combination with pembro. And I think what is very important, these are open-label trials. So, we obviously have had and have a continuous opportunity to follow the data, and we are looking forward to be sharing this in the second half of this year.

And your next question comes from the line of Brian Cheng from JPMorgan.

Congrats on the quarter. Maybe just first, out of the 400 patients that you're currently in the hub, can you talk about the pace of conversion that you're seeing to commercial products? And just curious if you can talk a little bit about just the pace of also recruitment into the hub. Are you seeing any uptick since you launch? Just curious if you can talk about the pace there. And then we have a follow-up.

Sure. Brian, thanks for the question. So, Phil here. So, I think the revenue is probably the first thing that speaks to the pace of conversion of the patients. It's a little early to go into definitive details on that. We are looking at that, of course.

And I think with the advent of the J-code, the permanent J-code, that's something that over the next couple of quarters, we'll do a deep dive on to understand exactly how quickly and how many of these patients are being converted and how we can help. We've implemented dedicated field resources to assist in that conversion. And the momentum that we're seeing coming into Q2 suggests that we're making great progress there.

In terms of the pace of recruitment into the hub, I mean, you've seen the numbers steadily increase as we started to report on hub numbers. And remember, this is only the Precigen hub that we are commenting on. And there's a significant number of patients who are not using our hub who are being identified and treated. So that's another dynamic that is important.

Yes. And perhaps Brian, I can also add, this is Helen. I think what is very important and Phil pointed that out is also the number of the patients that are coming through the community centers because this is extremely important. And as we reported, now we have 25% of the patients are coming from community. So, this really points out not only the large or expanded efforts on medical centers, but now the community docs and the centers are participating. And again, a lot of those are not necessarily in the hubs, and they are treating the patients as we speak.

And also, another important point is this is not basically in regard of doesn't matter the severity of the patient, which is very, very important, again. So we are very excited about the reach and the way that PAPZIMEOS has been basically embraced by physicians and patients.

Maybe just a follow-up here. As we think about how to model second quarter and obviously, moving into the rest of the year, what are some -- are there any specific considerations that we should really think through as we run through our modeling exercise on 2Q, 3Q and so on? And just like you did for the first quarter number, are you able to provide some guardrail in terms of what we could see numerically for the second quarter number?

Okay. Yes. Thank you, Brian, for the question. So clearly, we have said we are not, at this moment, providing the guidance However, as you saw with the -- from Q4 to Q1, and we have gone to over $21.5 million. And also, we have an acceleration, as you have seen in really treatment and expansion of the treatment, both at medical centers and community centers. I think we are looking forward definitely to our Q2 and the results that we will be sharing as far as revenue is concerned.

And as Phil said, I think the revenue will speak for itself as it gets presented, which really shows the bringing in the number of the patients continuously and treatment as we are expanding.

And one of the good indicators, you can see that just from our hub, again, which is limited because it's only our hub and doesn't include patients from the others necessarily, you can see a continuous expansion in the number of the patients or increase in the number of patients, which is, again, it speaks to the fact that this therapy is very much in an accelerated fashion is taken up by the field.

And one other thing that maybe I can speak to and Phil can add is from a perspective of what we are seeing at the conferences and the fact that how the physicians are speaking and basically putting the patients on this treatment. And it's really amazing and it's quite encouraging in regard to what we have. Phil?

Yes. I would just add, Brian, that there's a few things that we're very confident about and looking forward to reporting on more. Obviously, the strong payer position we cemented quite early, and that gives us a firm foundation for what's to come.

I would say, as Helen mentioned, we expect the continued activation of accounts who are ordering and using PAPZIMEOS and not only in the IDNs, but in the community, we would expect that community trend to continue to strengthen. And ultimately, the patient identification in line with our broad label to continue as we go through Q2 and beyond. And ultimately, all of that is laying the firm foundation for the long-term success of the product over multiple quarters and years and not just over a single quarter.

And your next question comes from the line of Swayampakula Ramakanth from H.C. Wainwright.

Obviously, a fantastic quarter with $21.6 million in revenues. Phil, if you can help us understand that number a little bit more in terms of what portion of that was either part of pent-up demand or flow from Q4 to Q1 in terms of getting the payer policies processes set up versus patients who were treated.

In the same vein, you disclosed 400 patients in the hub with 25% coming from the community. So how much -- how many of these 400 or so patients that you have in the hub have been infused at this point? And also, what's the average time somebody takes from enrollment to getting dosed?

And the last question for me is on the data itself that's expected at the ASCO conference in terms of the durability data. How should we think about the data? Would that be helpful and supportive of any label expansions? And also, how should we think about that in terms of the current studies, whether it is pediatric or redosing? Will that give us some sort of feel for how these studies should eventually read out?

Thank you very much, RK, for the questions. This is Helen. And maybe I'll take the last question first, and then I will give the rest to Phil.

In regards to the ASCO presentation, we are actually very excited about the durability response and the data that is going to be presented at ASCO. Clearly, we continue seeing the same kind of a momentum. And as far as both safety, durability of response and the efficacy that we have reported, and we are now building further on that at ASCO. So, this is all going to be quite exciting for us.

And yes, that data will be helping in further really adding for the durability of the response and expansion of the indication. So, we are looking forward to that. And also, that data further adds to the -- really the robustness of the platform, which is simply this is something that we are very excited about the AdenoVerse platform to be used across a number of the indications and specifically on HPV-related indications, both in rare diseases, but also in oncology. And we think that, that data is another feeder in the cap of AdenoVerse platform, which we are moving towards the platform designation with.

So, with that, I'm going to hand it to Phil to answer the other question.

RK, thanks for the question. So let me tackle your hub question first. I did refer to this a little earlier. I think we'd like to see another couple of quarters before we communicate details of exactly the hub conversion and time to conversion and so on. I mean what I would say is that it's pretty much as expected at the moment. But I think we do need another quarter or two to really understand the meaningful trends there.

Your first question was about carryover revenue. Yes, absolutely, given that we've got a three-month or 12-week regimen at the end of each quarter, you will see some revenue spill over into the next quarter. I would say from Q4 into Q1, that was pretty minimal given the level of revenue that we had in Q4, but you would expect that to be more as we go forward. And that -- the key thing there is that it's new patients that is fueling the business opportunity that we've seen in Q1.

Yes. Maybe I can add to that. That what -- especially with what achievement with the J-code that has been also extremely helpful in not only for institutes to be able to process the patients through much more rapidly. And I think we are seeing that trajectory going up, and we are seeing the same thing actually in Q2. So we are very excited about that.

And there are no further questions at this time. I will now hand the call back to Dr. Helen Sabzevari for any closing remarks.

Thank you, operator, and thank you for all of the thoughtful questions. We appreciate the opportunity to provide you with this update on this historic product launch. I believe we are building the foundation of a meaningful full portfolio for Precigen and for the community of our patients. We look forward to updating you as the launch continues and specifically also further on our portfolio progress. With that, I wish everyone a wonderful evening. Thank you.

Thank you. And this concludes today's call. Thank you for participating. You may all disconnect.

Good morning. I'm RK, a senior sell-side biotech analyst at H.C. Wainwright. So -- and we are thrilled to be hosting Precigen for this fireside chat this morning. So 2025 has been a transformational year for Precigen, marked by the landmark FDA approval of PAPZIMEOS, the first immunotherapy for adult RRP. So as we sit here in late March of 2026, the company has officially transitioned into a commercial stage entity reporting its first quarter of launch very recently.

So joining us today are Dr. Helen Sabzevari, President and CEO; and Phil Tennant, Chief Commercial Officer. Good morning, folks, and thank you very much for joining us this morning.

Helen, as we get started, especially with your experience of developing various therapies. And now with this particular one, PAPZIMEOS. So how do you see this new excursion with this drug. And also, if you can, please describe the molecule itself and what it does for this particular set of patients?

Well, first of all, I would like to take the opportunity to thank you, RK, for having us and also to say good morning to the audience here. Clearly, the PAPZIMEOS molecule at the center of all of this for the recurrent respiratory Papillomatosis is a very innovative molecule and the premise of this molecule is built on AdenoVerse platform that we have at Precigen, which, by the way, we fully have the ownership of the IP of this gorilla based adeno vectors that are very much differentiated from the rest of what field is used to as far as adenoviruses and other viral vectors. And why would I say that? Because there has been this perception that all adenoviruses are similar, and from perspective that they have limited capacity to the number of genes or epitopes that they can present usually around 5 KB or less.

Also, there is that perception of all adenoviruses can be only given once at best maybe twice, but then you have this immunogenicity to these vectors, which doesn't allow you to repeat those any further. And also the manufacturing of these adenoviral all have been put in the same category. When we started developing this platform, actually, we went completely on the other side and make sure that we are working on a platform that is fully differentiated from the rest of the adenoviruses and in general, even other viruses in a number of ways.

Number one, the capacity of gorilla adenoviruses we have up to 12 KB, and we can extend that. So you can imagine how many genes and how many epitopes it can be containing as we use now. These are non-replicating viruses by the way. And one very, very important premise here is that you can repeat dose with these vectors. Why? Because humans have not been exposed to these vectors before, so we don't have already neutralizing antibodies or immunogenicity so you can start that. And especially the gorilla adenovirus and the backbone that we have used for PAPZIMEOS and also in our PRGN-2009 for the rest of the molecules. It has a very unique ability that it pushes more towards CD8 response rate as opposed to the humoral responses, which then your neutralizing antibodies do not come to play as much.

And we have shown this. First of all, in all the healthy humans, both in the United States and in Africa, when we look at over thousands of individuals, you see either very little or no immunogenicity at all against these vectors. And on top of that, in our clinical trials, after every repeat dosing, and we have done sometimes over 1.5 years of dosing in our cancer clinical trials. You see that the expansion of CD8 it keeps on going up higher and higher, completely opposite of what you see with other adenoviruses. And clearly, also the capacity of these molecules, we have been able to design many epitopes, especially in HPV-related indication in cancer or in PAPZIMEOS for RRP, we have put in a number of epitopes and then also new epitopes, that Precigen has basically generated it's in this.

And then finally, the manufacturing of our AdenoVerse platform, we have a cell line that is highly productive, and we can produce large amount of these vectors. So having said that, what we have done originally is designed PAPZIMEOS in such a way that to address the actual issues that exist in recurrent respiratory papillomatosis. This is a disease that for the past century, there has been no treatment except continuous surgery. As a result of HPV6 and/or 11 you get the formation of these benign tumors and on vocal cords or in trachea. Therefore, the patients cannot speak or they can't breathe.

Now this infection can take place either in onset of children as they pass through the birth canal, they can get infected or it can happen in adults through sexual transmissions. And what these patients go through is correct because some of these patients on a yearly basis, for instance, they have to have like 10 surgeries to just be able to speak or breathe. And some of the children, some of the patients that we have treated as an adult, they have had this disease since the age of 1. So imagining that your child has to go through this on a monthly basis.

And one other thing that I would add is the studies at Hopkins has clearly shown that by the fifth surgery, there is irreversible damage to trachea or the vocal cord, so these surgeries are really damaging and also dangerous for the patient. Having said that, what we did was we designed the PAPZIMEOS the molecule that contains the epitopes that addresses HPV6, prominent epitopes in HPV6 and 11. And we also identified new epitopes, which we have full IP around that, and it's put in the context of our gorilla AdenoVerse platform on the backbone of this gorilla vectors. The way the mechanism of this molecule is -- we give this molecule subcutaneously, very easy, just as you might receive a flu shot, for instance, right?

And then what happens is simply at the site that is given, the molecule gets presented and it starts training your own T cells, which sometimes I refer to as the army of your body. Now these T cells become a specialized forces to recognize these specific epitopes wherever you have infected cells that express the HPV6 or 11 epitopes. When they see that, this is their enemy and they destroy it. And in that setting, you are really addressing the root cause of this disease as opposed to the surgery that is just like mowing the lawn, you are cutting the tumor, but it keeps coming back because underlying infection, you're not removing that. And that is specific to PAPZIMEOS and as immunotherapy has become extremely effective and with the excellent safety profile.

Thank you very much for that, very helpful. Having said what you said in your pivotal study, you saw a 51% complete response rate. So there's obviously the other 49% of patients still experiencing the disease. So in thinking about them, obviously, we'll talk a little bit more about the redosing study that you're doing. But as -- just based on the pivotal data that you've seen, what do you think is the resistance mechanism? Or why are those 49% of the patient population not having a complete response or response good enough so that they don't need to be under the knife again?

Great question. So when our pivotal studies, we did a couple of things that maybe I should mention. First of all, we went to the most severe patient population, which was defined as having minimum of 3 surgeries per year. And some of our patients, as I mentioned, they have more than 10 surgeries. So that was one aspect. We wanted to make sure that patients benefit from this. And secondly, we put a very robust endpoints, which was a complete response, which was designed as having a minimum of 12 months surgery free or without any other treatment for that matter. And that was very important because here, we wanted to ensure that these patients they have, especially for someone who gets 10 surgeries per year to go from 10 to 0. It's unbelievable.

But with that perspective, what we saw was, as you mentioned, 51% complete responders which, by the way, the durability of response has been extended now and in some of those patients have passed 3 years. And at the same token, we saw the overall reduction in the number of surgery, which was 86% in all patients. So 35% of the patient, even though they didn't go to complete response, they reduce their number of surgery. And this is very, very important.

Now what would be the reason? Based on that, actually, even FDA very much was excited about this data, for the reason that what we saw in this -- what we refer to as partial responders because they didn't go to a complete response, was that they built the immune system to HPV6 and 11. So we saw the increase in their number of their CD8, but it didn't come to the same extent as the complete responders were. What could be the reasons for this? As you know, immune system of different patients are somehow beaten up worse than the others, depending on the length of the infection, depending on the capacity of the infected cells.

And you should remember that your immune system is continuously is in connection to these infected cells, which they -- for the lack of better word, they energize your immune system eventually. Your immune system becomes exhausted. So for various reasons, there might be that you are starting at a different threshold. And what actually in the discussions with FDA, we were very thankful for the suggestions of FDA. Based on the safety that we would see in using PAPZIMEOS, but also the efficacy, it was believed that by redosing, you can probably push the immune system to that threshold of a complete responders. And that's one of the important things. And it becomes really relevant now having the gorilla AdenoVerse platform because that allows you to repeat dosing because it's not a onetime silver bullet, you can keep using that. And for that reason, we believe that by redosing, you can also push the immune system of those individuals with the partial responses, hopefully to a complete response.

So Phil, just talking through some of the initial launch metrics and also how you're seeing the patients adherence to the therapy. So the label currently says you need to take subcutaneous injections -- 4 subcutaneous injections over a 12-week period. So not -- the first question is, do you know or do you have an idea of what percent of the current patient group have gone through the full course. And how do you see -- or how do you ensure that the patients will get started go through the full 3-month cycle?

Yes. So as you can imagine, as we mentioned on the earnings call last week that we started dosing patients back in November, so you follow the 3 months through. And yes, you can see that there are patients now starting to complete their courses. We are not aware of any patients who haven't completed all 4 doses. It's a fairly simple regimen. Yes, it's spread out over 3 months, but it's 4 subcutaneous injections. I think the centers that we're dealing with, they are all very well versed in much more complicated regimens than PAPZIMEOS, and so we don't really see it as an issue in terms of just scheduling the patient.

Our label allows for certain flexibility around each of the doses. One thing that we're doing within each center is encouraging them to purchase the first 2 doses upfront because they're only 2 weeks apart, and then you have the 6-week and the 12-week dose. But there's real room around each of those doses. So it doesn't -- it's not that the patient has to be in a center in a certain day at a certain time as a bit of flexibility, which can suit the patient schedule.

Very good. And then in terms of your commercial strategy itself, obviously, your strategy is a little bit different from regular -- from the launches that we have seen. So if you can explain a little bit of that. And also, what is the market, what is the initial market you're going after in terms of the IDNs and the community hospitals that you're still looking to get the drug into?

Yes. Well, our go-to-market model was made a lot of sense for companies like us approaching its first commercial mobilization asset. We announced last year a pre-approval that we were partnering -- we had a commercialization partner to predominantly in the field and some of the commercial support services. But the way it works is my direct reports, my head of medical affairs, sales and marketing, market access, distribution, they're all Precigen employees, full-time employees, but their organizations that spread out into the field, they are on the EVERSANA books, but they're dedicated to PAPZIMEOS. They have Precigen e-mail addresses. And obviously, we treat them very much as part of the Precigen family. So that model is working really well for us.

In terms of the addressable market or the institutions out there, we had conducted a detailed claims, electronic health records and claims analysis prior to launch, which clearly showed that these patients were stacked up as it were in the large academic centers institutions, the IDNs, and we set our commercial footprint accordingly. We'd identified approximately 500 hospital systems where the bulk of these patients were housed and within that approximately 100 systems that had sort of 80% of that potential. So our initial commercial footprint was geared to that opportunity.

Obviously, as we're now launching, we are learning and we're refining as we go forward, but we still have a relatively small commercial footprint but one which covers 90% of the patient potential that we see. And on top of that, the final point I would make is that we obviously have nonpersonal promotion and digital channels where we can reach any of the more remote HCPs and practices.

So in practical terms how long do you think it will take for you to make sure that you have at least met your initial -- you've done your initial detailing with every single one of your target entity?

Well, we've already covered. I mean, all those target institutions that I mentioned, we've already engaged with all of them basically and more. And one of the aspects of the launch that I mentioned on the earnings call was how the community is now also stepping up and embracing this as the new standard of care. That's a facet of the launch that we'll talk more about in the future. We talked on the earnings call last week of we've got some simple low-cost solutions for community centers that maybe don't have the ultra cold chain capability, but we're able to get the drug there for it and get it to the patient. So there's really no way that we can't ship the drug. And yes, that community aspect has been very pleasing and one that we'll comment on more as we go through the subsequent quarters.

This next question is to both of you. So RRP is one of those, which historically was underdiagnosed even it's kind of interesting, as I say that, because in your introductory remarks, Helen, you were saying some of these patients see it very, very early in life, like even when they're 1 year old. So it's interesting that it also says underdiagnosed. So what is the reason for that? And now how do you -- what are the strategies that you are undertaking to ensure that there is enough of disease awareness and also get the drug to all the patients that are diagnosed or that also could be potentially patients.

As I mentioned, this disease has been there for well over 100 years actually has been diagnosed, and it's there and -- it's not because of lack of trying, everyone has tried everything, including checkpoint inhibitors and all the other molecules, and unfortunately, nothing had worked until PAPZIMEOS has been approved as a first and only product here. The reality of the situation for these patients is that, first of all, the HPV-related infections that existed. And sometimes, these HPV-related is quiascent for a while, and then it starts showing itself at the different stages.

And this -- and to start with a lot of the ENT specialists and a lot of the physicians, they misdiagnosed basically this indication, unfortunately, until the severity of the disease starts. And then there has been a lot of issues with really reporting. When we go back into 1990s, the original reports that came up about the number of the patients that existed, there is a variety of factors reports anywhere between 10,000 to 14,000 patients. And then since nobody was really working on this rare disease for developing a specific drug for it.

Then there was a period from 1990s until 2021 that we basically started and we started working very, very closely with not only investigators, but also with the patient advocacy groups. The numbers that was reported was referring back to those original articles in 1990s. But you can imagine that in a span of 2.5 decades, obviously, the number of infections increased as well as the number of the patients with the disease, both in children as well as in adults.

So what we have done is, first of all, through the -- having a very, very solid collaboration with a patient advocacy group for RRP and this is Disease Awareness Day, for instance, on June 11 is the RRP Day that we hold every year with conjunction and collaboration with our RRP Foundation. First of all, make sure that the patient's story comes out, but also the investigators around the country has been now joining, and it's interesting to see how many of investigators, they have these large pocket of patients across not only just big centers, but what Phil was referring to, the community centers that they have numbers of patients, and it keeps getting added to this.

And I think Phil can speak to the very, very nice study that our commercial team did in absence of any code because no code existed until now the J-code that has come out in prior and they really analyze the patient record in order to get a handle on the number of patients, which is around 27,000. And maybe, Phil, you can expand on that.

Yes. As Helen said, I think we feel that the prevalence has been underreported historically, and we did conduct a detailed analysis of electronic health records and claims database, even though there's no ICD-10 code, we were able to paint a very vivid picture of what these patients actually look like from their diagnostic codes, and their surgical codes and then looked at the broader data base to identify the patients who look like those patients who were definitively identified as having RRP. So that's where the 27,000 adults comes from. I actually think that will increase -- the diagnosed prevalence will increase over the next few years because of heightened education awareness of treatments, obviously, PAPZIMEOS a new standard of care.

The other thing I would say is that many of these patients, they're very well known to the health care system. They're on a revolving door of surgeries in and out of these institutions and community practices. So they're very well known, but our label is a broad one, and it's basically any adult with this condition. So as you would imagine, our marketing efforts, our commercialization efforts are using our in-person channels and our nonpersonal channels to make sure that basically, patients are aware that there is a new standard of care that it has a broad label and that they didn't need to have the conversation with their treating physician about the potential for them to benefit from this.

Helen mentioned the foundation. We're so thankful for the partnership that we have with the foundation. They've had a very strong campaign that highlights a reduction in even a single surgery for these patients is actually very meaningful. And our clinical data not only speaks to that, as Helen mentioned, 86% of the patients in our pivotal study showed a reduction in surgeries. But we also have those durable complete responses in a significant portion of the population. And so every patient who has this condition deserves to have a conversation with their HCP about those things and ultimately seek treatment, should they be appropriate.

So having said what you guys said just now and also I'm trying to triangulate between that and your excitement about the first quarter and your bullish guidance of at least $18 million for the first quarter. Considering that, -- and is -- how much of that is coming from a bolus of patients that you're seeing in the first quarter? And knowing how you're able to find pockets of patients across? Should we, as investors assume these boluses are going to be there for at least in the first full year of launch?

Yes, I can maybe kick off, Helen and if you want to add. So you're exactly right. We have a 3-month treatment regimen for all of these patients. So there's going to be a time of every quarter where you'll have some carryover from quarter-to-quarter as we go forward. We did see that to a certain extent, coming from Q4 into Q1. We'll see it going from Q1 to Q2 and for subsequent quarters. So there will be a carryover depending upon how many doses that patient carries over into the next quarter.

But the important thing I would say is that what we talked about in Q1 is actually reflective of the new patients that are continuing to be identified. That is really what has accelerated through Q1, and we expect that to continue in Q2 and beyond. We do believe, based on the work that we've done and there is a significant bolus and it's going to take several quarters for us to work through that as we go forward. So yes, we would expect this trend to absolutely continue through '26.

Yes. And I echo what Phil said, the reality of this situation is, first of all, these patients and their physicians, they are anxious for these patients to receive their treatment immediately. Reason for it, as I mentioned, by the fourth or fifth surgeries, you have caused an irreversible damage to the trachea and the vocal cords of this patient. So what we hear from our physicians and what we hear from the patients, it's very simple. They don't want to let the patient get to that point because they want to stop their damage.

Now the ones that have been carrying this severe, basically, they consider as a severe patient, clearly, unfortunately, for many years prior to PAPZIMEOS being approved, they had to go through this surgery. But those are the first one that actually both physicians and patients are asking that they'd be immediately treated as Phil says, because they don't want to have any further surgery, that's number one. But at the same token, what we are seeing because of the broad label that we have again, which goes to all adults with the RRP, regardless of the severity of the disease, we are seeing that physicians and patients that are asking as they are being diagnosed with RRP, to receive this. Why? Because they do not want to join that group that has a damage already, and that's very important.

So you -- Phil, you gave us a number in terms of how many patients are there within the company's hub, which is 300. So just trying to understand how this hub works to a certain extent. And also, in terms of a payer and if there is any -- not only payer access, but also any resistance from payers in terms of the price points that you've put out there, any commentary? And also, are you planning to give this hub number quarter-to-quarter? Or is this just so that -- just for the initial launch metrics, they are using that because I'm just trying to understand because it's really difficult because we don't know when the bolus of patients will come from the second quarter and third quarter and so on. And is the hub away for us to keep track of the potential growth -- the potential future growth of the revenues?

Yes. Let me clarify, when we talk about the hub, what do we mean by that? We mean the manufacture of patient support hub, which most manufacturers have and patients are able to be registered with the intention of them, obviously, getting treated benefit verification and then being treated by their institution. So we reported steady growth, as we've said quarter-on-quarter and then over 300 now in our hub. There was another source of patients, though, which are in the institutions, and they don't call it a hub themselves. They're just say patient support services themselves.

And so what I mentioned last week was in our patients that have been treated so far, we see patients significant proportion of patients from both of those sources. So I think moving forward, it is an important lead indicator that we will continue to comment upon. Obviously, revenue becomes very important as we go forward. But we will continue to talk about patients in the hub sort of top of the funnel as it were. You talked about payers. We've been thrilled with the speed of payer coverage. We talked about the 215 million lives from the commercial payer segment. But if you add on Medicare and Medicaid, we're closer to 300 million lives which is 90% of the insured population in the U.S., and the majority of those are covered to label.

But you're right, we do see some plans that have some restrictions related to surgical -- prior surgical number. We're very confident, and we've said all along that the treating HCP can have a very robust conversation with any payer that may have put restrictions in place. You've got the high unmet need. You've got the patient history that goes beyond just the prior year and probably is a lifetime for some of them. You have our clinical data, our efficacy and safety data, you have the durable responses, which are ongoing, the complete responses, and then, of course, you have now the consensus statement from the foundation and the 16 thought leaders across the country who put pen to paper to say this is the new standard of care for all adults with RRP irrespective of their surgical history.

And so with those data available, we feel very confident that we can support any clinician to have a conversation with any payer to make sure that the patient gets treatment. And to date, we are not aware of any payer that is flatly rejected any patient for treatment.

Very good. So from tomorrow morning, we're going to have the J-code?

Yes.

So with the J-code, do you -- are you gearing up for another big bolus or is the J-code just helps payment, but it really doesn't bring in a ton of patients just because you have a J-code?

Yes. No, great question. And the permanent J-code is an important factor in any company's drug launch. We had done some analog research prior to approval that showed that for some drugs, there was help when the permanent J-code came on board because some institutions, they're not willing upfront to take the financial risk for a buy-and-bill drug. If you recall, we made the drug available through specialty pharmacy and buy-and-bill because we foresaw that, that might be a challenge.

But some institutions say, no, where buy-and-bill we're going to wait until the permanent J-code. So we expect and we know that there are institutions out there that are in that category. And so we do expect those to be activated as well as the ongoing activation of institutions in general that we are seeing. So the permanent J-code definitely helps and should give us further impetus. But in general, it just smooths and streamlines the whole patient access process.

I know we are not stopping here. You're trying to expand the market either, obviously, both by filing -- having filed the MAA going into Europe. How should we think about that commercialization there? And also, is there any conversations going on regarding trying to get a partner to do to help you out in these geographies? Or do you think it will be done just by yourselves?

Yes. So maybe I can start and Phil can add. Clearly, we are excited about the expansion of the indication and global expansion of the PAPZIMEOS. And as you mentioned, it is currently under review with the EMA, and we are looking forward to later on this year from that perspective. I think what has become very important first of all, some of the work that Phil and the team has done and very clearly showing that, for instance, even in the European market, you have a similar number of patients, number or even somewhat a little bit more that -- so therefore, this drug is very, very important.

As far as the commercialization effort is concerned, our focus is really on just United States, even though we are going through the regulatory path. But at this moment, we do not have a plan to put boots on the ground in Europe for commercialization. And as we have already mentioned, we are looking at various partnership aspects with that we can commercialize this and make this drug available to the European community and others. And I think as we are now a commercial company with obviously a very exciting drug, it is very clear that the companies like us, they are at the center of discussions, and there would be a lot of number of discussions from a perspective of partnerships or BDs, which as we go through, we are evaluating, and then we will be discussing as the time comes.

And the only thing I would add, RK, is the landscape work that we've done so far, some of the initial sort of pricing work and so on, it's clear that many of the issues that we see in the U.S. or we saw ahead of our approval in the U.S. are absolutely applicable to what we're seeing ex U.S. in terms of high unmet need, lack of a standardized approach to treatment and a real need for something that addresses the underlying cause of the disease.

So one quick question on physician feedback. What are you hearing from the physicians and the ENT specialists who have already used the drug? And are they slowly becoming champions of the drug?

I think, for instance, last 2 weeks ago, I think was the UroGen, which is one of the biggest meeting for laryngologists and specialists in that area. And what we have heard very effectively through a number of presentations. First of all, RRP was a dominant topic during this meeting. So it really speaks to the expansion and recognition of this indication, but also the discussion around PAPZIMEOS and physicians referring not on the safety of the PAPZIMEOS, which they was referred to as excellent efficacy, especially the complete response of 51% it was considered impressive, but also adding the durability of response, which has passed 3 years now this was the really physicians have been calling it outstanding indication that you can imagine, there has been nothing for the past 100 years as far as treatment is concerned.

So I think the field is very excited, the physicians, the patients, patient advocacy groups, and clearly, we are extremely excited that we could bring this drug to the patients.

I should -- even I'm tempted to call it life cycle management. I don't want to call it yet. But you certainly are planning on -- have started the redosing studies, and also trying to look into pediatrics, right? Because as you said, there is quite a bit of population. We don't get this diagnosed very early in life. What are the plans there? And what are the milestones that we as investors should be on the lookout for in these 2 areas?

Excellent question. So first of all, as you mentioned, we currently hold a label for all adults with RRP. And based on, again, and I keep stressing this point because this kind of drug with the ease of administration and the safety and efficacy that has shown -- I mean, let's remember that this drug has only grade 1 or maybe grade 2, which is very similar to when you get a flu shot, maybe a little bit of a rash on a site that you have received that will go away or maybe a little bit of fever, which will resolve itself within a day.

So -- and a subcu injection that can be done in the office of the physicians. Now imagining, especially for a pediatric population, they has to go through this. This is a really a treatment that lend itself for this patient population and especially and unfortunately for these children that they have to go it's horrendous this. So as FDA very much has been supportive of this and so on we have already communicated. We will be starting our pediatric trials by the end of this year in 2026. So we are very excited about that to bring not only have this for adults, but eventually to be approved for children.

And from the perspective of redosing, again, it's -- first of all, it's extremely important to make sure that the partial responders that we can turn these to a complete responder, that 35% of the population and as you mentioned, the redosing arm has already started, and we are looking forward to start providing data in that in 2028. And that will definitely expand the indication but also from the data that we are getting in general from redosing the studies and also from our long-term complete responders we are gaining much more view into the immunological responses and needs of the patients over the years, which then it can offer different ways of using PAPZIMEOS as these patients move forward.

The other interesting aspect that you put out last week was regarding initiating studies in PRGN-2009, not initiating continuing the work that you've been doing, which is exciting. So can you highlight what PRGN-2009 is and how it is -- it also comes from the same platform that PAPZIMEOS is?

Great question. And I'm really happy you asked this question because we are extremely excited about PRGN-2009 as the second group of drugs that are coming forward. And to start with, we had around the same time that in 2022 or so we had started the trials going into HPV-related cancers, which, as you know, it really contains 5% of all cancers. It's a huge number of patients and market. And we had the Phase I with the PRGN-2009. What PRGN-2009 is exactly on the same backbone of PAPZIMEOS the gorilla vector. It's exact same structure.

So you can imagine the safety, the manufacturing, the talks, all of that is very, very similar. The difference of PRGN-2009 is addresses HPV16 and 18, which is the root cause of infection in the cancer patient, which leads to the indications such as cervical cancer, head and neck, anal cancers. And with that, if you look at the history of these patients, in a cervical cancer, their first line of the treatment is current chemo, radiation, checkpoint inhibitors, surgery altogether and then these patients fail unfortunately. And then there is nothing.

On a head and neck, even with the checkpoint inhibitor approvals you are also having somewhere between 15% to 18%, in some cases, maybe pushes to 20%. In our Phase I data, what we did was we developed PRGN-2009 on the same background with number of epitopes of HPV16 and 18 and also new epitopes that we have identified, again, owning the full IP around not only the platform but the molecule. We put it in a Phase I in all comers HPV-related cancers, which they had failed, they were relapsed refractory patients that had failed at least 3 or 4 lines.

We presented that data at ASCO. We showed in these patients, and they had, by the way, failed checkpoint inhibitors. We put PRGN-2009 plus the checkpoint inhibitor back. We show 30% objective responses. Patients had complete responses and ongoing for more than 2 years. These are patients Stage 4 that they would have had months to live. Then we obviously started a Phase II trial on cervical cancer, but simultaneously, we had started a Phase II in head and neck in oropharyngeal carcinoma patients. And we are really excited about what we are looking at.

And as I mentioned last week, end of this year, we are looking forward to report the first set of data from this trial. So it's quite an exciting time for Precigen. With coming back with now the second molecule. And to your point, as far as we are very much looking forward to having discussions with the FDA on a platform designation because clearly, this can apply there as the molecule, basically, the backbones are the same, and then you can even move much faster from that perspective.

Thanks for introducing that topic. The platform technology designation, right? What is it? And to apply for it, I believe there have been only like 3 companies who have been awarded that designation. So in your case, what sort of data do you need to compile? And once you apply for it, what are the benefits that you're getting? And how long does it take for the FDA to keep you that designation?

This is a very exciting program from FDA, and we are very, very happy about this. The kind of information is already what we have generated on PAPZIMEOS as far as the platform is concerned, which is your safety, your manufacturing talks and also, we have shown efficacy and durability of responses. So you can use that and with the -- for instance, the molecule, such as PRGN-2009, you can combine that. The benefit, and this is one of the reasons, as we have heard the commissioner really, the whole point of these programs is to make the review processes much faster because now, basically, you have established the CMC manufacturing already. And since the backbone is exactly the same, you have established the safety of a non-replicating AdenoVerse platform.

You have established the efficacy that you can keep giving this number of times. And that basically you're seeing benefits from that perspective. And also all of the other clinical like studies with bio-distribution and so on and so forth. So you can imagine now when the second generations of the molecule in a different indication, but on the same platform comps, now you can move much faster because these things from perspective of regulatory bodies have been already established. And as part of that platform designation then you can move much faster through pivotal trial.

So that is good on the regulatory side that you don't have to send a ton of paperwork that you need to send. But on terms of the development timeline, and also the cost of development. How does that designation help you? And can you kind of give us an idea of like what are we talking about? What is the savings you're talking about in terms of time and money?

Yes. So I think from the lot of repeat studies that needs to be done for regulatory like -- for instance, CMC or preclinical or even in the clinical studies, if they ask for repeat, those studies will not become relevant any further, right? Because a lot of those have been done. A lot of those assays has been accepted already. So you don't need to reinvent the wheel. And you can rely on the basically the system that has been shown it works and use that. So it saves a lot of resources and investment from that perspective.

But at the same token, it saves a lot of time in pushing through this because as you are well aware there is an aspect of doing the clinical trials. But then there is a tremendous amount of preparation that you have to do for your manufacturing and making sure that all of that is good. And with Precigen, but it becomes also very important, we have the manufacturing know-how at Precigen because we are commercially producing PAPZIMEOS. So we are very well versed in production of these gorilla vectors and manufacturing of it. So you can imagine that we have gone through the first drug and then hopefully, in upcoming drugs for the next indication, which is a large, very large indications in cancer then we can move very, very rapidly.

So besides 2009, are there any plans once -- if you get this platform designation in place, which is obviously a great thing. So now you will have 2 molecules of that, one approved which is PAPZIMEOS, you'll have the PRGN-2009 going. Is there -- are there any thoughts about developing another indication or another molecule that you can use the same platform on? I'm just trying to understand how much more potential is there on this platform?

It's a tremendous amount of potential. So what we did from originally when we developed and added gorilla AdenoVerse platform, we look at not only the infectious diseases and rare diseases. And RRP was the first one that we thought we can move very rapidly and we did in a matter of 4 years, we took it from discovery to the approval, which is a record time, but also PRGN-2009 in other indications. We have a number of targets, both in cancer as well as in rare diseases and in infectious diseases that actually we have those already at the preclinical level.

Originally, when we started, as you know, we had to focus all of our resources, and it was during the global pandemic, and very difficult market challenges. So what we did was by choice, we decided to prioritize PAPZIMEOS, which was the right choice for the company to get it across the finish line in a record time, and we did that. And now that we are a commercial company and with revenues coming in and with a number of options in front of us in regard to partnerships and others, then I think we have the tremendous ability to expand our portfolio, which is really tremendous because this platform, as I mentioned at the beginning, and I stressed at the end it differentiated. This is not another me-too platform. This is not another just adenovirus like everybody else.

This is a very unique platform with the opportunity to really go across indication. And our portfolio actually contains many other indications in there. And we are prioritizing as we also generate revenue and resources and look at the future BD developments that how we can expand this portfolio continues.

So in closing and the last question. With $100 in the bank as of end of the year. And obviously, we anticipate it could growth in revenues in PAPZIMEOS this year and potentially getting to be breakeven by the end of 2026 as folks are expecting it to? How should we think about deployment of this incremental dollars that you would have. And at the same time, on the flip side, if things don't go the way you expect, what are the things -- what are the -- what are the options that you have to make sure you have a sustainable growth?

So first of all, I think for what you mentioned, absolutely. Now we are a company that with revenue that it's coming in, and we are very excited about our commercial path as we see it. Currently with 100 -- a little bit over $100 million in a bank. We already have basically looked at our budget and for instance, the redosing the pediatric initiation of the pediatric trial, and the expansion of PRGN-2009 is already within our budget for this year.

As you can imagine, in the past year, we had to incur a lot of costs for the CMC, which those were onetime costs that we had to do, and we don't have that. So we can redeploy those resources to our portfolio and clearly also the revenue that comes in. Where we have always extremely good, RK, is really making sure that we have our bets on winning horses. And we do our work upfront on the assets that we know they have a very, very high possibility of hitting the target and getting to the finish line, combining the indication, the regulatory path and the technology to ensure that we've gone, PAPZIMEOS was a great example of that.

And so we keep applying the same kind of discipline and pressure to that, of course, ensuring that our front-runner asset PAPZIMEOS is well capped and with a high priority for us in the U.S. And then we deployed our resources accordingly to their priority program. And in -- like any other time, and we have done this over the years when it was the global pandemic or markets had a very difficult time, we continuously evaluate our budgets against our asset. And if there needs to be decisions made accordingly, we would make those decisions. And we have shown that we are that company that we can do that and then still continue to progress our portfolio and get it to the finish line.

So since there is 30 seconds left, so I can still ask one last question. So as we -- as you stated, last week, you gave us a quarterly expectation for the first quarter. So until PAPZIMEOS gets to a certain steady state, is that going to be a way of communicating in terms of revenue guidance on a quarterly basis? Is that the explanation that investors should have for the second, third and the fourth quarter?

No.

No. The call was so late in Q1. It made sense for us to give that guidance because there was so much happening. But we won't be giving that guidance in the middle of the subsequent quarters when we fall into that rhythm. But we will be talking about all the things that we've talked about in terms of HCP awareness, understanding intention to prescribe about patients being adopted and coming into the top of the funnel about institutional activation and about payer coverage. We'll continue, obviously to talk about all.

And of course, every quarter, you will see the revenue and it will speak to it.

Thank you, thank you both for spending the hour with us. Really appreciate your time and good luck. And I know it's -- we're entering into a very exciting 2026. Thank you.

Thank you, RK.

Thank you. Bye-bye.

Good afternoon, ladies and gentlemen, and welcome to the Precigen Full Year 2025 Financial Results and Business Updates Conference Call. [Operator Instructions] This call is recorded on Wednesday, March 25, 2026.

I would now like to turn the conference over to Steve Harasym. Please go ahead.

Thank you, operator, and thank you to all those joining us for our Fourth Quarter and Year-end 2025 Update Call. Joining me today are Helen Sabzevari, our President and CEO; Phil Tennant, our Chief Commercial Officer; and Harry Thomasian, our CFO.

Before we begin our prepared remarks, I remind everyone that we will be making certain forward-looking statements. These statements are based on our current expectations and beliefs. We encourage you to review the slide in the presentation and in our SEC filings, which include risks and uncertainties that could cause actual results to differ from today's forward-looking statements.

With that, I will now turn the call over to Helen.

Thank you, Steve. I would like to extend a warm welcome to all those joining us for our update call today. In the short time since the early and full approval of PAPZIMEOS in August, the standard of care first-line treatment for adult RRP, we are seeing a tremendous progress with the first-ever therapeutic commercial launch in RRP.

These substantial advancements constitute a pivotal milestone for all the stakeholders impacted by RRP, including patients, their families, health care providers and the RRP Foundation.

As we commenced commercial sales in Q4, Precigen has completed the transformation from an R&D company to a product revenue-generating commercial biotech company. Phil will detail the specifics of the launch progress later in the call, but I wanted to highlight the accelerating trajectory we are seeing in the revenue growth. We do not plan to provide revenue guidance on a regular basis. But instead, focus on indicators, we believe are important for gating progress of the launch trajectory from a long-term perspective. That said, as we are only a few days away from completion of Q1, which is the first full quarter of PAPZIMEOS' commercial sales. We think it is helpful to provide investors with color on the PAPZIMEOS sales ramp-up.

As reported in our 10-K, net product revenue for Q4 2025 was $3.4 million, with shipments commencing in November. As prescribers at major medical centers and community practices continue to add PAPZIMEOS to their practice, we are seeing a strong momentum in Q1.

As a result, based on the commercial activity to date, we expect revenues in Q1 to exceed $18 million. This is a clear sign of the enthusiasm we are seeing from patients and physicians alike, leading to a robust uptake in the therapy.

I will now provide a brief recap on the reasons we believe we are seeing such a strong interest in PAPZIMEOS. PAPZIMEOS received full FDA approval with a broad label for adult RRP with no restriction based on the number of prior surgeries. This reflects the truly transformative clinical data, including unmatched efficacy, a strong and durable ongoing responses and a pivotal study powered by prospectively defined primary endpoint of complete response rate. Thanks to its mechanism of action, PAPZIMEOS also offers the potential for redosing, if needed, which is being evaluated in the clinic now.

With the full approval powered by unmatched efficacy, we have significantly raised the bar for any future competitor entering the adult RRP space. Let's examine the key facts which led to FDA's approval. PAPZIMEOS directly addresses the root cause of RRP by eliciting a targeted immune response against HPV 6 and/or 11. To be clear, we enrolled and treated more severe RRP patients and achieved an unmatched complete response rate with an impressive durability of responses with more than 3 years of follow-up, which is echoed and appreciated by physicians in the field.

It not only surpassed the highest statistical bar using the most rigorous efficacy endpoint ever evaluated in RRP, but produced the strongest data demonstrated in the field to date. Given the underlying cause of RRP, these results readily extrapolate to less severe patients as reflected in the FDA's broad label approval for PAPZIMEOS. In contrast, extrapolating results from a less severe population to a more severe cases is far more challenging and less reliable.

What I just detailed has been supported by landmark expert consensus paper sponsored by the RRP Foundation and authored by 16 leading U.S. physicians specializing in RRP published in laryngoscope, a top peer-reviewed journal in the field. The paper recommends PAPZIMEOS as the first immunotherapy, which is the newest standard of care and preferred first-line treatment for adults with recurrent respiratory papillomatosis, or RRP. These developments represents a pivotal advancement for the RRP community, prioritizing medical therapy over repeated surgical interventions to improve patients' outcome. I will now turn the call over to Phil for details around our commercial launch. Phil?

Thank you, Helen, and hello, everyone. I'm delighted to share the most recent highlights of our launch efforts with comments on Q4 results, but also bringing everyone up to speed on the exciting progress we are making with the PAPZIMEOS launch in Q1 of this year. As mentioned earlier, we made great progress in Q4 in setting the platform for accelerated brand uptake. This included continued progress in expanding payer coverage, further activation of accounts across the country and the initial prescriptions for PAPZIMEOS.

As we speak today, I can give you more granularity on some of the leading indicators of strong launch performance. Hub patient numbers continue to grow. As of JPMorgan in mid-January, we had over 200 patients in the Precigen patient support hub. As of today, that number is well over 300 indicative of the pent-up demand for the new standard of care for adults with RRP.

Payer coverage continues to expand. In early January, we had approximately 170 million lives covered, which has now increased to approximately 215 million, including nearly all major payers across commercial, Medicare and Medicaid. Including regular Medicare and Medicaid fee-for-service lives means that we now have approximately 90% of insured lives covered in the U.S., which is phenomenal progress for a rare disease drug like PAPZIMEOS. Brand utilization is accelerating across the country in both the large institutions and academic centers as well as in the community setting.

Pleasingly, we are seeing utilization across a range of patient severities, which speaks to the broad label of the brand. And finally, as Helen mentioned, the publication in January of the expert consensus paper clearly positioning PAPZIMEOS as the first choice for adult patients with RRP is a significant statement of intent from the KOL community and a testament to the strong efficacy and safety profile of the drug.

The significant increase in revenues anticipated in Q1 that Helen mentioned clearly shows how the health care system is embracing the first and only approved medicine to treat adult RRP. We are very pleased with the momentum we are seeing, and we'll, of course, provide final revenue numbers during our Q1 earnings call later next quarter.

In terms of outlook, we expect these trends to continue, assisted by the assignment of the permanent J-code from April 1 and supported by the continued durability of response that we are seeing in patients. We expect continued institutional activation as well as significant utilization within community practices.

We look forward to sharing further progress with you at the Q1 call as we continue to drive this fundamental transition of a debilitating condition that has been surgically managed for over 100 years into one that is now therapeutically managed. I'll now turn the call over to Harry for an overview of our financials. Harry?

Thanks, Phil. We sure are exciting times for both Precigen and the RRP community as a whole. I want to spend a couple of minutes discussing our results for the year ended December 31, 2025, and our financial position as of that date.

Revenue for the year totaled $9.7 million versus [ $3.9 ] million in 2024, resulting in an increase of $5.8 million or 149%. This increase was primarily driven by the commencement of PAPZIMEOS product revenue, which totaled $3.4 million in 2025. It should be noted that the first sale of PAPZIMEOS was recorded in November of 2025. Thus, revenue for the year only reflects a partial first quarter of the PAPZIMEOS launch. While speaking of revenue, I do want to reiterate that the first quarter of 2026 is showing a tremendous ramp of PAPZIMEOS revenue from the fourth quarter of 2025.

As Helen mentioned, based on our commercial activity to date, we expect revenue for Q1 of 2026 will exceed $18 million. We're thrilled with the early launch results and encouraged by the launch trajectory. I also want to repeat that we do not plan on providing forward-looking revenue projections in the future.

Due to the timing of our year-end earnings call being close to the first quarter end, which provides us an understanding of where we believe first quarter revenue is trending, we feel we can provide this guidance as a help to our investors' understanding of the PAPZIMEOS launch trajectory.

Continuing with expenses on our statement of operations, research and development expenses decreased by $11.7 million, or 22.1% and compared to the year ended December 31, 2024. The decrease was primarily driven by a $9.4 million reduction in costs as a result of the strategic prioritization of the company's pipeline announced in 2024.

In addition, the company, upon FDA approval of PAPZIMEOS, began classifying manufacturing-related costs to inventory which ultimately will be recorded as cost of products and services when the related inventory is sold. Manufacturing costs related to PAPZIMEOS were recorded as research and development expenses prior to the FDA approval of PAPZIMEOS. Selling, general and administrative expenses increased by $28.8 million, or 69.8% compared to the year ended December 31, 2024. This increase was primarily due to a $27.3 million increase in costs incurred related to PAPZIMEOS' commercial activities. Our net loss attributable to common shareholders was $429.6 million, or $1.37 per share for the year ended December 31, 2025.

These results include two large noncash items related to our preferred stock and related warrants in 2025. In 2025, the preferred stock was converted to common shares and the warrants were reclassified to equity, thus such items will not recur in the future. These noncash items totaled $318.5 million or $1.02 per share of the $1.37 loss per share reported.

Turning to the balance sheet. We ended the year with $100.4 million of cash, cash equivalents and investments. Based on our current projected business plans, we believe that these funds plus anticipated cash to be received from PAPZIMEOS sales will fund operations through cash flow breakeven, which we currently expect to occur by the end of 2026.

For more information on our financial statements, I refer you to today's press release and our 10-K, which were filed with the SEC after market close this afternoon.

With that, I'd like to turn it back to Dr. Sabzevari.

Thank you, Harry. I wanted to briefly provide other portfolio updates. We are actively advancing plans to commence a PAPZIMEOS clinical trial in pediatric RRP population. We hope to have this initiated in the fourth quarter of this year. Additionally, we have begun efforts for geographic expansion. This is seen with the validation of the marketing authorization application to the EMA for PAPZIMEOS. Of note, we are seeing positive feedback from top leaders in Europe on the prospect of a new medical standard of care.

To that end, we are also pleased to announce that we will be sponsoring activities around the third annual RRP Awareness Day in June. This will present another opportunity to help spread global awareness of this disease and the new standard of care for its treatment.

Other than PAPZIMEOS, we continue to advance the platform with PRGN-2009. This program utilizes the same AdenoVerse technology as PAPZIMEOS. PRGN-2009 is designed to activate the immune system to recognize and target HPV16 and 18, the root cause of HPV-associated cancers, such as head and neck and cervical cancers that represent almost 5% of all global cancer patients.

PRGN-2009 is currently being investigated in combination with pembro in multiple Phase II clinical trials in head and neck and cervical cancer. I'm very excited about the prospect of this program and look forward to updating you in our upcoming Qs.

With that, I will now turn the call over to the operator for Q&A. Operator?

[Operator Instructions] Your first question comes from Jason Butler of Citizens Bank.

Congrats on the progress. And specifically, really, thanks for giving the 1Q guidance. That's really helpful. Two questions for me. First, can you help us think about how you guys are planning the flow of patients from the hub to receiving reimbursed drug? Do you expect the majority of the 300 patients to ultimately get reimbursed treatment? And in what kind of time frame, understanding it's still early in the launch? And then second question, are you now at the point where patients are starting to get their second dose in the treatment regimen? Then can you give us any color about like the proportion of patients that are eligible or are getting the second treatment?

Jason, thank you for the questions. And definitely, I think for the first question, I'm going to defer it to Phil. Phil, maybe you can go through that.

Yes. Well, obviously. Jason, we're obviously very pleased about the continued recruitment of patients into our hub. And just a reminder that, that isn't a complete picture because we are seeing significant conversion of patients from our hub, but we're also seeing utilization from patients that are not in our hub, as we've talked about previously, that's not the complete picture, the Precigen support hub. So we're pleased that we're seeing patients being treated from both sources. In terms of that conversion speed, we -- clearly, the patients that are in our hub, that is a clear intent from the market that those patients are in need of treatment, and we want to make sure that the vast majority, if not all of those patients are converted on to treatment. That is obviously our goal.

In terms of the speed at which that is being, that will happen and the patients will be converted. It really will vary by patient by patient and institution by institution. What we've done in the fourth quarter and continue to do in the first quarter is get all the pieces of the puzzle in place, in particular, the payer coverage and obviously, the identification of patients.

Now it's really up to the IDNs to continue to be activated. And once you have all of those things in place, the actual prior authorization with the payer should only take a matter of weeks. But really, it's about the activation of the IDNs and that is, for some patients, the rate-limiting step, but we've made great progress throughout Q4 and into Q1 in terms of converting those patients.

And Jason, maybe I can add further to what Phil mentioned. Our hub, clearly, the patients keep coming in, and you're absolutely correct that they are converted, but this is a continuous process for the hub. It is not a onetime thing that the patient comes as patients get basically prepped and treated then new patients are entering to our hub, but it's very important to stress what Phil mentioned that our hub is not the only source for the patients, there are a number of other hubs that, for instance, large centers, they have their own hubs. And they can be entering, and we have seen that for the enrollment.

In regard to the second question that you had as far as have the patient moved from the first treatment to second, absolutely. The patients are moving through all their treatments and some of them that have started last year, for instance, they have moved through their last treatment. So this is, as I mentioned, is a very fluid momentum in the hub that patients enter. They get prepped and Phil can speak further to that. And as they go through their treatment, other patients walk-in.

I was just going to make another point about the hub because obviously, we mentioned that we will have the permanent J-code as of April 1. And that will streamline and smooth the whole process by which patients pass through from our hub benefit verification institutional readiness, and then prior authorization with the payers. So that's going to be a help as we go into Q2.

Your next question comes from Swayampakula Ramakanth of H.C. Wainwright.

It's great to notice that not only the launch is going well, but certainly this year -- this year or this quarter, it has ramped up quite a bit. Having said that, I'm just trying to understand a little bit more of the nuances, especially with the flow of patients through the hub into the conversion. And also, how is the J-code, how is that helping out in terms of adding more patients not only in this quarter, but also getting them up for the next quarter. I would think that it takes a certain amount of time between the patient coming into the clinic, and then getting the therapy.

RK, thanks for the question. So it's Phil here. The J-code really does simplify the workflow and billing process from both a provider perspective and a payer perspective. We are aware, looking at some analogs of rare disease launches that some payers have been hesitant to take on the financial risk and that, of course, with our experience. But now with the permanent J-code, that sort of disappears and it's a streamlining of the administrative process and it increases certainty and, of course, speed at which these patients should be processed.

Yes. And maybe I can add that, RK, this is not specific to PAPZIMEOS. This is for any drug that is out there, including all the checkpoint inhibitors. There is always that transition and it would be the streamlining and making it easier on some of the centers to do that. And I think this is the trajectory that we see, which we are extremely excited to go from Q4 to Q1, exceeding, as we have said, $18 million, it's very important in the preparation that the team did at the early onset of approval after approval and really appreciating the number of the payers that the team got in the first -- in the beginning of the fourth quarter, because as we all know, for patients entering to the hub and even in the other hubs, the reality of the situation stands with the payers and making sure that all of the elements for getting treated, is there and big part of that was the payer's approval.

And now with more than 200 million lives covered, which is an amazing amount. This is why you are seeing the trajectory of very fast acceleration from the Q4 to Q1 going from where we were in Q4 to excess of $18 million in Q1. And I think this is quite exciting, and we're having now all of the components of the commercialization in place the payers, the hubs, the institute coming in. And finally, the J code, this just makes it for the next trajectory as we move to the Q1, Q2 and Q3 and Q4.

Perfect. No, I certainly sense the excitement and what you're experiencing. Thinking about the MAA and also the European -- potentially European launch. In terms of your discussions with the regulatory body there, where are things now? And do you expect the approval in the first half of '27? Or should we assume it is going to be later? And also in terms of the launch. So should we send a fill back to Europe and get that launch going over there?

Yes. So as you know, we had submitted our EMA application as we shared with the market last year. And it has been -- the application is under review. So we are excited about that. And I think from -- for instance, what we are receiving from physicians across Europe. And we just had a presentation at UroGen, which is one of the major conferences in the field of HPV and especially on RRP, there has been a tremendous enthusiasm from the physicians really looking forward to having this first line and a standard of care therapy, which is now a U.S. also to be applied in Europe. So we are looking forward, obviously, as the BLA undergoing review in Europe, and we obviously will not -- it will be, I think, your assumption around the time. It perhaps is a good guess, but we will leave it to the European authorities when they have a decision and they communicate, we will definitely share with market. So we look forward to that as well.

Your next question comes from Brian Cheng of JPMorgan.

Just a couple from us. Can you clarify on the $18 million revenue guidance here? Is the $18 million guidance inclusive of collaboration and service revenues, in addition of PAPZIMEOS product revenue? Or is the $18 million only referring to PAPZIMEOS' product revenue?

Brian, this is Harry. Good to talk to you. Yes, that $18 million, which you said, we expect revenue to exceed includes all the PAPZIMEOS. No other revenue.

Okay. And can you talk about the $18 million projection? Is there a stocking effect that accounts into the projection compared to patients that have received PAPZIMEOS. And then maybe just on top of that, can you talk about the number of doctors that are now actively prescribing PAPZIMEOS? And how effective is the conversion rate from your patient hub compared to the academic hub?

Yes. Thanks, Brian. In terms of the stocking, so there's very little stocking that we see. We do see a range of orders in terms of the vials that order. Remember, each institution can order 1 vial at a time or they can do all 4 vials at a time. We do see some 4s and 2s, but predominantly, it is 1s, but we do see a mix. So -- but very little stocking as such from the institutions.

In terms of the number of doctors, I mean, obviously, the number of prescribers is increasing, and we've -- for all the reasons that we've talked about, and we see that increasing momentum as we hit in Q1, we've obviously still got more work to do and more prescribers to bring on board, but we're very excited by the response that we're getting from the institutions and the prescribers, and that number is increasing consistently.

Yes. And maybe what I can add, Brian, to this is, clearly, the consensus paper, it really has now make it very clear that PAPZIMEOS is the first and only a standard of care for RRP and for all adult RRP, which is actually very interesting because we see the enrollment of the patients or treatment of the patients across the severity of the disease. And this is another important point that we have said according to the label that was given to PAPZIMEOS, which is for broad RRP patients regardless of severity, and that's exactly what we are seeing as far as the treatment is concerned and how the physicians are taking up this treatment.

Brian, just to your question on hub versus nonhub. I mean what I would say there is that we're seeing conversion from both sides and patients that are in our hub, but patients who are not in our hub, and we're seeing a significant contribution from both.

Your next question comes from Michael DiFiore of Evercore.

And congrats on the obvious product progress you've had in the launch. Two questions for me. You called out community uptake as a pleasant surprise. Like I know it's early, but as the community channel develops, what have you learned about what differentiates the community sites that become repeat prescribers versus those that adopt more of a wait-and-see approach? And I have a follow-up.

Yes. Thanks, Michael. It's Phil here. Look, we always had community in our sites. That was an obvious part of our strategy. I think what we saw when we were soon out of the blocks after the approval was the extreme interest from the community in utilizing PAPZIMEOS. And we've got various mechanisms in place so that we can, for a low cost, provide them all the logistics they need to use and uptake the drug. So we actually think the community is going to be a significant contributor to our overall business as we go forward for those reasons. And the initial experience is very positive.

And I can add -- this is Rutul, Mike, I can add to it, as Phil pointed out, we have done is, in addition to our end-to-end cold chain validated logistics in place, as Phil pointed out, we have multiple solutions now available for community practices who may not have cold-chain storage to acquire them at a very low cost as well as just in time shipments to essentially completely avoid need for the cold storage. So that is also aiding in our efforts to get them on board and continue to prescribe PAPZIMEOS.

I see. Very helpful. And my last questions are, if there's any color you could add on the current channel mix of U.S. payers and how we should think about gross to net cadence for the balance of the year?

Yes, I'll let Harry talk to gross to net. In terms of the payer mix, it's pretty much as we expected, and we communicated prior to launch, which was about 60% to 65% commercial, and that is indeed what we're saying, and then the rest, Medicare, Medicaid and on the government channel. So yes, 65% or so is commercial.

Mike, this is Harry. On the gross to net, we've historically guided, and we continue to guide. We anticipate the gross to net will be in the high teens, low 20s. And we've seen those play out as we've seen revenue to date.

There are no further questions at this time. I will now turn the call back over to Dr. Sabzevari. Please continue.

Thank you again for joining us for our year-end 2025 update call. As you can see, we are making tremendous progress on the PAPZIMEOS commercial launch. We are looking forward to providing the full Q1 results and detailed commercial progress in May. Have a good evening.

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.

Good morning, everyone. Thanks for joining us for another session at the 44 JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analyst at the firm. On stage, we have Precigen Therapeutics, I'll now pass the mic to them for a short presentation followed by a live audience Q&A. Helen, the stage is yours.

Thank you very much, Brian, and thank you for the invitation to the JPMorgan meetings. And I would say good morning or afternoon to some of the audience that are on the webcast. Today, what I would like to do is take you through the advancements of our portfolio at Precigen. Obviously, I would be making some forward-looking statements. Please read that.

And first of all, I just want to introduce really for those of you who might not be familiar with Precigen and Precigen story who we are. We are a biotech company that has focused on a cell and gene therapy for various indications, including rare diseases and in oncology. We are located in Maryland. And our approach has been from the very beginning and start of a company is to really have a differentiated technology and platforms that can be applied to a specific indication with a very specific regulatory strategy. And as I take you through the basically presentation, you will see how we have done that with our first drug that has been approved last year, PAPZIMEOS in a very, very rapid manner to go from really discovery development to approval in 4 years.

So with that in mind, today, I'm going to have the focus on our main platform, which is an AdenoVerse platform. This is a viral vector platform, but it's unlike any other adenoviruses. These are actually gorilla adenoviral vectors that are nonreplicating, but the major difference, as you see on the right side of this slide is, first of all, their large payload capacity so for instance, if a regular adenovirus or other viruses, they have somewhere between 3 to 4 or 5 kb, you're looking at somewhere between 12 to 15 kb of capacity, which means you can put more epitopes, much more jeans. And this is really unique and differentiated from that perspective.

Also, what is very different in our platform for AdenoVerse platform is the ability to repeat dose. And in a regular adenoviral vectors as you all have seen is you can give 1 dose and perhaps by the second time that you go in, you have seropositivity because all of the people healthy or some of the patients they already are seropositive. They have neutralizing antibodies to these viruses because they have seen it before. The immune system has seen it, has generated neutralizing antibody and by second third time that you start injecting these viral vectors, basically, you are getting very high titers of neutralizing antibody, which inhibits their capability of activating the immune system. And as a result, it's like really shooting basically empty bullets. That's what it happens.

Not in the case of AdenoVerse platform here because and we have done extensive studies both in healthy volunteers in U.S. and also in Africa. There is -- majority of the people are either completely seronegative and the few percentage that they have is seropositivity is very, very low. And the way we have designed these vectors, which is very interesting, it pushes towards a T cell immunity and not humoral B-cell. So even upon injections of these multiple times and by that, I don't mean 2 or 3 or 4 times, we have had clinical studies in our cervical cancer and head and neck studies that we have -- patients have received over 16 injection over a period of 2 years. And you do not see those high titers, and you keep seeing the expansion of a specific and high affinity T cells. So this is very, very important for this, and we have the full IP around this platform, and we are the only company that has established this and have the IP.

And obviously, as I spoke, it pushes more toward T cell immunity than the B cell immunity, at least the designs of the vectors that are currently I'm speaking about. And a very high productive manufacturing basically process, which has been really one of the bases for us having our own manufacturing in-house and has allowed us to move very rapidly. On the left-hand side, you see the portfolio that is associated with our AdenoVerse platform. Of course, at the top is our PAPZIMEOS is a drug for a rare disease, as I will take you through the journey of it today and which we received the approval -- full approval from FDA last year and followed by exactly the same platform and the same vectors, but now addressing HPV 16 and 18, which is the cause of head and neck in the indications for cervical cancers, head and neck, anal cancers.

It's the reason that these tumors are developed, and we are in 2 phase II at this point and actually quite interesting data, some of it we have reported and some we will be reporting in the upcoming quarters and year. And it's very, very interesting. Obviously, I will talk about the platform further. So as has been our tradition, we always go to what did we -- was our goals and what did we accomplish in a prior year coming to JPMorgan and as you see on the top of the list is the full approval for PAPZIMEOS for the treatment of all adults with recurrent respiratory papillomatosis, and I will again take you through what this disease is for those of you who might not be familiar with it.

We also have commenced our commercial U.S. launch of PAPZIMEOS and we have launched the manufacturing. And currently, we are -- patients across United States are being dosed with PAPZIMEOS and this is quite exciting. And finally, we have secured up to $125 million in non-dilutive findings to fortify our balance sheet. So quite an exciting year for us, definitely a paradigm shifting for a company as we have moved now from an R&D company to a commercial company with a first FDA-approved drug in the history of this drug, which is over 100 years for RRP.

So what is RRP? And very shortly explain recurrent respiratory papillomatosis, is caused by the infection of HPV 6 and 11. And this can happen in children or adults and that's the root cause of formation of these benign tumors, which takes place on either the vocal cords or in trachea. It's quite a devastating disease because the patients, they can't speak or the picture that you see in the center, this is through the trachea that you're looking at or they can breathe the only treatment that was available. And this is not because other treatments have not been tried in this indication, but the only thing that works is continuous strategy until before the approval of PAPZIMEOS. So you can imagine that how devastating this is for if you have it from childhood or in the cases of adult.

So just to give you a little bit of perspective because at the beginning, I said what is the vision of our Precigen and how we are advancing ourselves. This is really a snapshot of what we did, Precigen was basically initiated in 2020 so 5 years. And what we did in 2021, we cleared the basically IND Phase I and we finished the Phase I in the middle of pandemic and started our single-arm Phase II and of course, the discussions with the FDA at that time. And by 2023, you see that we basically FDA granted accelerated path 2024, we at ASCO, we presented the data, a pivotal data from our Phase I and Phase II and by actually in August of 2025 despite of the fact that we were on an accelerated path for a conditional approval based on the safety, efficacy and durability of the response, which I will take you through in a very short slide. FDA decided that there is no need for further trials, and we were granted actually a full approval in advance of our PDUFA day, which we were very pleasantly happy with this news.

And as you can imagine, our commercial team start hitting the ground running in September of 2025. So first and only FDA-approved therapy, this is what PAPZIMEOS is. And that means a lot for the patients and also for the physicians that, by the way, they do not like using surgery because they know that surgery is not a treatment for these patients. This has been the only way that they could have kept the patients from actually tremendous difficulties and even death because if they can't breathe, obviously, we know what the outcome is. So first and only FDA-approved for a disease that I mentioned is chronically challenging and debilitating rare disease. And we have shown a really transformative clinical data, which I will take you through. And this has been the basis for the FDA decision.

And finally, we have been able to use this platform. This is really the, I think it showcased the ability of AdenoVerse platform. And for those of you who have heard Commissioner yesterday, Dr. McCurry. Actually, 1 of the strategic ways of FDA moving forward is really the platform approvals now when a platform works across a certain indication and how it can be rapidly moving for other indications. So we are very excited about this for our portfolio. So let's look at a little bit about the pivotal data, again, for those of you who might have not seen it and the mechanism of action. PAPZIMEOS is really a drug that is given just subcutaneously, very simple injection, and it doesn't require any device. It doesn't require any kind of special challenges simply like the way you receive flu vaccine, you get it in the either arm or in the leg, very easy administration. However, quite a sophisticated mechanism of action, what it basically does, it contains a number of epitopes and it will basically sort of educate your immune system to find the infected cells or the cells that is the cause of these benign tumors and destroy them simply. That's the mechanism through the high affinity T cells.

So with that, this is the pivotal data from our clinical trials. On the left-hand side, you see the response of our patients. We went to the most severe patient population actually, and this was designed by purpose because if you can make the drug work in that setting, obviously coming to the less severe patient population. It's well accepted. And that's what you see. We have patients in here that they had 10, for instance, surgeries in a prior year. And then by receiving 4 injection of PAPZIMEOS in a span of 3 months subcutaneously, they went to 0. They are looking at the complete responders. And first, when we started was the minimum of 12 months. But what you see on the right-hand side, these patients now have been followed for years. And in the last actually news that we had out was we have followed these patients. Now they have passed median of 3 years, and they have not required any surgery or any other treatment for that matter. So this is quite exciting.

And by the way, they are continuing to be in the response. And another group of the, what we refer to as partial responders, they also responded by reducing their number of surgeries, but they clearly didn't go to 0, which gives the ability for us to redose these patients, especially in view of the safety of this drug that basically, when you receive it, it's a grade 1 or maybe a grade 2, which is equivalent to when you get a flu shot, a little bit of fever, a little bit of rash on the arm and then it goes away in a few days. So this is quite exciting, and this is the data that FDA has seen and the safety data and has allowed to move from a single arm pivotal to full approval. So PAPZIMEOS, the commercial opportunity, and we will take questions afterwards.

The 27,000 patients in U.S. excess of 150, and we have done these studies now also in Europe. There are 4 countries in Europe plus the U.K. and Japan, we will be in excess of 35,000 patients, 50,000 patients in other territories. And clearly, in China, a very high population excess of 85,000. So quite a large patient populations that -- and this is adult in these cases. One of the things that there is a lot of discussion about the biotechs and how ready they are to commercialize. And the indication for the commercialization to support a successful launch is, first of all, you have to know your market size before you obviously launch your commercial teams out.

And we had done that prior to approval, 27,000 patients in the U.S. You have to optimize your footprint knowing where these patients are located. So you don't have to deploy 300, 400 salesperson all across in the territories that they might not be that many patients. We had done those studies prior to the approval and had a very, very good understanding of the territories and also discussions with the payers to be able to establish a price that is going to be accepted by payers.

Obviously, build awareness both patient education as well as physician education besides just KOLs that they are out there, and we did that prior to our launch and approval and finally set up a distribution important. You can do all of that, but if you don't have your commercial material and you don't have your supply chain and distribution, obviously, that is a recipe for failure, and we were not going to do that. So with that in mind, after we receive our approval in August of 2025, we exactly executed against all of that. And we went to a full mode of commercialization, full promotional campaign, and Phil will talk about this with me. We have now more than 96% of our target centers has been covered in the past 3 months. This is incredible speed by anybody's count.

As far as formulary and IDN and community support, we have more than 50 accounts here and that they have been prepared and ready, and they have been also prescribing PAPZIMEOS. The payer pull through, this is very important because this is a rare drug disease with, obviously, a different pricing. And we have already got coverage through Medicare, Medicaid. We have covered more than 170 million lives through big and small, basically private health insurances. And we will discuss this. This is almost close to 80% of the coverage for these patients.

And finally, the patient support hub. And I just want to stress this is the hub just for our company that we have set up. In November, they were already more than 100 patients there and we just reported in a matter of 1.5 months it's more than 200 patients in this hub. This hub does not represent all the patients because the centers of excellence they have their own hubs that they enter the patient. So as you can see, this is just a fraction of the patients that are coming in, and this is directly to the Precigen hub. And just to give you a view that a significant increase in PAPZIMEOS brand awareness since approval, we went from 7% to 66% in a matter of 3 months and in the community centers, again, from 6% to 58%. This is a huge increase, and it shows the interest of the patients and the physicians in this drug because this is the one and only FDA-approved drug for this rare disease.

And looking ahead, what is in front for us is, obviously, we are laser focused on the commercialization of PAPZIMEOS in the U.S. This is what our commercial team is out and continuously, we are focusing to expand that. And we are very, very excited with the reception that this drug has had among the patients and physicians. And by the way, this drug, the FDA has given a very broad label for PAPZIMEOS that all RRP patients regardless of severity can receive this. So if an RRP patient is just recently diagnosed, they can receive this drug. And if the RRP patient has been dealing with this disease for 10, 20, 30 years and we had patients that they had this disease from age of 1, if you can imagine, excess of 300 surgeries, they will receive it as well. And this is extremely important because this drug is not just for severe patient population. It's for any adult RRP patient with diagnosis.

And I would like to add 1 other point. Why is this important? The studies that has come out have very clearly shown these patients, by the time they are into their fifth surgery, they have irreversible damage to their vocal cords and to their trachea. And actually, over the years, a good 1/3 of these patients actually might have to go through tracheotomy. So that's why the patients want to receive this, the physicians want to prescribe it because they know what the end result is. One more surgery is 1 more damage to these patients an irreversible damage. The regulatory expansion of PAPZIMEOS is very important for us.

And as we have communicated already last year, we submitted our application to EMA. We received actually acceptance validation of that and it currently is under review for EU and in EMA. We are planning to submit to Japan very rapidly, and we have had very, very constructive discussions with Japan FDA and very exciting ones. And we are initiating our PAPZIMEOS pediatric because this is a drug that based on the safety, efficacy and durability of response, it fits perfectly for children, and we do not want to be leaving children behind.

Again, we heard from the FDA Commissioner how important it is to make sure that there are more drugs for pediatric population. And finally, as I mentioned at the beginning, this is the proof of the platform for AdenoVerse. And we are very excited about what we are seeing in our 2 Phase II data that will be reported in the future, both in cervical cancer and in head and neck because we are applying the exact same actually vector with the same safety with the same profile and in HPV-related cancers. So we are very excited with that and also from a perspective of regulatory strategy that we are moving with that.

And finally, I'm going to finish by simply addressing we have a very -- Precigen has a very strong foundation for long-term value creation. PAPZIMEOS for us is our first, and we are very excited about a commercial drug but it will not be the only one. And on our AdenoVerse platform, as I mentioned, we have 2 others that are in Phase II and rapidly moving with this. So clearly, we have a technology that is differentiated. We have a commercial asset that is quite exciting and it's out there. We are also expanding our territory to ex U.S., and we have derisked the technology platform and clearly, a very, very solid leadership team that, as I showed you, from our start or initiation of Precigen in 2020 despite of all the challenges in -- with pandemic we have gone from a discovery drug development in 4 years to approval. So this speaks to the expertise on every level of the company, research, development, manufacturing, and we have it inside manufacturing as well as commercial. So we are very excited about that.

So on that, obviously, we also have established a very strong balance sheet that clearly, it allows us a runway that with the revenues of PAPZIMEOS to get us through the cash flow positiveness. So with that, I would like to thank all the audience and Brian and we'll be happy to take questions. And I invite our Chief Commercial Officer, to come with me also so we can answer any questions that audience might have and Brian. Thank you.

Well, thank you so much for joining us. Let's start the Q&A. [Operator Instructions] How has the PAPZIMEOS launch been going so far? And are there any surprises from your vantage point today?

Okay. So I think I will let Phil answer that.

I will answer that. I mean we're very pleased with the launches. You saw some of the leading indicators in terms of patient identification, site activation, I think the surprises that we've had have been positive ones been nice surprises. A couple I would call out is, one is the speed of payer uptake. That number of 170 million -- approximately 170 million covered lives, plus Medicare plus Medicaid, and that's a significant portion of the target market already covered within 1.5 quarters of the full launch. So we're thrilled with that. The second pleasant surprise has been community interest. A lot of those patients that Helen talked about in the hub are actually from the community. So not only the academic institutions, the large hospital systems or IDNs, but the community and that has been very pleasing from a market perspective in terms of embracing this as the new standard of care.

On 1 of your slides, you said that more than 50 accounts have prescribed PAPZIMEOS. Can you tell us if these 50 accounts are -- are these numbers reflective of the commercial products, meaning that this is revenue generating and they should reflect in your fourth quarter number?

So the prescription means that those patients have been selected by the institution to go into the process by which they have benefit verification and ultimate payer adjudication so there's a transmission mechanism from prescription to revenue realization. We'll talk more about some of that at the next earnings call, we won't be talking about specific numbers of patients or revenue projections. But that is the first step in getting these patients on to treatment.

Yes. And maybe I can add. What is very important and I think should be recognized that if you can imagine that our commercial teams basically will receive this approval in August of 2025. And then there is a process, especially for bringing in the centers of excellence because all of them, they have their committees, approvals that especially for a drug that has -- and there is no precedence for it. And then formulary, committees that has to go. So obviously, the team has done an outstanding job in the Q3, Q4, covering all of that and very rapidly bringing this, which will be leading to -- sorry, Q1, Q2 and really the increase in the prescription and as well as the -- we already have seen enrollment of the patients and the patients have been dosed across the nation from East Coast to West Coast, and we are very happy that also that speaks to our supply chain and manufacturing capabilities.

Brian, the thing I would add is just to remind everyone that we have fundamentally transitioning, transforming this therapy this condition from what was a surgically managed condition to a medically managed condition. I mean that's a deep systemic change that has to impact all facets of the health care system. So we don't take that lightly. But as you can see, the early signs and the momentum that we've created is very pleasing, and I think consistent with the establishment of a new standard of care in the therapy area.

With the unrestricted label, how should we think about just the receptivity of usage among the milder versus the more severe subset of the population?

Yes. I mean, I'll say a couple of things, and then maybe, Helen, we've got clear signals. Helen showed the increase in awareness, which comes from our quarterly ATU research. We do that every quarter to understand how sentiment trial utilization is happening in our target audits. There's a clear indication from those doctors in the community and in the academic institutions to use the drug across all severities. I don't think we should be surprised at some of the earlier patients of maybe more severe. That's where the highest unmet need is. And we see that in many drug launches across many therapy areas, but we fully expect as we go forward that we will see utilization across all severity.

And maybe I can add, this is what we are hearing from our patients. As I mentioned, the study that came out, I believe it was either a 1.5 years ago maybe from John Hopkins. It pointed out to the patients that by their fifth surgery, as I mentioned, they have irreversible damages. And therefore, patients are very educated about their disease. And what we are hearing is really the need to receive these as early as possible. So they do not even need to have 1 extra surgery at this point. And I think this is very, very important. And the physicians and the surgeons, we have to say. They agree with that because the surgeons in general, this is not the type of the surgery that they like to do because they know the outcome what it is, which means another surgery and further damage to these patients.

Any questions from the audience? So just going back to your comment earlier, related to committee approval and formulary. Can you talk about just the process, the steps involved in terms of getting patients on drug. So if a patient gets a prescription for PAPZIMEOS, what happens after? And I guess, what are the steps involved? And also how long does it take for patients to get the first dose of PAPZIMEOS.

Yes, there's no single answer in terms of how long it takes. It's very specific to each patient actually in each institution. But certain things have to come together. Obviously, the patient has to be identified, and we've seen that already from the numbers that Helen mentioned. That then starts the process of benefit verification to make sure that the patient is supported from a benefits perspective. They have -- you have to interact with their health plan. The payer has to then sign off on the coverage. And of course, the institution has to be ready from a formulary perspective to be able to administer the drug, although actually, in advance of some of these formularies being set, and we are seeing a lot of formularies already come on from these big institutions. But even in those that haven't had their formularies approved yet, we are seeing use through a medical exception process. So there's a number of steps that have to come together.

I wouldn't put a time line on that. In some cases, it's relatively quick and others, it can take a bit longer. But the most important thing from our perspective is that signal of intent, which is represented by the patients in our hub, but also the patients that we know are going through the IDNs are not necessarily in our hub. And some of the early patients that have been treated have actually not come from our hub. So there's sort of 2 parallel paths of patient demand that we're working through at the moment.

And maybe if I can just add this. The most important thing was getting the coverage by the payers, imagining that in 3, 4 months to cover almost 80% and 170 million lives and even Medicare and Medicaid through the government shutdown. This speaks again to payers having been educated about what is the need and the power of this drug and then also having these approvals from the all large and small payers and insurance companies it really has helped the patient uptake.

And in fact, in a few cases, we've had a payer that hasn't issued its formal policy yet approve the drug through a medical exception process when they've had peer-to-peer discussions with the treating physician, which again, I think speaks to the high unmet need and the value that we are delivering to the treatment of the condition.

Great. Can you talk about just your current financial outlook towards cash flow breakeven. What are the assumptions that go into the projection that you will get there? How do you think about the projection of also revenue accumulation over time from PAPZIMEOS?

Okay. So as we have mentioned, the guidance that we have given with the cash that we have at hand, and we raised actually last summer, which -- without dilution to our shareholders. This will put us in place with the revenues that will be coming. Currently, we are not giving any guidance on -- from a perspective. But we have said and continue saying that this will bring us to the cash flow positive in by the end of this year. And we will be obviously communicating further as we go along.

But Brian, to your point about '26, '27 outlook, I mean, -- we've obviously looked at analogs. We looked at rare disease uptake. We've looked at the situation that we are the first and only treatment for this condition. So we expect our trajectory to be consistent with that -- the philosophy of establishing a new standard of care in this therapy area.

Okay. What will be a fair comp, just kind of latching on your last comment, what will be a fair comp just to understand how the trajectory will look like?

So I think from a trajectory, we -- obviously, we are expecting a Q1, Q2 and we are increasing in our patients uptake, and we will be -- that is what we have accounted for. And I think with -- we are very pleased with what we are seeing, again, through the patient coming in not only to our hubs, but to the others and also from our physicians that across the United States have been reaching out and going back to this concept of community, which was a very pleasant surprise because we originally thought all our majority will be through the actually centers of excellence, and we are finding that, that is not the case. Actually, this is a huge boost, and we are very excited about that, that the community basically physicians are very, very advanced in knowing what this drug is all about and wanting to prescribe it to their local patients.

Great. And maybe just in a minute we have left, how do you think about just the ex U.S. opportunities, how do we think about partnership potential as well?

Absolutely. As we mentioned, we have already submitted our application and is validated for EU and we are planning for Japan submission as well soon. This is obviously very important ex U.S. But definitely, we are also very much interested in looking at partnership for ex U.S. as our focus is currently and laser focus is on U.S., and we are evaluating various options from that perspective as hopefully, we receive the approvals around the world.

And in the meantime, we do a lot of the work, the groundwork, obviously, on pricing market research, understanding sequence of countries and all the work you need to do. We're part of the new JCA process in Europe at the moment. So we're doing all the groundwork. But as Helen said, partnership is one of the key options.

Great. Well, thank you so much for your time. Thanks for joining us.

Thank you for having us.

Good afternoon, ladies and gentlemen, and welcome to the Precigen Third Quarter 2025 Financial Results and Business Update Conference Call. [Operator Instructions] This call is being recorded on Thursday, November 13, 2025.

I would now like to turn the conference over to Steve Harasym.

Thank you, operator, and thank you to all those joining us for our third quarter 2025 update call.

Joining me today are Helen Sabzevari, our President and CEO; Phil Tennant, our Chief Commercial Officer; Rutul Shah, our Chief Operating Officer; and Harry Thomasian, our CFO.

Before we begin our prepared remarks, I remind everyone that we will be making certain forward-looking statements. These statements are based on our current expectations and beliefs. We encourage you to review the slide in this presentation and in our SEC filings, which include risks and uncertainties that could cause actual results to differ materially from today's forward-looking statements.

With that, I will now turn the call over to Helen. Helen?

Thank you, Steve, and thank you to all those joining us for our third quarterly update call.

The approval of PAPZIMEOS in August marked a monumental turning point for all those impacted by recurrent respiratory papillomatosis or RRP, patients, families, physicians and the RRP Foundation line. We would like to welcome you to the new era of RRP treatment with PAPZIMEOS poised to become the standard of care. PAPZIMEOS is the first and only available treatment for adults with RRP, and it represents the best data, and that's by a wide margin ever generated in adults with RRP.

Why is PAPZIMEOS a groundbreaking therapy? Let's look at the facts. First, PAPZIMEOS addresses underlying root cause of RRP by generating an immune response against HPV-6 and 11 infected papilloma cells. Secondly, PAPZIMEOS has demonstrated transformative clinical benefit. What do I mean by that? 51% of patients achieved complete response, requiring no surgery for 12 months post treatment with the durability shown in 15 of 18 complete responders remaining surgery-free at median duration of 3 years without any additional treatment.

Also, overall, 86% of our patients had reduction in their surgical burden after PAPZIMEOS treatment. PAPZIMEOS has a very favorable safety profile with nothing greater than grade 2 TRAs, which are similar to those of all receiving a flu vaccine, for instance. Also, the ease of administration of PAPZIMEOS, it's given as a subcutaneous administration that can be administered at any clinic or any of the physician offices.

Furthermore, PAPZIMEOS is not associated with a painful device necessary for administration. Let me be very clear here. We have treated the most severe RRP patients and demonstrated unmatched complete response rate, which has been durable with excellent safety profile.

Based on the RRP pathology, it is easy to extrapolate PAPZIMEOS results to a less severe patient population, which has been reflected in FDA's review and subsequent grant of a broad label for all adult RRP patients irrespective of severity of their disease. In contrast, it is very difficult to extrapolate the results achieved in a less severe patient population to a more severe RRP population as is the case with a competitor.

I would like to emphasize that PAPZIMEOS's pivotal study is the first and to date, the only clinical trial in RRP conducted with this robust, prospectively defined statistical primary endpoint. PAPZIMEOS clinical data not only beat the high statistical bar set for the pivotal study using the most robust clinical efficacy endpoints ever evaluated in RRP, it furthermore demonstrated the strongest data shown to date for RRP.

In summary, PAPZIMEOS was granted full approval by the FDA with a broad label of adult RRP that does not include restriction on a number of prior surgeries. This is a testament to the transformative clinical data that include unmatched efficacy and a strong ongoing durable responses from a pivotal study with a prospectively defined statistical primary efficacy endpoints of complete response rate. In addition, due to the mechanism of action of PAPZIMEOS, there is an opportunity for redosing of PAPZIMEOS.

And with full approval, we have significantly raised the bar for clinical data for any competitor to enter the adult RRP space in the future. This approval also marks a pivotal transition for Precigen, propelling the company into a commercial state. Delivering this transformative therapy to market with exceptional speed and agility is a remarkable achievement.

In the short time since approval, we have made great strides towards recognizing the robust commercial opportunity and building the strong foundation for PAPZIMEOS to be the new standard of care treatment. As always, our dialogue with the FDA continues to be very productive, including the completion of a successful post-approval meeting.

We are currently working towards initiation of PAPZIMEOS clinical trial for the pediatric RRP population. In addition, we have initiated our efforts for geographic expansion of PAPZIMEOS. With that in mind, I'm pleased to announce that we have submitted marketing authorization application with the EMA.

I will now turn the call over to our Chief Commercial Officer, Phil, to walk us through our commercial development. Phil?

Thank you, Helen, and I am delighted to share with you all today the exciting progress we are making with the launch of PAPZIMEOS. We've achieved a lot in a relatively short space of time.

As a reminder, the approval in mid-August was the trigger to bring the full sales team of 18 key account managers on who were hired, onboarded and deployed in September. In the few weeks since full team deployment, we have made great progress towards our goal of quickly establishing PAPZIMEOS as the new standard of care for adults with RRP, so let me highlight the key achievements to date.

Firstly, the drug is available and has started shipping to prescribers in the U.S. for the treatment of all adults with RRP. Our field team has now engaged with 90% of our target institutions, which cover a significant portion of the 27,000 adult patients with RRP. These engagements are focused on supporting and expediting the formulary inclusion process, and we have been very impressed by the enthusiasm of the HCPs in accelerating that process. We have already seen multiple formulary approvals nationally.

We're also working with HCPs in those institutions to enroll patients who are waiting for treatment. To that end, we have over 100 patients registered in our Precigen patient services hub, and a significantly larger number also being processed through institutions own patient services teams. In line with our expectations, there is clearly pent-up demand at these hospital systems that is now being processed for treatment with in PAPZIMEOS.

Pleasingly, it's not just the large academic sites or IDNs that are expressing an interest PAPZIMEOS. We're also making good progress with a number of community practices to expedite product uptake, including some of the super groups affiliated to ENT and oncology networks around the country.

This clearly reinforces what we heard in our market research ahead of launch, and we're now seeing in practice. There is a strong preference for PAPZIMEOS due to its efficacy, durability, safety, and the mode of administration. The drug can be shipped anywhere as well as stored and forward easily. No device needed, no training on device needed, just a simple subcutaneous injection. And as Helen said, no need for painful electroporation.

Payer coverage is advancing rapidly. As of last week, over 80 million lives are covered. and a number of other policy updates are expected to be announced in the near future. Importantly, PAPZIMEOS is also covered through Medicare and Medicaid. Suffice it to say, we're extremely pleased with this momentum, which is in line with our expectations.

Finally, we're seeing strong support from physicians, whether from a large institution or a community practice, again, reflective of the speed at which our teams have engaged with our target customers. We continue to see strong support and efficacy from the RRP Foundation. We have published important new data regarding the significant burden of RRP, both at the individual level and to the health care system, including the data released this week at the ISR meeting in Europe. These data, coupled with the impressive and evolving durability profile of PAPZIMEOS, is helping to propel us forward as we look to establish a new treatment paradigm.

In summary, we are extremely pleased with the progress being made. The market is embracing PAPZIMEOS as expected, and we also expect to further build on this momentum throughout the rest of Q4 and into Q1 2026. I look forward to continuing to share further progress across key indicators of success as we complete Q4 and move into the new year.

I will now turn the call over to our Chief Operating Officer, Rutul Shah, to give a brief update on manufacturing. Rutul?

Thank you, Phil, and good afternoon, everyone. I'm excited to share PAPZIMEOS manufacturing operations updates today.

As part of our strategic commitment to long-term value creation, we have made significant investments to have control over our cGMP manufacturing operations. We operate a dedicated in-house cGMP facility for commercial PAPZIMEOS drug substance manufacturing.

Our facility has been fully operational, had a successful pre-approval inspection by the FDA, and has been manufacturing PAPZIMEOS drug substance since prior to approval. With significant in-house expertise in the production of adenoviral vectors, we are executing on our operational plan to supply PAPZIMEOS to both current and anticipated future demand.

I'd like to take the opportunity today to briefly address the cold chain requirement of PAPZIMEOS. We have done our homework in detail regarding this topic, and our interactions indicate no impact on the adoption of PAPZIMEOS. In fact, post-COVID, the significant majority of our target IDNs and community centers are equipped to handle frozen drug products like PAPZIMEOS. We have end-to-end validated logistics in place to distribute PAPZIMEOS efficiently. And as Phil mentioned, PAPZIMEOS drug product is available on the shelf is being ordered and shipped to our customers.

With that, I would like to turn the call over to Harry, our Chief Financial Officer, for a financial update. Harry?

Thank you, Rutul, and good afternoon to those participating in this call.

Before touching on the quarter, I want to thank our long-term shareholders for providing us the support necessary through the development and ultimate approval of PAPZIMEOS. It has been less than 5 years for this drug to go from the lab to approval, and we could not have achieved this momentous feat without your support. In addition, I'd like to say that I am proud to be part of the team that has provided patients with the first and only therapy targeting the root cause of RRP.

Turning to our quarterly financial statements, specifically starting with our balance sheet. At September 30, 2025, we had $123.6 million in cash, cash equivalents, and investments following our recent drawdown of the first tranche of our credit facility which was entered into during the quarter. We expect this balance plus our projected revenues from PAPZIMEOS to fund our operations to cash breakeven, which includes continuing PAPZIMEOS launch costs and further development of our pipeline.

I want to pause and repeat this point. We expect that our cash and investment balance plus expected projected revenues from PAPZIMEOS to fund our operations to cash breakeven. We remain confident in Precigen's financial future as we continue to execute on our upcoming milestones.

Additionally, on the balance sheet, we ended the quarter with approximately $3 million in inventory, which represents the manufacturing costs that we have incurred subsequent to the approval of PAPZIMEOS. Costs incurred in manufacturing the product prior to the approval have been expensed as part of our R&D expenses. Lastly, during the quarter, all of our preferred shares were converted into common shares, providing a simplified capital structure going forward.

In regard to our statement of operations, the one item to note within our operating expenses is the increase to our SG&A costs of approximately $14 million in the quarter ended September 30, 2025, versus the same quarter in the prior period. The majority of this increase was driven by increased commercialization spending related to the PAPZIMEOS launch and to a lesser extent, additional employee-related costs, most of which is attributable to the accounting for share-based awards.

Additionally, our net loss attributable to common shareholders for the quarter ended September 30, 2025, includes 2 large accounting-related non-cash items, a change in the warrant liability, and a deemed dividend related to the conversion of our preferred shares. Those 2 items combined represent $0.95 per share of the $1.06 per share loss attributable to common shareholders. We do not expect these 2 items to recur in future periods.

For more information on our financial statements, I refer you to today's press release and our 10-Q, which was filed with the SEC after market close this afternoon. I do want to provide certain guidance relating to our gross-to-net revenue adjustment. We anticipate that this adjustment will be in the high teens to low 20%, which is consistent with peers in our industry.

Lastly, it has been quite a year at Precigen. As we prepare for the approval of PAPZIMEOS, we made a number of infrastructure investments, including the implementation of a new ERP system this past year. With these investments, we have positioned Precigen with appropriate systems, personnel, and controls to manage the various processes of a commercial company.

With that, I'd like to turn it over to the operator for Q&A. Operator?

[Operator Instructions] Your first question comes from the line of Jason Butler from Citizens.

Congrats on the launch. Wondering if you can give us any color on whether any patients have received reimbursement approvals yet, or whether any patients have been dosed with the first dose of PAPZIMEOS? And then a follow-up is, how should we think about the cadence of the pull-through from patients that are now registered in the hub to getting a reimbursed drug?

Thank you, Jason. And I think for the first question, I would refer to our Chief Commercial Officer, Phil. Phil?

Sure. Jason. Yes, Phil here. So, as we mentioned, we started shipping PAPZIMEOS to institutions basically for patients who are being scheduled for treatment as we speak. And as I mentioned, we've got payer coverage coming through thick and fast. So those two things are coming together.

And we're not going to go into details about specific patients being dosed at the moment. But I think in Q4, we'll see that come through and we'll be -- when we report our Q4 earnings, we'll be able to talk specifically to numbers of patients dosed and, of course, the earnings and the revenues that go along with that.

The second question regarding patients in the hub. Again, those -- they're sitting there now ready for benefit verification and prior authorization. So -- and we're also seeing a whole load of those patients who are not necessarily in our hub but are going through the institution's own patient services systems.

So that pull-through will be institution by institution, but we expect that to be starting to pick up the pace as we go through Q4 as these processes come together, both on the institution side and the payer side. But we're very pleased with the number of patients that we're seeing coming into the top of the funnel ready to be activated and treated.

Sorry, can I just squeeze in a quick clarification point there? So, Phil, do you expect the majority of patients that go into one of the hubs to actually become -- to pull through into receiving drug?

That would be our expectation, yes.

And Jason, maybe I can add on these patients, both the ones that are being registered at the PAPZIMEOS hub or at the centers that they have their own registration hub, basically, they are various adult RRP patients that through their physicians have been identified for the treatment and will be joining to receive. So that's very exciting. And I think prior to approval of PAPZIMEOS, our analysis have shown that there will be a large patient population. And as you have seen it, the estimate is 27,000 in the United States. And it's really important to say that we are seeing that kind of a demand coming through from the various centers.

And just to reinforce, Jason, a lot of these centers, they prefer to use their own expertise and systems and patient services initially. Now obviously, if they want to explore co-pay support or free drug support where for appropriate patients, they would need to ultimately come into our hub. So, we've, as you said, sort of got these 2 hub components that are co-existing at the moment, both of which suggest that the pent-up demand that we identified is absolutely there.

Your next question comes from the line of Swayampakula Ramakant from H.C. Wainwright.

Congratulations, everybody, everyone on the team there. It's a great moment, and it's a transitory quarter for you guys. Excellent. So, for my one question, I want to check with Harry regarding the statement saying that you are funded to cash flow breakeven, which is obviously a significant statement you're making. What sort of assumptions are you taking into this in terms of either revenue or patient penetration, how should we think through to get there?

Yes. RK, good to talk to you and appreciate the question. I would say at this point, we're not guiding on revenue. So, it's kind of difficult to say when or how we get to cash flow breakeven. But I think we're willing to state that by the end of 2026, we'll be cash flow breakeven.

Your next question comes from the line of Michael DiFiore from Evercore ISI.

Huge congrats on all the progress here. Number one, just given the obvious pent-up demand and bolus of patients that are expected to go on therapy soon, could you give us any color as to how long that bolus may last, just considering the reimbursement hurdles that any new therapy encounters during the first year? And I have a follow-up.

Well, we do -- we look at analogs of rare diseases and the uptake where you do have pent-up demand. So, we think that's going to last for quite a while. The 27,000 adult patients that we've identified are already there in the system. Obviously, some more severe than others, some see the health care practitioner more often than others. But those are the patients that are actually there in the treatment, and then you would have the incident population on top of that. So, I think this bolus of patients is going to be there for quite a while to come.

And Michael, maybe I can also further add is the importance of our broad label, which covers basically all adult RRP, which means anyone who is also going to be diagnosed immediately, or they had, for instance, even 1 surgery, and it will be continuously added to these hubs for the treatment.

And it's very clear, at least from what we are seeing from the patients' enthusiasm as well as the physicians, that based on the data that has been published from Hopkins prior, that basically patients by fifth surgery, they have irreversible damages to their either trachea or vocal cords.

Clearly, now the patients as early as their diagnosis, they will be joining. So, the pent-up demand, obviously, all of the severe patients, but also now all of the patients that have been diagnosed or going -- undergoing diagnosis, they are basically eligible to receive the PAPZIMEOS and the physician, actually, this is the importance.

And as for instance, if you look at our press release today, Dr. Best, which is one of the renowned physicians for the treatment of RRP in the world, he refers to PAPZIMEOS as nothing short of remarkable data for these patients' treatment of adult RRP and then also positioning it will -- it's poised to become a standard of care, which then covers all that population. And I think that's very important.

Excellent. And just my quick follow-up is just for modeling purposes, how should we think about subsequent cycles of therapy? And would payers even allow subsequent cycles beyond the first 4 doses?

Yes. I think this is an excellent question. First of all, it's very important, and this was one of the interesting concept that FDA has encouraged us very much for redosing of the PAPZIMEOS and for the expansion of that. And the reason has been based on the safety, obviously, the efficacy and the durability of the response results that we have seen.

And at the moment, of course, in the label, it's at the discretion of the physicians in order to re-dose. So, if they feel that the patient needs to be re-dosed, they can prescribe to that. And of course, as we are moving forward, we are further generating further data on redosing of the patients. So, I think there is a huge expansion from that side.

And one of the other things that we have mentioned is that our partial responders, as I mentioned, 86% of our patients, they reduced their number of surgeries. And it's very, very important, and that was part of the discussions along for our BLA that clearly, they will benefit, it seems, that from the redosing because their immune system is being enhanced to address the root cause of this disease, which is HPV 6 and 11. And I think this is one of the areas that we are also expanding besides our pediatric clinical trials. It's further generation of the data on the dosing of the patients, redosing of the patients, I should say, which is initiated in the next year.

And I would just add from a payer perspective, the one characteristic of the drug that really stands out for them and will support us in any redosing conversations is the durability. So, we started off with the 1 year from our clinical registrational studies. We then get the 2-year follow-up in our label. We've just published our 3-year data. All of this is very important data for the payers. And obviously, we share that with them, build that into our value proposition so that we can support the concept of redosing.

Your last question is from the line of Brian Cheng from JPMorgan.

Congrats on your progress here. I just want to clarify how you record PAPZIMEOS revenue on your financial statements. Do you recognize revenue following each injection or at the end of the 4 injections? And I have a follow-up.

Brian, this is Harry. Thanks for the question. Yes, we recognize revenue when title transfers to -- we're either shipping through a specialty pharmacy or directly to the IDN or the community hospital, and we recognize revenue upon receipt by those entities. So, we don't wait until the injection occurs, which generally is going to be within a day of it being received.

And as we think about the registered patient population within your patient hub and also the institutional patient hub. I'm curious if you can help us think about the size and the trajectory of the registered patients. And then is it safe to assume that all these registered patients will get PAPZIMEOS within a defined period of time?

Yes. I mean, look, our hub and the hubs that we are understanding are being set up and implemented at the institutions, they're recruiting patients rapidly. There's a lot of momentum there, and we would expect that to continue, obviously, with the bolus of patients that we know is out there. They'll be worked through, as we said earlier, those patients are there for a reason because they've been identified for treatment with PAPZIMEOS. And so, we would expect the vast majority of those to ultimately then make it on to PAPZIMEOS.

The period of time is difficult to pin down, but there's a high sense of urgency that we have picked up in our interactions with the physician community, whether it's at the IDNs, but actually also at the community level with physicians approaching us and wanting to expedite access at the community level. So, I do think there will be an expedited uptake from the initial pool of patients that we're seeing, but that will continue for quite a while.

Yes. And maybe, Brian, I can add really to what Phil said. I think what we are seeing, especially with the broad label that now we are going to be treating the patients that as early as having 1 surgery or actually just being diagnosed and they have to go through the surgery plus all the other severe patient population that exists there, and they are being scheduled by their physicians.

And as we have already knew prior to the approval, but clearly have been seeing it post approval as well from the physicians, physicians do not want to do these surgeries, and they are trying to prevent having these surgeries as soon as possible for these patients because they know that with every surgery, there is basically closer to that damage line of 5 surgeries that causes irreversible damage for these patients.

So, I think collectively, when you look at all of that, there is a continuous patient addition and with the understanding that, of course, these patients not only are identified and they will be getting a treatment and they are enrolling as we speak and actually, the prescription is ongoing.

There are no further questions at this time. So, I'll turn the call over back to Helen Sabzevari for closing comments.

Thank you to all those participating in the call today. As you can see, times are very exciting for us at Precigen and for the RRP community as a whole. We look forward to providing you with further updates as our launch progresses. In closing, I would like to leave you with words from a PAPZIMEOS patient who is one of the complete responders from the clinical study.

The sound of hope living with RRP in the last 24 years has been the sound of my own voice when I have it. It's being heard even when this virus is trying to destroy my vocal cords. RRP not only took away my voice physically, but also emotionally. So, hope for me has been the moment I've been able to speak, and others have been able to hear me.

Power of voices is camaraderie and advocacy, being part of a community that refuses to be silenced. When my voice is weak, others are standing beside me and if needed, speaking up for me. That's power and that's hope. Today, hope sounds different. It's a physician telling their long-time RRP patient, you don't need another surgery. There's something new. Today, the sound of hope is PAPZIMEOS.

Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.

Greetings, and thanks for joining us to have a conversation with Helen Sabzevari, Chief Executive Officer; and Phil Tennant, Chief Commercial Officer of Precigen. Precigen is a biopharmaceutical company specializing in advancement of innovative precision medicines to address difficult-to-treat diseases, which are -- which have high unmet need. Recently, the company received approval for PAPZIMEOS, which is the first and only drug approved for treating adults with a rare and debilitating and potentially fatal disease, recurrent respiratory papillomatosis.

The drug is a nonreplicating adenoviral vector-based immunotherapy against HPV 6 and 11 that are believed to be the cause of the disease. FDA has granted a full approval to the drug on August 15, almost 2 weeks ahead of the PDUFA date of August 27. And management is planning to launch the drug in early fourth quarter of this year.

So to know more about the drug and the commercial strategy and welcome Helen and Phil to this fireside chat. Good morning, Helen and Phil. Glad to see you both, and appreciate you accepting our invitation to talk to our audience today.

Good morning, RK. It's great being with you and the audience.

Helen, so just for starters and for those people who are not yet aware of Precigen, what's the business plan here for the company? And also, how successful have you been in executing the plan to date?

So first of all, thank you for the opportunity. And the business plan, we are an innovative, as you mentioned, biotech company that has been really focusing on bringing innovative platform with the right indication and right regulatory strategy. So from the very beginning. And with that as our business plan at the core of it, what we have done in the past few years to advance two platforms forward. One is our AdenoVerse platform, which is a very unique and differentiated platform, which Precigen has a full IP around it. And the other is our overnight CAR-T cells that is manufactured at the side of the hospitals, and it's really autologous CAR-T overnight.

What we had done originally was really, first of all, make sure that the both platforms come to clinic and show its capability for scaling up and commercialization, which we have been very successful in showing the power of both platform. And especially for AdenoVerse, which we moved that very, very rapidly, as you are aware. Even during a pandemic, starting the program, starting the IND in the middle of the pandemic in 2021. And receiving, as you mentioned, a full approval by the August of 2025, which is an unprecedented, really, speed for a drug development. It doesn't matter which organization, you are part of it as big pharma or biotech. This has been an incredible journey with a lot of effort from the teams involved.

So -- and part of really, our business development, I will go back, is on really understanding the science and the platform and applying it to the right indication with the right -- basically regulatory strategy from the very beginning. And this has allowed us to move very rapidly despite of all the challenges that globally, all of the companies have been -- had to face. But we have been very successful. And as you are aware, quarter-after-quarter, we have delivered or exceeded our goals for that quarter, which I'm very proud of the accomplishments of Precigen.

Yes. Congratulations on that. I should underscore the 4-year effort which went in to bring this drug to the market and potentially should be in the market by the end of this year. So just so that people understand a little bit more, can you describe the platforms at a high level? Obviously, we'll go more into the AdenoVerse platform, so PAPZIMEOS, but at least a little bit more on the CAR-T part of the platform?

Absolutely. Our CAR-T part of the platform is an autologous CAR-T that basically, we have initiated a very unique and differentiated platform. It's a nonviral platform that -- because of that, you do not need an extensive manufacturing that is required with viruses and also the cost that is associated. The way it works is very simply, the patients, they come. They have their apheresis done. And their own T cells are -- basically, we have a platform and UltraPorator with our ultra vectors that generate a specific autologous T cell overnight in the hospital. And then the next day, the patients are capable of receiving their own autologous CAR-Ts.

We have done an extensive Phase I, both in hematological as well as solid tumors. And it's end of Phase Ib, especially in AML, which we reported a very significant 27% to 28% complete responses as well as partial responses in the patient population that basically had 2 to 3 months to live. And we have finished our Phase Ib, and we are in the process of having to go for the end of Phase Ib, meeting with FDA and discussions for pivotal studies for Phase II.

Fantastic. So going straight to the topic for our fireside chat today. What is RRP? And how big of a patient population suffer from this indication?

RRP, as you mentioned at the beginning, or recurrent respiratory papillomatosis, is a rare disease, it's debilitating and devastating. It's -- the root cause of this is infection of HPV 6 and 11. And this can -- basically, on take of RRP can happen during childhood as children pass through the birth canal of the mothers and they get infected, so they can start having this benign tumor developed on vocal cord or trachea as early as age of 1 and continue for the rest of their life. Or you can basically get infected as an adult through sexual interactions, and as a result of that, be infected and develop these tumors.

As you mentioned, for the past 100 years, this disease have been known, but unfortunately, did not have any FDA-approved therapy that addresses the root cause of this, which is the chronic infection of HPV 6 and 11. And now for the first time with using our AdenoVerse platform, which is differentiated than all the other platform in the sense of not having much higher capacity to express number of epitopes and genes in our gorilla adenoviral vectors that are nonreplicating, but also the ability to be repeat dosing it and keep enhancing the specific CD8 responses, which is at the core of the mechanism of action of this drug, which directly now targets the infected cells. And they can also maintain, and by giving a redosing of this, you can enhance the immune responses.

And this is very, very important for people to understand that some of these patients, they go -- up to before the approval of PAPZIMEOS, the only thing that was available to them was really repeated surgeries. And the studies have shown that by the -- almost the fifth surgery, more than 76%, 80% of these patients have now irreversible damage either to their vocal cords or to their trachea. So it's quite debilitating. And in some cases, as you mentioned, it can also metastasize and lead to the fatal disease. So we are very excited that now, PAPZIMEOS is the first and only treatment, FDA-approved treatment for this patient population, which has been set a very high clinical bar out there in regard to the treatment.

So regarding the disease itself, in terms of progression of the disease. So for example, you said at some point, patients could go through 5 to 7 surgeries in a year. So is this something that progresses over time? Or how does -- I'm just trying to figure out, like if I find out that I'm suffering from this, should I first go straight to the medicine? Or can I wait? How does that work?

Yes. No, absolutely. It's very, very important to the -- upon the diagnosis really to go to the physicians. And now with PAPZIMEOS being approved and for a broad label which is for all adult RRP, the patients, upon really diagnosis, they can directly go to receive this drug. And this is very, very important. And the fact of this broad label, it allows -- as you mentioned, some of our patients, actually, even in our clinical trial, they had, per year, 10 surgeries. Can you imagine? Every 4 to 6 weeks, you have to go under a surgery in order just to be able to speak or breathe at this point.

And it -- obviously with the data that came out of John Hopkins, it has shown very clearly, as I mentioned, by fifth surgery, you have done irreversible damage. So clearly, neither the patients nor the physician wants this to happen. Because once that damage is done, you cannot reverse it.

And the risks of every surgery, it keeps adding up. And this is one of the reasons that physicians really do not like to do these surgeries. And now with the approval of PAPZIMEOS for all adult RRP patients, patients can receive it at any stage of the disease that they are. If they are just diagnosed or they have had a number of surgeries, all of them are -- can be receiving the PAPZIMEOS for treatment.

So for patients who get infected, unfortunately, through their mother during -- as they pass through their birth canal, as you said, do the HPV vaccines like CERVERIX and GARDASIL that have been approved for almost a decade or more now, can they help these patients out in terms of progression of the disease? Or that really -- those vaccines don't really -- those prophylactic vaccines really don't work for this particular indication?

As you mentioned, the GARDASIL is a prophylactic vaccine, which means that you -- like many other vaccines, you get vaccinated prior to getting infected. And the effect is really -- it's effective in that setting. But once you are infected, actually, GARDASIL does not have the same effect. And I can tell you, some of our patients that they have been diagnosed with RRP before entrance to our trials, they have received GARDASIL, and it didn't have any effect.

So for our pediatric population, it also -- FDA has been very, very interested in because of the safety, efficacy and durability of response that we have shown with PAPZIMEOS that this really be used in the pediatric population. And currently, part of our immediate plans is to move in that direction as well and expand the indication for the pediatric patient population.

RK, just to add to that. In our discussions with thought leaders, there's a general sense that it's going to take a few generations before any significant vaccination in a preventative sense would have an impact in the adult population, and that's in the 2040s and beyond.

Okay. And Phil, in terms of the patient population, both in the United States and Europe, I know you have done some work on that. So what's the number that we can think that is real? Because that has been changing over the last couple of years.

Yes. Yes. I'll let Helen comment on the literature, but I'll speak to the work that we did. We think it was pretty innovative and pioneering and the most robust look at the patient numbers that's ever been done in the U.S. Because there's no ICD-10 code. So you can't go into claims data and electronic health records and just pluck these patients out.

So what we did is we worked with a company that provided access to tens of millions of electronic health records and hundreds of millions of claims data. And we were able to definitively identify patients in their electronic health records because the physician had basically typed in something, like this patient has RRP. But based -- what we did, we built algorithms around those patients based upon the diagnostic codes and the surgical codes that they had and used AI algorithms to then lift and shift what those patients look like, the definitive patients, into the broader database. And that estimated 27,000 adults in the U.S. alone.

Now if you extrapolate that -- obviously, we don't have access to claims data and such ex-U.S. or not in the same way. But if you were to extrapolate that to ex-U.S., then you're looking at 100,000, 120,000 or more patients in the top markets ex-U.S. as well. So it's still a rare disease, but there's still a significant burden on patients in the health care system.

Okay. No, that's good. And in terms of starting off to talk about commercialization. I know you were not expecting -- I don't know if you were expecting the full approval, but we were not expecting it. So since you got the full approval, how do you regard the label? And were there any surprises in the label itself that you got?

Helen, do you want to go?

So from a full approval, clearly, FDA has granted us accelerated path, as you know, with the confirmatory trial. And throughout the interactions with the FDA, we have been updating our clinical data, which is -- not only it included the safety, which was Grade 1, Grade 2 and nothing more than that and no DLTs, but also a very robust efficacy, 51% complete responders, which means that they didn't require any surgery for a minimum of 1 year. And 86% overall responses, which patients that they reduced the number of surgeries.

As you know, RK, we had a very, very robust endpoint. We didn't go just for a reduction in the number of surgery, but really to eliminate the surgeries at least for 1 year. And then with the durability of a response, which -- the minimum has been 24 months, and we have patients that they have passed 3 years, and we will be reporting on those fairly soon. In meetings and publications, that was also updated.

And as a result of that, this is -- was something that the FDA, based on a very robust prospectively -- prospective -- statistically significant data powered pivotal Phase I, Phase II. And durability, plus the efficacy, plus the basically safety, FDA, I think, took into consideration all of that for the patients with this debilitating disease. And instead of having accelerated with confirmatory trial, they gave a full approval, which now has set the PAPZIMEOS as really a standard of care for RRP [ and health ] patients. So with that, I hand it back to Phil.

I would just say, RK, I think the broad label just speaks to the illogical nature of trying to treat a chronic infection with risky surgeries. And I think through the great work my colleagues did, we were able to work with the FDA to pull through that logic and secure a broad label, which obviously, from a commercial perspective, is great news.

Yes. So Helen, you just was -- were speaking a little bit earlier regarding the severity of the disease, how severe it can get and in terms of getting to the fifth surgery and almost getting into a very bad situation by then. So in your clinical trial, I'm sure we'll get all these details a bit later in the year. But in general, can you talk to the patient population itself and the mix of the patient population that were in the trial? Were there any patients where you -- or where they had to be debulked a little bit before vaccination, I mean, before giving the PAPZIMEOS? Or is it irrespective of how severe the disease is when they come in, they can be given PAPZIMEOS?

So the way that our trial, pivotal Phase I and Phase II was designed is basically the severe patient population, they will come in. And usually, this patient population is very simple. They go to their doctors when they cannot speak or they cannot breathe. And the reason for that is that the benign tumors have grown on a vocal cord or trachea. And as a result, there is this [indiscernible] on the patient.

So the first thing is what these benign tumors, if they were obstructing a vocal cord or trachea, the physicians, they removed it. And then they started the treatment, which is considered a 4 -- a subcu injection is a very easy to administer -- 4 subcu injection over 3 months period. And then the patients were followed for a minimum of the 1 year. Of course, all of our patients have been followed for much longer than that. But the endpoint was no requirement of surgery for a minimum of 1 year. And that's the way that the trial was designed.

Yes. So it doesn't matter at what stage of the disease progression they are in, they can be taken in and be given the treatment without additional surgery?

Yes. And I think what becomes important as we were talking about the broad label, now the patients that -- they are just diagnosed with the disease, they can go in and get treated with PAPZIMEOS. Or patients that have had the disease for many years, they can go in and get it. So the severity of the disease is not the issue, it's as soon as the patient is diagnosed or requires, then they can go in and receive this.

So a follow-up to that question is, let's say, a patient goes in, gets the surgery done. Can you -- can that patient be dosed with PAPZIMEOS immediately after the surgery so that they don't have the next surgery?

Absolutely. And that's the whole plan. That the moment that they are diagnosed or if they have had already the disease for many years, but then they have required to go in, they go in, and then they can receive their PAPZIMEOS immediately.

Okay. All right. No, those are good. And -- but Phil, when you were looking into the patient numbers, you -- I know that you had looked into the claims as well. So were there any of these patients where they were in a -- once we start taking into this neoadjuvant settings and other patients, will that patient number start to grow? Or is that -- it doesn't matter because all of them were taken into account in the numbers that you have?

Yes, the 27,000 that I mentioned was based upon a combination of diagnostic and surgical codes that we looked at around these patients. So that patient population is fixed as it were, but we have seen a phenomenon in other rare disease launches where there have been no treatments available or approved treatments, and then you have 1 or maybe 2 come to the market in quick succession. You do see an increase in diagnosed prevalence. So we do expect there to be an increasing diagnosed prevalence over and above the numbers that we've quoted.

Okay. No, that's good. So Helen, as we're going into this PDUFA date, you had an ongoing Phase III study as well. So what's happening with those patients? And a part of that trial was also to include redosing phase. So how will that be taken care of as you launch the drug?

So as you mentioned, as part of the accelerated path originally is a requirement to start a confirmatory trial. Which, by the way, it was a single arm as well by FDA. And we had already initiated that prior to submission of our BLA. But now with the full approval of PAPZIMEOS, obviously, there is no further requirement for the confirmatory trial. That trial has gone on hold. Of course, the number of the patients that they had already sort of applied through that, they -- we will -- as we always have said that we will leave no patient behind, and they will be included in other upcoming trials.

In regard to -- one of them is, as you mentioned, the redosing, and this is one of the things that we are closely working with the FDA for the expansion of the indication. Even though with the broad label that currently exists, I have to mention that the redosing is at the discretion of the physicians. There is no friction on that. But in order to further also generate the data, we will be looking at what are the best and fast options and to add to that data with repeat dosing of some of the patients. And this is something that we will be discussing. But currently, as I mentioned, the label, really, it's at the discretion of the clinicians to see when or how many times they like to do so.

So just to complete the thoughts on the label and regulatory approvals. What are your plans regarding ex-U.S. approvals? And also in terms of patient population, should we assume similar patients in Europe [ FIL ]? Regarding the 27,000 in the U.S., is that about a similar number outside of the U.S., especially [ in Europe ]?

So maybe I'll start by telling what are the plans, and Phil can take over the numbers. Currently, we are in the process of also advancing the submission for EMA and Japan. So definitely, this is part of the expansion, global expansion of PAPZIMEOS with the same data, pivotal Phase I, Phase II that we have from United States. And we are obviously looking forward to do this as soon as possible. And Phil, maybe you can speak to the number of patients?

In terms of the work that we've done ex-U.S., you've mentioned Europe. We're getting a similar sense that, yes, it's a rare disease, but perhaps there are more patients out there than initially anticipated than the literature suggests. So we would expect there to be, again, tens of thousands of patients across Europe, with more potential in countries like Japan, China and others that we've looked at. So yes, a rare disease, but a significant burden to the health care system, and obviously, with many patients who have no treatment options at the moment.

Fantastic. And then, Phil, regarding commercialization of the drug itself. Can you, at a high level, give us your thoughts on how you plan to take this to the market?

Sure. Well, our ambition is nothing short of establishing a new standard of care for adult RRP patients. That's fundamentally what our efforts are about. And we've been having a good look at this market for a couple of years before I joined Precigen just over a year ago, but really to understand the unmet need, speak to patients, speak to physicians and truly understand the opportunity. And the more that we've looked, the more that we understand that our value proposition is extremely significant for this rare disease, where basically there are no approved treatment options.

So we looked at the patient population. We talked about the work we did for those -- to identify those 27,000 patients. And we've seen that they are overwhelmingly concentrated in the hospital systems, these IDNs, academic institutions, community hospitals. That's where they are currently being treated. And so initially, of course, a lot of our activity is there, educating physicians that now at long last, there is a treatment that addresses the underlying cause of the disease.

As we've gotten closer to launch, we've been able to deploy some of our field teams. So our MSLs have been out in field for a few months, establishing relationships with thought leaders at the national and subnational level. We've had our payer specialists out there talking to payers and starting to get them to think about bringing PAPZIMEOS into their workflows. And similarly, we've had our sales leadership in place, and they've been able to talk to population health decision makers at the IDNs again about bringing PAPZIMEOS into their workflow.

Now with the approval, we're able to activate the full sales team across the 18 territories that we've identified that cover over 90% of the identified patient potential. And they're being activated as we speak, primarily supporting the IDNs and the patients to bring them together to make sure that we deliver access as quickly as possible.

I would also say something about our distribution group, we've built in full flexibility there. So if you are an IDN or an institutional hospital, you can purchase either through buy-and-bill or through specialty pharmacy. It really is about whatever their preference and their need is. And we continue to work with patient advocacy groups, in particular, the foundation with Kim McClellan. And maybe Helen can talk a little bit more about some of the work that we've done there.

As Phil mentioned, we have been in very close interaction with the patient advocacy group from the very beginning. And this goes back to really our mentality and our strategy that I mentioned, that pairing the innovative platform with the disease and the patients that have an unmet need, and then obviously, our regulatory strategy. And as a result of that from really since 2020, 2021, we have been in close interactions, and part of the result has been our Global RRP Day in conjunction with the RRP Foundation, which has been bringing all the patients, the voice of the patient, as well as the physicians to the table and making sure that all of the patients receive the treatment that addresses the underlying cause of this, which is now PAPZIMEOS. And really also physicians that they are very, very dedicated to ensure that surgeries are not used because they know that, that is not a treatment for this disease, and really now, PAPZIMEOS as a standard of care can be used.

So Phil, when you said you have identified 18 territories, I have two questions. One, what is the private versus payer mix, whether it's private or through the Medicare, Medicaid services? What's the mix there? And also among those 18 territories, should we assume this going to be a full blast across the 18 territories? Or is it going to be in waves where high concentration areas first and then go down the pipe?

Okay. To your first question, so we looked at a payer of last record in the database, the claims database that we looked at. And it shows that we expect 60% to 65% to be commercial, 30% to 35% will be Medicare, and the rest would be Medicaid and others. So we're working within that framework.

And then in terms of waves, no waves. The 18 territories and the 18 key account managers that we're activating, they cover 90% of the potential that we've identified. Usually, when you bring a sales team on, you aim for 80% or more. We're actually north of that, and we've identified more than 90% of the procedures, and the patients are covered by that footprint. And so no, it's not in waves. We are providing full support from the get-go to this pent-up demand that we know is waiting at these institutions.

Okay. So talking about pent-up demand, right? So I had the fortune of watching GARDASIL and those drugs get launched when they got launched. So there was a big, huge influx of drug initially and adoption and then slowly kind of weaned out. But of course, they are vaccines, and so you expect that to happen.

In this situation, how should we think about this? Because again, this can be curative, right? As you said, the clinical data showed 51% of them did not have to go back for surgeries or for additional therapy.

So how should we think about the initial demand?

Yes.

Yes. Well, we're very excited about that. But as we know, for rare disease launches, there is a bit of a dance that the payers, the providers and the patients have to go through initially, which takes a few weeks before the patient is ready to secure access. So we're providing all the support necessary to -- for that process to accelerate that where we can. In particular, we're providing patient support through our hub services that includes financial assistance where appropriate. Basically, our goal is to ensure that all eligible patients get access. And that's what we're doing, and that's how we're activating the market. But as I said, it does take a few weeks for that all to come through, but we're ready. We have the drug. We're manufacturing enough to cater for that, and we're ready to go.

And RK, maybe I can also add. From a perspective of the patient population, clearly, 51% of the patients did not require any surgery for a minimum of 1 year, and they continue to be in -- basically response, a minimum of 24 months are now going to 3 years and beyond as we follow them. But at the same token, we are -- have the ability of what we refer to as partial responders, as I mentioned, to add for redosing. And I think that's going to be very, very important from that perspective of the expansion of the indication as Phil and the team.

And then coming to the reimbursement, I know, Phil, you're working on trying to get a J-code in. How does reimbursement work as of today? And what's the -- what should we expect, the progress in terms of appropriate reimbursement?

Now as I said, it can take a few weeks for this process to work its way through at the institutional level to bring the patient and the payer together. So we're supporting that process. It can take 3, 4 weeks or so at the institutional level.

You mentioned J-code. So we're in the next wave of applications, which is October 1, and we expect that to be 6 to 9 months before we get the permanent J-code. But in the meantime, that doesn't stop physicians prescribing the medication because there are miscellaneous J-codes that can be used and should be used and will be used to support individual patients' access in the interim period.

Very good. So talking about the rest of the pipeline outside of PAPZIMEOS. So I know you're really focused on this drug for almost 12 to 18 months now. Now that you kind of crossed that, what do you expect needs to get done so that you can start thinking about the rest of the pipeline? And of the different places that you could go, which drugs would you actually start working on if funding was not a question?

No. As you mentioned, we focused for the past year, 1.5 years on PAPZIMEOS, and now that's across the finish line. Obviously, it has transformed the company to go from R&D company to a commercial company with the future revenues, which is quite exciting, and it will add tremendously for our portfolio and expansion of our portfolio.

Clearly, one of the first things that we are focused is the expansion of the indications, for instance, to genital warts in HPV-related, basically, field. And that, as you are aware, that it's a quite a large indication which is -- with a similar sort of infection indication. Also focusing, obviously, expansion of indication in the pediatric setting. We are clearly expanding the global -- for getting approval ex-U.S. And also our PRGN-2009, which is built on the exact same platform of our AdenoVerse, the platform that PAPZIMEOS is on and the same group of viral vectors, but it's in HPV 16 and 18 related cancers, such as [ skull ], head and neck and anal cancer, which -- it made up 5% of total cancers around the world, if you can imagine the number of the patients.

And in our original ASCO data that we showed, our PRGN-2009 had a significant response with a very, very favorable safety profile in basically checkpoint inhibitor patients that they had relapsed and showed 30% basically objective responses, including complete response and partial responses going up to 2 years of complete response and based on the activities. So that's also in our portfolio. And as I have mentioned in regard to our UltraCAR-T, that is a program that we obviously go for end of Phase Ib meeting with the FDA. And we are looking for a partnership that basically can provide the resources for the CAR-T.

So Phil, if I can go back for one more question on PAPZIMEOS. So when either hospitals or physicians order for the drug, do -- two questions, actually. One, in terms of ordering, does an order include all the 4 subcu injections? And two, once started, is it like antibiotics, once I start, I have to complete the course? Or can I stop once I get through two of them and I feel good, that I don't need to go through it?

Yes. No, good question. So the prescription and the coverage for the patient will be for all 4 doses. That's what our clinical trial clearly showed. It had the benefit -- the excellent benefit that we've seen. But the institutions can order the vials one at a time. So we don't expect there to be inventory built up. They can order just in time as necessary for each and every patient.

Perfect. So coming to the end of this. What are the catalysts that investors should be looking out for, say, over the next 6 to 12 months, Helen?

So from what I mentioned clearly, our commercial sort of launch has been already funded, as well as our manufacturing, as maybe it was not mentioned. But Precigen is manufacturing PAPZIMEOS at site. We have our cGMP manufacturing, which is quite -- have been producing the commercial material and continue to do so and providing all the doses that is necessary across United States and ex-U.S. So that's quite exciting as we have changed the paradigm with now, setting up a standard of care, PAPZIMEOS, in the site.

From a perspective of all of our CapEx have been paid as well with our manufacturing. And currently, as we have communicated, we have a good runway to basically revenue and generation of revenue next year. And we are not planning to do any dilutive raises, and we have a number of inbound options in front of us in regard to non-dilutive manner which we will take into consideration, what is the best option, and this will be communicated.

But currently, I think we are really excited about our commercial launch, and as a result, transforming Precigen from a R&D biotech company to a commercial biopharma that with a very strong portfolio that can benefit from the platform of AdenoVerse, expand the indications and basically similarly move for our patients in unmet need in a very agile format, as we have shown to do with PAPZIMEOS and expand basically and bring the needs of the patients center up front.

So as a final question, in terms of your financial position and the strength of the balance sheet, what's your current cash position? And what sort of a runway do you expect from it, not considering what the revenues that you'll be making?

As we have communicated already in the last quarter, we had $59 million in the cash runway. And as I mentioned, we clearly have already, and that's funded our commercial launch as well as our manufacturing. And this clearly will advance us to the revenues. But also, as I mentioned, there are a number of inbound nondilutive requests to us which we will be considering and look at the options that are in front of us. But clearly, we are not doing any kind of a dilutive -- equity dilutive raises.

Thank you. Thank you very much. Good luck with the launch, and I'm sure we'll be talking soon.

Thank you very much.

Thank you, RK. Thank you.

Good morning, and welcome to the Precigen PAPZIMEOS approval call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Steve Harasym, Head of Investor Relations. Please go ahead.

Thank you for joining us to discuss the U.S. FDA approval of PAPZIMEOS, the first and only FDA-approved therapy for the treatment of adults with recurrent respiratory papillomatosis, or RRP. With me are Helen Sabzevari, the President and CEO of Precigen; Phil Tennant, our Chief Commercial Officer; and Rutul Shah, our Chief Operations Officer.

Before we get into this call, I would like to remind you that we will be making certain forward-looking statements. These statements are based on our current expectations. We encourage you to review the slide in this presentation and our most recent SEC filings, which include information that could cause actual results to differ from those in the forward-looking statements.

After the prepared remarks, we will open the call to Q&A. With that, I will now turn the call over to Helen. Helen?

Thank you, Steve, and a warm welcome to all participating in call today. Yesterday was a day of great significance for all those in RRP community, treating physicians and the RRP foundation.

For the first time since RRP was recognized as a distinct disease, there is now an FDA-approved therapy for adults. We are thrilled to announce that PAPZIMEOS has been approved for the treatment of adults with RRP. It is the first and the only approved therapy for RRP and the first and the only approved therapy that treats the underlying cause of the disease.

As you all recall, Precigen completed submission of a rolling BLA in December 2024 under an accelerated approval pathway. I'm excited to announce that the FDA has granted PAPZIMEOS a full approval. With this full approval, the confirmatory study is no longer required. The approval of PAPZIMEOS also signifies the transformation of Precigen to a commercial stage company. Bringing this medicine to market with utmost efficiency and agility is an incredible accomplishment.

I would like to send my profound gratitude to all those involved in this achievement. I will now take a few minutes to briefly give an overview of this rare disease.

RRP is a rare, difficult-to-treat and potentially life-threatening chronic disease of the respiratory tract caused by either the HPV 6 or HPV 11 infection. Until now, RRP was mainly managed by repeat surgical interventions. This disease affects both adults and children and can cause severe voice disturbances, compromised airway, fatal pulmonary lesions and invasive cancers.

Based on the extensive analysis of claims data, we anticipate a patient population of 27,000 adult patients in the U.S. alone. Given this patient data and the broad label, we believe we have a significant opportunity to maximize our reach and impact adults with RRP.

PAPZIMEOS has potential to define a new treatment paradigm for this disease.

Let's look at the prescribing information. We are excited to announce that we have received full approval for PAPZIMEOS, which eliminates the need for the confirmatory trial. This is a testament to the clinical data, including a strong efficacy and durability and a favorable safety. In addition, we received a broad label, which makes all adult RRP patients eligible for PAPZIMEOS and positions PAPZIMEOS to become the standard of care treatment in this patient population.

This broad label that covers all adult RRP patients will allow treating physicians to intervene at an earlier stage of the disease and potentially reduce the risk of irreversible damage that occur from repeated surgeries. PAPZIMEOS is a non-replicating adenoviral vector-based immunotherapy. It is administered via subcutaneous injection of 4 doses over a 12-week interval.

Importantly, the safety profile is extremely favorable. PAPZIMEOS was well tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2. Here, I will take you through the pivotal data that led to the approval of PAPZIMEOS. PAPZIMEOS' mechanism of action targets the root cause of RRP. Upon subcutaneous administration, PAPZIMEOS acts by generating an immune response directed against HPV 6 and HPV 11 infected papillomas in the patients with RRP. 51% of those treated met the primary endpoint of a complete response. This is defined as no need for surgical intervention for a minimum of 12 months following the completion of PAPZIMEOS dosing.

In addition, complete responses have been durable and a vast majority of complete responses are ongoing. Specifically, 15 of 18 complete responders remained in an ongoing response at 2 years. We plan to present additional data at an upcoming medical conference showing ongoing durability of responses up to 36 months. PAPZIMEOS induced HPV 6, HPV 11 specific T cell responses in RRP study patients with a significantly greater expansion of peripheral HPV-specific T cells in responders compared with nonresponders.

I would now like to turn the call over to Phil to walk us through our commercial strategy and launch plans. Phil?

Thank you, Helen, and thank you to everyone listening in on this historic day. Let's turn to what makes PAPZIMEOS a compelling opportunity for this rare disease population. This approval positions PAPZIMEOS to become the new standard of care. Importantly, the product has a broad label, covering adult patients with RRP and it demonstrates durable complete responses. In fact, as mentioned, the vast majority of complete responders remain in complete response for 2 years, which speaks to the long-term efficacy and potential for sustained treatment impact.

From a commercial standpoint, the value proposition for PAPZIMEOS is extremely compelling. We are servicing a concentrated patient population. Integrated delivery networks, or IDNs, and community hospitals account for over 90% of patient potential. And this allows us to focus our commercial efforts efficiently and support early adoption. In summary, PAPZIMEOS combines its status as the first and only approved therapy for RRP with clinical durability and a targeted commercial footprint, making it a compelling breakthrough for RRP patients and the broader health care system.

Let's talk about launch execution, where we stand today and why we are confident in our ability to scale quickly. We know that there is demand for a therapeutic treatment option that addresses the underlying cause of the disease, and we are ready to meet the demand with the launch of PAPZIMEOS. We've built a robust commercial infrastructure to support PAPZIMEOS. Our 18 dedicated sales territories cover over 90% of the ENT patient potential. This footprint ensures our ability to reach the highest volume of prescribers at launch.

Our field teams, including medical science liaisons, payer engagement specialists and sales leadership have been in place since April and making substantial progress in building key relationships. We've completed targeting across IDNs, community hospitals and other health care providers, covering over 90% of the account, patient and procedural potential.

Pre-approval information exchange or PI presentations with population health decision-makers have also laid the groundwork for market entry. We've also built a strong base of national and regional thought leaders to champion early access. And our commercial distribution channels, patient hub services and support platform, papzimeossupport.com, are fully operational to support launch. In addition to the online portal, we have established a dedicated support line for providers and patients to be able to call.

To put this in perspective, 93 IDNs and community hospitals account for 80% of our target potential and our total IDN-community hospital universe includes approximately 500 accounts. We're also supporting formulary and P&T processes across payers and IDNs.

As we look ahead, we've outlined a clear framework for tracking the commercial success of PAPZIMEOS in several key areas, and some of those critical areas are shown on this slide. We have begun and will continue to monitor national and regional KOL advocacy and support for PAPZIMEOS. We'll be tracking detailed prescription metrics at the individual and institutional levels to understand the breadth and depth of utilization. In addition, we'll be paying close attention to market access metrics to understand the proportion of lives who are increasingly covered with favorable access. And finally, we will utilize our hub to provide the data we need to ensure all eligible patients are securing the support they need to access the treatment.

Together, these metrics form the backbone of our commercial dashboard and will guide investor expectations as we build towards sustained revenue growth. On the subject of patient support, we're not just launching a product, we are delivering a full service experience designed to accelerate adoption and ensure continuity of care.

From a pricing perspective, we are priced competitively and the price point is representative of the innovation and value PAPZIMEOS brings to the market as the first and only approved treatment. Our support program is built to remove barriers for both health care providers and patients. It includes treatment education, insurance navigation and order coordination through specialty pharmacy services. These resources streamline the onboarding process and reduce administrative friction for prescribers.

We've also prioritized financial assistance and coverage support. Patients receive help understanding their insurance benefits and accessing affordability programs, which is critical for ensuring adherence. For providers, we offer dedicated support through the treatment journey from education to logistics, making PAPZIMEOS easy to prescribe and manage.

This infrastructure is not just about access, it's about scalability. By enabling smooth engagement across IDNs, community practices and payers, we're positioning PAPZIMEOS for sustained growth and long-term market leadership. With that, I will now turn back to the operator.

[Operator Instructions] With that, our first question comes from the line of Jason Butler with Citizens.

Congrats on the approval. Two for me. First, sorry if I missed this, but what is the list price of the drug? And then secondly, the RRP Foundation has a database of a large number of -- sorry, RRP patients. I guess to what extent have you been able to leverage this already? Or can you leverage this in the future to help refine patient and physician targeting?

Jason, thank you for the questions. I think in regard to the pricing, the first question, I'm going to ask Phil to answer and I take the second question.

Jason, thank you for the question. So -- as we all know, it's 4 subcutaneous injections over 12 weeks. And as I mentioned, we've priced it appropriate to the degree of innovation that it's bringing to this market as a rare disease treatment and the first and only approved treatment.

So the Wholesale Acquisition Cost or WAC price for each vial of PAPZIMEOS is $115,000. And we believe this will support broad utilization of PAPZIMEOS in adult RRP patients. I'd like to stress, of course, that we have a comprehensive patient support program in place, which does include financial assistance for those that require it, ultimately helping RRP patients access therapy. And we have a clear goal which is to ensure every eligible patient will have access to PAPZIMEOS.

And in regard to the RRP Foundation and the question, as you know we have been extremely sort of active in working very, very closely with the RRP foundation from the beginning of this journey. And -- especially in the past 2 years, as you have seen on RRP day that we have cosponsored with the patient advocacy group and Kim has been a tremendous inspiration and help in advancing this treatment for the patients in an indication that there has not been any approved therapy for -- let's think about this, 100 years, for the past 100 years, people have known about this disease and the therapy, believe it or not, from a 19th century, the 20th century to 21st century has been the same, repeated surgeries which cause the damage.

So we are working very closely with the patient advocacy group and of course, in establishing the not only making sure all patients have access, but also from perspective of the data bases that can be very, very useful across the United States to identify the patient and to ensure that all patients have access to this treatment. And we look forward to a continuous work and excellent work that patient advocacy group has done in this manner.

Great. And just to clarify, on the price, it's 4 vials per course of treatment, correct?

Correct.

And your next question comes from the line of Jennifer Kim with Cantor Fitzgerald.

Congrats again on the approval. Maybe to start on the broad label, and this might be a question for Phil. What are the expectations in terms of market access based on your conversations with payers in terms of treatment to trial criteria versus treatment to label?

And then my second question is, just looking at the label, are there any limitations around redosing? I know that was a consideration for the confirmatory trial, but that's not required any longer.

Thank you, Jennifer. Thanks for the question. Yes, in terms of discussions with payers, as you would imagine, we've had extensive discussions with them. And there's a high degree of anticipation. I mean, fundamentally, they understand the unmet need. They understand the inappropriateness of surgery as a long-term solution for these patients. They're impressed by the clinical efficacy and the value that this drug will bring as the first and only treatment. So we expect in line with our label that every patient is in a position to benefit from PAPZIMEOS, and we'll be working with payers to secure broad access accordingly.

And Jennifer, in regard to the redosing, as we have been communicating, the FDA has been extremely interested in these aspects. Our pivotal study included obviously a single course of 4 subcutaneous injections of PAPZIMEOS, which could make a lot of scientific sense here to redose the patients to further elevate the immune responses against papillomas to potentially improve the responses in partial or nonresponders and eventually to extend the duration in the complete responders.

As published in Lancet Respiratory Medicine, 86% of our patients had a clinical benefit in reduction or elimination of their surgical burden in 12 months after treatment. So based on that, we have a very -- and based on the safety also and the efficacy that has been seen from our pivotal study, redosing makes a lot of sense. And at this point, it will be for physicians to evaluate patients and decide on redosing.

And your next question comes from the line of Swayampakula Ramakanth with H.C Wainwright.

Congratulations. I know this is a great -- it's a big win for you folks and also for the patients. A couple of quick questions. So Phil, are these vials a single-use vial or can it be multiple use? And then also in terms of the launch itself, is it going to be in some sort of waves in the sense, initially you reach out to the IDNs and then to the community hospitals and so forth? Or is it going to be a complete launch across the different segments of the patient population?

Yes. Thanks, RK. So firstly, to the first question, yes, single-use vial. And regarding the launch, no, I wouldn't say it's going to be in waves. We've clearly identified over 90% of the patients and the procedural concentration in the IDNs and the community centers. So our initial footprint includes both. But we do know that the patients are concentrated in those centers. They've been on a tremendous journey for many years and ultimately end up having surgeries at these hospitals. And as I mentioned earlier, of the 500 or so IDNs and community practices that are in the total target list, there are just under 100 of those that represent the vast majority of the potential there, and that's where we'll be focusing our initial work.

Thank you very much, RK. So with that, I'd like to thank you for taking the time to join us today. We are profoundly grateful to the NIH clinicians, the FDA and most importantly, the patients and families whose trust, commitment and perseverance made this breakthrough possible.

The FDA approval of PAPZIMEOS marks a truly historic milestone for the RRP community, delivering the first and the only approved therapy for adults with this rare, debilitating and potentially life-threatening disease. With an estimated 27,000 adult patients in the U.S., this approval represents a fundamentally new era of treatment.

This is a proud day for Precigen, especially our team who have worked so hard to bring this to reality. We look forward to swiftly delivering PAPZIMEOS to physicians and patients and to continuing our mission to advance meaningful innovations for those with high unmet needs. Thank you again for participating.

Thank you, presenters. And ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.