Inovio Pharmaceuticals, Inc. Aktie

Hello, everyone, and thank you for joining us today. It's my pleasure to introduce Dr. Jacqueline Shea, President and CEO of Inovio Pharmaceuticals. Jacqui has more than 25 years of experience across the life sciences and biotech industries and has led Inovio since 2022.

Prior to becoming CEO, she has served as the company's Chief Operating Officer and earlier in her career, held leadership roles at Aeras and Emergent BioSolutions with much of her work focused on the development of vaccines and therapies for infectious diseases. She holds a PhD from the National Institute for Medical Research in the U.K. and currently serves on the Board of Trustees of the Sabin Vaccine Institute.

Jacqui, thanks very much for coming today and joining us, and I'll turn it over to you.

Thank you. It's a pleasure to be here today and tell you about some of the exciting work that we're doing here at Inovio. So before I move into the presentation in full, this is just a standard slide that says during the presentation, I'll be making forward-looking statements, and I refer you to our most recently filed 10-Q and 10-K documents for further details.

So to provide you a quick overview of Inovio, we're a clinical stage biotech company. We're focused on developing and commercializing DNA medicines to treat and protect people from HPV-related diseases, cancer and infectious diseases. Our lead program, INO-3107 for the treatment of Recurrent Respiratory Papillomatosis or RRP, is currently being reviewed by FDA under the accelerated approval program. So we have a BLA on file with a target date of October 30 this year.

RRP is a rare HPV-related disease with significant unmet need, and we believe a significant commercial market opportunity. We've been granted both Orphan Drug and Breakthrough Therapy Designations by the FDA, and we have Orphan Drug Designation in the EU. The FDA review is advancing. We're currently in the late stages of the review, and I'll be discussing our regulatory progress in further detail later on in the presentation. And as we approach our PDUFA date, our commercial preparations are also ramping up. And we believe that we have an opportunity for 3107 to become the new standard of care for RRP with an improved risk-benefit profile over existing treatments.

Following on behind 3107, we have a deep clinical pipeline with multiple near- and midterm catalysts, and in this presentation, I'll be touching upon our new partnership with Akeso for the evaluation of 5401 in combination with Akeso's bispecific checkpoint inhibitor for the treatment of glioblastoma. And also the positive data that's recently been reported by our partner, ApolloBio, in China from their pivotal Phase III trial of VGX-3100 for the treatment of cervical dysplasia. In terms of cash, we have a cash runway into late first quarter next year through the potential launch of 3107.

So to give you a quick overview of our technology, our DNA medicine platform is really focused on producing targeted proteins within the body. And we start off by identifying the genes for the target protein that we want to produce. We then use our proprietary algorithms to really optimize that gene sequence. We insert the optimized gene sequence into a circular molecule of DNA called the plasmid. And then we deliver those plasmids to either skin or muscle cells within the body using our proprietary delivery devices called CELLECTRA. So once the DNA plasmids are within the nucleus of the cell, the DNA is transcribed to RNA. The RNA is then used to produce proteins and then the proteins are released from the cell. And these proteins can either drive an immune response or they can be the therapeutic agent themselves.

So in terms of driving an immune response, we can drive antigen-specific cytotoxic T cells and we use this primarily to treat virally mediated diseases or oncology indications. We can also produce both antibodies and T cells, and these are primarily for our infectious disease indications. And then the proteins that we are producing can be the therapeutic agent themselves. So we can use our DNA medicines technology to produce monoclonal antibodies directly within the body to either prevent or treat disease or the proteins that we're producing can be therapeutic proteins to treat diseases with missing -- or defective proteins that need to be replaced.

So to move on to our lead candidate 3107 in more detail. RRP is a really difficult disease that really exerts a terrible toll on patients. It's a rare disease, and it's characterized by these small wart-like growth throughout the respiratory tract, particularly in the larynx and the vocal cords. And what this does is it can make it very difficult for a patient to talk, to breathe, to swallow. And it's driven by infection by HPV-6 or 11 viruses. And we think why people get RRP is that there's an insufficient immune response that prevent either fails to prevent infection in the first place or fails to clear that infection. And that's what leads to RRP.

It's a rare disease, but not that rare. It affects an estimated 14,000 people in the U.S. with about 1.8 per 100,000 new cases in adults annually. And RRP can be diagnosed at any age. Recurrent and repeated surgery remains the standard of care. And because the surgery really isn't really -- isn't addressing the underlying cause of the disease, the virus, these papillomas grow back time after time after each surgery. So it really requires, in some cases, hundreds of surgeries over a patient's lifetime to control this disease. And every surgery takes a toll on patients.

Every surgery entails both significant risk to the patient as well as emotional financial physical costs and every surgery comes with the potential for irreversible damage to the vocal cord. What patients are really concerned about are these surgeries, and they're really desperate to reduce the numbers of surgeries that they require to control their disease. And we believe that 3107 addresses the patient's primary concern, reducing need for surgery to control their disease. And 3107 was designed to generate an antigen-specific T cell response against both HPV-6 and 11, which are the targets underlying the cause of RRP.

So to move on to where we are in terms of our regulatory submissions. We're in -- as I mentioned, we're in the late stage of the review. We've completed our late-cycle review meeting and all of our scheduled FDA inspections. We also held an informal clinical meeting with FDA in July following the recent change in both CBER and the Office of Therapeutic Products Leadership. And during this meeting, we had the opportunity to present the totality of our data supporting 3107 safety and efficacy as well as our highly differentiated approach in treating RRP and our rationale for accelerated approval eligibility.

We also discussed the current standard of care and the ongoing need for additional therapies. However, in the meeting, FDA did not discuss its preliminary comment that they made in the file acceptance letter regarding accelerated approval eligibility. They did, however, indicate that their feedback on the design of the confirmatory trial would be forthcoming. Our next scheduled interactions with the FDA are going to be our label negotiations anticipated in September this year.

So to tell you a bit about the trials that supported our BLA submission, we conducted 2 trials, RRP-001, which was a Phase I/II study and then a follow-up study called RRP-002, where we were following up the same patients and looking to see how they did after RRP-001 completed. So with RRP-001, we evaluated patients who had 2 or more surgeries required to control their disease in the prior year. These were patients who had HPV-6 or 11 caused disease. And what we were looking to do here was to see whether or not treatment with 3107 could reduce the number of surgeries these patients needed to control their disease.

So patients entered into the study by requiring a clinically required surgery to control their disease. They were given 4 doses of 3107. And we counted every surgery that was required to control their disease after day 0. So every -- any surgeries that were required during the dosing window were counted against our endpoint. And in terms of what we were focused on was obviously safety as this was a Phase I/II trial. And in terms of our efficacy endpoint, what we were looking for was the change in number of surgical interventions in the 12 months prior to treatment versus the 12 months afterwards.

And then in the durability and extension trial, what we were looking to see was how those patients did following treatment. So they weren't getting any additional treatment. And we were able to collect a median of 2.8 years of follow-up for those patients following treatment. So this is the data that -- these were the trials that generated the data that underpins our BLA submission.

So when we look at what we saw coming out of the trial, we were very pleased to see what we saw as promising clinical benefit. So when you look at in terms of the 50% to 100% reduction in surgeries prior to the year before, we saw 72% of patients in year 1 at this endpoint, and this improved to 86% in year 2. In terms of patients that required no surgery at all after day 0, this was 28% in the first 12 months and improved to 50% in the second 12 months. And this is the data that we also use to justify eligibility for accelerated approval.

And when there's a product that's received a full approval to obtain accelerated approval, you need to demonstrate 2 things. One is a meaningful therapeutic benefit over the existing treatment. And the other point we have to prove is the potential to meet remaining critical unmet need. And we believe INO-3107 does exactly that across its efficacy, its safety and its differentiated MOA. So as I mentioned, we don't conduct any dosing or scoping during the treatment window, and we counted every surgery after day 0.

In contrast, the approved product requires what they call minimal residual disease surgeries during the dosing window. So prior to doses 3 and 4 to maintain minimal residual disease during treatment. And 83% of the trial participants from their Phase I and Phase II trials require these MRD surgeries during the dosing window. Surgery also remains the current standard of care. The vast majority of RRP patients are still receiving surgery to treat their disease. And PAPZIMEOS to date has reported treating about 200 patients as of the second quarter of this year.

And a key differentiator for INO-3107 is its ability to treat patients who are not served by existing therapy. So in relation to PAPZIMEOS, because we're -- because 3107 is a DNA medicine, it doesn't have any impact on clinical benefit from pre-existing neutralizing antibodies unlike viral vector products like PAPZIMEOS. And it doesn't -- and we were able to show that there was no impact on clinical benefit from immunosuppressive factors within the papilloma microenvironment. And in contrast, PAPZIMEOS has reported that an immunosuppressive microenvironment inhibits their efficacy.

So as you can see across efficacy, safety and a differentiated mechanism of action, we believe that we provide meaningful therapeutic benefit over existing treatments as well as the potential to meet the remaining critical unmet need. And I'm very pleased to say that we've had the support of the RRPF Foundation. So that's the Recurrent Respiratory Papillomatosis Foundation, who are the patient advocates for RRP patients. And they continue to highlight the need for new innovative therapies to treat RRP. And they explain that every surgery matters to every patient, every patient matters to the RRP community and every patient deserves treatment that works for them.

We started off our program working very closely with the RRP Foundation, and we're delighted to have their support as we move through our regulatory process. So this slide just really provides why we believe that 3107 delivers what patients and health care providers want most from a therapy to treat RRP. First of all, patients are really focused on reducing these numbers of debilitating surgeries that they require to control their disease. And as we walk through the data, 3107 does that. It doesn't require additional exposure to surgery during the treatment window to maintain minimal residual disease.

And there's no potential impact on clinical benefit from either the pre-existing neutralizing antibodies or immunosuppressive papilloma microenvironment that may impact the efficacy of approved products. Because we're not doing those minimal residual disease surgeries, it minimizes the recovery days needed during treatment. And unlike the approved therapy, we don't require a specialized ultracold chain. So that means that 3107 is easier to use across multiple different clinical settings. So we believe there's a real opportunity to establish 3107 as the new standard of care in RRP.

And to do this, we plan to leverage experienced field teams in conjunction with the contract sales organization. We'll be developing a targeted marketing campaign in conjunction with our agency of record, and we'll be using a patient hub to provide strong patient support services. Together, we're aiming to drive health care provider and patient preference for 3107 based on our differentiated product profile. We aim to establish broad access among payers and hospital systems, and we aim to grow the market by educating patients and caregivers about the potential product profile of INO-3107.

So following on behind 3107, we have some late-stage candidates that I'll briefly just touch upon. As you can see from our pipeline, most of our later-stage candidates are focused either on HPV-related diseases or oncology indications. We also have some very promising earlier-stage technology, which are our DMAb and our DPROT protein candidates, and I'll talk briefly about those as well.

So in terms of our later-stage candidates, we were very pleased with the announcement earlier on this year, that our partner in China, ApolloBio, their pivotal Phase III trial of VGX-3100 for cervical dysplasia met its primary endpoint. And ApolloBio are planning to use this clinical data to potentially file for approval within China and related territories. What this means for Inovio is obviously the potential for regulatory and sales-based milestone payments as well as a royalty payment should VGX-3100 be approved in China. And we also believe that this data further validates our DNA medicines platform in HPV-related disease.

Moving on to oncology indications. Earlier on this year, we announced a partnership with Akeso. And in this partnership, what we're looking to do is to combine 5412 in combination with Akeso's bispecific checkpoint inhibitor and see if this novel combination improves survival rates and delays disease progression in glioblastoma patients. And glioblastoma, as I'm sure you're aware, is one of the most deadly and common brain cancers, which unfortunately has a very poor 5-year survival rate and for which there really haven't been new treatments over the past decade. This also involves a partnership with the Dana-Farber Cancer Institute, and we plan to evaluate this combination regimen as part of the Dana-Farber Cancer Institute's INSIGhT trial, where they're the sponsor. So we're very excited about this program.

Moving on to those earlier-stage platforms in terms of our DMAb technology, and this is where we're producing monoclonal antibodies in the body. We were able to show in a Phase I human trial as a proof of concept that we were able to produce 2 different monoclonal antibodies against SARS-CoV-2 that we could produce them at potentially therapeutic levels out to 96 weeks and that the production level of the antibody was stable in the blood throughout out to 96 weeks. Very importantly, we didn't see any antidrug antibodies being raised against these antibodies. And these antibodies were functional.

We were also able to increase the level of antibody that we were able to see in the circulation by redosing. And we saw that the treatment was very well tolerated with the most common side effects just being injection site reactions. So we were really excited to see this data. And we're now taking the same technology and also applying it to other proteins, for instance, for missing or defective protein diseases. And it really is building on our DMAb technology.

And what we're aiming to do by producing these proteins is to address the shortcomings of conventional therapeutic protein or enzyme replacement therapies where patients are having to receive regular injections or infusions of these proteins or have gene therapy to try and correct the underlying defect. In terms of the protein -- in terms of the preclinical programs that we presented on, we presented very promising preclinical data on Hemophilia A at recent conferences as well as announced our work in Fabry disease and hypophosphatasia. And we're currently seeking partnerships to advance these exciting programs as well as other rare disease targets.

So in summary, we're really focused on working to deliver INO-3107 to patients as we approach our PDUFA target PDUFA date of October 30. Following on behind, we're advancing our diversified clinical pipeline and with most of our resources focused on 3107, we're primarily doing this through partnerships. And then we have some very exciting technology coming through in terms of our DMAb and our DPROT candidates. And again, we're seeking partnerships to advance these programs. So thank you very much for your attention.

Jacqui, thank you. With INO-3107 approaching its October 30 PDUFA date, there's clearly a lot happening at Inovio over the next few months. It was also great to get a sense of how the program fits the broader DNA medicines platform and the opportunities you're pursuing across the pipeline. Once again, we really appreciate the update and your time with us today. Thanks.

Thank you. It's been a pleasure.

So Inovio represented by Jacqui Shea, the company's President and CEO. My name is Eric Schmidt. I'm one of the biotechnology analysts at Cantor Fitzgerald, and I'm sharing this fireside chat with my colleague, Alexa Deemer. So Jacqui, thank you for coming. Maybe just high level, I know you've got an important FDA action date coming around the corner, which we're going to get into. But for those less familiar with Inovio, what are the 2-minute highlights?

Yes. Well, first of all, thanks very much for the invitation. It's nice to be here today. So Inovio is a clinical-stage company. We're focused on developing DNA medicines to help treat and prevent HPV-related diseases, cancer and infectious diseases. As Eric mentioned, we've got a very exciting PDUFA date coming up in a few weeks' time, on the 30th of October, for our lead program, which is INO-3107 for the treatment of recurrent respiratory papillomatosis or RRP. And following on behind that also based on our DNA medicines platform, we have a deep clinical pipeline of other candidates.

So tell us a little bit more about your DNA medicines platform, what that means, what that entails?

Yes. So DNA medicines have been around for quite a while. And what makes Inovio different is really our delivery system. So we start off by identifying target proteins that we want to produce within the body. We then optimize them using our proprietary algorithms. And then we insert the optimized sequence into a circular molecule of DNA called a plasmid. And then we use our proprietary delivery system called CELLECTRA to enable the DNA plasmids to enter the cells. And CELLECTRA works by very brief electrical pulses, which open pores in the cell membrane, allow the DNA plasmids to enter the cell and then the pores close back up again. And these are really rapid electrical pulses, millisecond pulses.

So once the plasmids are in the cell, they are transcribed into mRNA, then translated into protein. And then depending on how we design the protein, they can either be secreted from the cell or processed within the cell for antigen presentation. So our DNA medicines platform is very flexible. We can produce pretty much any kind of protein. And then we can use that protein to either drive an immune response. DNA medicine is particularly good at driving T cell responses, which is important for treating cancer and virally mediated diseases. And it's also very good at producing sustained protein levels. So this is particularly good for treating diseases where you've got a missing or a defective protein and you need to supply that protein. So those are really the core advantages of the platform.

And then the CELLECTRA device, how is that delivered? What's the patient experience going through that. Tell us a little bit more about what it looks like.

So we use our CELLECTRA devices to either deliver our DNA medicines to either skin or muscle cells. With the muscle cells, it's pretty similar to an IM injection, but then followed by these rapid electrical pulses, which enable the DNA plasmids to enter the cell. And it's a very simple, straightforward administration. Our device consists of a base station, a handset, a single-use disposable needle array. You insert the plasmid drug cassettes into the single-use needle array, attach it to the handset, remove the safety cap, apply it to the deltoid muscle that you previously used an alcohol wipe on. And then it's a single button press and that injects the plasmids, delivers the electrical pulses, whole process is over in seconds. Any health care provider can be trained to use it. And patients tell us whilst there is mild-to-moderate injection site discomfort, that resolves pretty quickly within 5 to 10 minutes. And patients tell us overall, it's a very tolerable process. But the key thing about DNA medicines, though, is unlike other T cell generating approaches like viral vectors, you don't get the systemic kind of responses, systemic flu-like symptoms that you can get with other systems. So after the injection site discomfort resolved, we really see very, very few adverse events.

We'll talk about the lead program, 3107 for RRP in a moment. But does the device itself require approval concomitantly?

So that really depends on the territory. So in the U.S., it's regulated as a combination product. So it doesn't have a separate approval. Ex U.S., the device can be regulated independent. So for instance, in the EU, we have CE marking for the device already.

And then sticking with the high level as we start to dive down into the story, what do you think investors are missing about Inovio today?

Yes. So I think investors are perhaps not quite appreciating how close we are to bringing the first DNA medicine potentially to approval and commercialization and then the deep pipeline that follows behind based on the platform. I think those are the -- we have a lot of exciting potential catalysts coming up.

Your DNA medicines platform could, I guess, in theory, go into so many different directions. I know over the course of the company's history, you've investigated a few different things. Why is RRP the right opportunity? And what are other kind of landscaping exercises you've been [indiscernible] land here?

Yes. So I think RRP is really a great opportunity for DNA medicines because it's really leveraging a core strength of the platform, this ability to generate antigen-specific T cells that can go after the virus that causes RRP. So RRP is caused by HPV 6 and 11. Inovio has had a long history of working in the HPV space, and we have demonstrated the ability to eliminate the virus in other HPV-related indications. So it was a combination of our expertise in HPV treatment, a disease with really high unmet need as well and then really leveraging this ability to drive the strong T cell response.

So how are patients with RRP managed today? And maybe you can elaborate a little bit more on what the unmet need is.

Yes. So to tell you a bit more about RRP because it's a rare disease and everybody may not be familiar with it. RRP is caused by HPV types 6 and 11. It can be -- you can get disease throughout the respiratory tract, but it mainly forms around the vocal cords. And what happens is you get the growth of these wart-like papillomas on the vocal cord. It can make it very difficult to talk, swallow, breathe. In some cases, RRP can spread throughout the respiratory tract, go to the lungs, become malignant. And in those cases, the outcomes are pretty poor. So treatment today or standard of care today really remains surgical reduction of the papilloma, either by laser or by scalpel.

And because you can't cut a virus out with a scalpel, these papilloma grow back time after time, hence, the name recurrent respiratory papillomatosis. And these surgeries, they're not curative. They're not eradicating the virus. And the problem is the surgeries themselves come with a risk to the patient. And the risk is permanent damage and scarring of the vocal cords and of the respiratory tract tissues. And that scarring in itself can lead to future surgeries as well. So it's a horrible cycle of disease, surgery, more surgery.

And just so maybe we can understand the burden of the current standard of care, on average, how many surgeries would you say that patients get per year.

Yes. So there's not a lot of data out there. We enrolled patients who'd had between 2 and 8 surgeries in the prior year into our clinical trial. And we think that's pretty representative of the population with active disease. So on average, about 4 surgeries a year.

Okay. And maybe now you can walk us through the Phase I/II trial. What was the study design, patient population, enrollment criteria? What endpoints did you evaluate and what the data showed? And maybe you can also comment how the data compared to your initial expectations.

Yes. So I think the first thing to bear in mind is what patients are most concerned about is reducing the number of surgeries because each surgery comes with this risk of permanent vocal cord damage. So that's what they're really focused on. And we designed our clinical trial with that in mind. So what we were doing is really looking for a reduction in surgery. So this was a Phase I/II trial, 32 patients. We enrolled patients who had between 2 to 8 surgeries in the year prior. And we enrolled patients who had either been diagnosed with HPV-6, HPV-11 or a combination of the 2 serotypes so they had to have had confirmed HPV 6 or 11 disease before trial entry.

And then our regimen is when patients required a clinically required surgery, they had that surgery, they entered into the trial and then we gave them 4 doses over a 9-week time period, so 1 dose every 3 weeks. And it's very important to note that we counted every surgery after day 0 because as I said, every surgery matters to patients. And we were really pleased with what we saw. So in the first year following treatment, 72% of the patients experienced a 50% to 100% reduction compared to the year prior. And this clinical efficacy strengthens into year 2, where that figure went up to 86%. If we look at patients who required no surgeries during year 1, that figure was 28%, strengthening into 50% in year 2. So we saw a really good clinical response. We were really pleased with that.

So I guess maybe taking a step back, you said that patients needed to either have HPV-6, 11 or both. So what percentage of RRP patients are either 6, 11 or both?

Yes. So it's estimated over 95% of RRP patients are 6 or 11. The majority of the disease, about 2/3 is HPV-6. HPV-11 is actually potentially correlated with slightly worse disease course. And then some unfortunate patients have both serotypes.

Okay. And you commented on the very impressive efficacy profile. Maybe now you can elaborate a little bit more on safety and tolerability.

Yes. We were really pleased with the safety and tolerability profile we saw, mainly grade 1/2 adverse events, very few systemic events. With DNA medicines, we really don't see the flu-like symptoms that you see, for instance, with viral vectors.

Okay. Got it. So then the BLA was submitted under the accelerated approval pathway, but then the FDA flagged that the data package may not be adequately eligible for the accelerated approval pathway. So maybe you can comment on what the company has done since then to strengthen the case and where things stand today.

Yes. And I think it really goes back to the fact that there was a product previously approved last year. So when you have a previously approved product that has a full approval under accelerated approval, you have to do 2 things. You have to show that there's a continued unmet need and then you have to show that you provide a meaningful therapeutic benefit over the available treatment. And we think we've done exactly that through INO-3107 efficacy, tolerability and a patient-centric treatment approach.

What I mean by that is the currently approved product, it doesn't work in all patients. And it also requires surgery as part of their treatment regimen. So over their 12-week treatment regimen, they scoped their patients at doses 3 and 4. And if visible papilloma were present, those papilloma had to be removed. In contrast, with 3107, we don't require the scoping and surgeries at doses 3 and 4. So we have a significant safety advantage because we're not requiring those additional surgeries as part of the treatment regimen.

We're also using different antigens as well. And because of the different delivery systems, we're not impacted by pre-existing neutralizing antibodies or the papilloma microenvironment. So we believe that we can treat patients that Papzimeos doesn't work in.

And did the FDA ever comment why the data package may not be eligible for the accelerated approval pathway?

So when we received this comment in the file acceptance letter, and it was a preliminary conclusion of a potential review issue that we may not be eligible for review under the accelerated approval pathway. We requested a Type A meeting. FDA denied that request saying that our review was ongoing, we weren't stalled, but they did offer an informal clinical meeting to discuss the review pathway. And they asked us to complete an assessment phase. So we put all of our clinical data and efficacy and safety data in the BLA into the Assessment Aid template. We also completed some additional analyses that FDA had requested. And then we submitted this Assessment Aid back in February.

Unfortunately, FDA took some time scheduling that clinical informal meeting, and it wasn't until we had new leadership in place at CBER and OTP that, that meeting was scheduled in July. So we held our clinical informal meeting in July. We presented the totality of our clinical data for efficacy and safety. We were also accompanied by representatives from the Patient Advocacy Foundation, the Recurrent Respiratory Papillomatosis Foundation as well as a KOL physician who treats a large number of patients. And they both testify to the continuing unmet need and the meaningful clinical benefit that they see with 3107 and 3107's ability to meet that unmet need. We thought it was a very productive meeting. Unfortunately, FDA told us that due to the late stage of the review, they were unable to comment on the review pathway at that time. So since then, we've completed all of our pre-licensure inspections, just had one observation, which we believe we've now resolved, and we're now expecting to enter labeling discussions in September.

Okay. And maybe you can remind us when the PDUFA is and if you have any outstanding thoughts going into that PDUFA date?

Yes. So our PDUFA date is October 30. As I mentioned, we're expecting to enter into labeling discussions. And we also will need to confirm the design of any confirmatory trial under the accelerated approval pathway with FDA.

Okay.

Will you be informing the investment community if you enter labeling discussions? Or what are the next communicable milestones?

Yes. Well, of course, we'll continue to keep everybody informed of any material information. But until FDA issue a final decision, I think it's important that we comment on sort of real facts as we go through these final stages of the review process.

And how are you thinking about the design of a potential confirmatory study?

So we had previously proposed to FDA a placebo-controlled design, so 2:1 randomization active to placebo. It would be about 100 patients. We had alignment with FDA on that design ahead of submitting our BLA, and we're obviously waiting to see FDA's comments on that design. They did say at the late-cycle meeting that they will be providing us a comment.

How does that satisfy full approval relative to what you're hoping to get under accelerated approval?

Yes. So it's an interesting question. So our competitor was approved on a similar magnitude of data from a single site. They received approval based on a reduction of surgery endpoint in year 1 and then duration data in year 2. And we've provided data for both year 1 and year 2, demonstrating a reduction in surgery.

So what else do you think you might need to do in a confirmatory trial?

So I think the purpose of a confirmatory trial under accelerated approval is really to confirm the clinical benefit that you've shown. And I think year 1 and year 2 readout should do that.

Even though you've shown some of that data already?

We believe that we've shown that already as part of our Phase I/II trial, but FDA can always ask for additional patients, additional endpoints, et cetera.

Any sense of the size of a confirmatory trial or...

So we've previously -- based on our placebo-controlled design, we previously estimated about 100 patients.

So as you mentioned, there's a recently approved competitor product on the market. In the first quarter of this year, we saw around $22 million in sales; second quarter, $53 million. So how do you interpret that sales trajectory in terms of the market opportunity? And any sort of read-through for 3107's potential launch?

Yes. So we think it's encouraging for us. I think it's a demonstration of the high unmet need and the pent-up demand out there. When we think about the numbers of potential RRP patients out there, we estimate -- epi data suggests that there are at least 14,000 patients. Based on some claims database work that we've done, we estimate it's significantly more than that. So based on our competitors' quarter 2 data, they claim to have completed treatment of about 100 patients, another 100 patients enrolled. So by the time of our PDUFA date, they will still only basically have single-digit market penetration. So we believe the vast majority of the market will still be available to us.

And then, of course, there are new patients being diagnosed every year, about 1.8 per 100,000. So those new patients will also be available to us. I think also very importantly that because the trials were done in different ways, our competitor enrolled patients who have had 3 or more surgeries in the prior year. We enrolled patients who have had 2 or more surgeries in the prior year. If payers are restricting reimbursement to clinical trial criteria, then we should have a slightly broader patient population that we can access.

So then how does 3107 differ from the competitor product, I guess, mechanistically and then in terms of the patient experience? And then how do you potentially see these 2 products coexisting on the market?

Yes. So both products are generating T cells against the virus. So they approach this in a very different way. But the competitor, they're doing these scoping and surgeries at doses 3 and 4. We don't need to do that. They've previously published data that they're inhibited by the papilloma microenvironment. We've shown that we're not inhibited. Our efficacy isn't inhibited by the papilloma microenvironment. So while both are generating T cell approaches, we're generating T cell approaches against different antigens and in a different way. And we think the quality of the immune response is really different.

We think the surgeries that they're doing as part of the treatment regimen is another key differentiator. Over 80% of the patients in their trial required those surgeries, over 40% of them required 2 surgeries. So again, that's another key differentiator. I think it's really important that patients have options. The existing product clearly doesn't work for all patients. And I think this is where 3107 can really step in and provide a solution for a broader population of patients. In the recently published guidelines from the RRPF Foundation, they indicated that should 3107 be approved, they would recommend it as first-line therapy.

So upcoming PDUFA date. So where do you stand on commercial readiness?

So obviously, we're really ramping up our implementation plans now. So we've made a lot of the key strategic decisions. We have our partners in place in terms of specialty distributors, specialty pharmacy, patient hub, 3PL, et cetera. We also announced at our recent earnings call that we'll be working with Syneos Health in terms of a contract sales organization. And we're also using Syneos Health in terms of MSL deployment. So we're really excited about the upcoming PDUFA date and the opportunity to potentially commercialize 3107.

Okay. And then I guess in terms of RRP patients, where are they primarily located? And what sort of physicians are treating these patients?

Yes. So it's really a small concentrated market. So RRP patients are treated by laryngologists, which is a subspecialty of ENT. We believe the majority of patients here in the U.S. are treated by 300 to 400 laryngologists, and those laryngologists are based in about 100 treatment centers. So it's really a small focused market, and we think we'll be able to address that with a relatively small field sales force.

Is there an ex U.S. opportunity? And what would be your strategy for addressing?

Yes. I mean, unfortunately, HPV is everywhere. So yes, there is a significant ex U.S. opportunity. And we have interacted with the regulators, the European regulators and the guidance we received from them was that we were likely to require a placebo-controlled trial in Europe for approval.

So the trial that you're contemplating would satisfy...

Potentially.

All right. So I guess -- how are you thinking about potential pricing?

So the competitor product is priced at $115,000 per dose, so $460,000 for a full regimen. And we'll be talking about our pricing strategy a bit closer to launch. But clearly, we've been thinking carefully about our pricing.

Okay. And then I guess beyond 3107, what pipeline programs are you most excited about? I know you have a lot going on.

We do have a lot going on. One of the big advantages of a platform like ours is you can address so many different diseases. So we've really been trying to concentrate on the strength of the platform. What can DNA medicines do better than other approaches. So we've been focused on where T cells, antigen-specific T cells are really important. So our lead clinical programs are really focused around HPV or cancer where those T cells are important. So following on behind 3107, we have 3112 addressing HPV 16 and 18 positive head and neck cancer. We have partnered with Coherus there with their PD-1 that's been approved for nasopharyngeal carcinoma here in the U.S. And then we have a program in glioblastoma, where we have partnered with Akeso with a bispecific CTLA-4 PD-1 inhibitor. So those are the next clinical programs.

At the moment, the vast majority of our resources are going into moving 3107 forward, and we look forward to advancing those late-stage clinical programs when we have the resources. We also have some really exciting early-stage work where we're leveraging DNA medicine's ability to generate these proteins to go after diseases with missing or defective proteins such as Hemophilia A, Fabry disease and hypophosphatasia. So T cell approaches and then protein replacement in the early stage.

Okay. And then I guess when the opportunity arises, how do you plan to prioritize these different late-stage pipeline programs?

Yes. It's going to be a tough challenge. I mean we've been seeking partnerships for the early-stage programs. I think partnering is going to continue to be a key part of our strategy to enable to move these multiple candidates forward. We have a partner in China, for instance, ApolloBio, who are moving forward VGX-3100 and recently reported positive top line data for HPV-16, HPV-18 positive cervical dysplasia. So I think partnerships are going to be key to us really exploiting the potential of the platform.

Okay. I know we only have a few minutes left, but perhaps you can remind us what investors should be watching for over the next 6 to 12 months and then maybe perhaps over the next 18 months as well.

Yes. I think from my perspective, clearly, the PDUFA date is going to be pivotal for Inovio. And then I think it's going to be us starting up the clinical trials for 3112 for 5412 and hopefully announcing some partnerships in the DPROT space. So that's our protein replacement disease preclinical programs.

Okay. And then maybe you can give us an update on the balance sheet and what your current cash runway is.

Yes. So at the end of the second quarter, we had $36.7 million in cash. We then completed an offering that brought in another $18.3 million net. And so our cash takes us into the end of the first quarter '27 and through a potential launch of 3107 if approved.

Okay. I think that's all the questions that we have today. Jacqui, thank you so much for joining us, and thank you, everybody, for attending this fireside chat.

Thank you very much.

Good afternoon, ladies and gentlemen, and welcome to the Inovio Second Quarter 2026 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Wednesday, August 12, 2026.

I would now like to turn the conference over to Jennie Willson, Director of Communications. Please go ahead.

Thank you. Good afternoon, and thank you for joining the Inovio Second Quarter 2026 Financial Results Conference Call. Joining me today are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Michael Sumner, Chief Medical Officer; Steven Egge, Chief Commercial Officer; and Peter Kies, Chief Financial Officer.

Today's call will review our corporate and financial information for the quarter ended June 30, 2026, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segment. During the call, we will be making forward-looking statements regarding future events and the future performance of the company.

These statements relate to our business plans to develop Inovio's DNA medicines platform, including the FDA's ongoing review of our BLA for INO-3107, including the October 30, 2026, PDUFA target date and our recently completed informal meeting with the FDA, our belief that INO-3107 fulfills the criteria for accelerated approval, the potential benefits of INO-3107, including our belief that it has a positively differentiated product profile, our belief regarding its competitive advantages relative to existing treatments, including PAPZIMEOS and the potential to become the preferred product and new standard of care for patients and their physicians, if approved, our expectation to receive orphan drug market exclusivity for INO-3107, if approved, and the anticipated timing of label negotiations, the anticipated commercial launch of INO-3107, if approved.

Our commercial launch infrastructure and preparations; our engagement of commercial partners, including Syneos Health and other third-party partners in preparation for a potential launch, the recent positive Phase III data announced by our partners for Greater China for VGX-3100 as a potential treatment for cervical dysplasia and ApolloBio's plans to seek regulatory approval for VGX-3100 in China based on that data, the advancement of our DPROT technology platform, capital resources, including our estimated operational net cash burn of approximately $18 million for the third quarter of 2026 and the expected sufficiency of our cash resources into late first quarter 2027 and through a potential launch of INO-3107 and our expectations regarding competition, market size and acceptance of INO-3107 if approved.

All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release. This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded.

I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

Good afternoon, and thank you to everyone for joining today's call. Since our last quarterly call in May, the FDA's review of our BLA for INO-3107 has continued to advance with several important steps in the regulatory process now complete. We are on track for the October 30 target PDUFA date. And while Mike will go into greater detail on our regulatory progress, the highlights are that the FDA has completed its late cycle review meeting and completed all of the scheduled pre-licensure inspections.

The FDA also granted the previously requested informal clinical meeting, where we had the opportunity to present the totality of data supporting INO-3107's safety and efficacy and highly differentiated approach in treating RRP, a chronic HPV-related disease that has a devastating impact upon patients. We believe there remains significant unmet need for treatment options that reduce the need for RRP-related surgery. And we believe the efficacy, tolerability and patient-centric approach of 3107 could enable it to become established as the new standard of care.

With that goal in mind, we have continued advancing our commercial launch preparations, including initiating the build of our critical launch infrastructure, which Steve will expand upon. We also completed an equity offering that provided approximately $18.3 million in net proceeds in late July to support these efforts, which we expect to extend our runway into late first quarter 2027 and through a potential launch of 3107, if approved.

While our resources are focused on advancing 3107, Inovio's partnerships have enabled important progress with other promising candidates across our pipeline. ApolloBio, our partner for VGX-3100 in Greater China, announced positive top line results from its pivotal Phase III trial as a potential treatment for HPV-16 or 18 positive cervical dysplasia. This further highlights the potential of Inovio's DNA medicine platform as a nonsurgical treatment option for HPV-related diseases.

Inovio also presented promising preclinical data on our next-generation DNA-Encoded Protein or DPROT technology targeting Factor VIII production for the treatment of Hemophilia A at several scientific conferences during the second quarter. Of note, we have added 2 new rare disease targets for the platform, Fabry Disease and Hypophosphatasia.

I'll now turn it over to Mike for some additional details on our regulatory progress with 3107.

Thanks, Jacqui. As Jacqui noted, over the past several months, we have made considerable progress with INO-3107 on the regulatory front as the FDA's review of the BLA continues to advance under the agency's accelerated approval program. The FDA has now completed its late cycle review meeting and all scheduled pre-licensure inspections, which included clinical, drug manufacturing, in-house drug testing and our delivery device facility.

I am pleased to say that there was only one reported observation from the inspections, which we believe we have appropriately addressed, and we are in the process of submitting our response to the FDA. Following the recent change of leadership at CBER and the Office of Therapeutic Products, the FDA also held a clinical informal meeting in July. During this meeting, we had the opportunity to present the totality of data supporting the safety and efficacy of 3107 and highlight its highly differentiated approach in treating RRP.

We continue to believe we have provided a strong rationale for eligibility under the accelerated approval program, highlighting the ongoing need in the RRP community for therapeutic alternatives to existing treatments while also sharing our rationale for how 3107 demonstrates a meaningful therapeutic benefit over those existing treatments. During this informal meeting, the FDA noted that the BLA review was ongoing and did not discuss their preliminary conclusion regarding accelerated approval eligibility, which was noted as a potential review issue in the December 2025 file acceptance letter. They did, however, indicate that their feedback on the design of our confirmatory trial will be forthcoming.

To provide more context around 3107's eligibility for accelerated approval, when there is already an existing product that has received a full approval, the FDA's guidance indicates that a product candidate reviewed under the accelerated approval program should provide both a meaningful therapeutic benefit over existing treatments and meet a remaining critical unmet need among patients.

We believe that 3107 meets both of those criteria based on 3 factors: First, clinical efficacy as demonstrated in our Phase I/II trial, where the vast majority of patients experienced a 50% to 100% reduction in surgery in year 1 with continued clinical improvement in year 2. Second, 3107 has been shown in clinical studies to be well tolerated, potentially offering a beneficial safety profile that does not include the requirement for scoping and surgery during the dosing window to maintain minimal residual disease, or MRD, which is required for PAPZIMEOS and included in their labeling.

Third, 3107 has a differentiated mechanism of action, not impacted by pre-existing neutralizing antibodies or an immunosuppressive tumor microenvironment, both of which may impact the efficacy of PAPZIMEOS. These 3 key strengths, clinical efficacy, safety and a differentiated MOA underpin why we believe 3107 is eligible for review under the accelerated approval program and has the potential to become the new standard of care for RRP. Importantly, a representative from the RRP Foundation and a healthcare provider specializing in the treatment of RRP were able to join the informal meeting as well. Both provided statements reiterating the significant continuing unmet need in the RRP community and their belief in the ability of 3107 to meet those needs.

From the start of our development work on a treatment for RRP, we have been working closely with the foundation, patients and other RRP experts to understand and highlight what matters most to them, providing every patient with relief from the risks and costs that come with every surgery. We are thankful for their continued support as we work to deliver on the promise of 3107 for patients. We believe we are now in the final stages of the regulatory review process and anticipate starting label negotiations in September. It is also important to note here that if approved, we would expect to receive 7 years of orphan drug market exclusivity for 3107 based on our differentiated delivery and mechanism of action. Finally, we are also initiating our medical science liaison team to begin scientific engagement with potential customers.

With that, I will now turn it over to Steve to provide an update on our commercial progress and strategy.

Steve?

Thanks, Mike. We're excited about the opportunity to bring 3107 to patients who are waiting for new treatment options. We see a significant unmet need in the market for alternatives to surgery and certainly, the early uptake of PAPZIMEOS validates this unmet need. The early reported uptake is encouraging with approximately 200 patients treated. This still only represents low single-digit penetration among a prevalent population, so the vast majority of RRP patients in this market are still open for a new treatment option.

And 3107 is a product that was designed to deliver what we believe patients and healthcare providers want most: clinical efficacy, tolerability and a simple patient-centric treatment approach that reduces the need for surgery. As you can see on this slide, 3107 offers many competitive advantages. First, 3107 treats RRP without requiring additional scoping and surgeries during the dosing window. In the dosing section of the prescribing information for PAPZIMEOS, scoping and surgeries to remove any papilloma are required prior to dose 3 and 4.

In the Phase I/II trial for PAPZIMEOS, the vast majority, 83% of participants, required at least 1 MRD surgery during the dosing window. When given a choice, we believe patients would prefer a therapeutic option that does not require additional surgery as every surgery comes at a risk and a cost to patients. An additional advantage of not requiring surgery during the dosing window is that this also helps minimize any recovery days needed during treatment.

As Mike noted, with 3107, there's no potential impact on clinical benefit from an immunosuppressive papilloma microenvironment and no potential impact on clinical benefit due to preexisting neutralizing antibodies. And finally, 3107 does not require specialized ultra-cold chain handling, so there's more flexibility in terms of care settings where the product can be administered. These competitive advantages are foundational to our belief that 3107 has the potential to become the new standard of care for RRP, should it be approved.

To execute on this opportunity, we plan to leverage experienced field teams, and we're pleased to share that Syneos Health, who has deep experience in rare disease launches, will serve as Inovio's contract sales organization to support commercialization in the U.S. We also plan to execute targeted marketing in partnership with our agency of record and establish a strong patient support team through our hub partner. Together, these efforts will enable us to establish access with payers and hospital systems, drive preference with healthcare providers and patients, and over time, grow the market by educating patients and caregivers. We're now ready to move to the implementation phase of our launch planning. There's important work ahead, and it will continue to be driven by the needs of RRP patients and the opportunities we see for 3107 to meet those needs.

I'll now turn it back over to Jacqui for a pipeline update.

Jacqui?

Thanks, Steve. While our resources are focused primarily on 3107, we've continued to look to partnerships to help advance other promising candidates in our pipeline. Collaborations will continue to be essential to the growth and evolution of our platform. An example of this is the partnership with ApolloBio I mentioned earlier. They recently announced positive top line results from their pivotal Phase III trial of VGX-3100 for the treatment of cervical dysplasia patients.

The trial successfully met its predefined primary efficacy endpoint of CIN 2 or CIN 3 lesion regression and HPV-16 and 18 viral clearance and demonstrated an overall favorable safety and tolerability profile. ApolloBio plans to use the results from the study to support a future filing for regulatory approval for VGX-3100 in China. Furthermore, the positive data from this trial provide additional support for the potential of DNA medicine to treat HPV-related diseases and eliminate and/or reduce the need for surgical interventions to control the potentially devastating implications caused by HPV infection.

We are also working to build partnerships to accelerate the development of our next-generation DNA medicine platform. During the second quarter, we shared exciting research on our DNA-Encoded Protein or DPROT technology targeting Factor VIII for Hemophilia A at several scientific conferences, including the American Society of Gene and Cell Therapy Annual Meeting and the World Orphan Drug Congress. Based on this promising research, we are looking to form partnerships to advance DPROT candidates in various rare diseases, including Fabry Disease and Hypophosphatasia and have ongoing discussions with a number of potential partners.

Now I'll turn it over to our CFO, Peter Kies, for a financial update.

Peter?

Peter's having trouble. He's dialing in again.

Hello? Hello?

Peter, go ahead.

Yes. Thanks, Jacqui. Today, I'd like to provide an overview of Inovio's financial results for the second quarter of 2026. As Jacqui noted, our primary goal is to advance INO-3107 towards approval and to enable an efficient launch, if approved. We're now entering an important phase of the build-out of critical commercial work streams requiring additional resources.

To that end, I'm pleased to report that the company strengthened its balance sheet with an underwritten public offering in July 2026. Net proceeds from the offering after deducting underwriter discounts, commissions and operating expenses were approximately $18.3 million. We ended the second quarter of 2026 with $36.7 million in cash, cash equivalents and short-term investments compared to $58.5 million as of December 31, 2025.

With the addition of the July public offering, we expect to extend our estimated cash runway into late first quarter 2027 and through a potential launch of INO-3107. This projection includes an operational net cash burn estimate of approximately $18 million for the third quarter of 2026. These cash runway projections do not include any further capital raising activities that we may undertake and are based on current projections and assumptions. We will continue to be mindful of our cash burn while ensuring we are ready to launch 3107, if approved.

Turning to our operating results for the second quarter. Operating expenses dropped from $23.1 million in the second quarter of 2025 to $18.6 million in the second quarter of 2026, a 19% decrease. When you look at the first 6 months, of 2026, we reduced operating expenses by 16% compared to the same period last year. Again, this is due to ongoing strategic efforts to manage our resources to support progression of the 3107 program.

Inovio's net loss for the second quarter was $6 million or $0.07 per share, basic and dilutive, compared to a net loss of $23.5 million or $0.61 per share, basic and dilutive, for the second quarter of 2025. The decrease in net loss was primarily driven by a $13.9 million noncash gain on fair value adjustment related to our warrant liabilities for the 3 months ended June 30, 2026. As the fair value of the warrants fluctuates with our share price and other market inputs, this adjustment can result in a significant variability in our reported net loss. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our quarterly report on Form 10-Q filed with the SEC.

And with that, I'll turn it back over to Jacqui.

Thanks, Peter. I'd now like to pause to open up the call to answer any questions you might have.

Operator?

[Operator Instructions] Your first question comes from the line of Liang Cheng from Jefferies.

I guess for me, I wonder, could you provide more detail on 3107 informal clinical meeting and whether any new efficacy, safety or CMC-related questions were raised by FDA?

Liang Cheng, nice to hear from you. Mike, do you want to provide a bit more detail on that informal clinical meeting?

Yes, happy to. I mean, we were delighted that FDA granted the meeting as it really gave us an opportunity to share with them the entirety of our compelling data set as it relates to the efficacy and safety of 3107. I mean, during the review process, we've had the opportunity to submit the assessment aid back in February and obviously respond to some clinical questions. So the FDA had seen the entirety of the data that we submitted to them.

And we really didn't get into too much discussion around that. They certainly have not disagreed with our positioning in terms of how we've presented our efficacy and safety data. But unfortunately, as you heard me say, they weren't in a position to comment on the eligibility question as the file is under active review.

Okay. And could you provide any updates on the confirmatory trial design, including the patient population, endpoints and the potential initiation following approval?

Yes. So we are still awaiting the FDA's comments on our submitted protocol to the IND. They did say during that informal meeting that comments would be forthcoming. Obviously, this is relatively late in the review process now. So we obviously will be discussing with them their expectations around starting that trial, but we have no reason to believe that getting that trial up and running will impact our approvability or our PDUFA date.

[Operator Instructions] There are no further questions at this time -- we do have one question coming from Yi Chen from H.C. Wainwright.

This is Katie on for Yi. Should investors expect another capital raise before the PDUFA? Or is the plan to bridge launch through revenue and financing partner?

Katie, nice to hear from you. So as we discussed on the call, we're currently funded through late first quarter 2027, which is after the anticipated launch. So we're currently funded through projected launch date.

Peter, do you want to comment further?

No, Jacqui, I think you covered it. Thank you.

Just as a quick follow-on. Does that first quarter '27 bake in pre-launch inventory build and launch marketing spend? Or does it assume a straight to launch scenario without those costs?

No, those are built in throughout fourth quarter and first quarter.

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

Thank you. As we enter the critical final stages of the BLA review and prepare for a potential launch of INO-3107, we are focused on the important work ahead and excited about the potential we see to meet the unmet needs of the RRP community. We are grateful for the continued collaboration and support of the RRP Foundation, whose advocacy inspires our work every day. And together, we are driven by the understanding that every surgery matters, every patient matters and every patient deserves a treatment that works for them.

I look forward to sharing more on Inovio's progress in the pivotal months ahead. Thank you for your attention, and good evening, everyone.

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

Welcome everyone to Jefferies 2026 Global Healthcare Conference. My name is Roger Song covering sMICA Biotech. It is my pleasure to introduce our next company, Inovio, CEO, Jacqui Shea, and then she will do a company overview, and then we will have Q&A towards the end. Thank you.

Thanks, Roger. Yes, thanks for the opportunity to present today. It's great to be at the conference. So moving on, for those of you who are not familiar with the Inovio story, I'd like to provide a quick overview of the company and our lead asset, INO-3107, which is in development for treatment of recurrent respiratory papillomatosis or RRP.

This is just our standard forward-looking statements disclaimer slide that during this presentation, I'll be making forward-looking statements, and I refer you to our most recently filed 10-K for further details.

So to give you a quick overview of the company, Inovio is a clinical stage biotech company. We're really focused on developing -- sorry, I can't really see the slides on the monitor. Can someone switch the monitor into a bigger view because I can't really see them? No. Okay. I'll just work off this main screen then. So we're focused on developing and commercializing DNA medicines to treat -- that's better, thank you -- to treat and protect people from HPV-related diseases, cancer and infectious diseases.

Our lead program for treatment of RRP, 3107. Our BLA is currently under review with FDA with a PDUFA target date of October 30, 2026. RRP is a rare HPV-related disease. And even not though there is an improved product on the market, there remains a high unmet need and a significant market opportunity.

3107 has been granted orphan drug and breakthrough therapy designations in the U.S. has orphan drug designation within the EU. And during our file acceptance letter, FDA noted preliminary comment in the letter regarding eligibility of 3107 for review under the accelerated approval program that we're looking to resolve with them and that they promised us an informal meeting to discuss.

We have established our commercial scale manufacturing for our DNA component of our combination product, our plasmids, at external contract manufacturers, and we manufacture our devices in-house. Following on behind 3107, we have a deep clinical pipeline with multiple potential near and midterm catalysts.

So how do DNA medicines work? So to tell you a bit about the mechanism of action, we start by identifying the protein that we either want to generate an immune response against or that we want to use to replace a missing or defective protein or to produce a monoclonal antibody. We then use our proprietary algorithms to optimize that gene sequence.

We insert that sequence into a circular molecule of DNA called the plasmid. And then we've administered the plasmid into either the skin or muscle cells using our proprietary delivery devices called CELLECTRA. They use a process called in vivo electroporation, which are very short transient pulses of electrical energy that allowed the plasmids to enter the cells. Once within the cells, the plasmid's drive protein production, and then that protein can either drive an immune response, either T cells or antibody or the proteins that are produced and secreted themselves can be the therapeutic agent.

So DNA medicines are particularly good at driving T cell responses which is very good for targeting treatment of cancers or viral infections. As part of the proteins that we produce, we've shown that we're able to produce DNA-encoded monoclonal antibodies, which are assembled within the cells and then are secreted into the circulation. And we can achieve therapeutic levels of these transgene encoded proteins.

So moving on to 3107, our lead candidate. As I mentioned, our BLA has been accepted by FDA for review under the accelerated approval program, and we have a PDUFA date coming up in October 30 of this year. RRP is rare disease causes the small wart-like growth saw papilloma throughout the respiratory tract, but primarily on the vocal cords, where it really impacts the patient's ability to speak or talk, can inhibit the ability to breathe.

The papilloma can also grow down into the lungs and can also become elegant, in which case, the prognosis is very poor. It's caused by HPV 6 and 11 serotypes primarily. It's a rare disease, but not that rare, about 14,000 cases in the U.S., about 1,800,000 new cases each year and repeated surgery is still a standard of care. And every surgery comes with a significant cost and risk to the patient.

The risk is permanent damage to the vocal cords or scarring of the airway. And there's the potential for irreversible damage with every surgery. The cost is obviously the impact of quality on life, financial, constant recovery from surgery. Some of these patients have had hundreds of surgeries over their lifetime.

And 3107 was really designed with this need to reduce surgery in mind. It's designed to generate an antigen-specific T cell response against HPV 6 and HPV 11 and eradicate HPV impacted cells and thus target the underlying cause of RRP.

So what really matters to patients? What really matters to patients with their disease is this constant process of surgery. And the cumulative risk of surgery for injury increases after every single surgery. And ultimately, it only takes one surgery to cause permanent damage. By the time patients have had 5 or 10 surgeries, almost all of them have permanent damage to their airway or to their vocal cords. So when we started to develop our 3107, we really took the patient needs in mind. So our treatment regimen requires 4 doses given over a period of 9 weeks. And we counted every surgery after day 0 because every surgery matters to patients and our efficacy endpoint was reduction in surgery.

The competitor product, PAPZIMEOS, which was approved last year in contrast is really a drug surgery combination. They also give 4 doses but over a longer time period and they conduct cleanup surgeries at doses 3 and 4. So any visible papilloma that they see, they remove doses at the time period of doses 3 and 4. And they only start counting surgeries after the treatment regimen has completed. So they start counting surgeries at week 12. So these are very different treatment approaches. Our approach is really focused on minimizing surgery for all patients.

So as I mentioned, in our file acceptance letter, FDA commented on a potential review issue that we may not be eligible for review under the accelerated approval pathway. FDA have agreed to have an informal meeting to discuss this, and we have submitted an assessment aid to support that and we're waiting for FDA to schedule that meeting. We very strongly believe that 3107 does meet the FDA criteria for review under the accelerated approval pathway because it provides a meaningful therapeutic benefit over existing treatments, and it has a potential to meet the remaining critical unmet need for patients. And this is what the FDA guidance specify.

So on the efficacy side, we were very pleased with the efficacy we saw. We saw 72% of patients had a 50% to 100% reduction in the number of surgeries compared to the prior year. This went increased to 86% in year 2 and 28% of patients in year 1 and 50% of patients in year 2 required no surgeries at all to control their disease.

We also have an enhanced safety profile compared to the improved product because we don't require these additional surgeries during the dosing window. And in the approved product, over 80% of their patients require these surgeries during the dosing window, including over 70% of their complete responders. So there are patients who remind no surgery after treatment. So it's really a very different profile.

So moving on to also how we're different to the PAPZIMEOS program and our ability to treat patients that are not served by existing therapy. We don't see any impact because we're a DNA medicine that's delivered via electroporation, we don't use any viral vectors, and we see no impact from neutralizing antibody, therefore, against biofactors. We also have shown that we see no impact from an immunosuppressive papilloma microenvironment on 3107 efficacy.

So as you can see, we're very different to the approved product. And market research that we conducted continues to support that we believe that we have the preferred product profile in this area. This is based on efficacy, tolerability and a simple patient-focused treatment regimen. As I mentioned, our efficacy improves over time. We're very well tolerated.

Most of our AEs are associated with injection site pain, which then very rapidly resolved. We don't need an ultra cold chain, 3107 is able to be given in the doctor's office. And very importantly, there's no requirement for the scoping or surgeries during the dosing window. And we've worked throughout this program. We've worked very closely with the RRPF, so the Recurrent Respiratory Papillomatosis Foundation, which is the patient advocacy organization for RRP patients, and they also continue to be very supportive of our efforts. They continue to see an unmet need even with an existing product on the market because there really are patients for whom the approved product just isn't meeting their needs.

So moving on now to our development pipeline. We have a number of other candidates in development with multiple near- and midterm catalysts. To give you a quick overview of our pipeline. As you can see, we have VGX-3100 in Phase III and our partner in China, ApolloBio, just reported positive top line data for that Phase III trial and that, that trial met its primary endpoint. We also have some other HPV-related candidates as well as some cancer-related candidates in Phase II which I'll talk about in a bit more detail in a moment. And then as I mentioned, our very promising depot candidates currently in the preclinical space.

So to turn to 5412, briefly, 5412 is our candidate for glioblastoma, one of the most deadly and aggressive forms of brain cancer, one of the most common forms as well. very poor prognosis. We had conducted a previous study in glioblastoma, where we had shown some promising data in terms of the ability to extend median overall survival in both methylated and unmethylated patient groups.

And what we are planning to do now in this trial that is sponsored by the Dana-Farber Cancer Institute is to combine 5412, which is driving T cell responses against tumor-associated antigens, which are increased in glioblastoma tissue is combine that with a dual checkpoint inhibitor from Akeso and look to see if we can see an extension in median overall survival. And we're looking to start that trial after we have had our PDUFA data on 3107.

Then turning to our DMAbs and our DPROT programs. Last year, we published some really groundbreaking data in Nature Medicine, showing that we were able to produce 2 different monoclonal antibodies, driven off DNA plasmids within the same patients. These monoclonal antibodies were produced at therapeutic levels, were functional and were produced at stable levels up to 96 weeks. And this is really the first time any group has been able to show production of monoclonal antibodies like this.

Now monoclonal antibodies are, of course, just a form of complex protein. And we can apply this technology to other candidates in our pipeline, such as our DPROT candidates for missing or defective proteins. So our initial program was in the hemophilia A where we were looking to produce Factor VIII. In our preclinical data, we were able to demonstrate that Factor VIII can be effectively produced assembled within the muscle cells and then secreted into the circulation. And treated mice very importantly, showed reduced bleeding time and blood loss in a hemophilia model.

We also have preclinical programs in Fabry disease in hypophosphatasia, are also working up some other rare disease targets and are currently seeking partnerships to advance these programs more rapidly.

So to summarize, in the near term, our focus is really on our upcoming PDUFA date and 3107 and working to deliver 3107 to patients. Midterm, really focusing on advancing our diversified clinical pipeline. And then we're also very excited by our next-generation DNA candidates, particularly DPROT candidates and they're looking to generate some partnerships to move these along more rapidly. Thank you very much for your time.

Thank you, Jacqui. And then we're also joined by Michael, our Chief Medical Officer, here. Maybe Jacqui, I would say that the real most pertinent question is how is the regulatory kind of review process looking like? We were quite surprised and then how confusing the language is when you got the acceptance letter.

So it is accelerated approval path but they also say you're not eligible for this. So you are still -- maybe just walk us through right now what's the state of our in terms of the review process looking like? And then I know you say you are requesting informal meeting to confirm your eligibility for the accelerated approval? And then what's the key topics you want to bring up to that meeting? And then what's the potential outcome from that?

Yes. All great questions. So as you mentioned, we submitted our BLA after rolling submission under the accelerated approval program and FDA has accepted our BLA. In the file acceptance letter, they noted a preliminary conclusion, which could be a potential review issue that we had not provided sufficient data to justify eligibility for review under the accelerated approval program.

Now we strongly disagree with that. We have requested a meeting with the FDA to discuss eligibility for review under the accelerated approval program. And FDA has agreed to an informal meeting. We've also completed an assessment aid, which we submitted to them, and we're waiting for that meeting to discuss it with them.

In the meanwhile, the review is proceeding as normal. And we're really very comfortable with how the review is proceeding. We've had our mid-cycle review, had no new issues raised. We're looking forward to our late cycle review meeting, which will be in the third quarter. And we expect to have had all of the various inspections that are required as part of the BLA process, also completed ahead of that late-cycle review meeting.

So generally, we're very happy with how that review is going. We are continuing to encourage FDA, of course, to schedule the informal meeting to discuss the review pathway. And really for eligibility under the accelerated approval pathway, there needs to be a continued unmet need, which there very clearly is. The approved product doesn't work for all patients and also can't work in some patients, so patients who have neutralizing antibodies against the vector or who have an immunosuppressive papilloma microenvironment.

So we're going to be really talking about why we believe that there continues to exist an unmet need and why we think 3107 provides a meaningful therapeutic benefit over the approved product. And that's really across the efficacy, the tolerability. We're not requiring these additional surgeries during the dosing window. So we have a very differentiated safety profile. And also, we have a differentiated mechanism of action where we don't use a viral vector for delivery. We're including different transgenes. We're not impacted by the papilloma microenvironment. So very clearly, very different products.

Yes. I think I agree. A lot of the point you brought up is pretty compelling to qualify the accelerated approval and we'll see how the FDA agree with that.

Okay. And then we are kind of experiencing or observing all the changes happening within FDA. So what have you been experiencing in terms of the review team and leadership? And then do you think this accelerated approval eligibility will be impacted by any of those changes on the top?

Yes. Since I mentioned, we've been very happy generally with how our review has been progressing. Clearly, we still need to get this informal meeting to discuss the review pathway in place. And we really can't comment at this time on changes in leadership. There have clearly been a lot of changes over the past few months. And we're encouraged by the signs that we're seeing from the new leadership. And we look forward to collaboratively working with them on the review of 3107.

Okay. Got it. And then another component of the review is you are filed under accelerated approval, which means you are -- you will need to do a confirmatory study to get a full approval. How is that part going and then what -- how this will fit into the whole process right now?

Yes, great questions. So we have submitted an amendment to our IND for our confirmatory trial. We have about 20 clinical sites up and ready to start that confirmatory trial. Once FDA gets back to us on the protocol. But until FDA gets back to us on the protocol, I don't think I can really comment on the design of the trial.

And then do you expect any surprise there or any incremental comments so far from the FDA or it's still kind of an ongoing discussion?

Yes. It's still an ongoing discussion, and we're waiting for their feedback on the protocol.

Got it. And then in terms of the timing of the SPAR and the enrollment of the confirmatory study versus your PDUFA day, so how you should think about it substantially underway or in you enroll one patient or something like that?

Yes. Well, FDA are clearly looking for a commitment to get your complementary trial moving in an appropriate way. And I think we'll be able to demonstrate that we have -- we've taken all of the steps necessary to do that. FDA ultimately have discretion as to what stage your complementary trial needs to be at, at the time of approval.

Got it. Okay. Good. And then move forward, you get accelerated approval, happy result. And then moving to the commercial stage. One is how you think of the pricing strategy over there. You do have another approved drug in similar population, but not entirely the same.

Yes. So obviously, we're thinking rare disease pricing is appropriate. We've conducted market research, which has validated that assumption. We'll be talking about our pricing a bit closer to approval.

Got it. And then do you think you want to launch the drug? It's orphan drug and then not by yourself or you want to seek a partner?

Yes. So we're planning to launch the drug ourselves in the U.S. We'll probably use a contract sales organization. We have the other elements of that we're going to require to commercialize such as the 3PL, our patient hub, our specialty distributor, specialty pharmacy. So we have all of our partners lined up, and we're really waiting for our PDUFA date. Ex U.S., we're really looking to partnerships to commercialize.

Got it. Okay. Makes sense. And then to the extent you can comment on how the first approved RRP drug on the market and how they perform and what you can learn from them in terms of the commercial dynamic and then the ramp-up look like.

Yes. So we're obviously very closely watching the PAPZIMEOS launch and seeing what we can take away from that launch and how we can -- how that can benefit our launch. I think what we're seeing is encouraging uptake. I think that's because there's a very high unmet need amongst RRP patients. And we continue to believe that we have the preferred product profile.

And I think there are plenty of examples, particularly in the rare disease space, of a fast follower coming on to market with a better product profile that can rapidly capture market share. So we're excited by the market opportunity for 3107.

Yes. Based on your feedback from your adviser and then the cognition, you've been interacted. Do you think they are ready to adopt your drug versus others? And then how they think about in terms of the patient readiness and then how the ramp-up is going to look like. It's a rare disease, but I think with even better drug, they do they -- do you think they will be more ready to use the drug?

Yes. So when we've conducted market research, what both physicians and patients really like is the fact that 8 out of 10 patients really see a marked improvement in terms of reduction in surgery compared to the pretreatment period. So for a patient taking 3107, they have a very good chance of seeing a significant reduction. So that's very appealing to them.

The fact that they don't require additional surgeries or scoping during the dosing window is very appealing to them. And then the fact that 3107 can be given in the doctor's office and the physician doesn't have to worry about could my patient have neutralizing antibody against the vector? Could the papilloma microenvironment be inhibiting efficacy as for the approved product? That really doesn't apply to 3107.

So it's a much more straightforward decision. Patients can expect to see a good reduction in surgery. They're not going to have to undergo the scoping and surgeries and they're not going to have to worry about factors that may mean that they're not a good candidate for 3107.

And how do you think about the durability going to play into the decision here and also the potential label? I understand it's pretty long lasting for a lot of patients. And then will this become -- at some point, they need to read those. If that's the case, how the label is going to be looking like and how the payer is going to decide to reimburse that.

How about ...

Happy to. So I mean, as you saw, Jacqui present, we saw 72% of patients 50% or greater reduction. That actually increased to 86% in the second year. When you look at the complete responders, i.e., 0 surgeries after the first dose. We saw 7 of those continue that into the second year. So the vast majority of patients are seeing a significant reduction that is durable.

And as you mentioned, one of the benefits of our DNA medicine platform is the fact that we can redose. So following approval, we do plan to do a continued treatment protocol. And obviously, we hope to certainly be able to maintain that excellent response we saw with the initial treatment. But obviously, also hope for further improvement with continued treatment.

Yes. And with regard to your comment about payers and how they would view continued treatment, I mean, clearly, the current approved product is quite an expensive drug. It's marketed at about $115,000 per dose. And I think really what payers are looking for is they're looking for long-term durable control of disease. And if that requires additional doses to do that, then that's in the patient's best interest. So I think from our discussions with payers, they've been open to continue treatment if it's really delivering results.

Got it. And then the -- in terms of the durability, those patients, if they are durable and then it will become interesting dynamic if they continue to responding and then you're waiting for them to do potentially relapse and then you can do the redose? And then how the time certainty or uncertainty will play into the decision for payers to cover this.

I mean, we're dealing with a chronic viral infection here. So I mean, we're not eradicating the virus in most of these patients. So it actually, I think, makes much more sense to have a well-laid-out treatment protocol for these patients so that we can. So we're not necessarily waiting for them to relapse and we have a treatment protocol that hopefully eventually can eradicate the underlying viral infection.

Okay. So you're not waiting them to relapse to do the redose. Maybe I ask another question is, how are you going to test this redose regimen? It's in your confirmatory study or you can just follow those patients you already treated and then see any signal you can start to retreat them? That's maybe a more fair question.

Yes. So I mean, we -- as you heard Jacqui mentioned, we haven't aligned on yet what our confirmatory protocol will look like. We'll obviously use all opportunities we can to show the evidence of 3107's ability to redose. But we have also seen that ability with previous plasmid in HPV targeting 1618. So we're very confident of what 3107 will be able to deliver.

Got it. And then interesting, we just saw the news, the current drug that they filed for or get accepted for the orphan drug designation. How does that impact your regulatory approval and then also commercial?

Yes. Great question, Roger. So the approved product just received orphan drug exclusivity. And what that means is that you can't basically bring the same drug for the same indication to market. 3107 is very clearly different to PAPZIMEOS. We're not delivered via a viral vector. We encode different transgenes. We're a different product. So 3107 isn't impacted by the orphan drug exclusivity, and it doesn't impact our regulatory pathway.

Excellent. All right. Time's up, and thank you so much, Jacqui and Michael. And thank you, everyone, for watching and listening.

Thank you.

Good afternoon, ladies and gentlemen, and welcome to the Inovio First Quarter 2026 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Wednesday, May 13, 2026. I would now like to turn the conference over to Jennie Willson. Please go ahead.

Good afternoon, and thank you for joining the Inovio First Quarter 2026 Financial Results Conference Call. Joining me today on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Steve Egge, Chief Commercial Officer; and Peter Kies, Chief Financial Officer.

Today's call will review our corporate and financial information for the quarter ended March 31, 2026, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segment. During the call, we will be making forward-looking statements regarding future events and the future performance of the company.

These statements relate to our business plans to develop Inovio's DNA medicines platform, including the FDA's ongoing review of our BLA for INO-3107, including the October 30, 2026, PDUFA target date and our yet-to-be scheduled meeting with the FDA to discuss eligibility for the accelerated approval program, our belief that INO-3107 fulfills the criteria for accelerated approval; the potential benefits of INO-3107, including our belief that it has a positively differentiated product profile and the potential to become the preferred product by patients and their physicians, if approved; the anticipated commercial launch of INO-3107, if approved, and our engagement of commercial partners in preparation for a potential launch; our collaboration with Akeso Inc. to evaluate INO-5412 in combination with a novel dual checkpoint inhibitor for the potential treatment of GBM, the advancement of our DPROT technology platform, capital resources, including our estimated operational net cash burn of approximately $18 million for the second quarter of 2026 and the expected sufficiency of our cash resources into first quarter of 2027 and our expectations regarding competition, market size and acceptance of INO-3107 if approved.

All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release. This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded.

I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

Good afternoon, and thank you to everyone for joining today's call. These are very busy times at Inovio as we remain focused on achieving our top priority, advancing our lead candidate, INO-3107 through the regulatory process and toward its October 30 target PDUFA date.

Our goal is to ensure that every patient with recurrent respiratory papillomatosis or RRP has access to a therapeutic option that can work for them to reduce the need for surgery. If approved, we believe that our innovative therapy has the potential to become the preferred product for patients suffering from RRP, a rare and debilitating disease of the respiratory tract with a critically high unmet need for effective nonsurgical treatment options. The BLA for 3107 has been in active review since December when the FDA accepted the file for review under the accelerated approval program.

While Mike will provide a more in-depth regulatory update, I'd like to comment on a couple of key highlights. The FDA recently completed their standard mid-cycle review with no new significant issues being raised and scheduled the late cycle review for the third quarter. As you will recall from our last quarterly update, the FDA had previously agreed to an informal meeting to discuss the potential review issue they noted in their file acceptance letter regarding eligibility for review under the accelerated approval program.

As a part of communications about the mid-cycle review, they reiterated their intent to schedule that meeting, and we look forward to the discussion. While we made progress with 3107 on the regulatory front, we've been advancing our commercial readiness plans, including continuing to gather key strategic insights from the RRP community. And while the majority of our resources are focused on 3107, we're continuing to leverage the power of partnerships to advance other promising candidates in our pipeline, including an exciting opportunity to work with Akeso and the Dana-Farber Cancer Institute to build on our previous immuno-oncology work in glioblastoma or GBM.

We're also advancing our innovative next-generation candidates and I'm pleased to have recently presented promising preclinical data on our DNA-encoded protein or DPROT technology work targeting Factor VIII production in hemophilia A and announced 2 new rare disease targets in Fabry disease and hypophosphatasia for the platform. We are laser-focused on these strategic priorities and excited about what's ahead for Inovio as we work to deliver on the promise of DNA medicine for patients.

I'll now turn it over to Mike for some additional details on our regulatory progress with 3107. Mike?

Thanks, Jacqui. As Jacqui noted, since our BLA for INO-3107 was accepted for review under the accelerated approval program in December of 2025, the FDA has been actively reviewing our submission. We have been responding to routine requests for information and meeting regular top milestones in the review process, including the FDA completing its mid-cycle review of our BLA, where no new significant issues were raised.

At the time of the mid-cycle review, the FDA indicated that it is continuing to review the assessment aid we submitted in February, which outlined our rationale for accelerated approval program eligibility. They also reiterated their intent to schedule the previously agreed to informal meeting to discuss this potential review issue, which they noted in their file acceptance letter. In addition, we reported last quarter that we had submitted an updated protocol for our confirmatory trial to the IND, which is required under the accelerated approval program.

We are waiting for feedback from the agency on both the informal meeting and the confirmatory trial protocol so we can finalize the study design. We look forward to having the opportunity to discuss these issues further with the FDA and to emphasize why we believe that 3107 fulfills the criteria for accelerated approval by meeting a significant unmet need and providing a meaningful therapeutic benefit over existing treatments.

I'd like to take a moment now to elaborate on that rationale. Based on published FDA guidance, our eligibility depends on the ability of 3107 to provide a meaningful therapeutic benefit over existing treatments and the ability to meet a remaining critical unmet need among patients. We believe that 3107 meets both of these criteria based on 3 factors: First, effectiveness as demonstrated in our Phase I/II trial, where the vast majority of patients experienced a 50% to 100% reduction in surgery in year 1 and with continued clinical improvement in year 2.

Second, an improved safety profile that does not include required surgery to maintain minimal residual disease during the dosing window. And third, a differentiated mechanism of action that does not come with the risk of reduced clinical effectiveness due to known immune factors that impact the efficacy of the approved product, including preexisting neutralizing antibodies or an immunosuppressive tumor microenvironment, thus providing an important opportunity to treat patients who are not served by existing therapy. It is important to emphasize again that at the heart of our belief in 3107's eligibility for accelerated approval are the patients, patients who face the risk of permanent damage to the vocal cords and significant social, emotional and financial costs every time they require surgery to manage their disease. Every surgery matters to patients, and we believe that every patient should have access to a treatment option that works for them to reduce the need for surgery.

A compelling example of the remaining unmet need for therapeutic options for RRP patients is the fact that the recently approved gorilla adenoviral-based immunotherapy does not work for a number of patients according to that product's published data. Further, the treatment regimen for this product requires surgery prior to the third and fourth doses if visible papillomas are present to maintain a state of minimal residual disease. This means that nonresponders or the patients for whom this product didn't work, had 2 surgeries during the treatment window and then saw no clinical benefit or improvement in the following year according to the published clinical trial data. That's why additional treatment options are so critical for the RRP community. There will continue to be patients not served by existing therapy.

This need was highlighted in a recently published RRP Foundation-sponsored position statement, where 16 leading RRP physicians outlined a contemporary evidence-based approach to the management of RRP in adults. They highlighted the benefits of HPV-specific immunotherapy to address the underlying disease that causes RRP and recommended HPV-specific immunotherapy as the preferred first-line therapy for adults, including the recently approved immunotherapy and 3107 should it be approved.

These are some of the key discussion points we've provided to the FDA, and we look forward to having the opportunity to discuss them further. In the meantime, we will continue working collaboratively with the agency to advance our BLA through the regulatory process.

I'll now turn it over to Steve for a commercial update. Steve?

Thanks, Mike. On the commercial front, we are continuing to advance our commercial readiness plans in anticipation of a potential U.S. approval in 2026, and we're planning to manage commercialization ourselves with the support of a contract sales organization. We've completed targeting, segmentation and product positioning work that supports a positively differentiated product profile. We've also engaged or identified key commercial partners, including a third-party logistics provider, specialty distributor, specialty pharmacy, patient hub and agency of record.

In recent months, we've also been watching and incorporating key learnings from the launch of our competitors' recently approved product, building where they seem to be having success or challenges and optimizing our own commercial plans accordingly. Importantly, there are key differences between the Gorilla adenoviral-based product and 3107. And some of the challenges our competitor faced will not impact our launch, including the fact that we don't require an ultra-cold chain and we don't require surgery to maintain minimum residual disease during the dosing window.

We've also continued to gather important insights from the RRP community and recently attended the Combined Otolaryngology Spring Meeting or COSM, a key conference for laryngologists. In conversations at that conference with physicians specializing in the treatment of RRP, we heard repeatedly that there continues to be a high unmet need for effective immunotherapy options that work for each patient. Both patients and doctors are highly motivated and very receptive to new treatments, which indicates that this market has significant unmet need and commercial opportunity, particularly for a potential product like 3107 that has a positively differentiated product profile across efficacy, tolerability and simplicity of the treatment regimen.

I'll now turn it back to Jacqui for a pipeline update. Jacqui?

Thanks, Steve. With our resources focused primarily on 3107, partnerships will continue to be a key part of our strategy to advance other promising candidates in our pipeline. In March this year, we announced an innovative collaboration with Akeso to evaluate INO-5412 in combination with their novel dual checkpoint inhibitor as a potential treatment for glioblastoma, the most common and aggressive form of brain cancer. The study, which builds on our previous promising research in GBM will be part of a Phase II adaptive platform trial sponsored by the Dana-Farber Cancer Institute. We've also continued to advance our exciting next-generation DNA medicine platform and shared research on our DNA-encoded protein or DPROT technology targeting Factor VIII at several key conferences, including the World Federation of Hemophilia Global Conference and the American Society of Gene and Cell Therapy Annual Meeting.

Building on the promising DNA-encoded monoclonal antibody research published in Nature Medicine last year, our DPROT technology aims to enable long-term protein expression within the body and address the shortcomings of conventional therapeutic protein or enzyme replacement therapies. Based on positive preclinical data on Factor VIII production for hemophilia A, Inovio is developing additional DPROT indications in the rare disease space, including Fabry disease and hypophosphatasia, and is in discussions with potential partners to accelerate development of this promising platform.

Now I'll turn it over to our CFO, Peter Kies for a financial update. Peter?

Thanks, Jacqui. Today, I'd like to provide an overview of Inovio's financial results for the first quarter of 2026. As Jacqui noted, our primary goal is to advance INO-3107 towards approval and we remain focused on optimizing resources to support that program.

I am pleased to report that the company strengthened its balance sheet with an underwritten public equity offering in April 2026. Net proceeds from the offering after deducting underwriter discounts, commissions and offering expenses were approximately $16 million. We finished the first quarter of 2026 with $37.7 million in cash, cash equivalents and short-term investments compared to $58.5 million as of December 31, 2025.

With the addition of the April public offering, we have extended our estimated cash runway into the first quarter of 2027 beyond the target PDUFA date of INO-3107. This projection includes an operational net cash burn estimate of approximately $18 million for the second quarter of 2026. These cash runway projections do not include any further capital raise activities that we may undertake and are based on current projections and assumptions.

Turning to our results to the first quarter. Operating expenses dropped from $25.1 million in the first quarter of 2025 to $21.9 million in the first quarter of 2026, a 13% decrease. Inovio's net loss for the first quarter of 2026 was $19.7 million or $0.28 per share basic and dilutive compared to a net loss of $19.7 million or $0.51 per share basic and dilutive for the first quarter of 2025.

As a reminder, you can find our full financial statements in this afternoon's press release as well as in our quarterly report on Form 10-Q filed with the SEC. And with that, I'll turn it back over to Jacqui.

Thanks, Peter. I'd now like to pause to open up the call to answer any questions you might have. Operator?

[Operator Instructions] Your first question comes from Ted with Piper Sandler.

And it sounds like things are going well with the review. I saw the PAPZIMEOS numbers of $21.6 million were pretty good. Any comments? Can you expand a little more about how you expect to launch and differentiate versus the currently marketed product?

Ted, nice to hear from you. Steve, do you want to take that one?

Sure. Ted, yes, so we saw the [ Precigen ] performance as well and kind of how we're thinking about the market and how we'll compete is we have, we think, a positively differentiated product profile when we look across efficacy, tolerability and the simplicity of the treatment regimen. So we think we can be well differentiated in the market. And then the overall market opportunity itself, there's a very significant number of patients 14,000 RRP patients is the most kind of recently published number, although that's quite dated.

And our own estimate of claims data demonstrates that, that's probably a significant underestimate. I think Precigen has noted 27,000 RRP patients. So by the time we get to market, we expect Precigen or PAPZIMEOS would have had single-digit penetration into the market in the first year. So the vast majority of the opportunity will remain by the time we get to market. And we do expect to be a fast following second entrant, and there's many examples of second entrants fast following that do very, very well in the market and in some cases, take market leadership.

And if I can just add here, Steve. I think PAPZIMEOS launch also gives us the opportunity to learn from their successes and challenges, and we'll certainly be baking those learnings into our go-to-market plans as well. So I think the progress that we see Precigen making in the marketplace is really an indication of the high unmet need for these patients for therapeutic alternatives to surgery. And we're really excited by the opportunity for 3107.

Very great. And then if I may, just a quick follow-up. When it comes to the informal meeting with FDA, what are the primary issues that you intend to discuss there?

Mike?

Yes, happy to. So I mean this is really about confirming accelerated approval eligibility. I think it's -- I don't think we'll have much discussion around the clinical unmet need. That's very obvious, I think, to everybody concerned. So it's really around the discussion of meaningful therapeutic benefit. And as we've stated, we firmly believe we have a significant safety advantage without the requirement for those minimal residual disease surgeries and our differentiated mechanism of action will enable us to treat patients that the existing product won't be able to.

Great. That's really helpful. And I appreciate how you laid it out on the call earlier.

Your next question comes from Jay with Oppenheimer.

Can you just maybe talk about some of the key discussion points with the FDA when you meet on 3107 and remind us any additional data or evidence that you have submitted or will submit, and then I had a follow-up, if I could, please.

Yes, sure. So nice to hear from you, Jay. So I'll start off, and then I'll ask Mike to chip in here. So if you remember, we submitted our assessment to FDA back in February. Ahead of the informal meeting, and that was in direct response to a request from the agency. And that assessment aid doesn't include any new clinical data, but it did include additional analysis of the data that we performed. So at the upcoming meeting, as Mike indicated, what we principally expect to be discussing with the agency are the arguments that we've laid out in the BLA and also in the assessment aid as to why we believe 3107 is eligible for review under the accelerated approval pathway. And that's really around providing meaningful therapeutic benefit over the existing product and that we -- that 3107 has the potential to meet this unmet need.

Mike, do you want to go into some more specifics?

I mean I certainly can. I mean, in terms of the differentiated mechanism of action, which should enable us to treat a different patient population than PAPZIMEOS. We've talked previously about the presence of neutralizing antibodies to the gorilla adenoviral platform that will decrease the immune response that those patients will see with PAPZIMEOS. And we've also talked about the requirement that they have for performing those minimal residual disease surgeries is based on the immunosuppressive papilloma microenvironment that they utilize those surgeries to overcome.

We have shown with that data that was published in Nature Communications that the elements that Precigen identified did not impact the efficacy of INO-3107. So we believe there's a meaningful therapeutic difference of the two products. And I think also into -- when you look at the two different platforms, we've talked about DNA medicines having the capability of redosing and continuing to generate that T cell response.

RRP is a chronic viral illness, and we believe redosing is going to be an important part of the treatment regimen to ensure these patients can hopefully become surgery-free long term.

Great. That's super helpful. And If I could just ask one follow-up. Could you please talk about when you expect to receive feedback from the FDA on the confirmatory study design? And what sort of feedback do you expect to receive from the FDA?

Yes. Great question, Jay. I mean we expect -- as the confirmatory trial design is really linked to the review pathway and the requirement to conduct that confirmatory trial. We would expect that feedback to be linked to the informal meeting. So I think as part of the informal meeting and discussion of the review pathway, we would hope to learn when we'll get feedback on that confirmatory trial design.

Okay. Great. We look forward to that.

Your next question comes from Sudan with Stephens.

Great to hear all the progress. So to piggyback off the confirmatory trial questions that was just asked, since there is still a high unmet medical need for RRP despite the PAPZIMEOS being on the market, can you let us know to what capacity you're still treating old or new patients with 3107? And secondly, will you get any longer-term durability of response data from 3107 this year since if I remember correctly, 3107 shined on the previous long-term analysis readout.

Yes. Thanks, Sudan, for the great question. Our original Phase I/II trial incorporated the initial 4-dose regimen. And then the follow-up data was actually just a retrospective look back on the same patient population with no additional dosing. So we -- at present, we do not have any planned readout of data on 3107 with continued dosing. We have previously talked about data that we have for INO-3100, which has shown the ability to continue to generate a T cell response 6 to 9 months after the completion of the initial treatment. So we are excited to discuss with the agency what a redosing strategy will look like following approval of 3107 if it gets approved.

Great. And secondly, I just wanted to ask also, how have your interactions with the RRP Foundation been recently as you near your PDUFA date amidst also the PAPZIMEOS launch currently happening? Do you feel like you have an opportunity here to further utilize this patient advocacy group as a resource to specifically reach the community setting that PAPZIMEOS, I think, currently has only penetrated about 25% to date?

Yes, that's a great question, Sudan. And I'm very pleased to say that the RRPF Foundation and the RRP community have been incredibly supportive. And we're very much aligned with them. We recognize that the current approved therapy doesn't work for all RRP patients and every RRP patient deserves a therapy that works for them. Every surgery matters to RRP patients. So our goals are very much aligned with the foundations. We continue to work very closely with them, and we are very grateful for their support. And we'll obviously continue to work with them going forward. But yes, understanding the patient perspective and the remaining unmet need is absolutely critical to what we're trying to do with 3107.

Your next question comes from Yin with H.C. Wainright.

This is [ Jan De ] sitting in for Yi Chen. I have 2 questions. The first is with respect to the FDA. Do you expect the resignation of the current FDA commissioner to introduce any sort of uncertainty in the review timeline of INO-3107.

Yes. I don't think we can really comment on the inner workings of the FDA at the moment. But what I can say is we continue to engage with our review team and respond to information requests and the review seems to be proceeding. As we commented around the mid-cycle review, they did reiterate that they're still reviewing the assessment aid and that they plan to schedule the informal meeting. And we encourage them to -- we continue to encourage them to schedule that meeting. We're keen to discuss it with them. So I think where we are at the moment is really just continuing to progress the review, and we're very keen to have that discussion.

And my second question is about when INO-3107 gets approval. So once that happens, what would be your marketing strategy or approach to seize market share from PAPZIMEOS?

Yes. So we believe, as Steve, I think, has outlined, we believe that 3107 has a positively differentiated product profile and could become the product of choice for patients and RRP physicians. And this is really based on its clinical effectiveness, our tolerability and a simple patient-centric approach to treatment with 3107. So clearly, we've been learning from the PAPZIMEOS launch. We'll be incorporating key learnings from their launch into our go-to-market plan, and we're planning to be a fast follower. As Steve also outlined, we're expecting the vast majority of the prevalent pool or the available market to still be available when we come to market if approved. And there are also new patients being diagnosed every year. So we think we're in a good position to be able to compete with the approved product. Steve, anything you want to add?

No, I think that's good.

Your last question comes from Liang Cheng with Jefferies.

This is Liang Cheng on for Roger Song. I guess from us, how should we think about the potential label at approval, particularly the eligible patient population and anticipated restrictions versus the Phase I/II population?

Liang, nice to hear from you. It's a great question. So we would expect to have a very similar label to the approved product. And that's based on the fact that we recruited patients who have had between 2 to 8 surgeries in the prior year. In our patient population, we had a good balance of patients who were infected with HPV-6 and 11 and even a combination of them both. And we have no evidence from our mechanism of action that efficacy would depend on severity of disease or number of surgeries in the prior year. So we would expect a very similar label with no restrictions.

Okay. Got it. And at a higher level, what -- how are you thinking about pricing relative to Precigen?

Yes. So we are thinking of rare disease pricing. Clearly, in our payer research that we've conducted, payers recognize that rare disease pricing is appropriate for this indication. We'll be conducting some price optimization research and we'll be commenting on pricing a bit closer to launch.

There are no further questions at this time. I will turn the call back over to Jacqui Shea.

Thank you. As we've outlined here today, Inovio is intent on meeting the milestones ahead for INO-3107 and the other promising candidates in our pipeline. We're motivated by the potential opportunity to deliver on the promise of DNA medicines for RRP patients and grateful for the support from the RRP Foundation and larger RRP community. They have waited so long for relief from the devastating impact of their disease.

We believe every patient deserves access to a treatment option that works for them because every patient matters and every surgery matters. We're working every day to help make that vision a reality. Thank you for your attention, and good evening, everyone.

Good afternoon, ladies and gentlemen, and welcome to the Inovio Fourth Quarter and Full Year 2025 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Thursday, March 12, 2026.

I would now like to turn the call over to Jennie Wilson. Please go ahead.

Good afternoon, and thank you for joining the Inovio Fourth Quarter and Full Year 2025 Financial Results Conference Call. Joining me on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Steve Egge, Chief Commercial Officer; and Peter Kies, Chief Financial Officer.

Today's call will review our corporate and financial information for the quarter and year ended December 31, 2025, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segment.

During the call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions, our interactions with the FDA regarding our BLA for INO-3107, including our yet to be scheduled meeting with the FDA to discuss eligibility for the accelerated approval program. The potential benefits of INO-3107, along with capital resources including the sufficiency of our cash resources, our expectations regarding competition, the size and growth of the potential market for INO-3107, if approved, and our ability to serve those markets. The rate and degree of market acceptance of INO-3107 and strategic matters. All of these statements are based on the beliefs and expectations of management as of today.

Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which, under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release.

This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded.

I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

Good afternoon, and thank you to everyone for joining today's call. These are very exciting times for Inovio with our first BLA for INO-3107 as a potential treatment for adults with recurrent respiratory papillomatosis or RRP, currently being reviewed by the FDA. In late December last year, we were pleased to announce that the FDA accepted our BLA review under the accelerated approval program. The FDA granted a standard 10-month review with a Prescription Drug User Fee Act or PDUFA target date set for October 30 of this year.

While the BLA was accepted under the accelerated approval program, in the file acceptance letter, the FDA noted as a potential review issue, its preliminary conclusion that the company has not provided adequate information to justify eligibility for the accelerated approval program. This preliminary conclusion was made during the initial 60-day filing review period and was the first time a potential issue with respect to eligibility have been raised.

As Mike will explain later in the presentation, we strongly believe that INO-3107 does fulfill the criteria for review under the accelerated approval program, by meeting an unmet medical need and providing a meaningful therapeutic benefit over existing treatment. The FDA has agreed to meet with us, we have provided additional documentation, and we're waiting for them to provide a meeting date.

In the meantime, we are continuing to advance our commercial preparations, focusing on optimizing and expanding our resources towards our October PDUFA date. To achieve this, Inovio has taken steps to further conserve its financial resources, rescoping projects and activities and eliminating roles that don't directly support our primary goal for advancing INO-3107 towards U.S. approval. These efforts have enabled the extension of our estimated cash runway into the fourth quarter of this year.

While the majority of our resources are directed to advancing our lead candidates towards approval, we are continuing to leverage the power of partnerships to advance other promising candidates in our pipeline. We have recently announced an exciting opportunity to build on our research in glioblastoma through an innovative Phase II adaptive platform trial sponsored by the Dana-Farber Cancer Institute, where we'll collaborate with Akeso to evaluate INO-5412 in combination with their novel PD-1, CTLA-4 bispecific antibody checkpoint inhibitor. Like our lead program, INO-3107, this program utilizes the antigen-specific cytotoxic T cell generating ability of our DNA medicines platform, but in this instance, to target cancer cells.

We have also continued to advance some of our earlier-stage next-generation DNA medicine candidates, which I'll touch on later in this presentation. I look forward to advancing these programs in tandem with our top priority for 2026, achieving FDA approval of our first product and bringing INO-3107 to patients.

Now I'll turn it over to Mike for some additional insights on our regulatory progress with 3107. Mike?

Thanks, Jacqui. As Jacqui outlined, we have made significant progress with our BLA as outlined on this slide, including the acceptance of our file for review under the accelerated approval program, with a PDUFA date of October 30, 2026. We believe our BLA makes a strong argument outlining how INO-3107 meets an unmet medical need and provides a meaningful therapeutic benefit over existing treatments, thus fulfilling the accelerated approval program criteria.

Our next step is to discuss this with the FDA. In preparation for this meeting, they had requested that we complete an assessment aid, which we submitted in February. In this document, we reiterate and expand on our rationale for accelerated approval review. It is important to note that while we wait to meet with the FDA, the BLA is under active review, and we have been responding to routine requests for information. In addition, we submitted an updated protocol for our confirmatory trial to the IND and are awaiting feedback from the agency regarding finalizing the study design.

I'd like to take a moment to focus on why we believe 3107 meets the accelerated approval criteria. Following the unexpected full approval of PAPZIMEOS in August last year, the regulatory landscape changed with respect to the requirements for eligibility. Based on published FDA guidance, when there's an already approved product, eligibility for accelerated approval depends on a candidate's ability to provide a meaningful therapeutic benefit over existing treatments and its ability to meet a remaining critical unmet need among patients. We believe that 3107 meets both of those criteria based on demonstrated efficacy and improved safety profile that does not include required surgery during the dosing window and a differentiated mechanism of action that provides the ability to treat patients who are not able to be served by existing therapy.

Getting into more detail. In our trial, the majority of patients experienced fewer surgeries after treatment with 3107, with most experiencing a 50% to 100% reduction compared to the year before treatment. That clinical benefit continued to improve in the second 12-month period post treatment with half of the patients requiring 0 surgeries during that time. Efficacy was achieved without the vast majority of patients requiring surgery during the dosing window, a key differentiating advantage of the 3107 safety profile.

Remember, in our Phase I/II trial, our protocol counted every surgery conducted after day 0. In contrast, surgeries conducted during the 12-week treatment window in the PAPZIMEOS trial were not counted against the efficacy end point, and 72% of the reported complete responders in the single-site Phase I/II trial had at least 1 surgery during the 12-week dosing window. To maintain what is referred to as minimal residual disease, or MRD, a protocol that is required for the efficacy of that product and is included in the label. Additionally, 3107 offers a differentiated mechanism of action, which provides the ability to treat patients who are not served by existing therapy, and thus address an unmet need in the RRP treatment landscape.

PAPZIMEOS utilizes a gorilla adenoviral vector, and it is well established in the scientific literature that efficacy of adenoviral vectors may be impacted by preexisting neutralizing antibodies as they have been shown to limit the immune response that patients with these antibodies can generate. In addition, several immune factors relating to the papilloma microenvironment were identified by the investigators as being linked to the lack of efficacy for PAPZIMEOS.

In contrast, ad data published in Nature Communications shows that efficacy of INO-3107 is not impacted by the papilloma microenvironment. We look forward to discussing our rationale for review under accelerated approval with the FDA.

And with that, I will now turn it over to Steve for a brief commercial update. Steve?

Thanks, Mike. The burden of RRP on patients is significant, and there's an urgent need for treatment options that reduce the need for repeated surgery. RRP is characterized by chronic wart-like growth called papilloma, to grow in the respiratory tract and can cause difficulty speaking, swallowing and breathing. Surgery is still the standard of care and patients have numerous surgeries, sometimes hundreds of surgeries in the most severe cases throughout their lifetime. Every surgery matters to patients because the risk is well established. Every surgery carries the risk of permanent damage to the vocal cords and airways, and the cost of surgery can have a significant impact as well. Traveling hundreds of miles for specialized RRP care, missing work and social functions while preparing for or recovering from surgery, the anxiety and frustration of impaired voice quality making it difficult to communicate, and the psychological trauma of undergoing repeated surgeries. This is why we're committed to delivering on the potential of 3107 for RRP patients. And that potential has been validated in market research, which supports our belief that this product is approved to become the preferred treatment based on its efficacy, tolerability and simple treatment regimen.

I shared these insights previously, but I think they bear repeating. Physicians we engaged in market research were most interested in the fact that the vast majority of patients by 50% to 100% reduction in surgery from 3107 and for many of them, that clinical benefit continued to improve over time. Physicians were similarly impressed with the tolerability data, which shows that 3107 was generally well tolerated, limiting the impact on patients return to daily life. This is important considering the treatment protocol includes 4 doses over a relatively short period of time.

And in terms of the treatment regimen itself, 3107 takes into account concern of both physicians and RRP patients. It can be administered in the physician's office without an ultra cold chain requirement. The device is simple to use and importantly, there's no requirement for surgeries to maintain minimal residual disease during the treatment window. This is a key area of differentiation from Precigen's gorilla adenoviral based therapy, which, as Mike noted, requires scoping and surgery during the treatment window to maintain minimal residual disease. Precigen's data publication indicates that these surgeries are required to mitigate the effect of the immunosuppressive papilloma microenvironment to maximize the chance of clinical benefit from the product. We believe this key difference makes 3107 a more patient-centric approach to treating RRP.

I will also mention that the recently published RRP foundation position statement on the management of adults with RRP now recommends immunotherapy as first-line treatment for RRP and notes that 3107 if approved, would also be included as a first-line treatment option.

I would also like to share just a few updates on our ongoing commercial launch preparations. Over the past year, we've executed critical market research, which informed strategic choices on launch preparations for 3107. We completed targeting segmentation of product positioning work and developed our pricing strategy. On the operational front, we've selected key commercial partners, including our third-party logistics provider, specialty distributor, specialty pharmacy, patient services hub and our agency of record. We are also finalizing our go-to-market model and planning the build-out of our commercial organization. I look forward to providing further updates on our progress next quarter.

I'll now turn it back over to Jacqui for a pipeline update.

Thanks, Steve. While we remain steadfastly focused on INO-3107, in the past few quarters, we've also provided some important updates on how we're continuing to advance our DNA medicine platform. That includes promising Phase I proof-of-concept dMAb data published in Nature Medicine in October of last year, which demonstrated the technology's ability to durably and tolerably produce monoclonal antibodies, a complex protein within the human body for up to 72 weeks without generating antidrug antibodies. Additional data presented this year has now demonstrated consistent production of dMAbs out to 96 weeks.

Our DPROT technology builds on this research, aiming to enable additional types of complex proteins being made within the body. Preclinical work evaluating the potential to expand into in vivo production of other types of therapeutic proteins, which presented at the World Federation of Hemophilia Global Forum last November, including our first data on Factor VIII production. We see great potential for this DPROT technology to treat multiple diseases and are actively seeking partnerships to advance additional rare disease targets into clinical evaluation.

We also announced an exciting opportunity to build on our research in glioblastoma, or GBM, the most common and deadly brain cancer, through an innovative Phase II adaptive platform trial sponsored by the Dana-Farber Cancer Institute. In this trial, we will partner with Akeso to evaluate INO-5412 in combination with cadonilimab, their first-in-class PD-1, CTLA-4 bispecific antibody checkpoint inhibitor. The trial is planned to initiate in the second half of this year.

INO-5412 is composed of INO-5401, which encodes for 3 tumor-associated antigens. And then INO-9012, which encodes for IL-12 and immune stimulants. When combined with a checkpoint blockade, this targeted DNA immunotherapy has the potential to overcome the limitations for immune checkpoint therapy alone by stimulating a T cell-based immune response against the tumor antigen, and driving T cell infiltration into the GBM tumor micro environment.

Combining 5412 with Akeso's novel checkpoint modality represents an important evolution of our research in GBM, building on our previous data showing the potential to improve patient outcomes and highlights our ongoing commitment to advancing innovative treatments for rare diseases with significant unmet need. We are looking forward to collaborating with these 2 trailblazing partners and leveraging a unique opportunity to efficiently advance another promising late-stage candidate.

Now I'll turn it over to our CFO, Peter Kies, to give financial update. Peter?

Thanks, Jacqui. Today, I'd like to provide an overview of Inovio's financial results for the fourth quarter and full year of 2025. As Jacqui noted, our primary goal is to advance INO-3107 towards approval, and we remain focused on directing resources and extending our cash runway towards a potential launch date in 2026. With the October PDUFA date in mind, we have further prioritized programs and resources, including recently reducing head count by approximately 15% and have focused on continuing to reduce spending to extend our cash runway.

We now estimate our cash runway to take us into fourth quarter 2026. This projection includes an operational net cash burn estimate of approximately $22 million for the first quarter of 2026. Historically, our first quarter operational net cash burn runs higher than other quarters. These cash runway projections do not include any further capital raising activities that we may undertake. We finished the fourth quarter of 2025 with $58.5 million in cash, cash equivalents and short-term investments compared to $94.1 million as of December 31, 2024.

Turning to our results for 2025. Our total operating expenses dropped from $20.5 million in the fourth quarter of 2024 to $17.5 million in the fourth quarter of 2025. Our full year operating -- operational expenses decreased 23% from $112.6 million in 2024 to $86.9 million in 2025. Inovio reported a net income for the fourth quarter of 2025 of $3.8 million or $0.06 per share and a dilutive net loss per share of $0.26. Our total net loss for the full year of 2025 was $84.9 million or $1.81 per share basic and dilutive.

The net income for the fourth quarter 2025 was primarily driven by $21.2 million noncash gain on fair value adjustment related to our warrant liability as the fair value of the warrants fluctuates with our share price and other market inputs, the adjustment can result in significant variability in our reported net income or loss. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our annual report Form 10-K filed with the SEC today.

And with that, I'll turn it back over to Jacqui.

Thanks, Peter. I'd now like to pause and open up the call to answer any questions you might have. Operator?

[Operator Instructions] And we have our first question from Ted Tenthoff with Piper Sandler.

Great. I wanted to first start just with respect to the conversations with the FDA upcoming regarding accelerated approval. Are there any additional data that you would need to submit? Or what other factors will go into that conversation for potentially transitioning the review to accelerate our approval?

Thanks, Ted. Great question. So there's no new clinical data. However, we have already submitted new documentation to the FDA in the form of an assessment aid, which we submitted in February. So we are now waiting for the FDA to get back to us regarding the date of the meeting.

Mike, anything you want to add to that?

Yes. The only thing I'd add, Ted, is we utilize that document to sort of reiterate what we put in our original BLA submission and really expand on our rationale for accelerated approval review. So we're -- as I mentioned, we're looking forward to having those discussions with the agency.

We have our next question from Jay Olson with Oppenheimer.

Thanks for providing this update and taking our questions. We had a couple of questions. I guess maybe to start with, if you do eventually gain alignment with the FDA on a priority review, how would a 6-month priority review timeline impacts your ability to launch? And any launch preparations that you have underway. If you could just talk about that, that would be great. And then we have 1 follow-up, please.

Thanks, Jay. Nice to hear from you. So our focus at the moment is really on ensuring we have align with FDA for review under the accelerated program. We're not really focused on priority review at this stage. However, having said that, we are well advanced in our commercial preparations.

And I'll ask Steve to make any comments here.

Yes. So as I mentioned in the prepared remarks, I mean, we've done a lot of market research with physicians, with patients, with payers. So we feel like we know the market opportunity quite well. We've built kind of our strategies around that. We've got our commercial partners kind of onboard or selected. And we will be prepared to get out of the gate really, really quickly, should we get approved. So I think we're doing everything that we need to, to be prepared and to move very quickly once the FDA makes a decision.

Okay. Great. And then if we could follow up on the publication in Nature Communications and The Laryngoscope. Can you just talk about any feedback that you got from KOLs and patients and how you might anticipate that feedback to translate into the uptake trajectory upon approval?

Yes. Great question, Jay. So as we mentioned on the call, we do believe that we have the preferred product profile in this space, and that's based across efficacy, tolerability in a very patient-centric treatment regimen. And when we have conducted research and with research conducted by third-party providers, both patients and physicians really appreciated and preferred the product profile for 3107. And what was really interesting to them was the fact that the majority of patients see a significant reduction in the numbers of surgeries. So 72% of patients see a 50% to 100% reduction in the first year following treatments, and that improves up to 86% in the second year with 50% of patients in the second year, requiring no surgeries at all. So a very strong efficacy profile.

With regards to tolerability, the fact that we don't require these minimal residual disease surgeries during the treatment window is very well received. And for the competitor product, over 70% of the patients required surgery during their treatment window, requiring one or more surgeries during that treatment window. Actually -- sorry, that number was actually 83%, and it was 72% of their complete responders. So as you can see, the competitive product -- patients receiving competitive products in their trial actually required a lot of surgery during the dosing [ period ]. And the fact that INO-3107 doesn't require these surgeries maintain minimal residual disease is very attractive.

And then as I think Steve mentioned, it's our ability to administer 3107 in the doctor's office, and the simple patient-centric treatment regimen, again, is very attractive to patients.

Steve, anything else you want to add to that?

No, I think you covered it. I mean the research has shown really repeatedly a lot of evidence that we have the potential to be the preferred product in this space.

We have our next question from Sudan Loganathan with Stephens.

This is Kesav on for Sudan, and congrats on wrapping up the quarter. Just a quick one. So as you engage with the third-party logistics and commercial partners ahead of launch, are you specifically using those partners to incorporate learnings from the PAPZIMEOS rollout to inform your distribution strategy, site activation plannings, reimbursement approach and overall launch execution for 3107?

Sure. So yes, I mean, obviously, we would -- we're watching carefully what our competitors doing and learning from that. I don't know that they're necessarily the same commercial partners that Precigen is using but they have very deep broad experience in the rare disease space. So we're learning from that as well. So I would say the more general rare disease experience, but also Precigen's experience as well to do everything that we can -- to ensure that we're kind of very well prepared from a launch standpoint.

And if I can add, there were some key differences for 3107 to PAPZIMEOS. We don't require any ultra-cold chain also -- so we don't have those logistical issues setting up an ultra-cold chain. And also as we don't require these minimal residual disease surgeries during the treatment window, physicians don't have to plan for scoping and possibly doing surgery as well, which obviously makes the treatment regimen very attractive to physicians and to patients.

Our next question is from Roger Song with Jefferies.

This is Nabeel on for Roger. I had a question on the Akeso partnership. If you could just kind of walk us through that biological rationale of the dual PD-1, CTLA-4 blockade. How does that sort of add on top of the T cell priming that you've shown before with 5412 and GBM?

Yes, great question. So in the previous study, we combined 5401 plus IL-12 plus a PD-1 inhibitor from Regeneron called Libtayo. And what we saw in that study was encouraging data where we saw beneficial patient outcomes linked to the immune responses against the antigens that were encoded within 5401. So by partnering with Akeso in this innovative trial, what we're hoping is that the CTL4 element in addition to the PD-1 inhibition by providing an additional pathway for checkpoint inhibition will allow those immune responses against the tumor-associated antigens to provide additional benefit. So we're excited to be partnering with Akeso and excited to get the study underway.

Mike, anything else you would like to add?

The only point, I mean it's well established that there is significant synergism between CTLA-4 and PD-1. So as Jacqui said, we think it will be a very nice combination to 5412.

Yes. That's exciting. A follow-up on that. I think inside, historically, you guys emphasized the O6-methylguanine methyltransferase the unmethylated group. Any idea, this is like early, but in terms of subgroups, like does the methylation status influence any expectations for like the immunotherapy responsiveness?

Yes. So it is a prior trial. We saw benefits in both methylated and unmethylated groups. So we were very encouraged by that data. Sorry, Mike, you wanted to say something?

I was going to say exactly the same. But the INSIGhT trial is actually in the unmethylated population. So while it's very sad for the patients that will lead to a quicker readout as they have a poorer prognosis.

We have our next question from Yi Chan with H.C. Wainwright.

This is [ Katie ] on for Yi. Taking a look at your pipeline, if 3107 is approved, what are your plans to move forward with 3112? Are you guys planning to reinvest internally or seek partnership for that type of program?

Yes. Great question. So for those of you who are not familiar, 3112 is our program in HPV-16 and HPV-18 positive head and neck cancer, oropharyngeal squamous cell carcinoma. And there, we announced a partnership with Coherus for their PD-1 inhibitor, Loqtorzi, which is approved in nasopharyngeal carcinoma. We're looking to start a Phase III trial. However, at the moment, the vast majority of our resources are going towards moving 3107 forward. So should -- should 3107 be approved later on this year and we have sufficient financial resources available, then we'll be looking to move forward with the other candidates in our pipeline. But we're very excited by our later stage candidates, which are predominantly focused on T cell mechanisms.

So 3107, 5401, 3112, are all focused on driving T cell responses, either against viral antigens or against cancer antigens. And then we also have our earlier stage pipeline around our DPROT and our dMAb candidates, where we're looking to move those candidates into the clinic through partnerships. So partnerships are going to be very important to us in terms of how we see our pipeline developing going forward.

Thank you. We have no further questions. I will now turn the call over to Jacqui Shea for closing remarks.

Thank you. As we've outlined here today, our strategic focus for the months ahead is clear, advancing the BLA review for 3107 and optimizing our resources to extend our cash runway towards our October 30 PDUFA date. At the same time, we'll continue driving progress across our pipeline where possible, leveraging partnership opportunities and the potential of our platform in GBM, hemophilia and other rare diseases.

As I close today, I'd like to reiterate our belief that 3107 can address the unmet needs of RRP patients. Patients who have faced the risks and burdens of their disease were far too long. We're moving forward committed to making sure that every patient can find relief from repeated surgery that they deserve. Thank you for your attention, and good evening, everyone.

And thank you, ladies and gentlemen. This concludes our conference call. We thank you for your participation. You may now disconnect.

All right. Welcome back to the Citizens Life Science Conference. My name is Silvan Turkin, and I cover precision sciences at Citizens. It's my pleasure to host Jacqueline Shea, President and CEO of Inovio. Thank you so much.

Thank you so much, Silvan. It's a pleasure to be here today, and thanks for having us.

So I'm going to kick off by just giving you a quick overview of Inovio. Those of you who are not familiar with the story. Just a quick normal looking forward-looking statements disclaimer slide that I'll be making some forward-looking statements during this presentation. So to provide you a quick overview of the company, we're a clinical stage biotech company. We're focused on developing and commercializing our DNA medicines to treat and protect people from HPV-related diseases, cancer and infectious diseases.

We submitted our BLA for our lead program, INO-3107, and it's been accepted for review by FDA under the accelerated approval program. It's a potential treatment for a rare disease recurrent respiratory papillomatosis or RRP, which is caused by HPV types 6 and 11. We have a PDUFA target date, October 30 this year, and we have orphan drug and breakthrough therapy designations and orphan drug designation in the EU.

We've requested a meeting with FDA to discuss some preliminary comments we received in the file acceptance letter related to eligibility for accelerated approval pathway, and we're not currently planning to seek approval under the traditional pathway. We continue to believe that the accelerated approval program is the best and fastest path to approval for 3107. We believe even with one product on the market, there's a significant remaining unmet medical need and significant market opportunity.

We've currently established our commercial scale manufacturing for plasmids at CMOs, and we do our device manufacturing in-house. So 3107 is a combination product. It's a combination of both a DNA medicine drug as well as a delivery device to deliver it.

And following on behind 3107, we have a deep clinical pipeline with multiple potential near and midterm catalysts. We recently announced a new collaboration with Akeso and the Dana-Farber Cancer Institute to evaluate a combination immunotherapy to treat glioblastoma in the Phase II INSIGhT trial. And we also have some very exciting next-gen therapeutics in earlier-stage development poised to enter clinical evaluation. So how do the DNA medicines work?

Well, we start off by identifying the target gene that we either want to raise an immune response against or that we want to express to either produce monoclonal antibodies or to produce therapeutic proteins themselves. And then we use our proprietary algorithms to optimize those DNA sequences for expression. We clone those DNA sequences into circular molecules of DNA called plasmids. And then we're able to deliver those DNA plasmids into either skin or muscle cells using our proprietary delivery devices called CELLECTRA. Once they're in the skin or muscle cells, the DNA is transcribed to RNA, the RNA is translated into protein, and then the proteins can be secreted from the cell.

Now these proteins can either drive an immune response. So in the case of 3107, we're really looking for them to drive a T cell response. They can also drive antibody and T cell responses for normal vaccine indications. And then as I mentioned, we can actually encode monoclonal antibodies within the DNA plasmids, have them assembled and then secreted from the cells into the circulation. And we can also produce potentially therapeutic proteins as well. So as you can see, this is a very versatile platform.

So moving on then to our lead candidate, 3107 for RRP. To tell you a bit more about RRP. RRP is a rare disease. It's characterized by these small wart-like growth called papillomas that can form throughout the respiratory tract, but principally form around the larynx and the vocal cords. And that can make it very difficult to speak. It can make it difficult to swallow or even breathe. And in some cases, these papilloma can spread throughout the respiratory tract and into the lungs. It can become malignant and it can be a fatal disease. And we think that what leads to RRP is after you've had an infection with either HPV 6 or 11, there's an insufficient immune response, which really fails to clear the virus. And that's what leads to the cellular proliferation and the wart-like structures that form in the respiratory tract.

It's a rare disease. Epidemiology suggests that there are about 14,000 active cases in the U.S., about 1.8 per 100,000 new cases annually. And you can get diagnosed with RRP at any age. There are kind of 3 peaks of disease instance around age 5 for pediatric RRP around age 30 and around age 60. And unfortunately, repeated surgery is the standard of care. If you can imagine your vocal cords, they're very delicate structures. They don't regenerate and they have to vibrate at hundreds of times a second for you to be able to talk.

So surgery on these delicate structures is really challenging. And severe RRP can require hundreds of surgeries over your lifetime. So it's really a very difficult disease for patients and their caregivers to manage. And every surgery comes at a risk, the risk of the potential irreversible damage to the vocal cords and a cost in terms of impact to quality of life, preparing for recovering from surgery as well as the financial costs of a chronic disease. So 3107 is our DNA immunotherapy. It's designed to generate an antigen-specific T cell response against HPV 6 and HPV 11, the viruses that cause RRP. And in this way, it's really targeting the underlying cause of RRP. It's getting to that root cause rather than just continuing to cut away of the disease through repeated surgery.

And what's really important to patients and what's really important in this disease is that every surgery matters to patients because the surgery in many ways is worse than the disease itself. And the cumulative risk for injury increases after every surgery. Ultimately, it only takes one surgery to irreversibly damage your vocal cords and damage your larynx. And after patients who have had about 10 surgeries, most of them will have had some irreversible damage to their vocal cords. So we believe, based on third-party market research that we potentially have the preferred product profile in the space.

And that's based across 3 kinds -- 3 main elements: efficacy, tolerability and a simple patient-centric treatment regimen. In terms of efficacy, we saw an improving response over time. We saw a good response in the first year after treatment of 72% of patients seeing between a 50% and 100% reduction in surgery compared to the year prior to treatment. And this rate improved into the second year and went up to 86% in year 2. And in terms of complete response, so these are patients who required no surgeries at all. We saw 28% of patients in year 1 requiring no surgeries, 50% in year 2. And what physicians tell us is really meaningful is that this means that for their patients, 3107 is very likely to help reduce the number of surgeries that their patients need, which is what -- exactly what they're looking for. And because we don't require any scoping or surgeries during the dosing regimen, it comes without that added risk.

In terms of tolerability, 3107 treatment was very well tolerated. The most common adverse events were transient injection site pain in about 30% of participants, a little bit of fatigue. Very importantly, we didn't see any discontinuations. And when physicians look at this tolerability profile, they think it's good. They think this means that their patients will be able to get back to work quickly. And that's important, especially when patients are receiving multiple doses over a relatively short time frame and have been managing a chronic disease.

3107 is able to be administered in the doctor's office. The CELLECTRA device is very easy to use. Any health care professional can be trained to deliver 3107. And there is no requirement for scoping or surgeries during the dosing window. And that's really important to patients because they're not being exposed to additional surgeries.

So in the near term, we're really focused on delivering 3107 to patients. As I mentioned, our BLA has been accepted under the accelerated approval program. We have a PDUFA date in October. We have requested a meeting with FDA to discuss their preliminary comments in the file acceptance letter. And we believe that we have the potential to have the preferred product profile in this space if approved.

Following on behind 3107, we have some other exciting candidates, 5401 in combination with Akeso's PD-1/CTLA-4 drug. 3112 in combination with Coherus LOQTORZI in HPV-related throat cancer. These candidates are both T cell-based. And then our dMAb candidates where we published our proof-of-concept clinical data from our Phase I study showing that we're able to produce monoclonal in the body for therapeutic levels that are stable and out to -- and at therapeutic levels out to 72 weeks, which is very exciting.

And then moving on to our next-generation candidates. We're starting to use this ability to produce proteins within the body to start going after protein replacement diseases. And we presented our first preclinical data for Factor VIII production in hemophilia last autumn.

Now I think we are going into a quick fireside chat. Thank you.

Thanks for the presentation. Maybe you'll just drill down a little bit more on the regulatory interactions that you had and what is to come. So the FDA came back to you saying accelerated approval may or may not be open to you. What is the -- what's your view on this? And what's the case that you're going to make in front of them in this meeting that's coming up outlining why it should be open to you?

Yes, great question. So let's go back to the beginning, perhaps and see how we got to this point. So we completed our rolling submission of our BLA under the accelerated approval program in October last year. The FDA accepted our BLA under the accelerated approval program in late December. But instead of the priority review, we'd asked for, they granted us a standard review. And we also got a comment in the final notification letter about a potential review issue, so just potential at this stage. And it was a preliminary comment that at that time, we hadn't provided sufficient or adequate information to justify review under the accelerated approval program.

So in January, we asked FDA for a meeting. FDA came back and said they were willing to meet, but they asked us to complete an assessment aid. And then an assessment aid is really a document that allows us to put forth our case and our rationale in quite a lot of detail as to why we think we're eligible for approval under the accelerated approval program as well as some other clinical and other data that they asked for. So we submitted that assessment aid in February, and we're now waiting for FDA to schedule the meeting.

So we hear, right? I mean it's hard to interpret what you hear from the FDA and you don't want to speak for them, right? But it seems like they just want to help additional information to make the case for cellular approval rather than being against the cellular approval and you have to convince them otherwise. Is that correct or...

Well, the final notification letter was the first indication that we've had from FDA that they had any concerns about eligibility under the accelerated approval program. We do very strongly believe that we are eligible for review under that program. We have made the case and the assessment aid, and we're looking forward to our meeting with FDA. And if I can just briefly comment on our rationale. The guidelines are very clear for accelerated approval. You have to provide a meaningful therapeutic benefit over existing treatments and you have to meet an unmet need.

We believe that we do this by having an improved safety profile. Unlike the approved product, we don't require scoping or surgeries during the dosing window, which gives us a better safety profile, we believe. And we also have a differentiated mechanism of action. So the approved product is an gorilla adenoviral-based product. And that means that it can be impacted by neutralizing antibodies that can be preexisting in the population or that can be formed during the treatment regimen itself. As we're not an adenovirus, we don't have that issue.

And it also -- and we also have a differentiated mechanism in that the approved product, they published data that shows that certain elements of the papilloma microenvironment restrict their efficacy. We tested the same elements, and we didn't see any restriction in our efficacy. So part of this, we think, is due to the fact that we're delivering via DNA and not by an adenovirus. So we think the 2 products are very different. There's clearly an unmet need. Papzimeos doesn't meet the needs of all patients. And we think we have a strong rationale for review under the accelerated approval program.

Great. And needless to say, the review of Papzimeos was abbreviated by the FDA creating the situation in the first place. So I would think that they would be a little bit open to such requests. Maybe talking -- I might have missed this, but outside of the FDA, for example, EMEA or other regions, what's your progress there for and your thinking about filing?

Yes. So we've gone and received scientific advice from CHMP in Europe. We've also discussed with the U.K. regulators. So we have orphan drug designation in Europe. We have ILAP designation in the U.K. We also have ATMP designation in Europe as well, which basically means that they've looked at our clinical data package and our preclinical data and agreed that it meets the -- and CMC data and agreed that it meets the standards required for submission.

However, the feedback that we received from the European regulators was quite different from FDA. They're really looking for placebo-controlled data, and they're really looking for data from 2 efficacy trials. So we're going to continue our interactions with the European regulators, but 2 very different regulatory feedbacks.

And you mentioned that you're currently not looking at a Phase III controlled trial, right, that could turn off...

If we're -- obviously, if we continue down the accelerated approval pathway, we will need to conduct a confirmatory trial. And we have put in an amendment to our IND for the confirmatory trial, and we hope to finalize the design of that confirmatory trial with FDA as part of these discussions.

Great. Maybe shifting a little bit, and you've touched upon some of these things already, I think, when you were saying for the case for accelerated approval. But how -- given that the Papzimeos is approved out there, how are you thinking about differentiation with the data that you have today, maybe from a patient's perspective and also the practitioner's perspective?

Yes. I mean, obviously, as a second market entrant, it's going to be very important that we have an efficient launch. But I think what's really key to the opportunity here for us is our differentiated product profile. And we do think we have the ability to have a preferred product profile in the space. And this is based across the efficacy, also across the fact that we have an improved safety profile and that the product can be given in the doctor's office. And when you compare this to the approved product, the approved product needs these scoping and minimal residual disease surgeries if disease is present at doses 3 and 4.

It also requires an ultracold chain. So that makes it more difficult to be given in the doctor's office. We're waiting to hear actually how -- what channels Papzimeos is actually being given through, but it makes it more challenging. And obviously, in terms of the patient, knowing that they're not going to have additional surgeries during the treatment regimen, it's very attractive to them.

On average, how many do they have as of today? I mean, the launch is quite early, but how many fewer surgeries would they have with your product on average? And maybe if you can comment around the burden that each of these surgeries has for the patient? How long does it take the patient to heal? Or would this patient be out of commission?

Yes. So let's start by talking about the surgeries. So most of the surgeries, as you can imagine, your vocal cords, it's very hard to do these under local anesthetic. It's possible in some cases to do the laser under local anesthetic just in the doctor's office. But the majority of these surgeries require general anesthetic. And the recovery from these surgeries can be really difficult. In some cases, patients have to go on a liquid diet. They have to be on voice rest for weeks. And even after that voice rest, their speaking voice can be impacted. So it's actually a really challenging surgery for patients to recover from, very painful surgery as well.

So in terms of differentiation between the 2 products, for the Papzimeos product based on their published data, 83% of their patients required 1 or 2 surgeries during the dosing window. And of their complete responders, 72% of their complete responders required surgery. So in comparison, none of our complete responders required surgery during the treatment window. And that's really -- and the impact on the safety profile, I think, is really a key difference between the 2 products.

Great. Maybe on the manufacturing side, how is this product being manufactured? And who does that for you? And where is that with respect to a potential launch in October?

Yes. So as this is a rare disease, it's not a huge amount of product, obviously, to manufacture. So we manufacture our plasmids at contract manufacturers that have been FDA and inspected and approved. We produce the drug substance with one manufacturer, and then we fill the final product with a different manufacturer. In terms of assembly of the device, we are buying components and then we assemble the devices ourselves in-house. And we have CE marking for our 5PSP device in Europe. So in Europe, it's already regarded as a commercial-grade device. But here in the U.S., we're regulated as a combination product. So both the drug and the device have to be approved together.

Okay. And that was with the PDUFA in October.

Yes. Exactly.

And then you presented one slide on kind of some of the, I guess, survey activities you're doing. But like overall, what are some of the pre-commercial activities that you're currently running ahead of PDUFA?

Yes. So we were clearly preparing for a PDUFA date midyear. So we're well underway with our commercial preparations. So we've conducted critical market research. We are now conducting a price optimization research as well now that the Papzimeos price is established. And on the operational side, we really have all of our core pieces in place. So we have our 3PL, third-party logistics provider on board, our channel distribution partners identified, our patient hub partners identified. And we also are working, obviously, with our agency of record around the promotional materials, et cetera. So we're really pretty advanced in terms of our commercial preparations. We haven't put people really in field yet. Obviously, we're looking to get this issue with the FDA resolved first.

And what kind of sales force do you need? And how should we think about the ramp of spending if there's a launch?

Yes. So this is a very concentrated market. We estimate between 300 to 400 laryngologists treat the majority of RRP patients. So it's not -- you don't really need a very big field force to help support that size of market. I think Precigen have said they've got somewhere in the order of 18 to 20 sales representatives. So it's not a big field force that we're looking for.

And I'm sure you've touched base with a lot of laryngologists. What's some of the feedback on your product while they presumably maybe taking a look at Papzimeos. Do they understand the difference? Is there anything that you can say?

Yes. First of all, I would say laryngologists clearly see the need for therapeutic alternatives to surgery for their patients. The disease really places a heavy burden on their patients. They don't like doing these surgeries because they're repeated, they're not curative. And so they're really looking for a therapeutic alternative. When they look at the 2 different product profiles, as I commented, I think they see the reduction in surgery that we've demonstrated where they can say to their patients, you are likely to see a substantial reduction in surgery or even require no surgeries at all. That's very attractive.

The ability to use 3107 in the doctor's office, not have to refer those patients out to the infusion center, et cetera, that's also very attractive to them. And then the other logistical issues of not having to schedule scoping and potential surgeries. And remember, the majority of patients who received Papzimeos in their clinical trial required surgery as part of the dosing window. So the fact that they don't need to schedule the scoping and these surgeries as part of the treatment regimen is also relieves the logistical burden from them.

Good. And obviously, all eyes are presumably on this asset and how the interactions go with the FDA. But within your pipeline, you have a partnership with Akeso that you mentioned and some others and then obviously, the antibodies further back, like what is something you want to point investors to being like, hey, we also have this going on in the background?

Yes. So clearly, our ability to drive T cell -- antigen-specific T cell production is really, really strong. And that's what's underpinning 3107, 5401, 3112. And these are exciting assets. We're really pleased with the partnership with Akeso to move 5412 forward. But at the moment, we're having to focus the majority of our assets towards 3107.

We're also looking to move forward some of our earlier-stage therapeutic protein preclinical programs forward, some of our dMAb programs forward. And we're primarily looking to move this forward in partnerships -- so lots of exciting stuff going on at Inovio. T cells closest to approval. But I think the dMAb and the DPROT technology is truly groundbreaking and very exciting. And with the clinical data that we published last year, we're getting some good interest now on the partner side.

Great. Well, thanks so much for joining us today, and thanks for your insights.

Thanks very much for having us. Thank you.

Hello, everyone, and welcome to Oppenheimer's 36th Annual Life Science Conference. I'm Jay Olson, one the biotech analysts here at Oppenheimer, and it's a pleasure to welcome you to our discussion with Inovio Pharmaceuticals. And it's an honor to introduce Jacqui Shea, the CEO; and Mike Sumner, the CMO of Inovio. With that, I'll turn it over to you, Jacqui, for a few slides to set up our discussion before we start to fireside. And thank you so much for joining us here today.

Thanks, Jay, and thanks for having us today. It's nice to be talking with you again. So I'm going to kick off with just a few slides just to give you a quick overview of Inovio, our technology, our pipeline and our lead candidate and then looking forward to the Q&A. So first of all, this is just a standard disclaimer slide that during this presentation, I'll be making forward-looking statements. And then to give you a quick overview of the company, Inovio is a clinical-stage biotech company. We're focused on developing and commercializing DNA medicines to treat and protect people from HPV-related diseases, cancer and infectious diseases. We recently had our BLA for our lead program, INO-3107 accepted for review by FDA which is a very exciting milestone for the company. And it's a potential treatment for a rare disease caused by HPV-6 and 11 called recurrent respiratory papillomatosis or RRP. So FDA accepted our BLA under the accelerated approval program and granted us a standard review, which gives us a PDUFA target date of October 30 this year.

FDA has also granted us orphan drug designation and breakthrough therapy designation, and we have orphan drug designation in the EU. As part of the file acceptance letter, we did receive a note from FDA with some preliminary comments regarding our potential eligibility for the accelerated approval pathway. And we've requested a meeting with the FDA to discuss those comments. We're not currently planning to seek approval under the traditional pathway. There is a product that was approved to treat RRP last year. However, that product doesn't work for all patients and we believe that there's a significant remaining unmet need and market opportunity, and we believe that we have the potential to have the preferred product profile in this space.

Regarding manufacturing, we've established commercial scale manufacturing for the DNA component of our combination plasmid at CMOs that manufacture commercial scale products for other companies. And we manufacture the delivery device that we use to deliver INO-3107 as part of our combination product in-house. Following on behind 3107 we have a deep clinical pipeline with multiple potential near- and midterm catalysts, although we are focusing most of our efforts on getting 3107 to approval. We also have some exciting earlier-stage technology which we believe is poised to further unlock the potential of DNA medicines. It's a very exciting DPROT technology that I'll talk about later on in the presentation.

So to give you a quick overview of how DNA medicines work, we start off by identifying the target gene for the protein that we either want to drive an immune response against or we want to use as the therapeutic agent itself. We then use our proprietary algorithms to optimize that DNA sequence. And we insert that optimized DNA sequence into a circular molecule of DNA called a plasmid. We can manufacture these plasmids at commercial scale using typical fermentation technology. And then we deliver our DNA plasmids to either muscle or skin cells using our proprietary delivery devices called CELLECTRA.

Now CELLECTRA use a process called in vivo electroporation, which are very short pulses of electrical energy to help the DNA plasmids get into the cells. And what these short pulses of electrical energy do is open up transient pores in the cell membrane that allow the plasmids to enter. Once the DNA plasmids are within the cell, the DNA is transcribed to RNA and then translated to protein. And then depending on the application, these proteins are either processed for antigen presentation to generate an immune response or we can add secretion signals and have these proteins secreted out from the cell to be the therapeutic agent themselves.

So a key thing to remember about our DNA medicines platform is DNA medicines are really good at stimulating immune responses, T-cell immune responses particularly cytotoxic T-cell responses, which are important in treating chronic viral diseases and also cancer. And then we're also able to secrete these proteins out of the cell into the circulation where they can perform as a therapeutic agent. And we're able to generate monoclonal antibodies within the cell and have them secreted into the circulation as well as therapeutic proteins. So as you can see, it really is a very versatile platform, but really focused on either driving T-cell responses or driving protein production to be the therapeutic agent.

So our lead candidate, INO-3107 for RRP addresses a rare disease. So RRP really results in these wart-like growths or papillomas in the airways. It's caused by infection with HPV or the human papillomavirus 6 and 11. And it's really an insufficient immune response, particularly a T-cell response within the patient that fails to prevent first of all, the infection and then fails to clear the infection. And what happens is you get these wart-like growths primarily in the respiratory tract particularly in the larynx where you can see that they can potentially obstruct the airway, cause difficulty swallowing. And because they're growing on the vocal cords, they also impact your voice. In some cases, RRP can spread throughout the respiratory tract, form pulmonary lesions and can also become malignant.

So it's a really serious disease. You can catch RRP at any age. There are 3 general peaks of incidents, so around age 5 for pediatric RRP and then at around age 30 and around age 60 in adults. The most recent epidemiology estimates that there were about 14,000 active cases of RRP here in the U.S. So it's a rare disease, but not that rare. And repeated surgery, it's the standard of care. Severe RRP may require hundreds of surgeries over a lifetime. And it's the surgery itself that's part of the problem. And I'll talk about that in a bit more detail now.

So every surgery comes with both a risk and a cost to patients. The risk is irreversible damage to the vocal cords as well as the pain and recovery associated with those surgeries and then a cost, of course, obviously, the impact of quality of life and financial. So we designed INO-3107 as an immunotherapy and is designed to generate antigen-specific T-cell responses against both HPV-6 and HPV-11 antigens by generating the cytotoxic T-cell response, it's able to target the HPV virus, which is the underlying cause of RRP.

So every surgery matters to patients. These patients have -- many of these patients have had tens up to hundreds of surgeries and patients can have hundreds of surgeries over their lifetime and the cumulative risk of injury increases with every surgery. But ultimately, it only takes one surgery to permanently damage the vocal cords and the larynx. And so patients are really focused on reducing the number of surgeries that they require to control their disease and a reduction of even one surgery is clinically meaningful to patients.

So we've -- as I mentioned, we've conducted some market research that we believe shows that INO-3107 has the preferred product profile in this space and that's across 3 main elements: efficacy, tolerability and simplicity of the treatment regimen. And this is market research that was conducted by a third party with physicians who treat RRP patients. And what these physicians told us was they really liked the improving response that we see with INO-3107 over time. So we see a good overall response rate. So that's a reduction of 50% to 100% reduction in surgeries after treatment compared to the year prior to treatment of 72% in year 1, which improves to 86% in year 2 or the second 12-month period, and we also see some patients who required no surgeries after treatment.

This was 28% in year 1, improving into 50% in year 2. What this means for physicians is when they have an RRP patient treatment with 3107 gives them a really good chance that the patient is going to experience a significant reduction in surgery. And that's what they find really interesting about this profile. 3107 was also very well tolerated. The predominantly most adverse events were just transient injection site reactions, which resolved very quickly. We saw no discontinuations. And for patients who are having 4 doses over a relatively short time period as part of the treatment regimen, this tolerability profile is important because it really minimizes the amount of time people need to take off from work, and it means they can get back to work quickly.

And we have a very patient-centric treatment regimen. We have office-based administration, which leaves the doctor in control. So we have no requirement for ultra-cold-chain unlike the gorilla adenoviral competitor. Our administration device is very easy to use by health care professionals and any health care professional can be trained to use it. And very importantly, unlike the competitor, we don't require any scoping or surgeries to maintain a minimal residual disease state during the treatment window. So again, physicians found this very attractive.

So moving on then to upcoming milestones for the rest of the pipeline and for 3017. We have our PDUFA date coming up in October this year. We've requested a meeting with the FDA to discuss their preliminary comments in the file acceptance letter. And we believe we have the potential to be the preferred first-line treatment, if approved, based on our product profile. Following on behind 3107, we have additional clinical candidates where we're looking primarily to move those candidates forward as part of partnerships. And these include 3112, where we're looking to start a Phase III trial, 5401 where we're looking to start a randomized Phase II trial in glioblastoma, and then DPROT platform, where we're looking to advance those candidates from preclinical into Phase I. So exciting things happening across the pipeline. And I'll wrap up here. Thanks, Jay.

All right. Thank you, Jacqui. Appreciate the update and congrats on all the progress you're making for RRP patients. Maybe just to start off our discussion we can focus on that recent regulatory update on 3107 which I guess that's probably top of mind for many investors. Can you just share with us what was your initial reaction to the file acceptance letter from the FDA. And I guess we've seen a lot of regulatory surprises across the industry recently. But is there any regulatory precedent in this case, to your knowledge?

Yes. Great question. So we were obviously pleased that the FDA accepted the file for review under the accelerated approval program. We're excited about our upcoming PDUFA date, but we were obviously disappointed not to receive the priority review. So the 6 months shorter review period that we've requested. The majority of BLA is accepted under the accelerated approval program to receive that priority review. I would also note that the file acceptance letter was the first indication we had from FDA of a potential review issue regarding eligibility for review under the accelerated approval program. However, this is only a preliminary conclusion from FDA and a potential for review issue.

And we continue to believe that 3107 provides a meaningful therapeutic benefit over existing treatments and meets the criteria for accelerated approval. In terms of the regulatory environment, generally, I would say that the full approval of Precigen's gorilla adenovirus-based product last year, came as a surprise to us. That candidate had been also filed under the accelerated approval pathway. However, we believe the statute and the guidance for rare disease product candidates really outline FDA's current thinking in this area, and we look forward to discussing the review pathway with FDA for 3107.

Okay. Understood. That's super helpful. Thanks for explaining all that. And maybe just a little more on the FDA's view that Inovio did not submit adequate information to justify eligibility for accelerated approval. Do you -- I guess what do you think is behind that? Do you think that's related to the full approval of Papzimeos?

So Jay, yes, so we do believe it's related to the full approval of Papzimeos. And, Mike, maybe you can comment on some of the detail behind this.

Yes, absolutely. So with the approval of Papzimeos, we knew that based on the accelerated approval pathway guidances, we knew we would have to demonstrate a meaningful therapeutic benefit over available therapies. And that was actually part of our initial BLA submission. When you look at the guidances, first of all, you have -- there has to be a clear unmet need. Clearly, patients are still not adequately treated with available therapies. And then when you look at the individual criteria, you have to demonstrate comparable efficacy. While trials are very different based on the different treatment regimens, we do not require those minimal residual disease surgeries during the treatment administration window.

We do believe very strongly that there's comparable efficacy and then we moved to the meaningful therapeutic benefit. And we think that comes in several forms. First of all, an improved safety profile because we are not doing those surgeries during the dosing window. For the patients that were treated with Papzimeos that didn't see any therapeutic benefit they actually had more risk because they actually underwent 2 additional surgeries at both those week 6 and week 12 time point. So we do feel we have a very favorable safety profile.

And then with a differentiated mechanism of action, we believe we have the ability to treat patients who are not served by existing therapy especially those with neutralizing antibodies to the gorilla adenoviral vector as well as Precigen laid out several criteria in the papilloma microenvironment where their product wasn't as successful. We looked at the same criteria and did not see that they impacted the efficacy of 3107. So we do believe we will be able to treat patients who, as I said, are not served by existing therapies.

Okay. That makes perfect sense. And recognizing that you probably have a considerable amount of supporting information, can you just talk about any additional follow-up data including feedback from KOLs or patient advocacy groups that could further strengthen the case for 3107 that you may share with FDA?

Yes. So as part of FDA agreeing to have a meeting with us to discuss this, they asked us to submit an assessment aid. So we took data from our BLA filings and predominantly, you have the same arguments that we made in the BLA submission to support our justification for review under the accelerated approval pathway. So we've submitted that assessment aid. And as Mike has outlined, we do believe we meet all of the criteria for review under the accelerated approval pathway.

Okay. Understood. And then, I guess, is there anything that you can share with us about the time line for that FDA meeting? And do you expect it to occur before the PDUFA?

So obviously, that's up to FDA. We're currently waiting for them to schedule that meeting. But we would expect that meeting to be held in a timely fashion.

Okay. All right. That makes sense. And then just going back to the pivotal trial for 3107. I think the original plan was to initiate that in the first half of this year. Is that still something that you're planning? And I guess what additional FDA feedback or discussions do you need to start that trial? And I guess, latest thinking on timing of initiation.

Yes. Mike, do you want to take that one?

Yes, happy to. So obviously, you'll remember our original confirmatory study design was going to be a placebo-controlled study. I think with the approval of our competitor, we saw that the FDA have shifted more that a single arm study is now adequate to support registration in RRP. And so as we've worked with them, we have submitted an update to our IND for a revised confirmatory trial design, and we would expect to be hearing back from them fairly soon.

Okay. Makes sense. And then any thoughts you could share with us on additional features of the Phase III confirmatory study design?

Yes. I think we really need to hear back from FDA as to their thoughts around our accelerated approval pathway. And then I think we'll understand a bit more around what they're really looking for as part of the confirmatory trial.

Okay. All right. Understood. And then just, I guess, looking beyond the U.S. regulatory process and considering that, I guess, Precigen has indicated that the EMA validated their MAA for Papzimeos, would you think that the Phase III study is required to support ex U.S. filing for 3107?

Mike?

Yes. So we obtained clinical advice from both the CHMP in Europe and the U.K. regulators. And they both informed us that a successful approval would require data from 2 placebo-controlled trials to demonstrate both efficacy and also to meet their expectations around the size of the safety database. While we fully recognize there is the same clinical need in Europe, there does seem to be a disconnect between the feedback that we have received in the past and with Precigen's decision to file an MAA based on a single-arm study data. So I mean, we can obviously only share with you what our interactions have produced, and we can't comment on their interactions, but there definitely seems to be a disconnect.

Okay. All right. Now I guess coming back to the opportunity in the U.S. and since Papzimeos has been approved for a while now, can you just talk about any feedback you're hearing from the RRP community and physicians on the uptake and interest level in Papzimeos. And I guess, I know, Jacqui, you touched upon this earlier, but in terms of the points of differentiation between 3107 and Papzimeos and some of the remaining unmet needs there, what do you think the RP community expects 3107 to bring to the table, especially in terms of potential advantages over Papzimeos.

Yes. Great question. So first of all, I would say there seems to be a growing awareness and excitement within the RRP community about the availability of new therapeutic options. So there's certainly good awareness based on the research we've been conducting. We continue to believe that 3107 offers additional advantages over available therapy based on the improved safety profile and the different mechanism of action, which means it may work better in different patient populations to approve therapy. So it's really about 3107 meeting the needs of -- meeting these unmet needs within the existing patient population. So I think what we're hearing from the community is they're very supportive of 3107 and they're looking -- they're following our regulatory progress with interest.

Okay. Understood. And maybe just to follow up a little bit. One of the things we wanted to specifically touch upon is the issue of immunogenicity. Can you compare the adenovirus approach to DNA plasmid-based therapy? And how should we think about a potential redosing strategy for RRP patients?

That's a great question. So I'll talk -- maybe I'll talk about the immunology, Mike, and then maybe you can talk about the redosing strategy. So when we start off with 3107. As I mentioned during the presentation, 3107 is a combination product. It contains DNA plasmid encoding HPV antigens and it's delivered to the cells using the CELLECTRA device. So what this means is there's nothing to generate an immune response. We don't have any viral vector. So the immune system is really just focused on generating immune responses against the antigens that we're providing by the DNA sequences. In contrast with adenoviral based approaches, they're using a virus to take the antigen DNA into the cell. And when that happens, you have the potential of generating antibodies against the virus itself.

And you can also have preexisting antibodies that are cross-reactive against the adenovirus you used because adenoviruses are very common viruses. They cause the common cold. So it's quite common to often have cross-reactive antibodies against adenovirus in the general population. So for those patients who already have neutralizing antibodies against the virus that means that products that are using an adenoviral vector may be less efficacious. And for a DNA platform, we don't have that issue. And that's one of the key advantages of the DNA technology versus the adenoviral vector platforms.

So what that means for redosing is that with 3107 we believe we can go in and redose multiple times, continue to boost and stimulate an immune response, which may be very important for a chronic lifelong disease. And we don't have to worry about generating neutralizing antibodies which either prevent the therapy from working in the first place or which can make redosing difficult. So Mike, do you want to explain how we're thinking about redosing?

Yes, absolutely. So I mean as you saw from our Phase I/II data, we're seeing significant clinical efficacy and we're seeing durability of that clinical efficacy, but this is a chronic viral disease. We know based on longitudinal data that these patients can grow papilloma after a significant period of time. And so we want to keep generating that cytotoxic T-cell response that we know we can generate because we've seen it with other HPV targeted plasmids. And so what we are thinking at the moment is hopefully following approval, we will submit a protocol so that we can start redosing these patients on an annual basis to see if we could continue to drive that cytotoxic T cell response and further improve the clinical efficacy that we have seen to date.

Okay. Makes sense. Thank you for that thorough explanation. And then I guess, looking ahead to the launch of 3107. You've got a lot of market research to support your launch strategy. What's your latest view on the market size for RRP and the key unmet needs?

Yes. So the epidemiology estimates that there are about 14,000 to 15,000 active cases of RRP here in the U.S. Based on some claims database analysis that we've done, we believe that, that's a significant underestimate of the market opportunity. So we think there's actually a really significant market opportunity here particularly given that the competitor priced their treatment regimen at about $115,000 per dose, so $460,000 per treatment -- for a treatment regimen as part of rare disease pricing. So it's a rare disease, but not that rare and attractive rare disease pricing in terms of a commercial opportunity.

Okay. Excellent. That's super helpful. And we don't want to neglect your early-stage pipeline. So looking beyond 3107, you gave some interesting updates on some of your earlier programs. Maybe you could share with us your latest thinking on anything you'd like investors to pay attention to this year in your earlier programs.

Yes, so our later stage clinical pipeline, we -- clearly, we're putting the majority of our resources into moving 3107 forward, but we will look to move forward some of those candidates as part of partnerships. We think we can, through the power of partnerships, we think we can do a lot to move those candidates forward. And then we are also very excited about our DPROT platform. We presented the first preclinical data for our -- for DPROT candidate at the World Federation of Hemophilia Global Forum late last year. This was producing Factor VIII. And we have some further preclinical programs that we hope to be presenting data on later on this year and obviously, looking to partner those programs to try and move that technology forward quickly. So a lot going on in the pipeline. Really excited though with our first BLA and proof-of-concept for the technology with RRP and our BLA, but lots following on behind as well.

All right. Well, we look forward to those updates. Maybe just wrapping things up here. Any other key catalysts or milestones for Inovio in the next few months ahead of your PDUFA? I know a lot of investors are focused on that. But anything in the near term we should be watching out for?

I think we're really focused on that PDUFA date. The file is under active review. We're getting the normal requests from information that you would expect. And as soon as we have any news that we can share following discussions with the FDA on the regulatory pathway, obviously, we'll be talking about that.

Excellent. We'll wrap things up there. Congrats again on all the progress on behalf of RRP patients. Thank you both so much for sharing your time with us here today and bringing us up to speed on the work you're doing at Inovio.

Thank you so much, Jay. Have a great day.

Our pleasure. You, too. Thanks, everyone.

Thank you.

Good morning, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between VIPER and our next presenting company, Inovio, which are posted both at the back of the room and also at the registration desk.

Inovio is awaiting BLA acceptance for INO-3107 for recurrent respiratory papillomatosis, which additionally, Inovio is developing a unique pipeline as well as in vivo protein production technology that I think is really, really interested and ultimately could dwarf even the opportunity in RRP.

Here with us today is Jacqueline Shea, PhD, President and CEO; and also Michael Sumner, Chief Medical Officer. Thanks both for joining us for making the trip up.

Thanks for having us, Ted.

So Jacqui, perhaps you can start out by describing recurrent respiratory papillomatosis. What do patients experience? And what is sort of the current standard of care -- surgery and treatment?

Yes. Great. So recurrent respiratory papillomatosis or RRP is a rare disease. So you may not have heard of it. It's a serious nasty disease. And it's caused by the human papilloma virus type 6 and 11. And what the virus does is it causes the growth of work-like growth in the airways.

What this means for patients is that it can be very difficult to talk because these papilloma primarily grow in the larynx and on the vocal chord. It can make it very difficult to swallow. It can inhibit breathing. So it really impacts the patient's life. There's also a risk of spread of the papilloma to the lungs about in 8% of cases, you get this pulmonary spread. And once you have pulmonary spread, it's your risk of malignancy goes up as well. So this is a really tough difficult disease for these patients to deal with.

And the current standard of care is repeated surgery. So it's either laser surgery or scalpel and just removing the papilloma from the larynx and the vocal cords. And the vocal cords are really delicate tissues. They don't regenerate, they have to vibrate hundreds of times a second for you to be able to talk. So by the time you've had 8 to 10 surgeries, you've got kind of an 80% chance of having permanent damage to your vocal cords.

And the recovery after the surgeries themselves is difficult for patients. You have to go on voice rest. It can be difficult to eat. They're on a liquid diet. So these patients are in a horrible cycle of constant surgery and never knowing when their next surgery is going to be as well as the risk and the fear of is my disease going to become malignant. So it's a really tough time for patients.

Yes. That's a really helpful background and very clear and compelling in terms of what these patients are experiencing. So tell us about INO-3107. Maybe first to scribe it and how it's delivered and then we can get into some of the data.

Yes, Mike?

So INO-3107 is a DNA medicine. It is delivered using a proprietary CELLECTRA device, which delivers it via electroporation so we do not use lipid nanoparticles or a viral vector. So we see a very low frequency of systemic side effects. The actual electroporation procedure and the drug administration actually can be completed in the doctor's office and takes about 10 seconds to actually deliver the drug and the electroperation.

So it's a very simple administration process. And so we studied 3107 in a broad range of patients, range of 2 to 8 surgeries with a median of 4, and those 4 surgeries were in the 52 weeks prior to the day 0 dosing. And that's actually very similar to our competitors' population that they studied.

And Mike, just to get this in there, what is the actual drug? And what is the actual mechanism?

Okay. So the actual drug produces antigens to the E6 and E7 oncoproteins that are found in HPV 6 and 11 that actually drive the cellular growth. So they basically -- we basically generate cytotoxic T cells that target those infected cells and destroy them.

Yes. And it's been very effective. So walk us through some of the data that you've shown that's really gone into the BLA that you've submitted.

So there's really three key takeaways. So first of all, we saw a clinical and statistical significant drop in the number of surgeries. So as I said, there were four surgeries in the year prior to treatment. That decreased to a median of 1. The majority of patients are seeing a 50% or greater reduction in surgery.

And in that first year, we actually saw 28% of the patients require no surgeries at all following that day 0 dose. And then we also looked at how these patients continue after that first year of treatment. And what we were delighted to see was actually these patients clinically continue to improve. So in that second 12-month period, we actually had 50% of patients requiring no surgeries at all. So we really are delighted with the efficacy and the safety profile that we're seeing at 3107.

And with 3107 do you redose? Have you redosed? What could that benefit extend longer term?

Yes. So one of the benefits of the DNA medicine platform is that you can redose. There's no viral -- I mean with viral vectors, you get neutralizing antibodies to that. So it limits the ability to do that. And so we have in one of our previous programs demonstrated that we're able to see a significant boost in those cytotoxic T cells from redosing. And so with 3107 following approval, we do want to run a redosing program as we think we can maintain the excellent responses we saw and actually hopefully improve upon the patients that didn't see those zero surgeries.

Especially considering the clean safety signal and the tolerability that patients are experiencing in the reduction in surgery. So what is the current status on the BLA? What are the steps to approval?

So we completed our rolling submission on October 30. So we are expecting to hear back by the end of the year from the agency with respect to acceptance of the file and a proposed PDUFA date. If we get the priority review that we requested, we're expecting a PDUFA date in the middle of next year.

Great. So that's very exciting. I'm going to switch gears to the competition, Precigen [indiscernible] They've gotten approval of PAPZIMEOS, which is a similar yet that there's pretty significant differences between 3107 and PAPZIMEOS. Maybe you can kind of highlight some of those differences to start with. And if you want to sort of compare data, whatever makes sense to you. But, how are 3107 and PAPZIMEOS different?

Yes. So the Precigen product is a gorilla-based adenoviral product. But its treatment regimen is actually fundamentally different from 3107. So what do I mean by that? So both products deliver 4 doses. And we all start administration of our products after the patient has had a clinically warranted surgery to remove the papilloma and that induces a state of what we call minimal residual disease.

But that's really where the difference is end because Precigen have decided they need to maintain that state of minimal residual disease throughout the whole treatment administration period. So if you're receiving Precigen's product at the third and fourth dose, which is at week 6 and week 12, you have to be scoped and if there are any papilloma present, you have to have them surgically removed.

So you heard from Jacqui just how devastating these surgeries are for patients. So we feel it's sort of just contradictory to what you're actually trying to achieve from a therapeutic point of view to add additional surgeries into the treatment regimen. So when you look at efficacy, they start counting their surgeries after completion of their treatment regimen, whereas we start at day 0 include any surgery that patient has. So we really don't feel you can compare because 83% of their patient population had at least one of those minimal residual disease surgeries and 40% actually had two. So it's very difficult to -- in our mind, a surgery as a surgery to a patient. And so we don't like to compare the results.

Yes. It's difficult to compare them directly. And it certainly confounds the experience. I think maybe physicians and patients are going to have a preference and we can kind of talk about that in a little bit. When you look at the safety side and the tolerability, how does 3107 compare to PAPZIMEOS, you can make maybe a little bit more of a comparison there.

Yes. So as I said for 3107, we actually see a very clean systemic side effect profile. We actually ran a placebo-controlled study with one of our previous HPV targeted products. And we really see very little difference, if any, from placebo. Whereas if the Precigen product, because it's a gorilla adenovirus, you get the very typical systemic side effects as your body reacts to the delivery platform.

Yes, absolutely. And I think higher injection site reactions, fatigue and chills and all that stuff. Now have they launched PAPZIMEOS yet? And maybe you can tell us about the price and we'll sort of get into competition.

Yes, sure. So FDA approved Precigen's product in August this year. And we understand from their website and their earnings call that PAPZIMEOS was made available to order in late October. We haven't heard any sales figures reported yet. They priced their products, their gorilla adenovirus products at $115,000 a dose. So for the 4-dose regimen, that's 460,000 and that obviously doesn't include the scoping and the minimal residual disease surgeries that are required as part of their treatment regimen.

Yes. So we -- you touched on sort of what the patients go through. Maybe you can describe the market in a little bit more detail on how you plan on competing with Precigen.

Yes. So while RRP is a rare disease, it's not that rare. The epidemiology data is a little old, but it predicted that there are about 14,000 active cases here in the U.S. From some work that we've done on claims database analysis, we think that, that's likely an underestimate. And then there are also new cases each year, new instant cases of about 1.8 per 100,000.

So we -- based on other analogs in the rare disease space, we estimate that Precigen will likely have single-digit market penetration within the first year. So the majority of the prevalent pool is still going to be available to us, hopefully, when we come to market. And also, there will be the new instant cases each year as well.

Yes. Excellent. And what about overseas? Have you guys been thinking about sort of those markets? Would you consider potentially partnering? What is sort of the early -- or what is the plan for overseas?

Yes. So before I come on to that, I would just like to say we do believe we have the preferred product profile in this area. I mean, as Mike has outlined across both efficacy, tolerability in this patient-centric treatment regimen. Our market research that we've had conducted by third parties indicates that both patients and physicians prefer our product profile.

And that's because we see that the broader efficacy with the majority of patients seeing a good reduction in surgeries. And that clinical benefit improves into the second year. We have a very good tolerability profile without the need for the scoping and minimal residual disease surgeries. And it's a very patient-centric treatment regimen.

We don't have these additional scoping and surgeries. We don't have the side effect profile so that they can get back to work quickly. We don't have any ultra cold chain issues. So the patients can receive the product in their normal doctor's office as well. So all of this makes it much more tolerable for the patient and easier for the doctors.

So obviously, RRP is everywhere, unfortunately, wherever you find HBV, find RRP, so Europe and is also an important market for us. There's a relatively high level of RRP in many European countries. We have been in contact with the European regulators. And Mike, maybe you want to recap on where we are on the regulatory side there?

Yes, certainly. So as Jacqui mentioned, we got medical device from CHMP. And they're taking a different stance to the FDA. And they told us that because RRP is not that rare, they did feel that you can still run a placebo-controlled trial, and they did want a reasonable safety database as part of your submission package. So as we said, we always felt we had to do more clinical work to meet those requirements.

Yes, so I'll just pause and see if there's any questions on 3107. So Inovio has a very rich pipeline. Are there other development programs that we should be paying attention to? And then I'll kind of ask about the in vivo protein production tecnhologies.

Yes. Great. So following on behind 3107, we have two other later-stage candidates that I'd like to highlight. The first one is INO-3112, where we're going after HPV-positive head and neck cancers, so HPV-16 and 18 positive head and neck cancer. We've had some encouraging Phase II data, and we're now looking to start a Phase III trial there in combination with Loqtorzi, which is a PD-1 inhibitor developed by Coherus BioSciences and which is approved for nasopharyngeal carcinoma here in the U.S.

So very similar mechanism of action to 3107 going after HPV and really driving the production of antigen-specific cytotoxic T cells. And then the other candidates I'd like to highlight is I know 5401, where we saw some very promising data in newly-diagnosed glioblastoma, both methylated and unmethylated. Here, we're also driving T cell responses but this time going after tumor antigens.

And the next step for that candidate will be a randomized controlled trial in combination with a PD-1 inhibitor. So very excited about both of those candidates, both really focused on driving those T cell responses. And that's one of the things our DNA medicines platform does really, really well is drive those cytotoxic T cell responses and also build a memory T cell response, so you get sustained T cell responses, which is really important.

And another thing that your technology can do is endogenously produce proteins or antibodies really anything that you decide to encode in the plasmid. So walk us through -- I think this is actually some of the most interesting work that you guys are doing. Walk us through your in vivo protein production technologies. I know you kind of call them different things depending on what you're producing. But maybe you can tell us about some of the early data that you've reported and how you envision developing these technologies?

Yes. So I'll start off by telling you a bit about the technology. And then Mike, maybe I'll ask you to talk about some of the development work we're doing.

So with our 3107 candidate, we are producing antigens, viral antigens within the cell, and we're using that to drive an immune response. But our technology is also really good at just producing high level of protein within the cell, which you can then engineer to be secreted out of the cell and into the circulation.

And that's what we've done with our dMAb program, where a few weeks ago, we reported our first data for clinical data there for this program in Nature Medicine. And this was a clinical proof of concept where we were producing two different monoclonal antibodies against SARS-CoV-2.

And we were able to show that we could get both of those antibodies produced at potentially therapeutic levels the level of production and secretion into the circulation remain constant. Those antibodies were fully functional. Very, very importantly, we didn't generate any antidrug antibodies. So we're really very excited, very encouraged by this data.

And if you compare that data to what you see with in vivo protein production from mRNA. With mRNA, you see a very rapid peak and then a decade with DNA in contrast because we're delivering the DNA to these long-lived muscle cells. We see a very sustained level of protein production, which we -- which in the paper we published, we showed went out to 72 weeks, and we're continuing to collect data on that.

Now obviously, monoclonal antibodies just a form of complex protein. That means we can produce other kinds of protein. So I'll hand over to Mike to talk about some of our preclinical work that we're doing in that space. Mike?

Yes. So I mean, as you can imagine, we're focusing on that long-term in vivo protein production. And we've actually got several preclinical candidates now in development. And we actually presented the first one at the World Federation of Hemophilia meeting last month. And we're now seeing that we're capable of producing those therapeutic proteins.

And I think the reason the platform is important. I mean if you look specifically at hemophilia, they had an AAV-based gene therapy come to market. It wasn't successful, and the reason behind it not being successful was the variability in the response and the fact that the response waned over time, and you couldn't redose with DNA, we're going to be able to hopefully titrate to clinical response.

And then as that wanes or as the patient grows and they require more of the enzyme or the protein, we'll be able to give further doses so that the therapeutic effect can be maintained for the patient.

We are looking for co-development partners. As you can imagine, this has numerous potential. So we're in conversations with several companies. And what that will really give us is the ability to develop these products faster over a broader range and also bring in other companies' expertise to the development program. So it really is an exciting time for us at the [indiscernible]

Yes. Makes a lot of sense. I'm looking forward to updates there. So I'm just going to finish with a question on sort of the balance sheet. You guys ended third quarter with cash of around $51 million. And subsequently tacked on another 29%, 28%, 29%, something like that. So pro forma cash is in the mid-70s range.

Additionally, you have some Series A warrants that are exercisable within 30 days of the BLA acceptance. So that could be coming up sort of in the first quarter of next year, depending on news from the FDA, and that could bring in an additional $24 million. So somewhere around $100 million in capital back of the envelope math, how long does this fund Inovio and what does it enable you to accomplish?

Yes. So following the recent fundraising, that gives us a cash runway into the third quarter next year. And assuming that we get a priority review, that should give us a PDUFA date about middle of next year. So our current funds should take us through to our PDUFA date.

And then if these short-term warrants are exercised after pilot acceptance, that will extend our cash runway into the fourth quarter. And what our recent additional fundraising really allowed us to do, was to invest more into our launch preparation, making sure that we can have people out in the field earlier. FDA allows us to interact with payers about 6 months ahead of approval. So we're really spending those additional funds on being prepared for a quick and efficient launch if we're approved.

Great. Well, very exciting time for Inovio. Next year, we'll be sitting here and knock wood will be talking about the launch of 3107. So thank you, everybody. Jacqui, Mike, thank you so much, and good luck with everything through year-end and into 2026.

Thank you, Ted.

Good afternoon, ladies and gentlemen, and welcome to the Inovio Third Quarter 2025 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Monday, November 10, 2025. And I would now like to turn the conference over to Jennie Wilson. Thank you. Please go ahead.

Good afternoon and thank you for joining the Inovio Third Quarter 2025 Financial Results Conference Call. Joining me today on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Peter Kies, Chief Financial Officer; and Steve Egge, Chief Commercial Officer. Today's call will review our corporate and financial information for the quarter ended September 30, 2025, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer session.

During the call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions of our request for priority review by the FDA of our BLA submission for INO-3107 and our expectation that the FDA will accept the submission by the end of 2025, along with capital resources, including the sufficiency of our cash resources, our expectations regarding competition, the size and growth of the potential markets for INO-3107, if approved, and our ability to serve those markets, the rate and degree of market acceptance of INO-3107 and strategic matters. All of these statements are based on the beliefs and expectations of management as of today.

Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the Risk Factors heading identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release. This call is being webcast live and a link can be found on our website, ir.inovio.com and a replay will be made available shortly after this call is concluded.

I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

Good afternoon, and thank you for joining today's call. Today, I'm very pleased to share some important updates on the key progress we've made recently. First and foremost, we have achieved our primary objective for this year, which is completing the rolling submission of our BLA for INO-3107. This represents a milestone in our work to deliver on the promise of DNA medicine for the RRP community and is our first BLA submission, an important moment for Inovio as well. We are now focused on the next steps in the process of bringing 3107 to patients. First, we expect to receive file acceptance by the FDA by year-end, and we have requested a priority review of the BLA, which, if granted, would provide for a potential PDUFA date around mid-2026. Second, we are continuing to drive commercial efforts forward in preparation for a swift and efficient launch, if approved.

Although we will be second to market, we continue to believe that INO-3107 has compelling advantages that could make it the preferred treatment by RRP patients and their health care providers. Based on its clinical results and tolerability to date and the simplicity of its patient-centric treatment regimen. As we work toward a potential launch date for our first commercial product, we're also advancing our next-generation DNA medicine candidates. I'm pleased to report that landmark proof-of-concept data on our DNA-encoded Monoclonal Antibody or DMAb technology was recently published in Nature Medicine. We are also preparing for an upcoming presentation of promising preclinical data from our DNA encoded protein or DPROT technology at the World Federation of Hemophilia Global Forum. Both of these programs leverage a key strength of our DNA medicine platform, the ability to drive sustained targeted protein production within the body. We believe our DMAb and DPROT technologies have immense potential to treat multiple diseases and I look forward to sharing more on our progress in the coming months.

Now I'll turn it over to Mike for some additional details about our regulatory progress and next steps for 3107. Mike?

Thanks, Jacqui. This is indeed a pivotal moment for our RRP program and for Inovio. We completed the rolling submission of our BLA on October 30, submitting a strong application package that we believe clearly articulates the clinical efficacy of 3107 and demonstrates a tolerable safety profile in clinical trials to date. We submitted under the accelerated approval pathway and have requested a priority review. So we anticipate file acceptance by year-end. and if priority review is granted, a PDUFA date potentially mid next year. In the meantime, we are preparing for our pre-approval inspections for both in-house and external manufacturing sites. And you may remember that the FDA completed our clinical inspection in August this year. We are also working to finalize our confirmatory trial plans.

We had previously aligned with the FDA on a design for a randomized placebo-controlled trial based on guidance indicating that a placebo control arm was required for an indication in patients who had two or more surgeries in the year prior to treatment. We now recognize that the landscape has changed following the recent full approval of Papzimeos including how the FDA might view data requirements to support product approvals. The agency has confirmed that we only need to have initiated the confirmatory trial and enrolled the patient prior to approval, which we believe is achievable based upon our progress to date.

As you will recall, we are working with more than 20 U.S. academic sites and have made significant progress with site initiation activities, which should enable us to rapidly initiate our confirmatory trial and deliver results in a timely manner. We nevertheless want the opportunity to further discuss potential options for our confirmatory trial design with the agency and have submitted a request for a Type D meeting. With a potential approval approaching, I'd like to take a moment to highlight the strengths of our RRP program, strengths that have been foundational to our progress so far and that I believe have the potential to position 3107 as a paradigm-shifting treatment preferred by patients and their health care providers.

First, we believe that there is a significant unmet need among the adult RRP patient community, even with an approved treatment on the market, and they deserve to have therapeutic options that work for them to reduce the number of surgeries needed to control their debilitating rare disease. Next, 3107 has a mechanism of action that elicited an antigen-specific T cell response that corresponded to a reduction in surgery in our Phase I/II trial. In fact, the majority of patients experienced fewer surgeries with most experiencing a 50% to 100% reduction compared to the year before treatment. That clinical benefit continued to improve for most patients in the second 12-month period post treatment without additional dosing. I also want to highlight that our innovative CELLECTRA administration technology is an integral part to the effectiveness of INO-3107, enabling the targeted localized delivery of a DNA immunotherapy and offering a simple, effective and well-tolerated treatment experience.

Building on these foundational strengths, I think what really sets 3107 apart is its potential to address the biggest concern that RRP community has shared time and again. First and foremost, we know that RRP patients, every single surgery matters. As we shared at the European Society for Medical Oncology Congress recently, INO-3107 demonstrated continued clinical benefit with a persistent decline in the mean number of surgeries through year 2 post therapy. For patients, that means a substantially lower average number of surgeries per year, a 78% drop from baseline to year 2, meaning less exposure to the risks and costs of surgery. We also believe one of the key strengths of our DNA medicine platform is the ability to continue treatment beyond the initial treatment regimen, further enhancing the immune response as we have demonstrated with other HPV-targeted DNA medicines. We believe this provides an opportunity to consider a longer-term treatment strategy to potentially extend or further improve clinical response, which is important for a chronic often lifelong virally mediated disease.

The RRP community has also been very clear in their goal to make surgery a last resort, not a first-line treatment. As I said earlier, that was top of mind when we set out to study 3107 and our treatment regimen stands in stark contrast to Precigen's recently approved product. In their clinical trial prior to the third and fourth doses, patients were scoped to identify any residual papilloma tissue. And if any was found, a surgery was performed to maintain what is referred to as minimal residual disease or MRD. This process is reflected in the dosage and administration section of the prescribing information. They report these surgeries are performed to mitigate the effect of the immunosuppressive papilloma microenvironment and maximize the chance of clinical benefit for their product.

So what does this requirement for maintenance of MRD during the dosing window mean for patients? 83% of patients in their clinical study underwent at least one of these surgeries with 40% undergoing surgery at both time points. For the patients who later went on to have a complete response, 72% of patients or 13 out of 18 received surgery in the dosing window. These MRD surgeries during the dosing window were not counted against their efficacy endpoint as they only started counting surgeries following completion of dosing. In contrast, in our trial for 3107, we counted every surgery following the first day of treatment against our endpoint. We believe that every patient deserves a treatment that reduces the number of surgeries they face and that includes any surgeries that are part of a treatment regimen. That's just one of the core reasons we see so much potential for 3107 and believe it could become the product of choice for RRP patients and providers.

With that, I'll turn it over to our Chief Commercial Officer, Steve Egge to provide an update on the commercial front. Steve? Thanks, Mike.

I'd like to start with why we're confident that 3107 has the potential to become the product of choice in the RRP market. A key advantage for 3107 is a positively differentiated product profile that I believe will appeal to laryngologists and to their RRP patients who are looking for an effective, well-tolerated treatment that minimizes exposure to the risks and costs of surgery, including during the treatment window.

And this belief is founded on market research. The physicians we've spoken to were most interested in the fact that the vast majority of patients saw a significant benefit of 50% to 100% reduction in surgeries from 3107. And for many of them, that benefit continued to improve over time. Physicians were similarly impressed with the tolerability data, which shows that 3107 was generally well tolerated, limiting the impact on patients' return to daily life. This is very important when considering the treatment protocol includes 4 doses over a relatively short period of time.

And in terms of the treatment regimen itself, 3107 offers a more patient-centric approach that takes into account real concerns of both physicians and their RRP patients. It can be administered in the physician's office without an ultracold chain requirement. The device is simple to use. And as Mike noted, very importantly, there's no requirement for minimum residual disease surgeries during the treatment window. We believe and the market research supports that there are many laryngologists and RRP patients who, given a choice, don't want to risk additional surgeries as part of the treatment that is intended to provide relief from surgery.

And finally, as Mike noted, 3107 has been studied in a broad population of RRP patients, specifically in patients with as few as two surgeries during the year prior to treatment. We believe it's important for patients to start treatment as soon as possible after diagnosis to avoid the risk of irreversible damage from repeated surgery. Of course, in addition to these strengths, we'll learn from the launch of Papzimeos, and we will plan to be a fast follower in a market that we believe will continue to have significant unmet need when we enter.

Moving now to a few updates on launch preparations. We've continued on pace with our regulatory progress. Since our last quarterly report, we've made noted progress on both the market research and operational fronts. We've continued critical research with payers, developed our initial pricing strategy, commenced price optimization work and completed targeting segmentation and product positioning work supporting a positively differentiated product profile. We're preparing for commercialization. We're finalizing contracts with our specialty distributor, specialty pharmacy and patient hub partners, finalizing our go-to-market model and advancing the build-out of our commercial organization. I look forward to providing more updates on our progress next quarter as we further advance our commercial preparations. We're planning to get out of the gate quickly if approved and I'm excited about the opportunity to bring this much-needed treatment to the RRP community.

With that, I'll turn it over to Peter for a financial update. Peter?

Thanks, Steve. Today, I'd like to provide an overview of Inovio's financial results for the third quarter 2025 and provide a snapshot of the year so far. I am pleased to report that we have continued to align our resources to support the development of our lead candidate, INO-3107 and we will be focused on the critical needs ahead as we work towards a potential launch in mid-2026. As you can see here, we've continued to reduce our operating expenses over the past year. Operating expenses dropped from $27.3 million in the third quarter of 2024 to $21.2 million in the third quarter of 2025, a 22% decrease. When you look at the first 9 months of 2025, we reduced operating expenses by 25% compared to the same time period last year.

Our net loss for the quarter increased to $45.5 million or $0.87 per share basic and dilutive, primarily driven by a $22.5 million noncash loss on fair value adjustments related to our warrant liabilities. As the fair value of the warrants fluctuate with our share price and other market inputs, this adjustment can result in significant variability in our reported net loss. However, the net loss from operations prior to other income and expense items for the third quarter of 2025 decreased 22% to $21.2 million from a loss from operations of $27.3 million in the third quarter of 2024.

On a per share basis, both basic and dilutive, the loss from operations for the third quarter of 2025 dropped 58% to $0.41 per share from $0.97 per share for the third quarter of 2024. You can see similar reductions in our net loss from operations for the first 9 months of 2025 versus 2024 as we continue to conserve and direct our resources to support the 3107 program. We finished the quarter of 2025 with $50.8 million in cash, cash equivalents and short-term investments compared to $94.1 million as of December 31, 2024. We estimate our cash runway to take us into the second quarter of 2026. This projection includes a net operational cash burn estimate of approximately $22 million for the fourth quarter of 2025. These cash runway projections do not include any further capital raise activities that we may undertake. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our quarterly report Form 10-Q filed with the SEC today.

And with that, I'll turn it back over to Jacqui.

Thanks, Peter. While our primary focus continues to be on 3107 and a potential launch mid next year, we see immense opportunity across the rest of our pipeline as well. We're excited about the potential we see for INO-3112 for head and neck cancer and INO-5401 for glioblastoma as well as a potential cancer prevention treatment in people with BRCA mutations. And while we're currently focusing resources on 3107, we look forward to exploring opportunities to advance those programs. And as I mentioned during my opening comments, -- earlier in the clinical pipeline, proof-of-concept data on Inovio's DMAb technology was recently published in Nature Medicine. This study led by the Wistar Institute in collaboration with Inovio, AstraZeneca and clinical investigators at the Perelman School of Medicine at the University of Pennsylvania was the first clinical demonstration that monoclonal antibodies, which are complex proteins, can be durably and tolerably produced within the human body without generating antidrug antibodies.

Our DPROT technology builds on this research and our promising preclinical work evaluating the potential to expand into vivo production of therapeutic proteins will be presented this week at the World Federation of Hemophilia Global Forum, including our first research on Factor VIII production. Our deep approach aims to address some of the shortcomings of conventional therapeutic protein replacement treatments, including gene therapy approaches. As we work to bring the first approved DNA medicine to the United States, we are actively looking for future partnerships and development opportunities to advance these and other promising candidates across our pipeline.

I'd now like to open up the call to answer any questions you might have. Operator?

[Operator Instructions] And your first question comes from the line of Ted Tenthoff from Piper Sandler.

When it comes to Papzimeos, have you guys heard if they've officially launched yet? And I'm wondering how big of a deal do you think this head start that they have is, especially in a market where it's going to be a lot about education and educating physicians about new therapeutic options.

Thanks, Ted. Yes. So what we've heard from their public statements is that Papzimeos became available to order as of October 21. So Steve, do you want to talk about our expectations of being a fast follower and how we see our market entry?

Sure. So we would expect when we look at rare disease analogies and in the time period kind of between when they're out and when we would expect to be approved in mid-'26, if the current time line holds, we would expect single-digit penetration into the prevalent population in that time period. So at the time we enter, the majority of the prevalent population will be available. Obviously, the incident annual diagnosed patients will be available. And then over time, we've talked about, we would expect continued treatment or redosing also to represent an opportunity. So by the time we arrive, the vast majority of the opportunity will remain. And like we've talked about previously, we do expect to have the preferred product profile in this space. So over time, we think there's still a significant opportunity, of course, for 3107.

And your next question comes from the line of Jay Olson from Oppenheimer.

Congrats on the progress. Our first question is, do you expect to have a similar label for 3107 versus Papzymeos? And do you think the requirement for debulking with Papzymeos is something that could present a key differentiator in the label for 3107? And then our second follow-up question is related to -- I think you mentioned you're still planning to run a pivotal study for full FDA approval. Is that study also required for ex U.S. approval?

Thanks, Jake. Great question. So Mike, maybe I can ask you to take the label question, first of all.

Yes, certainly. So I mean, from a patient population perspective, we studied a broad population. We had 2 to 8 surgeries pretreatment with INO-3107. And we demonstrated clinical efficacy across the entire range of surgeries. As you are aware, we have a well-tolerated product profile. So we do believe our data would justify a broad label similar to what Papzimeos received.

So in terms of the minimal residual disease surgeries that Precigen's treatment regimen requires, we do think that, that's going to be a really key differentiator. What we're hearing from our market research is Physicians have questions around the logistics of scheduling those surgeries, so do payers as well. So we think in addition to what it means for patients, patients clearly don't want to undergo additional surgeries as part of the treatment regimen. But just from the logistical point of view as well, it also creates some challenges. Steve, Mike, I don't know if you'd like to add to that.

No, I think you've covered it. That's good.

And then in terms of the confirmatory trial, Mike?

Yes. So I mean, obviously, you heard me say today that we have submitted a Type D meeting request to the agency to align on what that confirmatory study is going to look like. It's difficult to say exactly the value of that study to a European filing without knowing the exact design. But clearly, any data collected under -- in a rigorous manner is going to help define our efficacy and safety profile. So I think any study that we perform will be of value to our European filing.

And your next question comes from the line of Sudan Loganathan from Stephens.

Congrats on the quarter. This is Felix Ampomah for Sudan. I have 1 or 2 questions. Number one, can you please comment on the sales force preparedness post 3107 approval? And then secondly, if 3107 is approved, given that it's a DNA-based medicine and also Papzimeos is virus-based, can you comment on switching from Papzimeos to 3107, if there wouldn't be any cross reactivity issues there?

Great questions, Felix. So maybe, Steve, you can take the commercial readiness question.

Yes. So we're -- as I mentioned in the prepared comments, we're advancing our launch preparations. In terms of what a field force would look like, we are planning to have MSLs as well as an access team out ahead of approval to begin to engage in scientific exchange as well as work with payers on pre-approval information exchange. And then we haven't guided in terms of the timing on the sales force. You've probably heard Precigen has shared that they expect a sales team of 18 or 18 territories. And I think it's a safe assumption that we would be kind of in that neighborhood, but we haven't provided specific guidance there. But we're certainly advancing commercial plans and plan to get out of the gate very, very quickly post approval.

Mike, the cross-reactivity?

Yes, certainly. So there's certainly no reason to suspect there would be any cross-reactivity issues for patients who have previously received Papzimeos to receive INO-3107. The one thing we would anticipate, though, is it will be important to give the entire treatment regimen as clearly, we present different epitopes to patients. So they will need to have all 4 courses of the treatment.

And your next question comes from the line of Ram Selvaraju from H.C. Wainwright.

This is Eduardo on for Ram. I guess some questions related to the DMAb and the DPROT technologies. I was hoping if you could comment a bit on the levels of expression that you're achieving for the DMAb. I know that there was a SARS-CoV neutralizing antibodies that you guys published in Nature Medicine, as you mentioned. Curious about what kind of titers you guys are achieving and if that compares favorably to kind of existing recombinant kind of titers and doses and where you can -- how you're envisioning prioritizing programs within each of these technologies and platforms?

Yes. That's a really great question. So we're excited around our DMAb technology. In the Nature Medicine paper, we described production of 2 different monoclonal antibodies against SARS-CoV-2 within the body. We were able to get sustained expression over 72 weeks. We didn't see any antidrug antibodies being produced. And this was a dose escalation and safety study, and we were able to see a dose response with an increasing amount of the DNA medicine being administered and we were able to increase the dose by giving -- sorry, increase the amount of monoclonal antibodies that we were able to detect in the blood by giving a second dose.

So we were able to demonstrate in this first clinical proof-of-concept study, a concentration in the blood of about of over 1 microgram per ml. And that would certainly put us into the right range for a number of different antibody therapies as well as potentially some protein replacement candidates as well. But this was the first proof-of-concept study. We were able to show that these monoclonal antibodies were functional as well and as functional as the native monoclonal that we designed this program around. So we think this is very promising and has read through to production of other proteins within the body. At the end of the day, monoclonal antibodies are a complex protein to produce and we think this data bodes extremely well.

Great. And any thoughts or comments on what specific programs you're going to potentially prioritize in further development down the line?

Yes. So we've -- this week, we're going to be presenting our first data on some of the preclinical work on some undisclosed targets that we've been conducting. And this first target that we're presenting on is Factor VIII for the treatment of hemophilia A. As we're progressing these programs, clearly, the majority of our resources are going towards 3107 at the moment supporting the potential launch of 3107. And so we're going to be looking to advance these programs once we get into the clinic through partnerships or once we have additional financial resources available.

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

Thank you. Before we close, I'd like to reiterate the key catalysts ahead. We're now focused on the next milestones for 3107, which include expected BLA file acceptance by year-end and a potential PDUFA date in mid-2026. We'll also finalize our confirmatory trial design with FDA and have this study underway before approval. And we'll continue to advance our commercial preparations so that we'll be ready to launch our first commercial product in the year ahead.

In closing, I'd like to take a moment to thank all the patients, advocates and doctors of the RRP community who have made our progress with 3107 possible. You are at the heart of our efforts to deliver on the promise of DNA medicine and our mission to provide every RRP patient with effective and durable relief from the devastating cycle of surgical interventions. As always, we're moving forward with the patient in mind, knowing that every day and every surgery matters. Thank you for your attention, and good evening, everyone.

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