Replimune Group, Inc. Aktie

Hello, and welcome to the 2026 Annual Meeting of Stockholders of Replimune Group, Inc. Please note that today's meeting is being recorded. [Operator Instructions] Please see the general information and supplemental rules for more information. It is now my pleasure to turn today's meeting over to Mr. Philip Astley-Sparke, Executive Chairman of the Board of Directors of the company. Mr Astley-Sparke, the floor is yours.

Good morning. I am Philip Astley-Sparke, Executive Chairman of the Board of Directors of Replimune Group, Inc. Will the meeting please come to order?

Let me take this opportunity to welcome you to the 2026 Annual Meeting of Stockholders of Replimune Group, Inc. At this time, I would like to introduce you to Shawn Glidden, the SVP, General Counsel, Chief Compliance Officer and Corporate Secretary, who is present today and will act as Secretary for the meeting. I would also like to note that representatives of Morgan, Lewis & Bockius LLP, counsel to the company and PricewaterhouseCoopers LLP, the company's independent registered public accountants, are also present virtually today at the meeting.

Before proceeding to the business of this meeting, there are certain legal matters which we must dispose of in order to make certain that we are conducting a duly authorized meeting. But as soon as these are completed, I would like to introduce you to the other officers and directors of the company and also to describe to you the matters proposed for your consideration and action at this meeting. The company has designated Sharmila Amladi of Computershare Trust Company to serve as the Inspector of Elections. Ms. Amladi took her oath of Inspector of Elections earlier today. The oath shall be filed with the minutes of the meeting. Will the Inspector of Elections please take charge of any proxies that have been filed and provide her report regarding the number of shares of common stock of the company represented at the meeting, either virtually or by proxy?

Ladies and gentlemen, they are represented at the meeting, either virtually or by proxy at least 63,759,937 shares of common stock out of the total of 84,026,071 shares of common stock outstanding and entitled to vote at the meeting.

The report of the Inspector of Elections indicates that there are present at the meeting virtually or represented by proxy the holders of a majority of the total number of shares of common stock of the company outstanding and entitled to vote at the meeting. There is, therefore, a quorum present, and the meeting is competent to transact business.

On the virtual meeting platform, you have access to the notice of the Annual Meeting of Stockholders dated July 28, 2026, concerning the matters to be considered and acted upon at the meeting and a copy of the proxy statement and annual report to stockholders for the fiscal year ended March 31, 2026. Additionally, I have an affidavit of mailing executed by an employee of Computershare Trust Company, N.A., proxy service -- proxy processing service provider for the company. The affidavit of mailing will be filed with the minutes of this meeting.

Thank you. Now that the technical organizational phase of the meeting has been completed and before proceeding to the business to be transacted at this meeting, I would like to take this opportunity to introduce to you the other officers and directors of the company.

Let me first introduce the following directors of the company: Sushil Patel, who is our Chief Executive Officer; Madhu Balachandran, and Joseph Slattery. I would also like to introduce you the following officers of the company: Emily Hill, our Chief Financial Officer; and Konstantinos Xynos, our Chief Medical Officer; and Michelle DiNapoli, Chief Commercial Officer. I will now describe the matters to be voted on at today's meeting. The following matters are deemed to be properly brought before this meeting.

Matter A, a proposal to ratify the selection of PricewaterhouseCoopers LLP as the company's independent registered public accounting firm for fiscal year ending March 31, 2027.

Matter B, a proposal to approve on a nonbinding advisory basis, the compensation of the company's named executive officers for the fiscal year ended March 31, 2026.

And Matter C, proposal to approve an amendment to the third amended and restated certificate of incorporation of the company to increase the number of authorized shares of common stock par valued $0.001 per share from 150 million shares to 300 million shares.

We will now move on to the voting. The virtual polls were opened at the top of the hour and will remain open for a reasonable time for you to cast your vote upon the proposals. Any stockholder who has not previously provided his or her proxy or voted electronically is requested to click on the voting button of the web portal and follow the instructions therein with respect to all matters being voted upon. If you have already submitted your proxy card, your shares will be voted in accordance with the instructions on the proxy. We will now pause for a moment for you to complete your vote.

[Voting]

The polls are now closed. The Inspector of Elections will give her report concerning the votes upon the aforesaid proposals to the Secretary. Will the Secretary please report the results of the voting?

I have received a report from the Inspector of Elections, which states that the proposal to ratify the selection of PricewaterhouseCoopers as the company's independent registered public accounting firm for the fiscal year ended March 31, 2027, has been duly passed by the stockholders of the company.

The proposal to approve on a nonbinding advisory basis, the compensation of the company's named executive officers for the fiscal year ended March 31, 2026, has been duly passed by the stockholders of the company.

And the proposal to approve an amendment to the third amended and restated certificate of incorporation of the company to increase the number of authorized shares of common stock par value $0.001 per share from 150 million to 300 million shares has been duly passed by the stockholders of the company.

The formal business of this meeting is now complete. If there is no further business to be raised from the floor, I would like to thank all of the stockholders for attending today's meeting virtually. The legal portion of the meeting is now adjourned, and you may now disconnect.

This concludes the meeting. You may now disconnect.

Good day, and thank you for standing by. Welcome to the TUDRIQEV FDA Accelerated Approval Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I'd now like to hand the conference over to Arleen Goldenberg, Vice President, Corporate Communications. Please go ahead.

Thank you, operator. Welcome, and thank you all for joining us on this exciting day to discuss the FDA Accelerated Approval of TUDRIQEV. I'm Arleen Goldenberg, and I'm joined on the call today by Sushil Patel, our Chief Executive Officer; Kostas Xynos, our Chief Medical Officer; and Emily Hill, our Chief Financial Officer.

A short time ago, we issued a press release announcing the FDA accelerated approval of TUDRIQEV. The press release and the slide presentation to accompany today's call are available in the Investor Relations section of our website at replimune.com.

Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements may represent our views as of today, August 6, 2026, only. A replay of the call will be available on the company's website following its completion.

On today's call, we will discuss the U.S. Food and Drug Administration's accelerated approval of TUDRIQEV, including plans for commercial launch. Following our prepared remarks, we will open the call for your questions.

And with that, I am pleased to turn the call over to Sushil Patel, Chief Executive Officer of Replimune, who will take us from Slide 3.

Thank you for joining us today to discuss the FDA accelerated approval of TUDRIQEV, formerly known as RP1. This is a key milestone for Replimune and an even more important moment for advanced melanoma patients who are in desperate need of new treatment options.

I want to take a moment to acknowledge the hard work and dedication of the entire Replimune team in getting us to this pivotal stage in our mission. The focus of today's call will be to review highlights of our broad label, reflective of the real-world population we enrolled in the IGNYTE trial. In addition to the label, we will also discuss the launch strategy and key activities that we believe will enable successful commercialization.

We have always operated with a focus on patients and today marks an important step in the journey to help as many of them as possible. Patients like Erin, whose treatment had failed to respond to initial immunotherapy for advanced melanoma. Erin received TUDRIQEV in combination with nivolumab as part of the IGNYTE clinical trial, and she has no evidence of disease since completing the treatment, which has allowed her to continue to enjoy life with her friends and family.

We are incredibly grateful to the patients, families and clinicians who participated in our clinical trials as well as the many others, including leading melanoma experts from around the globe as well as advocacy groups who have supported our work over the past year. Today would not be possible without you.

Slide 5. Replimune was founded to develop the next generation of oncolytic immunotherapies. To date, the RPx platform has been tested in approximately 1,000 patients, and we have now reached a major milestone with our first FDA approval. This marks an important moment and opportunity to potentially help thousands living with advanced melanoma.

Today, we are proud to announce that the FDA has approved TUDRIQEV in combination with nivolumab for the treatment of adults with unresectable advanced cutaneous melanoma that progressed on a PD-1 antibody-based regimen.

Slide 5 -- Slide 7, sorry. We are pleased that our label reflects a broad population of advanced melanoma patients, inclusive of all subgroups studied in our trial. The label describes the meaningful clinical effect in non-injected lesions, the ability to treat superficial, deep and visceral lesions and has no requirement for prior BRAF treatment. The label also allows for the retreatment of those who are benefiting from therapy after their initial 8 doses.

With that, I will turn over to Kostas Xynos, our Chief Medical Officer, who will review some of the more specifics of the U.S. prescribing information.

Thank you, Sushil. Please advance to Slide 9. Good afternoon. My name is Kostas Xynos, and I'm thrilled to be here today. I will share with you the main points of our U.S. label.

I would like to start with a brief overview of the IGNYTE study, our global multicenter trial that formed the basis of TUDRIQEV's accelerated approval. IGNYTE was designed to evaluate RP1 in combination with nivolumab in patients with advanced melanoma using rigorous criteria for PD-1 failure as patients had to progress while on treatment. This is an important distinction as it represents patients with true resistance to checkpoint inhibition, where existing treatment options are limited.

In addition, patients without confirmed disease progression were able to continue or reinitiate treatment with RP1 if it was clinically indicated by the treating physician. This feature reflects how patients are managed in real-world practice and allows the treating physicians the flexibility to tailor the therapy based on the ongoing clinical benefit.

Next slide, please. The patients enrolled in IGNYTE were representative of a real-world hard-to-treat advanced melanoma population, reflecting what clinicians usually see in their practice. The study included challenging to treat subgroups such as patients with Stage IV disease, those with prior adjuvant treatment, PD-1 neg -- PD-L1 negative patients and those with lung and liver lesions. Nearly half of the patients had lung lesions and 1/4 of them had liver lesions. Important note is that we observed no overall difference in safety or effectiveness in elderly patients who often represent a significant portion of the advanced melanoma population.

Next slide, please. Moving on to the core efficacy data and starting with our primary endpoint, the label reflects the efficacy analysis of 91 patients with non-injected lesion response. TUDRIQEV plus nivolumab achieved an objective response rate of 24.2%. The median duration of response was 14.1 months with 55% of the patients remaining in response for 12 months or longer. The clinical results from the IGNYTE trial are further detailed in the primary publication in the Journal of Clinical Oncology. Overall, this data demonstrate that TUDRIQEV delivers deep, durable and clinically meaningful responses that support its long-term value in this disease setting.

Next slide, please. TUDRIQEV is an off-the-shelf treatment practically for everyday clinical practice that minimizes logistical complexity and treatment delays and ensures that patients with aggressive disease receive immediate care. Dosing and administration is designed to be simple and flexible for health care professionals with a dose calculated as 1 milliliter per centimeter of tumor diameter with up to maximum of 10 milliliters injected. Clinicians will have versatility when choosing which lesion to inject, including both superficial and visceral lesions.

Our guidance is to prioritize the most rapidly growing or largest lesions, whether new or existing, provided they are suitable for injection. Importantly, in terms of scheduling, TUDRIQEV does not need to be given the same day as nivolumab.

Next slide, please. Here, I want to briefly show you how intuitively our therapy is administered. TUDRIQEV is injected directly into the tumor. All images are included in the USPI guiding injections. This slide illustrates the injection techniques for superficial tumors and demonstrate the straightforward and versatile administration techniques for TUDRIQEV, making it easy for health care providers to deliver the drug effectively to both superficial non-ulcerated as well as ulcerated tumors.

These are standard and well-understood injection techniques, both in dermatology and oncology, requiring minimal specialized training and can be performed by all HCPs, including physicians, physician assistants, nurse practitioners and registered nurses.

Next slide, please. These images address how our therapy is delivered to deep or visceral tumors, which are often the site of more advanced disease in organs such as the lung, the liver, the kidney or deep lymph nodes. Interventional radiologists are very familiar with these injections as they routinely perform them. These injections can be considered simpler than a biopsy as a much thinner needle is used. These injections are performed under image guidance, typically ultrasound for more accessible organs like the liver or CT scan for deeper lesions like the lung, assuring accurate placement and maximize safety. For IRs, this is their everyday life as these are routine procedures, common daily practice for them.

Next slide, please. TUDRIQEV combined with nivolumab is a generally well-tolerated regimen with no reported contraindications. The most common adverse reactions were generally mild to moderate, consistent with previously reported data and were predominantly grade 1 and 2 constitutional type side effects. Importantly, there were no grade 4 or 5 common adverse events.

On the right-hand side of the slide, you can see some additional safety highlights. A critical safety finding is that there has been no reported transmission to close contacts. Furthermore, TUDRIQEV can be managed as biosafety level 1, which is the lowest possible biosafety level and can be effectively cleaned using standard disinfectant procedures.

Next slide, please. In closing, this is the trial design of our confirmatory study, IGNYTE-3, that will also serve as the foundation of our global patient access. IGNYTE-3 is a global randomized trial of RP1 in combination with nivolumab versus physician's choice in advanced melanoma patients with the primary endpoint of overall survival. The study is well underway, and it is expected to complete enrollment in 2030.

Thank you very much for your attention, and I will now pass it back to Sushil to walk you through our commercial strategy.

Moving to Slide 17. Thank you, Kostas. We are now laser-focused on delivering TUDRIQEV to advanced melanoma patients. We know there are roughly 10,000 advanced melanoma patients a year in the U.S. who progress on a PD-1 containing regimen who could be candidates for TUDRIQEV plus nivolumab. Roughly 20% of these patients will present with superficial lesions only. 20% will present with both superficial and deep lesions and the remaining 60% tend to present with deep lesions only.

It's important to remember that until today, there really was only one FDA-approved option. We very much look forward to providing a much-needed additional option for a broader population of these patients, including those with hard-to-treat visceral disease.

Slide 19. As our team begins product promotion, our strategic focus will be to position TUDRIQEV as the first choice after progression on a PD-1 containing regimen. In an effort to generate awareness and demand for TUDRIQEV, our specific launch strategy will be grounded in 3 critical success factors. Firstly, instilling confidence to drive targeted and rapid adoption. Second, we really want to ensure a positive experience and seamless patient journey. And one of the unique groups we've established to enable this is the operational excellence team. This is a cross-functional group of oncology nurses, pharmacists and interventional radiology experts dedicated to working with new treatment centers to establish TUDRIQEV's operational workflows.

The team's efforts will accelerate site activation and ensure that positive first experience and drive repeat use. And finally, we want to ensure that we deliver a meaningful value proposition for all stakeholders.

Slide 20. During profiling last year, our teams met with nearly all of our early adopter accounts with several key insights identified throughout that profiling process. For example, our teams have a clear path in understanding who the interventional radiology and medical oncology champions are in roughly 90% of these accounts. The team has also received significant proactive requests for engagement immediately following approval.

Slide 21. In regards to the early adopters that I just mentioned, these 200 accounts represent the accounts with the highest patient treatment potential based on claims data. They typically have the most well-integrated interventional radiology teams within their centers and all have prior intratumoral injection experience.

In order to establish a strong launch foundation, our team's initial focus will be on establishing TUDRIQEV in the early account -- adopter accounts. These represent about 30% of the national melanoma patients treated annually. Once established in early adopters, we'll then add to our focus the next 250 accounts, which will represent in total, just over half of the patient treatment volume in the U.S.

Longer term, we'll then roll into the next 750 accounts, which will allow us to reach about 80% of the potential patients treated annually. Early in the launch, the majority of our patients will be treated in the hospital setting with this evolving to a more balanced mix across hospital and nonhospital settings over time.

Slide 21 -- Slide 22. Our team will continue to ensure payer coverage is in place to support usage. To date, the team has presented pre-approval information exchange presentations to national and regional payers who represent nearly 80% of medically insured lives, which we believe will help establish a streamlined process for coverage policies, and we'll continue to focus on this closely in the months to come. Whether patients are injected with TUDRIQEV by an interventional radiologist in the hospital for deep lesions or a medical oncologist or nurse in their office, meaningful procedure codes already exist.

Finally, during the period of time when a new oncology product is approved and awaiting a permanent J-code to help facilitate reimbursement, we typically see a site of care shift from the community into the hospital setting where reimbursement is more easily supported. For the majority of patients with deep lesions, this is exactly where we want them to go since this is where interventional radiologists tend to practice. Once there, in addition to the procedure codes being in place, most accounts will benefit from 340B pricing since TUDRIQEV is administered on an outpatient basis.

Finally, for oncologists who want to maintain that patient treatment continuity, they can begin administering nivolumab for up to 2 years in their office where reimbursement is already reestablished. So again, we believe that today's reimbursement model supports the patient journey that we're looking to establish with the availability of TUDRIQEV.

Now this patient journey shown here on Slide 23, begins once a patient has progressed on the PD-1 therapy and the medical oncologist selects TUDRIQEV for their patient. The treatment selection process has become more streamlined given that our final label doesn't require prior BRAF-targeted therapy before starting treatment with TUDRIQEV.

To expand a little further on the patient journey, once TUDRIQEV is chosen, the key next step in the process takes place when the multidisciplinary treatment team collaborates on establishing a patient treatment workflow, where the team will review the scan and create a plan. We surveyed more than 100 medical oncologists and 97% said they are willing and interested to collaborate with interventional radiology, and the IR community has been very enthusiastic to adopt RP1.

Selecting an appropriate dose based on patients' tumors has also been simplified with our straightforward label dosing guidance of 1 milliliter per centimeter. Once product is in the channel, we will be implementing our drop ship next-day delivery model across treatment settings to quickly meet the anticipated demand while demonstrating a strong sense of urgency for patients.

On the day of administration, TUDRIQEV injections are administered in the outpatient setting with standard cleaning procedures in place to help further support routine usage. Another critical step in the treatment journey is, of course, having a meaningful patient and provider support program in place to ensure that positive treatment experience.

Next slide, Slide 24. On that front, I'm really pleased to announce that the ReplimuneConnect Plus, our patient and provider support program will be available in the coming weeks ahead of drug in channel. In addition to the traditional offerings, we are proud that ReplimuneConnect Plus will have a suite of concierge-level offerings, including on-staff nursing support to address treatment-related questions, text message reminders of scheduling and appointments through our case workers with additional support services available to caregivers.

In establishing our depth of understanding of the advanced melanoma market as well as our patient resources, which include the development of Connect Plus, an important step in the process was ensuring we stayed close to the needs of our providers and the voice of our patients.

With that, I'll turn it over to Emily Hill, our Chief Financial Officer.

Thanks, Sush. On Slide 26, I'd like to start by describing some of the pillars for the RP1 platform to drive our long-term success. First, we are proud to have our own in-house manufacturing facility based right here in Massachusetts, where we have the capacity to support not just the imminent launch, but long-term global commercial supply of RP1 and future RPx expansion.

We expect to start shipping TUDRIQEV from this facility within approximately 60 days. We expect the cost for a typical TUDRIQEV real-world patient to be approximately $450,000 for a course of therapy. Overall, we believe this pricing is in line with comparable treatments for advanced melanoma and reflects the efficacy and differentiated safety profile of TUDRIQEV.

On Slide 27, with this approval, we have derisked the RPx platform and now have the opportunity to unlock additional value. Our pipeline here shows how we will start to achieve that value for patients and shareholders. These trials are designed with the aim to bring benefit to patients beyond skin cancers.

We are proud to have achieved the milestone of TUDRIQEV approval. We have a number of exciting milestones ahead of us. As we transition to a commercial company, we look forward to our first time reporting TUDRIQEV revenue and future data publications to support potential NCCN listings for RP1. In addition, we look forward to sharing updates from our REVEAL and HCC/BTC studies.

Replimune has the right components to become a leading and highly valuable oncolytic immunotherapy company with an experienced team, a development plan guided by clinical evidence and now our first approved product. We look forward to delivering on our long-term potential.

With that, I'll turn the call over to the operator for Q&A.

[Operator Instructions] Our first question comes from Ally Bratzel with Piper Sandler.

Big congratulations on the news today. Maybe just the first question for me. How has the widely publicized nature of the RP1 review process just affected physician and patient awareness and expected adoption trends?

And then just a second one for me. Just looking at the efficacy data on the label, Section 14, it looks like FDA got their 91 patient 24% ORR analysis in there. Does that matter at all to docs or to payers? Just any thoughts there?

Thank you for the question. Firstly, you're absolutely right. We've had tremendous awareness. And I think one of the sort of benefits of the AdCom was just the tremendous sort of public and physician support and awareness it's created for RP1. And I think when you listen to the open public forum, it was very clear that this is a treatment that patients very much need and physicians want. So in that regard, we think this is actually a very positive thing for us and actually looking forward to being able to meet that demand.

In terms of the 24% number, yes, we believe that's determined from the efficacy evaluable population from the FDA, and that's 91 patients with at least one non-injected lesion, which resulted in an ORR of 24.2%. We don't believe that that's going to be a challenge for us in any way, shape or form, given the unmet need, given, I think, the breadth of the profile, the efficacy and safety profile we bring to these patients who are clearly an unmet need, we don't believe this will be a significant hurdle to adoption and actually are very much looking forward to communicating the efficacy and safety benefits of TUDRIQEV to our prescribing population. And again, we don't also expect any payer issues with the data given the FDA approval. The data will also be submitted to NCCN in the very near future.

Our next question comes from Roger Song with Jefferies.

And my huge congrats for this achievement. Maybe 2 from us. One is given the label and then the pricing and the awareness, how do you think about this launch ramp going to look like?

Second is in terms of the confirmatory study, understanding FDA used to have some comments around the design. And then just curious, have you get alignment on the confirmatory study comparator arm and then the primary endpoint? And then when should we expect to see the data from the confirmatory study?

Thank you for those questions, Roger. I'll take the first question. And on the confirmatory trial, I'll ask Kari Jeschke, our regulatory lead to take that one. So firstly, I think we have a very competitive label. And in terms of what the commercial uptake looks like, I think this is a profile that physicians and patients want, as I mentioned. But however, we really want to make sure that physicians and patients have a positive initial experience, and we're in the process of rehiring our commercial team.

As I mentioned in my prepared remarks, we expect the initial uptake to be in hospital-based settings where temporary J-codes can be utilized and there are in-house interventional radiologists. And over time, Roger, we expect to expand into these community practices. We do believe that TUDRIQEV will become a new standard of care for patients who progress on a PD-1 containing regimen. And given the size of the patient population and pricing, we believe this represents a significant market opportunity. And then Kari, I think you had a question on the confirmatory trial and whether there was any communication with the agency in terms of the appropriateness of that study.

Right. Thank you. No, we have not had any request from the FDA to make any changes to that study. We've discussed it with them along the course of the way. And at this point, we're expecting to have our overall survival data endpoint readout in 2030.

Our next question comes from Daina Graybosch with Leerink Partners.

Congratulations from me as well. Many questions here. The first one in this 91-patient subset, the 24% that made on the label, that looks pretty much the same as what we saw in the briefing documents. And FDA separately had some concerns with response analysis for some patients. Was there no overlap? Or did they get over their concerns? I just wondered where that landed and how you ended up with this 91-patient response analysis?

And then the second question is if you can help us understand the pricing breakdown for the average real-world patient where you quoted a price per course?

Okay. Thank you. In terms of the 91, our understanding is the patient -- the FDA determined an evaluable patient needs to have at least one noninjected target lesion. So that's all we can really comment in terms of how they got to the 91 patients. It was very similar, as you mentioned, to the sensitivity analysis they had in their briefing book that presented at the AdCom. And in terms of the pricing breakdown, I'm going to hand that over to Emily, who will address that.

Thanks, Sush. So we described a price of $450,000 per typical real-world patient. That's based on a volume use of 18 milliliters. As you may be aware, the volume of TUDRIQEV per patient is based on their tumor burden. And in our IGNYTE study, we saw a median use of 18 mls. Of course, there is a range of volume used in patients that will be above and below that. So we are basing the typical real-world patient price off of the median experience in the IGNYTE study.

Our next question comes from Anupam Rama with JPMorgan.

Huge congrats to you guys. Really a testament to your guys' perseverance and persistence here for this patient population, really cool to see. A quick one from us. On the top 200 accounts, can you remind us of the size and scope of your initial field team to kind of address that first 30% of advanced melanoma patients? And with drug being shipped out here in the next 60 days or so, like where are you on the build-out of that team?

Yes. Thanks, Anupam. So we're about 1/3 of the way through the overall commercial build-out. Ultimately, we expect to have about 50 commercial, including field-facing teams. That will be around 20-or-so sales representatives. What's been really exciting is that a number of the team has actually come back to Replimune because I think they very much believe in the mission and what we're trying to do for patients. So we've already got a group of reps and sales managers who already have good training and understanding of the product, and now we're currently in the process of hiring the remainder of those. So watch this space. I think we're in good shape right now, and we look forward to being able to bring RP1 to patients very soon.

Our next question comes from Li Watsek with Cantor Fitzgerald.

I wanted to add my congrats as well. Maybe just first question on the manufacturing side. Just wondering if you have enough drug on hand right now for the launch? And when will you be able to ship RP1 to the patients?

And then second, on the confirmatory study, just wondering if you can share the enrollment status. And when you might be able to share interim OS analysis? And is there an FDA requirement in terms of the time line?

Yes. Thank you. I think there were 3 questions there. So I'll take the first couple, and then I'll hand the confirmatory study over to Kostas. So in terms of how much drug supply we have, we have about a year of inventory on hand. So I think we're in good shape there. We expect to ship RP1 in approximately 60 days from now, and the team is working very hard to ensure that we can deliver on that. And in terms of the confirmatory trial and time lines in terms of accelerated approval and current enrollment, I will hand over to Kostas.

Sure. Yes. So the confirmatory study IGNYTE-3 is ongoing with an overall survival endpoint, event-driven study. We expect the enrollment to complete 2030. In terms of recruitment, we have recruited about 1/3 of the study already, and we're moving forward with opening the ex U.S. sites.

Just to clarify, that's data in 2030.

[Operator Instructions] Our next question comes from Daina Graybosch with Leerink Partners.

There's a lot for us to understand here. Two more commercial questions. I wonder if you've done an analysis of the overlap of your 200 early adopter accounts with those authorized treatment centers that currently offer AMTAGVI? And also on the interventional radiologists, do you have a sense of how broad the awareness is beyond the champions you identified in IR in each of the 200 accounts?

Yes. So in terms of the 200 accounts, yes, one of the kind of criteria we looked at -- well, there were a number of criteria we looked at for those. As I mentioned, do they have integrated interventional radiology? Do they have an intratumoral experience? Are they clinical trial sites? And yes, one of the overlaps is AMTAGVI, and there's a very significant overlap with AMTAGVI treatment centers, as you can because our initial focus is in these hospital-based and academic accounts. So I think there's probably an 85%, 90% overlap with AMTAGVI treatment centers. And then secondly, sorry, your question was on...

The IR awareness beyond those champions.

Yes. So we had done previously as we were preparing for launch, we've done a lot of work with the interventional radiology groups, both groups like SIR, Society of Interventional Radiology and SIO, the Society of Interventional Oncology. So they were very excited and really looking forward to having RP1 available. Obviously, we will need to sort of ramp up some of those activities. But I would say in terms of some of the key oncology interventional radiologists and other key large academic sites, I think the awareness is very good, but that's certainly something we'll be using the sort of next few months to make sure that we ensure that they have what they need, they're aware and that we're hitting the right people.

Our next question comes from Evan Seigerman with BMO Capital Markets.

This is [ Hadin ] on for Evan. So during the AdCom process, it was noted there was a very large disconnect between how melanoma specialists and regulators thought about TUDRIQEV and its potential. So coming out of that, how do you think this might create implications for the IGNYTE-3 trial? And is there anything that can be done from a strategy perspective to help bridge the gap there and provide some derisking into IGNYTE-3?

I don't think there's a lot of read over to the I-3 study. Firstly, the primary endpoint in I-3 is overall survival, which really has the response criteria and assessment really has no impact on whether the patient ultimately lives longer or not. So I don't think there's a lot of read-through on that. I don't think this label and then sort of what the discussion was at the AdCom really has much impact on where we expect commercial uptake to be.

As I mentioned, the -- and as you heard from physicians, I think they're very excited about having a different option that treats this really hard-to-treat patient population. And given the safety and efficacy profile and the fact that we can treat a broad range of patients, I think that's going to trump any sort of conversations or downside from the AdCom.

That concludes today's question-and-answer session. I'd like to turn the call back to Sushil Patel for closing remarks.

Thank you. So in summary, we are proud to be delivering the first approved oncolytic viral therapy to advanced melanoma patients following PD-1 progression. We're extremely pleased by the broad label received by TUDRIQEV, and we believe it provides a novel and differentiated treatment option for patients that has both a compelling efficacy and safety profile. We are incredibly grateful to those internally and externally who fought so hard for patient access to this innovative and important therapy. Thank you for joining our call today.

This concludes today's conference call. Thank you for participating. You may now disconnect.

All right. Let's go ahead and get started. Welcome everyone to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, [ Joyce Zhou ], Priyanka Grover and [ Rati Pinhe ]. Our next presenting company is Replimune, and presenting on behalf of the company, we have CEO, Sush Patel.

Thank you, Anupam. I'll just refer you all to our...

Sush if the slides don't work, do you want to just make this a fireside, where you and I can just have a chat.

Happy to do that.

All right. Safe harbor statement.

I'm playing catch up now. All right. I'll refer you to our forward-looking statements. So it's been a -- 2025 was a tumultuous year for Replimune, but as Anupam and his team at JPMorgan have sort of tagged us as the turnaround story. And I'm excited to share the resilience we've shown and why we're actually now poised to deliver on the promise of oncolytic immunotherapy for patients. So near term, we're looking forward to our approval, and we're already ready to execute on our commercial launch plans. That involves working very closely with the oncology and interventional radiology stakeholders. We've done a lot of work on now and ready to go. And we're also worked to simplify the logistics for our modalities so that we can enable next-day delivery and also stability at room temperature for our asset.

Now one of the things that we're really confident on is this is something that can be used broadly for a treatment of many cancers. And one aspect of that is when you look at the first-generation drugs such as T-VEC, these were predominantly used for the injection of small superficial lesions. What we've been able to do now is show through deep injections, including viscera, lung and liver, that we can get to a lot more patients. And we've been able to do this reproducibly and that we've now done more than 1,000 deep injections, which I think is really important as we think about the potential of this modality longer term. We've also treated more than 1,000 patients, and we have many HCPs that have a lot of experience with RP1, including in the U.S. We've seen durable responses, systemic responses, which are again very important. We're now moving forward with randomized trials and also moving beyond skin cancers to other more prevalent tumor types.

So as we think about Replimune's mission, we really were founded with the intent to develop more potent and systemically active immuno-oncology drugs. And this really starts with our first 2 assets, RP1 and RP2, which encode a number of proteins and transgenes to really drive a more potent and systemic activation of the immune system. So one thing we have is GALV, which is a fusogenic protein, that drives immunogenic cell death, both our assets RPQ and RP2 have that.

We also have GM-CSF in the constructs. And then RP2 was really designed to drive even more potent activity in more immune insensitive tumors, and that includes CTLA-4. Now one of the things we want to do beyond the assets themselves is really our approach to injecting, how we inject, where we inject. Now what we have seen is when you just inject superficial lesions, we are able to see uninjected responses, including in the viscera, lung and liver, which is great. However, we've always believed that when you have a patient that has both skin and deeper injections, it will actually maximize outcomes if we're able to inject both of those locations or if they've only got deep lesions. And what you -- what I'll show you shortly is that this hypothesis is actually now translating into clinical benefit for patients.

So I'm going to start with our pivotal data set in anti-PD-1 failed melanoma, and that's from the IGNYTE trial. I think one of the important things really to provide context of the data is to understand that from the outset, we selected a very rigid and rigorous criteria for PD-1 failure. Because what we want to know is that this is a combination regimen, and we want to make sure that further PD-1 therapy in these patients really would not be expected to do anything probably in the 5% range. And so we use this criteria where essentially we ensured that there was sufficient prior exposure to PD-1-based treatments. That means at least 8 weeks, although 95% of patients had at least 12 weeks of treatment.

The last treatment before coming on to the IGNYTE trial was a PD-1-based regimen and that these patients progressed while on that regimen and had confirmed progression. So this is one of the most rigid criterias for any trial to ensure that these patients have definitely failed their treatment. So now I just want to give you an exert to some of the data we presented at an oral presentation, a late-breaking oral presentation at the SITC meeting this year. And it sort of just further highlights the benefit we're providing to very tough to treat patients. These were particularly difficult subgroups from that trial.

For example, if you look at the primary resistant population, we see that we get about 32% response -- sorry, 34% response rate, which is actually very similar to the overall patient population. Primary resistant patients are patients who actually blown through their prior treatment in less than 6 months, difficult to treat. And it's great that we can actually see a very similar benefit for those patients as we see for the overall population. We also see benefit in patients who have failed both CTLA-4 and PD-1 as well as later-stage patients with a very consistent benefit. So again, these are really important things as we think about how we position this regimen and the unmet need in this population.

So one of the important questions you always get when you're doing a single-arm trial, particularly with the combination is well, what is RP1 contributing? And I mentioned one of the ways we got to that was this very strict criteria so that we know that further PD-1-based treatments really wouldn't do very much, as I said, about 5%. So when you see about a 34% response rate, we know that the RP1 is really contributing. However, we've also done some additional analysis, and this is what I'm sharing on the next couple of slides.

This is looking at patients as their own control. And so if you look at the 11.5% response rate, this is looking at the response rate patients had before coming on to the IGNYTE trial. And then if you look at the 29.8% response rate, that's what they experienced after receiving RP1 and nivo after they definitively failed their prior treatment. So in oncology, it's very rare that you actually have an earlier line treatment and then in later line treatment, you actually see the response rate increasing.

If you look at another subgroup here, primary resistance, as I mentioned earlier, these are particularly hard-to-treat patients. Those patients had a 0% prior response rate, and we got them into a 28% response rate on the IGNYTE study. So again, this is just another way to try and explain and show the contribution of RP1 to these patients. Secondary resistant patients, yes, they had about a 30% response rate. Even that's lower than what you might traditionally expect from frontline immunotherapy, you get about a 40% response rate. But after definitive progression, then we managed to get another 1/3 or so of those patients back into response. So again, this is very meaningful for treaters, and it's why physicians tell us that this is something that they really want for their patients given how difficult these patients are to treat.

Now responses are important, but the other thing you want to know is are these responses durable? And so this is another analysis we've done looking at time to progression prior treatment, which is the red line on these graphs and then after the patients have received RP1 plus nivolumab on the IGNYTE trial. The slide on the left is looking at all patients. And you can see that we start to raise that tail -- we start to raise that curve and see a tail, which is what you want to see with immunotherapy. And then on the right, you see that really for responders, this is quite a striking difference from the benefit they receive versus their prior treatment. So again, very important to show that what RP1 is contributing.

So now at our Type A meeting and subsequent communications, we have got a confirmation from the FDA that this is an acceptable trial design for registrational purposes. And just so you know that one of the questions we had is, well, you have a limited dealer's choice, why do you allow PD-1 monotherapy on that trial? Well, actually, that was -- it is an NCCN approved option, although in reality, it's very rarely used. And what we were able to share with the agency is even though it's an option, nearly all the patients in this trial, which has now enrolled about 60 patients are actually getting Opdualag in the control arm.

So they felt comfortable with that. So this should be fine moving forward. The study is going really well. It's enrolling. And as I mentioned, we have over 60 patients enrolled now. That's predominantly in the U.S., but we've now recently started enrolling patients in Europe and have expansion plans for the U.K. and Australia in the very near term. We plan an interim overall survival analysis from this study in the second half of 2027.

So that's just sort of now transitioning on to preparing for the commercial launch in melanoma. Now we have a significant patient opportunity ahead of us here. There's about 10,000 addressable patients, about 80% of these patients will have something they can inject and be eligible for RP1 treatment. Now as I mentioned, the IGNYTE trial really showed a broad benefit across different patient subtypes and will really be an option for all patients when they fail on their PD-1 containing regimen regardless of the line of setting they came from. So for example, if they had adjuvant failed, they could be used -- could be treated in frontline with RP1 plus nivolumab or frontline patients whether they received Opdualag, ipi/nivo or monotherapy PD-1. So really, I think, a very practical regimen that can be used broadly. And also the safety profile we see is very tolerable. So again, it's something that I think is going to be practical and broadly used in the treatment of these patients.

Now for us to sort of maximize that opportunity and treat as many patients as possible, it will be important that we could do image-guided injections. It's about 80% of patients will have sort of deeper lesions, and that's going to involve interventional radiology. We've done a lot of work with that stakeholder group, a lot of research. And I think the great news is they're excited to do this, and they really think about this as sort of reverse biopsy. So we're actually injecting something versus something they do quite routinely in terms of taking something out of a tumor, and they're very excited to do this.

Now they're also really impressed with the systemic non-injected responses we see with RP1 plus nivolumab. They predominantly work on local treatments, so they don't see that and they find that quite compelling. So this is something that we've also gotten quite excited about. Now many of these interventional radiologists are, however, involved in the treatment of HCC and liver metastases, and they use procedures such as embolisms, TACE, TARE which tend to be a lot more complex than what we're asking them to do in terms of image-guided injections of RP1 plus nivolumab. So again, this is something they feel very comfortable being able to do with some basic education. And so they're also excited about taking this modality and adding it to their treatment armamentarium beyond the existing sort of local treatments they have today.

Now as we think about the patient opportunity ahead of us, it's roughly split 50% in the hospital, 50% in the community as we think about the melanoma patient population. And our initial launch focus is going to be on about 150 accounts. Now these are accounts that account for about 25% of the overall patient volume, but there are also accounts predominantly hospitals that have integrated IR within the facility. So if we're asking them to do these deep injections, it's something that they can do from a logistical perspective in a more straightforward way. We've also seen that these accounts tend to be in larger academic centers, but we've also had a lot of experience for these patients within our clinical trial.

We've seen experience in top academic sites, but we've also seen that we can then take that 150 or so sites into a broader population in the community. And actually, what we've shown through our expanded access and compassionate use program is that those requests have not just been coming from the hospital and academic sites, they've also been coming from some of the community sites. So now we have experience with, for example, Kaiser on our EAP program and some large oncology community sites such as Minnesota Oncology, Baptist and Memorial in Florida. So again, the idea that we can initially start in a targeted approach with these integrated predominantly hospital academic sites, but broaden this out to something the community can use and actually treat the patients where they are.

We have also got commercial supply for RP1 ready today, and we have an end-to-end manufacturing facility in Framingham, Massachusetts, where we produce drug product, drug substance, we do the fill-finish. We do the packaging and labeling and actually are ready to then send the product to our 3PL so that we can enable next-day delivery for patients.

So now if we think about beyond melanoma, we've actually also generated quite a lot of data in other skin cancers beyond PD-1 failed melanoma, got a nice body of evidence. We also have monotherapy RP1 activity in these patients and actually have an opportunity to treat these patients in a very unique way actually. So in terms of monotherapy, we often see that these immunocompromised patients really aren't able to receive checkpoint inhibition for various reasons. Shortly, I'll share some data with you that we have on solid organ transplant patients who unfortunately often develop non-melanoma skin cancers. I'll also share some data with you in early disease because this is an obvious area where we want to take the modality to see if we can cure patients. We've got some data in low-risk patients in CSCC, but an interesting area that we can pursue in the future is looking at high-risk patients for sort of cancer prevention approaches.

So just now moving into some of the data from our experience. This is looking at RP1 monotherapy in locally advanced CSCC patients who have received solid organ transplant. Now today, the management of these patients is quite challenging. Physicians will use checkpoint inhibition in these patients, but predominantly for renal transplant patients because if they do see organ rejection, they have the fallback of dialysis. There really isn't great options for other types of organ transplant liver, heart, lung. And one of the objectives of the ARTACUS study is to broaden out the types of organ transplant failure patients we have. So what we see with the RP1 monotherapy is we see about a 34% response rate and a nice disease control rate in these patients and that response is very durable.

But we've also seen that we don't see any allograft rejection, whether it's renal, heart, lung or liver. So this is an option now that can broaden kind of the options for these patients who are desperately in need and really don't have other great options. So that's something we're very -- certainly very excited about. One of the things that's important for these patients is that you also want to make sure you don't sort of modify their steroid kind of regimens, or immunosuppressive regimens, and that was one another benefit that we saw in this study that we did not need to do that. But the other thing we saw is that the monotherapy was very well tolerated and actually seeing a similar kind of side effect profile than we see in non-immunocompromised outside the fact that we don't see any of these organ rejections.

Now this is another setting that's very interesting as we think about future potential for RP1 as monotherapy. This is looking at low-risk resectable CSCC patients. Now these patients are predominantly managed by dermatologists today. They are patients who get a lot of lesions. They had a lot of mos surgeries. They just keep getting cut as new lesions pop up. Now what happens is they often reach a point of sort of surgical fatigue or there may be areas where lesions pop up in regions that are just very hard to actually do further surgery. So this data is from an investigator-sponsored study we did and the investigator enrolled 10 patients. What we saw was a 100% response rate and 83% complete response rate or [ PAT ] CR rate.

Again, this means that these patients could then not have to go through surgery. This is actually something that's a great option for these patients. And one of the nice things that we know with dermatology is they're very used to injecting things. And because you don't have to use this in combination with checkpoints, this is also a benefit for that stakeholder group because they don't typically infuse or have infusion capability in their practices.

So now as we think about expanding RP1 beyond skin cancers, it's going to be important, as I mentioned, to be able to do these deep injections. As I mentioned, we've done more than 1,000 of these. One of those deep lesions that's very common or a couple of these lesions are common at sites of the liver and lung metastases. And unfortunately, these patients have a very poor prognostic outcome. And what we've shown is that we're able to do that. We've actually done more than 800 lung and liver injections now and that we see a nice benefit. In fact, we're taking that experience and we're already using it in our registrational trial in uveal melanoma because uveal patients nearly all metastasize to the liver, and we're seeing that we can do that. We're also seeing that we can inject primary tumors in HCC and BTC, and we've also got a cohort that we've initiated in that setting.

So as I mentioned, it's not only important to show the feasibility of these deep injections, but what's the outcome and benefit. So this is looking at some -- excuse me, this is looking at some data from the IGNYTE trial. And if I sort of guide you to the left-hand side, this is looking at a table where we look at the response rate for patients who only had superficial lesions, we see about a 30% response rate consistent with what I shared with you from the IGNYTE data earlier. But as I mentioned, one of the things we always want to know is if I inject both superficial and deep lesions or only deep lesion, lung and liver, how does that result in terms of outcomes? And what's encouraging is that we see at least a similar response rate and actually numerically higher for those deeper lesions, which is one of the things we've always wanted to see because these patients tend to do worse. And so it's great that we can actually numerically improve the outcomes.

Now the other important aspect here is that can you do this safely? And if you look at the safety profile of superficial versus deep lesion injections, we say they're actually quite similar. For liver, we actually see a very low rate of bleeds because we're using a very thin needle. And so that's something actually the IRs also tell us is actually very attractive. And even for lung injections, yes, we see pneumothorax at a similar rate that you would see for lung biopsies, but these are self-resolving and it doesn't actually prevent patients getting the full amount of treatment for RP1.

So not only are liver and lung metastases a big problem, they're very common across a number of different tumor types. And if I just sort of refer you to the uveal, as I mentioned, these have a lot of liver metastases. More than 70% of these patients have liver metastases. This was an obvious area for us to investigate. Now uveal is actually a very tough to treat disease. It's not like cutaneous melanoma. It tends to be immuno-oncology insensitive. So checkpoint inhibition doesn't work very well in this patient. So we made the decision to actually use RP2 because we wanted to drive more potent activation in these patients. And so this is some Phase I data that we have in uveal melanoma, where, again, we get about 1/3 of patients into response, whether you use monotherapy RP2 or RP2 in combination with nivolumab. And we also see a disease control rate of around 60%.

These patients, as I mentioned, had repeat liver injections, and we showed that we could do that safely and reproducibly with a very limited bleed rate. This data led us to actually then move forward with a registrational trial in uveal melanoma, which is called REVEAL. This is a checkpoint naive population. So while we're predominantly expecting second-line patients who have either failed tebentafusp or the IDEAYA combination in HLA negative, we actually see that we're actually getting quite a lot of frontline patients, which is actually encouraging. We have more than 50 patients already enrolled in this randomized trial, which is, I think, great news. And again, patients do need options.

We expect to have some preliminary data for about 90 patients as we think about Phase II to Phase III transition in early 2027. However, the primary endpoint of this trial is overall survival, but we have an opportunity to also look at PFS because it's a seamless Phase II/III design where you can show PFS and then get full approval on overall survival. The more time-based endpoints of PFS and formal OS will take a little bit more time in the '28, '29 period. But again, we're well on our way to taking the next asset forward in a registrational trial.

Another area, as I mentioned, moving from liver to primary injection of liver and other tumors is looking at cohorts in HCC and biliary tract carcinoma. Now the HCC cohort is used in combination with atezo-bev. And we've now recently also asked based on sort of some of the investigator feedback, they'd like to add a monotherapy cohort. So we've done that. We should have data from these 10 or so patients either at the end of this year or early next year. So that will be our first data set in primary liver. And now in Q4, we also enrolled the first few patients in the biliary tract carcinoma. So again, we're kind of sort of executing on that vision that we have, which is shown here is moving from a Wave 1 sort of focuses on skin cancers, and we've done that extensively to moving to that Wave 2 primary liver metastases -- primary liver cancer and liver metastases with the data I shared in uveal, HCC, et cetera.

And really now, the team is actually gearing up for, okay, where can we go next? So there, the idea is looking at liver, liver metastases and also some other settings that are actually tough to treat, including PD-1 failed renal cell, GI cancers and sarcoma subtypes. So that's sort of what's coming next as we think about where we can take the pipeline more broadly. So to conclude, I hope I've shown to you why we're poised to deliver on the promise of oncolytic immunotherapy pending and pending near-term approval, we're ready to launch. We're ready today, and we have commercial supply available.

We're also very much excited about expanding the benefit for RP1 through a number of trials that we have ongoing, the 7 or so trials I mentioned, moving beyond skin cancers through deep liver and lung injections to other indications outside of skin and addressing really a difficult-to-treat patient population with a high prevalence. And then in summary, we have a cash of around $270 million. That allows about a year runway for us, but that does also allow us to fully fund our commercial launch. So thank you for your attention.

Thanks, Sush. I'll ask the first couple of questions. But to the extent there are any questions in the audience, feel free to raise your hand, and I will -- I can call on you. So with the PDUFA coming here on April 10, this is a Class II resubmission. Just remind us of the time lines and cadence of meetings with the agency with a Class II resubmission.

Emily, do you want to take that one because you've been on...

Sure, I'm happy to. A Class II resubmission doesn't have a predictable cadence of interactions with the agency, but we are very happy that they've been collaborating with us with regular information request that we've been able to respond to on time or ahead of time and hope that we are working together towards our PDUFA.

Yes. And like along those lines, right, like I know you're not going to give us a ton of details here, but have the nature of your communications been addressable quickly with the known data that you have? Has there been any surprises in the nature of their requests, that type of thing?

Yes. No surprises, predominantly follow-up from the Type A meeting, as you would expect, and we've been able to respond to them in a timely manner because there was data we had on hand that we could provide at times data that was in our prior BLA that we were able to point to and clarify.

Okay. And I just want to kind of confirm that your review team kind of at the oncology division, CBER, that's not seen meaningful turnover in terms of team leads and things of that nature?

It's hard to know because as I stated, we don't have interactions and meetings where you can see everyone around the table. We do believe there are some new faces based on the follow-up questions from our prior BLA, but we know our project manager has remained the same.

Yes. Just so we know in the Type A meeting, we did have some new attendees, new people, including OCE representatives at that meeting, and we believe they're probably now also involved in the ongoing review and information requests that we're getting.

Questions from the audience? So our understanding is that before the CRL, you guys were in label negotiations based on the questions that you've received, could the label be more similar or different relative to what your prior expectations were?

Well, just as I shared with you, we really demonstrated a broad benefit for patients across different subtypes. So we would expect the label to reflect the population we studied. And again, therefore, we would expect to have an equally broad label as we get to that point in the resubmission.

And then how is enrollment going in IGNYTE-3? And how has the regulatory process here impacted your kind of confirmatory enrollment here in the U.S.?

Okay, I'll let Kostas take that.

I can take that. So like Sush said, we have over 60 patients now in IGNYTE-3. There's continuous excitement and support by the PIs as we move forward. The study is expanding to Europe. We had our first patients coming in late last year, and we're expanding to the U.K. and Australia sometime soon. The CRL was a big surprise and disappointment to all of us to the scientific community also but we got overwhelming support by our PIs. After the CRL, you would expect to see a dip on the recruitment.

To the contrary, what we saw is that the trajectory continue at the same pace, maybe even better than that. So that shows that the scientific community is supporting and believes in that treatment. In addition to that, what we saw was an increase in the compassionate use requests, which is also another signal that the scientific community believes in this treatment, but also the fact that there is great need for additional treatments in this patient population in advanced melanoma.

Questions from the audience? Just to be clear, has the FDA provided any guidance on the specific number of patients needed in IGNYTE for an approval? Because I remember previously, there was no requirement.

No. They've been very consistent in saying the trial need to be underway. We have been providing regular updates on enrollment. And look, we're very committed to actually getting this trial done. As you saw from Kostas, it's going well. We've always provided a very robust assessment and projections to the agency. And so we have had not any further communication or questions on that front.

Any final questions from the audience? I have a couple more, but -- then I guess from a physician perception standpoint, has the physician perception changed at all for RP1 with this kind of prolonged regulatory process.

Again, I'll let maybe Chris and Kostas take that.

Yes, I'll take it. So what we hear from the physicians is that there is a great need for additional treatments in this patient population. That hasn't changed. What also happens out there is that after patients fail ipi/nivo, they have very limited options to be treated. TILs have been approved recently, but they come with some challenges in geographic access and also some tolerability access. We present the data at SITC on the biomarkers that is still more confidence in the mechanism of action and how the platform works that show that not only we recondition the tumor microenvironment, but we also resensitize the tumor to the treatment of PD-1 by increasing CD8 for the lymphocyte infiltration as well as PD-L1 expression. I think all of those things show that the sentiment that we get from the medical affairs side, I should say, is that there is a lot of support. There's a lot of interest. And sometimes there is a lot of anxiety from the PIs and the KOLs, when this system is going to become available for their patients.

We've also seen a big increase in compassionate use requests. So again, I think just indicating that patients that need access and physicians really want to give their patients access.

We've got a question in the portal, which is, can you ask management, if any change -- if there's going to be any change in who the patient population will be with this resubmission versus the first time around?

So during the Type A, we obviously discussed the different patient populations. The FDA did not indicate that there will be a narrowing or they want to see a subgroup. Obviously, we'll have to have those conversations so we continue the review. But at this point, as I mentioned, the study population was broad, and we saw consistent benefit across subgroups. So we should -- I would expect the label to reflect that.

Okay. Last chance. Any questions from the audience? All right. Thank you, Sush and team.

Thank you.

Thank you so much.