REPL - NASDAQ

Good morning and welcome to the Replimune Fiscal Year Fourth Quarter 2025 Financial Results and Corporate Update Conference Call. Currently, all participants are in listen-only mode. This call is being webcast live on the investors and media section of Replimune's website at replimune.com, and a recording will be available after the call. I would like to introduce Arleen Goldenberg from Replimune. Please go ahead.

Thank you, Operator, and good morning, everyone. Thank you for joining us today for a discussion of Replimune's fiscal year fourth quarter 2025 business highlights and financial results. Leading the call today will be Sushil Patel, our Chief Executive Officer. He will be joined by Chris Sarchi, our Chief Commercial Officer, and Emily Hill, our Chief Financial Officer. After our prepared remarks, we will open the call for Q&A an audio recording and webcast replay for today's conference call will also be available online as detailed in the press release announcement for this call. During today's call, we will be making certain forward-looking statements, including, without limitations, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans, partnerships and prospects. These statements are subject to various risks such as changes in market conditions and difficulties associated with research and development, and regulatory approval processes. These and other risk factors are described in the filings made with the SEC, including our annual report on Form 10-K and our Form 10-Q filed today. Forward-looking statements are based on the assumptions, opinions, and estimates of management at the date the statements are made, including the non-occurrence of the risk and uncertainties that are described in the filings made with the SEC or other significant events occurring outside of Replimune's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, May 22, 2025. Replimune's disclaim any obligation to update such statements, even if management's views change, except as required by law. With that, let me turn the call over to Sushil Patel, Replimune's Chief Executive Officer.

Thank you, Arleen, and welcome everyone to today's earnings call. We appreciate you joining us as we review our fiscal fourth quarter and full year 2025 results. Today, we'll highlight the significant progress we've made across regulatory, clinical, and commercial as we approach the potential approval and launch of RP1. You'll also hear updates on our confirmatory Ignite 3 trial, pipeline developments for RP2 and our financial position as we prepare for commercial readiness. I'll begin with a strategic overview before turning the call over to Chris to walk through launch preparation and Emily to cover our financials. Replimune was founded to pioneer the next generation of oncolytic immunotherapy and is now poised to realize that promise with a substantial body of evidence supporting our mission. In particular, data from the Ignite Study shows that roughly one-third of patients are able to achieve durable response in a high unmet need setting with few options. I'm delighted with the tremendous organizational advances we've made, allowing us, if approved to be ready for a strong commercial launch of our first therapy in anti-PD-1 failed melanoma. This would not have been possible without the efforts of the entire Replimune team. Over the past year, we have made significant regulatory progress, resulting in a recognition of RP1 as a breakthrough therapy with priority review and a PDUFA date of July 22, 2025. We remain actively engaged with the FDA and recently completed the late-cycle meeting and manufacturing inspections. The Ignite 3 confirmatory study is underway and has a primary endpoint overall survival. Enrollment in the U.S. is on track, with over 100 sites planned globally. While we have seen important advances in the melanoma treatment landscape, the unmet need remains significant. We believe upon FDA approval, RP1 will be well-positioned to be the first choice for advanced melanoma patients who have previously received an anti-PD-1 containing regimen. This is based on a combination of compelling safety and efficacy data, a comprehensive understanding of the patient population, and prescribe the base and a launch model optimized to unlock the potential intra-tumoral injections. Building upon the strong, systemic and visceral activity we've seen with RP1 in advanced melanoma, we are equally excited about our pipeline development, which are focused on the potential of deep lesion injections with RPX to benefit patients beyond skin cancer. We look forward to establishing our RPX platform as a new interventional immuno-oncology treatment paradigm, which we believe will be enabled through the collaboration between oncologists and interventional radiologists. Our U.S. manufacturing facility has produced commercial inventory to support the RP1 launch with capacity to support long-term global demand. We are well capitalized to execute on our commercialization plans and have recently completed the build-out of our customer-facing organization. Now, let me turn the call over to Chris Sarchi, Chief Commercial Officer of Replimune to discuss the RP1 launch in more detail. Chris?

Thanks, Sush. Before I get into our commercial plans, perhaps a brief introduction for those of you on the call who I haven't yet had the opportunity to meet. I joined Replimune about two and a half years ago to help lead our commercial organization. Prior to joining Replimune, I helped spearhead the launch of Libtayo as a new standard of care for the treatment of cutaneous squamous cell carcinoma. Upon approval, the successful launch of RP1 will be my 10th oncology product launch that I've had the opportunity to be a part of, and now I look forward to helping to build Replimune into a leading oncology company. Our team is really excited and ready to launch RP1 for a broad range of patients upon approval. We believe RP1 will be well-positioned for most patients who progress on a PD-1 containing regimen based on the deep and durable response rates, as well as the safety profile demonstrated in our Ignite Registrational trial. With our PDUFA date fast approaching, our primary focus has been on the commercial preparations. We have a deep understanding of the market landscape, prescriber adoption and referral patterns, and an established launch plan that's optimized for intra-tumoral delivery across all customer segments. The commercial opportunity for RP1 to help improve the lives of those with advanced melanoma is considerable. We estimate approximately 13,000 patients progress on or after PD-1 treatment annual in the U.S., and about 80% of these patients would be eligible for RP1 distributed evenly across hospital and non-hospital settings. Importantly, RP1 is administered in the outpatient setting and doesn't require hospitalization. For community-based oncology, we believe the introduction of RP1 will allow providers to maintain treatment continuity for their patients within their practice for the full course of RP1, as well as nivolumab for up to two years. For superficial injections, we anticipate administration will most often take place in the patient exam room, and while medical oncologists may be some of the early injectors, the primary injector over time will likely be advanced practice providers. We expect that this approach will help support the broad and rapid adoption of RP1 in the clinical practice. From our research, we know that for patients in the advanced melanoma setting, who would be candidates for RP1, about eight in 10 will have deep lesions or a combination of both superficial and deep. In these cases, interventional radiologists will work closely with the oncologist and play a key role using image guidance. Interventional radiologists are excited that RP1 may afford them the opportunity to play an even greater role in actively treating patients. Both oncologists as well as interventional radiologists are impressed with the data showing the systemic activity of RP1 plus nivolumab in non-injected visceral lesions, which provides them with added confidence in selecting tumors for injections. Interventional radiologists have also expressed that administering RP1 is straightforward and can be readily adopted into practice upon approval. Importantly, procedural codes already exist to support RP1 deep and superficial injections with a routine RP1 drug buy and bill reimbursement process that further minimizes barriers to access across all settings. The geographic distribution of patients with advanced melanoma allows us to be very focused and targeted in our launch efforts. Even more importantly, there's a high and overlapping concentration of providers, primarily interventional radiologists and medical oncologists, who treat most melanoma patients. We've identified roughly 350 key accounts that we believe treat half of the melanoma population. Beyond that, we know that nearly all of these patients are being treated in healthcare settings that have interventional radiology on site or readily accessible through existing referral processes. Further supporting our belief in the broad and rapid adoption of RP1. Our comprehensive understanding of the market drove how we built our commercial organization, which we believe will accelerate the launch of RP1. We recently completed the build-out of our commercial infrastructure. The customer-facing team's been trained in comprised of approximately 60 people, with have focused on demand generation and the remainder on supporting pull group. The new and differentiated role we've created is the interventional radiology oncology coordinator or IROC. This team has a significant level of experience working in the interventional radiology space. Their focus will be coordination between medical oncology and interventional radiology, ensuring that we're able to connect the dots between these functions while supporting RP1 image-guided administration. We also have a team of oncology nurse educators who will provide guidance on superficial administration, drive positive early experiences with RP1 and work across the medical oncology multidisciplinary team. Our national accounts team is actively engaged with payers, and our field reimbursement specialists, regional marketers and strategic account managers round out our customer-facing teams. Our distribution model is now complete with specialty distributor agreements and key state licenses in place, which will support next-day delivery to accounts across the country. At launch, our patient support hub, Replimune Connect Plus, will provide critical services to patients and caregivers to ensure a positive treatment experience. You may have noticed several programs already in market. Our HCP unbranded awareness effort, the Oncolytic Frontier, which highlights the importance of collaboration across multidisciplinary treatment teams, is live online now. A few months ago, we also launched a program called melanoma PATH, focused on unbranded disease education featuring real advanced melanoma patients and caregivers. Much of this content was created with the support of our advanced melanoma patient steering committee. We've been actively engaged with the melanoma community through the support of many key organizations, including the Melanoma Research Foundation. We're excited to be one of two presenting sponsors at their annual breakthrough consortium meeting, admitted this year at ASCO, the consortium of 30 cancer centers of excellence collaborating to develop the most promising therapies in melanoma. As you can hear, we're excited with our progress to date and looking forward to hitting the ground running. Of course, ultimately, our goal is to ensure that no patient is left behind and all appropriate patients for RP1 are offered this valuable treatment once available. Our team is confident in the plans we put in place to help deliver on this important goal. With that update, I'll turn the call over to Emily to discuss our financial results. Emily?

Thank you, Chris. I'm going to start today with an update on the Investor Relations front. We are excited to be in the process of planning an upcoming Investor Day for June 24. During Investor Day, you will be able to hear from our management team and leading key opinion leaders on the current melanoma landscape and the opportunity to deliver oncolytic immunotherapy to patients and our RP1 roadmap for commercial success upon approval in anti-PD1 failed melanoma. Our KOL panel includes expert interventional radiologists, medical oncologists and pharmacists in the melanoma space. We will also share more about our future development of RP2, including our registration-directed trial REVEAL in uveal melanoma and our study in hepatocellular carcinoma. Finally, we will discuss our strategy for RPx long-term pipeline development. Now turning to our financial results for the fiscal year and quarter ended March 31, 2025. We ended the fiscal year with cash and cash equivalents totaling $483.8 million as compared to $420.7 million as of fiscal year ended March 31, 2024. Based on the current operating plan, the company believes that existing cash, cash equivalents and short-term investments as of March 31, 2025, will enable the company to fund operations into the fourth quarter of 2026, which includes scale up for the potential commercialization of RP1 in skin cancers and for working capital and general corporate purposes. This current cash runway excludes any potential revenue expected. Research and development expenses were $54 million, for the fiscal fourth quarter and $189.4 million for the fiscal year ended March 31, 2025, as compared to $42.6 million for the fiscal fourth quarter and $175 million for the fiscal year ended March 31, 2024. This increase was primarily due to an increase in personnel-related costs as we scaled operations in preparation for commercial launch, as well as consulting and facility-related costs. Research and development expenses included $4.5 million in stock-based compensation expenses for the fiscal fourth quarter and $18.4 million for the fiscal year ended March 31, 2025. Selling, general and administrative expenses were $25.4 million for the fiscal fourth quarter and $72.2 million for the fiscal year ended March 31, 2025, as compared to $16.2 million for the fiscal fourth quarter and $59.8 million for the fiscal year ended March 31, 2024. The Selling, general and administrative expenses included $3.8 million in stock-based compensation expenses for the fiscal fourth quarter and $16.6 million for the fiscal year ended March 31, 2025. The company's net loss was $74.1 million for the fiscal fourth quarter and $247.3 million for the fiscal year ended March 31, 2025, as compared to a net loss of $55.1 million for the fiscal fourth quarter and $215.8 million for the fiscal year ended March 31, 2024. I will now turn the call over to the operator to open our question-and-answer session. Operator?

[Operator Instructions]. Our first question comes from Anupam Rama with JPMorgan. Your line is open.

Thank you very much for taking my question. With the PDUFA around the corner, what sort of medical education work are you going to be doing at ASCO ahead of the launch of RP1? I noticed that you guys had a couple of posters at the conference? Thanks so much.

Anupam, thanks for the question. Yes, we've got a busy ASCO coming up. We had a couple of important posters. As you mentioned, we build the data that we presented previously on IGNYTE showing systemic and visceral activity, including a non-injected liver and liver amasses. What we'll be doing at ASCO is actually sharing what the response rate looks like when you inject superficial lesions versus a combination of superficial visceral lesions versus visual-only leasing such as lung and liver metastases. And I think that data is going to show that there's going to be a strong rationale for physicians to want to inject deeper lesions to maximize outcomes for patients. We also have a biomarker biodistribution and safety poster, which is going to show that you can use routine cleaning using disinfectants that are routinely available for physicians in their practices and that RP1 is neutralized very rapidly. And then also that patients don't see infections or their close contacts. So, we're excited about that data. And I think it's going to build on the evidence of the data we previously presented with the IGNITE data.

Thanks so much taking my question.

Our next question comes from Roger Song with Jefferies. Your line is open.

Great. So maybe given the dynamic for the launch between the oncologists and mentioned on radiologists, can you just give us some color around your expectations for the launch trajectory, considering some of them are superficial only lesion and then some of the market mix, and then some are about visceral only?

Thank you. Roger, this is Chris. So, we are anticipating a broad and rapid adoption across hospitals and communities, really with a heavier lift initially within the hospital setting, we've identified, as you heard, around 350 of our top accounts across the country. We, by the time of the launch, expect that roughly 150 of these accounts will have experience within tumor injections or have been trained on that by the time we get approved. The vast majority of these accounts will have access to interventional radiology within their centers. We've done a lot of research, as you can imagine, across the space between medical oncologists and interventional radiologists. And over 90% of the folks we've spoken to are willing to utilize RP1 routinely upon approval. And so, when you think about this level of excitement, the familiarity and experience, this really does support broad and rapid adoption of RP1 post approval.

Got it. Thank you. If I can have a follow-up question. Assuming you will get approval for the PD1 cell of the melanoma in the upcoming PDUFA day, what would be your NCCN listing strategy to maybe potentially expand to some other subgroup and then also maybe beyond the melanoma, like a CSP? Thank you.

Thank you for the question, Roger. In terms of the IGNYTE data, obviously, we'll be able to get approval straight away when we get the FDA approval for anti PD1 failed melanoma. And yes, we would though still submit that data once we have the publication, which we're hoping to have around the time of the PDUFA date, which will again just further sort of solidify our position in NCCN, although it's not necessary as we will have FDA approval. As we think about future indications, I think what we're going to do is obviously see what the data looks like from those different indications, whether that's non-melanoma skin cancers such as SURPASS or the ARTACUS data in solid organ transplant, we'll be publishing the data and then determining the best path to provide access to patients, Roger.

Yes. In addition to that, Roger, upon approval, we'll be immediately submitting our information to the drug compendium, so that hospitals can download this into the system. What we've done is making is to make sure that we have rapid adoption within the electronic medical record systems as quick as we can. On day one, we'll be submitting a package to the companies that represent roughly 85% of all the electronic medical records databases in the country. And we put in place sort of a reactive mode as well, so that for those that don't readily adopt into the EMR system, our customer facing teams will have an app they can go to right away, reach out and let the third party group we're working with know where those haven't taken place yet and we'll resolve those issues very, very quickly to ensure we minimize barriers to access as Sush was saying.

Excellent. Thanks for the comments. Congrats.

Thank you. Our next question comes from Jonathan Chang with Leerink Partners. Your line is open.

Hi, guys. Good morning. Thanks for taking the questions. Congrats on the progress and for hosting what I believe is your first earnings call. First question, can you discuss the impact you're seeing from the recent regulatory changes and provide any color on recent FDA interactions? And then on second question on Ignite, can you discuss the translation of response rate into metrics like PFS and OS? And what benchmarks are you pointing to for PFS and OS in the anti-PD1 field melanoma setting? Thank you.

Thanks, Jonathan. This is Emily. I'll take the first segment of your question. So just as a reminder for those on the call, we received breakthrough through designation late last year and then submitted our BLA for RP1 and PD1 failed melanoma. Our BLA was accepted in January with a priority review. And since that 6 January, we've been responding to information requests from the FDA in a timely and thorough manner. We're very grateful to have seen committed and consistent engagement from our review team, and we haven't seen any changes to the cadence of that commitment. Having recently completed both our late-cycle meeting with the FDA and our manufacturing inspections. We're very pleased with the outcome of those interactions, and we believe there are no impediments. We're on track for our July 22 PDIFA.

And Jonathan, just to address your second question. And yes, you're right, it's the first call, which we're very excited about. So, in terms of the data that we've seen for IGNYTE, just as a reminder, we've seen around patient 1/3 of patients achieved durable responses, which you look at median duration response of more than 20 months. This is a single-arm study, as you're aware. And so obviously, there are some limitations of PFS and OS in this study. However, we've seen a PFS of around 4 months and the overall survival, which I think is actually very impressive, where we've seen more than about 55% of patients still alive at 3 years. And so, we think that's going to be very meaningful relative to other options in this space. You asked about the benchmarks we should be using. And I think it is important to remember that the IGNYTE did use a very strict criteria for anti-PD1 failure, and there is an exact apples-to-apples comparisons. But if you think about some of the other studies and assets or molecules used in this space, such as ipi/nivo or Opteolag having failed either ipi/nivo or Opteolag in the frontline setting, you see about a 12% response rate. And typically, physicians and KOLs will tell you would not expect to see median overall survival of more than 12 months. So, I think that's a reasonable benchmark that most people use. Further checkpoint inhibition after failure of prior checkpoint inhibition really only results in a response rate of 6% or 7% with very modest overall survival benefits.

Understand. Thanks for taking my question.

Thank you. Our next question comes from Allison Bratzel with Piper Sandler. Your line is open.

Good morning. Thanks, guys, for taking my question. Just on the confirmatory IGNITE3 trial, I think you initiated dosing of patients last summer. So, could you just talk to your experience to date with that trial and what you're seeing in terms of enrollment, opening of trial sites and things like that. And just expectations on a time line for completing enrollment. Any color there would be helpful. And second, could you talk to your expectations on the potential label or label discussions for RP1? And just what gives you confidence in a broad label and achieving broad access? Thank you.

So, just in terms of IGNYTE or IGNYTE3, just as a reminder for people, this is a large randomized study a confirmatory Phase III trial with 400 patients where we're combining RP1 with nivolumab versus limited dealers' choice, which includes [indiscernible], chemotherapy or single-agent checkpoint inhibition. This is a trial that's going to have more than 100 sites globally. And as you can imagine, we've been providing the agency the updates on the timelines for the overall study and enrollment updates on a regular basis. We expect the trial to take a couple of years to complete enrollment given the study population and size of the study. But -- and as you can imagine, right now, we're intentionally focusing on enrolling in U.S. sites given the upcoming PDUFA, and when we realize that at approval patients will not want to be randomized into the control arm. So, given that we're really focusing our efforts and driving enrollment in the U.S., it's going very well. There's a lot of excitement around the trial. And what we're actually now doing is spending a lot of time on the rest of world expansion. So, at PDUFA, we would continue to see enrollment in that study in countries such as The U.K, Australia and Europe. And again, there's equally high-level excitement from ex U.S. Investigators around the trial. We look forward to speaking to many of them at the upcoming ASCO meeting. And then you asked the second question, I believe, on the broad label. Is that correct?

Yes.

I'm not all likely. Yes. Just as a reminder, IGNYTE, we enrolled a real-world population, which included really pretty much every type of anti PD1 felt presentation. We saw consistent benefit across all the subgroups. So, we would expect the label and as you know, now that we finished the late cycle meeting, we'll be going into labeling discussions to very much reflect the study population that we investigated in the INITRAL and would expect a label to reflect that broad population.

Thank you.

Thank you. Our next question comes from Evan Seigerman with BMO Capital Markets. Your line is open.

This is Connor on for Evan. Thanks for taking our question. Ahead of the potential commercial launch, can you maybe talk a little bit about how you're planning for manufacturing resiliency, including second sites to provide RP1 product? And then I also believe you have an attractive cost of goods profile with RP1. Can you maybe remind us what the drivers are there? Thank you.

Yes. So just in terms of the manufacturing and again as a reminder, we're manufacturing our own product at our facility that was designed specifically for the manufacture of RPX in framing them in The U.S. And yes, you're right, we have an attractive cost of goods. It was one of the strategic reasons that we actually invested in the manufacturing early. And we do anticipate to have a off-the-shelf product that positions utilize order and use the next day. We'll have sufficient inventory for rapid and broad-supported launch, and also have sufficient supply to ensure that we have mid to long-term supply for expansion of RP1. In terms of the capacity, we again, we have a lot of redundancy within the facility to produce sufficient supply way beyond the initial launch. And we're also looking to produce other product, including RP2 and RP3 at the facility in the future.

Great. Thank you.

Our next question comes from Peter Lawson with Barclays. Your line is open.

Great. Thank you so much. I wonder if you could just talk through any of the gating factors that exist between now and due to date, especially around CMC? And then kind of your thoughts around kind of in light learnings from the pure launches, how you're thinking about giving revenue guidance and thinking about market penetration? Thank you.

Yes. So, I'll just take the first question. As I mentioned earlier, we did complete our late cycle meeting and we did complete our factoring inspections both at Tamrielton Park facility, which does our process validation and analytical methods and then the main manufacturing facility in framing them. So, we feel we're well positioned there. And as you would imagine, there was discussions on CMC and other clinical questions at the late cycle meeting and we remain on track.

In terms of revenue guidance, I anticipate that we'll be providing metrics for you to track the success of the launch, including, ultimately, patient numbers and payers, and we'll hold off on revenue guidance until further into the launch.

Does that mean any kind of formal or informal feedback you've got from the FDA regarding, I guess, manufacturing or any other components there?

Yes. I mean, of course, we are under an active BLA review. We have completed the inspections, and so there is formal feedback associated with those inspections. And none of that formal feedback should provide a bottleneck towards our July 22 PDUFA.

Peter, thank you for the second question. While there's been significant advances in the treatment of advanced melanoma in recent years, there still remains a pretty significant unmet need when it comes to either deep responses, durable responses or safety profiles. And so, we know that today, when patients progress on a PD1, they started on PD1 here in the front-line setting, half of them are going to progress within 6 months. And so, for these patients, they don't have oftentimes 6 weeks, 8 weeks or 10 weeks for the next treatment option to be employed. When we talk to physicians in the community melon experts around the country, when they start a patient on a treatment and it's working well and it's tolerated well, they will rarely remove that patient from treatment. And so, our position is that RP1 will be positioned as a first-line option for patients who progress on PD1 therapy based upon our deep and durable response rates, our safety profile and our next-day distribution and off-the-shelf use of convenience, which again, really helps to support broad and rapid adoption once approved.

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Sushil Patel for closing remarks.

Thank you. So, in summary, it's been a productive few months and with a very exciting inflection point as we prepare for our first approval and commercial launch with RP1. We look forward to our upcoming milestones, including data updates on our deep in visceral activity and safety at ASCO and our upcoming Investor Day and potential approval announcement. Finally, I just want to acknowledge everyone at Replimune. I'm proud of the efforts of our team and want to thank them for their dedication as we work to deliver important treatment options to patients in need. Thank you for joining our call today.