Replimune Group, Inc. (REPL) Earnings Call Transcript & Summary

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.