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

All right. Let's go ahead and get started. Thanks, everyone, and welcome to the JP Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by my squad, Priyanka Grover, Malcolm Kuno and Rathi [indiscernible]. Our next presenting company is Replimune, and presenting on behalf of the company, we have CEO, Sushil Patel?

Thank you, Anupam. So it's certainly been a very busy and exciting year for Replimune, and we now have reached a pivotal stage of the company and have a substantial body of evidence to support our Oncolytic Immunotherapy platform. Now starting in skin cancer and RP1. We've now demonstrated a very compelling data set in anti-PD-1 failed melanoma, where we've been able to get 30% or almost 1/3 patients into durable response and have seen strong systemic activity, including hard-to-treat visceral disease and with a very nice safety profile. Importantly, we've also been able to progress the pipeline forward, with our second asset RP2 in a registration study in Uveal Melanoma, and we recently enrolled our first patient. We've also moved forward with our first patient enrolled in HCC, and this is a study that's in atezo-bav failed patients. We are now actively enrolling a number of U.S. sites. Now based on the strength of the anti-PD-1-failed RP1 data, we received breakthrough designation from the FDA. And shortly, we should be hearing about our BLA acceptance most likely in the coming few weeks. Now as a result of the breakthrough designation, we're planning for a priority launch in the second half of 2025. And we feel very confident that we'll be successfully launched, and that confidence is further bolstered by a strong cash position where we have more than $500 million available. And we also had a very attractive cost of goods, which comes from Replimune manufacturing its own products, including RP1 at our facility in Framingham in Massachusetts. Our Oncolytic Immunotherapy platform is really based on a dual mechanism of action, and it's really derived from a Herpes simplex backbone with a number of immune stimulating payloads expressed. Now this results in injected local responses as a result of direct tumor killing. But we also see non-injected systemic responses due to the ability of tumor lysis and neoantigen release, which is then further bolstered by the expression of these immune stimulating virus payloads. Now these immune expressing payload differ across our different constructs. RP1 includes a GM-CSF and also GALV, which causes cell fusion and a potent immunogenic cell death, which enhances direct killing, but also drives broader systemic immune activation. Now in addition to GM-CSF and GALV, RP2 also includes a CTLA-like antibody. And the idea here is that we express CTLA-4 locally so that we don't deal with some of the systemic toxicity totally associated when using this immunotherapy. So the therapeutic objective of both the RPX platform, in combination with our ability to precisely administer the drug locally intra-tumorly result in a number of benefits and overcomes various limitations we see with other agents such as checkpoint inhibitors, such as resistance, which invariably results in many patients. Another advantage is our ability to combine with a number of different modalities, include targeted therapies and avoiding some of the toxicity burden that typically comes when you use these combination approaches. So now I'm going to talk about RP1 in Melanoma and our potential of the pipeline to deliver on the promise of Oncolytic Immunotherapy and the data we have to support that. I'll just remind you that, we made significant progress in melanoma, there remains significant unmet need in the refractory setting. When patients have progressed on a PD-1 containing regimen there's still are really very few treatment options and very few good treatment options. Now if we retreat patients who are truly resistant with single-agent PD-1, we really wouldn't expect to see a response rate of more than 6% to 7%. Now if we're going to use combination immunotherapy in these patients for patients who have failed on frontline ipi/nivo or [indiscernible], we typically wouldn't see more than a 12% or 13% response rate. And this comes often with a significant toxicity burden of Grade 3/4. And finally, the only approved agent in this setting is TIL therapy. But unfortunately, this really isn't an option for many patients due to the timely costly logistics associated with the treatment and the significant toxicity that patients experience with nearly all patients having Grade 3 or 4 toxicity. So I think this unmet need and the unique opportunity that RP1 presents to improve outcomes for melanoma patients is quite exciting. Now in the next few slides, I'm going to be sharing with you our IGNYTE data. Now this was the basis of our recent BLA filing and breakthrough designation from the FDA. And this is looking at the response rates that we've seen for the study. Now firstly, if we look at all patients enrolled in the study, we see almost 34% response rate. I also want to highlight 2 important subgroups here. The first subgroup is patients who failed CTLA-4 and PD-1 combination treatment or ipi/nivo where we see almost a 28% response rate in this group, it's a particularly tough to treat population with very few options afterwards. Importantly, 2/3 of the patient population was primary resistant. This means that they blew through their prior treatment in less than 6 months and really have very poor outcomes. And in that group, we see almost a 36% response rate. Now importantly, these responses are durable, and we see a median duration of response from response initiation of 21.6 months. Now undoubtedly, these durable responses are contributing to the promising overall survival benefit we're seeing. And if you look at the 3-year landmark survival, almost 55 patients are still alive, at 3 years. And currently, the median survival from this study has not been reached at the time of this analysis. Now what we hear as most sort of notable aspect of the data was most compelling is the systemic benefit we see, particularly in visceral un-injected responses where we see deep and durable responses. Now if you look at the left-hand side, this is a waterfall plot of all responders. And you can see the patent of response and depth response is similar, whether you inject the lesions, which is in the blue lines or the non-injected lesions, which are the red lines. Now turning to the right-hand side, most of these non-injected lesions were actually visceral lesions, almost 50% of them. And if we look at the visceral lesion responses are injected, we see almost 2/3 achieved at least 30% or more response. Now specifically looking at the liver and lung lesions within that, which comprise most of those visceral lesions, we see almost a 70% response was achieved 30% or more. And again, these are particularly hard to manage manifestations in the setting. We also hear that this data is particularly compelling for the KOLs who tell us that whilst they've seen some systemic benefit [indiscernible] agents, they've not seen this extent of benefit, and this is something that's highly differentiating. Importantly, safety is another consideration when we're thinking about treating these patients. RP1 plus nivolumab was extremely well tolerated, with predominantly Grade 1 constitutional like symptoms, fevers, chills, indicative of immune activation. However, we didn't see any Grade 5 toxicities. Now in line with our objective to move forward rapidly with accelerated approval, we've also initiated a confirmatory Phase III trial, IGNYTE-3, and this is a study with a primary overall survival endpoint, we also have a planned interim overall survival. This is rapidly enrolling. We enrolled the first patient in August and are working very diligently to make sure that we enroll this trial in a timely fashion and expect that to be about 2 or 3 years. We've been discussing with the agency the enrollment updates in line with recent guidance and feel confident that we're meeting those. We're also expanding beyond the U.S. sites that we currently have to Rest of World and particularly Europe, as this study is going to form the basis of our global pricing and reimbursement. Recently, we just started our expanded access program. Now this is a complementary to the I-3 study, and it's going to allow a utilization outside the traditional clinical trial sites, including trial sites in the community. So in summary, we have a differentiated data set across patient subgroups, including strong systemic benefit, which really should allow us to address the significant commercial opportunity. We've got a lot of commercial work underway. And then the next few slides, I want to share with you how we consider the commercial opportunity and what we're doing to capitalize on it. Now we have 13,000 patients and a significant opportunity here. And when we break down that patients, these are patients who progressed on a PD-1 containing regimen, about 2,000 of those have progressed in the adjuvant setting. We estimate around 80% of these will be injectable by RP1. And importantly, these will be injectable in the outpatient setting. So these will not require inpatient treatment. And as you think about the lesion location, 4 out of the 10 patients will have a superficial lesion, and 8 out of 10 patients will have a deep lesion. Now our lesion location is mutually exclusive. What's really important is when you have these deep lesions that will require the involvement of image guidance and interventional radiology and we're very confident that our commercial model will allow all eligible patients to be able to be treated. We've also done extensive analysis on understanding where these patients are treated. And we see that as quite a concentrated patient population with 80% of treated -- patients treated either in academic or hospital-based systems or in large community networks such as those shown on this slide. Now as I mentioned, to capitalize on the patient opportunity is important that we have image-guided injections and work with interventional radiology. And then importantly, 50% of these patients are in academic centers or hospital-based systems where interventional radiology is on site, our in-network and has access to electronic medical records and can easily manage patients. Now another 30% of these patients are in these large community networks, and these have established relationships with interventional radiology. And one of the jobs of our commercial team is really to ensure that we support patient co-management and also ensure that RP1 could be efficiently administered by interventional radiologists. Now one of the most exciting aspects of the modality and I think is very different in the treatment of Melanoma and really provides a new tool for oncologists is the idea of working together with interventional radiology in this space. Now interventional radiologists are certainly not new to oncology procedures. They do a lot of things such as ablation, taste and tear and also things like Y-90. And when we shared the IGNYTE data with them, they're very impressed with the data and excited to be part of the new treatment dynamic. Now what they consistently tell us in our market research is they're very impressed with the systemic benefit, particularly in un-injected visceral lesions. And I think this is nicely demonstrated by the quote in the middle from Dr. Sheth from MD Anderson, who has an extreme amount of experience using intra-tumor agents. The other thing we hear from interventional radiologists who when we walk them through the procedure is this is quite simple and way more simpler than most of the procedures they do, which take a lot more time and a lot more complicated. And the analogy they may most often refer to is this is like a biopsy or actually more accurately reversed biopsy because we're injecting something versus taking something out. And then the other important aspect of RP1 injections is we use a very thin gauge needle. So the risk of bleeding events is quite low relative to repeat biopsies, for example. So beyond the RP1 data itself, there are a number of product attributes that should enable broad and rapid uptake. This includes off-the-shelf therapy that can be ordered and used immediately as opposed to a number of cell-based treatments which may require some time for the treatment to be made. Importantly, RP1 is administered in the outpatient setting, and this allows utilization of the community. And then finally, there are very favorable economics and RP1 will be built by standard buy and bill and importantly, is used in combination with nivolumab. So we believe we'll be well positioned to be the first choice after PD-1 progression for most patients. And this is based on a combination of I think, compelling safety and efficacy data, a comprehensive understanding of the patient population and prescriber base. And the launch model that's really going to enable us to do intra-tumor injections and work closely with interventional radiology to do this efficiently. Now importantly, we'll also be able to meet demand because we have commercial in-house manufacturing established. So now I'm going to move on to RPx expansion opportunities in the next few slides and where we see the pipeline going. So starting with RP1, beyond anti-PD-1 failed melanoma. We also see a very compelling data set in anti-PD-1 failed non-melanoma skin cancers, including merkel cell carcinoma, basal cell carcinoma and cutaneous squamous cell carcinoma, where we see about a 30% response rate and there's an attractive patient opportunity here. Another highly underserved area is solid organ transplant patients, and many of these develop non-melanoma skin cancers, and we see almost a 35% response rate with a high rate of complete responses in these patients. Now this is a setting where there's no approved treatments, and single agent checkpoint is typically not used because of the risk of organ transplant and RP1 is used as monotherapy here in a little different way because these patients have underlying immune suppression. So we're really treating them chronically. And the dosing we use is a bit different. The course of the treatment here is 26 doses versus the typical 8 doses we use in other settings. Now moving on to RP2. We see encouraging activity here in Uveal Melanoma and this is really not so much a skin cancer, but cancer of the eye. And nearly all these patients have progression in the liver. And when that happens, the prognosis is extremely poor. Now if I draw your attention to the patient case, what we see, which we've also seen with RP1 is that we see the ability to shrink both injected lesions, which is shown in red, and non-injected liver lesions shown in yellow. And these responses are very durable. So I think this is a very compelling data set. And when we look at 19 patients that we treated here, we see almost a 30% response rate and a 60% disease control rate, which is very meaningful for these patients. Importantly, there's a favorable safety profile and that we've demonstrated that we can actually do repeated liver injections without a significant risk of additional bleeding risk, which is important. Now this has resulted in us rapidly moving into a registrational study in checkpoint naive metastatic uveal melanoma, where we recently enrolled our first patient. This study has a co-primary endpoint of PFS and overall survival. And the final PFS analysis, we should be able to file for accelerated approval with conversion on our overall survival at the final analysis. So just starting at the bottom of this graph, we're looking forward to bringing RPX to skin cancers and now have a substantial body of evidence where if we are able to treat all the patients and skin cancers that we've seen activity, and we would almost have 15,000 treatable patients. However, I think what we're most excited about is really the ability to build on the systemic and visceral activity we've seen with RP1 and also RP2, and then take that into more prevalent tumor types such as primary liver cancer. And here, we, as I mentioned, started our first trial in hepatocellular carcinoma in atezo-bev failed patients. Now the ability to inject these lesions also and inject many other more prevalent tumor types is only increasing with improvements in image guidance, injection technology, robotics, and when we consider the lung and liver lesions and metastases are very common in these cancers. I think this opens up a lot of possibilities because those are very problematic to manage and a cause of significant mortality. So we look forward to providing more information on how we want to move forward with RPX in an R&D day that we have coming up shortly. So in summary, it's been a very productive 6 months, and we've now achieved a number of the regulatory dates for RP1 in anti-PD-1 failed melanoma. We've also rapidly moved RP2 into a pivotal study in Uveal Melanoma and Liver Cancer. And now I want to draw your attention to some important upcoming milestones for the company. So as I mentioned, we're eagerly anticipating our BLA acceptance in the coming weeks. And as I just mentioned, we're planning an R&D day to provide more guidance and information on the expansion possibilities, in the first half of 2025. Now given breakthrough designation, we are at plan for a priority U.S. launch in the second half of 2025 and are now actively working on our commercial plans, and I look forward to sharing more of those with you in the coming and months, and we're very excited about the possibility to treat as many patients as possible with RP1. Thanks for your attention.

Do you want to invite the team up there?

Yes. So we just want to introduce a few of the Replimune team here. So we have Emily Hill, Kostas Xynos, our Chief Medical Officer; and Chris Sarchi, our Chief Commercial Officer.

I just want to remind everybody that there's three ways to ask a question, right? So you can raise your hand, the old-school way, you can send an e-mail to me, or there is a question portal thing here that -- maybe you can use hand. Looks like there are some question. But I will start out here with a quick question on with the BLA filing now complete for RP1, you got breakthrough designation granted as well. What are the key regulatory milestones and time lines we should be considering?

Yes, I'll take that one. So as Sush mentioned, we submitted our BLA to the FDA in late November. So based on the anticipated regulatory time lines, that would lead us to expect the FDA to file or approve our BLA in the coming weeks, late January or early February. At that point, they'll officially give us our PDUFA date, which based on breakthrough designation, we expect to be a priority review. And in the interim between that and the expected approval at the end of the summer, we would have manufacturing inspections, and we're preparing for those as we speak.

So what are -- I mean you mentioned in the slides, many of you kind of pre-commercial activities, if you could dig in a little bit about how you're educating the market? How you're mapping patients besides what you talked about in your presentation?

I'll let Chris take that one.

Yes. So we're going to do over the next couple of months, we're going to continue to generate in-depth understanding of the market, while we complete our commercial build-out, as Sush said. Now we also mentioned that this is a highly concentrated market with roughly half the melanoma patients being treated across 200 accounts in the U.S. We expect by the time of approval, to have completed in-person profiling of all 200 accounts, again, at the time of approval. From there, we're also going to be continuing to gather very valuable insights in terms of ways of working between medical oncologists and interventional radiologists. While we also uncover some of the unmet needs that still exist that we believe our commercial model is going to help successfully address the additional probably key milestones that are coming in the next few months are going to be the completion of our distribution model, as well as our patient support hub, which -- while we've already begun pressure testing those, we have several different pressure tests coming in the months ahead to ensure we have a seamless execution upon approval.

We have a question on who the company is leading the regulatory process with the FDA?

That will be Kerry.

Yes. So the regulatory -- basically, the regulatory lead is, what kind of experience do they bring to the table?

She has a very extensive experience from a regulatory perspective, she has also been at the company for quite a few years now, and I think came in from a very extensive career in regulatory in big pharma.

Questions from the audience? What is going to be the size and scope of the field force that you're ultimately going to have out there?

So one of the beauties of having such a concentrated market is our ability to be pretty targeted with our approach. So when we actually, by mid-April, we'll have a trained team of about 30 sales representatives ready to support the product. We'll also have some surround sound for teams to help support patient pull though, we'll have a team of oncology nurse educators, we'll have a team of market access and reimbursement specialists. And we'll have a dedicated team of interventional radiology, oncology coordinators or IROCs, and this is a team that's going to be challenged with helping to coordinate the efforts between medical oncology and interventional radiology. And so that's going to help ensure a positive first patient experience upon approval. We won't be having company cars that are Corvettes for the IROC team. They are Camaros, that's right.

The metal educators and the IROC, they're going to be separate from your 30 new customers.

Exactly. Yes. Total footprint, and I'm -- probably about 65 for that field -- the field-facing teams that I just described.

We had a number of the medical affairs team out there several years now under Kostas' guidance really educating the market as well.

We have 10 MSLs that are out in the field now already.

Questions from the audience?? We've got another portal question here. Would you expect that all RP1 administration by interventional radiologists would be only for deep lesions? Is that how T-VEC was formally used?

I can start that and then we can go on to Chris. Now T-VEC was predominantly used in superficial lesions and did not have a label for deep injections, which is really comes from the fact that we really haven't demonstrated the un-injected systemic benefit that we've seen, including visceral [ organs ] with RP1. So I think that was just a consequence of the data they had. And I don't know, Chris, if you want to talk about the second part of the question?

Yes. So superficial lesions will primarily be injected in the medical oncology office and all the interactions we've had with interventional radiologists, there's absolutely an appetite to inject both superficial and deep lesions when patients are there, and it will be dependent upon more practice-specific needs, whether it's contained within the institution or if it's a community-based hospital or community-based account that's having the IR work done in a local hospital.

And another portal question is, you said, you don't need to be substantially enrolled in IGNYTE-3. Is that because you've reached an agreement with the FDA? And/or is that because your approval would be in a different population than IGNYTE-3?

Sure. No, I'm happy to take that. There have been a lot of questions recently about FDA draft guidance that suggests study should have a confirmatory trial fully enrolled before accelerated approval. Because we've had breakthrough designation, we've had several interactions with the FDA, starting with a pre-BLA meeting in September, where we outlined the expectation for our accelerated approval confirmatory trial IGNYTE-3. That trial will take 2 to 3 years to enroll the FDA is well aware of that time line and subsequently granted us breakthrough designation. So we feel that not only have we had clear communication with the agency around the expected enrollment time line the are doing a diligent and thorough efforts to ensure it is rapidly enrolled in the U.S. and then pivots to continue to enroll ex U.S. as it will ultimately be the foundation for our global pricing and reimbursement strategy.

Questions from the audience? There is a little bit of back and forth on The Street on the commercial opportunity for RP1. What do you think -- you did a good job outlining all of the levers to think about here in the presentation. But what do you think The Street is really missing on this opportunity?

Yes, if I can -- so we know that 80% of these lesions can be injected with RP1. We also now know that the vast majority of these patients can receive access to interventional radiology either through in-house, in-network or with relationships that exist. I think for us, over the last 6 to 12 months with all the market research, the medical interactions we've had, the key findings for us, I think, have really been at the level of excitement, not that they're excited, but the level of excitement across the interventional radiology community with the data, what that data means for patients and their ability to take part in the injection process. And so for us, a key objective here is going to be to where those relationships don't currently exist to establish those where they do exist to strengthen those to ensure that when a patient presents, who is a candidate for RP1. That RP1 is presented in the most valuable way. And this is going to be a key functional role that IROC team, I noted a minute ago.

Yes, I would say that there really is no other option in the marketplace that I think provides the combination of the efficacy we've seen and in particularly, the systemic visceral activity, as well as the as the safety profile that we bring to which I think really does allow us to treat a lot of patients and hopefully expand the treated patient population.

We have another portal question is, is your R&D Day in the first half going to focus largely on commercial? Or will it focus also mostly on the broader pipeline strategy?

We haven't fully determined the content, but mostly on the R&D strategy.

Questions from the audience? You said that from right now, the IGNYTE-3 would take 2 to 3 years to enroll? Is that right?

A few years for enrollment and the FDA is aware of that.

Yes. We have about 50 sites selected for IGNYTE-3 and half of them are already activated, and recruiting. So we expect about 2 to 3 years.

And those are U.S. sites? They're all U.S. sites?

Correct . And our global strategy is well underway. So we're implementing the strategy.

We would expect to have more than hundred sites globally once we're up and running.

Yes. And then you've kind of disclosed that you've started the studies for RP2 uveal melanoma and HCC already. How do you think about the enrollment curves of those 2 studies?

So both studies had the first patient last week. We have several sites that are open, and we have a few sites that are coming up next time in the next few weeks. For HCC, we're looking to expand the study ex U.S., and we're looking at countries that have a high prevalence of disease. So both of our studies are ongoing at the moment.

Question from audience? Maybe a final question for me. Just find us of your cash runway and what milestones are assumed within that runway?

Yes. So our cash position unaudited at the end of 2024 was $536 million that takes us to the second half of 2026, at which point we would expect to have generated several quarters or a few quarters of revenue. So that puts us in a position not only to fully fund our launch but also to invest in expanding our pipeline, which we have started as well as to fund the IGNYTE-3 study.

All right. Thank you, everyone.

Thank you for having us.