These guys in the back.
They turn it on for you.
Okay.
Take the middle, please.
I was going to tape with this one because this is on a mic.
Okay.
You can tape where you want.
Chris, would you like to be in the middle?
No.
Okay.
Rose between two thorns.
All set.
Hi.
Okay. All right. Welcome, everyone, to Jefferies 2025 Healthcare Global Conference. My name is Roger Song, one of the senior analysts covering MedCare Biotech in the U.S. It's my pleasure to have the next five-star chat with Replimune Group. We have a whole team here. We have CEO Sushil Patel, we have a CFO, Emily Hill, and then we also have the Chief Commercial Officer, Chris. All right. Great. Thank you for being here. Then let's dive right into your corporate updates. Maybe, Sushil, can you give us some high-level overview of the recent updates because you just hosted an earnings call, I believe it's for the first time for Replimune, and then give us some updates for the PDUFA review, the status for your RP1 in PD-1 failed melanoma, and then we can have a discussion.
Yeah. Thank you, Roger. Yeah, very exciting time for the company. As we announced in our earnings, we're making significant progress on our regulatory interactions. As you all know, we have a PDUFA date on July 22nd, 2025. In our earnings call, we announced that we'd completed our late cycle meeting and that we'd be moving into label negotiations soon. We also mentioned that we'd completed our manufacturing inspections. I think things remain on track, and we're very excited about the road ahead. In terms of new information, we just had ASCO, which was very important for us, and we had a couple of important data readouts at the meeting, one being we sort of built on the data we've shared that RP1 has uninjected systemic activity, including in visceral lesions, which was building on the data from ESMO.
At ASCO, we also showed that if you look at the response rate by different lesion locations, whether that's superficial, mixed superficial, or deep lesions or deep-only lesions, including lung and liver, you really see a numerically increased response rate in those deep lesions, which has always been our hypothesis that, yes, you can inject superficially and see abscopal uninjected responses. What would be even better for patients is not that you only not only inject those superficial lesions, but you also inject those deep lesions. I think that data was very much supportive of that. Importantly, if we're going to ask patients and interventional radiologists to inject these patients in deep lesions, we showed a very nice safety profile. When you do liver injections, we did not see an increased rate of bleeds.
When you do lung injections, yes, there was some pneumothorax, as you might expect. It was self-resolving, and patients could get multiple repeat lung injections. We shared a lot of this data with the KOLs, other physicians, and I think they were very excited about the data. They wanted to see that you can not only do these superficial lesions, but these deep lesions really can add value for patients, excuse me. I think that was well received. The other aspect of the data that we put out at ASCO was, as we think about commercialization, one of the areas that we've heard again and again is things around logistics and just biosafety. While we have a really nice safety profile, we put out information that this can be used in terms of standard cleaning procedures, standard disinfectants.
You don't need to do anything unique or very rigid or stringent. RP1 is neutralized very quickly using routinely available disinfectants. We also showed that you don't see a higher incidence of herpetic infections in patients even after many thousands of samples were collected, whether it was at the injection site, dressing, or in urine or blood samples. I think this is important information as we think about commercialization, getting out to the community and nursing and other staff who are going to be handling the product. We felt really good, and I think it's further supported what we've always known about RP1, that it's not an airborne virus, that it actually should be handled under BSL level one, not necessarily BSL level two. I think this is all supported data as we think about sort of community adoption and also broader academic adoption.
Excellent. Yeah, I was there at ASCO. I do see your booth, and we took a video, and then you were part of it. I attended your poster session, and a lot of people there, including your investigator and then some of the investors as well, they seem to be looking for that data because the abscopal effect and then also the biosafety, that's what really matters to them for enroll the patient and then eventually the commercial use, right? Maybe just to follow up on this and then stay on the ASCO since we just came back from there. You mentioned your physician advisor is very positive feedback. Maybe just give us a little bit more, given you are doing the pre-commercial preparation, maybe Chris is doing a lot of work there. What are the feedback there?
What are the use cases they are starting to build with all the new data and then also with the potential approval in the coming months and then how they think about initial early adopter and then how they're going to expand this use for the RP1?
Yeah. In terms of the KOLs and others that we talked to, I think the narrative has flipped now to how do I incorporate this into my practice? How do I start working with IR? As we think about really sort of maximizing the benefit of RP1, we really want to make sure that, as I mentioned, you aren't just injecting these superficial lesions. Just for everyone's awareness, about 20% of patients who are injectable have superficial-only lesions or two out of 10. Two out of 10 have these mixed presentations of superficial and deeper lesions, and about six out of 10 have these deeper lung, liver, lymph involvement, which requires image guidance. We wanted to make sure that people are aware of that and then that we could essentially address that need.
Yeah. One of the granular questions is, as we start to see those uninjected lesions have the response, and then have your advice or those kind of investigators, how do they decide which lesion they will inject? Do they really need to inject all the lesions given you have the abscopal effect?
As I mentioned, now the narrative has turned around about figuring out how do we do this. One of the questions obviously comes out is, how do we do this? I think the guidance that we're providing is actually really resonating in that generally we have some general guiding principles. One is inject as much as possible, inject as many lesions as you can, inject new rapidly growing lesions. The nice thing with the fact that we have eight treatment cycles is you do not need to do all these injections at one time. You could start with superficial, you can move on to deeper lesions, and you can rotate. As I mentioned, what's sort of important is you try and inject tumors in different anatomical sites to really sort of ignite that immune response.
That resonated very well with the KOLs, and I think it's very practical as well. We have 10 ml of injectate that you can inject at each treatment cycle, and you kind of allocate that depending on the number of lesions. We provide some very simple guidance on how much to inject based on the size of the lesion. As a rule of thumb, it's roughly a centimeter per milliliter. I don't know, Chris, if you also want to talk about as we think about adoption beyond just the academic sites and what we're doing to prepare the market, that may be also relevant.
Yeah, thanks, Sush. We know that there's roughly 350 accounts across the US that treat just over half the melanoma patients here in the United States. That's broken out roughly 60-40 hospitals to non-hospitals. However, within that, there's another 150 accounts that we're considering sort of our hyper-targeting at launch, first 45 days. We've chosen this group because they represent the greatest patient volume of the accounts. They have in-house deep integration with IR, and they also have experience in injecting intertumoral lead. For us, that's going to become a really key priority at launch. We believe this targeted rapid approach to adoption is going to be the best indicator for long-term success for RP1.
When those physicians choose which lesion or how many lesions they want to inject, what kind of data are you going to supply them? Is there any data you can suggest to them, okay, which lesion is better for you or just no real difference?
Yeah, I think the great news on Ignite and the fact that we've seen this activity in uninjected lesions means that you don't have to be completely precise on this. What's important, as I mentioned, is you use some general principles that the oncologist and the IR get together and use their clinical judgment. And when we've actually put people together, invariably, they actually end up doing the right thing. It is really not that complicated. I mean, they do far more complicated things and decisions. What's important is they get together, they develop a plan, and again, there's practicality and flexibility in that plan as things evolve.
Yeah. Seems more using the common sense and then their practice preference. You do not see real difference if I inject this many lesions or this sequence, I will see completely different clinical results.
We gave some general guidance in the Ignite study. Even despite not having some of this data, we saw a great outcome, as you see from the trials. I think now that we've learned more and we've done that analysis, we have some general thoughts that it is better to do some of these deep injections based on the ASCO data. I think this provides further evidence for how we evolve that treatment thinking and dynamic.
Yeah. Got it. Okay, great. Another part of the consideration is the payer reimbursement, right? Physicians can do whatever they want to do, based on their practice, and how the payer is going to see this because that speaks to how many volume, and maybe they want to do more or less. How should we think about the reimbursement situation?
We've done a lot of payer engagement. I'll hand over to Chris, who can talk a little bit about that.
Yeah. Our team has been actively out sharing information through the pre-approval information exchange. Information to date, when you look at the value, has been really well received. The reimbursement model today really does support what we've just been talking about, about adoption across hospitals and communities. When patients arrive at the hospital for interventional radiology support, there's existing procedural codes in place that'll help support the use there. In the community, for physicians that will be using Nivolumab, they'll have reimbursement immediately based on its presence in the market today, so.
I would say that payers also recognize the unmet need in this disease setting. We did not hear anything on they're going to use any more rigid prior authorizations than they would for any other treatments used for these patients. Given our efficacy safety profile, I think that resonated very well as well. We are eight courses, so it is not this sort of infinite treatment. Yes, we can allow patients to be retreated, but this is not something that they are worried that you are going to use indefinitely. I think that also resonates with payers. They like predictability.
Yeah. And then understanding is you have a 10 mL for one dose, and then you have eight doses at one course. And then does that really matter how many lesions they inject within the one dose? Or it's mostly just how many volume the RP1 is?
Again, we try and encourage, depending on the different presentations, they inject multiple lesions. If, for example, in the first course, they may start with injecting a couple of superficial lesions. The second course, they may say, "Okay, I'll continue doing that." Maybe third or fourth course, if they've got a lymph or a deeper node, they may go to inject those through interventional radiology. Again, it's very flexible.
Okay. Once they go to the deeper lesion and then working with the IR, that reimbursement code is a little bit different, and they will get a bit more.
I'll let, again, Chris, talk a little about both the reimbursement for the drug and the procedure.
Yeah. Procedural codes exist for superficial lesions as well as deep lesion injections. There are different codes for liver and lung. Typically, what we see is in the order of $500- $700, close to $700 for a deep lesion injection for the procedure itself. In talking with IRs around the country, we've met with 50 or 60 of them over the recent months. This is a meaningful recognition for what they're going to be doing for those deep lesions.
If you want to talk about the J- code as well.
Yeah. So what typically happens is, again, going back to the J- code at launch, we'll have a temporary J- code, which is more meaningful in the community. In a hospital, they are under a different reimbursement model, so that's less important. However, we do typically see a site of care shift for patients until a permanent J- code is in place. For us, that actually works out very well with the treatment path we're looking to establish. Since the majority of patients will benefit from deep lesion injections with IR supports who are in the hospitals, this model will actually create a site of care shift, so patients will be going to the hospitals for those initial treatments exactly where you want them to be. Again, the coding will not be an issue in that setting.
Over time, as a permanent J- code is established, in probably six to nine months, you may see a slight shift back to the community for the superficial lesions primarily. That model and that treatment flow is exactly what we want to be to maximize patient outcomes.
Got it. I think in terms of, I think, Chris, you mentioned 350 as the key account, but also you have an early adopter because they have a closer relationship with the IR. Just give us a little bit the segment-wise, 50%, maybe early is 30%, and then expand to 80%. How those relationships between the oncologist and then the IR, because eventually we hope to see that RP1 can be broadly applicable, but we also have the trajectory, the ramp-up for the adoption.
Yeah, that's great. Thank you. What's going to happen is once a patient progresses on a PD-1 containing regimen, the oncologist will be the decision maker to decide to use RP1. If a patient has both superficial and deep lesions or deep lesions alone, they'll reach out to their IR. At that point, they'll establish their treatment plan. What we're hearing is that most interventional radiologists, they're busy, but none of them, given that this is a treatment, none of them said they can't begin therapy within two weeks. What they'll likely do is establish scheduling for all eight doses and begin that process. That'll be within that early segment. We've built our organization to really concentrate and focus on this 350 accounts, as you mentioned, that treat roughly half the patients, just over half the patients in the U.S.
The second six months of our launch will begin to shift towards adding another 800 accounts, which will take us to a critical mass of just over 80% of patient treatments across that space. We don't, however, want to leave any patient behind. For the remaining 20%, we've hired an inside sales force who will be reaching out to those practices to make sure that as we identify patient needs, we have the internal commercial infrastructure to align them to a referring IR who can help with those deep injections.
Got it. Then.
Just so you're aware of that 350, about 150 are the kind of initial targets, and that'll be about 25% of the volume and another 25% for the remaining 250 or 200.
For the initial 150 and then another 200 account for the whole 350, how many of them are having direct IR, in-house IR? They have a very established relationship. You do not need to because we know physicians are busy, and then the changing practice is very difficult for them. You want to just, if they have very established referral or the treatment paradigm, they do not need to change anything. They just make a call, and then I have a new patient for you, and then the patients still belong to me.
Yeah. Among the 150, they all do, and among the 350, the vast majority do, or they have an existing referral network in place that will continue to strengthen and develop over time.
Okay. How about the rest of the another 800 to cover the 80%?
Yeah. As we get broader out into the community, we needed to make sure that we could help support that referral pattern even more. We built in part of our commercial model a team of interventional radiology experts, a team with about 18 years of experience working in interventional radiology. They're going to be meeting with those IRs locally to make sure that when a patient is identified among that 800, if they don't have an IR within their own immediate center, they can provide the guidance they need to refer them to a treating IR who has experience there.
Got it. You said they have access to the IR, although they have not the in-house IR.
Yeah. Most of those 800 won't be integrated IRs, but they'll be an existing referral network. They use them for things like biopsies and those kinds of things, and we will establish who within that referral network is ready to inject RP1.
Got it. Okay. Seems the IR are going to play a pretty critical role for the broad adoption. How much have you discussed on kind of having the conversation with the IR group, how excited they are, and then how they think the treatment can fit into their common practice?
Yeah. This has been one of the more exciting things we've learned in our market research and in a lot of the interactions we've had with IRs. They've typically played the role of diagnostics. However, they've really wanted to play a role in the active treatment of these patients. RP1 is going to allow them to do that. What we've learned is that since they aren't actively involved in treatments today, a 33% response rate has to be put in the right context. When they realize the benefit that they can provide through the active treatment, there's a tremendous amount of excitement building. We're working with some of the IR communities as well as some of the preeminent thought leaders around the country when it comes to coding. How do we maximize the communication that takes place between medical oncology and interventional radiology?
In fact, some of the tools they've suggested have already been created to further that connection, and they'll be included in our EMR once we go live. We're already using that today in our confirmatory IGNYTE-3 trial to make sure that we understand which lesions and we're following closely, which lesions have been injected, how much drug was administered into those lesions, and that treatment process throughout the full eight doses.
Maybe just one thing to add. I mean, they're really excited to get into the IO game because right now they do things like procedures, Y90, but this is really the first time they can get to work with an oncologist with a treatment and help these patients. They're very excited about that.
How do you think about the learning curve for those IR? Maybe take a step back for the Ignite and IGNYTE-3, those visceral deep lesions, they're already conducted by the IR, so you have some early experience from those physicians, the IR?
Yeah. I mean, they do much more complicated procedures. They do embolisms and other things, taste and tear. Generally for liver, it's ultrasound. Some of the IRs have a little bit less experience in lung injections, but at least the ones on our trials are very comfortable doing those as well. As you saw in our ASCO poster, we see a very good safety profile even with repeated lung injections. I think they're excited to do it, and it's something that they are very much looking forward to being part of moving forward.
Got it. Okay, great. I think we talk a lot about the commercial dynamic, which is rightfully to do because you have the PDUFA upcoming. Let's take a step back on the PDUFA because that's the first step you need to complete. I think the recent update is you say you completed the late cycle review and then even the site inspection. FDA gave you some feedback. You already responded. That's maybe a couple of weeks ago. Anything happened between then and now? Anything you want to say about because it's really upcoming a couple of weeks from here? Anything you can tell us? Typically, you don't do the play-by-play update, but anything you can give us the more confidence, that will be very helpful.
Thanks, Roger. That's right. We did, on our earnings call, share that we had completed our late cycle review. At that time, the FDA had shared with us that an advisory committee was not expected and that a REMS would not be expected after a potential approval. We did state at that point that manufacturing inspections had been complete. At this point, we can update that the clinical site inspections have also been completed. The remaining steps would include, in the coming weeks, entering labeling discussions with the FDA. We're still under an active BLA review, and then we believe we'd be on track for our PDUFA of July 22nd .
Okay. So labeling negotiation and any outstanding during the BLA review, that's just common course. Regarding the FDA's feedback or response, you don't see anything will prevent you to be able to get everything done by the PDUFA date?
Yeah. The FDA has been highly engaged with us, and we've been responding to their information requests in a timely and thorough manner, so we don't believe that there are any bottlenecks. Like I said, we are under an active review, so we will continue to respond to any information requests that arise and enter labeling discussions soon.
Yeah. And then obviously, the whole process, you are experiencing the change of the FDA and then including CBER. Do you see any change in terms of your interaction with the review team and then any staff difference between before and after the new administration?
Yeah. We haven't seen any changes. We've been happy since receiving our breakthrough designation late last year and then our priority review BLA acceptance early this year. We've had a very engaged review team from the agency, and we've seen the same individuals attend our mid-cycle and late cycle review with the same level of commitment and consistency. We believe that will continue and don't anticipate any change.
Okay. Good. In terms of the label, your IGNYTE pivotal study is pretty broad in terms of the use of the PD-1 different settings. The very good thing is your response efficacy data is pretty consistent across all the subgroups. How confident are you you can get a broad label? I don't know. I don't want to put the language to you, but obviously, it's FDA's decision. How likely are you going to get this broad post-PD-1 or PD-1 failed melanoma as the initial label?
Yeah. I mean, as Emily said, we haven't gone into label negotiations yet, but if you think about what's the basis of the label, it's the study population. We did, as you said, enroll a real-world study population. It includes different presentations of PD-1 failure, including patients who failed in the adjuvant setting, stage four visceral patients, IpiNevo failed patients, and again, the consistency of the benefit we've seen across those subgroups. These are all patients who are in need of additional treatment. Two-thirds of our patients had primary resistance, and those do particularly badly, even adjuvant failed patients. We really believe this is an unmet need population and that they should all have the opportunity to benefit from RP1 plus Nivolumab.
Got it. Your confirmatory study is specifically, say, post-PD-1 and then CTLA-4 unless CTLA-4 is not eligible. That's just to confirm the efficacy for the RP1. You don't expect this will change the label indication because it's a little bit narrower than the expected label for the IGNYTE.
No. I mean, that study will read out obviously several years from now, and we would have that label based on the population we had in IGNYTE. It was a narrower population because we wanted to focus on an OS endpoint in a population that really has very few options, which is in the IpiNevo failed population. It's sort of a subgroup of the IGNYTE study, but we don't think that'll have any implications on the label. Of course, we're focused on getting that trial enrolled as quickly as possible. We've had a lot of excitement on that trial, both in the U.S. where we have 50 sites, and we're obviously trying to enroll as many patients as we can before PDUFA because we know patients are going to not be excited to be enrolling in the control arm there.
We're doing all we can in terms of XUS expansion to make sure that we finish that study in a timely manner.
Awesome. Great. Maybe back to you, Chris, in terms of the commercial infrastructure you're building for the team. It seems the strategy is you're going to launch the drug by yourself in the U.S. at least. How big is the team you are building, and what's the potential cost to kind of launch the drug?
Great. Thank you. Yes. In the U.S., we'll be the SOLC launch team. Our commercial organization is in place already. They were hired back in April. They've gone through training and right now are going through the profiling phase where they're getting all the information they need from those 350 accounts, right? Understanding the formulary process, electronic medical records, and other key elements that'll help ensure a seamless launch introduction. We have 27 salespeople in place, which is really the demand-creating arm of our organization. On the other side, to make sure they stay focused, is a team that's going to help pull through to make this routine for patients and providers. That'll be a team of nurse educators, a team of what we call IROCs, Interventional Radiology Oncology- Coordinators who are dedicated to focusing and support the IR community.
We have a team of field reimbursement managers who are really going to help ensure awareness and clarity around coding, billing, and reimbursement. That customer-facing team is about 60 people in total. I do not know if Emily, if you want to talk about the costs.
Are you asking about price, Roger?
Maybe just in terms of the commercial SG&A, the building for the commercialization, and then also the costs and then the pricing, if you have any guidance on that.
Yeah. I'll start with price. We won't be talking about price until after approval. When you think about our OpEx, as Chris mentioned, our commercial team is fully on board. Our manufacturing facility is at capacity, and IGNYTE-3 is underway. I think between that and the uveal and HCC study, our OpEx is probably pretty right-sized for the foreseeable future. Our COGS are pretty favorable. This is a virus, and we control our own manufacturing. Those are probably closer to, if you're estimating, vaccine COGS than true biologics. I think that will continue to keep our OpEx manageable.
Got it. The OpEx, we're not expecting to have a big jump as you'll start to launch the drug because you already start to build out the commercial team.
That's right. We'll be pretty disciplined when we think about future pipeline expansion. We already have the uveal and HCC studies underway, and I think we want to see some launch success before we think of any additional expansion.
If we think about uveal, it's really a subset of sort of skin cancer anyway, so we wouldn't need additional sales force to focus on uveal. They'd be able to manage that quite easily.
That's right. And then let's talk about that for the skin cancer because the vision is you can expand to the entire, at least a broad skin cancer and the PD-1 failed melanoma as the initial indication. What's the strategy there and then how much data you need to generate in order to get there?
Yeah. So we do envision RP1 forming the basis of a skin cancer franchise. That'll start with RP1 and anti-PD-1 failed melanoma. We've seen a lot of interesting data and exciting data in high unmet need areas such as solid organ transplant patients in our Arcticus trial. These patients develop, unfortunately, skin cancers, and there aren't great options for them because you don't really want to use things like checkpoints because of the risk of organ transplant failure. We've been using RP1 monotherapy up to 26 doses and seeing that we really can help those patients as well. There really aren't great options for those. That's one area that we will be generating additional data and either talking to the agency around whether there's a path forward there in the registration perspective or providing that data in a publication so that customers have the option through Compendia.
We also have seen data in non-melanoma skin cancers, anti-PD-1 failed non-melanoma skin cancers beyond melanoma, including CSCC and Merkel cell, basal cell, where again, we see about a 30% response rate. There are really no approved options for these patients either. Again, I think the plan there is to continue to enroll some patients to determine whether there's a publication or Compendia strategy available. One of the areas we're very excited about moving the RP1 and the platform forward is into earlier disease settings. We'll be talking more about that. Neoadjuvant is an obvious area. As we think beyond skin cancer, we've got RP2 already started in uveal melanoma. That trial's going well, and U.S. sites are coming on board rapidly, and then we'll be expanding that outside the U.S. as well. Again, an area of high unmet need.
These patients have liver metastases, and we do see a nice outcome based on our signal-seeking data. We saw about a 35% response rate for these patients. I think there's lots of opportunities to think about how we expand the platform. It's a natural progression as you think about uveal in terms of liver going to deeper lesions in other tumor types. As we think about what that strategy looks like, we'll be sharing more at our Investor Day on June 22nd.
June 24th.
Oh, sorry 24th .
Yeah. June 24th.
Right. Awesome. Yeah. We look forward to the event ahead of your PDUFA day, and then good luck with the last minute with the FDA. We look forward to the event and then the potential approval.
Yeah. Thank you, Roger.
Awesome. Yeah. Thank you. Thank you, everyone.