Good morning, everyone. Welcome to our day two of the Cantor Healthcare Conference. My name is Li Watsek, a biotech analyst at Cantor. It is my great pleasure to be hosting our next company, Replimune, for a fireside chat. With me today is CEO Sush Patel and CFO Emily Hill. Congrats on the approval of TUDRIQEV. Maybe we can kick things off with a quick overview of where things stand.
Yeah. We are at a very exciting stage for Replimune. We are now a commercial stage company. Got our first FDA approval of RP1, now known as TUDRIQEV, in combination with nivolumab for unresectable advanced melanoma patients who progress on a PD1-containing regimen. We are very excited about that, and now we are very much geared up to getting that product in channel into patients. And we previously guided, after the August 6th approval, that within 60 days we should have product to patients, and we are still tracking very much to that timeline.
Sush, can you maybe tell us a little bit more about how are things going with the launch prep? I know we are one month past that approval. How is the team preparing to be launch-ready within that 60-day [crosstalk].
Yeah.
[crosstalk] window?
Yeah. We are right on track. After the approval, we had product, and now we have product approved for release.
That's triggered a number of things. We have [uncertain] and we're doing the artwork, packaging, and serialization, working with our 3PL to make sure that we can then ship the product to customers. The other aspect of it is just making sure that we build the commercial infrastructure so that we can get this to patients. On that front, we announced in August, Michelle DiNapoli is our Chief Commercial Officer, so she's been on board, getting up to speed with the team and the plans. The other aspect is that we're now just really re-hiring the team. We've hired about 70% of the team already and should have the full commercial team in place by the time product is in channel. We already have reps out there talking to customers and making them aware of the product.
Obviously, there was high awareness already, but they're also focusing on making sure the operationalization happens in a very quick fashion once we get product to the end user.
What is the main gating step here? Is it just a matter of bringing the sales force back?
There really isn't [crosstalk].
To [crosstalk].
Too much there. It's really just around training and onboarding.
About a third of the commercial team was actually previously at Replimune, so we brought them back. So that's been really good because they already have very [crosstalk].
Yeah.
Good familiarity with the product, the customers, what we need to do from the workflow perspective to get this to patients. So that's been really helpful, and they've been helping onboard the new people coming on board. So, it's really just sort of getting them trained and getting them out in front of customers. Now waiting to get the product to the customers so that we can get it to patients.
Great. What are the key priorities during the first six months of launch for you guys to ensure a successful rollout?
Yeah. The number one factor for us is to have a positive customer and patient experience. It's not about, for us that means being very deliberate in our launch and our approach. What we've done is we've taken a very targeted approach to doing this because we want to get it right. Because we believe if we get it right, that's going to lead to long-term sustainable growth and uptake of the product. By that, we've focused on these 200 target accounts. The reason we focused on these, what we call early adopter target accounts, is the hospital academic accounts that have all the infrastructure and experience to really uptake and onboard and utilize TUDRIQEV quickly. That means they've got interventional radiology there because we need to do these deep injections to maximize the patient opportunity. They have T-VEC experience. They've got prior RPx experience.
They can just handle a product such as ours in a much more quick fashion before we get out to the broader community, which will be more of a year plus timeframe for us.
I guess during the first few quarters, what are the key metrics would you be sharing with the street?
Yeah. We think of the metrics going back to this sort of customer experience as having what we call a healthy account, and an account ready to uptake TUDRIQEV, and that means things like making sure that they've got the workflow in place, they've got injectors, whether it's for superficial or deep lesions with interventional radiology. They've got the EMR and the formulary kits together. They got the order sets ready. We're really looking at a number of metrics to make sure that they can do all those pieces so that once a patient walks into the center, they're ready to go.
I assume you guys will be sharing new patient starts.
Yeah. What we'll be sharing is, that'll be [crosstalk].
Right.
What percentage of adoption do we get in these 200 accounts? The other aspect we will be looking at is what is the utilization of reinitiation? Did you just order TUDRIQEV? Did you do a second order? So those are some of the metrics that we will be using. One important thing to be aware of as we think about when we start reporting earnings, that will be more in the Q1 February timeframe. But one of the things that you need to be aware of is we have two doses of TUDRIQEV. We have a 10^6, which is about a tenth of the price of the maintenance dose of the 10^7. So that early uptake, you just need to be aware that you are going to see a lower earnings because it is that lower dose.
Then as patients catch up, we see more of a blended rate of the 10^6 and 10^7. You will see those revenues increase quite rapidly.
I also wanted to touch on the J-code. When do you guys expect to obtain J-code for reimbursement, and how important will that be just from adoption perspective? We heard mixed views from physicians. Some think it is important, some think not so much in oncology.
Yeah. We'll have a permanent J-code in April. In between, we'll have a temporary J-code. And one of the reasons we went to these targeted accounts is these are larger academic hospital accounts that can actually handle miscellaneous temporary J-codes. Which is very standard in oncology. The reimbursement is still very straightforward for these products because these institutions can handle that. That was one of the reasons why before we go out to the community where if you don't have a permanent J-code for the community, that could be more challenging. But for these target accounts, we don't anticipate significant problems, and it shouldn't hinder uptake.
How should we think about the initial launch ramp? Should we expect relatively rapid uptake just given very high unmet need or more gradual build because obviously there are some nuances here?
Yeah.
So maybe just talk a little bit about that. Should we expect an inflection point in uptake once the permanent J-code is in place?
Yeah. I think, as I mentioned, we're very targeted. I think we will see a gradual uptake for this first six months as we get our commercial team back online, we get all these accounts ready to go through all the workflow pieces that are needed to get this into a steady state. I think we'll start to see that acceleration in the second half of the launch year, so Q3, Q4. I don't necessarily feel that the permanent J-code is going to impact that so much because we're not really focusing on getting more broadly into the community for really a year plus.
Yeah.
What we're doing is these 200 accounts, the next wave around six to nine months out will be the next 250 accounts. That starts to get into some larger community practices which can handle. By that time, we'll have a permanent J-code. But before we get out to the sort of 80% of the market, which involves about 1,200 accounts, at that point, we will have a permanent J-code. I don't necessarily think the J-code per se will. To me, it's more around getting this operational workflow in these target accounts up and running.
We also got a lot of questions around the timing and mechanics of billing. I wonder if you can just walk us through how this buy-and-bill process works. Obviously here we're looking at a combination, and then we also have procedure and also the drug itself.
Mm-hmm. Yeah. Let's think of it. Let's break this up. Let's look at the drug component. So, we're a typical buy-and-bill oncology product, just like any other product. So, we're in combination with nivolumab, which is also buy and bill. That has a J-code, will have a J-code eventually. So that's a very standard process that they'll bill through like they do for any product. So, the drug piece is one thing. Then you're right, there's also another aspect of our modality, as I mentioned, is we're an intratumoral injection, and then there's sort of procedure code for the injection. So, there's two aspects of that. There's the superficial codes, which are already existing. They're used for T-VEC and other intratumoral superficial injections. Those codes exist today. And then we also have deep injection codes that also exist.
Things like liver and lung biopsies and procedure codes exist that IRs can use. They also have codes for image guidance, whether it is ultrasound or CT. Those codes exist. Obviously, one of the things we will be doing is educating customers on billing and coding and reimbursement through our appropriate teams.
Do you expect a little bit of education upfront just because you have different codes for different components?
A little bit, although, again, these target accounts, they have interventional radiology. They are quite familiar with these codes.
Okay.
They use them for a lot of other procedures. Certainly, there may be some that are less familiar, and we have all the resources and materials we need to make sure that they are aware of what to do.
Okay. Maybe comment a little bit on the gross margin for TUDRIQEV and gross to net assumptions.
Do you want to take the gross?
Sure. Yeah, happy to. As Sush mentioned, this is a buy-and-bill product, so our gross to net is in line with newly launched buy-and-bill oncology products. We are initially targeting the hospital-based settings where we expect to have a higher percentage of 340B patients than when we expand into the community centers. There is an opportunity for gross to net improvement over time. On the margin side, our cost of goods are really the main contributor to our margins, and they are about 10%.
For gross to net assumptions, do you guys have a range that we can sort of look at?
We haven't disclosed a range. I think just looking in line with other buy-and-bill newly launched products is probably most appropriate, then looking for opportunity for improvement over time.
For the reasons that Emily mentioned, [crosstalk].
Yeah.
Because the initial, there will be a lot of 340B use. As we get more into the community, we would expect that to sort of adjust.
In terms of the volume that you would expect for TUDRIQEV use in the real world, obviously, I think in the clinical trial, it is up to eight injections. But we heard from physicians that they would try to inject as many lesions as possible. They are open to retreatment, treat beyond progression. Is it possible that we might see maybe a higher median volume use per patient in the real world?
Do you want to take that one, too?
Sure. Yeah. We priced around the 18 mL [crosstalk].
Yeah.
Volume usage, which was the median usage seen in the IGNYTE study. But the dosing for TUDRIQEV is approximately 1 mL per centimeter of tumor volume. There is a bell curve of volume used in patients based on their tumor burden, from patients with smaller superficial tumors to obviously patients with a larger tumor burden, including deep visceral tumors. The $450,000 we disclosed is based on the 18 mL with the caveat, remember, for modeling purposes that Sush described of starting with the 10^6 dose, which is both a tenth of the viral load and a tenth of the price of the 10^7 maintenance dose. Usually, when you transition from clinical trials to the real world, of course, you'd expect some discount in usage.
Yeah.
I think because this is a bell curve, the 18 mL is probably the right median. In IGNYTE, 18% of patients did have retreatment, as you describe, that's not included in the median calculation. Our label does allow for physicians to re-treat at their discretion. There will be opportunity for upside, but again, I think we'll have to look at what that bell curve looks like in the real world.
Yeah, I think it's hard to model, but if we're successful with doing these deep injections, you might expect there's to be volume increase over time. But as Emily said, we'll have to wait and see how that uptake looks.
In terms of deep lesions, as we know, maybe 60% of these patients may need deep lesion injections. Can you talk a little bit about your educational efforts around IR capacity and coordination?
Yeah. We've done a lot of research with IRs and looking at capacity. Most of them can handle this. Obviously, IRs are very busy. It's going to be account by account. What's most important for us is having that collaboration and coordination between oncology and IR, because they can then help sort of schedule a treatment plan. What's important is if you have that discussion early and you schedule those interventional radiology appointments out early, it makes it much easier versus just kind of doing it ad hoc and trying to get on their schedule. So that's one of the sort of best practices they've talked about.
What you have to remember is these don't tend to be longer procedures like they do for embolisms or ablations. These can usually be 30-minute procedures. Again, if they can schedule those out early in the treatment plan with the oncologist, we don't think capacity will be a major issue. We talk to a lot of these target accounts that they should be ready. The IRs are very excited to do this because this is something now that they can get involved in the IO game. Right now, they do things like procedures, but they really are excited about being involved in the treatment of the patient.
Among those 200 accounts, sounds like they are pretty sophisticated. Would you say they are pretty educated in terms of this coordination between IR [uncertain] ?
Well, most again, these accounts included a lot of RPx clinical trial sites.
I see. Okay.
We have an ongoing IGNYTE-3 study, so there is collaboration with IR and oncology already happening there. They do a lot of deep injections. We have the RP2 study in uveal melanoma. All those patients have liver metastases, so again, IR is very involved. These are sites where they have got some experience with doing deep injections, either with RPx or other procedures.
Any other initial training or onboarding activities going on at these new hospitals?
What we are doing is making sure that there's injectors ready now that if they are superficial, these can be NPs, PAs. It is pretty straightforward. If you look at our PI, there is actually quite a nice summary of information on how to do these superficial lesion injections. As I mentioned, a good number of these 200 accounts have got some T-VEC experience. They have got someone in the site. Who's already done superficial intratumoral injections, so we're leveraging that. We're leveraging certain nurse education to make sure that they're ready to do this. And then the other aspect, as I mentioned, is working with the interventional radiologists in these institutions who, again, got a lot of already have experience. We're making sure a broader group of IRs within the institution has either experience or understanding of how to do these.
They think of them as reverse biopsies. It's pretty straightforward. It's not like it's a very complex procedure for them. Just making sure they're aware of how to think about doing this, some of the considerations of when you're doing either a liver injection or a lung injection with RPx or TUDRIQEV. So those are just things we're educating them on and making sure that our field teams have the materials, resources to make sure that both superficial and deep injection are done appropriately.
In terms of handling, storage, there's no special training required?
No, and again, we're working with one of the operational aspects of talking to these accounts is working with the pharmacy. Making sure they understand how to order, how to store, how to prepare syringes, et cetera.
Mm-hmm. You also mentioned before there is a pretty high overlap between your top 200 accounts with maybe TIL treatment centers.
Yeah.
Just curious about what are you hearing in terms of sequencing at these centers? What are some of the early feedbacks that you hear from physicians?
Well, I think firstly, the unmet need is super high here. We've got a really broad label. We can treat about 80% of these 10,000 eligible patients. I think they're excited firstly to have more than one option for these patients. We have, I think, a very attractive safety profile and a good efficacy profile, durable responses. This is something that could be ordered the next day, and these patients can't wait. I think having that option really positions us very well in terms of this treatment conversation. I think it is a conversation between the patient, the physician, and what makes most sense. There may be some TIL patients that they feel this patient's a TIL candidate. But we also feel that given our profile, there'll be a lot of candidates, given the breadth of our label, that'll be TUDRIQEV candidates. I think it'll be a patient-by-patient conversation.
Mm-hmm. In terms of your ongoing phase III confirmatory study, IGNYTE-3, sounds like you guys are approximately a third enrolled, and then you are enrolling in Europe right now. How should we think about the trajectory from here, just from a patient enrollment perspective and just from the FDA perspective? Is there a requirement that you have to finish the enrollment by a certain timeline?
Well, when you're on accelerated approval, yes, there is an expectation that we complete the study in a timely fashion. We've communicated that we should have a readout in the 2030 timeframe. It's event driven. It's a primary OS point. The study remains on track, and now what we're discussing is when to stop U.S. enrollment, because once you have commercial products available, obviously, it makes sense to start to shut down U.S. enrollment. We've got some ex-U.S. sites already enrolling and we're adding some European sites. So, we feel that the trial will continue to be enrolled well. There's a lot of interest and excitement outside the U.S. In terms of just our confidence, what we've seen in the IGNYTE trial is that we have durable responses, and those durable responses we presented through year overall survival from the IGNYTE trial at ASCO.
We saw about 50% of patients were still alive after three years. We feel confident that if we're doing this trial well and monitoring it well, making sure we do these deep injections, because we know when patients get deep as well as superficial lesions, they tend to have higher responses. We feel very confident that we should hit that overall survival endpoint.
You're pretty confident that you're going to get sufficient coverage in the deep lesions as you go into [crosstalk].
Yeah. I mean, one of the [crosstalk].
Different sites.
Yeah, one of the benefits is now that we have the IGNYTE data and that we've been talking, and then these sites have been doing this actually with I-3. We have this data published, we are seeing that they are doing more deep injections on the I-3 trial, which is exactly what we wanted, liver, lung, lymph nodes. That is happening.
Mm-hmm. What is your conviction level that the overall survival benefits? You're going to see overall survival benefit in the phase III study, and I believe you guys also had some early look from the phase III, some patients.
Yeah, that was really like I said, it was a very small number. A very short follow-up. We feel confident based on what I just sort of mentioned. The fact that when we see responses, they're durable. When we looked at the three-year survival data at ASCO, we presented that we have 50% of these patients alive at three years. You don't typically see that for advanced melanoma patients who are rapidly progressing on their treatment. That does give us a lot of confidence. Then we just learned a lot around how to best give TUDRIQEV, and we're implying that to the I-3 study in terms of just how we're monitoring, making sure we're doing these deep injections, and I think that's going to maximize outcomes for patients and translate into a good benefit, including overall survival.
Can you touch on maybe manufacturing inventory? Was there any disruption to the manufacturing capacity?
When we had the RIF, we definitely prioritized ensuring that the RP1 supply did not get impacted, so we have about a year of inventory. As I mentioned earlier, we've now have that product approved for release, and we're in the process of getting that ready, packed, and shipped to send out. No, we haven't had any meaningful disruption, and because we manufacture our own product, as we get out there in the marketplace, we'll be able to monitor demand, and if we need to make more RP1 or TUDRIQEV for commercial, we can do that.
Mm-hmm. Can you talk a little bit about how you expand beyond melanoma for RP1?
Yeah. I think we're very interested in really developing an RP1 skin franchise. Previously, we've not only presented data in checkpoint failed melanoma, we've seen that checkpoint failed other skin cancers, non-melanoma skin cancers, MCC, BCC. We're also able to help a lot of those patients. We get about a third of those patients into durable response. I think that's an interesting, exciting opportunity. Another area in data we previously presented is monotherapy RP1 in organ transplant patients. These patients develop skin cancers, typically non-melanoma. CSCC is one of the common skin cancers they develop. They don't have great options. In fact, there's nothing really approved for those patients. PD1 is contraindicated. People use them because there isn't anything else, but you then have a risk of organ rejection.
In our ARTACUS trial, we showed, again, a very durable response rate, about 30%, with the fact that we can continue to treat these patients and provide an option without having to taper their steroids or not seeing any organ rejections. This is something that we've got data. We're going to be publishing that data shortly and also determining if there's a path forward in terms of an indication. That could be an NCCN listing, for example, as well as the non-melanoma skin cancers that failed PD1 treatment. Then the next step for us to think about other sort of skin cancer indications we want to pursue with TUDRIQEV.
Then, switching to your next-gen product, RP2, maybe give us a quick update on the phase II/III trial that you guys are conducting in uveal melanoma.
Yeah. The phase II you are referring to is the REVEAL trial, and this is in checkpoint-naïve, metastatic uveal melanoma patients. It is enrolling right on track very well, actually. A lot of excitement about that trial. This includes both first line and second line patients because it is checkpoint-naïve, and it is regardless of HLA status. So, whether you are HLA positive or negative, patients are enrolling in that trial. So, I think it is going very well.
When do you expect to share data from that study?
Yeah. It is about 280 patients, and it is a PFS OS primary endpoint, and as Emily mentioned earlier, the near-term thing we are looking for is the phase II/III transition, which we will be looking at. It will be a go, no-go transition early next year, and then the first readout from a data perspective will be PFS from that trial, and that probably around the 2028 timeframe, 2028 timeframe.
What is the bar for go, no-go?
It's predominantly safety, and we haven't disclosed a specific efficacy bar.
That the IDMC will look at. It won't be something we sort of present externally.
Mm-hmm. How are you thinking about RP2's positioning in the metastatic uveal melanoma space? We've had some pretty exciting developments in the frontline setting, so how big of a market is there for the checkpoint-naïve patients.
Yeah.
For RP2?
Yeah. Just like melanoma, I think patients desperately need options for uveal melanoma. Obviously, we've got tebentafusp in the HLA-positive patients, and that's been available for a few years. We just saw the [uncertain] data in HLA- negative patients. It looks exciting. That'll probably get an approval early, sort of middle of next year. That means that you've now got an option for HLA-positive and HLA-negative frontline patients. They may even get a broader label, depending on what the data shows. However, I think you have to remember that not everyone responds to those [ crosstalk].
Yeah.
Treatments. As exciting as the efficacy is and having these options, there's also toxicity challenges, and as I mentioned in our REVEAL study, despite having tebentafusp available, we're still getting a fair number of HLA-positive frontline and HLA-negative frontline patients treated in that trial. I think, having these options, so whether you're frontline ineligible for whatever reason, or you can't tolerate it or get one of these other treatments that'll be available. Then there's a lot of patients, sadly, that still progress, and so having an option for second-line patients is really important. If we think about the opportunity, the second-line opportunity, regardless of HLA status, is probably not that dissimilar than if you look at the HLA-positive or negative segments frontline. Obviously, there'll be some attrition. Not everyone makes it to second line. But so, we think there's a significant opportunity there.
So, it sounds like you guys wanted to focus more on second line. What would be the right PFS benchmark there?
That's hard. There isn't a lot of published [crosstalk].
Yeah.
[crosstalk] data out there, and we're going versus Ipi/Nivo. So, you really wouldn't expect to see more than sort of three or four months PFS. In fact, I think the [uncertain] only had around, if you look at the control arm, I think it was three point one months' PFS benefit. Second line is probably even worse than that.
Okay, great. Looks like we're out of time. Thank you so much, Sush and Emily.
Thank you.
Thank you. Appreciate it.
Appreciate the time.