Good afternoon, everyone. Thank you for joining us here. It is my great pleasure to introduce Sushil Patel, CEO of Replimune. We were thrilled to have here at our 45th Annual Healthcare Conference. Sushil, thank you for joining us. Look forward to walking through your presentation.
Thank you, Ryan. Good afternoon, everyone. Just to remind you of our forward-looking statements. So, Replimune was founded with the goal of really developing more potent and systemically active oncolytic immunotherapy. And right now, we have two assets in the clinic. RP1, which is very much focused and has generated compelling activity in a range of skin cancers, including anti-PD-1 failed melanoma, and I'll be sharing some of that data with you shortly. And we're now well on the way for a BLA filing in the second half of 2024. RP2 is very much focused on looking at rare cancers and hard-to-treat cancers. Again, we've seen activity in a range of those. The plan is to move forward in uveal with a registrational study, which again, I'll be telling you a little bit about more shortly.
And just to remind everyone of the mechanism of action, there's really a twofold approach here. There's local tumor killing, which releases neoantigens, which then drives a more broader systemic reaction. The platform is based on a herpes virus, HSV1, a very lytic virus for cancer. And then there are a number of transgenes encoded into the virus. With all our platform, we have one that's a fusogenic protein that drives sort of cell-to-cell fusion. So it creates quite a potent local immunogenic killing, but it also drives immunogenic cell death, and that really is quite potent and drives a more systemic reaction. And so that GALV protein, which is based on another virus, gibbon ape leukemia virus, has a very potent activity in this construct.
In addition to GALV for RP1 and 2, we also have a GM-CSF, and with RP2, we also encode a CTLA-4 molecule, which again, the idea there is to drive even more potent and systemic immune activation, particularly for more immune-insensitive tumors. So, as I mentioned, RP1's focused on skin cancers. I'll be sharing some of the data in skin cancers with you shortly, and then RP2 is focused in some of the rarer cancers. You can inject these both superficially and viscerally, and I'll talk a little bit about that as well.
We've seen systemic and visceral activity with both assets. So now I'm going to move on to the RP1 data in skin cancer, starting with our IGNITE data, and we're very excited about this in anti-PD-1 failed melanoma. Let me just remind you of the environment, the landscape. Despite a recent approval in the anti-PD-1 failed melanoma space TIL therapy, the significant unmet need remains.
You know, the existing drugs either have, you know, modest response rate, limited durability, or come with significant toxicity, and so there really is an opportunity to advance the landscape from multiple angles. It's when you look at some of the existing treatments and data in the anti-PD-1 failed space, the criteria used for resistance is quite varied. One of the things that we've done, I think, a very good job of, is having a very specific and stringent criteria, so that these patients really would not benefit from additional treatment. These patients had confirmed progression while on a PD-1. They had to have been on PD-1 for at least 8 weeks, and that progression was confirmed by 2 scans.
So we can really be quite confident that these patients have truly had will not benefit from further treatment. And this is one of the differentiators that you'll see from many other trials in this space. So this is the data I'm going to share with you, which we just presented at ASCO. It's on 156 patients. It's a 140-patient registration-intended cohort, plus 16 patients from our phase I experience for 156 patients. All these patients have been followed up for 12 months. And so I think one thing we feel very confident is it represents a truly real-world and broad population of and presentations of anti-PD-1 failed melanoma.
I would sort of direct you to the M1, M1c, the B, C, and D, which is these are patients who had visceral active involvement, about 50%. About 50% had also received prior ipi/nivo. And then we had impressively, about 2/3 of the patients had primary resistance to a checkpoint inhibitor. That means they blew through their prior treatment in less than six months. These are, quote, "what they call the bad actors," who really do not do very well with further treatment. So it's a real-world population. It's one with a high unmet need, where existing subsequent treatments really would not do very well. Here's the efficacy that we presented at ASCO. We had a 32.7% response rate overall, also a 27% response rate in patients who'd failed both ipi and nivo. Again, very tough population.
As I mentioned, that prior primary resistance population was two-thirds of the populations, we saw a 34% response rate. So one in three respond, and we see very good activity across these different subgroups. One of the important things with intratumoral agents is, do you see both systemic as well as local activity? And there's always the idea that, well, we're only seeing a local activity here. And so this is an analysis we did on the first 28 patients, where we looked at all lesions, uninjected and injected. The red is the injected lesions, the blue is the uninjected lesions. And as you can see, the response dynamics are really similar, where the lesion was uninjected or not injected, and 70% of responding patients had non-injected lesions.
So again, hinting to the systemic activity and that we're really seeing not just the local activity, but that systemic activity that I talked about. Importantly, when you are treating these patients, you want responses, but you also want very durable responses, and that's the case here. We've seen 100% of patients last at least six months from time of baseline, and we see a median duration response of more than 36 months. One of the nice benefits of the modality is the really nice safety profile. But if you look at the combination of RP1 plus nivolumab, we see generally mild to moderate side effects, constitutional side effects, mostly grade one and grade two. We do see a smattering of grade three and four side effects, but we have not seen any grade five reactions.
Again, this is very different to many of the other treatments that patients have in this setting today. So in conclusion, RP1 with nivolumab shows, in patients who had confirmed progression by strict criteria, shows deep and durable systemic responses, a very favorable safety profile. As I mentioned, about one in three patients respond across the different subgroups, enrolled, and these are very durable. Now I'm going to transition from t hat was the investigator-assessed data of the 156 patients. This is the primary analysis that we just presented in investor event last week on the 140 patients, which is our registrational intended cohort. And so, I'll start on the left. The, if you remember, I just shared with you, modified RECIST data from the 156 patients. That was 32.7.
In this of the 140 patients, you see 32.1, so consistent. Now, moving to the right-hand side, the two investigator-assessed, central reviewed, independent reviewed data. This is the primary analysis of the study. The middle number is 33.6%, which is increased over what we saw with the investigator modified RECIST, which was encouraging. The other number you see there is RECIST 1.1. This was an analysis the FDA requested just so they can really cross-compare our data because we use the modified RECIST criteria to other treatments in the landscape. And again, you see a very consistent 32.9%, even in RECIST criteria as well.
But just to give you an example of a patient, this is a highly treated patient, had multiple previous lines, including experimental treatments. Just to orient you, the red circles are where RP1 has been injected. In those, you can see there is some decline in the lesion size. Then you have the yellow are the uninjected lesions, and here we see activity in bone. We also see abdominal reductions in lesions and importantly, visceral lesions in lung on the bottom right. So again, when we summarize the central review data relative to the investigator data I shared with you, very similar consistent patterns in terms of a third of patient response. As I mentioned, the ORR actually increased marginally to almost 34%.
Responses remain durable, whether they were by investigator-assessed or the independent review, and that the safety continues to be very well tolerated in terms of grade one and grade two, relative to grade three and four side effects. This full data with additional subgroup analysis will be presented at upcoming congress. Now I'm going to move on to the next steps in terms of regulatory. At central review data, the top-line data has already been shared with the FDA. We'll be requesting a pre-BLA meeting.
But just to sort of orient to previous conversations we've had and why we feel that we're meeting the criteria that we've had based on those discussions with the agency, we had a type B meeting and a type C meeting more recently. The FDA gave us a lot of direction on what they wanted to see. As I mentioned, one of the key things was to make sure that we had a real-world population, that we saw clinically meaningful activity across subgroups, which I shared with you.
We believe we've met that bar. As I also mentioned, the FDA wanted to see RECIST 1.1 data from central review. Again, that data is held up relative to the investigator-assessed data. And then one of the important things that the FDA did say is we're a combination treatment, so, you know, how are we going to look at the individual contribution? It is a tough setting to actually identify that, given the heterogeneity of the population. But they did say that we can use individual contribution of components by literature.
As I mentioned, if you use the criteria we used, we would not really expect to see any more than 10% response rate for single agent anti-PD-1. So again, we believe we've met that criteria as well. And again, we're going to now start enrolling in our confirmatory phase III study. The FDA was very clear that they wanted this underway. We're hoping to have the first patient enrolled in that study, our IGNITE-3 trial, in Q3. This is the study. It's in advanced melanoma patients who have progressed on IPI and nivolumab, or are ineligible for CTLA-4.
They can also get a dealer's choice in the control arm of Opduolag chemotherapy or further re-challenge with monotherapy anti-PD-1. The primary endpoint of this trial will be overall survival. And as I mentioned, the idea is to get as many of these patients enrolled. There was a lot of excitement on this trial coming out of ASCO, so we want to get as many patients enrolled prior to BLA. But now I'm going to move on to monotherapy data.
Previously, I presented combination data with RP1 plus nivolumab. Now, let's look at monotherapy data. This is in the setting of organ transplants. These patients sadly will eventually get a skin cancer at some point in their lifetime, most likely. This is a high unmet need because for those patients, you really can't give further checkpoint inhibitors because of the chance of organ rejection, particularly for liver, lung, and heart transplants, where you really don't have a fallback. Obviously, you have a kidney transplant, you go back to dialysis. That's still not optimal for the patients.... This is single agent RP1.
It's a bit of a different dose and schedule to what we use in combination, where we use up to eight doses. Here we use 26-- up to 26 doses, and you can redose the patients. These patients usually develop of the different types of skin cancers. It's almost always cutaneous squamous cell. They develop, so about 90% of them, which is consistent to real world, actually develop CSCC, and this is what we saw in this study. We saw a very impressive response rate of 35% and a 22% complete response rate.
Now, what's so meaningful is, as I mentioned, for many of these patients, you really can't get further checkpoint inhibitors, or if they do risk choosing a checkpoint because you've got the choice of either dying from your cancer or rejecting your organ, you know, you can also have to make a deal to change their steroid regimen and immunosuppression. One of the benefits in our trial was we did not have to change their underlying immunosuppressive drugs, so they could maintain those, and we saw no organ rejection. Early data, but quite encouraging. We're looking to enroll more patients, including heart, liver, and lung. But just to give you a little bit of background on what's the sort of opportunity size and patient population, it's about 1,500 patients.
We are seeing a real explosion in the number of organ transplant patients that occur in the U.S. There's been more than a doubling over the last eight years. As I mentioned, these patients have a significantly increased risk of developing cancers and loss of organ rejection. And as I mentioned, I shared the data there and the dosing and schedule and our safety profile. So we're excited about this opportunity. This is an area where we may be able to take this data, given the unmet need for a potential registrational path.
Now, I'm going to move on to another trial that we did, CERPASS. This was a locally advanced or metastatic CSCC. This was a randomized trial of RP1 plus cemiplimab versus cemiplimab. Unfortunately, this trial narrowly missed its primary endpoint of CR or dual, one of its dual primary endpoints of CR. However, what we did see is a really, a compelling activity in locally advanced CSCC, where we saw a doubling of the complete response rate seen in, red on the bottom there, 48% complete response rate in the control in the experimental arm versus 22% in the cemiplimab alone arm.
We're going to continue to follow this trial, and the reason it is because we do see significant benefit for patients. These patients on this trial, some of them had very, very significant tumor burden, very large outward growing tumors that we could get into complete response. This is really meaningful. So if you can bring some patients like this into complete response, it means a lot to the patients and their treating physicians. So now I'm going to just move on to the commercial opportunity with RP1, and I talked about a lot of the different skin cancers starting on the left side. About 13,000 anti-PD-1 failed melanoma patients.
I'll just break that down for you a little bit. There's about 2,000 patients who come from prior adjuvant treatment who fail. You know, it's sort of misunderstood sometimes that those patients can actually, if they've got primary resistant disease, can blow through treatment quite quickly and are just as in need of treatment as other patients in melanoma. About 8,000 patients have second-line failed melanoma from frontline ipi, nivo, Opduolag, or a BRAF inhibitor, and then there's a 2,000 or 3,000 third-line plus patients. So significant opportunity there.
We also, as I mentioned and showed you some of the data we have in non-melanoma skin cancers, there remains a significant opportunity there. I mentioned the locally advanced CSCC, the solid organ transplant. We also see activity, just like we saw in melanoma, for anti-PD-1 and failed non-melanoma skin cancers as well. Some of these may be compendia listings if we're able to get RP1 approved. Others will be potential registrational path we'll pursue. What's really exciting about the modality and really, really lends itself is to moving it to the earlier stage neoadjuvant setting, and there are a significant number of patients there, a lot of drug development going on there, and we do think we can further raise that already high bar in some cases.
So as we think about how would we use and position RP1, we do think it can be broadly adopted in the U.S. across different settings. As I mentioned, we believe that we are a great first option for melanoma patients who have progressed on either their first adjuvant treatment or the first-line setting, given the deep and durable responses, the safety profile, and the ease of administration relative to some other options like TIL therapy. We also believe it provides a compelling option for a range of PD-1 failed presentations, and we've done some analysis around 80% of melanoma will have something that you can inject. It will either be a superficial lesion or something that can be image-guided deeper lesions that will involve interventional radiology.
So we do think not only do we have help a range of anti-PD-1 failed melanoma, but we can also help a broad range of patients within that group. And this can be done in most healthcare settings, including in the community. It allows community physicians to keep and treat their patients prep versus having to refer them to academic centers for certain treatments. As I mentioned, we've also seen compelling monotherapy activity in hard to treat non-melanoma skin cancers, which have failed other options and solid organ control. So just talking a little bit of manufacturing. I shared with you some of our prior FDA interactions and feedback. We also had a recent Type C meeting on our CMC specifications, where the FDA provided more clarity on what they need in terms of assay and validation.
That was a very productive meeting, so we now know what's required from that perspective. We have a state-of-the-art manufacturing facility in Framingham, Massachusetts, where we're making all our own drug, and we'll have enough supply for global production of RP1 and RP2, and that commercial inventory is also underway. One of the other nice aspects of this modality is a very attractive cost of goods and off-the-shelf practicality relative to other things like cell therapies, which can be a significant cost. We're just now moving on to RP2.
So that was RP1. RP2, as a reminder, has all the components of RP1, in addition to the CTLA-4 encoded. We know that CTLA-4 is a potent immunostimulator, and if it can be given locally without the systemic activity and toxicity that CTLA-4 often can causes, that can be very beneficial for patients. On the bottom there, you see two examples of uveal melanoma, which are hard to treat, where we on the first, we see an expansion of the T cell clones, not only existing clones but new T cell clones, suggesting there's underlying immune activation happening.
And on the right, we see another uveal patient who actually has an upregulation of the CD8, so infiltration of T cells, post-treatment and up-expression of PD-L1. So just talking about uveal melanoma a little bit. It's called melanoma, but really, it's cancer of the eye, and one of the sad and tragic things about it is most of those patients will have liver metastases. 70%-90% of those patients will get liver metastases with a very bad prognosis. Of course, there's been a recent approval with Keytruda in the frontline setting. However, that's predominantly for HLA-positive patients.
There's still an unmet need in HLA-negative, and not everyone can tolerate or can get Keytruda, and so there is certainly a need for better and newer options for patients. So we also shared our uveal data at this ASCO, and again, we saw some very encouraging activity. We saw almost 30% response rate in these patients who are very hard to treat, almost a 60% disease control rate. And this certainly got some of the uveal melanoma treaters excited, and that's why we're moving forward with a with a potential registrational study. A couple of important aspects, we saw activity whether the patient had HLA positive or negative disease, and that 70% of these patients had failed ipi/nivo. Just like I showed you with RP1, the toxicity profile for RP2 is very good and very tolerable.
We do see a slightly higher incidence of grade one and two constitutional reactions, as you might expect with the CTLA encoded, and we also see some more grade three. Importantly, we did not see any bleeding because a lot of these patients I mentioned had liver metastases and injection of their liver metastases in a repeated fashion. And so this can be done repeatedly. These are a thin needle that you use. It's not like a core biopsy. This is just a patient example. This was a patient who was highlighted on TV in the UK. In red, you see these very large liver lesions that were injected and that went away. We also see uninjected liver lesions, and other lesions disappear, and this patient is a continuing response for 19 months.
So just to sort of summarize the RP2 approach, we've seen active RP2 in a number of rare tumors. I shared with you some of the uveal data. We've also seen activity in chordoma and spinal cord tumors, which are difficult to treat, and sometimes surgery can't be done. And we've also seen activity in other sarcomas, mucoepidermoid sarcoma, et cetera. We've seen mono and combination activity with RP2. And importantly, rare cancers do represent about 27% of all cancers and about 25% of all cancer deaths. There's certainly a significant opportunity there. We look at sort of uveal as our foundational trial, but an opportunity to build on beyond that, as I mentioned, in the areas there, but also soft tissue sarcomas, head and neck rare head and neck cancers, et cetera.
So just to summarize, you know, we're excited about the centrally reviewed data from IGNITE. We're gonna be submitting now or we have submitted the top-line data to the FDA, and we're requesting a BLA meeting. Looking forward to getting our first patients enrolled in our confirmatory trial, doing the submission before the end of the year, starting the uveal trial with RP2, and then really, we're very much ramping up our commercial activity and readiness, in preparation for RP1. Just as a reminder, all our programs are wholly owned, and we have a potential to deliver significant revenue starting in late 2025. We have a very strong financial position.
We have $420 million in cash, as of April or sorry, March 31st, and a runway into the second half of 2026. So that was a summary of what we've got going on at Replimune, and we're very excited to be talking to the agency and hopefully bringing our first asset to patients in need soon. Thank you.