Scancell Holdings plc (SCLP.L) Earnings Call Transcript & Summary

Good afternoon, ladies and gentlemen, and welcome to the continued improvement in PFS with iSCIB1+ in advanced melanoma Phase II update, ESMO IO. [Operator Instructions] I would like to remind all participants that this call is being recorded. I will now hand over to Phil L'Huillier, Chief Executive Officer, to open the presentation. Please go ahead.

Thank you. Good afternoon. Good morning, everyone. Thank you for joining us today. Today, I'm excited to share with you an update on the SCOPE data. And we're calling this presentation redefining the standard of care of advanced melanoma. Because of the data that we're seeing from the SCOPE study, we believe we are starting to see that we could really redefine the standard of care. Today, for this presentation, I'm joined by the Chief Medical Officer of the company, Nermeen Varawalla, and she will walk you through the data shortly. Here's our forward-looking statement for reference. And let me start off and summarize some key highlights in the presentation today. Firstly, we have -- we're seeing a very strong progression-free survival signal or iSCIB1+ with the checkpoint blockade combination. And the data is, in fact, demonstrating a 74% PFS at 16 months. That's a significant delta over standard of care and over historic controls. And we're seeing a strong progression-free survival data that is also showing through in populations that typically have had a poor prognosis to checkpoint blockade, and Nermeen will walk you through that data. And then, we showed also today and this week, an early overall survival signal where we're seeing a delta of 14% improvement. And this is with Cohort 1, SCIB1, because that cohort started earlier, a delta of 14% at 26 months over the standard of care historic controls. We're really pleased with the SCOPE study. It's achieved the objectives that we set it out to do. First of all, as we highlighted during the year, it's enabled us to select which one of the two products to move forward, and that has been iSCIB1+. We've selected that to move forward. It's showing strong efficacy, but also importantly, it works in a broad patient population, and it has a long patent life. Based on the data that has emerged from the SCOPE study, we've also been able to define a broad HLA eligible population, and that represents 80% of advanced melanoma patients. This means we will have a tool, a selection tool, as I call it, that will enable us to identify the responders to come into the Phase III registrational study. We've also been able to determine how to deliver the therapy and also the dose and the frequency of the regimen. And we will be using a needle-free intramuscular delivery. And then finally, we've started, as you know, on the planning for the Phase III, we expect progression-free survival to be the primary endpoint for the future study. And that's why we're really focused in on that data now. We've had, over this quarter some really good interactions with the FDA, but also EMA and HRMA (sic) [ MHRA ] around our plans to move into registrational development, and we've got supportive responses from those regulators. So I believe, overall, we have a Phase III-ready asset with a potential to redefine the standard of care in advanced melanoma and really bring greater benefit to advanced melanoma patients. Let me walk you through to two market and commercialization slides. So, here's a slide laying out the journey for a melanoma patient, but also the market opportunity and the market size. Firstly, starting over on the left-hand side, the unmet need is still substantial in melanoma, even though checkpoints do work well for some melanoma patients, but about half really don't respond or relapse very quickly. And in fact, 5-year survival for some of our patients in our stage in melanoma is only still 23%. We are focused down here in the patient journey. Patients come in and are screened. They can go into neoadjuvant therapy and then have their tumor removed. And then go on to adjuvant therapy. But when they reach the stage of metastatic, the melanoma has spread through the body, that is when they're eligible to come on to our type of study, it's called frontline advanced melanoma. And that's where we are focused. On the right-hand side, have listed the existing therapies, and the main ones here are the checkpoint blockade, pembrolizumab, ipi/nivo, and relatlimab. And finally, on the bottom of the slide, some new analysis just out of the U.S., showing how the market share is divided in advanced melanoma, and it highlights and really supports our decision to move forward not only for scientific reasons with ipi/nivo, but also for market reasons. 63% of the U.S. market is dominated by the combination of ipilimumab plus an anti-PD-1. So it supports our estimates of the market for the advanced disease around $3 billion. But if we have the opportunity to go to earlier disease settings, the neoadjuvant setting, then there's an even larger market opportunity. On the back of the progression of data and the progression of our plans into Phase III, we've also, behind the scenes, been working on the commercial building blocks to get us ready not only to execute a registrational study on our own or with a partner, but also to head towards a seamless registration and commercialization. So, you can see here, we've now defined our product. We're seeing really meaningful clinical benefit and excellent safety. We have a very, very strong IP position, IP out on to 2039 on the product. I've referenced manufacturing before, but this is a straightforward off-the-shelf manufactured product readily available, accessible to the patients. And we have now been able to scale that process, and we have long stability on our product. In fact, that stability is currently out to about 7 years. So that we can store product. We can manufacture straightforwardly and we can store product for a long period of time. We have a commercial relationship to access the device to deliver the therapy intramuscularly, and that's for clinical development, but also registration. And I've touched on the regulatory support we've seen over this quarter from various regulatory agencies. And putting all that together, what we're aiming for in parallel with the development in the clinic is towards partnering for seamless registration and commercialization. We get all this in place, then at the moment we are scheduling that we could well reach commercialization late in 2029. Let me show you and remind many of you about the science behind what we're doing. And then I'd like to hand over to Nermeen. iSCIB1+ is a DNA ImmunoBody, it has a very novel mechanism. It's delivered to patients as a plasma DNA, a DNA molecule, I've mentioned that. And we've created over time, two products, a first-gen product, SCIB1, and a second-gen product, iSCIB1+. Both contain epitopes from two melanin -- two proteins involved in the production of melanin: gp100 and TRP-2. The mechanism of action is based on the modified antibody that is encoded by the DNA, and that relates to targeting the CD64 receptor on activated dendritic cells. And there's, in fact, a dual mechanism here of both direct and indirect Fc targeting of the CD64 on activated dendritic cells. This leads to more potent T cells. iSCIB1+ was designed to target a broader repertoire of HLA types that are listed here. This list of HLA epitopes was designed, epitopes was designed such that we would work in 100% of melanoma patients. And what we did in Cohort 3 and Cohort 4 was to screen patients for HLA type before they came on to the study and we've been able to identify from our work that in fact, the A1 HLA type, which represents about 20% of patients was not as efficacious as the other HLA types. And that's why we now are focused on a set of HLA types that represent 80% of the advanced melanoma population. We have shown that SCIB ImmunoBody works as a monotherapy, some early work that Lindy and our colleagues did as a monotherapy, we've seen activity. But now we're synergizing with the checkpoint blockade to modify the tumor microenvironment and create really potent T cells. And you could say, what's the synergy here? Well, the checkpoint blockade is effectively taking the brakes off the immune system, and iSCIB1+ provides the gas and the accelerator to the immune system. Now let me stop here, and I'd like to hand over to Nermeen, to talk you through the data update.

Thank you, Phil. So, let me now start by giving you the update for our SCOPE study data. And I think many of you are aware, Scope is a Phase II open label multi-cohort translational study, which we've been conducting at 16 U.K. clinical trial sites and has enrolled over 100 patients. And as you've heard, the objective of the study was to help us inform in a risk-mitigated and precise way of follow-on Phase III registration study. And again, as Phil has shared, I'm delighted to say that we've achieved that objective. But now let me walk you through the study and the -- and remind you of the study design. So, we have -- the study population is first line advanced melanoma, in combination with standard of care checkpoint inhibition. These are patients who have histologically confirmed unresectable Stage III or Stage IV disease, the first line, the ECOG Status is 0 or 1. They have at least one measurable lesion per the RECIST 1.1 criteria, and we know the HLA status. We've excluded patients with acral, ocular, and mucosal melanoma, those who have CNS metastases and those who have been exposed to checkpoint inhibition previously in the adjuvant setting in the previous 6 months. In the first 2 of these Cohorts that you see depicted there, we have used our first-generation vaccine, SCIB1. And SCIB1, our first-generation ImmunoBody was designed to work in patients with the restricted HLA haplotype, i.e, A2 only. Whilst Cohorts 3 and 4 have introduced our next-generation vaccine, and I remind you, iSCIB1+ is the ImmunoBody agent that we have decided and are eager to progress into the follow-on Phase III study. In these cohorts, the difference between the cohorts is that in Cohort 4, we've introduced what we call accelerated priming, slightly modified the dosing schedule and introduced and evaluated the intradermal use of the vaccine. For all except 10 patients in Cohort 2, the companion therapy remains the checkpoint blockade, standard of care, ipi/nivo. And apart from seeking to confirm the efficacy of our ImmunoBody agents, we also seek to improve the outcomes that have been reported with standard of care, in particular, the PFS. Now let me walk you through that data. But before I do that, let's look -- and this is important. Let's look at the baseline characteristics of patients in -- who have been given the first-generation vaccine, the second-generation vaccine. And here, we compare them that with the -- if you like, our benchmark, which is Checkmate 067. And as you look at this data, you see that, although there are some differences by and large, the populations are comparable. Notable differences include the difference in the proportion of patients who have BRAF mutated status vis-a-vis the wildtype status. And very importantly, in the SCOPE study, we have 15 patients who received a prior checkpoint inhibition anti-PD-1, while that has not been the case in Checkmate 067. In this slide, we're demonstrating the PFS delta that we've seen in patients who received our second-generation ImmunoBody agent, iSCIB1+, and comparing that to an illustrative only curve of doublet ipi/nivo, which is the standard of care. And you see a very impressive separation and an impressive delta in these PFS curves. And it is this delta that has informed the design of our follow-on Phase III study. It's also important to inform you that we have importantly noted that the PFS outcome with iSCIB1+, our second-generation ImmunoBody agent is superior by approximately 12% on to its predecessor. And this is a reflection of the increased avidity the product has, which is due to the AvidiMab modification made to the iSCIB1+ antibody. So, here what we've done for you is to demonstrate and give you a sense of when we were to -- when we had to compare in the data from our interim readouts to other data that have been reported to give you a sense of the advantage and the delta that we're seeing and why this is exciting for us. So for iSCIB1+, we are reporting at this stage, a 74% PFS at 16 months. For the combined cohort, so these are now 80 patients who have received both the first generation and the second generation ImmunoBody agent, we're reporting a PFS of 60% at 26 months. And then -- and for either of these cohorts, we've not yet reached median PFS. Whilst you see we've already laid out alongside the median PFS that's been reported for the study with LAG-3, for the Project Checkmate 067 and for the standard of care Real World data. And it's for us reassuring and exciting to note that this delta or this difference in PFS is something that we are able to deliver through our ImmunoBody agents in addition to that they enjoy through double checkpoint inhibition. Now this stage, and I'd like to spend some time walking you through this. What we've done here is we've divided or segregated our patients in the SCOPE study with into the important categories, which are believed to be prognostic markers for whether checkpoint for that response to checkpoint inhibition. So these are the ones that we've got here for you, and are the most important ones are the BRAF status, whether the patients have received prior checkpoint inhibition and the PD-L1 status. And you will see here that for each of these categories, there is a benefit in the addition of adding ImmunoBody over checkpoint. And so, here we've got for you the PFS. So we for the BRAF status, the 63% in 21 months versus 70% in the mutated status, similarly, for those who had exposure to checkpoint inhibition and mind you, that is a poor prognostic factor. Patients who have not had prior exposure, they're experiencing a 63% benefit vis-a-vis 49% of those who had prior checkpoint. And similarly, you see that for PD-L1. Though for PD-L1, the difference is perhaps less smart. But it's important to note that when you are to compare the PFS that we are reporting in the line that you see there alongside SCOPE, that PFS remains superior to that reported by Checkmate 067. And for Checkmate 067, what we've reported here is the median PFS of each of these groups. And I remind you that in none of these categories as yet for SCOPE, we've yet arrived at median PFS. So this is reassuring for us that the patient population on which we are determining this delta in PFS is broadly -- can never be exactly, but is broadly comparable to Checkmate 067, and therefore, the correct thing to do to progress our ImmunoBody agent into patient care is to conduct the randomized controlled trial, which is exactly what we want to do and what we're very excited about doing so. And this data set alongside our other data set gives us the confidence that we'll undertake this randomized study in a risk-mitigated manner. This shows you the best overall response rate for the combined population of 80 patients. This is our waterfall chart. We're always delighted to show this. And I highlight a very impressive disease control rate of 81%. And here, you see the spider plots, which plots the -- both the depth and the durability of the response, again, you see for our first-generation and second-generation vaccine, and it's reassuring to see the durable response. And the durable response, we believe, is being driven by the memory T cell response that is being -- that has been induced by -- induced and maintained by our ImmunoBody agent. Now let me walk you through the safety data. And for this interim safety data, we've included all 133 patients who had -- who received a single dose of our ImmunoBody agent. And it's fair and we conclude that it has -- the both SCIB1 and iSCIB1+ are generally safe and well tolerated at the 0.4 to 8-milligram dose. In this chart here, which is a busy chart, but yes, this is in the therapy with checkpoint inhibition does involve a lot of adverse events. So it's -- I tried to summarize this here for you. The number is the number of events, percentage is the number of patients who've experienced it. And we've categorized these events as to treatment emergent adverse events, those that are Grade 3 or more and serious adverse events. And the important point I'd make is that, if you look at the column related to checkpoint inhibitors, that is similar, that has -- to what that has been previously reported. There's nothing to suggest that the addition of our ImmunoBody agents changes the adverse event profile of checkpoint inhibition. Now if you look at those that were considered to be related to SCIB1 or iSCIB1+, the most important thing to say is that they were all transient. Of those that were less than Grade 3, which were reported in 55% of patients they were mainly elevated liver enzymes, injection site bruising, fatigue, GI, skin and eye disorders, all of which I repeat were transient. If you then -- if you were then to look at the adverse events that were more than or equal to Grade 3 or serious adverse events, all of these were duly related. Our investigators were unable to differentiate whether it was related to ImmunoBody or to checkpoint inhibition. So, on the basis of this, we are confident that the ImmunoBody is well tolerated, and there is no evidence to suggest or any concern about the potentiation of toxicity. Now let me talk you through some important translational data. And this data is very important, because this data underpins our confidence in the mechanism of action and therefore, in the efficacy signals that I've been sharing with you. So the first thing to say is that if you -- 72% of our patients, as you can see on the chart, 72% of the patients have responded to both epitopes, TRP-2 and gp100. And it is this dual response that reduces the risk of immune escape. And then, you see on the graph above that to all the 6 peptides there has been a response. And we've charted here the best response from baseline up to very high levels. Then if you look at the number -- the correlation between clinical response and a positive T-cell response, there's a very strong correlation. And ELISpot assays demonstrate that amongst our 61% of our HLA matched patients made a T-cell response. And this increased to 79% amongst the clinical responders. All 6 epitopes -- all 6 of our iSCIB1+ epitopes have generated the CD8 T cell response. And I remind you that is related to the cytotoxic effects of T-cells. And 83% or 10 out of 12 patients with the CD8 response had a clinical response. So this is a very, very satisfying validation of the mechanism of action. So, moving on. So on the back of the efficacy, translational and safety data that I've shown you, you can see why we are excited to move ahead with our Phase III double-blind, randomized, adaptive registrational study. It is this design that we've discussed with the FDA and MHRA and indeed await feedback from the EMA. And on the back of this feedback, we believe that this design is robust and we're eager to progress this. So the target population will remain the same. Our Stage 3, 4 and resectable melanoma, of course, we will go for 80% of the population that match our target HLA haplotypes. The control arm will remain standard of care ipi/nivo. And we would like to randomize initially 450 patients to approximately 233 per arm to receive either iSCIB1+ with ipi/nivo or placebo plus ipi/nivo. Following on from the occurrence of approximately 190 events, we would be in a position to conduct the first analysis. And there, the primary endpoint will be progression-free survival, and that primary endpoint is potentially the registrational endpoint. And the secondary endpoint would be overall survival. There is the -- you see there the stratification factors that are possible. And then the idea is that after that registration analysis, we would continue to follow up the patients so that in total, we would have a follow-up period of 48 months since first patient was in. But that -- how a lot of that follow-up would be following registration. And then the end point for that, the primary end point would be overall survival and the secondary endpoint would be progression-free survival. And it's fair to say that this is being an adaptive design at the first analysis, there is an opportunity, if necessary, to increase the sample size.

Thank you, Nermeen. Let me dive in a little bit deeper to the regulatory strategy, the positive momentum that we have in the conversations that we've held recently with the FDA, MHRA and EMA. And I've summarized here quite a bit of detail of important parameters that were discussed in some of those meetings. Firstly, the Type B end of Phase II meeting with the FDA. One of the key questions that comes up at this stage in these types of conversations is, the dose of the therapy that's going to be used. We had proposed an 8-milligram dose, and that would be delivered intramuscularly. Pleasingly, the FDA have supported that. And that's a tick for a program that the FDA run Project Optimus, which usually requires companies to look at multiple doses, but to date, they've been comfortable with our proposal of an 8-milligram dose. Similarly, they've looked at the data from the SCOPE study and indeed some of the earlier studies and preclinical data and accepted the data -- accepted the study design in outline, as Nermeen just described and the stats plan associated with that and the endpoints. Pleasingly, our CMC manufacturing process also got support that we could move forward potentially with a Phase III study based on the CMC process and the detailed analysis of the product coming out of that manufacturing process. They have requested some additional information about the comparability, how we compare one batch of drug to another batch of drug. We didn't put much detail actually in the material we sent to the FDA. So, we're now filling that out. We have all of the detail and all of the data and we'll add that into the IND. And they also agreed with us that we don't need to do a DART study. DART stands for Development And Reproductive Toxicity study. We don't need to do a toxicity study. And they've accepted a big body of non-clinical and pre-clinical data that we have. And the team has done a herculean job to pull all of that data together to be ready to submit an IND. Given the uncertainty that there has been around, well, it's geopolitical uncertainty these days, but uncertainty with the FDA over the last 12 months. We proposed and took forward a strategy to go to the FDA and to go to MHRA and EMA. So cover the U.S., the U.K. and Europe altogether all at the same time, given the uncertainty that's out there. So in parallel with the FDA conversation, we've had a conversation here locally with the MHRA. And there's good alignment from that conversation and good regarding the parameters that I mentioned earlier, a really good alignment with the MHRA alongside the FDA. And similarly, we propose to meet with the EMA, and that was scheduled for December. The EMA, in fact, asked for the minutes from the FDA and said that they're very much aligned with the FDA. So, we've got good support there. So, I'm pleased with the work that we've done to get all of our data and documentation and the early collaborative conversations with the agencies about a possible Phase III study. We're now in the process of preparing the IND that will be submitted before the end of the year. And along with that, we will also start to ask particularly the FDA questions around, can we get a breakthrough status for this product, given the data that Nermeen has just shared with you and what's the possibility to even get an accelerated approval, which helps our commercialization time line. So, great momentum with the regulators to date. Now let me turn change tracks and turn to the pharma perspectives and pharma conversations. I've mentioned in the past that we take a two-pronged strategy, build towards pharma partnerships. But as you can't always control the timing of those, we also have to have the resource on board to be able to go it alone. But let me say to you, we are leaning very heavily towards partnering the program or working with a partner for the next stage of development, and we have a very broad outreach to the large pharma, but also to mid-caps that are working in oncology and melanoma. And here's some perspectives that have come back from those conversations. In some cases, melanoma is considered to be treated reasonably well. And I touched on that earlier, half the patients do respond, but there's still a big unmet need. Cancer vaccines have had limited success. That's some of the feedback we have from pharma. And then some of the checkpoints like pembrolizumab, ipilimumab, nivolumab are starting to become legacy pipeline for the likes of Merck and BMS, and they will come off patent soon. And that creates both an opportunity, but it also means it influences how companies like that might look at our program. More recently, we've had feedback that our data is starting to look very, very positive. The data that Nermeen just showed you, is starting to really crank up some of those conversations. So, we're getting very positive feedback about the maturity of the data. On the positive side, some of the key things that are important for a pharma or a mid-cap to engage with us is that there is strong data. It is a novel mechanism with a platform that can potentially create other products. We understand very well how our product works mechanistically. And these are all things that really mean a lot to the pharma companies. It is a large unmet need. Remember, melanoma is the fifth largest cancer. And so it's an important revenue stream and product opportunity for quite a number of pharma companies and mid-caps. We have the patient population defined and a market that can be used to select patients. And that's a very, very rare thing in immuno-oncology development programs. And we also have the opportunity to go into earlier disease settings, the resectable setting, what we call the neoadjuvant setting where we could give iSCIB1+ for up to, say, 12 weeks and then the patients go into surgery. And that, as I mentioned to you earlier, is a big market opportunity. And then increasingly, as this data matures, there's an increasing positive view from the discussions we're having with pharma. So we are leaning heavily into these pharma conversations, and they are progressing well. Finally, let me finish off with just a few slides to show you the outlook. We've achieved a lot as we set out in 2025 and in quarter 4 also. In 2026 in quarter 1, we -- sorry, let me go back to quarter 4, 2025. We anticipate, as I mentioned, filing at least our IND by the end of this year and therefore, are aiming to have an IND open during the first quarter of 2026, and we'll also go into other regulatory conversations also. I want to flag here today that I'm moving the timeline to announce data on the Modi renal cohort into the first quarter of 2026. I had signaled to you before that, that would come out in this quarter before the end of the year. But I'm moving it into quarter 1, 2026. And I'm doing that for two reasons. One, the team has -- I've asked the team to heavily focus on pulling together the data and the documentation for the regulatory conversation for iSCIB1+ and it's enormous volume of work and paperwork and that has to be a really core focus for us, because for partnering iSCIB1+ and also for moving it forward, we need to have the regulatory support behind us. So there's been a very strong focus over Q3 and Q4 in that area. And then secondly, Modi is an opportunity based on the pharma conversations that we could potentially partner Modi, if we get the right data. And what I don't want to do to get partnering going on Modi is to drip feed pharma with data because if they see early data and then they're not so supportive, they will walk away and we've lost the discussion. So, I want to make sure we've got the right data set when we announce and when we go out to pharma for Modi that we can really have a proper partner in conversation. So signaling that are moving that milestone into Q1 2026. We have a lot of proactive business development going on, as I mentioned, and the team will be out to a major conference, which kicks off 2026, the JPMorgan conference in San Francisco for partnering discussions also. So let me just summarize that iSCIB1+ is ready for Phase III development in our view. We have a scalable manufacturing in place, a high-quality formulation, long stability and a GMP manufacturing process that is right for late-stage development. We have a needle-free device license and a lot of experience with this device to deliver iSCIB1+ Intramuscular in a painless and convenient way to patients. And our agreement on this device covers the development and commercialization. And then finally, as we finalize the clinical trial designs, we've had good discussions with the U.S. FDA and other regulators, and we will finalize that design shortly and submit our documentation to the regulators. The future development will be determined by what we can do with as a timely development program to move this to patients as quickly as possible. But also, we're very mindful that we want to have shareholder value in mind and build shareholder value as we develop the program forward. I think today, we leave the last word to Heather Shaw. Nermeen and I have just been to the QEII Center to the ESMO IO conference where Heather presented data from the SCOPE study just a couple of hours ago. And she did an amazing job of presenting that data. And as she describes it, the prolonged progression-free survival demonstrated by iSCIB1+ in combination with the checkpoints has the potential to redefine the standard of care. The therapy combination increases both the number of advanced melanoma patients that benefit but also the duration of their clinical benefit as well compared to checkpoint blockade alone. And this represents really an important step forward for patient outcomes. So, we're determined to move this forward, get this product to patients as quickly as possible and build value in turn and arising from that success. Thank you for listening, and we'll open up for questions.

[Operator Instructions] Our first question comes from the line of Julie Simmonds with Panmure Liberum.

Great data there. Excellent. I was just wondering in your discussions with potential partners, have there been any particular pushbacks that you've got? Because you talked about the positives. I was just wondering if there are any negatives that they had.

I think, Julie, I touched on one or two of the pushbacks as you described them there. Cancer vaccines have had limited success to date. And that's one of the questions that pharma do ask us, why do you think you will be successful when others have failed, is one way they put it. And hence, my comment about. We understand our product. We understand the mechanism, our data is maturing nicely. And the synergy with the checkpoint blockade is perhaps the piece that was missing 10 years ago from some of the cancer vaccine studies that were done.

Brilliant. And then, on the manufacturing process, you've obviously sorted -- you've got that in process. Is there going to be -- do you still need to actually manufacture the product for the clinical trial? Or is that now done and you're sort of waiting for the trial to start?

It's a good question, Julie, manufacturing. We have some product that we can kick off the study with, but we were also planning early in '26 to do further manufacturing.

Next question comes from the line of Mike Mitchell with Cavendish.

Just looking forward to the Phase III. You mentioned FDA alignment on PFS as primary endpoint. And I know you're still finalizing the design, but I just wondered what overall survival follow-up is expected? And also just to confirm that you do expect a single pivotal study is going to be sufficient?

Nermeen?

Thank you. So, the primary endpoint at the first analysis, which we expect to be the registration analysis will be PFS with the secondary endpoint being OS. The requirement for overall survival is a demonstrate -- for us to demonstrate that it is not discriminative. So it is not discriminative, but it is rather non-detrimental. And it is -- and it needs to be whilst being a descriptive reading. So it's a descriptive OS that has to be no-detrimental and we would like to and we have committed to demonstrating that readout at 48 months after the last patient is randomized. So, it's a long OS period. And hence, our thinking is that the registration will be on the primary endpoint, which is PFS, and that's an agreement with the scientific adviser received so far with the FDA. And then post registration, we'll continue follow-up to achieve this descriptive non-detrimental OS.

Next question comes from the line of Edward Sham with Singer Capital Markets.

Just two questions from me. So just the first one, so the data looks really exciting, but it's obviously quite technical, and there are a few moving parts to get our heads around, namely the ORR. So I was just wondering, can you give us your view on whether you feel more or less positive now following the updated readout? And then my second question was just around the discontinuation of the intradermal cohort. Has that partnership with the NHS Cancer Vaccine Launch Pad now ended then?

I'm very positive about our overall data set. And importantly, as Nermeen has just said, in the regulatory conversations, the regulator is now very focused on PFS and OS. And our data is very strong there. And our data was also very strong for disease control rate. So not only are we reducing the tumor size in those patients that respond, but we're stabilizing many more patients than the benchmarks. Just with respect to the overall response rate, when you look across quite a number of historic studies and also some of the current studies both companies like ourselves, but also some of the current real-world data sets that are out there. You, in fact, see response rates today in around the 35 to late 40s in the data. So, I'm pleased that we've got a delta on overall response rate. It's perhaps a bit lower than the really early data from the iSCIB1+ plus cohort signaled when a small cohort to date was published. Nermeen, would you like to add anything?

The only thing I'll add is that, ISR data has matured, and we've begun to also collect a lot of translational data. It's become clear to us that the benefit -- the real benefit of the vaccine is when after the T-cell response speaks at week 25. Then there's a maximum durability benefit. And it is this memory and durability benefit that's being reflected in disease control rate and in PFS. And not surprisingly, because of course, this is what's really important to our patients. That's what our regulators want, that will get registration. And in due course, that's exactly what our peers will be looking for as well.

Let me just answer your second question also. We signaled on Tuesday with the press release and a signaling here that we're curtailing Cohort 4, that's primarily to bring focus, conserve resource, but also to accelerate our further development. We've got the data we need from the intramuscular delivery to support moving that forward, and that's, in fact, saved us 6, maybe 12 months' time to be able to make that decision. On top of that, we do have some early T-cell data that has confirmed the accelerated immunization is the right path to take. And so Nermeen has made the decision in the Phase III study to include the accelerated immunization. So, curtailing Cohort 4 really is about focus and conserving resource. We've enjoyed our partnership with the Cancer Vaccine Launch Pad, and we are really hoping in the Phase III that a lot of patients will be recruited in the U.K. and that the Cancer Vaccine Launch Pad will work with us and our partners going forward.

And maybe I could just add that one of our great strengths has been the support and collaboration with our U.K. sites, our U.K. investigators, our U.K. patient groups and of course, the Cancer Vaccine Launch Pad. And it is this strength that will give you like, give us the wind beneath our wings to launch our Phase III study in a very positive way.

Our next question comes from the line of Ed Brounger with Edison Group.

I'm calling on behalf of Jyoti Prakash, our healthcare analyst. I only have one small question, as most of my questions have been answered. But the data looks very encouraging, specifically, the target HLA population in Cohort 3. We were wondering if you're able to share the combined all-comers data for Cohort 3, as reference for comparison with Checkmate 067?

So the way we've looked at the data is that patients who do not have the target HLA type, we call them the mismatch or the non-target population. They serve almost as an internal control, because these are patients where we're very clear that the ImmunoBody agent, SCIB1 or iSCIB1+ would have had no effect. And in that group, there is a significant delta -- in that group, in fact, the ORR is something like 40%. And the PFS is again, a very -- it's much lower. And that to us is, if you like, the baseline rate and the additive clinical benefit we're seeing, that we view as being the additional benefit of the vaccine. The only caveat to what I've said is that by definition, the group that is mismatched is small. So, we've got only 10 patients in that group. So although we have analyzed it, it's too small a group to have -- to get anything more from than a reassuring signal.

And that is all the questions we have on the conference line. We will now address the written questions submitted via the webcast page. I will now hand over to Mary-Ann Chang, Investor Relations to read this out.

A lot of the questions have been answered, which leaves us at the moment with just a couple. Going back to Cohort 4 in the discussion there, Nermeen, how many patients have been recruited to Cohort 4 to date? And will you still publish early data from this cohort as previously scheduled?

So, we've recruited 31 patients to date. And the data is still in a very early stage. We have some T-cell data, the efficacy data, and is yet to come through. And in due course, we'll take a view on the additive value of that data. And if we felt it would be valuable to the academic community, to our patient community, we then take a view on this publication.

Let me perhaps just add a comment here. To me right now publishing any Cohort 4 data will distract the conversations that we're having with pharma. They'll look at that data, and they're very, very good at saying to you, we like what you're doing, guys, but we want to wait, go and get some more data. And if they focus on the Cohort 4 data, then it takes us another 18 months to get good PFS data. So I'm very reluctant at this stage with these conversations going on to share data that distracts the conversations we're having with pharma. As Nermeen said, once the Phase III is up and going, then we may well say, let's publish this data at a conference for the clinical community to see the data.

Great. Okay. Thank you. That makes a lot of sense. And then we have a question about the partnering and funding decision, some of which have been answered. But we'll rephrase what's left a bit to say broadly, Phil, are you able to share any information on partnering versus go it alone? How that might impact development timetables?

How might partnering versus go it alone impact timelines? The short answer to that is, I'm hoping that it won't impact timelines. The reason for accelerating the development based on Cohort 3 and the regulatory conversations was because that information would support the partnering conversations as well as the possibility of raising resource to go it alone. And so, these sorts of things are working in parallel. So overall, I would hope that partnering versus going alone doesn't delay development. And as I said earlier, we want to take a path that does keep shareholder value in mind and maximize both the time, but also the shareholder value return from development of the program.

Great. That brings us to the end of our questions.

Let me just say, thank you for listening. We're excited about what we've shared today, the data that we have shared, the progress that we've made both on the SCOPE study, as well as the regulatory conversations and the partnering conversations that we've been having with Pharma and MidCap. There been a lot going on over this quarter. I do expect we will submit our IND before the end of the year and look forward to engaging further in early January with Pharma and MidCap potential partners at the JPMorgan Conference. So a lot coming up and a lot to do. And then, just let me reiterate that we do have a focus on the Modi program and also on GlyMab Therapeutics. But today, our focus has to be on getting the documentation in place to be able to accelerate the development of iSCIB1+ into a registrational program with a partner and/or go it alone and move it forward to patients. Thank you again for listening.