Good morning and welcome to the Sensei Biotherapeutics virtual KOL event. At this time, all attendees are in a listen-only mode. A question- and- answer session will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Sensei website following the conclusion of the event. I'd now like to turn the call over to John Celebi, President and Chief Executive Officer at Sensei Biotherapeutics. Please go ahead, John.
Thank you very much, Tara, and good morning everyone. Thank you for joining us today. Today marks an important milestone, not just for Sensei Biotherapeutics, but really for the broader field of immuno-oncology. What you'll see in this presentation today represents the first progression-free survival data and the most advanced clinical data to date for any VISTA-targeting antibody in development. Based on the promising data we'll share on today's call, we believe the Solnestretug regimen merits advancement into phase II development. The results point to a clear signal of clinical activity, durability, and tolerability that together suggest a differentiated mechanism of action at work. Finally, and perhaps most exciting, the concept of an all-IO doublet regimen for patients with secondary resistance to checkpoint blockade represents a potentially momentous leap for patients and a tremendous commercial opportunity for the field. I'm going to hand it off to Ron Weitzman and Dr.
Kyriakos Papadopoulos to get into the data. A brief word on forward-looking statements. Let's begin with the science behind Solnestretug. First, VISTA is a member of the B7 family, the same family of proteins as PD1. It's an immune checkpoint receptor that plays a major role in suppressing T cell activation. Unlike PD1 or CTLA4, VISTA is expressed not only on tumor cells but also across the myeloid lineage, giving it a particularly powerful role in maintaining immunosuppression. Importantly, VISTA has been implicated in both primary and secondary resistance to checkpoint blockade. That means it doesn't just have potential for tumors that are PD1-naive; it potentially helps the tumor microenvironment adapt after PD1 failure. Solnestretug was designed to break the resistance selectively within the acidic tumor microenvironment, where it blocks the VISTA-PSGL1 interaction, among others.
The result is a focused reversal of immunosuppression while avoiding the systemic toxicity that plagued earlier VISTA antibodies. In short, this is a highly rational next-generation design that's aimed at unlocking one of the most stubborn mechanisms of checkpoint resistance. Beyond the biology, the commercial opportunity is striking. PD1-targeted therapies, such as Keytruda, Opdivo, Libtayo, and others, are among the highest-grossing drugs in all of medicine, with combined sales exceeding $45 billion annually and still growing. Yet, within that success, secondary resistance remains the rule rather than the exception. VISTA's expression profile spans more cancer types than any other immune checkpoint, meaning its therapeutic potential extends across virtually all major tumor indications.
For context, a safe and effective VISTA-blocking regimen could, over time, play a key role in nearly every tumor type where PD1 is used today, and that's an enormous addressable market and an equally profound opportunity to help patients who currently have nowhere else to turn. The question you might be asking yourselves is, why hasn't this been done before? The short answer is toxicity. The first attempt at a VISTA antibody, run by Johnson & Johnson nearly a decade ago, was halted after just a dozen patients due to severe cytokine release syndrome, including grade 3 CRS. The problem stemmed from broad off-tumor binding and a highly nonlinear PK profile. Essentially, those early antibodies couldn't discriminate between healthy tissue and tumor microenvironment, and that limited their ability to get to pharmacologically relevant dose levels.
The lesson from the first-generation non-selective approaches is clear: VISTA is a powerful immune lever, but only if you can pull it selectively. That is where Solnestretug really shines and where it differentiates itself. Here you can see preclinical data demonstrating pH-selective binding, no detectable signal in peripheral tissues, but strong and rapid accumulation in the tumor itself. This design minimizes off-tumor engagement, providing a cleaner PK profile and a markedly improved potential safety margin. In other words, Solnestretug is the first VISTA-targeted antibody to see the tumor, not the host, and that selectivity is what allowed us to reach pharmacologically relevant doses and advance into the clinic with confidence. To take you through the clinical data, I'm going to hand it off to Ron Weitzman, Sensei's Chief Medical Officer, and Dr. Kyriakos Papadopoulos, Co-Director of Clinical Research at START and a Principal Investigator on this clinical study. Ron?
Thanks, John. Again, Ron Weitzman here. I'm a medical oncologist and the Chief Medical Officer with Sensei. It's a pleasure to share these data with you again, and you can advance to the next slide. Thanks. As I think you're all aware, Sensei has previously presented results on the phase I dose escalation portion of the study at ASCO 2024, over a year ago last June. In that presentation, we purely focused on the dose escalation component of the study, and you can see the outline of that, and this is just a refresher. We started at the same dose of 0.3 mg/kg that J& J eventually had to stop at due to dose-limiting cytokine release syndrome, and quickly, over seven months, efficiently enrolled and reached the top dose level of 15 mg/kg without any dose-limiting toxicity observed along the way as a monotherapy.
Trailing right behind that, we had shared data on our combination dose escalation with Regeneron cemiplimab. There you can see that in green below, where we started at 3 mg/kg and again reached and completed the top dose of 15 mg/kg without dose-limiting toxicity. In this presentation, over a year ago, we demonstrated the ability to reach those doses, which were an order of magnitude greater than what had previously been reached with non-pH-selective or conditionally active VISTA-targeting antibodies. In this dataset, we demonstrated a lack of severe cytokine release syndrome, an excellent PK profile that departed from what had previously been demonstrated with the non-selective VISTA-targeting antibodies, and we were now finally able to reach pharmacologically relevant dose levels of our agent and be in a position to test the clinical hypothesis around the VISTA approach. Next slide. Great. The monotherapy and combination was well tolerated.
It had a commercially acceptable and potentially best-in-class PK profile. This became the first and only agent to be dosed, as I mentioned, at pharmacologically relevant dose levels. Upon studying the single agent and the combination in escalation, where pretty well 90% of the tumor types were what we would regard as cold tumors, our decision was to pivot at that point to an expansion cohort of just over 40 patients that would now take patients who had received and failed a prior PD1 inhibitor, tumor types basically that could be regarded or that are regarded as hotter tumor types. That's exactly what our results focused on at this past ESMO meeting. On the right there, you can see the PK profile of the drug.
Unlike prior non-conditionally active agents that had half-lives measured in just hours, similar to a small molecule, we were able to demonstrate a half-life in the thousands of hours. Cytokine release syndrome was no longer an issue. All the events observed were grade one, and as I mentioned, no dose-limiting toxicities were observed. Next slide. I will now hand this over to our investigator, Dr. Kyriakos Papadopoulos at START. Kyri, all yours.
Thank you. I'm Kyriakos Papadopoulos, a Medical Oncologist at START, San Antonio, and one of the Principal Investigators in the study. Next slide. As mentioned, the focus was on hot tumors in expansion cohorts. We did explore colorectal cancer, which is traditionally a cold tumor, both in monotherapy and combination, but did not see any activity signal there. The focus being on hot tumors, which essentially were tumors with an indication for immunotherapy, and patients had previously progressed on or within 12 weeks of their last treatment with an immunotherapy. There was obviously encouraging activity, which I'll review now. Next slide. The expansion cohort of the basket of hot tumors essentially enrolled 44 patients who received a combination of Solnestretug in alternating doses of 3 mg/kg or 15 mg/kg. Of these 44 patients, the 3 mg/kg cohort was 41%, and similarly, 59% of patients received 15 mg.
Patients who were ongoing at the time of data cut included 11 patients, and most patients discontinued for disease progression. Next slide. In terms of the demographics of the 44 patients, the majority were male. They had a relatively good performance status. 41 of 44 patients, that's 93% of patients, had received prior immunotherapy at some time in their treatment. The majority of patients who were enrolled in the study were head and neck and non-small cell lung cancer and melanoma. Next slide. In terms of safety, the profile at the treatment emergent adverse events were consistent with that which one would expect with single-agent cemiplimab, so there was no signal of any significant increased toxicities.
Of interest, particularly because of the VISTA history, was that only one patient who was treated at the 15 mg/kg dose level had a low-grade cytokine release syndrome, which was easily manageable, and there were no grade 3 or 4 AEs attributable to Solnestretug. Next slide. In terms of the PK profile, in combination with cemiplimab, was very consistent with the single-agent PK profiles, both at the 3 mg and 15 mg cohort. The PK was supportive of three-weekly dosing, and although there was some increase with repeat dosing as expected, there was really no noticeable accumulation of drug despite prolonged dosing in these patients. Next slide. In terms of efficacy, and this is the 41 patients who had previously been treated with immunotherapy, this plot showed prolonged durable benefit with stable disease in patients, and some patients also had objective RECIST responses at the time of cutoff, as mentioned.
24% of patients were still on treatment, and most significantly, the six-month progression-free survival rate was 37% for these patients. Next slide. This waterfall plot illustrates the RECIST responses in the 35 patients who had measurable disease for evaluation and illustrates the one complete response and four partial responses obtained, but also clinically relevant reduction in tumor burden in a number of other patients with the variable tumor types. Next slide. In more detail for the respondents, for those that previously received PD1 therapy, there were two Merkel cell carcinoma patients, an MSI-high colorectal cancer patient, and then head and neck and esophageal cancer patients. Of note for these patients is that many of them had delayed onset of response and, in addition, a quite clinically relevant duration of response.
In a patient who was PD-L1 naive and non-small cell lung cancer patient with low PD1 expression, they also had late onset of response with a good duration of response as compared to what might be expected with single-agent and non-small cell lung cancer. Next slide. The analysis of the two dosing cohorts showed that for patients receiving 15 mg/kg, the six-month progression-free survival was almost 50%, and it's in this cohort that the five PD1 previously treated patients who had a response was found. Obviously, identifying this as the clinically relevant and active dose moving forward.
When compared to historical benchmarks for PD1 refractory settings, and obviously taking into account the caution of cross-study reference, the 15 mg/kg six-month progression-free survival was encouraging in the context of other populations, including second-line patients who had previously had PD1 therapy with non-small cell lung cancer receiving chemotherapy, but also for other IO combination therapies. Next slide. Just to illustrate two of the respondents, the patient who previously had had multiple PD1 inhibitor exposure with Merkel cell carcinoma had an excellent response with a duration of 12 weeks of 45% decrease in their tumor burden and have sustained their response at 36 weeks without toxicity before progressing.
In terms of the patient who had not had previous PD1 exposure, the non-small cell lung cancer patient who had low PDL1 expression, this patient experienced stable disease and then converted to partial response at 54 weeks, again emphasizing the late duration at which response occurred, which is atypical for PD1 therapy, but something that we've seen occurring in our patients. Next slide. I think, Ron, you were going to discuss this.
Actually, I think I'm going to give this to John.
Thank you, Ron. As you can see here, we have ongoing clinical biomarker data that supports this concept of a dose-dependent type of response we've seen with the Solnestretug regimen. Just to zoom out for a second, all six responses that we saw on this study were at the 15 mg/kg dose. The PFS6 data was double at 15 mg/kg what it was at 3 mg/kg. As you can see here, when we measure terminally differentiated CD8-positive T cells, a subset called TMRAs, we also see a difference between the 15 mg versus 3 mg/kg dose. CD8 TMRAs are an important subset of T cells that are highly toxic, terminally differentiated, and associated with immune activation and tumor reactive activity. Next slide. Okay. Ron, I'm going to hand it back to you.
Thank you, John. Phase I conclusions, the combination that you've just heard about in the hot tumor PD1-resistant population, we feel clearly demonstrates clinical activity in this population, and the statement is predicated on the fact that we saw durable clinical responses observed with a unique pattern of late-onset response in four out of the five patients. We also have a very encouraging overall rate of PFS6 of 37% in all patients. The data suggests that 15 mg/kg may have superior clinical activity over the lower dose tested of 3 mg/kg. All five responders were at this dose. The PFS6 of 50% at this dose is really encouraging. All the CRS events, all of which were grade 1 severity, occurred at this dose, with none occurring at the lower dose. In totality, we believe that the 15 mg/kg dose is a superior dose.
As perhaps a point of irony, having studied the 3 mg/kg dose in an early attempt to begin to try and address Project Optimist may have unintentionally diluted the efficacy signal somewhat by dosing just under half of the patients with what now appears to be a less efficacious dose of 3 mg/kg. We feel, within the limits of cross-trial comparison, of course, that the data compare favorably to the historical benchmarks that we listed in an earlier slide. We also feel that the combination regimen shows more than acceptable safety and tolerability profile. The treatment emergent adverse event profile does not appear different than that of single-agent cemiplimab, and the CRS events were rare and low grade. That would be in a population of patients who did not receive prophylaxis for CRS, and of course, no salvaged tocilizumab, for instance, was needed.
This was a really mild event when it occurred. The combination with cemiplimab offers potential for a generally well-tolerated all-IO doublet regimen, where both agents may be administered until disease progression, which isn't the case, of course, with doublets such as ipilimumab and nivolumab, where the ipilimumab needs to be capped typically after four cycles maximum. Next slide. The phase II strategy is rooted in the key observations made with the combination in the PD1-responsive cohort, where I just covered the results in the prior slide, so I won't repeat that for the sake of time. The basic assumptions incorporated into phase II planning are as follows: the highest level of activity appears to be in the hottest tumor settings, hence phase II will focus on such settings.
The level of activity observed with the combination may approximate the activity seen with IPI/NIVO doublet without the severe toxicity associated with that doublet. The late-onset responses and the durable stable disease suggest progression-free survival and possibly overall survival as an appropriate endpoint going forward. The indication selection balances both the large commercial opportunity, specifically non-small cell lung cancer, and a faster-to-market strategy, which would use a single-arm approach, and that would be in the Merkel cell carcinoma setting. Next slide. The phase II plan, as it stands now, pre-engagement of FDA, would be based or anchored in a two-study approach. The first study on the left is planned as a randomized study in a large indication of non-small cell lung cancer.
Here, we would take the combination at the top dose of 15 mg/kg in combination with an anti-PD1 agent and compare against investigator's choice chemotherapy, such as docetaxel or alimta. This would be in the second-line setting of non-small cell lung cancer patients, all of whom would have received and failed a prior anti-PD1-based regimen with or without chemotherapy. The idea here would be to utilize a sample size of around 80 patients. The phase II objectives would be the primary objective would be an endpoint would be progression-free survival, and the secondary endpoints would be based on response rate, duration of response, and overall survival, and of course, safety. This, we believe, would establish a clear and definitive signal in a commercially attractive indication. On the right-hand side is our faster-to-market strategy, which would utilize a single-arm approach.
Here, the combination would, of course, use the 15 mg/kg dose with an anti-PD1 agent. The population would be Merkel cell carcinoma patients, all of whom would have received and failed a prior PD1 therapy. The initial focus would be in 20 patients, and if we saw at least six responses or 30% overall response rate per resist or greater, we would expand this to a total of 100 patients. Primary objectives would be efficacy. The primary endpoint would be overall response rate, and the secondary endpoints would be progression-free survival, duration of response, and overall survival, and of course, safety. Our intention would be to pursue an accelerated approval in the PD1-resistant population, and if we were successful there with a robust overall response rate, we could consider breakthrough designation as a potential goal as well to speed things up. We can go to the next slide. Great, b ack to John.
Thank you, Ron. Before we wrap up today's portion of the call, I just want to quickly review our accomplishments to date and what we expect looking ahead. As you can see here, we've moved fairly rapidly from the early stages of clinical development, where we were dose-escalating Solnestretug, both in monotherapy and combination, to where we are today. You can do that when your regimen is well tolerated. Looking ahead, we plan to initiate phase II studies in early 2026. We believe we will be in position to have interim analyses sometime in 2027, with the goal of wrapping up both of these phase II studies for enrollment and have top-line data available in 2028. Go to the next slide, which is our last slide. Here, I'll hand it back to Tara for the Q&A portion of our call today.
Great. Thanks, John. At this time, we'll be conducting a question-and-answer session with our speakers. To the audience on the webcast, please use the written text box at the bottom of your webcast player to ask a question. Please hold for a brief moment. Our first question comes from Sudan Loganathan at Stephens. Please go ahead, Sudan.
Hi, John and Dr. Papadopoulos. Thank you for having me, and congrats, John and Sensei team, for achieving this great milestone for Sensei Bio and for the asset Solnestretug. My first question is, you know, when initially looking at the pH-conditionally active mechanism and the VISTA targeting, there was a theoretical hypothesis that Solnestretug could help convert cold to hot tumors. Despite that, it's great to see the responses that you're getting with the very tolerable cytokine release syndrome and broader safety profile in the hot tumor population. Between Solnestretug and cemiplimab, are there any biomarker studies or any mechanisms of action questions left uncovered or unknown that could be a meaningful secondary endpoint built into the phase II, or maybe any additional look at the phase I data that can help elucidate the benefits of this combination? I got some follow-ups.
Sure. Yeah, I can take an initial run at that one, and Ron, I'd invite you or Dr. Papadopoulos to comment as well. Sudan, first of all, I'd say that we are still in the middle stages of collecting all of our biomarker information. You saw the early data that we shared with you today regarding the CD8-positive TMRAs, but over the coming weeks and months, as we continue to receive new clinical biomarker data and analyze that data, we will continue to keep those data in mind as we further define our patient population, etc . The second thing I'd say is that we have not yet had a chance to fully explore Solnestretug as monotherapy in hot tumors. That's not unusual in today's world where PD1 therapies are approved in many different front-line settings. Therefore, patients receive PD1 as their first therapy right away.
Therefore, there just aren't that many PD1 naive patients available to test in early-stage clinical studies. However, that does begin to change as you advance into phase II development. You establish clear clinical proof of concept. You can then begin to address that as monotherapy in PD1 naive settings more easily. With regard to cold tumors, I think that was the first part of your question. Yes, we have preclinical models suggesting that the regimen does have potential in cold tumor settings, and that's still possible based on potential dosing or dose regimens, etc . In this early stage of clinical development where we tested the regimen in microsatellite stable cold tumors, which are the coldest of the cold tumors, we did not see a clinical signal of activity.
The way to think about our phase II studies is that this is a starting point for what could be a very broad set of studies across certainly hot tumors and possibly, as we look into alternate settings in cold tumors in the future.
Great job. Thank you, John. That kind of leads perfectly into my second question that I had. You're mentioning the intent to initiate a single-arm study for the MCCN indication. Maybe even from Dr. Papadopoulos, can you elaborate more on what is the current available treatment for the PD1-resistant MCC patients? If a single-arm trial would be sufficient for like an accelerated approval track, what other phase II clinical trial options are out there for both PD1-resistant non-small cell lung cancer and MCC that could be kind of competing against, that you could be competing against to get some enrollment as you go into the phase II?
Thanks for that question. Yes, there are several combinations that people are looking at in that setting. Traditionally, patients have been treated with combination IO with approved agents, and as mentioned, particularly with the CTR4 combinations. In this population, it's been very difficult for patients to tolerate that therapy. Additionally, most of these patients have undergone chemotherapy combinations with IO as attempts at salvage. There really is no effective standard for this population that will meet the needs for the majority of patients. Having a regimen that is well tolerated, that is showing at least some promising activity, I think certainly has the advantage there in terms of tolerability for this population of patients who are often elderly and have a lot of other comorbidities.
Yeah, thanks, Kyri. Ron here, Ron Weitzman here. Just to address the question about the Merkel cell study design, I think you were getting at, you know, it's a combination single-arm. Obviously, this is before we've gone to FDA and gotten their feedback, and there's a very legitimate question to ask. Can you do a combination of what appears to be two active agents in a single-arm setting and be successful? We wouldn't be the first to do that, number one. Number two, there is the legitimate question about composition of component and what role is, for instance, the co-administered PD1 playing and what role is the single agent VISTA targeting agent playing here.
If FDA came back and said, "Actually, please show us a little bit of data with a single agent," we could always dedicate 10 or so patients at a minimum to the single agent in the hot tumor setting, and if that looks promising, we'd continue it. If it doesn't, we'd shut it down and rely on the combination. The point is, though, that we do have about 28 patients' worth of monotherapy data, much of it, well, almost all of it in cold tumor settings, and it remains to be seen whether FDA accepts that as sufficient data in terms of composition of component. Regardless, we're ready to respond to FDA depending on their feedback.
Got it. Thank you, Ron and Dr. Papadopoulos. Lastly, I just want to squeeze this last one in. It looks like you had a reasonably good response in the MSI-high CRC patient that you also showcased. Was the competitive market in the MSI-high CRC market one of the reasons for not pursuing the indication into phase II, or are there other reasons? Although it seems like you're taking a shot at the non-small cell lung cancer population that is considered highly competitive, it would be great to get your thoughts, either from John, Ron, or Dr. Papadopoulos, just on the company's direction, or even the reasoning behind specifically the Merkel cell carcinoma or the PD1-resistant non-small cell lung cancer opportunities going forward and how that sets up the company.
Ron, do you want to take that?
Yeah, sure.
I'll chime in.
Yeah. I mean, in the spirit of candor, what we've done here is leverage, to some extent, the experience of other immuno-oncology agents that are approved today. In other words, there's, you could argue, four classes. There's PD1, PDL1. Some would lump those into one class, but they are distinct in some regards. Of course, there's LAG3 and CTLA4. I think one of the emerging themes across all four of these classes is that all of these classes seem to work and not work in similar settings. We believe, at least based on our emerging data, that we may fall into that, the difference being that there's only one VISTA agent targeting agent at this point, at this stage, and we're combinable in many, many settings across many different agents. That's obvious, but I'll say it anyways. Why did we pick Merkel cell over MSI-high?
We could have easily looked at MSI-high instead. It'd be great to have looked at both, but in a resource-constrained environment, we looked at the, we chose the indication where we saw the greatest number of responses, and there we saw two out of three patients with very nice durable responses, and even the third patient that didn't respond was on for quite some time. That, to be, that's the basis for why we picked Merkel, but it could easily have been MSI-high colon or MSI-high solid tumors. Why did we pick lung cancer? Again, it's commercially attractive. Yes, it's competitive. All the others are pretty competitive too, and it also happens to be a pretty hot tumor type, so that's basically the basis of picking that. Again, leveraging the prior IO experience that we're all aware of is a key component in that. I'll pause there.
Got it. Thanks again for all the questions, all the answers here, and congrats on the conviction you had on Solnestretug and seeing it through to have this kind of best-in-class outcome. Great to see all this. Thanks.
Thanks for the question, Sudan. Our next question comes from Matt Keller at H.C. Wainwright. Please go ahead, Matt.
Hey, everyone. Good morning. Congrats on the data, and thanks for taking our questions. Just two quick ones for you. The first one is, I was wondering if you have any additional updates on the response data that you can maybe comment on since the data cutoff that occurred, I think, in maybe September? The safety profile looks clean, but I was wondering if there's any other notable safety signals, any other anecdotes that we should be aware of? Thank you.
Would you like me to take that, John?
Yes, please, Ron.
Sure. Yeah, on the safety signal, again, within the limits of our 98-patient overall patient population across dose escalation and cohort expansion, I would say that the safety signal truly is excellent. I mean, the only, and I don't want to sound hyperbolic here, but the only sort of class-related adverse event, perhaps unique to the VISTA component, appears to be low-grade cytokine release syndrome. Besides that, it's hard for me to say that we've altered the single-agent safety profile of the co-administered cemiplimab. It's also hard for me to say that we've worsened any known safety events that you would otherwise expect to see with cemiplimab. It truly is a very well-tolerated agent, and you know, one of the patients, our longest-going patient, I just want to point this out, beyond week 72, is still getting the doublet together.
That's very different than how you give the other very active all-IO doublet regimen of ipilimumab and nivolumab. You have to cap early on the dose of the IPI. I'm sorry, the first part of your question was, I think I addressed the latter part, safety.
Yeah, no, the first question was, I wonder if you guys could comment. I'm trying to get kind of the durability of response or if any of the responses have changed since the data cutoff.
Oh.
Do you have any additional updates, anything you can share with us since the data cutoff?
Sure. Yeah, what's notable here is the late onset of the responses. I think, across all, we have six responses. Five of them are PD1 pretreated. One of them is a lung cancer patient. That was the bottom row on one of the tables that Dr. Papadopoulos shared. That patient had very low PDL1 expression, so the referring oncologist had not used an IO agent or a PD1 agent in their front-line regimen. They came on, and they were not expected to have a response or at least had a lower likelihood of response. They, after 54 weeks, had a response, which is so unusual. IO agents, when they, the median time to response with PD1 agents in the front-line lung cancer setting is roughly 2.2 months, and here we see it after a year.
The lateness of the response is unusual, and this follows a period of prolonged disease stabilization. Of course, four out of those six responders had late-onset responses, which is in line with that. One of the notable observations in the second Merkel cell patient on that table was that they had prior ipi/nivo prior to coming on to our study, and their best overall response there was stable disease, then came on to our study and had what looks like a deeper response, and they actually had a PR. That was interesting. We have a host of patients that are still ongoing that have tumor shrinkage but short of a response. It's entirely possible that some of those patients that remain ongoing will eventually convert to a response, but they haven't yet.
I've just told you about how we're seeing a pattern of late-onset response, so I would say it's entirely possible. That's what I have to say about our responders.
Yeah, great. Super interesting. Thanks again for taking our questions, and congrats again.
Thank you. Great question.
Thanks for the questions, Matt. We have a few questions from the webcast. The first one is, how much will the phase II trial cost?
I'll take that one, Tara. Thank you. With regard to that, what I would say is that, as has been noted on the call so far, the phase II plan is subject to FDA feedback, among other things. We are not prepared to comment on specific costs today until we have a fixed plan in place. Once that meeting takes place and we're able to put in place a clear clinical protocol for these two studies, perhaps we can elaborate further.
Great. Thanks, John. It looks like our final question. You mentioned potential breakthrough therapy and orphan drug designation for Merkel cell carcinoma. Can you please elaborate on where those discussions with the FDA stand and whether FastTrack or any other designation request has already been requested?
I think it's a good, you know, the last question was a good segue to this. We are in the process of coordinating with the agency a meeting to an end-of-phase I meeting. The purpose of that meeting is really to set the design for the phase II studies and, of course, review the data to date. We believe this is entirely possible, you know, some sort of special designation for these studies in Merkel cell carcinoma, but we don't have a clear answer for you today. The first priority is really to set the design of the phase II studies.
Great. Thanks, John. It looks like that's all the questions we had, so I'll turn it back to you for closing remarks.
Thank you, Tara. I think just in closing, as we step back, what we've seen today marks a milestone for the VISTA field and for immuno-oncology more broadly. Solnestretug has done something here that no other anti-VISTA antibody has achieved. It's reached a pharmacologically active dose and safely. It's demonstrated durable disease control, and it's generated the first-ever progression-free survival data in PD1-resistant tumors. These results give us confidence that this mechanism is real, that VISTA can be drugged, and that Solnestretug may offer a new therapeutic path for patients who've exhausted existing immunotherapies. With these encouraging signals, we are preparing to move into phase II, expanding into tumor types where the biology is strongest and the unmet need is greatest.
The idea of an all-IO doublet regimen for patients who failed prior IO therapy was, until recently, a little more than a dream, but today we can begin to see its outlines taking shape. Thank you to the investigators, the patients, the families who placed their trust in this trial and in Solnestretug, and also to our team for their creativity, rigor, and perseverance. We believe Solnestretug represents not just a scientific advance, but the beginning of a new chapter, and it's one that redefines what's possible for patients with secondary resistance to immunotherapy. Thank you.