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spk10: Hi, and welcome to the Surface Oncology Clinical Update for SRF388 and SRF617. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Jessica Fees, Chief Financial Officer at Surface Oncology. Please go ahead.
spk13: Thank you for joining today's clinical study update webcast. My name is Jessica Fees, and I am the Chief Financial Officer at Surface Oncology. With me on the webcast are Rob Ross, Chief Executive Officer, and Allison O'Neill, Chief Medical Officer. Please note that this call is being webcast live and will be archived on the Investors and Media section of the Surface Oncology website. Before we begin, a few forward-looking statements. This presentation has been prepared by Surface Oncology and includes certain forward-looking information within the meaning of the Private Securities Litigation Reform Act of 1995. The statements made in this presentation speak only as of the date hereof, and any forward-looking statements contained herein are based on assumptions that surface oncology believes to be reasonable as of this date. Surface oncology undertakes no obligation to update these statements as a result of new information or future events. I now turn the call over to Rob.
spk04: Thank you, and welcome, everyone. We are very pleased to be able to share today clinical updates on both our lead clinical programs, SRF388, and SRF617. Both are immuno-oncology antibodies directed at novel targets meant to activate the immune system to kill tumor cells and ultimately help patients. We are proud of the fact that, to our knowledge, we are the first to present clinical data on molecules targeting either IL-27 or CD39. The headline today, is that with SRF388, our anti-IL27 antibody, we have seen clear evidence of monotherapy activity in the form of a confirmed partial response in a patient with highly treatment refractory lung cancer. With any first-in-class agent in immuno-oncology, it can be a struggle to prove that the pathway you are targeting actually matters in people with cancer. Here we have clear evidence that, at least for this patient, not only does IL27 matter, but if you inhibited IL-27 by itself, that is enough to stimulate a significant anti-tumor response. Moreover, the drug is well-tolerated, the recommended Phase II dose has been selected, and expansion cohorts are actively enrolling. We can also announce today that we have entered into a clinical agreement with Roche to begin a trial in first-line advanced liver cancer, combining SRF388 with atezolizumab and bevacizumab, the standard of care for these patients. SRF617, our anti-CD39 antibody, has been similarly well tolerated, and we are currently at dose levels that we expect are biologically active. We have opened our combination arms in that trial and, to date, have seen a partial response in a patient with second-line pancreatic cancer treated with SRF617 along with chemotherapy. Without further delay, I'll let Allison O'Neill, our chief medical officer, walk you through the details of the clinical data on both programs. Allison? Thank you, Rob, and good morning, everyone.
spk12: We will turn to SRF388 first. IL-27 is a highly immunosuppressive cytokine that plays physiologic roles in controlling chronic infections and immunotolerance to cancer. SRF388 is a first-in-class IL-27 antibody that blocks the cytokine from binding to its receptor, as depicted in the graphic on the right. This blockade results in immune activation in the tumor microenvironment and decreased tumor growth, as observed in multiple preclinical models. Multiple internal and independent sources have shown evidence that there is IL-27 pathway activation in both the patecellular and renal cell carcinoma, and high circulating levels of EBI-3, one of the subunits of IL-27, can be associated with inferior outcomes in both. Additionally, a recent publication evaluating single-cell RNA-seq data has demonstrated that in non-small-cell lung cancers that are progressing, IL-27 is upregulated in myeloid immune cells. These data suggest that IL-27 upregulation may be important in refractory lung cancer, and treatment with SRF388 might have an important clinical effect in this disease. Next, we will discuss the ongoing Phase I study of SRF388. which is a first-in-human study to evaluate safety, tolerability, and efficacy in patients with advanced solid tumors refractory to at least one standard therapy. Before diving into the data, please take note of the schema of the SRF388-101 study design on slide 6. Part A on the left of the slide depicts dose escalation of SRF388 as a monotherapy, and I'll review the results of this portion of the study in a few moments. On the right, Part B includes the monotherapy expansions that we have just opened for patients with advanced renal cell cancer, or RCC, and hepatocellular carcinoma, or HCC, as well as an exploration of SRF388 when used in combination with pembrolizumab in patients with advanced treatment refractory clear cell RCC and HCC. Today, we'll focus on the results of the Part A dose escalation component. The study's primary endpoints were rate of drug-limiting toxicity, safety, and tolerability, with the overarching objective of determining the recommended phase 2 dose, or RP2D. SRF388 was administered intravenously every four weeks using an accelerated design for the first three dose levels, followed by a standard 3 plus 3 design. Slide 7 presents the key baseline characteristics of the 21 patients enrolled in the dose escalation portion of the study as of the April 16, 2021 data cutoff date. The population was predominantly female with ECOG performance status of one. This is a heavily pretreated population with over half receiving four or more prior lines of therapy and 80% having received prior PD-1 pathway blockade. Turning to slide eight to focus on the safety and tolerability data. SRF388 was well tolerated by all patients at all doses investigated to date with no observed dose-limiting toxicities. 15 of the 21 patients, or 71%, experienced a treatment-emergent adverse event, but these were generally low-grade. Fatigue was the most common, experienced by two patients. There were no grade 3 or greater treatment-related adverse events, and no treatment discontinuations attributed to SRF388. The swimmer's plot on slide 9 shows the patient's time on study and resist response grouped by starting dose. which is denoted by different lane cohorts. From lowest starting dose at the bottom, ascending to the highest dose level tested to date of 10 mg per kg. Disease assessment was performed at week 8 and then every 12 weeks. We are encouraged by the fact that a number of patients remained on study long enough to be able to escalate to higher doses, as depicted by the changing of the lane color at the time of dose increase. In addition, one patient with non-small cell lung cancer who was treated at 10 mg per kg experienced a rapid partial response. This was evident at the first response assessment at eight weeks and then confirmed at 12 weeks, as shown inside the red oval. We will share more details on this particular patient in a moment. Slide 10 provides a summary of responses to treatment in the evaluable patient population. The evaluable analysis set included all patients with measurable disease at baseline who received at least one dose of SRF388 at any dose level and had at least one post-baseline response assessment, or who discontinued study treatment within six weeks of their first dose. 18 patients met these criteria. The table on the left shows that in addition to the patient who had a confirmed partial response, 33% of patients, or six out of the group of 18, experienced clinical benefit in the form of disease stabilization, and five of those six had disease control persisting beyond 16 weeks. The waterfall plot depicts the best percentage change in the target lesions from baseline. You will notice the patient with non-small cell lung cancer with a 66% decrease in tumor size and the patient with pancreatic cancer who also experienced tumor shrinkage but eventually developed a new lesion. Turning to slide 11, we present images from a 64-year-old man with squamous cell non-small cell lung cancer with metastases to the mediastinal nodes, lung, and pleura. This patient was enrolled at the recommended Phase II dose of 10 mg per kg. Before walking through the images, a little background about this patient's cancer. The patient had treatment refractory disease, having progressed on three prior regimens, including chemotherapy and a PD-1 blockade prior to study entry. He had metastatic progression less than four months from completion of adjuvant cisplatin-based therapy and no response to subsequent chemotherapy for metastatic disease, including a pembrolizumab combination. It should be noted that the patient was progressively symptomatic prior to the initiation of SRF388 dosing. Target lesions are the medium gray color mediastinal nodes indicated by the red arrows. The CT images show shrinkage in the size of this patient's two target lesions from baseline, which was just prior to treatment with SRF388, to the first imaging evaluation at eight weeks, and then further shrinkage on the confirmation scan at 12 weeks. After two cycles of SRF388, this patient experienced a partial response with 42% tumor shrinkage in both mediastinal node target lesions. He also had significant improvement in his dyspnea. After three cycles, confirmatory scans demonstrated a 66% decrease in his target lesions. We're very encouraged by this confirmed response to 388 monotherapy, and the patient remains on study. Now on to the PK analysis. We observed that the pharmacokinetics of SRF388 are linear and dose proportional, with steady state achieved by the third cycle. The estimated half-life is 12 days, with no evidence of anti-drug antibody development to date. Our primary pharmacodynamic marker was inhibition of downstream phosphostat signaling in whole blood. We observed that complete inhibition was maintained through trough at dose levels of 0.3 mg per kg and higher. In conclusion, these results from the SRF388-101 study support further evaluation of SRF388 for the treatment of cancer, both as a monotherapy and in combination. We observed promising single-agent activity of this immuno-oncology agent in a heavily pretreated population, including a confirmed partial response in a patient who had not responded to three prior standard therapies, including PD-1 blockade, as well as evidence of disease stabilization in multiple patients. SRF388 was well tolerated by patients in the study at all doses tested to date, and based on the data we've discussed here, we've confirmed a recommended Phase II dose of 10 mg per kg and begun to enroll expansion cohorts. We look forward to continuing to evaluate SRF388 with an initial focus on patients with hepatocellular carcinoma, renal cell carcinoma, and non-small cell lung cancer. In particular, we have added non-small cell lung cancer as an indication of interest given the recent non-clinical data as well as our observed clinical response. We will provide an update as to our plans in non-small cell lung cancer later this year. Now, we'll transition to provide a brief update on the ongoing Phase I clinical study of SRF617. SRF617 is a fully human IgG4 antibody, which potently inhibits the activity of CD39, which is a critical enzyme in the adenosine pathway, upstream from CD73. CD39 breaks down extracellular ATP in the tumor microenvironment, or TME, which leads to the production of adenosine. Inhibition of CD39 enzymatic activity decreases immunosuppressive adenosine and increases ATP levels in the TME. SRF617 is designed to engage both the innate and adaptive arms of the immune system in the TME. It acts with a dual mechanism to reduce adenosine, leading to increased T cell proliferation and activation, and promote dendritic cell maturation via ATP stabilization. This marks a critical differentiation from anti-CD73 approaches that only affect adenosine and do not have the effect of increasing immune stimulatory ATP levels in the TME. Preclinical models have demonstrated anti-tumor activity of SRF617 and set the stage for a first in human trial. With SRF617, we are the first to present clinical data on the therapeutic targeting of CD39. In March of 2020, we initiated a phase one clinical trial to evaluate SRF617 in patients with advanced solid tumors refractory to standard therapy, as shown in this schema. The study was designed to evaluate both monotherapy dosing and in a staggered fashion, evaluate combination therapy dosing of SRF617 with both chemotherapy, specifically the combination of gemcitabine and braxane, and separately with an anti-PD-1, Pembrolizumab. SRF617 was administered as a flat dose intravenously every two weeks. Our update today will focus on the monotherapy dose escalation portion of the study. We will also share some early data from the currently enrolling combination dose escalation cohorts. Slide 17 describes the patients enrolled in the monotherapy dose escalation study. As of the April 9th data cutoff, 27 patients have been treated with a median age of 65. The majority of patients had an ECOG performance status of 1. As would be expected in a Phase I population, this is a heavily pretreated patient group. The majority have received four or more prior systemic anti-cancer regimens, and 30% have received prior PD-1 pathway blockade. Turning to slide 18 to focus on the safety and tolerability data, we see SRF617 as a monotherapy is well tolerated at all tested doses. There have been no dose-limiting toxicities observed to date, up to 1400 mix. There have been no grade three or higher related adverse events, serious adverse events, or treatment discontinuations attributed to SRF617. 85% of patients experienced a treatment emergent adverse event, the most common being low-grade fatigue and nausea. The swimmer's plot on slide 19 shows each of the 27 patients' time on study grouped by starting dose, as depicted by the different lane colors. The lowest dose tested is shown at the bottom, ascending to the highest monotherapy dose tested to date, 1,400 mg, shown here in red. Two patients were able to escalate to higher doses, as you can see by the changes in lane color. Although no monotherapy objective responses have been observed at the time of the data snapshot, 7 of the 19, or 37%, of the response-evaluable patients experienced disease stabilization at 8 weeks, with 4 of those persisting beyond 16 weeks. One patient with non-small cell lung cancer who had previously progressed on chemo and anti-PD-1 therapy achieved disease stabilization for 9 months prior to progression. Switching focus to some very early data from the combination therapy cohorts, we are pleased to report that five patients have been dosed with a combination of 200 mg SRF617 and full-dose gemcitabine and abraxane. One unconfirmed partial response has been reported at the first response evaluation in a patient with pancreatic cancer. We'll share more detail on that patient in a moment. We've also initiated dosing in the SRF617 plus pembrolizumab cohort with three patients dosed to date. Turning to slide 21, we present baseline and week 8 images from a 60-year-old man with pancreatic cancer and extensive liver metastases who received SRF617 at 200 milligrams plus gemcitabine and abraxane after he experienced progression on initial chemotherapy with fulfirinox. Note that the baseline images are in the top row with corresponding week eight images in the bottom row and the red arrows marking liver lesions followed for resist response. There is an approximately 50% reduction in the size of the target lesions, and I think it is evident even to a non-radiologist that all of the visualized metastatic lesions in the liver are decreasing in size. This patient remains on study. In this cohort, we have treated an additional three patients with pancreatic cancer, one of whom has progressed. We expect to share more detailed results from this ongoing study at a medical conference later this year. However, these preliminary results are encouraging for the future development of SRF617. SRF617 is well tolerated and has an appropriate safety profile for combination therapy. As a monotherapy, we have seen disease stabilization in a heavily pretreated population, even in patients previously progressed on anti-PD1 therapy. And though evaluation of SRF617 in combination cohorts is still early, we have seen one unconfirmed partial response in a patient with pancreatic cancer who had previously progressed on chemotherapy. These preliminary results support further evaluation of SRF617 and combination regimens in tumor types for which CD39 may be a particularly relevant immunotherapy target, including pancreatic cancer and gastric cancer. We are also announcing today that we have amended our clinical agreement with Arcus Biosciences to expand our approach in prostate cancer. In particular, we will be initiating a standalone Phase II trial of SRF617 plus a TRUMA, an A2A, A2B adenosine receptor inhibitor, and Zimborellamab, an anti-PD-1 antibody, in metastatic castration-resistant prostate cancer. We expect to begin enrollment into this study in the second half of this year. Now I'll turn it back over to Rob for some closing thoughts.
spk04: Thank you, Allison. We also issued a press release this morning detailing our clinical collaboration with Roche Based on our preclinical and translational data, we have a great interest in studying the effects of SRF388 in patients with liver cancer. Moreover, we believe that combinations with anti-PD-1 or anti-PD-L1 are likely to result in the best outcomes for the anti-cancer effect of SRF388. Therefore, it is with great pleasure that we can announce that we have reached an agreement with Roche to study SRF388, placetizolizumab, and bevacizumab In first line, advanced liver cancer. Roche will supply both drugs, and Surface will run the study. We will provide an update as to the design and timing of this study later this year. In summary, as Jeff described, we are very pleased with the clinical progress we have made with both of our programs, SRF388 and SRF617. Both have been dose escalated to biologically relevant levels safely, and both are well tolerated. We are encouraged to see early signs of activity with both molecules. The highlight, though, is the monotherapy partial response that was seen in a patient with non-small cell lung cancer treated with SRF388. It is particularly interesting that this patient was highly treatment refractory, having progressed after anti-PD-1 treatment and multiple lines of chemotherapy. We are gratified to see this effect in lung cancer, where there is emerging data around the importance of IL-27 in tumor progression, and the unmet medical need is so very high. We will be adding an additional clinical focus for SRF388 in non-small cell lung cancer, and we'll provide an update on these plans later this year. Today's presentation is the beginning of what will be multiple clinical data updates over the next one to two years. In particular, we intend to provide a clinical update on SRF617 at a medical meeting in late 2021, and the next clinical update on SRF388 will be at a medical meeting in early 2022. I would like to acknowledge the patients, caregivers, and families involved in this study, as well as the investigators and their study teams for their contributions. At Surface, we all share a passion for finding and developing novel drugs to help patients with cancer, and we hope this is an important step on that mission. Thank you very much.
spk11: Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the one key on your touch-tone telephone. If your question has been answered or you wish to move yourself from the queue, please press the pound key. Our first question comes from Boris Peeker with Cowan.
spk05: Good morning, and congratulations on this unexpected result.
spk03: Hey, Boris. Thanks so much. We're pretty excited about it.
spk05: Great. So let me just ask a couple of questions on 388. So you've determined 10mg per kick to be the dose expansion dose. I'm just curious, you're still dose expanding here or testing a higher dose. So if you see stronger activity at a higher dose, does your dose expansion protocol allow to incorporate this higher dose?
spk04: Yeah. So thanks, Boris. That's a great question. The determination of the recommended phase two dose is obviously based on both safety and efficacy in the clinic. but also based on our non-clinical and PKPD modeling, where it's very clear that we are at dose levels that far exceed what we expect to see to produce efficacy, in fact, maximal efficacy non-clinically. Having said that, if we are surprised when we go to 20 and see something that's even more impressive, it would certainly allow us to switch to dose as we move forward.
spk05: Great. And my second question on 388 is we've talked about some efficacy observations here, but I'm curious, do you have any biomarker data that perhaps is mechanism-related that either correlates with drug dosing or the observed response or anything else that can help us better understand the mechanism?
spk04: Yeah, Boris, it's something that we've been thinking a whole lot about and doing a fair amount of work on. Unfortunately, none of that data is mature enough now to share data. As we've talked with you and many others in the past, we have specifically looked at levels of EBI-3 as a predictor of efficacy. And what we can tell you is for this patient, their EBI-3 level was not in the upper half of the patients we studied. So with this particular patient, that EBI-3 hypothesis doesn't seem to follow through. We are very interested in the emerging IL-27 data in lung cancer, though, as we referenced in the presentation, and we're certainly digging more into that now. We've also broadly expanded our look at potential biomarkers of efficacy. It's much easier to evaluate biomarkers when you have monotherapy activity because you actually have something to measure against, and we're digging into all of those data now.
spk05: Great. Well, congratulations again, and thank you for taking my questions.
spk04: Thanks, Boris.
spk11: Our next question comes from Sumit Roy with Jones Trading.
spk07: Hi. Congratulations again on this encouraging monotherapy. Probably staying with the biomarker data, are you looking into reduction in PD-L1 on digit levels in the peripheral T-cells or any reduction in IL-27 in the serum to give us an idea in future?
spk04: Yeah, so thanks, Suman. That's a great question. We certainly are. So we're doing what's called T-cell phenotyping to evaluate changes in the types of T-cells and the expression level of multiple different checkpoint proteins on T-cells to understand if that's associated with outcome. We're also looking at circling IL-27 levels, as well as components of the IL-27 pathway. Remember, it's a little more confusing simply because our antibody, when it binds P28, when it binds IL-27, it means that the IL-27 can't be cleared. So the expectation is that those levels actually go up, despite the fact that the pathway itself is inhibited. This is very similar to what you see with Avastin and VEGF, So if you look at circling levels of VEGF in patients treated with VASP, and they actually go up simply because the VEGF itself is not cleared. So lots of great stuff for us to dig into here, Suman.
spk07: Got it. Just one last question. On the RP2D, so you decided on once every four weeks. Is that the frequency you were doing in the dose escalation?
spk04: Yeah. So the dose escalation schedule is once every four weeks. We're very comfortable moving forward with once every four weeks, given the trough levels we're seeing. Having said that, given the safety profile, the tolerability profile we've seen, we have a lot of opportunity to go once every three, once every two as well. So we'll change the schedule as it relates to the combination partner and patient convenience.
spk07: Thank you. Congratulations, Kim.
spk04: Thanks so much.
spk11: Our next question comes from Colleen Cussie with Baird.
spk06: Hi, good morning. Thanks so much for taking our questions and congrats on the data this morning. So for the responder, thanks. For the responder with 388, has there been any additional follow-up past the 12-week scan? And is the patient continuing to respond?
spk04: Yeah, so we've shown you everything we've got. So the patient had that nice response at their week 8 scan. We followed up four weeks later with a confirmatory scan, and the response had deepened. So that was terrific, and that's the most recent data we have. The patient remains on trial, and by all accounts, doing well. So it's been, to date, sustained. Admittedly, Colleen, right, it's still early. This response came in pretty recently, as you can imagine.
spk06: Yeah, excellent. That's great. And in terms of the kind of speed to response. Was this, based on your models, something you'd expect to see a response by the first eight weeks, or was the kind of rapid response surprising?
spk04: Yeah, it's a great question, and it did catch us a little bit by surprise, both the rapidity of the response and also just how heavily pretreated this patient was. So this is a patient with low PD-L1 expression, a patient who'd blown right through anti-PD1 plus chemo, blown right through second-line chemo, and had not done well with adjuvant chemo after their resection. And so, I mean, they were symptomatic coming into the trial. So it was really interesting to see that not only had they had a 40% tumor reduction within eight weeks, but their symptoms were also improving. You know, you can see this with IO. It's not crazy to see, but we were expecting responses that would take more time to manifest. So we were, quite frankly, rather delighted to see the rapidity of the response, especially in someone so heavily pretreated.
spk06: Yeah, that's fantastic. Thank you. And one on 617, in the pancreatic patient where you saw the unconfirmed partial response, would you expect a retreatment effect with chemo in that setting?
spk04: Yeah, so this is a patient who received first-line fulferinox, right? So importantly, they've never seen gemorabraxane before, but obviously fulferinox is a mixture of four different chemotherapies and is the most intensive therapy we give in pancreatic cancer. Moreover, this patient blew through chemotherapy, so their best response to first-line was progressive disease, right? They did not have a partial response to to first-line chemo. We know from the literature that the response rate to geminobraxane in the second-line setting, post-fulfirinox, is on the order of 10% to 15%, so it can happen. Typically, you'd expect it in someone who had a good response to first-line fulfirinox, right? So this is a little unusual, but we're definitely splitting hairs here in the context of a you know, a patient that had the response very recently and for whom this is in combination. So we are pleasantly encouraged, and I think it is interesting in that it ties into the work that we've done and ARCIS has done around the importance of the adenosine pathway in pancreatic cancer. So it continues to get us excited about the potential in pancreatic cancer, but it's obviously still quite early.
spk06: Great. Thank you so much for taking our questions.
spk04: Of course.
spk11: The next question comes from Sam Pakula with AC Wainwright.
spk08: Thank you. This is RK. Good morning, Rob and Jess. Congratulations on very interesting and encouraging data. Thanks, RK. Good to hear from you. So on 388, you know, you have chosen three different indications to go after. So I understand the non-small cell lung cancer basically on some of the data that you presented. for HCC and RCC, what gives you some confidence to go forward on them? And also on 388, now that you have the Roche collaboration to continue on the HCC, but you also have a collaboration with Merck for solid tumors. So I'm just trying to figure out How are you parsing between indications between the drugs from the different guys, whether it's Merck or Roche?
spk04: Yeah, so we're going to update later in the year as to our exact plans. What we were excited about with regards to the Roche collaboration was the opportunity to get into first-line liver cancer, right? patients with advanced liver cancer who'd never seen an IO agent before. As you know, the standard of care for those patients is bevacizumab with Atizo. And that's the label in the U.S., and that's also what's used around the world. So our ability to get to a truly IO-naive patient population is really limited to first-line HCC within the indications we've discussed. And so that's what we're so excited about with Roche. We'll lay out our plans later in the year around exactly what that trial will look like, but the focus is first line, which is an area that we had not planned on getting into with pembrolizumab as part of the Merck collaboration. With Merck, with Pembro, we're looking at both HCC and RCC, and now with this non-small cell lung cancer data, while we haven't officially said what we're doing, there are obvious opportunities there as well. The original plan was in the second line setting and in the third line setting, but we'll pull together our best thoughts on that and be able to further explicate later this year.
spk08: Okay, and then a question on 617. For prostate, I believe, if I remember it correctly, I believe you were trying to look at the doublet, 617. 6-1-7 and N-tributinant, but now you're talking about the triplet.
spk04: That's right.
spk08: So which one would you focus on, or are you trying to do both?
spk04: Yeah, so thanks, RK, because I want to be clear about this. So basically what we did with ARCIS was swap out a doublet expansion with a standalone triplet Phase II trial. So based on our own internal work, we believe the best way to use this molecule was actually as part of an IO-IO triplet. And so we had multiple discussions with ARCIS about making that happen since they both have a potent PD-1 as well as what we think is a best-in-class A2A, A2B. And we were able to reach an agreement that basically swapped out the doublet, so we're no longer doing the doublet, and instead focuses on the triplet in a castration-resistant post-chemotherapy patient population with that phase two starting later this year. So it's obviously a very, we think, a very robust trial to identify whether or not with just IO agents we can generate a signal in prostate cancer where we know we've seen single agent activity with some of the A2A small molecules.
spk08: Perfect. Thank you both. Thanks for taking my questions.
spk04: Yeah, of course.
spk11: Again, ladies and gentlemen, if you have a question or a comment at this time, please press the star, then the one key on your touchtone telephone. Our next question comes from Justin Zelen with BTIG.
spk15: Hi, Tim. Congrats on this very exciting data. Just had a question on 617 and understand that the trial is still in progress and still early, but as far as Getting a recommended phase two dose here, will you look into how the data looks in the highest dose here, the 2,000 milligrams before determining that? And if you could just remind us as far as the starting doses and the combination therapy cohorts, how you've come up with those. Thanks.
spk04: Yeah, thanks, Justin, and thanks for the kind words. So the bottom line, Justin, is we think we're very close, but we're still pulling together all the translational and non-clinical data We think the starting dose is likely either one of the two doses we just looked at or that two-gram dose. And we'll pull together that data, and we should be able to – we'll certainly be able to make a call and be public about that with a data update later this year. The other part of your question around the starting dose for the combination expansions with chemotherapy, we started at 200. And with Pembro, because that program started a little later, we started at 700 milligrams.
spk16: Got it. Thanks again.
spk11: And I'm not showing any further questions at this time. I'd like to turn the call back over to Rob Ross.
spk04: So thanks so much. We were certainly pleased to be able to present the beginnings of the clinical journey for both of these two agents. We are incredibly excited to be sharing data for the first time around both of these targets, and we think it's just the beginning of what will be multiple data updates over the next several years. So thanks very much, and have a good day.
spk11: Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day. Thank you. Thank you. Thank you. you
spk10: Ladies and gentlemen, thank you for standing by and welcome to the surface oncology clinical update for SRF388 and SRF617. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Jessica Fees, Chief Financial Officer at Surface Oncology. Please go ahead.
spk13: Thank you for joining today's clinical study update webcast. My name is Jessica Fees, and I am the Chief Financial Officer at Surface Oncology. With me on the webcast are Rob Ross, Chief Executive Officer, and Allison O'Neill, Chief Medical Officer. Please note that this call is being webcast live and will be archived on the Investors and Media section of the Surface Oncology website. Before we begin, a few forward-looking statements. This presentation has been prepared by Surface Oncology and includes certain forward-looking information within the meaning of the Private Securities Litigation Reform Act of 1995. The statements made in this presentation speak only as of the date hereof, and any forward-looking statements contained herein are based on assumptions that surface oncology believes to be reasonable as of this date. Surface oncology undertakes no obligation to update these statements as a result of new information or future events. I now turn the call over to Rob.
spk04: Thank you, and welcome, everyone. We are very pleased to be able to share today clinical updates on both our lead clinical programs, SRF388, and SRF617. Both are immuno-oncology antibodies directed at novel targets meant to activate the immune system to kill tumor cells and ultimately help patients. We are proud of the fact that, to our knowledge, we are the first to present clinical data on molecules targeting either IL-27 or CD39. The headline today, is that with SRF388, our anti-IL27 antibody, we have seen clear evidence of monotherapy activity in the form of a confirmed partial response in a patient with highly treatment refractory lung cancer. With any first-in-class agent in immuno-oncology, it can be a struggle to prove that the pathway you are targeting actually matters in people with cancer. Here we have clear evidence that, at least for this patient, not only does IL27 matter, but if you inhibited IL-27 by itself, that is enough to stimulate a significant anti-tumor response. Moreover, the drug is well-tolerated, the recommended Phase II dose has been selected, and expansion cohorts are actively enrolling. We can also announce today that we have entered into a clinical agreement with Roche to begin a trial in first-line advanced liver cancer, combining SRF388 with atezolizumab and bevacizumab, the standard of care for these patients. SRF617, our anti-CD39 antibody, has been similarly well tolerated, and we are currently at dose levels that we expect are biologically active. We have opened our combination arms in that trial and, to date, have seen a partial response in a patient with second-line pancreatic cancer treated with SRF617 along with chemotherapy. Without further delay, I'll let Allison O'Neill, our chief medical officer, walk you through the details of the clinical data on both programs. Allison? Thank you, Rob, and good morning, everyone.
spk12: We will turn to SRF388 first. IL-27 is a highly immunosuppressive cytokine that plays physiologic roles in controlling chronic infections and immunotolerance to cancer. SRF388 is a first-in-class IL-27 antibody that blocks the cytokine from binding to its receptor, as depicted in the graphic on the right. This blockade results in immune activation in the tumor microenvironment and decreased tumor growth, as observed in multiple preclinical models. Multiple internal and independent sources have shown evidence that there is IL-27 pathway activation in both the patecellular and renal cell carcinoma, and high circulating levels of EBI-3, one of the subunits of IL-27, can be associated with inferior outcomes in both. Additionally, a recent publication evaluating single-cell RNA-seq data has demonstrated that in non-small-cell lung cancers that are progressing, IL-27 is upregulated in myeloid immune cells. These data suggest that IL-27 upregulation may be important in refractory lung cancer, and treatment with SRF388 might have an important clinical effect in this disease. Next, we will discuss the ongoing Phase I study of SRF388. which is a first in human study to evaluate safety, tolerability, and efficacy in patients with advanced solid tumors refractory to at least one standard therapy. Before diving into the data, please take note of the schema of the SRF388-101 study design on slide 6. Part A on the left of the slide depicts dose escalation of SRF388 as a monotherapy, and I'll review the results of this portion of the study in a few moments. On the right, Part B includes the monotherapy expansions that we have just opened for patients with advanced renal cell cancer, or RCC, and hepatocellular carcinoma, or HCC, as well as an exploration of SRF388 when used in combination with pembrolizumab in patients with advanced treatment refractory clear cell RCC and HCC. Today, we'll focus on the results of the Part A dose escalation component. The study's primary endpoints were rate of drug-limiting toxicity, safety, and tolerability, with the overarching objective of determining the recommended phase 2 dose, or RP2D. SRF388 was administered intravenously every four weeks using an accelerated design for the first three dose levels, followed by a standard 3 plus 3 design. Slide 7 presents the key baseline characteristics of the 21 patients enrolled in the dose escalation portion of the study as of the April 16, 2021 data cutoff date. The population was predominantly female with ECOG performance status of 1. This is a heavily pretreated population with over half receiving four or more prior lines of therapy and 80% having received prior PD-1 pathway blockade. Turning to slide 8 to focus on the safety and tolerability data. SRF388 was well tolerated by all patients at all doses investigated to date with no observed dose-limiting toxicities. 15 of the 21 patients, or 71%, experienced a treatment-emergent adverse event, but these were generally low-grade. Fatigue was the most common, experienced by two patients. There were no grade 3 or greater treatment-related adverse events, and no treatment discontinuations attributed to SRF388. The swimmer's plot on slide 9 shows the patient's time on study and resist response grouped by starting dose. which is denoted by different lane cohorts. From lowest starting dose at the bottom, ascending to the highest dose level tested to date of 10 mg per kg. Disease assessment was performed at week 8 and then every 12 weeks. We are encouraged by the fact that a number of patients remained on study long enough to be able to escalate to higher doses, as depicted by the changing of the lane color at the time of dose increase. In addition, one patient with non-small cell lung cancer who was treated at 10 mg per kg experienced a rapid partial response. This was evident at the first response assessment at eight weeks and then confirmed at 12 weeks, as shown inside the red oval. We will share more details on this particular patient in a moment. Slide 10 provides a summary of responses to treatment in the evaluable patient population. The evaluable analysis set included all patients with measurable disease at baseline who received at least one dose of SRF388 at any dose level and had at least one post-baseline response assessment, or who discontinued study treatment within six weeks of their first dose. Eighteen patients met these criteria. The table on the left shows that in addition to the patient who had a confirmed partial response, 33% of patients, or six out of the group of 18, experienced clinical benefit in the form of disease stabilization, and five of those six had disease control persisting beyond 16 weeks. The waterfall plot depicts the best percentage change in the target lesions from baseline. You will notice the patient with non-small cell lung cancer with a 66% decrease in tumor size and the patient with pancreatic cancer who also experienced tumor shrinkage but eventually developed a new lesion. Turning to slide 11, we present images from a 64-year-old man with squamous cell non-small cell lung cancer with metastases to the mediastinal nodes, lung, and pleura. This patient was enrolled at the recommended Phase II dose of 10 mg per kg. Before walking through the images, a little background about this patient's cancer. The patient had treatment refractory disease, having progressed on three prior regimens, including chemotherapy and a PD-1 blockade prior to study entry. He had metastatic progression less than four months from completion of adjuvant cisplatin-based therapy and no response to subsequent chemotherapy for metastatic disease, including a pembrolizumab combination. It should be noted that the patient was progressively symptomatic prior to the initiation of SRF388 dosing. Target lesions are the medium gray color mediastinal nodes indicated by the red arrows. The CT images show shrinkage in the size of this patient's two target lesions from baseline, which was just prior to treatment with SRF388, to the first imaging evaluation at eight weeks, and then further shrinkage on the confirmation scan at 12 weeks. After two cycles of SRF388, this patient experienced a partial response with 42% tumor shrinkage in both mediastinal node target lesions. He also had significant improvement in his dyspnea. After three cycles, confirmatory scans demonstrated a 66% decrease in his target lesions. We're very encouraged by this confirmed response to 388 monotherapy, and the patient remains on study. Now on to the PK analysis. We observed that the pharmacokinetics of SRF388 are linear and dose proportional, with steady state achieved by the third cycle. The estimated half-life is 12 days, with no evidence of anti-drug antibody development to date. Our primary pharmacodynamic marker was inhibition of downstream phosphostat signaling in whole blood. We observed that complete inhibition was maintained through trough at dose levels of 0.3 mgs per kg and higher. In conclusion, these results from the SRF388-101 study support further evaluation of SRF388 for the treatment of cancer, both as a monotherapy and in combination. We observed promising single-agent activity of this immuno-oncology agent in a heavily pretreated population, including a confirmed partial response in a patient who had not responded to three prior standard therapies, including PD-1 blockade, as well as evidence of disease stabilization in multiple patients. SRF388 was well tolerated by patients in the study at all doses tested to date, and based on the data we've discussed here, we've confirmed a recommended Phase II dose of 10 mg per kg and begun to enroll expansion cohorts. We look forward to continuing to evaluate SRF388 with an initial focus on patients with hepatocellular carcinoma, renal cell carcinoma, and non-small cell lung cancer. In particular, we have added non-small cell lung cancer as an indication of interest given the recent non-clinical data, as well as our observed clinical response. We will provide an update as to our plans in non-small cell lung cancer later this year. Now, we'll transition to provide a brief update on the ongoing phase one clinical study of SRF617. SRF617 is a fully human IgG4 antibody, which potently inhibits the activity of CD39, which is a critical enzyme in the adenosine pathway, upstream from CD73. CD39 breaks down extracellular ATP in the tumor microenvironment, or TME, which leads to the production of adenosine. Inhibition of CD39 enzymatic activity decreases immunosuppressive adenosine and increases ATP levels in the TME. SRF617 is designed to engage both the innate and adaptive arms of the immune system in the TME. It acts with a dual mechanism to reduce adenosine, leading to increased T cell proliferation and activation, and promote dendritic cell maturation via ATP stabilization. This marks a critical differentiation from anti-CD73 approaches that only affect adenosine and do not have the effect of increasing immune stimulatory ATP levels in the TME. Preclinical models have demonstrated anti-tumor activity of SRF617 and set the stage for a first in human trial. With SRF617, we are the first to present clinical data on the therapeutic targeting of CD39. In March of 2020, we initiated a phase one clinical trial to evaluate SRF617 in patients with advanced solid tumors refractory to standard therapy, as shown in this schema. The study was designed to evaluate both monotherapy dosing and in a staggered fashion, evaluate combination therapy dosing of SRF617 with both chemotherapy, specifically the combination of gemcitabine and braxane, and separately with an anti-PD-1, pembrolizumab. SRF617 was administered as a flat dose intravenously every two weeks. Our update today will focus on the monotherapy dose escalation portion of the study. We will also share some early data from the currently enrolling combination dose escalation cohorts. Slide 17 describes the patients enrolled in the monotherapy dose escalation study. As of the April 9th data cutoff, 27 patients have been treated with a median age of 65. The majority of patients had an ECOG performance status of 1. As would be expected in a Phase I population, this is a heavily pretreated patient group. The majority have received four or more prior systemic anti-cancer regimens, and 30% have received prior PD-1 pathway blockade. Turning to slide 18 to focus on the safety and tolerability data, we see SRF617 as a monotherapy is well tolerated at all tested doses. There have been no dose-limiting toxicities observed to date, up to 1400 mix. There have been no grade three or higher related adverse events, serious adverse events, or treatment discontinuations attributed to SRF617. 85% of patients experienced a treatment emergent adverse event, the most common being low-grade fatigue and nausea. The swimmer's plot on slide 19 shows each of the 27 patients' time on study grouped by starting dose, as depicted by the different lane colors. The lowest dose tested is shown at the bottom, ascending to the highest monotherapy dose tested to date, 1,400 mg, shown here in red. Two patients were able to escalate to higher doses, as you can see by the changes in lane colors. Although no monotherapy objective responses have been observed at the time of the data snapshot, seven of the 19 or 37% of the response of valuable patients experienced disease stabilization at eight weeks, with four of those persisting beyond 16 weeks. One patient with non-small cell lung cancer who had previously progressed on chemo and anti-PD-1 therapy achieved disease stabilization for nine months prior to progression. Switching focus to some very early data from the combination therapy cohorts, we are pleased to report that five patients have been dosed with a combination of 200 mg SRF617 and full-dose gemcitabine and abraxane. One unconfirmed partial response has been reported at the first response evaluation in a patient with pancreatic cancer. We'll share more detail on that patient in a moment. We've also initiated dosing in the SRF617 plus Pembrolizumab cohort with three patients dosed to date. Turning to slide 21, we present baseline and week 8 images from a 60-year-old man with pancreatic cancer and extensive liver metastases who received SRF617 at 200 milligrams plus gemcitabine and abraxane after he experienced progression on initial chemotherapy with fulfirinox. Note that the baseline images are in the top row, with corresponding week 8 images in the bottom row, and the red arrows marking liver lesions followed for resist response. There is an approximately 50% reduction in the size of the target lesions, and I think it is evident even to a non-radiologist that all of the visualized metastatic lesions in the liver are decreasing in size. This patient remains unstudied. In this cohort, we have treated an additional three patients with pancreatic cancer, one of whom has progressed. We expect to share more detailed results from this ongoing study at a medical conference later this year. However, these preliminary results are encouraging for the future development of SRF617. SRF617 is well tolerated and has an appropriate safety profile for combination therapy. As a monotherapy, we have seen disease stabilization in a heavily pretreated population, even in patients previously progressed on anti-PD1 therapy. And though evaluation of SRF617 in combination cohorts is still early, we have seen one unconfirmed partial response in a patient with pancreatic cancer who had previously progressed on chemotherapy. These preliminary results support further evaluation of SRF617 and combination regimens in tumor types for which CD39 may be a particularly relevant immunotherapy target, including pancreatic cancer and gastric cancer. We are also announcing today that we have amended our clinical agreement with Arcus Biosciences to expand our approach in prostate cancer. In particular, we will be initiating a standalone Phase II trial of SRF617 plus a TRUMA, an A2A, A2B adenosine receptor inhibitor, and Zimbirellumab, an anti-PD-1 antibody, in metastatic castration-resistant prostate cancer. We expect to begin enrollment into this study in the second half of this year. Now I'll turn it back over to Rob for some closing thoughts.
spk04: Thank you, Allison. We also issued a press release this morning detailing our clinical collaboration with Roche. Based on our preclinical and translational data, we have a great interest in studying the effects of SRF388 in patients with liver cancer. Moreover, we believe that combinations with anti-PD-1 or anti-PD-L1 are likely to result in the best outcomes for the anti-cancer effect of SRF388. Therefore, it is with great pleasure that we can announce that we have reached an agreement with Roche to study SRF388, Placetizolizumab, and Bevacizumab In first line, advanced liver cancer. Roche will supply both drugs, and Surface will run the study. We will provide an update as to the design and timing of this study later this year. In summary, as Jeff described, we are very pleased with the clinical progress we have made with both of our programs, SRF388 and SRF617. Both have been dose escalated to biologically relevant levels safely, and both are well tolerated. We are encouraged to see early signs of activity with both molecules. The highlight, though, is the monotherapy partial response that was seen in a patient with non-small cell lung cancer treated with SRF388. It is particularly interesting that this patient was highly treatment refractory, having progressed after anti-PD-1 treatment and multiple lines of chemotherapy. We are gratified to see this effect in lung cancer, where there is emerging data around the importance of IL-27 in tumor progression, and the unmet medical need is so very high. We will be adding an additional clinical focus for SRF388 in non-small cell lung cancer, and will provide an update on these plans later this year. Today's presentation is the beginning of what will be multiple clinical data updates over the next one to two years. In particular, we intend to provide a clinical update on SRF617 at a medical meeting in late 2021, and the next clinical update on SRF388 will be at a medical meeting in early 2022. I would like to acknowledge the patients, caregivers, and families involved in this study, as well as the investigators and their study teams for their contributions. At Surface, we all share a passion for finding and developing novel drugs to help patients with cancer, and we hope this is an important step on that mission. Thank you very much.
spk11: Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the one key on your touch-tone telephone. If your question has been answered and you wish to move yourself from the queue, please press the pound key. Our first question comes from Boris Peeker with Cowan.
spk05: Good morning, and congratulations on this unexpected result.
spk03: Hey, Boris. Thanks so much. We're pretty excited about it.
spk05: Great. So let me just ask a couple of questions on 388. So you've determined 10mg per kick to be the dose expansion dose. I'm just curious, you're still dose expanding here or testing a higher dose. So if you see stronger activity at a higher dose, does your dose expansion protocol allow to incorporate this higher dose?
spk04: Yeah. So thanks, Boris. That's a great question. The determination of the recommended phase two dose is obviously based on both safety and efficacy in the clinic. but also based on our non-clinical and PKPD modeling, where it's very clear that we are at dose levels that far exceed what we expect to see to produce efficacy, in fact, maximal efficacy non-clinically. Having said that, if we are surprised when we go to 20 and see something that's even more impressive, it would certainly allow us to switch to dose as we move forward.
spk05: Great. And my second question on 388 is we've talked about some efficacy observations here, but I'm curious, do you have any biomarker data that perhaps is mechanism-related that either correlates with drug dosing or the observed response or anything else that can help us better understand the mechanism?
spk04: Yeah, Boris, it's something that we've been thinking a whole lot about and doing a fair amount of work on. Unfortunately, none of that data is mature enough now to share data. As we've talked with you and many others in the past, we have specifically looked at levels of EBI-3 as a predictor of efficacy. And what we can tell you is for this patient, their EBI-3 level was not in the upper half of the patients we studied. So with this particular patient, that EBI-3 hypothesis doesn't seem to follow through. We are very interested in the emerging IL-27 data in lung cancer, though, as we referenced in the presentation, and we're certainly digging more into that now. We've also broadly expanded our look at potential biomarkers of efficacy. It's much easier to evaluate biomarkers when you have monotherapy activity because you actually have something to measure against, and we're digging into all of those data now.
spk05: Great. Well, congratulations again, and thank you for taking my questions.
spk04: Thanks, Boris.
spk11: Our next question comes from Sumit Roy with Jones Trading.
spk07: Hi. Congratulations again on this encouraging monotherapy. Probably staying with the biomarker data, are you looking into reduction in PD-L1 on digit levels in the peripheral T-cells or any reduction in IL-27 in the serum to give us an idea in future?
spk04: Yeah, so thanks, Suman. That's a great question. We certainly are. So we're doing what's called T-cell phenotyping to evaluate changes in the types of T-cells and the expression level of multiple different checkpoint proteins on T-cells to understand if that's associated with outcome. We're also looking at circling IL-27 levels, as well as components of the IL-27 pathway. Remember, it's a little more confusing simply because our antibody, when it binds P28, when it binds IL-27, it means that the IL-27 can't be cleared. So the expectation is that those levels actually go up, despite the fact that the pathway itself is inhibited. This is very similar to what you see with Avastin and VEGF, So if you look at circling levels of VEGF in patients treated with VASP and they actually go up simply because the VEGF itself is not cleared. So lots of great stuff for us to dig into here, Suman.
spk07: Got it. Just one last question. On the RP2D, so you decided on once every four weeks. Is that the frequency you were doing in the dose escalation?
spk04: Yeah. So the dose escalation schedule is once every four weeks. We're very comfortable moving forward with once every four weeks, given the trough levels we're seeing. Having said that, given the safety profile, the tolerability profile we've seen, we have a lot of opportunity to go once every three, once every two as well. So we'll change the schedule as it relates to the combination partner and patient convenience.
spk07: Thank you. Congratulations, Kim.
spk04: Thanks so much.
spk11: Our next question comes from Colleen Cussie with Bayard.
spk06: Hi, good morning. Thanks so much for taking our questions and congrats on the data this morning. So for the responder, thanks. For the responder with 388, has there been any additional follow-up past the 12-week scan? And is the patient continuing to respond?
spk04: Yes. So we've shown you everything we've got. So the patient had that nice response at their week 8 scan. We followed up four weeks later with a confirmatory scan, and the response had deepened. So that was terrific, and that's the most recent data we have. The patient remains on trial and, by all accounts, doing well. So it's been, to date, sustained. Admittedly, Colleen, right, it's still early. This response came in pretty recently, as you can imagine.
spk06: Yeah, excellent. That's great. And in terms of the kind of speed to response. Was this, based on your models, something you'd expect to see a response by the first eight weeks, or was the kind of rapid response surprising?
spk04: Yeah, it's a great question, and it did catch us a little bit by surprise, both the rapidity of the response and also just how heavily pretreated this patient was. So this is a patient with low PD-L1 expression, a patient who'd blown right through anti-PD1 plus chemo, blown right through second-line chemo, and had not done well with adjuvant chemo after their resection. And so they were symptomatic coming into the trial. So it was really interesting to see that not only had they had a 40% tumor reduction within eight weeks, but their symptoms were also improving. You know, you can see this with IO. It's not crazy to see, but we were expecting responses that would take more time to manifest. So we were, quite frankly, rather delighted to see the rapidity of the response, especially in someone so heavily pretreated.
spk06: Yeah, that's fantastic. Thank you. And one on 617, in the pancreatic patient where you saw the unconfirmed partial response, would you expect a retreatment effect with chemo in that setting? Yeah.
spk04: Yeah, so this is a patient who received first-line fulferinox, right? So importantly, they'd never seen gemorabraxane before, but obviously fulferinox is a mixture of four different chemotherapies and is the most intensive therapy we give in pancreatic cancer. Moreover, this patient blew through chemotherapy, so their best response to first-line was progressive disease, right? They did not have a partial response to to first-line chemo. We know from the literature that the response rate to geminobraxane in the second-line setting, post-fulfirinox, is on the order of 10% to 15%, so it can happen. Typically, you'd expect it in someone who had a good response to first-line fulfirinox, right? So this is a little unusual, but we're definitely splitting hairs here in the context of a you know, a patient that had the response very recently and for whom this is in combination. So we are pleasantly encouraged, and I think it is interesting in that it ties into the work that we've done and ARCIS has done around the importance of the adenosine pathway in pancreatic cancer. So it continues to get us excited about the potential in pancreatic cancer, but it's obviously still quite early.
spk06: Great. Thank you so much for taking our questions.
spk11: Of course. The next question comes from Sam Pakula with AC Wainwright.
spk08: Thank you. This is RK. Good morning, Rob and Jess. Congratulations on very interesting and encouraging data. Thanks, RK. Good to hear from you. So on 388, you know, you have chosen three different indications to go after. So I understand the non-small cell lung cancer basically on some of the data that you presented. for HCC and RCC, what gives you some confidence to go forward on them? And also on 388, you know, now that you have the Roche collaboration to continue on the HCC, but you also have a collaboration with Merck for solid tumors. So I'm just trying to figure out How are you parsing between indications between the drugs from the different guys, whether it's Merck or Roche?
spk04: Yeah, so we're going to update later in the year as to our exact plans. What we were excited about with regards to the Roche collaboration was the opportunity to get into first-line liver cancer, right? patients with advanced liver cancer who'd never seen an IO agent before. As you know, the standard of care for those patients is Bevacizumab with Atizo. And that's the label in the U.S., and that's also what's used around the world. So our ability to get to a truly IO-naive patient population is really limited to first-line HCC within the indications we've discussed. And so that's what we're so excited about with Roche. And we'll lay out our plans later in the year around exactly what that trial will look like. But the focus is first line, which is an area that we had not planned on getting into with Pembrolizumab as part of the Merck collaboration. With Merck, with Pembro, we're looking at both HTC and RCC. And now with this non-small cell lung cancer data, while we haven't officially said what we're doing, there are obvious opportunities there as well. The original plan was in the second-line setting and in the third-line setting, but we'll pull together our best thoughts on that and be able to further explicate later this year.
spk08: Okay, and then a question on 617. For prostate, I believe, if I remember correctly, I believe you were trying to look at the doublet at 617. 617 and Intubadent, but now you're talking about the triplet.
spk04: That's right.
spk08: So which one would you focus on, or are you trying to do both?
spk04: Yeah, so thanks, RK, because I want to be clear about this. So basically what we did with ARCIS was swap out a doublet expansion with a standalone triplet Phase II trial. So based on our own internal work, we believe the best way to use this molecule was actually as part of an IO-IO triplet. And so we had multiple discussions with ARCIS about making that happen since they both have a potent PD-1 as well as what we think is a best-in-class A2A, A2B. And we were able to reach an agreement that basically swapped out the doublet, so we're no longer doing the doublet, and instead focuses on the triplet in a castration-resistant post-chemotherapy patient population with that phase two starting later this year. So it's obviously a very, we think, a very robust trial to identify whether or not with just IO agents we can generate a signal in prostate cancer where we know we've seen single agent activity with some of the A2A small molecules.
spk08: Perfect. Thank you both. Thanks for taking my questions.
spk04: Yeah, of course.
spk11: Again, ladies and gentlemen, if you have a question or a comment at this time, please press the star, then the one key on your touchtone telephone. Our next question comes from Justin Zelen with BTIG.
spk15: Hi, Tim. Congrats on this very exciting data. Just had a question on 617 and understand that the trial is still in progress and still early, but as far as Getting a recommended phase two dose here, will you look into how the data looked in the highest dose here, the 2,000 milligrams, before determining that? And if you could just remind us as far as the starting doses and the combination therapy cohorts, how you've come up with those. Thanks.
spk04: Yeah, thanks, Justin, and thanks for the kind words. So the bottom line, Justin, is we think we're very close, but we're still pulling together all the translational and non-clinical data We think the starting dose is likely either one of the two doses we just looked at or that two-gram dose. And we'll pull together that data, and we should be able to – we'll certainly be able to make a call and be public about that with a data update later this year. The other part of your question around the starting dose for the combination expansions with chemotherapy, we started at 200. And with Pembro, because that program started a little later, we started at 700 milligrams.
spk16: Got it. Thanks again.
spk11: And I'm not showing any further questions at this time. I'd like to turn the call back over to Rob Ross.
spk04: So thanks so much. We were certainly pleased to be able to present the beginnings of the clinical journey for both of these two agents. We are incredibly excited to be sharing data for the first time around both of these targets, and we think it's just the beginning of what will be multiple data updates over the next several years. So thanks very much, and have a good day.
spk11: Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.
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