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spk08: Good day and welcome to the Agenis first quarter 2023 financial results conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, please press star one again. For operator assistance throughout the call, please press star zero. And finally, I would like to advise all participants that this call is being recorded. I'd now like to welcome Mr. Zach Arman to begin the conference.
spk09: Zach, over to you.
spk01: Thank you, operator, and thank you all for joining us today. Today's call is being webcast and will be available on our website through replay. I'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development regulatory and commercial plans and timelines, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. Joining me today are Dr. Garrow Arman, Chairman and Chief Executive Officer, Dr. Stephen O'Day, Chief Medical Officer, and Christine Klaskin, Vice President of Finance. Now, I'd like to turn the call over to Garo to highlight our progress and speak to our outlook for the remainder of the year. Garo?
spk07: Good morning, everyone, and thank you for joining us for our first quarter 2023 update. Today, we'll primarily focus on the significant progress we've made with our run-breaking Botansilomat program and its potential to transform cancer treatment. across nine different solid genotypes that we've reported on so far. Over the past 10 months, we've presented data at the plenary or late-breaking sessions of five major conferences, including SOGI, CITSE, ASCOGI, SGO, and CITAS. We look forward to sharing further insights at upcoming conferences, such as ASCO in June, and ESMO-GI in July. BotancillaMAP, our innovative and multifunctional CTLA for anybody, aims to revolutionize cancer treatment by extending clinical benefit to cold tumors, which have historically been unresponsive to standard of care and other immunotherapy agents, including other CTLA for anybody. And impressively, Botansilumab has demonstrated clinical responses in both cold and hot tumors. In a diverse patient population of nearly 400 individuals across nine solid tumor types, all of them, had exhausted prior treatment options, Botansilumab has made significant strides in elicitin responses, offering renewed hope for those who have failed all other available treatments. Let's take a closer look at response rates achieved with Botansilumab. Across all non-solid tumors, we've observed remarkable response rates of up to 50% in highly refractory cancers. This is truly an impressive accomplishment, considering the patient population involved. Notably, many of these responses have proven to be durable responses. This is a critical factor in evaluating a treatment's potential to transform patients' lives in a meaningful way. But the story doesn't end there. Preliminarily, data suggests that Potensolimab may be exceptionally effective in colorectal cancer patients with cold tumors that have historically been unresponsive to immunotherapy. Even in hot tumors that have failed standard of care, including immunotherapy, of course, with or without chemotherapy, we are witnessing unprecedented responses. Similarly, deep responses are being observed in melanoma patients who fail PD-1 therapies as well as if in evil. For such patients who have exhausted all available therapies, botansilumab holds the potential to be a game changer. Moreover, early clinical data indicates that important responses may be achievable in the neoadjuvant setting, possibly introducing an entirely new treatment approach and enhancing patient outcomes. The clinical data generated with botansilumab is truly inspiring, and we're thrilled with the progress we've made thus far. We firmly believe that botansilumab has the potential to reshape how we approach treating solid tumors. And we eagerly look forward to further advancements in this crucial program. With our more advanced programs, as well as on the regulatory front, we're also making significant strides. Our phase two activate studies in colorectal, melanoma, and pancreatic cancers are set to conclude enrollment in 2023. And we are expediting enrollment into our refractory non-small cell lung cancer cohort where we have previously reported 50% response rates in patients who have failed prior PD-1 and chemotherapy. We plan to launch a randomized phase 3 study if the observed response rates persist in the extended cohort in non-small cell lung cancer. We're also proud to announce the fact that butt-bowel combination has generated or has been granted fast-track designation by the FDA for treating non-MSI high colorectal patients without active liver metastases. This acknowledgment of our potential to fulfill a significant unmet medical need could accelerate the development and review of our application for approval. In conclusion, our unwavering commitment to advancing our clinical pipeline and delivering innovative treatment for cancer patients remains stronger than ever. We are enthusiastic about potential MAPS progress and its potential to profoundly impact the lives of patients with solid tumors. I will now hand it over to Dr. Stephen O'Day, will provide further details on the latest data, and then I will be coming back with my concluding remarks after that.
spk04: Steven. Thank you, Gero. Together with our investigators, we presented updates from the bowel development program at two major medical meetings last quarter, including a late-breaking oral session at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium in January in San Francisco, and an oral plenary session at the Society of Gynecologic Oncology Annual Meeting in Tampa in March. I'll now briefly describe these data updates, beginning with colorectal cancer. As Gero said, Metastatic non-MS high colorectal cancer patients treated with standard of care have a reported 12-month survival rate of only 25%, and an overall reported response rate to third-line treatments of 1% to 2%. Immunotherapy treatments of combinations PD-1 and CTLA-4 Similarly, reported poor response rates of only 1% to 5% in comparable populations. Dr. Anthony Elko-Hurry, Associate Director for Clinical Research at the USC Norris Comprehensive Cancer Center and the Keck School of Medicine at USC, presented our latest update of botanycilamine programming colorectal cancer at ASCO-GI. the cohort of 70 evaluable patients had a medium of four prior lines of therapy, and a third of the patients had already failed immunotherapy. Patients who received the bowel combination showed a 12-month overall survival rate of 63%, more than twice the reported rate of 25% for standard of care. In the subgroup without active liver mets, the 12-month overall survival was 81%. This is the targeted population for our Phase II study where we recently received fast-track designation from the FDA. Even in patients with active liver metastasis, the 12-month overall survival was 40%. indicating a survival advantage over standard of care for all patients, regardless of the presence of liver metastasis. The overall response rate for the 70 patients was 23%, with 69% of the objective responses ongoing at the time of the data cut. The disease control rate, which is inclusive of complete responses Partial responses and stable disease was 76 percent. We will share updated data from this cohort at an oral presentation at ESMO GI Conference on June 30th in Barcelona, Spain. Next, moving on to ovarian cancer, the reported response rate for standard of care in recurrent platinum-resistant refractory ovarian cancer with chemotherapy is only approximately 10%. PD-1 and CTLA-4 combinations have reported response rates of three to 10% in comparable patient populations. Dr. Bruno Bacconi, assistant professor, Harvard Medical School, presented the update of the Boten-Silliman Program in ovarian cancer at SGO's annual meeting in Tampa in March. 24 valuable patients were presented who had a median of four prior lines of therapy, and 21% had already failed immunotherapy. The majority of patients, almost 80%, were high-grade serous histology, which is the most common and most aggressive form of advanced ovarian cancer. The overall response rate was 33% in this poor risk group, and the disease control rate was 67%. Responses were durable, like colorectal cancer, with median duration of response not reached. This cohort continues to expand and enroll in our Phase 1B study. While our primary focus remains advancing the clinical development of BOT and BAL, as we continue to progress a focused, we also continue to progress a focused number of additional programs and combinations to further expand the therapeutic potential of botansilumab. and to unlock the full potential of our portfolio. Several of these programs have been selected for presentations at the upcoming ASCO conference in June in Chicago. AGEN 2373 is our CD137 agonist designed to stimulate the activation of both cytotoxic T cells and NK cells while mitigating the liver toxicities which are common to the first generation target class. Complete results from the first inhuman dose escalation study of AGEN 2373 monotherapy in patients with advanced solid tumors will be presented during an ASCO poster discussion session on Saturday, June 3rd. We expect a complete enrollment of the Phase 1b study of AGEN2373 in combination with botancilumab in PD-1 relapsed refractory melanoma in the first half of 2023. Dr. Breeland Wilkie, Director of the Sarcoma Medical Oncology at the University of Colorado School of Medicine, will deliver an oral presentation on a single-arm, open-label phase two study of Baostilumab with Xalafrilumab, our first-generation CTLA-4 antibody, plus doxorubicin in patients with advanced sarcomas at ASCO on Monday, June 5th. Finally, Insight will be presenting three poster presentations of our clinical partnered programs during the ASCO conference. Now I'll turn the call over to Christine for the financial update.
spk03: Thank you, Stephen. We ended our first quarter of 2023 with a cash, cash equivalent and short-term investment balance of $189.2 million. This compares to $193.4 million at December 31, 2022. Since quarter end, we have raised $13.6 million through sales under our market issue and sales agreement. For the first quarter ended March 31, 2023, we recognized revenue of $22.9 million and incurred a net loss of $70.9 million, which includes non-cash expenses of $24.9 million. I now turn the call back to Gero.
spk07: Thank you, both Stephen and Christine. In conclusion, we're very, very excited about the progress that we've made in our clinical programs as demonstrated by the updates that Stephen and I shared with you earlier. Our bowel combination therapy has shown remarkable potential in improving response rate, which indicate deeper benefits for patients. At the ASCO GI Conference, we reported that this benefit has translated into improved survival in our metastatic colorectal patients. And we're very encouraged that it will also translate to improved survival in many and all of the cancers that we've studied so far. Our continued innovations and progress highlight our unwavering commitment to advancing cancer care. As Stephen reported earlier, this progress also includes our ongoing exploration of our diverse portfolio, including a very exciting molecule, our anti-CD137 molecule. This is an agonistic antibody. ILT2, on the other hand, is now in clinical combinations, and of course, the combinations of our checkpoint antibodies with MINK's allogeneic INKT cell therapies. A moment about MINK. MINK's latest update at the AACR conference reported clinical responses in solid tumor cancers with their lead candidate, agent 797, an off-the-shelf INKT cell therapy. These data underscored the launch of a clinical trial in metastatic gastric cancer led by Dr. Yelena Jengigyan, who is the chief of GI cancer at Memorial Sloan Kettering. And this is externally funded by non-diluted grant financing. Mink will supply the trial with its in-house manufacturing capability, which today can produce
spk10: 5,000 doses per year with rapidly expanding capacity.
spk07: To enable access to this exciting portfolio, we've issued a dividend of Mink shares to our agenist shareholders in order for them to have the opportunity to participate in the upside of Mink directly.
spk10: As we recognize our first quarter achievements,
spk07: We're grateful for the incredible support and momentum we've built with clinical experts and patients. Our determination to bring innovative treatments for cancer patients remains steadfast, and we eagerly anticipate pushing the boundaries of what's possible in cancer care. We're actively exploring discussions with potential partners and collaborators to maximize the potential of PotencilaMath and the rest of our pipeline. Our focus is not only on managing these assets prudently, but also on building our internal capabilities. In conclusion, as an organization, we're deeply committed to revolutionizing cancer treatment by making access to high quality medicines are a very tough priority. We aim to create a simple, progressive model that ensures patients receive the best possible treatments available to them. Drawing inspiration from value-based care, patient-centric care, and integrated care systems, we focus on delivering efficient, personalized, and top-notch care for everyone who can benefit from it. Together, we strive to transform the cancer treatment landscape by putting patients first and making state-of-the-art medicines accessible to all, all who need it. You will be hearing more about these strategies and how our initiatives will integrate into these strategies in our coming communications. With that, we'd like to now open the call for any questions you may have.
spk10: And thank you, everybody, for joining us today once again. Anna?
spk09: Thank you, speakers.
spk08: At this time, I would like to remind everyone that in order to ask a question, please press star then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Emily Bodner of Wainwright. Emily, please go ahead.
spk02: Hi, good morning, and thanks for taking the questions. Maybe could you expand a bit more on what we should be expecting you to present on at ASCO for Agenda 2373? and how you kind of think about what would be positive data in that study, considering it's monotherapy. And then maybe can you just discuss if there's any other Phase II or Phase III studies that you think you could initiate this year besides the lung and colorectal cancer studies? Thanks.
spk07: So let me make a couple of more comments, and then I'll turn it over to Stephen. As you know, Emily, 2373 is a very important product. very important product because it adds some very complementary attributes to patient care and patient treatment. For example, with Botansilamab, we're activating T cells, while we're also generating memory and depleting regulatory T cells, but activating T cells better than the first-generation Now, what 2373 does, in addition, is really concentrate on the memory component of the immune system, which becomes critically important in the durability of immune response and durability of patient benefit. So that's one bucket, and I think Dr. O'Day can expand on it. But secondly, you asked about other phase two. Now, we haven't really publicly announced any of our plans with regard to additional Facebook trials or data from other programs. But just as we do very properly until, for example, we get the abstract accepted at major conferences, we won't talk about it because it jeopardizes is that remember, as we said during our call today, since late June of last year, we have presented data at oral, plenary, opening sessions, at so many major conferences, which is really unprecedented for a single product, if you look at it. So very encouraged, but stay tuned for the rest of it. But Stephen, would you like to add any comments about 2373 and other plans that we may have?
spk04: Yes, thank you for the question. So our CD137, we're incredibly excited about, and as you said, we will be updating the Phase I monotherapy trial at ASCO in a poster discussion session in the coming weeks. You know, the IO world has been focused on inhibitory checkpoints, obviously for good reason for a long time, with with CTLA-4, PD-1, and the other. The agonists have struggled mightily with toxicity issues, particularly around liver toxicity with first generation. And there was great promise that by pushing the accelerator, in addition to blocking the break of the T cell, more extraordinary things could happen. So we've designed a next-gen CD137 that, you know, really will hopefully be an important combinational partner in our arsenal and obviously for patients. So what we're looking for, you know, just from my perspective, is obviously we want to see safety with this new drug design. And obviously single-agent activity would be great and is very important, I think, in any IO asset. And we'll be updating our data in a few weeks, so stay tuned.
spk09: Great. Thank you very much.
spk08: Our next question comes from the line of Mike King of EF Hutton. Please go ahead.
spk05: Hi, guys. Good morning, and thanks for taking the questions. Congrats on the progress. Just real quick, two things. Garo, you made a comment about your inclination to move forward with a randomized trial in non-small cell lung cancer based on the results of the single arm study, but I didn't catch quite what you had said. if you had set some kind of a bar for response rates or some other criteria that would motivate you to move into a randomized trial in non-small cell.
spk07: Sure. Very good question, Mike. Thank you. So as you know, lung cancer is a hot cancer, relatively hot cancer. And so while Botansilomab has shown profound activity in cold tumors, like colorectal, warm tumors, also are a target. And in lung cancer, we've shown that in PD-1 resistant, as well as PD-1 plus chemo unresponsive or resistant tumors, we're showing, with a small denominator, admittedly, but we're showing about 50% response rates, which is really a very, very major improvement for the patient. Now, as I said, the denominator is small, and so what we're doing is really expanding the cohort of lung cancer patients so that in a relatively short period of time, we can move the denominator up to 40-50 patients. And of course, if we can maintain the kind of response rates which you've seen in about 10 patients so far, in 40-50, you will see a a huge level of game-changer interest in this. Now, with the early data, a few outside groups have shown significant interest in doing randomized trials with SNF. These will be multiple armed trials with standard of care in the earlier stage setting. So stay tuned. We have not yet announced the specific plans. But these plans are well underway for a randomized phase three trial that will include botancilumab plus a current standard of care versus the other arms that we haven't disclosed yet. But that trial should be initiated sometime this year.
spk10: Sometime this year.
spk05: Okay.
spk10: All right, super.
spk05: I mean, I got a ton of questions, but I guess on ASCO, I'm sorry, the ESMO GI, I think the last time you showed data at ASCO GI in colorectal was 70 patients, and you had the one-year response at 63%. Are we going to get those updated? Is the end going to change maybe qualitatively? Can you tell us what the data is going to look like, you know, what the complexion will be at the ASCO GI meeting?
spk07: I'll turn this to Stephen.
spk04: Yeah, thanks again for the question. Yes, so we did report 70 patients at ASCO GI, and obviously that trial was continuing to enroll at the time. It has since completed enrollment as we've launched our Phase 2 pivotal trial. So you can expect more patients and longer follow-up with the next update at ESMO GI. Okay, great.
spk10: All right, thanks. I'll jump back in queue.
spk09: Our next question comes from the line of Mayank Mamtani of B. Riley.
spk08: Please go ahead.
spk11: Good morning, team. Thanks for taking our questions and congrats on the progress. So just a couple of quick follow-ups to questions being asked before and then I have a couple more. So it was curious to see your fast track designation come in line with how this CRC data is maturing. Could you comment or specify that this updated data was submitted as part of requesting the agency for fast track and if there are any other mechanisms like breakthrough therapy or others that are being explored as you get close to getting randomized control data from the phase two study.
spk07: I think I'd be wise not to elaborate on your question. we are obviously keeping not just the FDA but other agencies abreast of developments with CRC and some of the other indications as well. Now, one thing that is sure that I think needs to be stressed over and over again, when we treat patients which are not just metastatic, for example, in CRC, but also other indications. But these patients are typically third, fourth, fifth line patients. They have been treated with pretty much everything that's available and either haven't responded or failed after they have responded to these other treatments. So these are pretty sick patients. And the kinds of responses that we're seeing, which are in the neighborhood of 20% to 50%, depending on the indication, is really something very meaningful for the patient. And, of course, from a regulatory perspective, you may say, well, response is not enough. But please explain that to the patient, that the response is not a good thing. response is a very important criteria for a patient that has exhausted all options, particularly to the kind of durable responses we're seeing of the magnitude that I just talked about. They're very meaningful, but we're also diligently pursuing that these responses will translate to longer-term benefit to patients. And of course, the data that we showed at ASCO GI with survival curves indicates And of course, mind you, this is not a randomized trial, but the differentiation in this patient population in terms of overall survival is such that we are confident that the responses are going to translate to longer-term benefit, including survival. And, you know, I may add that with CTLA-4s, typically you do see response rates correlate very well with other benefits. The same is not necessarily true with other IO treatments or other cancer treatments, but with CTLA-4 targeting agents, generally, and Dr. Odey can elaborate on this, that it would be impossible to think about a trial where response rates will not translate to survival. Steven, would you like to bring in your experience with that?
spk04: Sure, Gero. Obviously, yes, I would agree. CTLA-4 as a target, because of the durability of responses and the fact that Rhesus 1.1 underestimates clinical benefit because minor responses in stable disease can be significantly durable, has correlated well with overall survival. And just I would redirect people to The initial ipilimumab study in melanoma, of course, only had a 10% or 15% sort of classic Rhesus 1.1 response, and yet the survival curve showed a hazard ratio of 0.67. So about one in three melanoma patients were having significant clinical benefit, which is double what the response rate was, and it mimicked the plateau of the survival curve at 20% to 25%. So I think in general, CTLA-4-based therapies, whether alone or in combination with PD-1s, have correlated well with survival. And we, based on our duration of response across Botansilumab, are very hopeful it will continue to do that as we look at survival curves in our different solid tumor clinical trials.
spk11: Very helpful. Thank you. And secondly, on the non-small cell lung cancer cohort, interesting to hear you're thinking of a randomized phase three there. Could you talk to what sample size you need to see here to, you know, confirm this 50% response rate over time? And we get a lot of questions about, you know, confirmed, So could you just clarify, there was one unconfirmed PR when you last reported. Has that been confirmed with the recent scans?
spk07: Right. So I'll just give you a little bit of a hint, which is factual. As you know, Daxapaxil is the only approved therapy for patients in non-small cell lung cancer who have failed chemo and PG-1. And so this is a low bar with 9% response. So the early indications of responses that we're seeing are far in excess of that. And the only risk here is, are we preferentially putting patients that are best prognosis? And the answer is categorically to that question, no. So the 50% response rate, if continued, in a larger denominator, will demonstrate a very significant benefit for patients who have failed chemo plus PD-1 and who are otherwise going to be treated with doxotoxone, which, as I said, shows a very low bar of 9% responses so far. And those 9% responses are likely not to really show a major benefit for patients. So that's the bottom line. And, of course, we haven't released all the details on this, and we will patients with low TMB and low PD-L1 expression, which gives you a sense of what the mechanism of botansilumab is in terms of both lighting up tumors, making tumors hotter. So if you can take low TMB patients and treat them with botansilumab to make them hotter, which we seem to be doing in our trial, and you're dealing with patients that typically don't respond to PD-1 with low PD-L1 expressions, those are two very important indicators as to the status of the patients being a very poor prognosis patient. So we're very encouraged with this outcome, actually, and clearly outside groups that we're working with who would be at least partially or entirely sponsoring the in this direction.
spk11: Did you say what denominator you might be targeting here? And then just my final... Sorry, go ahead.
spk07: We haven't disclosed those numbers yet, Mayank. I think we're in the process of going back and forth and trying to finalize these details. But be rest assured, it's not going to be a thousand patients.
spk11: Understood. Thank you. And my final question on the the 2373 bot combination study that is approaching enrollment completion in melanoma, PD-L1 refractory. Could you comment on what appropriate benchmarks are, Dr. Odey, since this is your arena and what might you be looking to deliver? And if I heard you right, the timeline for that data is within first half 2023, or is it just enrollment completion, you said?
spk04: So the accrual to the cohort we expect to complete in the first half of the year. We won't have data until later in the year at the earliest. But in terms of that cohort, obviously these are very extensively treated melanoma patients that are very refractory to IO and BRAF if they're mutant. So obviously any responses in this group would be of note, and we look forward to you know, observing this data as it evolves. So heavily pretreated melanoma patients that have had, the vast majority have had both CTLA-4 and PD-1 and in BRAF mutants have already exhausted BRAF mutant therapy.
spk11: Okay, that's very helpful. Thanks for taking our questions.
spk08: Our next question comes from the line of Matthew Phipps from William Blair. Please go ahead.
spk06: Thanks for taking my question. I know the Phase II in CRC has done a good job of showing contribution to components through different arms. But I'm wondering, as you move into more indications, such as if you launch the Phase III in non-small cell lung cancer, would you have to show contribution of components in those additional arms with a bone cell met model therapy arm?
spk07: So the answer is no. We do not have to show that all over again in each and every indication, Matt.
spk06: All right, great. Thanks, Carol. Can you remind us on the timing of any Gilead opt-in decision? Is it completion of this phase one, or does it also include the next study in combo with Bodensilomab and melanoma?
spk07: Okay, so I think, you know, it's reason for a couple of things here. One is, will our interest and Gilead's interests converge here. And we don't know the answer to that question from their perspective. But we regard 2373 as a critically imposed program for us. We also believe that we need to have freedom to operate with 2373 for the best interest of a Janus portfolio. So it'll be a question of negotiation. And stay tuned. Towards the end of the year, there will be more clarity as to how and if this option will proceed.
spk06: Great. Thanks, Gero. Last one. I know we're going to get the Balsal sarcoma data at ASCO. Is there any steps forward for that combination? I know the focus has rightly switched to Brunsel map, but just curious.
spk04: Matt, you know, obviously our focus is on the next generation CTLA-4. Having said that, we think we have an excellent first generation CTLA-4 that's been in combination in cervical, and now this will be the first real data in sarcoma. So, again, let's watch the data as it gets presented, and obviously we'll make decisions. But we certainly won't distract from our primary focus, which is botansilumab and getting to market.
spk10: Yeah, that makes sense. Thanks, Dr. Dent.
spk09: There are no further questions at this time.
spk08: I turn the call back over to Mr. Gower-Arbin for closing remarks.
spk07: Thank you very much, everybody. Thanks again for joining us today. Clearly, there's a lot going on, and we are very eager to communicate things to all of our constituencies, which include certainly our shareholders, but also very importantly, investigators, KOLs, who are major stakeholders in this because of their interest with their patients to either participate in these trials and or to have these products available to them with the allowances that are there prior to approval and certainly post-approval as well. So we're very, very grateful to all of your support. The biotech markets have been challenging in the last year or so, but we're proceeding in a way that really supersedes any of these challenges. options, but even patients that are in the earlier stages of disease and can benefit from our compounds in ways that will provide them with an option which is typically not being addressed properly or effectively with current treatments. So thank you again and stay tuned. We'll see you at these upcoming conferences as well as at our next
spk09: This concludes today's conference call. You may now disconnect.
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