This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk01: Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Agenis fourth quarter 2020 conference call and webcast. At this time, all participants are in a listen-only mode. If you require operator assistance, please press star, then zero. After today's presentation, there will be an opportunity to ask questions. To ask a question during the Q&A session, you will need to press star, then one. Please note that this event is being recorded and may be used in future Agenis promotional material. I would now like to turn the conference over to John Medina, Director of Investor Relations. John, please go ahead.
spk09: Thanks, Liz, and thank you all for joining us today. Today's call is being webcast, and we will be available on our website for replay. Before we start, I just want to quickly introduce myself. I know I've spoken with a number of you already over the last month or so, but I started here at Agenis back in February to help lead the investor relations efforts. Certainly, it's a very promising time for the company. I'm looking forward to being part of the conversations we're having with the investment community. With that said, I just want 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. As a reminder, this call is being recorded for audio broadcast. Joining me today are Dr. Gary Warman, Chairman and Chief Executive Officer, Dr. Jennifer Buell, President and Chief Operating Officer, Andy Hurley, Chief Commercial Officer, and Christine Klaskin, Vice President of Finance. Also available during the question and answer session will be Dr. Stephen O'Day, our Chief Medical Officer. Dr. O'Day joined Agenis earlier this year as well, along with a number of other key hires, and brings clinical development expertise to Agenis at this pivotal time. Now I'll turn the call over to Gero to highlight our key accomplishments and our goals for 2021. Gero?
spk07: Good morning. Thank you very much. In 2020, our pipeline continued to grow with an arsenal of agents designed to activate the immune system across different types of patients and cancers on one hand, while also addressing immunotherapy resistance pathways across many tumor types on the other. We expect these advances will contribute to the IO field on multiple fronts. For instance, we are advancing AGEN 1181's clinical development and generating responses in patients who are unlikely to otherwise respond to immunotherapy. We expect to advance AGEN 1181 to registrational studies this year. We've also made substantial advances with our TIGIT programs, demonstrating the unique attributes of our bispecific antibody, which is IND ready. One of our notable achievements during 2020 was the completion of patient enrollment and data analysis of our two most clinically advanced agents, Bostilumab, which is our PD-1 antibody, and Zolifilumab, which is our first-generation CTLA-4 antibody. We call these BAL and ZAL for short. We are progressing with the completion of our BLA filing for BAL, and we'll proceed with our strategy regarding a potential BAL plus ZAL filing once BAL's BLA filing has been accepted. It is our aim to use Balthilumab as the foundation for several of our pipeline agents, as well as offer our BAL for use with therapies from other companies which require combination with a PD-1 blocker. Our objective is to rapidly enable synergistic combinations to advance the field. Synergistic combinations for our agents include cell therapies through our subsidiary, Agentis. While we are continuing our allogeneic intelligent INKT cell therapy in patients with COVID-19, we will be advancing these intelligent cells into cancer trials with combinations around midyear. Separately, at a time when the world's need for higher quantities of vaccine production grows, we are advancing our plans for producing high quantities of QS21 adjuvant from a renewable source. QS21 is an antigen-sparing adjuvant. What that means is that a vaccine formulation with QS21 may require as little as 100-fold less antigen to achieve the same immune response. If this proves to be the case for some or most COVID-19 vaccines, you can appreciate the potential implications of QS21 to be able to significantly increase global COVID-19 manufacturing capacity, that is vaccine manufacturing capacity, without the need to add additional antigen production capabilities, which is one of the major bottlenecks of today. Several of these advancements I touched upon represent important milestones. We expect some of those to result in cash accretive corporate transactions starting in the second quarter of this year. In 2020, we built on a genesis foundation of innovation and integration. These are, that is, innovation and integration are the key pillars of our business model. While COVID has posed challenges for many, including a genesis, we were early to anticipate and adjust to life in the very early stages of the pandemic. We've also rapidly adjusted to address new needs such as INKT cell therapy in patients with most severe infections of COVID-19 who are dependent on life support. We published early data from the trial and expect to share more as our trial matures. Our teams are also preparing for the scenario of a rapid or emergency use path for INKT cell therapy should the trial data look encouraging. But with all of these adjustments, our whole mission is unchanged. We will continue to innovate and advance our programs with speed. This requires integrated capabilities to reduce our dependence on outsiders on one hand, but also very importantly, retaining and continuing to acquire high talent. High talent density is key to our ability to deliver innovation. Recently, we welcomed stunning talent into our leadership team, and I will start with Dr. Stephen O'Dea, our chief medical officer, and our chief commercial officer, Andy Hurley. These two professionals are among some of the most respected names in the field. Dr. O'Dea is a pioneer in immuno-oncology. and as a clinical investigator, has been an important contributor to the success we've seen so far with Agen 1181. As we advance in the discovery and development of high-performing immune therapies, and particularly combinations, we need to have formidable players, Dr. Odey, on our team. Dr. Odey played a key role in the successful development of Yervoy and Aptivo. CTLA-4, and PD-1 agents, as well as several other cancer therapies. He has the knowledge and expertise to build on our work with 1181, cemented in place in the IO landscape, and fully maximize the compound's potential as a blockbuster therapy for cancer patients. We have big plans for Agent 1181 and will pursue accelerated pathways to advance the molecule to the market. Andy Hurley will be a key driver of our aspirations to do this. In his role as Chief Commercial Officer, Andy joined us after three decades of building teams and commercializing product in biopharma. With a Balsilumab BLA filing expected in the first half of this year, Andy will help establish Agenis as a commercial company with Balsilumab as a key actor in our plans for our ambitious combination strategies. Given our mission to develop impactful combinations for patients, Agenis requires clinical scientists with extensive and established expertise. Dr. Joe Grossman joined our team as head of exploratory medicine from Harvard and Beth Israel. His specialty includes colorectal and pancreatic cancers. Dr. Grossman will drive our translational medicine strategy, which is a key aspect of a Genesis clinical development strategy. Dr. Jason Paragas, another recent addition to our team, is an expert in data analysis and artificial intelligence. He formerly served with DARPA working on threat detection for the U.S. government and associated defense departments. Jason joined us as Vice President of Strategic Initiatives. Jason will also be working with our team to industrialize and broaden the applications of our vision response prediction technology. Next, Adam Krause joined as Chief Legal and Compliance Officer to ensure our commercial readiness, and Mark Wiles joined as Vice President of Regulatory Affairs. It is a transformative period for Agenis, and the value each of these team members bring will help drive a new level of success for the company. We understand the ambitious scale of our mission as we seek to disrupt an industry that has been challenged with disruptive demands. We believe marshalling the best people and resources is paramount to achieving success. I would now like to turn the call over to our President and Chief Operating Officer, Dr. Jennifer Beal.
spk02: Thank you, Garo. As Garo indicated, our R&D engine has been enormously productive, with numerous discoveries, IND filings, and product candidates advancing in late stage trials. As a result, 2020 was a period of significant We presented data updates on our programs at all of the leading oncology conferences last year. At CITC, AACR, and ASCA, we presented data on clinical responses with 1181, as well as the differentiation of our five lead molecules. And finally, we also presented data on our response prediction platform, VISION. With our TIGET bispecific, AGEN 1777, we presented data revealing the potential to broaden the activity beyond first generation of anti-TIGET antibodies. We've engineered an important region of the molecule, the FC region, to improve responses, expand the population of responders, and generate monotherapy activity which is not currently seen with TIDGET monospecific antibodies available today. More recently, at ESMO just a few months ago, we presented preliminary data from the Balstilamab monotherapy and Balzel combination studies, showing breakthrough activity in PD-L1 positive and PD-L1 negative cervical cancer patients. As we look into 2021, including AACR next month, We will continue our aggressive approach to data presentations, providing clinical updates on our lead compounds, including agent 1181. On our BLA filings, our rolling BLA filing for belstilumab monotherapy and second-line cervical cancer is underway. Initiated in September, we expect to complete the filing during the first half of this year. And as we disclose in September, this timeline accommodates two additional late confirmed responders seen in our pivotal trial. We'll provide the FDA with six months of follow-up on those patients, as well as 12 months median follow-up on all trial participants. We believe Belcilumab's approval would represent a meaningful new option for the cervical cancer community. We note that pembrolizumab, Keytruda, is approved in the PD-L1 positive population only and shows no clinical responses in PD-L1 negative tumors. And in the largest IO clinical trial in this population to date in over 160 patients treated with belstilumab alone, we reported response rates of 19% in PD-L1 positive patients and 10% in PD-L1 negative patients. This compares favorably to Keytruda, which has 14% responses in PD-L1 positive tumors and no responses in PD-L1 negative tumors. In addition, the durability of response in our pivotal trial was impressive, lasting approximately 15.4 months. This is not observed with chemotherapeutic options currently available for these patients. The duration of response is a hallmark of effective IO agents and ours far exceeds the limited duration of response observed with chemotherapy for these patients. We believe these clinical data reveal emerging differential features of valstilamab. We plan to publish the full clinical data set of Belstilamab in refractory cervical cancer in a high-profile journal. Additionally, we will publish preclinical data from our vision platform that further elucidates Bel's superior tumor cell killing capabilities compared to the leading commercially available PD-1 antibodies. Regarding our plans for the Balacilumab plus Alefrelumab BLA filing, we've been in ongoing discussions with the FDA. The trial has completed enrollment. The patients have concluded the median of 12 months of follow-up, and we're collecting data on late responses in this trial as well. The data continues to improve as it matures with response rates and, most importantly, duration of those responses. Agenis will continue to keep the agency informed of additional data advancements. And as Garo just discussed, we plan to disclose the timing and strategy regarding BAL and ZAL once BAL's FDA filing has been accepted. Our first approval with BAL Stilamab would mark a strategic milestone for Agenis. Having our own approved PD-1 inhibitor would allow us the freedom and flexibility for the development and commercial pricing of our combination regimens with our own I-O compounds, including CTLA-4, TIGIT, and novel molecules targeting myeloid pathways and beyond. In addition, we see a significant opportunity with our PD-1 in combination with potential partner programs. Regarding 1181, to the emerging clinical profile of 1181. Again, this is also an engineered antibody. We've engineered the FC region of the antibody to improve its features. We designed 1181 for superior efficacy with improved T cell priming and the capability to deplete suppressive intratumoral regulatory T cells. We've also designed the molecule for better safety, avoiding complement-mediated toxicities, and broaden the patient population who can benefit from CTLA-4. That's because of improved binding to CD16, and we're seeing activity in patients with both the low-affinity and the high-affinity CD16 allele. We believe agent 1181 continues to show nothing less than extraordinary promise as a differentiated anti-CTLA-4. This potential is upheld in the new data Janice announced early in February that describes new confirmed responses. As of February, a total of six confirmed responses with 1181 monotherapy and 1181 plus bowel have been reported in colon, ovarian, and endometrial cancers, including two complete responses. Further, we've seen responses in cold tumors. These are tumors that have low tumor mutational burden, microsatellite stable disease, and PD-L1 negative tumors, as well as BRCA negative tumors, and tumors with a low affinity CD16 allele. This is what makes 1181 unique. These are tumors where current IO therapy is largely ineffective. In addition, no debilitating neuroendocrine toxicities or liver toxicities have been observed, unlike what we see in patients treated with Yervoy experiencing 10% to 15% toxicities. Looking ahead with 1181, currently in Phase II development, our goal is a fast-to-market strategy targeting indications that currently have few effective treatments and in patients who have failed prior standard therapies. Trials are continuing with 1181 alone and in combination with Belstilamab, with expanded cohorts in microsatellite-stable colorectal cancer, microsatellite-stable endometrial cancer, non-small cell lung cancer, and melanoma. With continued positive clinical data, a registration program expected to begin by the end of this year, and it's with great excitement that we brought on board Dr. Stephen O'Day. an expert in delivering effective IO agents to patients with cancer. Agent 1181 alone and as the backbone of high impact combinations could be a foundational therapy if approved, driving the next wave of IO treatments. Our initial registrational plan will focus on indications for rapid launch through the accelerated approval pathway as a monotherapy or on top of our PD-1 or any approved PD-1. Based on our preclinical and clinical data to date, our ambitions with 1181 plus PD-1 are to be the dominant IO combination with the potential to overtake Yervoy and Opdivo, or Chemo, and Keytruda as the market leader. We're actively seeking the right partner to execute this strategy and dominate in this sector. At the upcoming AACR conference in April, we'll present two abstracts featuring Agent 1181 alone and in combination with other IO mechanisms, such as our anti-PD-1 therapy, Valstilamab, will showcase how the unique design of this molecule is expanding the benefit of this important target to drive responses in all polymorphic variants, and the ability to provide clinical benefit in previously unresponsive tumors. We'll also show the benefit of adding 1181 to other checkpoint inhibitors, such as anti-PD-1, anti-TIGET, INKT activating therapy, and adoptive T cell therapy. Novel IO combinations will drive the next wave of IO therapy, and Agenis believes that 1181 alone and in combination with other mechanisms is the foundation of this next wave. Let's turn now for a moment to work on TIGIT. Not unlike CTLA-4 and PD-1, TIGIT is one of the key components in our immune system. It's found on T cells, and by suppressing unnecessary activity, like the activation of T cells, it helps keep the immune system properly balanced. Usually, TIGIT is invaluable to good health, but in cancer patients, TIGIT's suppression of the immune system allows tumors to grow. An important finding is that treatment with PD-1 actually upregulates TIGIT, consequently curbing the activity of TIGIT. Often using antibodies has become an area of intense R&D effort, and anti-TIGIT therapy is set to be another breakthrough in I.O., Agenis has two anti-tigit antibodies. This is Agen 1327, a mono-specific antibody that's also engineered, like Agen 1181, to improve performance, and Agen 1777, a bispecific antibody that includes a tigit arm that has also been engineered for FC enhancement. As a potentially best-in-class agent, we're prioritizing Agen 1777 for advancement into the clinic and expect to begin human studies this year. What makes AGEN 1777 potential best in class? Similar to 1181, we've designed the front end of 1777 for strong receptor binding. In this case, to TIGIT. We've also engineered the FC backend for improved T-cell and NK cell activation. in order to more effectively unleash the immune system. We've gone one step further with 1777 by engineering it as a bispecific antibody, co-targeting a second tumor escape mechanism to create a double blockade against cancer escape. This dual blockade is designed to address a potential alternate escape mechanism to TIGIT therapy. Overall, we believe the combination of our FC-enhanced and co-targeting with our agent 1777 bispecific gives it best-in-class potential. And as Garo mentioned, potentially provides strong efficacy not just in combination with other IO mechanisms, but also uniquely as a single agent. Some of this has already been demonstrated in preclinical tumor models, and we eagerly anticipate clinical trial initiation this year. Our TIGIT strategy was also recently featured and our first episode of Agenis Insights. This is our new R&D miniseries that provides insight into impactful areas of research and Agenis' contribution to immune oncology. We encourage you to watch the replay and to stay tuned for more episodes in the coming months. Through our Agenis subsidiary, we've developed a platform to produce invariant natural killer T-cells, or INKTs. INKTs are a type of self-directed, intelligent immune cells capable of producing responses from both the innate and the adaptive arms of the immune system. INKTs can combat multiple disease threats in an autonomous manner. In inflammatory disorders, INKTs help to restore the balance of the immune system, correcting conditions like the cytokine storm that we see in patients with severe cases of COVID-19. Earlier this year, we announced preliminary phase one data from our COVID trial, currently ongoing. Dose escalation for an initiation into a phase two trial is on track for the first half of this year, and data readouts are expected in the fourth quarter. Now in cancer, INKTs home in on tissues and direct the killing of tumor cells. They have an invariant TCR receptor. It doesn't need to be engineered to them. This will counter immune suppressor cells and block tumor escape mechanisms. You can imagine the benefit of this homing feature we observe in lung tissue in the infectious disease setting to be very impactful in diseases like lung cancer. And as a cell therapy, INKTs have the potential to be used on their own and in combination with additional anti-cancer therapies such as those already in our pipeline. Agentes' first INKT, phase one trial in cancer, is anticipated to start dosing during the first half of this year, and we're targeting human studies to be initiated in solid tumors soon thereafter. Lastly, while we often discuss our IO pipeline compounds in isolation, there's clearly tremendous value in the combination potential for the cancer pathways we're targeting. PD-1, CTLA-4, TIGIDS, INKT therapy, and other promising mechanisms and programs we have not yet discussed on this call. Stay tuned for more on these exciting developments and the balance of this year. I'll now turn the call over to our Chief Commercial Officer, Andy Hurley, to elaborate on our excitement regarding AGENT 1181.
spk10: Thank you, Jen. My decision to join the AGENAS team was driven by the excitement we all feel and the opportunities we have here under one roof. I'm also driven by our near-term prospects, which I believe could create substantial value. I'm particularly excited by how we can take our PD-1 Belstilumab and potentially grow it into a major franchise with a superior combination potential with Agent 1181. I believe 1181 will significantly expand the commercial opportunity of our anti-PD-1 with the potential to outperform current IO combinations. Clinical results to date have been very exciting, both as a monotherapy and in combinations across a wide array of tumor types. Specifically, as Jen said, cold tumors, such as microsatellite stable tumors, represent a significant portion within colorectal and endometrial cancers. And traditional PD-1 anti-CTLA-4 inhibitor therapies have not been as effective here. These are tumors which don't generally respond to cancer immunotherapy, and yet we are seeing responses with agent 1181. Practically and conceptually, we're not limited to any tumor type if the current response trends we are seeing continue. It's really a function of picking patients and indications which can get us to the finish line quickly and leverage this to expand on our broader opportunities. Having our own PD-1 to pair with our superior CTLA-4 And then having our own unique CTLA-4, which can add significant value to our PD-1, are advantages which are very exciting for us to pursue. And then there's the rest of our pipeline, including our intelligent cell therapy program, our vaccines, an exciting pipeline of antibodies with compelling early data. I feel the privilege of working with an exceptional team of people across all disciplines. I have worked at highly successful companies but what we have here is very, very unique and exciting. I hope to interact with you more frequently and do a deeper dive on our commercial strategy to create something exceptional. I appreciate the opportunity to express my plans, and I'll now turn the call over to Christine Klaskin to review our financials.
spk03: Thank you, Andy. For the year ended December 31st, 2020, we recognized revenue of $88 million, which includes revenue related to the upfront license fee from our transaction with Beta, in addition to non-cash royalties and milestones earned. For the year ended 2019, we recorded revenue of $150 million, which included revenue related to the upfront license fee from our transaction with Gilead and milestones earned, in addition to non-cash royalties earned. Net loss for the fourth quarter was $38 million, or 20 cents per share, compared to a net loss for the same period in 2019 of $31 million, or 22 cents per share. Net loss for 2020 was $183 million, or $1.05 per share, compared to a net loss for 2019 of $112 million, or 80 cents per share. We ended 2020 with a cash balance of $100 million as compared to $62 million on December 31st, 2019. I will now turn the call back to Garo for concluding remarks.
spk07: In closing, the progress Agenis has made in the past year has set the stage for an exciting 2021. We expect to achieve value-driving corporate events clinical and preclinical pipeline events starting in the second quarter of this year, and they will include completing our BLA filing for Balsilumab monotherapy in second-line cervical cancer, preparing for commercial launch in the second-line cervical cancer market, defining our BLA filing strategy for Balsal, clinical and preclinical data presentations at conferences including, or BALSAL, 1181, TIGIT, INKT cell therapy, and other agenus and partner programs. Initiating clinical studies with our TIGIT program, with the prioritization of AGEN 1777, continuing with our Phase II development for AGEN 1181 plus malthilumab with a goal of transitioning into registrational studies, continuing enrollment in the ongoing Phase I studies of INKTs in COVID and in cancer, expanding the Genesis West capacity for internal and partnered manufacturing support, producing a sustainable supply of QS21 for partnered programs, and lastly, delivering cash-accretive corporate transactions starting in the second quarter of this year. Thank you very much again for your interest, and now we're ready to open up for questions with myself, Dr. Buell, Andy Hurley, and Dr. Stephen O'Day present. John? Maybe it's the... Liz, if you could get the Q&A going, please.
spk01: Ladies and gentlemen, if you'd like to ask a question at this time, please press the star, then the number one key on your touchtone telephone. Again, that is star, then one, if you'd like to ask a question at this time. Our first question comes from the line of Birnamin with Jeffrey's.
spk08: Yeah, hey, guys, this is Jeet on for Barron. Thanks for taking my questions. Congratulations on the progress to date and looking forward to updates this year. Could you just maybe walk me through the timing perhaps between the BAL BLA filing and when you actually anticipate submitting the combo and perhaps when, you know, ultimate approval is perhaps expected there? And then second, just if you could talk through perhaps some of your go-to-market efforts to this point and any goals for the remainder of this year. And if there's any, you know, color on discussions with payers or thoughts on pricing, that would be great. Thank you.
spk07: Thank you, Viren. Let me start out addressing the Belzell question. As you know, and as we sort of alluded to, as data matures, looking at our past performance with data disclosures, we're delighted to see that the data is getting better. And I think, you know, given the size of our company and given the enormous demands on us for regulatory undertakings, we made a decision several months ago, which we articulated to the investment community, that our first priority is to file our BLA with Balcilla Map. And once that's done, we will provide additional guidance for our timelines associated with our Balsall filing. And of course, that will include disclosure of more mature data, which we're in the process of addressing both from a public disclosure perspective as well as disclosing it to the agency. Got it. As far as the market, go-to-market strategy, I'm assuming you're talking about go-to-product market strategy. And with that, I think, Andy, are you prepared to give us some initial remarks?
spk10: Sure. Yeah, it's a good question. You know, I've been here an unlimited amount of time, but I can tell you that the launch planning is underway. We're really evaluating how we're going to really address the unmet needs in the marketplace and position this product in a way that addresses those unmet needs. both at a physician level as well as at a patient level. And at the patient level, you bring up the question on pricing and access. That's going to be one of our absolute paramount priorities, is just to ensure unencumbered access to Valcilumab as we look at the landscape that that's going to follow. You know, we look at this as a pivotal... part in our relationship with payers because we don't believe this is going to be, of course, our first and only into the marketplace. We want to be able to follow on with other products. And establishing those relationships and making sure that they understand our goals, which is unencumbered patient access, is going to be really key. So we're going to be starting those discussions with payers. We've done a lot of market research to understand really what are the drivers to position our product. And we're really... encouraged by what we're hearing to be able to offer that in a setting both at the physician and patient level. So I can tell you that I'm week four into the role, and ultimately I'm very encouraged by the level of effort that's already been put in and our planning moving forward.
spk08: Got it. And if I could just ask one more follow-up question. On 1181, it seems like the AACR presentation will be fairly preclinical in nature. Just wanted to know if we can anticipate perhaps, you know, a robust clinical update on that perhaps later this year, and if we'll maybe get a look at that Phase II data in colorectal.
spk02: Thanks. Hi, Jeet. Thanks for the question. Actually, AACR certainly will include some preclinical information, but of course we will also provide a clinical update on where we are with the programs. So stay tuned for more on that.
spk01: Our next question comes from Mayak Mamthani with B Reilly Securities.
spk06: Good morning, team. Appreciate the comprehensive update, and thanks for taking our questions. And great to have Dr. Odeh and Andy be part of the discussion. So maybe just piggybacking on the previous question on the, you know, the upcoming 1181 clinical data at ACR. Would you also have a more updated cutoff relative to February 9th? Could you just clarify that? And maybe, Dr. O'Day, if you could comment on why MSS colorectal indication kind of makes the first to pursue as you think about fast to market. Could you just talk about the dynamics of that indication?
spk02: So before I turn it over to Dr. O'Day, Mayank, thanks for your question. At AACR, yes, we will have a more mature... data than what we've previously disclosed and this will include more information on duration as well as potential new responses in the program too. Now I'll turn it over to Dr. O'Dea to give you his thinking on MSS colorectal cancer.
spk04: Thank you, Myron. Well, as Andy said, I'm new to the company in recent months, but I have had the unique opportunity to be involved with 1181 over the course of the last several years, both in learning about its exciting drug design as well as preclinical data, and then obviously being involved as the principal investigator in the 1181 Phase I trial. What's exciting to me is the preclinical data of more activity and more Treg depletion, as well as more potential access to low-affinity CD16 alleles all seems to be playing out so far in the clinic with our Phase I trial. As you can imagine, with the competitive nature and approvals across IO indications and solid tumors, Phase I trials have attract fairly cold tumors that are MS stable, and there's no surprise that our trial has attracted those patients, particularly colorectal, endometrial MS stable, ovarian, and others. And what's exciting to me is to see objective responses, obviously, in both 1181 monotherapy and combinations in these cold tumors that are predominantly PD-L1 negative, MS stable, low tumor burden. And, interestingly, in CD16 lower heterozygous affinity polymorphisms. which is all consistent with preclinical data. So given that fact, obviously I'm excited to be part of the development of this drug as we go forward. And colorectal MS stable cohorts are clearly a huge unmet need with a low bar in the second and third line settings. So we're going to follow the data and expand these cohorts in cold tumors forward as well as look at our warm to hot tumors, both lung and then cutaneous tumors, melanoma and non-melanoma cutaneous skin tumors, are real opportunities for us to look both at this agent and single agent as well as combination. So it's going to be an exciting coming year for me and my clinical team to develop this very exciting drug.
spk06: Oh, fantastic. That's very helpful. And then on two quick ones for Jen, and I have one more for Gero to close. Jen, what would be the path for QS21, just from a clinical development standpoint, and also on the digit-by-specific? When do you expect, you know, disclosing the other target you're working on?
spk02: So let me start with Tidget disclosing. As you can imagine, this is an incredibly competitive space. We have a buy specific that is a first of its kind, we believe, and it's designed really to address an entirely new area. So we will not be disclosing that anytime soon, but we'll certainly keep you informed as the data continue to progress both pre-clinically and then clinically. And that may drive our decision on disclosures. For QS21, the development is really straightforward. So as you know, Bill and Melinda Gates Foundation had invested in our initiative to advance a sustainable supply of QS21. We've done so. We're in the process of doing so, but we've already generated early data and demonstrated the biocomparability of this new supply compared to the previous clinic version, which is now in the approved Shingrix vaccine, as you know. So the development is straightforward. It's preclinical comparability, and then the clinical program will be very abbreviated to bring this product into market with a number of vaccine products underway, and particularly at this time when we see the criticality of effective vaccines. We know that historical vaccines no longer cut it. Flu vaccines at 30% efficacy just won't do it, so we need to improve Our ability to take antigens allow for mass global production of those, and this is where QS21 is really critical at antigen sparing, allowing a fewer number or a lower amount of antigens to actually be quite effective. As you see with Shingrix, it's over 90%, up to 97% effective in adults and gets better with age. These are the kinds of findings that we're going to need across the board as we deal with these mutating viruses repeatedly.
spk06: Okay, very helpful. So a number of different disease indications that you may consider, including flu, including COVID, even shingles. Understood. Then last for Gero, as you think about these cash accretive transactions, can you just high level talk to the framework that you guys are kind of evaluating internally when you think about prosecuting these opportunities, you know, across the board, more advanced late-stage versus earlier-stage programs. Kind of how do you think about, you know, a lot of push and pull that might be associated with these transactions?
spk07: Right. So all I can tell you right now is stay tuned. As I said, in the – second quarter, starting in the second quarter, we will see cash accretive transactions, including corporate transactions. So, unfortunately, I cannot disclose anything more than that right now.
spk06: Okay. Thanks for taking my questions.
spk01: As a reminder, ladies and gentlemen, that is star then one if you'd like to ask a question. Our next question comes from the line of Matt Fitz with William Blair.
spk05: Good morning. Thanks for taking my question. Um, so this morning, Sanofi and Regeneron announced positive phase three results of Moteo and cervical cancer. I know you guys had previously kind of hinted at needing to get that accelerated approval BLA in before, uh, you know, a full approval was there. I assume, you know, given you guys are close to finishing the bowel BLA, that the phase three positive results aren't going to affect that, uh, at this point, but just wanted to confirm.
spk02: Hi, Matt. Thanks for the question. Yeah, I agree with you. So the accelerated approval pathway remains open until full approval is granted in the same indication. Based on where we are with our filing, we don't believe this will impact our plans.
spk05: And similarly, obviously, since the Val-Val combo, that accelerated pathway should still be there as well.
spk02: For Val-Val combo, absolutely. Yeah, there's actually – we're the front-runner there.
spk05: Yes. All right, great. Thanks for taking the question.
spk01: Thanks, Matt. I'm showing no further questions in queue at this time. I'd like to turn the call back to Garo Arman for closing remarks.
spk07: Thank you very much, everybody. I think we have covered some of the really important highlights. I know that there is a considerable amount in our roster here. We do prioritize some of the most important near-term priorities for us, And so bear with us, and I think with our new star team or added star team, I'm confident that we will be taking a number of these programs to the finish line expeditiously. Thank you very much, and we'll see you next time.
spk01: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
Disclaimer