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spk07: Greetings, and welcome to FSTAR first quarter 2022 earnings conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, John Francis, Managing Director of Life Science Advisors. Please proceed, sir.
spk03: Good morning, everyone, and thank you for joining us. With me today is the Chief Executive Officer of FSTAR Therapeutics, Elliot Forster, and Chief Financial Officer, Darlene Deptula-Hicks. We announced financial results pre-market today for the quarter ended March 31st, 2022. You can access the press release on the investor relations page of our website at fstar.com. Before we get started, let's quickly run through the forward-looking statements. Please note, that is a part of our discussion today, management will be making forward-looking statements. These statements are not guarantees of future performance, and therefore, you should not place undue reliance on them. Investors are also cautioned that statements that are not strictly historical constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause the actual results to differ materially from those anticipated. These risks include risks that and uncertainties detailed in FSTAR's filings with the SEC. The company undertakes no obligation to update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this conference call. With that, I'll hand the call over to Elliot. Thank you, John.
spk02: And thank you and good morning, everyone. As ever, it's a pleasure to speak with you today and review FSTAR's first quarter of this year. It's only been eight weeks since we last met, but every new month brings increased confidence in our portfolio. We're pleased with progress across all four programs, and in particular, their performance in the clinic. Against the backdrop of a tough ongoing biotech market, we're getting on with the job at hand. Our mission is, of course, to transform the lives of patients and ultimately achieve a future that's free from cancer. Looking back over the first three months of the year, I'm pleased to report that we've continued to build momentum across each of our programs. All four are progressing well in the clinic. In the last quarter, for each of our three tetravalent bispecific assets, FS118, FS222, and FS120, we've increased the number of clinical research sites and added new countries. So, as well as the patients enrolled in the U.S., we've also dosed our first FS118 and FS120 patients in Europe. We're very excited about the full set of important clinical data coming this year. As you recall, our preference is to release data at scientific conferences where possible. We strengthened our drug development capabilities by welcoming James Sandy to our company as Chief Development Officer. With more than three decades of clinical development experience, James brings valuable additional expertise to the team in accelerating cancer treatment programs through early stage and late stage development and that will greatly benefit our clinical development strategy. We were pleased to present a poster on FS118's novel mechanism of action at the American Association for Cancer Research annual meeting in April. Our data reveals the unique tetravalent structure of FS118 plays a crucial role in driving LAG3 shedding and cell surface reduction on tumor infiltrating lymphocytes, enabling FS118 to overcome compensatory upregulation of LAG3 induced by PDL or PD1 blockade. And with the positive news from the field, including the recent approval of BMS's LAG3 antibody in combination with PD1, LAG3 has become the de facto third checkpoint inhibitor. Our partnerships continue to advance well. In this past quarter, Merck KGAA Darmstadt, Germany, exercised a fourth licensing option to develop another bispecific program under our ongoing immune oncology collaboration. I guess it's Just as a reminder, the potential revenue from this collaboration is up to approximately $765 million in milestone payments. This is just one of the more than 20 partner programs that are advancing this year based on the discovery capabilities of the FSTAR platform. Also this quarter, the U.S. Patent and Trademark Office granted a patent protecting the composition of matter for FS118. This new patent is expected to provide FSTAR with exclusivity for FS118 out to at least August 2038. We also held a two-day meeting of our scientific advisory board in the last quarter. It's always time well spent to discuss our programs and hear the views and gain support from these internationally-rounded experts for our future development plans. By the way, I was particularly struck by one of our advisors reminding us that five in every six patients with head and neck cancer continues to face the most difficult conversations about their futures. And despite the remarkable progress of the immune oncology treatment over the past decade, we are very mindful of the majority of patients who are running out of options. We also continued with a busy program of meetings with existing shareholders and potential new investors. We're greatly encouraged by the interest shown in our programs across the portfolio and grateful for the opportunity to share information with those investors. As ever, it was a pleasure to present our programs at several investor conferences, and thanks to our analysts for arranging those. So, bispecifics have huge potential to deliver different and better outcomes for patients with cancer. This is backed up by our own data and by that above us. Bispecifics really are now coming of age. They behave differently from monoclonal antibodies and even combinations of monoclonal antibodies. It's this difference that brings hope for improvement treatment options beyond first-generation checkpoint inhibitors, particularly for hard-to-treat cancers in patients with few other options. The promise of next-generation immune oncology is reflected by the extraordinary amount of capital being invested in bispecific drug development. Bispecifics now represent nearly 20% of the clinical antibody pipeline, and new collaborations account for more than $18 billion in deal value over the past two years. For example, the AstraZeneca-Harbour Biomed deal, worth $25 million up front, further reinforces the growing importance of biospecifics. Today, four biospecific drugs have already been approved, and without question, we expect the pace of investment and future approvals for biospecifics only to accelerate over time.
spk05: We firmly believe our tetravalent biospecifics are amongst the best in class.
spk02: Our plug-and-play platform enables the rapid creation of natural, full-length human bispecific antibodies that are designed for safe, potent immune activation in the tumor microenvironment. Here you can see a model of the natural human IgG1 molecule with two natural binding sites at the top of the antibody highlighted in blue. We make our bispecifics by introducing two new binding sites at the bottom of the antibody structure highlighted in green. These are spatially closer together and in a more constrained structure, pointing outwards, enabling binding to both targets. To achieve these new binding sites, we're not adding additional loops or domains, but rather making direct changes to those amino acids in a highly conservative and effective manner. We're not disrupting the antibody structure and functions, but rather in an elegant way, making it tetravalent. That is, two binding sites for one target and two for the other. evoking novel biology we summarize as cross-linking, clustering, and conditionality. On top of all of this, with so few changes to the natural human antibody format, manufacturing is a straightforward process, giving us antibody-like yields and stability. All of this is protected by more than 500 patents, granted and pending. This is our most significant year as a clinical stage company, with data expected from all four programs before year end. These are the most important value drivers for F-Star. Success in just one of our four programs, and of course, we hope and anticipate for success in more than one, will be transformative for patients, the company, our shareholders, and for the field of immunotherapy. I'll now talk through our program, starting with FS118. FS118 targets two clinically validated inhibitory checkpoints. PD-L1, and LAG3. It's currently being tested in two different patient settings, checkpoint inhibitor-naive patients in non-small-cell lung cancer and diffuse large B-cell lymphoma, and in head and neck cancer patients with PD-1-acquired resistance. For this head and neck cancer patient group, we've commenced additional patient enrollment in Europe to account for fewer available biopsies than initially planned and in anticipation of the expansion of the proof-of-concept trial. As the war in Ukraine continues, our thoughts are with all of those affected, including the medical and patient community there. As we said in our last earnings call, the checkpoint inhibitor naive non-small cell component of the FS118 trials was affected by the conflict. But I'm pleased to say that the contingency plan we mentioned at the time is now being implemented. We remain confident about the prospects for FS118, and I look forward to updating you on preliminary data from the head and neck study in the coming few months. FS222 continues to promise best-in-class data, and we're encouraged by how well it continues to progress in the clinic. FS222 is designed to target a wide range of patients, including those with PD-L1 high and PD-L1 low expressing tumors. It benefits from all of the unique aspects of our platform technology. The program has the potential to be truly transformational for those patients who are not getting the full benefit of first-generation immune oncology therapies. It's worth highlighting that in preclinical studies, we observed 100% survival and tumor clearance with FS222, and that's without having to combine with PD-1 inhibitors. As we've previously described, FS222 is designed for avidity and, as such, balances the affinity profile against both the co-stimulatory CD137 and the inhibitory PD-L1 targets. This leads to dose-dependent, PD-L1-driven CD137 T-cell redirection and activation. We look forward to sharing the data from Part A of the Phase 1 trial, including safety and any early signs of efficacy, in the coming few months. First in class, FS120, with its triple immune activation, aims to improve checkpoint inhibitor or chemotherapy treatment outcomes for patients. Being tumor agnostic, it builds on the potential of current standards of care. FS120 co-stimulates OX40 and CD137, two key targets found on the surface of T cells. The start of a combination trial of FS120 with Merck's Pembrolizumab is on track, and we look forward to updating you on progress later this year. And finally, SB11285, our next generation intravenously administered novel sting agonist. Dose escalation is still ongoing successfully in phase one clinical trial. We look forward to sharing more clinical data with you later this year. Furthermore, we were pleased to read independent commentary from Dr. Michael Curran from the MD Anderson Cancer Center in Houston, who pointed out that SB11285 may have the best therapeutic window amongst systemic sting agonists currently under clinical evaluation. Under the terms of the Contingent Value Rights Agreement for SB 11385, we continue to explore partnering options for the program as a further source of non-dilutive funding for the company. We're also pleased with the high level of interest in next-generation sting therapies at the recent AACR. Discovery work also continues in the lab, of course, and we'll share news on this later in the year. We continue to benefit from ongoing and growing partnership income. It's clear that partnerships will continue to be part of our company's future, building on those we have today and bringing non-dilutive capital and further patient benefit from our extensive antibody discovery technology. Here's a summary of the milestones we anticipate over the next two years from our programs. As you can see, we're entering a data-rich period, which we believe will generate multiple value-driving catalysts. Our confidence in our portfolio grows day by day, and on this basis, we look forward to sharing clinical data from all four programs in the coming months. At the same time, we'll share with investors our plans to deliver on our future ambitions. It's been a pleasure to share this corporate update with you, and we'll continue our outreach to the investment community, providing insight into how we both plan to help more patients with cancer live longer and better lives, and unlock long-term shareholder value. And with that, I'll hand over to our CFO, Darlene, to give you an update on our financials. Darlene.
spk07: Thanks, Elliot, and good morning, everyone. As you've just heard, it's been a busy first quarter of 2022 for the company as we continue to build on the momentum we've carried through from last year. We're excited to be making great progress in all four clinical programs. And just as a reminder, success in any one of these four programs would be absolutely transformative for the financial performance of the company and for our shareholders. I'll now go through the financial results for the first quarter ending March 31st, 2022, which demonstrates strong financial performance as we execute against our strategy. We'll be happy to take questions at the end. Cash and cash equivalents as of March 31st, 2022, were $68.8 million as compared to $78.5 million at December 31st, 2021. As part of our partnering strategy, Merck KGAA also took their fourth licensing option during this first quarter. We expect our cash and cash equivalents will be sufficient to fund our projected operating plans, including multiple clinical milestones across all four programs through the first quarter of 2023. Revenue for the first quarter of 2022 was $2.6 million, as compared with $2.9 million for the same period in the prior year. In both periods, Merck exercised their option to acquire IP rights to their third and fourth molecules under our license and collaboration agreement. Total R&D expenses were $8 million for the three months ended March 31st, 22, as compared to $7.1 million for the prior year first quarter. This $900,000 increase is primarily due to an increase in clinical CRO costs of $1.4 million, resulting from an increased number of patients on our four clinical trials, an increase of $1.2 million of R&D staff-related costs, primarily to support clinical operations, and an increase of $0.4 million of other costs, all of which are offset by decreases in manufacturing costs of $0.4 million due to the timing of batch manufacturing activities, and $1.7 million increase in the UK Research and Development Tax Credit, which is recorded as a reduction of R&D costs. The total R&D expenses include $0.5 million and $0.4 million of non-cash stock-based compensation expense for both the first quarter of 2022 and 2021, respectively. Total G&A expenses were $5.7 million for the three months ended March 31, 2022, as compared to $6.4 million for the prior year first quarter. This $0.7 million decrease is primarily due to a decrease in stock compensation expense of $0.8 million, a decrease in legal and professional costs of $0.4 million, which is due to costs incurred in the prior year quarter for work related to the share exchange agreement with Springbank Pharmaceuticals. These decreased costs were offset by increases of $0.4 million in facilities and IT-related expenses and other general costs of $0.1 million. Total G&A expense also includes $1 million and $1.8 million of non-cash stock-based compensation expense for Q1 2022 and 2021, respectively. Net loss for the first quarter of 2022 was $12.1 million, or $0.57 per basic and diluted share, compared with a net loss of $9.7 million or $1.07 per basic and diluted share for the first quarter of 2021. In closing, the first quarter of 22 has brought growing momentum and increased confidence in our portfolio. We're well positioned to deliver on our strategy in the coming months, and we're very excited by the important data readouts across all four of our programs expected later this year. With bispecifics coming of age, it's a very important time for F-stars. We continue to pioneer bispecifics to help more people with cancer live longer and better lives. With that, operator, we'll open the call for questions now. Thank you. At this time, we'll be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. One moment, please, while we poll for questions. Our first question is from Dana Grace Bosch with SCB Securities. Please proceed with your question.
spk06: Yeah, one sort of process question and one science question for me. On the process side, on FS118 specifically, you know, you're guiding to preliminary data from phase two sort of in the midyear, but also guiding to medical conferences. And I wonder if you could give us any more details on what potential medical conferences you would be submitting to and about how many patients we could expect. And then on the science side, in your recent AACR poster, perhaps the most intriguing thing was the difference in the LAG3 cleavage dynamics for T cells in the tumor versus the blood. And I wonder if you could describe that and what you think is mechanistically driving the difference in those two compartments.
spk02: Morning, Dana. Thanks for both those questions. So just to pick off the process one first, as a company in common with many, our preference is typically to go to technical or medical conferences in order to present new data. Clearly, that's only if the timing of those conferences work with the timing of the delivery of the data. For FS118, we're working towards the reporting of the proof of concept study, as you mentioned, in head and neck. And we'll make a judgment over the coming few weeks as to where that data will be presented. So either at a conference or we'll use a company press release and conference call associated with that. And we're not far away from making that judgment right now. We've guided in the past that we're looking for a minimum of 10 valuable patients, so that's patients who have the right co-expression of LAG3 and PDR1 with the head and neck acquired resistance profile. And again, we'll be working to ensure we have at least that number available to present. And then for the second question, which relates to the AACR paper, the difference between lag expression on the tills versus in the blood. We're actually in the process of drafting a paper around this, so I'm going to be reasonably cagey on the mechanism. But I guess I think as you'd understand with the cross-linking and clustering in particular in the cell-to-cell environment, you'd expect to see in the tumor a dramatic regulation. And I think as far as I can go right now in the blood is to say that there is a possibility of compensatory mechanisms with respect to LAG3 expression. So that's one of the reasons we're potentially seeing some differences there. But as I say, we're working on that manuscript. But I guess fundamentally the key being we're seeing the drop in LAG3 in TILs in patients.
spk05: Great. Thank you very much. Thanks, Dana.
spk07: Our next question comes from Matt Phipps with William Blair. Please proceed with your question.
spk04: Good morning, everyone. This is Rob Andrew on for Matt Phipps here. I just wanted to return to the comments on the FS118 trial as well here. The addition of more trial sites in anticipation of expansion definitely seems like a positive step. Could you just remind us, have you specifically disclosed the bar for expanding that study? And how are you kind of accounting for the fact that you haven't been able to get biopsy samples from all those patients when you're thinking about the bar there? Did I catch it right that those patients without biopsies are not going to be considered among the 10 valuable patients she described? And then, you know, secondly, just a kind of a broader question. Clearly, the FDA is kind of focusing on the earlier stage clinical development and dose optimization with Project Optimist. We saw the FDA host a two-day panel on the subject of dose optimization last week in which some immunotherapies were kind of used as examples of where dose optimization could have been better in early stage development. So just kind of how you're thinking about that in the whole context of your own pipeline in terms of how to best satisfy FDA that sufficient dose optimization has been carried out in these kind of phase one studies across the pipeline. Thanks.
spk02: Great. Thanks very much, Robin. And thanks for your question. Good morning. So with respect to biopsies, what we've been doing is collecting biopsies, and then we have prospectively defined a retrospective analysis of the PD-L1 LAG3 positivity in the biopsies, and we're looking in reverse, as it were, to see how the patients do who have that appropriate biopsy biomarker profile with the head and neck cancer. What we haven't stated, as you rightly say, is what the bar for success is. However, what we have been doing over the past quarter is adding more patients through our sites in Europe to this and, of course, the other FS1-1A trials that are ongoing. And so we're I guess what we're going to ensure is that we have the right level of evaluability. And I think it's right to be prepared for success and hence why we're prepping for the second part of the study at the same time. So with respect to Project Optimus, really, I think this is a measure of ensuring we have a kind of lowest effective dose. For FS118, we're pretty comfortable given And some of this is about to be published in a full manuscript. We're pretty comfortable that we've now got what will be defined as an appropriately selected dose, obviously still to be discussed with the FDA. For the other programs, it also brings sort of new ways of thinking about the program. So FS-222 and FS-120, because we've got drugs that are really well tolerated, and we can continue to escalate the dose. What you'll see from us is that we've explored more than one dose level for each of those programs as we've gone through the early stages of development, really with a mind to being able to ultimately discuss with the FDA at the end of phase one or pre-phase two meeting as to whether they want us to carry one or maybe two doses forward And we're building a biological and patient rationale around each of those considerations. It's more pertinent for the FS222 and FS120 than for 118, where we're pretty comfortable.
spk05: We've got a package of data that gives us confidence in the dose level we're at. Great. Thanks very much. Thanks, Rob.
spk07: Our next question comes from Hartej Singh with Oppenheimer. Please proceed with your question.
spk00: Great. Thank you, Arlene and team. I guess, you know, when you're at the end of your rope, you just tie a knot and hold on, somebody once said, in this environment, but really looking forward to these readouts. You know, just a quick question on head and neck with FS1118. You know, the Bristol combo has been approved for a while now, or at least a few months, but of course in melanoma. Any insights that you've gotten, you know, more so from that? I know it's a different tumor. As to what gives you, you know, line of sight to FS118, the head and neck readout. And then what exactly are you looking for? What, you know, what were the parameters of what you're looking for in order to move the project forward? And then I just got a quick follow-up.
spk02: Yeah, sure. So, hey, Hartaj, good morning. And we're lucky in the sense that we have four ropes to hang on to, and so that's great. However, just let's go to that, the BMS data. So, you know, we're interested, as you know from previous conversations, in the LAG3 expression, and my response to Rob's question about biopsies, we follow that through, and that's true, not just in the head and neck setting, but also in the two checkpoint naive settings of non-small cell lung cancer and Diffuse large B cell lymphoma and that's that's really the central thread that's run through The the working clinical hypothesis you put together what we draw interestingly you've got to sort of go back to the fundamental mechanism of PD1 PDL 1 axis and lag 3 axis and and what we've demonstrated previously and it's actually been shown by others is if you suppress the PD-1, PD-L1 axis and the LAG-3 axis with a combination, what you in effect do is cause an upregulation of the expression of both of those receptors. And so in effect, even if a patient going into a combination study is an initial, in inverted commas, low expressor of LAG-3, during the course of their treatment, even though they'll be getting under control because they've got antagons in place, their baseline level of LAG3 will grow. And so, you know, for us, understanding that mechanism and understanding the fact that we, because of cross-linking and clustering, cleave the LAG3 and don't see that upregulation in the tumor microenvironment through the TILs really gives us a point of difference, but also the confidence that LAG3 expression and then the inhibition of its function, in our case through cleavage, becomes central to that kind of working hypothesis. So that's where we are with LAG3. We haven't disclosed on the second question what our hurdle rate is. Clearly, this is a patient group who have a few other options, having been through checkpoints They're often third or sometimes fourth line of treatment when they're on our trials. And, you know, there's a relatively low bar, but of course, we want to get much higher than that ourselves in order to give us confidence to go forwards. One, confidence to go further forward in this proof of concept study and head and neck, but also planning for you know, a kind of basket trial in which we would look at other acquired resistant patient settings. Of course, unfortunately, head and neck is not the only cancer in which patients who have been treated with PD-1 and have a response then become refractory, and we're interested around that LAG-3 hypothesis, but interested in those patient groups as well. So that's where we'll be going next. You said you had a follow-up, Hattash?
spk00: Yeah, thank you, Elliot. Yeah, no, that's great. Thank you so much for a detailed answer. And just a question of Darlene, which is that, you know, again, kudos for managing your P&L really well, you know, these kind of small but stepwise increases as your clinical activity increases. But, Darlene, you know, assuming you have one, two, or three of these kind of top-line readouts important to the company that are pretty material readout in the next six, 12 months, how to think about your kind of your R&D, you know, burn rate basically over the next year or two years? Thank you.
spk07: Yes. Hi, Haritaj. Well, as we said, we do expect that we have enough cash to get us well through the first quarter of next year and moving forward with all these programs and all these readouts. Now, obviously, as we take more patients on trial, costs will increase over time. So you're sort of seeing kind of level spending now with a little bit of build over the remainder of the year and into next year. So it will build some. while I expect G&A will sort of stay flat to potentially even come down just a tad. But, again, it's really kind of driven by patients on trial.
spk00: Great, Darlene. And, you know, do you give any updates as to your partner revenue? I mean, how does that affect, you know, your revenue run rate through the first quarter of next year?
spk07: Yeah. Yeah. So we have not given guidance on that until it happens, but we do have visibility into some of that, and that is factored into our cash flow projections. There's certain milestones that are shorter term and others that are longer term, and as they become more closer to solidified, we definitely run that through our cash projections, but we have not disclosed that. And we've not disclosed what those milestones are based on confidentiality with our partners. I can say, too, that one of the unique features in the UK is that they actually have these R&D research and development tax refunds, not just credits, but they're refunds. So we're in the process of... doing the calculations and submitting those now, but that, you know, that could be in the millions of dollars. And that's, you know, that's a definite, if you will, at least for the time being. So that's a nice thing. It's not just a tax credit. It's actually a tax refund. So we've got that built into the model as well.
spk00: Great. Thank you, Darlene. Thanks, Elliot. Thanks to the team.
spk05: Thank you.
spk07: Our next question comes from Patrick. with HC Wainwright. Please proceed with your question.
spk10: Hi, good morning, team. This is Jason on for Patrick. And my first question is just around SB11285. And we were just wondering in terms of kind of benchmarking the potentials of SB11285, and should we be looking at more of like MERCs or GSKs? And will it be a potential guide for the path forward? And I have a follow-up question after that.
spk02: Great morning, Jason. Thanks very much for your question. So, you know, we sit squarely in the kind of second generation of sting, so we can be given intravenously. And we gave an update at the end of last year, a few months ago, saying that, you know, to date, the ascending parts of the dose had been going well and were safe and well tolerated, some early signs of sting. You know, I think Where we've tended to benchmark ourselves is against other second generations. So of the two you've selected, we would kind of more point towards the GSK molecule. And certainly, you know, we're looking forward to seeing any data from that organization as it moves. One of the challenges of first generation, of course, was there was a kind of stepwise function in biological response to sting agonism. And it was a kind of all or nothing. And we were really interested to see Prof. Curran's work out of MD Anderson, who's been doing analysis of the current clinical sting assets, the stings that are in the clinic. And he had some positive things to say about SB11285 with respect to its kind of gradual uptake, my apology, uptake in sting agonism. So we're excited about what's going on in the clinic. We'll certainly report more in the later part of this year from that study as a monotherapy and in combination with the tasolizumab.
spk10: Okay, yeah, that's really helpful to know. And just kind of building off the last point that you just said in terms of data being released later this year, can you remind us, is this for the Part A or Part B? And just again, just to kind of clarify, what is the Part A and Part B of the Phase 1 study?
spk02: Of SB11285, Jason, just to be clear?
spk10: Yes, yes, or SB11285.
spk02: Yeah, so it's in two parts. There's a combination. Sorry, part A is just a simple monotherapy. A sending dose standard 3 plus 3, and part B is in combination with a flat dose of atazolizumab, a flat standard dose of atazolizumab. And I would anticipate will be tens of patients, maybe 30 to 40 patients, worth of data we'll be reporting towards the end of this year. So we're excited about what we're seeing and looking forward to more data.
spk05: Very great. Thank you so much. Great. Thanks, Jesse. Appreciate your call.
spk07: Our next question comes from Ahu Demir with Leidenberg. Please proceed with your question.
spk08: Good morning, Ting. Thanks for taking my question. My first question is on the FS118 program, just a follow-up on the AACR presentation. Knowing the tumor infiltrating lymphocyte aspect, do you plan to implement that, and do you expect patients with higher TIL expression to respond, and are we expecting any maybe clinical data on that side?
spk05: Yes. Hey, morning, Ahu. Nice to speak with you.
spk02: Just repeat, you just broke up slightly in there. So for the TIL-Lag3 expression, just... Yeah, my question... Yeah, sorry.
spk08: Yeah, happy to. Sorry, Elliot. No, no worries. Given the knowledge on the TILs, are we expecting to see perhaps better response rate with patients who have higher TIL expression and do Do you plan to show more data on that? What are the implementation on the clinical side?
spk02: Yeah, sure. So, I mean, this really comes back to our fundamental hypothesis that, you know, LAG3 and PD-L1 expression in the post-checkpoint setting and indeed in the checkpoint naive setting is really, really important. And I think, you know, if you look at the phase one data, then what we saw was a correlation between expansion of pill activity post-treatment with disease control and indeed one unconfirmed and one confirmed PR with high expression of LAG3 and PD-L1. And we expect to see that in the phase two proof of concept. It's a great question to try and get me to kind of spill the beans before the before we announce the data, but we're excited to look at the correlation between like-thread expression and clinical benefit in the head and neck proof of concept study.
spk08: Thanks, Elliot. I have one more question on the 4-1-BB site. You had two assets targeting 4-1-BB. Is there a particular one you are more excited about? And given that we'll see preliminary efficacy data on the 2-2-2 programs, I'm curious to hear if there are any other programs in the near term that perhaps investors can place more confidence for 1B as a target, maybe during ASCO or any other presentation. Just would like to get more information on that as well.
spk02: Well, so I've often asked my investors in particular kind of which is my favorite child. And I always argue that they're all lovely, but all different. And I think for the 241BB molecules, FS222 and FS120, they fall into that lovely and different category. It is true that FS222 will be reporting preliminary data in the coming few months. And we're very excited about what we're seeing with that. We've been particularly impressed by how the preclinical data have translated into the clinic. And I would say for that molecule in particular, we've got some reasonable benchmarks from which we'll need to differentiate, given some of the competitors who are also developing PD-L141BBs. In the non-clinical setting, we saw complete disease control without the need for a combination with PD-1. And we're happy to see that beginning to translate into the clinic. In addition to that, of course, we're going after both high and low PD-L1 expressing tumors. And non-clinically, we observe no sign of the so-called bell-shaped or hook effect that has been present with some of the competitors. So we know the kind of pillars of differentiation that we're aiming for, and we're excited to bring FS222 data forward in the coming few months. You may, from all of that, conclude that that is my favorite child. but it is lovely, but different from FS120. And as you know, FS120 is a first-in-class dual agonist. It's a really potent molecule. We're very excited to be combining it with pembrolizumab from Merck, and we'll talk about what we're doing beyond that towards the end of this year. But this is a molecule that is kind of tumor-type agnostic, and the way in which it can be used is in this combination. So PEMBRO is approved in about 17 indications, if I recall, of late. And so, of course, we can go into any of those settings. And some of our non-clinical data with three different types of chemo showed some real important synergies. So I would say, in a different sort of way, 120 is a really important and exciting molecule for us as well than 222.
spk08: Thank you very much for the detailed answer.
spk05: Thank you. No problem at all. Nice to speak with you.
spk07: As a reminder, if you would like to ask a question, please press star 1 on your telephone keypad. Our next question comes from Yael Chen with Laidlaw & Co. Please proceed with your question.
spk01: Good morning, and thanks for taking the questions. The first question I have is about 222. My understanding is that you might have two data reporting, in other words, another one after your initial one in this year. Is that correct? So that would be my first one.
spk02: Yeah, so 222 is going very well. And what we've done is managed to bring some of the data we were planning to update much later this year, sooner. So we'll do that in the coming few months. and we'll then have a look and see what else emerges beyond that. So there'll be more data in this first report than we'd anticipated. Clearly, we continue to explore the full spectrum of activity for FS222 in that both in those PD-L1 low and PD-L1 high settings. We also have, which we haven't disclosed yet, but we're also particularly interested in seeing some intriguing data in the clinic from another biomarker that we've been using in combination with that PD-L1 expression level as well. And almost certainly we'll be talking more about that in the months to come.
spk01: So should I interpret that as that you will have the first data report with a much more enriched data and possibly has a second one or otherwise will be maybe push the second data readout into next year?
spk02: Yes, I think your interpretation of a much enriched update in the coming few months is a good way of interpreting that, and we'll guide once we're through that as to when the next set of data will be coming.
spk01: Okay, maybe a quick follow-up in terms of 118, that I know the non-small cell long-end DLBCL enrollment has some issues there in terms of the Ukraine situation. What kind of remedial work currently you are trying to resolve this issue?
spk02: Yeah, and I'll repeat what I said, that what we're doing is trivial compared to the suffering of the people of Ukraine, but we also need to keep our programs moving forward to benefit patients that we can. And so what we've done, and we did it pretty much immediately, is added additional sites to the countries we were already opening and then quickly looked for feasibility in new countries. And that was part of our contingency planning around the war in Ukraine. And as I reported a little while ago, we are now pleased to say that those contingencies are coming into place. I think the reality is that... For data output, the diffuse large B-cell lymphoma should still be first quarter of next year. So that should be fully on track. And we think current estimates suggest we may lose about a quarter with the head and neck non-small cell, sorry, non-small cell lung cancer study. My apologies. And that will be then to the second quarter of next year, though we'll do everything we can to pull that forwards, of course.
spk01: Okay, great. Thanks a lot, and congrats on all the progress, and I look forward to seeing the data's readout.
spk05: Yeah, great. Thanks very much, Al. Appreciate the question. Nice to speak with you.
spk07: Our next question comes from Justin Walsh with B Reilly Securities. Please proceed with your question.
spk09: Hi. Thanks for taking the questions. I know that you can't provide specific details that haven't been announced, but I was wondering if you can maybe provide some color on what Merck KGAA has found so consistently attractive about the FSTAR development platform.
spk02: Yeah, so that's a great question. Morning, Justin. So look, I think one of the things that big pharma in particular are interested in is thinking about how to get a molecule to market. And if you look at our bispecific platform, it's a thing we kind of mention in passing often, but it actually is really important is that we can make these drugs in a really simple way. You take a standard cell line, put the sequence in, and nine months later, you're good to go with high yields, good stability, low aggregation, just like making monoclonals in the kind of 1990s. So I think that becomes really compelling. So in the background, the big checkbox for big pharma and big biotech is we've got something that's easy to manufacture as a platform. The second then, of course, is the hunting down of that biology that we're looking for in biospecifics. And as I mentioned in the earnings call, about 20% of all clinical activities now heading is in bispecifics, which is terrific. And of the bispecifics, obviously, we believe ours is, you know, one of the best, if not the best format, because we get with these simple changes, we get the tetravalency and the potency associated with that. And this novel biology, you know, some of which we've reported already for FS118, which is the cleavage of LAG3 from the surface of tills. And there's much more of that to follow from it and the other programs. And I think combining manufacturability, simplicity with that unique combination of cross-linking clustering in a conditional way seems to be the thing that has consistently attracted Merck as a partner. And we were really excited, by the way, to see what we used to call FS122. I don't recall what Merck call it now, but their data on that first program published at CITI last year.
spk09: Great, thanks. One more question for me. I was wondering if you could provide some color on any feedback from scientists, KOLs, and others working in the space on the AACR presentation for the FS118 differentiated MOA.
spk02: Yeah, so I think, you know, there's a growing body of evidence to tie the kind of lag three shedding hypothesis today. So one is there is a correlation between lack of effect with a checkpoint inhibitor and expression of ADAM, the cleavage mechanism for LAG3 from the surface. It's also clear that the expression of LAG3 is a poor prognostic factor for outcomes with checkpoint inhibitors. And, of course, one of the things that, you know, we have been showing in the clinic and elsewhere is, you know, this cleavage mechanism. And certainly, you know, people like Dario Vignali, who are, you know, leaders in the field, are very excited about this as a mechanism compared to others where, as I said in the very first response, I think, to Dana, you know, we see this change in symptoms. upregulation of LAG3 and PD-L1 if you're using just monotherapies in combination. And indeed, interestingly, and this was published in our AACR paper, is that you still see some upregulation if you use a PD-1 and LAG3, our difference being PD-L1 and LAG3, giving that cross-linking, clustering, and that shedding. So you get this kind of hierarchy of expression of LAG3, which is a you know, a really important player in exhaustion pathways. And I think, you know, that, so landing on that hypothesis is really where our SAB got pretty excited, as well as obviously, you know, talking about specific diseases where we believe we can bring benefit.
spk09: Great. Thanks for taking the questions.
spk05: Thanks, Justin. Appreciate it. Nice to talk to you.
spk07: Ladies and gentlemen, we have reached the end of the question and answer session, and I would now like to turn the call back over to Elliot Foster for closing remarks.
spk02: Great. Well, thanks, everyone, for the questions. And, you know, appreciate you joining this morning and the thoughtfulness that goes into that question and answer session. You know, clearly, 2022 is an important year for us at FSTAR, and probably our most significant one as a clinical stage company. given the data coming from all four of the programs. We believe that success in any one of these has real potential to deliver significant value to shareholders and, of course, transform the lives of patients with cancer. Our partnership strategy also brings new opportunities to patients as well as delivering that important non-dilutive cash. There really is a lot to look forward to backed up by the emerging data And I'd like to thank the FSTAR team, our partners and shareholders for your ongoing support. I'd also like to thank the patients participating in our trials and our expert clinical investigators. And with that, thank you and goodbye.
spk07: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.
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