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spk00: Thank you for standing by and welcome to Agen's first quarter 2024 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, press star one again. Thank you. I would now like to turn the call over to Zach Arman, Head of Investor Relations. Please go ahead.
spk10: Thank you, Rochelle, and thank you all for joining us today. Today's call is being webcast and will be available on our website for 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, among other updates. These statements are subject to risks and uncertainties, and we refer you to our SEC filings available on our website for more details on these risks. Joining me today are Dr. Garrow Arman, Chairman and Chief Executive Officer, Dr. Steven O'Day, Chief Medical Officer, and Christine Klaskin, Vice President of Finance. Dr. Robin Taylor, Chief Commercial Officer, and Dr. Todd Yancey, Chief Strategic Advisor, will be participating in the Q&A session. Now, I'd like to turn the call over to Gero to highlight our progress in the first quarter. Gero?
spk03: Good morning, everyone. Thank you for joining us on today's call. Three decades ago, Agenis was founded with a profound commitment to transform the landscape of cancer treatment. Ever since, we have been relentlessly pursuing this mission, leveraging the power of the immune system to develop groundbreaking therapies that could dramatically change the lives of those battling cancer. Today, as we edge closer to realizing our goals with our Leading But Foul program, I'm thrilled to share a significant milestone that will propel us into the next phase of our journey. This morning, we announced that we entered into $100 million Royalty Financing Agreement with Ligand Pharmaceuticals. It's very important to realize that this agreement allows us to keep ButtVal in its entirety and also open up our options to bring in partners for this program. This pivotal minimally dilutive capital infusion will support key development initiatives in the ButtVal program. including our planned confirmatory phase three study in relapsed refractory MSS CRC, which stands for colorectal cancer, and our commercialization resonance activities, which are currently underway. Ligand's initial commitment is for 75 million with an option to add 25 million more. And importantly, in addition to this, We can add $100 million more in a syndicated transaction from other parties, several of whom we are already in negotiations, making the total as much as $200 million. This agreement strengthens our financial position and reinforces our commitment to bringing Buck Bell to patients. Our cash balance as of the end of the first quarter was $52 million. With the additional cash received from this transaction, we are positioned to ensure the progress of our mission-critical work to bring butthole to patients in need. We're also in discussions for additional capital infusion mechanisms to further strengthen our balance sheet as we enter a critical phase of our effort across our BOTBAL program. Also very importantly, over the last few quarters, we have successfully reduced our cash burn rate and will continue to do so, even with our strengthened cash position. Our detailed financial scenario planning includes various partnership outcomes and potential regulatory timelines, ensuring we are well prepared for the challenges and opportunities ahead. Our reverse stock split during Q1 was implemented to achieve three key objectives. One, to satisfy the eligibility criteria for the Russell Indices. to regain compliance with NASDAQ listing requirements. And three, to maintain a stock price about $5 a share, enabling investments by certain institutional investors that require a minimum share price. We've confirmed regaining compliance with NASDAQ listing requirements last week. And based on our market cap as of the close of the trading on April 30th, which is the Russell Rent Day, we are more confident in our continued inclusion in the Russell 2000. Our strategic initiatives are expected to broaden our investor base and to lower our cost of capital, benefiting both our shareholders and optimizing our ability to bring valuable medicines to patients. I will now turn the call to Dr. Stephen O'Day, our chief medical officer, who will provide an update on the latest developments in our BASBAL program. Stephen will focus particularly on our progress on colorectal cancer. This focus is in part our potential accelerated filing pathway in advanced stages of disease and also This focus is vital as we expand treatment options in earlier lines of therapy through externally funded and global investigator-sponsored trials. I might add that we have had requests for an unprecedented number of investigator-sponsored trials in our queue. The results from both agenist-sponsored studies and those ISTs continue to reinforce our confidence in BotVal's potential to address significant unmet needs across various solid tumor cancers. Thank you again for your continued support and commitment to Agenis. We're excited about the future and look forward to sharing more updates on our progress in the near future. Steven.
spk09: Thank you, Gero. Botansilumab in combination with Baustilumab has demonstrated deep and durable responses across a wide variety of poorly immunogenic or IO refractory solid tumors. These poorly immunogenic tumors represent the majority of adults with cancer. And this large group of patients have not previously benefited from the success of established IO therapies. Currently, our BOT-BAL program is focused on our lead indication, relapsed refractory colorectal cancer, which is not MSI high or DMMR and is without active liver metastasis. We continue to make substantial progress. As provided in our press release of April 12th, we've seen this data set from our expanded phase 1B cohort mature. In the 77 patients in this indication, treated with a combination of botansilumab and bostilumab, there is now almost 14 months of median follow-up. The confirmed overall response rate in all patients treated is 23%, with a median overall survival of 21.2 months, a 12-month overall survival estimate of 71%, and an 18-month overall survival estimate of 62%. The most common safety observations are immune-related diarrhea and colitis. which is managed in accordance with standard therapies. Grade 3 or greater treatment-related diarrhea colitis occurred in approximately 16% of patients. These data, which continue to mature, stand in stark contrast to standard of care therapies in this treatment setting, with overall response rates of 1% to 6%, and a median overall survival of 12 months or less. In November 2023, we completed enrollment in a large randomized global phase two trial with 234 metastatic colorectal cancer patients whose tumors were not MSI high or DMMR and were without active liver metastasis. This trial was designed to evaluate dose and contribution of components for the bowel regimen in this indication. And importantly, also included a contemporaneous standard of care arm. Results from a March data cut from this trial demonstrates consistency with our phase one results at a similar stage of follow-up. We look forward to submitting more mature results from this trial to a scientific meeting in the second half of 2024. Data from this Phase 2 trial, along with data from the expanded Phase 1 cohort and a real-world evidence data set, support our anticipated BLA filing by the end of the year. We plan to gain alignment with the FDA on the filing and the design of the confirmatory Phase III trial in an upcoming meeting anticipated in July 2024, so that the Phase III trial will commence this year and enroll in time to support an accelerated approval. We will also discuss our obligations, which include our Phase III dose and regimen and the structure and cadence of submission. In the earlier lines of therapy for colorectal cancer, we have important investigator-sponsored trials ongoing, as Gero has referred to. These include the NEST trial with Dr. Tasi at Cornell, which showed major pathologic responses in six out of nine MS-stable colorectal patients treated in a neoadjuvant setting, including two pathologic complete responses and three out of three complete or near-complete responses in MSI-high patients. None of these patients had surgery delayed due to treatment with BOT and BAL. This NEFS trial is continuing to rapidly expand and enroll. Longer follow-up data from the original 12 NEST patients will be presented at an upcoming medical meeting. The second important early-line metastatic colorectal trial I want to highlight is the FOLFOX 3B regimen with Dr. Marlon Fakim at City of Hope. He is investigating BOT and BAU combined with standard of care FOLFOX plus bevacizumab in first-line metastatic or FOLFOX re-challenged metastatic patients. To date, the regimen has been well-tolerated and continues to actively enroll patients. Going forward, FOLFOX3B could serve as an active regimen across several different malignancies, including colorectal cancer, in early-line metastatic settings, for example, upper GI malignancies. Our goal is to improve outcomes in both late-stage and earlier-stage colorectal cancer, a disease growing in prevalence and impacting younger patients. Additionally, we continue to follow maturing Agena-sponsored Phase II trials with BOT or BOT-BAL in several important areas. The first is a refractory melanoma phase two trial with BOT alone or BOT-BAL combination. And the second is a refractory second line metastatic pancreas study comparing BOT-Gemabraxane to Gemabraxane alone. We hope to provide updates on these data in the second half of 2024. Now I'll turn the call over to Robin Taylor, who will provide more insight into our commercial strategy and operations. Robin?
spk11: Thank you, Stephen. In parallel with our planned BLA submission, all of us at Agenis are focused on preparing for the launch of Bott and Bell, our Emeryville-based CMC team is well prepared to supply BOT and BELL both through our third-party CMO partners and subsequently at our wholly owned and operated GMP-grade commercial facility. With respect to commercial preparations, I have hired a highly experienced and passionate leadership team across sales and marketing, market access, and commercial operations. Together, the members of the commercial leadership team have successfully led or participated in over 20 launches of novel therapeutics or label expansions in colorectal cancer and other solid tumors. We are partnering closely with our global medical affairs and clinical teams to gather insights from the world's experts in GI oncology, and we've conducted market research with over 150 US-based GI oncologists across academic and community settings. From both the market research and our direct discussions with GI oncologists, it is clear that there is significant anticipation for BOT and BAL, which underscores the urgency we feel to deliver this important treatment option to patients. Now I'll turn the call over to Christine to discuss financials.
spk05: Thank you, Robin. As Garyl mentioned, We ended our first quarter of 2024 with a cash and cash equivalent balance of $52.9 million. This compares to $76.1 million at year end. Also, as Garo mentioned, this morning we announced a $100 million agreement with Ligon Pharmaceuticals consisting of an initial investment of $75 million with an option to invest an additional $25 million, thus strengthening our cash position. Our cash used in operations for this first quarter was $38 million compared to $40 million during the fourth quarter ended December 31, 2023. For the first quarter ended March 31, 2024, we recognized revenue of $28 million and incurred a net loss of $63.5 million, which includes non-cash expenses of $38 million. This compares to a net loss of $70.9 million, which includes non-cash expenses of $25 million for the same period in 2023. Our net loss per share for this first quarter is $3.04, which compares to $4.31 per share for the first quarter of 2023. I'll now turn the call back to Garo. Thank you very much, Stephen.
spk03: Robin and Christine. As we conclude today's earnings call, I want to recap the pivotal developments we anticipate in the coming months of eGenesis. We are on track to secure a significant cash infusion of up to $200 million by mid-year, which will strengthen our cash position and support our critical research and development activities, our registration efforts, our commercialization efforts. Another key milestone will be our meeting with the FDA and importance before we have their concordance in initiating our biologics license application. Additionally, we will present our phase two data for colorectal cancer, along with additional data in this indication from investigator sponsored trials, which we believe will further strengthen the strong rationale of our therapies. And these data presentations are expected to be happening at major conferences. Furthermore, we expect to release, as Steven said, promising Phase I and II data in melanoma, lung cancer, sarcoma, and pancreatic cancer in the second half of this year. We're very encouraged with the outcomes of these trials. These all represent cancers where there is a critical need for effective therapies. These developments underscore our dedication to innovation in oncology and also highlight our potential to make a meaningful impact on patients' lives by offering potentially chemo-free, durable for patients who have limited or no treatment options left. Thank you very much once again to our shareholders for your continued support and trust in Agenis. We look forward to sharing more about our progress in these exciting endeavors as the year unfolds. Now, I believe we're ready for any questions you may have.
spk00: Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad. If you would like to withdraw your question, simply press star one again. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. Again, press star one to join the queue. Your first question comes from the line of Emily Bodnar of HC Wayne Rice. Your line is open.
spk01: Hi, good morning. Thanks for taking the questions and congrats on the progress. My first question, could you confirm how many patients you've treated with spot val at the recommended phase two dose across the phase one B and phase two studies specifically for MSS CRC patients without liver mets and your confidence, I guess, that you have enough efficacy data to support an accelerated approval? And then second question, if you can kind of discuss how you're thinking about strategy for Bob Bell in melanoma and pancreatic cancer, and if you feel like these are indications that you may also seek regulatory approval for if the Phase II data are positive, or if your kind of near-term commercial focus is just on CRC. Thanks.
spk03: Certainly, Emily. Thank you very much for your question. I will give you some top line answers to your questions, and then I'll have Dr. O'Dea get into some depth. First of all, as you may know, for the last almost six months, we have been intensively involved in pulling together the data from all the trials, including tracking the maturity of the data, as Steven alluded to, to see how we can make a compelling package in an upcoming meeting with the FDA. And our conviction, based on the data from all three cohorts, including the Phase II randomized study, as well as the durability and maturity of the data, is stronger today than ever before that we will make a compelling case. Of course, we cannot make a definitive statement until the outcome of the FDA meeting, and we need to get their concordance on our condition. But we are in an optimal state of preparedness with where we are right now. And more developments on the progress on this will be coming forth in the next several weeks. In terms of the numbers of patients from each cohort and other questions about whether melanoma, pancreatic, and lung cancer can lead to approval, those are, of course, very important questions that we are actively considering in collaboration with key opinion leaders in these fields. And we will be alluding on the potential of this in coming months. But please understand that we are absolutely fixated on CRC right now because that is our focus for our first potential approval. So everything else is a little less of a priority, but with the additional financial resources that we expect to put into place between now and the end of the year, those other programs will come to the focus as well. But Steven, if you can address some of the more specific questions Emily asked.
spk09: Thanks, Gary. So we're not going to get into the specific numbers, but we can, what I can say is with the phase one and the phase two trial, we have two active doses and a significant number of patients on the combination of BAL in both the phase one and the phase two randomized trial. that we think are supportive with safety, efficacy, and clinical pharmacology to discuss with the FDA an accelerated pathway, given the unmet need in this setting.
spk08: Okay, great. Thank you.
spk00: Your next question comes from the line of Mayank Mamthani. of B Reilly Securities. Your line is now open.
spk06: Good morning, team. Thanks for taking our questions and congrats on the updates noted earlier. So in prior, especially as a team, you've mentioned that your emerging data in phase two is encouraging. And today, I think you said it's comparable to what you noted in phase one at a similar stage. Are you able to give a little bit more detail on what parameters we are talking about and if it's comparable to your expectation at the outset, and especially given you're enrolling slightly earlier stage patients there? And then secondly, on the, you know, if you are able to clarify the FTA meeting has been scheduled, and if there's a minimum follow-up from the phase two cohort that you're trying to accomplish before you're able to submit a package that would go alongside that FTA meeting. And I have a couple of follow-ups.
spk03: Okay. On the first question, Mayank, we have said repeatedly that we will not discuss the details of this study. And please understand, everybody, that we're not trying to be cute here. It is just a courtesy call that we will not discuss the data until we have an opportunity to present it to the FDA. And subsequent to that, our preference is, of course, to present the data, which we consider a very important set of data that will address selection of the dose, contribution of the elements, and the efficacy to support the data that we have seen in earlier trials at a major conference. That would be our preference to do. So you will get no further details on this until these steps are underway. Now, in terms of the FDA meeting, the FDA meeting request is going in as we speak. And we expect that based on the timelines, we will be granted a meeting sometime in the second half of July. And this is data that we have not released before, so we're now making it public. And as soon as the meeting is scheduled, of course, depending on the circumstances, we may make certain statements about it. But I believe that the outcome of this meeting will be one of the most important milestones for the company as we potentially gear up for accelerated approval filing in the next months following the meeting. But be rest assured that we are going on all full cylinders, as they say, on all modules or are getting ready in a state of readiness for all modules that could potentially be submitted post the FDA meeting.
spk06: I appreciate that color, Gail. Thank you. On the follow-up from the Phase 2, like you're at, I think, 14 months follow-up from the Phase 1, is there a particular requirement or best practices in terms of how much follow-up you need to have from Phase 2, or is that sort of subject to discussion?
spk03: Okay, so on this, of course, the FDA has guidance that is based on historical precedence on the minimum follow-up. But we have had significant input from our regulatory advisors on what that minimum should be. Of course, ideally, you can wait five years, but we're not going to do that. But the minimum enrollment in the Phase II ended in October 2023. And based on that, you can sort of extrapolate what the follow-up period will be between now and the potential FDA meeting, and then beyond that FDA meeting from that point to the filing of a BLA with the clinical module.
spk06: Makes sense. Thank you. And then on the number of ISTs that have come up on clinicaltrials.gov, are you able to comment on what sort of broad dose level you're using in most of these ISTs? And also about CRC specifically, I believe there's one IST data that you expect in the relative near term in the earlier line setting. Steven, if you're able to comment on the implications of that data set in informing what the phase three trial could look like. And then I have one last financial question after that. Okay.
spk03: So, as I've said, thank you, Mayank, for that question. We have been confronted with an unprecedented number of ISDs. Now, what is that number? It's well over 50 ISD requests. Even our resources, and I don't mean just financial resources because a number of the ISPs do not require much financial resource from the company, but people, human resources. We cannot satisfy all of these ISP requests. So we have zeroed in on a handful of them. And these handful of ISPs are selected based on potential data generation for approval of our agents in subsequent trials. And also, of course, the rationale of generating significant clinical data that will be supporting the rationale of pursuing BOTVAL in several different indications that are important to us. So, these will be reviewed or are in the process of being reviewed on an ongoing basis. and we'll make prudent decisions in collaboration with some of our advisors and KLFs. But also, be rest assured that during the time of our regulatory discussions, we are particularly sensitive to not expanding our ISD programs so that we do not get caught in generating data that cannot be tabulated, cleaned up, in time to be provided to the FDA for a potential VLA consideration. So all these considerations are a critical part of our thought process. Now, in addition to that, I think you had another question on ISDs, whether or not it's specific to CRC. Not, of course, a great number of the ISDs. are not specific to CRC. They are in pancreatic, melanoma, lung, sarcomas. There's a great deal of interest in sarcomas because of the efficacy that we've seen, or I shouldn't say efficacy, I should say significant clinical activity that we've seen. The reason I'm saying I shouldn't say efficacy is because that's a term that the FDA has to bliss. So until that happens, we have to be careful how we use the terms of activity. But because of the significant activity that we have seen in sarcoma patients that have failed everything else and they're not responding to any other treatments, there is, of course, a lot of interest in pursuing not just ISDs but also approval strategies. But as I said earlier, we are very, very cognizant of the focus that we need to have on CRC work.
spk06: Got it. Thank you. And then lastly, in the non-dilutive financing, the total 200 million, if you include some of the expected syndicated offerings, if you're able to comment on how much, you know, contribution board value versus the other six partnered programs in this broader deal construct, that would be helpful, just a rough range, Gero, and thanks again for taking that question.
spk03: So, I mean, there is, the relative contribution is articulated in our press release, or the press release that was put out this morning at 730. So, but other than that, we cannot discuss any additional details. Suffice it to say, that this financing completely provides us with the freedom to pursue BotVal on our own and pursue BotVal in connection with partners worldwide. So this particular transaction has absolutely no bearing or puts any restrictions on our ability to advance BotVal to to in collaboration with partners and by ourselves. In other words, the economics of this transaction are defined, and that was in the press release. And beyond that, I believe that we are in a position to exploit our commercial opportunity with Buckbath. And that will be, of course, for the benefit of both the company
spk08: our future potential partners and for the benefit of LIGID.
spk00: Your next question comes from the line of Kelly Shih of Jefferies. Your line is open.
spk04: Hi, this is Dave for Kailishi, and thank you for taking our question. My question is about the catalyst in the second half. You said there will be a number of data in melanoma, lung, pancreatic in the second half. Can you provide, like, expectation, what kind of data we should expect and number of patients and those details? Thank you.
spk03: Okay. So, then, clearly, if the data... was expected to be not positive, we wouldn't be talking about it. But can I provide you with specifics on the data that will compromise our ability to present data at conferences? The answer is no. So we'll have to see. As the data matures, we're very encouraged with what we're seeing across a number of indications. As we said before, that includes melanoma. lung cancer, sarcoma, pancreatic cancer, and even others. So, please be patient and allow us to make the appropriate disclosures and have an opportunity to present the data at peer review conferences and also in publications.
spk08: Okay. Thank you.
spk00: Your next question comes from the line of Matthew Phipps of William Blair. Your line is now open.
spk12: Hi, Gero. Congrats on the Ligand financing. The additional $25 million that can come from Ligand, is that purely based on Ligand's decision, or is there anything that can trigger that decision?
spk03: Yes, it is based on Ligand's decision.
spk12: Great. Thanks. Maybe for Dr. O'Day, the melanoma on the slide that says a frontline trial and frontline registrational trial versus standard of care. Wondering if you consider that to be PD-1 monotherapy, PD-1, a different PD-1 C2LA4 or PD-1 LAG3 at this point.
spk03: A perfect question for one of the world's foremost experts on melanoma, and that is our Dr. Stephen O'Day.
spk09: So, Matt, can you clarify the question? Again, I didn't quite get the first-line piece of it.
spk12: Yeah, sure. There's a slide, you guys, in your news deck that says first-line melanoma registrational study versus first-line standard of care. Just kind of curious what you consider to be that standard of care right now, because there's maybe three different IO regimens out there.
spk09: Yeah. Well, as you know, the first-line treatment is split sort of between PD-1 monotherapy, PD-1-like 3, or PD-1-CTLA-4. I think what we're discussing going forward and presenting later this year is our refractory setting. And obviously, we need to see what that data, as it fully matures in the coming weeks and months. This is in a refractory PD-1 and PD-1, CTLA-4, and BRAF refractory setting. So depending on the strength of this data and sort of further discussions, obviously, if there is an accelerated path, it would likely lead to a first-line confirmatory trial. Again, the FDA would have to advise on the best comparator arm in that setting.
spk08: Okay. Thanks for taking my question.
spk00: Once again, if you would like to ask a question, please press star 1 on your telephone keypad. Your next question comes from the line. I think we lost. All right. So we have the next question from Gabriel Kim. Your line is open.
spk02: Hi. Congratulations on the LIDAN financing.
spk08: Could you just say when is the anticipated closing date? And then I had a follow-up. Hello? Hello?
spk07: Yes, we can hear you.
spk03: Hi. I think we mentioned that we expect to close the transaction this month.
spk02: Oh, okay. Wonderful. And then in terms of share count, are you able to provide an end of quarter or current share count?
spk03: I don't have the share count with me, but I believe going into all of this, it was 20 million, something like that.
spk02: Okay. Christine, do you have the exact share count?
spk05: Yeah, it's just over 20 million. And we did file our 10Q this morning, so you can see that on our file.
spk02: Okay. Okay. And is that also, okay, wonderful. Thank you. So that's a current share count as well?
spk03: yes thank you very much okay thank you thanks a lot very no further questions at this time i will now turn the conference back over to garo armin for the closing remarks thank you very much uh thank you very much for your attention and uh your patience uh as you know a number of our shareholders were concerned about conditions strengthened our balance sheets strengthened and what i expect is that today's announcement is the very first step in this process and that throughout the next weeks months we will see additional activities that i expect will strengthen our balance sheet and allow us to be able to pursue our very important mission of getting bucked out to the finish line Thank you very much.
spk00: Thank you. That does conclude our conference for today. Thank you all for joining. You may now disconnect.
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