Good morning. My name is Audra, and I will be your conference operator today. At this time, I would like to welcome everyone to the Agenus Inc. Fourth Quarter and Full-Year 2023 Results Conference Call. Today's conference is being recorded. All lines have been placed on mute to prevent any background noise. After the speakers’ remarks, there will be a question-and-answer session. At this time, I would like to turn the conference over to Zack Armen, Head of Investor Relations. Please go ahead.

Thank you, Audra, 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. Garo Armen, 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 Yancy, Chief Strategic Advisor, will be participating in the Q&A session. Now, I'd like to turn the call over to Garo to highlight our progress in 2023 and to speak to our outlook for 2024. Garo?

Thank you very much. Ladies and gentlemen, today it is with great enthusiasm that we gather to share the remarkable strides Agenus has made over the past year. Our journey has been marked by significant achievements, pivotal milestones, and a steadfast commitment to innovation in the field of oncology. In 2023, Agenus reached crucial milestones, particularly with our BOT/BAL program, a cornerstone of our operational focus. BOT/BAL therapy has undergone rigorous testing in over 900 patients, demonstrating promising activity in cancers that represent significant unmet medical needs, notably colon cancer, where we are poised for potential first approval. The impressive response rates, sustained durability, and overall clinical efficacy observed across multiple challenging cancer types have garnered attention and excitement from leading experts in the field. It is essential to note that the patients enrolled in our trials have exhausted available standard treatments, making clinical responses achieved all the more meaningful. Our achievements in the past year underscore the immense potential of Botensilimab, both as a standalone therapy and in combination with Balstilimab and/or chemotherapy. All of these trials are currently ongoing. The presentation of our data at six prestigious scientific forums and publication in five peer-reviewed journals is a testament to the robustness and significance of our findings. Dr. O'Day will delve into the clinical data shortly, providing more detailed insights during this call. The resounding feedback from over 1,000 physicians we engaged with over the past year underscores the transformative impact of our work and the impact it could have on patient care. Furthermore, the fast track designation granted by the FDA acknowledges the urgent need for new treatments in our lead indications, which is refractory, MSS-CRC in non-liver metastatic patients. As we stand on the threshold of a critical phase in our regulatory journey, our focus is squarely on advancing activities for a potential accelerated approval filing. Our immediate efforts are directed towards ensuring that our development strategies align seamlessly with the FDA's rigorous standards. In 2024, our primary objective is to pursue a global regulatory strategy for BOT/BAL in our fast track indication. Following alignment with the FDA, we intend to initiate the submission of our Biologics License Application, otherwise known as a BLA, for potential accelerated approval. Subsequently, pending feedback from scientific and regulatory advice in Europe, we plan to submit to the European Medicines Agency, known as the EMA, in 2025. To achieve our regulatory objectives, we are intensifying our efforts to provide regulatory authorities with a comprehensive data package that demonstrates the safety, efficacy, and clinical pharmacology of BOT/BAL in refractory MSS-CRC. Our Phase 2 study completed enrollment in October 2023, was meticulously designed to evaluate BOT/BAL's dosage and the contribution of its components. Additionally, by the end of 2024, we anticipate initiating a Phase 3 study in the patient population of our proposed indication. Our commitment to transparency and stakeholder engagement remains unwavering as we progress towards delivering these potentially life-altering treatments to patients. Looking ahead, our mission to enhance the lives of cancer patients through the power of the immune system remains steadfast. That's been our mission from day one, 30 years ago, of course, today, with BOT/BAL leading the charge in our dynamic portfolio of agents. To expedite this transformative journey, we are actively exploring strategic partnerships. Our ongoing collaborations have already yielded significant returns, exemplified, for example, by the recent $25 million milestone payment from BMS, triggered by the commencement of a Phase 2 study with BMS-986442. This is a TIGIT bispecific antibody discovered, and the early development was done by Agenus and it was licensed to BMS. We have received a total of $250 million from this collaboration thus far. Moreover, we are progressing our efforts to monetize non-core assets and explore royalty financing and project funding opportunities with the potential to generate an additional $100 million to $200 million in the relatively near term. Furthermore, we're engaged in discussions with several prospective pharmaceutical partners, exploring avenues for co-marketing and co-development agreements, specifically for BOT/BAL. Dr. O’Day will provide an overview of our latest clinical findings, further highlighting the groundbreaking progress we've made so far. Thank you for your continued support and confidence in Agenus. Together, we are pioneering a new era in cancer treatment, one that offers hope and healing to patients worldwide. Dr. O'Day?

Thank you, Garo. Together with our investigators and key opinion leaders, we presented updates from the BOT/BAL development program at ASCO-GI, Society of Gynecologic Oncology; ESMO-GI, CTOS and at a corporate event hosted during the ESMO Congress in October. Throughout 2023, new clinical data was presented for nearly all of our programs, and I refer you to our press release issued today that provides a comprehensive summary of our 2023 clinical development updates. Today, I'd like to share a selection of our data updates from the last year, which highlights some of the compelling opportunities we have to transform care for patients. Starting with safety, we continue to observe a manageable safety profile. As of May 2023 data cut from our solid tumor Phase 1B study with doses of 1 milligram per kilo or 2 milligrams per kilo of Botensilimab in combination with Balstilimab, the most common adverse events were immune-related, with the most common of these being diarrhea and colitis. Grade 3 or greater treatment-related diarrhea or colitis occurred in 14% of patients. These findings are consistent with the mechanism of action of BOT and BAL, as both are immuno-oncology agents. Now turning to our CRC development program for BOT and BAL, where we have made significant progress. As of our latest update during our corporate event in October 2023, our Phase 1b expanded cohort of 70 evaluable patients had a median follow-up now of 12.3 months and RECIST confirmed overall response rate of 24%. Based on literature review, the response rate in a similar population treated with standard of care therapies ranges from 1% to 6%. In addition, patients in our trial showed a 12-month overall survival rate of 74%. Median overall survival has not been reached. We anticipate having top line data from the Phase 2 trial publicly available in the second half of 2024, to align with our planned regulatory timeline and allow for sufficient data maturation. At ASCO GI in January of this year, data was presented from an investigator-sponsored trial being conducted by Dr. Pashtoon Kasi at Weill-Cornell Medical Center, in which 12 patients with colorectal cancer were treated with one dose of BOT at 75 milligrams and two doses of Balstilimab at 240 milligram in a neoadjuvant therapy window of opportunity setting. Surgery was performed on average 4 weeks after the initiation of immunotherapy. All 3 of 3 MSI high colorectal patients had complete or near-complete pathological responses. And even more importantly, 6 out of 9 patients with MSS stable colorectal cancer had pathological responses of 50% or greater, including two complete pathological responses. None of the 12 patients had tumor growth during the treatment interval, and no surgeries were delayed due to immune-related toxicities. There were only two instances of Grade 3 treatment-related adverse events, diarrhea, and fatigue, which were reversible. These results represent an important opportunity to move into earlier non-metastatic lines of therapy and potentially change the treatment paradigm, particularly for early-stage MSS stable colorectal cancer. This IST is currently adding an additional 24 patients. The expansion extends dosing of immunotherapy and the timing of surgery from 4 to 6 to 8 weeks, which is more reflective of traditional neoadjuvant therapy studies. Depending on the data, we plan to prioritize neoadjuvant development and are evaluating study designs for further pivotal studies. And lastly, in second-line pancreatic cancer, we reported data on six patients with the combination of Botensilimab and two chemotherapy agents, gemcitabine and abraxane as a triplet therapy. All six patients had progressed following the most aggressive first-line metastatic regimen of FOLFIRINOX chemotherapy, and all six had liver metastasis. Four of the patients achieved marked and sustained tumor marker reductions. We reported two of the four patients achieving a partial response at 16 weeks with confirmed target lesion reductions of 47% and 37%, which was pending confirmation at the time the data was reported. Two other patients showed stable disease at their first 8-week scan with tumor reductions of 20% and 13%, respectively. A randomized Phase 2 study is currently enrolling, and we anticipate preliminary data being available in the second half of this year. These results demonstrate clear activity of Botensilimab in cold tumors in both the refractory setting and in early disease, combining Botensilimab with either Balstilimab or chemotherapy. And this offers hope for patients and families where current standards provide limited benefit. We remain committed to improving patient outcomes and are grateful for the support of our team, trial participants, and stakeholders. Now I'll turn the call over to Christine to discuss financials.

Thank you, Steven. For the year ended December 31, 2023, we recognized revenue of $156 million and incurred a net loss of $257 million or $0.69 per share. For the fourth quarter ended December 31, 2023, we recognized revenue of $84 million and incurred a net loss of $49 million or $0.13 per share. Revenue primarily includes revenue under our collaboration agreements, including milestones achieved and revenue related to non-cash royalties earned. We ended the year with $76 million in cash, subsequent to which in January 2024, we received a $25 million milestone payment from BMS triggered by the commencement of a Phase 2 study with BMS-986442, the Agenus discovered TIGIT bispecific antibody. Additionally, we've progressed in monetizing non-strategic assets and future milestones and royalties from ongoing partnerships. These efforts are expected to yield significant cash proceeds by mid-2024. Accordingly, we anticipate being funded through 2024. In parallel, we're pursuing potential partnership discussions with five biopharmaceutical parties to further expand our cash resources. I'll now turn the call back to Garo.

Thank you, Steven and Christine. As we look ahead, of course, we're excited about the opportunities that will lead both cancer patients and Agenus in 2024. Our steadfast indication remains centered on providing cancer patients with enhanced treatment options, a mission that not only benefits patients but also enhances shareholder value and secures the long-term prosperity of our company through continued innovation. Innovation has been critical to our existence and our growth, and it will continue to be. This year, a paramount objective for us is to present a compelling data package to the FDA, seeking their consent to initiate the filing of our Biologics License Application. At Agenus, pioneering advancements in oncology has been more than a mission for us. It's been our enduring commitment over many years. We expand our heartfelt gratitude to our shareholders, partners, and the entire Agenus team for their unwavering support. Together, we stand at the threshold of a transformative journey, one poised to make a profound impact on the lives of patients worldwide with the ultimate aim of delivering chemotherapy-free treatment options. Thank you very much for your time and attention. And now we invite any questions that you may have. Audra?

We'll take our first question from Emily Bodnar at H.C. Wainright.

My first one is on the neoadjuvant CRC study. You mentioned that you're extending the treatment period from 4 weeks to 6 to 8 weeks. So I was curious if you could discuss how you think the longer treatment period may impact efficacy and if there are certain metrics that you think could improve with a greater treatment period? And also if you're following patients in that study post-surgery to eventually look at their surgical outcomes. And then second question on MSS CRC. Could you just confirm that the timing of the BLA submission? And I believe you were previously saying mid-2024. So that’s still the object, or is that looking more like the second half now?

So Emily, I'll start with the last question on the timing of the BLA submission. So as we've guided investors before, the very first step for us is to meet with the FDA, which we're planning on doing mid-year, and they will give their specific guidance on our BLA submission. So we do not want to jump the gun ahead of that meeting and provide different guidance than what we will get out of that FDA meeting. So bear with us; I think we're talking about only a few months from now, that we will be able to give you much more specific guidance on our BLA solution. Yes, Emily, in terms of the neoadjuvant, the very exciting neoadjuvant data, very exciting. And in fact, when I was talking to one of our long-term advisers yesterday, the first thing he mentioned in the conversation was how remarkable this neoadjuvant data has been because of all the reasons you cited, Emily, and Dr. O’Day will elucidate further.

Thank you, Garo. Emily, yes. I mean, given that MSS stable colorectal cancer immune therapy has not previously been effective, the 4-week window period was what surgeons were comfortable with allowing, which was essentially no delay in the surgery. And these results are remarkable in terms of the percentage of patients with deep tumor regressions in four weeks. So the extension of the study will allow now a proper 6- to 8-week treatment period. And we do anticipate that over that time, we will see further deepening of responses. So we're looking forward to that. The study is really looking at surgical outcomes and obviously post-surgery relapses. So this will be a comprehensive neoadjuvant study.

We'll go next to Mayank Mamtani at B. Riley Securities.

Appreciate the comprehensive update. So maybe just on the Phase 2 MSS-CRC data, are you able to comment on what statistically we should be focused on? And if the slight push-out here relates to you wanting to have the OS data or mature durability data, which I could see makes sense if you're thinking about Phase 3 design? And maybe if you can also comment on thinking and timing for launching that Phase 3, should we be aware of any planned regulatory meetings, discussions around that? And then I have a couple of follow-ups.

Yes. As previously mentioned, we completed enrollment in October. Typically, 80% of the patients respond within six months of the first dose. Therefore, when we finish enrollment in November, we will begin monitoring responses around May. We have already started cleaning up the data and preparing all necessary processes to provide outcomes as quickly as possible. We expect this information to be available in the coming months, with the first step being to share the data with the FDA, as the timing for data generation and the FDA meeting will be closely aligned. Following the FDA meeting, we intend to make the top-line data publicly available.

Phase 3, design, timing of launch, could you comment on that?

Steven, would you like to take that, please?

Yes. I mean, our plans with the Phase 3 trial are in the same line of therapy as the Phase 2, and we anticipate getting that trial started by the end of the year so it can be substantially enrolled at a potential PDUFA date in 2025.

Got it. And then you're being a bit more precise about your biopharma strategic discussions than you've been before. Garo, could you comment on what areas are more or less aligned that could unlock the deal structure that it looks like you're prioritizing, and maybe how much does the neoadjuvant CRC opportunity kind of play a role? Because it obviously expands the market, but it also comes with a commitment of doing a long-term study.

I think it's very important to address your question in a way that doesn’t violate any confidentiality. So we have, as you know, talked about partnering BOT/BAL for the last couple of years. Now, of course, when we started our discussions with prospective partners, we had a fraction of the data we have today. A fraction of the data. And thanks to our enthusiastic physicians, investigators, and of course, patient inquiries, we have had an explosive growth in our clinical trial enrollment. I mean if you look at, for example, our Phase 2 trial enrollment, we enrolled 230 patients in less than five months, which is a record that has surprised many people. Now with all of that, you would expect, of course, that there's a fair amount of enthusiasm by prospective pharmaceutical companies amidst, as we've talked about earlier, all of the fascination with treatments that result in weight reduction and radiobiopharmaceuticals as well as ADCs. But when I asked a question to experts, I say, do ADCs and biopharmaceuticals cure cancer? The answer is often not, no. Now, of course, we don't know if we're curing cancer. We don't know that. And the term curing cancer is a very dicey term because how do you demonstrate it? How do you clinically demonstrate curing cancer? And the only thing that we know for sure is that there is a product called Yervoy that has cured, de facto cured a slice of melanoma patients. But it's been mostly restricted to melanoma. In fact, Dr. O’Day was one of the pioneers in the clinical development of Yervoy. Now, of course, one of the attributes of the Yervoy is that it binds to CTLA-4, a very important receptor in the activation of the immune system, specifically T cells. Now we also know that our Botensilimab binds to CTLA-4, but it does so many other things. So we are hopeful, hopeful that eventually, Botensilimab’s activity will be broader than what Yervoy's activity has been in melanoma. And so with that, of course, we're excited about what we're going to be doing with it. And that makes the question of a like-minded partner that will put in the resources to develop Botensilimab and Balstilimab for the kinds of cancer patients that deserve it, meaning that our aim is that once we get the regulatory buy-in and we go for our first BLA filing, our aim is an explosive expansion for the development of Botensilimab. Explosive expansion because, as you know, we have said, across nine different indications, with varying denominators of 900 patients in total, we've seen some remarkable activity. There is no two ways about it, remarkable activity. And that is, of course, the basis for why the right partner that will be selected hopefully, in the next several months would be the partner, not just for us, but for the benefit of the patients to develop this product in the way it deserves to be developed. So again, we have, I think, Christine slipped a number of active discussions. There are a number of active discussions right now that are going on. And unfortunately, on one hand, these discussions take a long time. Our longest corporate discussion that has resulted in a significant partnership has taken nearly two years. The shortest one was a year. So I'm not suggesting that the partnership is going to be a year from now. But I just want to give you guidance that these things take time.

Very helpful, Garo. And just maybe lastly on that marketable activity just on the pancreatic and this TKI refractory lung cohort data, which seems new, could you talk to what patient numbers you're expecting to have in your mid or second half update for pancreatic and maybe lung, if you could just comment on that. Thanks again for taking our questions.

If I may ask either Steven or Todd to address this question, and if you have more specific clarification for the questions, please feel free to ask.

So yes, Mayank. In terms of pancreas, we have a randomized Phase 3 trial, and we expect to treat 60 patients total, 30 on each arm, and that trial is actively accruing for further proof-of-concept. In terms of the lung data, we have expanded the cohort, as we've said, to approximately 50 patients. This data is maturing. We're showing you the preliminary TKI data in our press release today. You can see in that very refractory TKI population of seven patients, we had two patients have responses and both of them were complete. The overall data continues to mature, and we’ll have more data in the second half of the year to report.

Next, we'll go to Colleen Kusy at Baird.

Can you just comment on what are some of the outstanding items you think you need FDA feedback prior to the MSS CRC filing?

Is the question, what are the alignments with the FDA that will come to potential BLA filing?

Yes.

We want to start by mentioning that we have made a strategic decision as we rapidly enrolled participants in our clinical trials, particularly the important Phase 2 trial that we plan to present to the agency. This trial was crucial for dose selection and provided valuable data, although it included a small reference arm. It's important to note that this trial is not statistically powered to show any differences between the arms, but it is structured to address key questions. If we approach the agency with abstract queries, we anticipate that they will advise us to return with concrete data for further analysis. To ensure we present a compelling case to the FDA, we have decided to wait until all the data has matured. We expect this maturation to begin before the middle of the year. As you are aware, requesting meetings and preparing a comprehensive data package takes time. We intend to ask for a meeting soon and hope to schedule it around mid-year, plus or minus a month.

Great. And then just one follow-up on the pancreatic development program. I know we'll have data from the Phase 2 trial midyear. What would the next steps look like in the development path towards approval there?

For the pancreatic?

Yes.

To summarize, the data package that we will present to the FDA for the CRC indication includes roughly 150 patients from our Phase 1 trial and 230 patients from our Phase 2 trial. Regarding pancreatic cancer, the next step is to analyze the randomized data outcomes from the expansion cohort of the current trial. We have seen notable activity in second-line pancreatic cancer patients who were treated with full fury and subsequently relapsed, with abraxane currently being the standard of care for these patients. Unfortunately, this standard treatment is not curative, leading to quick relapses, and expert estimates suggest response rates of only 10% to 15%. Although our initial data comes from a small cohort, it shows that all patients have experienced a significant reduction in cancer counts and tumor shrinkage. While not all are classified as responses, the reduction in tumor size gives us strong confidence to expand the trial, which we are currently doing. We have enrolled around 30 patients in this randomized trial, and as the data matures and we confirm outcomes from the initial smaller group, we may approach the FDA for potential accelerated approval for this indication. Additionally, there are other indications we may pursue approval for, subject to confirming results from the smaller cohorts. For instance, in lung cancer among EGFR mutant patients, we will expand our research to verify the substantial tumor size reduction observed in earlier trials. This approach mirrors what J&J did with a larger patient population for their bispecific therapy, which reportedly is projected to generate billions in sales despite a smaller patient population. We see opportunities in small trials with very specific patient groups that tend to yield high response rates, often using biomarker-driven methods for patient identification. This includes specific subsets of lung cancer and approaches related to neoadjuvant therapy. Particularly, our neoadjuvant trial shows potential for surgery-sparing outcomes which are crucial, especially for younger patients facing radical surgeries that could significantly impact their quality of life. We are thoroughly exploring all these options and more.

That's very helpful. One really quick follow-up, if I can. Just on the neoadjuvant, the next neoadjuvant setting study, will that allow for the potential to get surgery altogether? Or will all of those patients proceed to surgery?

Well. Okay. So I'll let O'Day elaborate, but I know at least one patient after a complete response refused to have surgery. Now of course, that's a tricky situation. We got the ethical considerations, in which we don't have an approved product in that indication yet. And hence, that recommendation cannot be made by a physician for ethical reasons right now. But if a patient refuses to have surgery, it's their prerogative; it's their life. But you are seeing that kind of potential develop. And of course, I want to stress the fact that everything has to be done properly with appropriate regulatory guidance. And everything has to be done in an ethical way so that we don't jeopardize the well-being of patients.

We'll go next to Matthew Phipps at William Blair.

So just curious, when you said data in the second half from the Phase 2 colorectal study, do you think you'll have PFS data by that point? It seems like given the poor prognosis in this patient, that could be possible.

So I will refer to our regulatory experts, but PFS in these patients relative to OS is such a short interval difference that I think OS is the gold standard, PFS is much less so. Steven, Todd, do you have any comments on that?

Yes. Steve, go ahead, and I'll talk.

Matt, yes. We will monitor response rate, duration of response, progression-free survival, and preliminary survival in these patients as they evolve throughout the year since they were enrolled. It's a composite endpoint. However, as Garo pointed out, response and duration of response are key factors that influence the survival curve. Therefore, our main objectives are response, duration of response, and ultimately, the gold standard of survival.

And I guess just curious, Garo, why not disclose at least some indication of the top line results, I guess, in May, given the six months follow-up by that point? Why wait till after you meet with the FDA to at least, I guess, say whether or not or endpoint has been met or something like that?

It's strictly regulatory courtesy. I think it would be not appropriate if we're ready to present that data to the FDA to make that public right before our FDA meeting.

And next, we'll move to Kelly Shi at Jefferies.

So just one question on the lung cancer update. Given you've shown 50% overall response data in patients…

Sara, your voice is coming very faint and there's some crackling in the line, if you can speak closer to the microphone.

How about now?

Yes, better.

Okay, got it. So just one question on the lung cancer update. Given you've shown 50% overall response data in nine patients, wondering what would be the efficacy you need to see on the next update to advance the program into the next stage of development? And if so, what would be the going forward plan for lung cancer? And also just wondering, can you remind us what other data disclosure we should expect in 2024? I believe the BMS partner TIGIT data is also expected this year as well? Just wanted to confirm.

Sure. We have made some adjustments to the enrollment process for the lung cancer trial. Currently, we are analyzing the data and focusing on subsets of patients who have demonstrated notable responses. By significant response, I mean complete or rapid complete responses at our low dose level, which we consider important. We are now working on defining our next steps for these biomarker identifiable patient subsets, and we expect to move quickly on lung cancer. Regarding data for the rest of the year, we anticipate mature data from larger cohorts of pancreatic cancer patients in a randomized trial, with preliminary results possibly by mid-year and more detailed findings by year-end. We will also have more mature data related to melanoma and will provide insights into the sustainability of responses in sarcoma. Additionally, you can expect to see a substantial amount of data in colon cancer soon after our regulatory meetings.

And there are no further questions at this time. I would like to turn the conference over to Garo Armen for closing remarks.

Thank you very much, Audra, and thank you very much for your attentiveness and sort of fantastic questions, actually. And I think we've covered a great deal here, and I just want to make sure that our stakeholders are assured of our commitment to make sure that we stay focused, first of all, because we're in a very unique environment, where resources are not as abundant as they were in the past. And so maybe that's a good thing because it forces companies, not just us but the industry, to do things more rationally. So we intend on delivering outcomes with efficiency. We are poised to be able to potentially launch product, both from a CMC perspective, as well as from a commercial perspective. We have a terrific team in each category to do this. In addition to that, we have assembled a very, very competent medical affairs team so that we can drive our processes through education, education of the system, patients, regulators, as well as physicians that will eventually prescribe our medicines. So we are attending to all of these very important components. We are a small, large company in that sense and an old young company in many ways. Thank you very much for your attentiveness and we will communicate with you appropriately at the next time.

And this concludes today's conference call. Thank you for your participation. You may now disconnect.