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. [Operator Instructions] 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 subjects 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 forms 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 clinical and a critical phase in our regulatory journey,…

Thank you, Garo. Together with our investigators and key opinion leaders, we presented updates from 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, and the most common of these were diarrhea and colitis. Grade 3 or greater treatment-related diarrhea 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…

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?

[Operator Instructions] 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 obstract or is that looking more like 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're giving 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 a much more specific guidance on our BLA solution. Steven O’Day: Garo, would you like me to?

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. Steven O’Day: Thank you, Garo. Emily, yes. I mean, given that MS-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 is relating 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. So as you know, we have -- as we said before, we've completed enrollment in October. And typically, 80% of the patients respond within six months of the first dose. So when we complete enrollment by the time the patients get the first dose you're talking about November. And by the time we get the 6-month readout or 80% of responses, it's sometimes around May. Now needless to say, we have already started cleaning up the data and all of the nitty gritty process so that we can provide all of the outcomes as soon as possible. So it will be in the next few months and our first step is to share this data with the FDA because the timing of the data generation and the FDA meeting will be very close. And then after the FDA meeting, we plan on making top line data public appropriately.

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

Steven, would you like to take that, please? Steven O’Day: Yes. I mean our plans with the Phase 3 trial is 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 alignment that could unlock the Coco 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. 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 radio biopharmaceuticals as well as ADCs. But when I ask a question to experts, I say, do ADCs and biopharmaceutical 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 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…

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. Steven O’Day: 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 what are some of the outstanding items do you think you need FDA feedback prior to the MSS CRC filing?

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

Yes.

Okay. So we want to -- first of all, we've made a strategic decision because we were moving, as I said earlier, we were enrolling our clinical trials rapidly, for example, Phase 2 trial and go very rapidly and it was a very important trial for us to go to the agency with because of the dose selection as well as the contribution of the elements. And of course, we had also a small reference arm. Now of course, mind you, this trial is not powered statistically to show any differentiation between the arms. However, it is designed to address the project optimist questions. And so the question was for us, if we go to the agency and ask them a question in an abstract form. What is this? What is that? The answer is likely to be, well, when you have the data, come back to us, present it to us, and we'll give you an intelligent answer. And so in order to for us to be able to get to that point, we made a strategic decision, Colleen, that we would wait until all the data mature to the point where we had a compelling package with to present to the FDA. So that's the reason why we are waiting until the data matures, which will begin somewhat before the middle of this year. And as you know, procedurally requesting meetings and being granted meetings or in a discussion with a comprehensive data package takes a little time. So we are planning on asking for the meeting very soon and planning on having the meeting sometime 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.

Okay. So just to recap, the data package that we will go through the FDA with for the CRC indication is approximately 150 patients in our Phase 1 trial and the 230 patients in our Phase 2 trial. Now with pancreatic, the next step for us, and I will ask Dr. Steven O’Day to elucidate more. But the next step for us is to look at the randomized data result from the expansion cohort of the existing trial. As you know, we observed some remarkable activity in second-line pancreatic cancer patients that were treated with full fury and then relapsed. And the standard of care for them is abraxame. Now the standard of care, unfortunately, is not curative. And these patients relapse within a short period of time. Furthermore, the response rates for these patients according to the experts and published information is in the range of 10% to 15%. So we're talking about reference arm being 10% to 15% with response rates being very short in duration. Now, of course, the denominator of the data that we presented is small, but the fact that all patients have seen a significant drop in their cancer counts. And all patients have seen a shrinkage in tumor, now remind you, not all of them are classified responses, but patients have seen a shrinkage in their tumor size, has given us a high level of confidence that the trial should be expanded, and this is what we're doing. So we have enrolled, I believe, around 30 patients in a randomized trial now. That data is maturing. And as the data matures and we confirm the results from the smaller denominator of the initial patients, then I think we will have a reason to go to the FDA and ask them for the requirements…

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, refuse 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 a 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. Steven O’Day: Matt, yes, I mean, obviously, we'll have response rate, duration of response, PFS and preliminary survival in these patients as they mature over the course of the year from their last -- from when they were accrued. So obviously, it's a composite endpoint. But to Garo's point, clearly, response and duration of response is what drives and prolonged stable disease drive the survival curve. So our primary endpoints are obviously response, duration response and then ultimately, the gold standard 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.

Okay. And I assume then you’ll make disclosures publicly after receiving the minutes from that FDA meeting. So adding a little bit of time for that.

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

This is Sara on for Kelly. So one quick question on non-small cell lung cancer. So for the next update, given you've shown 56% 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. So a couple of things here. On the lung cancer, as you know, we slowed down overall enrollment in the trial. So what we're doing right now, having dissected the data and looked at subsets of patients that have had significant responses. When I say significant response, I'm talking about complete responses, rapid complete responses at our low dose level. That, to us, is a significant outcome. So we're in the process of now defining how we would proceed, as I said earlier, with those subsets of biomarker identifiable patients. And so that's our next step in lung cancer, but that's going to happen very quickly. With regard to data for the balance of this year, we have data coming -- mature data coming from larger cohorts of pancreatic cancer patients in a randomized trial, that would be some time, maybe preliminary data will be by mid-year, but more mature data by the year-end. We'll have more mature data in melanoma. We will provide the sustainability of responses in sarcoma. And of course, you will see substantially more data in colon cancer shortly after our regulatory meetings.

Super helpful.

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 insured 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.