AGEN - NASDAQ

Good morning and welcome to Agenus Inc.’s First Quarter 2025 Earnings Conference Call. Currently, all participants are in a listen-only mode. A question-and-answer session will follow the formal remarks. As a reminder, this conference is being recorded. I will now hand the call over to

Thank you, operator. Welcome to Agenus’ first quarter 2025 financial results and corporate update call. Earlier today, we issued a press release detailing our financial results and key corporate developments. A copy of the press release is available on our website at www.investors.agenusbio.com. Before we begin, I'd like to remind everyone that today's discussion will include forward-looking statements. These statements are subject to risks and uncertainties, which may cause actual results to differ materially from expectations. Please refer to our SEC filings for further detail. Joining me today are Garo Armen, PhD, Chairman and CEO; Dr. Steven O'Day, MD, Chief Medical Officer; Robin Taylor, PhD, Chief Commercial Officer; Richard Goldberg, MD, Chief Development Officer, and Christine Klaskin, VP Finance and Principal Financial and Accounting Officer. Now, I'll turn the call over to Dr. Garo Armen.

Thank you, everybody. Thank you for joining us today. Before we start on today's call, I will cover 6 priorities, or I should say we will collectively cover 6 priorities. First, we're going to present to you the newest BOT/BAL data, validating durable responses in historically untreatable cold tumors, and I might stress that we're talking about new data and more mature data. We're going to talk about the strategic hire of Dr. Richard Goldberg and his mandate to steer our regulatory path. Next, we'll talk about operational efficiencies that are on track to cut our operational cash burn to below 50 million annualized in the second half of this year. And fourth, 4 formal near term transaction proposals that we have received, including an Emeryville facility sale. A significant equity investment at a big premium, and 2 BOT/BAL licensing deals, each individually or in combination are designed to materially strengthen our balance sheet. And lastly, the changes in the new FDA policies that could favor rapid approval of transformative therapies and our recent request for a Type B meeting. And we'll provide you with some details as to the rationale of this. So, before I get into the business update, I'd like to acknowledge a critical and growing public health crisis. This underpins everything we do at Agenus. Colorectal cancer is on the rise. Particularly among younger people under the age of 50. Colorectal cancer incidences have doubled in the U.S. adults under 55, from 1995 to 2019, less than 25 years. By 2030, colorectal cancer is projected to become the leading cause of cancer related deaths in men under 50 in the United States. These younger patients especially need treatments other than chemotherapy, radiation, and life-altering surgeries, particularly in the young. This is important for the young and the old, but particularly in the young. These life-altering treatments can have a lasting devastating effect. And hence they deserve an alternative without life changing side effects. And that's what we think we offer to patients. These younger patients. The new leadership is particularly aware of this. The new leadership at HHS and the FDA recognized this grim reality of today's treatment. One of the president's first actions with Secretary Kennedy was to set up the Make America Healthy Again Commission, which is set to ensure and issue its report any day now. Secretary Kennedy has pledged to root out conflicts of interest, and FDA Commissioner Dr. Marty Makary has repeatedly stressed the need to accelerate approval of meaningful treatments. I underline meaningful treatments. This shift in regulatory environment is deeply encouraging to us. And for the entire research community, discovering and developing novel and effective therapies. So, it's an exciting time for us, and some of our peers. We have new data, new leadership, new efficiencies, and a new environment at the FDA and the government. So, we'll talk about these one by one. For botensilimab and balstilimab, which we call BOT/BAL as you know, we are generating consistent and compelling data across different lines of treatment. Both in the neoadjuvant setting and in later line. And across multiple cold tumors that have historically defined standard immuno-oncology therapies. These include MSS colorectal cancer, a huge problem. Certain breast cancers, sarcomas, hepatocellular carcinoma, and many more. At AACR 2025, 2 weeks ago, there was a groundbreaking presentation by Dr. Myriam Chalabi of the Netherlands Cancer Institute. She presented results from the investigator-sponsored study of NEOASIS and cancer study. Remember this is many different types of cancers. In the neoadjuvant setting, and if you remember, so far, prior to this, we had generated data in the neoadjuvant setting of colon cancer. So, this takes that concept and broadens it to many other cancers. The study showed pathological complete responses across multiple cancers. No dose limiting toxicities and all patients proceeded to surgery on schedule, very important. As Dr. Chalabi stated, these findings substantiate the importance of this immunotherapy in early treatment settings, or I should say earlier treatment settings, because these patients are not really early cancer patients, they're stage 3. And highlight the broad potential utility of this combination, she was speaking of BOT/BAL. In liver cancer, Dr. Anthony El-Khoueiry, Chief of Section of Developmental Therapeutics at the USC Norris Comprehensive Cancer Center, presented Phase 1 data in HCC cohort data of BOT/BAL in patients heavily pre-treated with available therapies, including PD-L1 blockade, plus Avastin, which are the standard of care in last-line, and still demonstrated deep and durable disease control. Very important for patients. Let me talk about our new leadership and of course we have fantastic leadership, but this is new leadership to be added on. To support this next phase of development, we welcome Dr. Richard Goldberg, a world-renowned GI-Oncology expert, as our chief development officer. His leadership will be pivotal as we advance towards regulatory filings in metastatic CRC and other tumor types. Dr. Goldberg recently authored a guest editorial in the cancer letter arguing that IO approvals should be customized to spare patients unnecessary, life-changing toxicities, the same thing that we talked about. Rather than speak on his behalf, I'd like to invite him to share his perspectives directly with us today, Dr. Goldberg.

Thank you Garo for that kind introduction. Five years ago, I stepped away from formal leadership roles in academic oncology and from active clinical practice. That time has allowed me to support companies working on new treatments for GI cancer and to deepen my involvement in patient advocacy. But throughout that time, I keep hearing the same message from patients, from their families, and from colleagues, we need better treatments, especially for colorectal cancer. People want more time, better time, and ultimately they want hope for a cure. This need is especially acute for patients with MSS colorectal cancer, where existing immunotherapies have offered little benefit. As an advisor, I've had the opportunity to evaluate many programs. What stood out about Agenus and what ultimately brought me back into a full-time leadership role was the potential for BOT and BAL. This combination represents one of the most promising advances I've seen in my career. It has the potential to shift outcomes, not just in colorectal cancer, but across a range of difficult to treat solid tumors, which represent the biggest challenges in achieving cancer cure. The opportunity to help move these agents forward to gain FDA approval and make them accessible to oncologists and patients across the world is what's compelled me to reenter the field. I'm excited to be here and I look forward to working with the exceptional team at Agenus to bring forward new hope and meaningful treatments for our patients. These patients especially need treatments other than chemotherapy and radiation and life altering surgeries. They deserve an alternative without life changing side effects. The new leadership at HHS and FDA recognize this. Thank you Garo.

Thank you very much, Richard. It's a real privilege to have you on board, given your career and given the fact that you know this disease inside out, and you've been gracious enough to invest the time to really understand our data inside out. And so with that kind of endorsement, we're very grateful for your leadership in our next chapter. As we indicated in our March call, we are on track to cut our annualized operational cash firm below 50 million in the second half of 2025. This is going to free resources to unlock BOT/BAL and its full potential, not just in colorectal cancer, but beyond, because as we mentioned, BOT/BAL is a very powerful IO agent that shows activity, and this is corroborated by some of the leading experts across different cancers that are familiar with IO. So, before we move on to the financial review by Christine, let me address capital strategy head on. Over the past several weeks, Agenus has received 4 formal written proposals that would inject or should have the potential to inject substantial new capital. The proposals would allow us to monetize on our state of the art Emeryville biologics facility. Each of these proposals also have the potential to expand into broader strategic collaborations. A third proposal offers a significant equity investment at a meaningful premium to our current share price. And at fourth contemplates a BOT/BAL licensing agreement with upfront cash, milestones, and double-digit royalties. Our Board and our advisers are evaluating these proposals with a high sense of urgency, I might add. And we anticipate announcing at least one of these transactions in the coming days or maybe a few weeks. Any of them would materially strengthen our balance sheet while preserving long-term upside for shareholders and most importantly, accelerating our mission to bring life-saving therapies to patients. With strong scientific momentum, we remain equally focused on operational discipline. With that, I will turn it over to Christine to briefly review the financials. Christine?

Thank you, Garo. We ended the first quarter 2025 with a consolidated cash balance of $18.5 million compared to $40.4 million at year end 2024. Cash used in operations for the first quarter ended March 31, 2025 was $25.6 million, which is reduced from $38.2 million for the same period in 2024. For the first quarter ended March 31, 2025, we recognized revenue of $24.1 million and incurred a net loss of $26.4 million or $1.03 per share. For the first quarter of 2024, we recognized revenue of $28 million and incurred a net loss of $63.5 million or $3.04 per share. Our revenue primarily includes non-cash royalty revenue. I'll turn the call back now to Garo to close out the call.

Thank you very much, Christine. So, in closing, for all the reasons we've discussed today, which include new data, new leadership, new efficiencies, and a new regulatory environment in addition to anticipated near-term corporate transactions, we believe Agenus offers a great deal for patients and all stakeholders. It is for these reasons that on May 5, Agenus formally requested a Type B meeting with the FDA for BOT/BAL. Our dossier built on rigorous data for more than 1,200 patients, and now that is with a 2-year follow up showing deep and durable responses. And these deep and durable responses, by the way, are the hallmarks of effective IO treatments, as our chief medical officer has always said. And so we believe our dossier meets every statutory criterion for potential accelerated approval. We're hopeful that the agency will engage promptly and judge our submission on its merits. Our conviction in BOT/BAL’s curative potential has never been stronger, and our team is absolutely resolved in delivering this breakthrough to patients, who have waited far too long, far too long. Thank you very much for your continued support and attention. And operator, we are ready for questions now.

[Operator Instructions] Your first question comes from the line of Emily Bodnar from H.C. Wainwright. Your line is open.

Hi, good morning. Thanks for taking the questions. I guess, to start with your commentary about regulatory interactions. How much like longer term follow up you have from the Phase 2 study and have you hit on the overall survival endpoint yet? And then assuming that you speak to them, if they come back and say that you still need the Phase 3 study, can you comment on your ability to run a Phase 3 study and what that might look like?

Sure. So, I will ask Dr. Steven O'Day to comment on the longer term efficacy data, and perhaps I can ask Dr. Buell, who has graced us with her presence today. In addition to her responsibilities at MiNK, as you know, she is the chairman of the executive board of Agenus and overseeing all of our regulatory efforts on the Phase 2 question -- on Phase 3 question. Dr. O’Day.

Thank you, Emily. So, last year when we presented to the FDA our data set, both our Phase 1 and our Phase 2 was in July based on a March data cut, so we'll have approximately 1 more year of data both in our Phase 1 and our Phase 2. The median follow up for the Phase 1, which now includes 123 patients is 18 months. A substantial increase in duration from last year. The Phase 2 trial has approximately just over 12 months of median follow up, also significantly more than it did last year. So, the combination of both our Phase 1 and Phase 2 data with the longer follow up will obviously be a significant factor in the next review with the FDA.

Thank you Steven and also remember what's remarkable about these 3 seemingly separate studies, that is Phase 1 cohort 1, Phase 1 cohort 2, and Phase 2, is the consistency of data across the board, which obviously makes the results much more credible. And in terms of our next steps, as you know, last year when we had the meeting with the FDA, they made, in our opinion, an erroneous judgment based on a paper that was published, which excluded some critical references and some critical data. And of course, this is not their fault, but because they have a lot on their plate, but this erroneous decision resulted in them telling us that perhaps this study, even with longer term follow up, may not be adequate for approval. But, what is very clear and strikingly clear to us is that the longer term follow up is very indicative of survival benefit. I mean these patients you can follow up for 2 years, 5 years. At some point, you need to give in and say this is indicative of survival. And this is what we're basically making a point at. And Dr. Goldberg, of course, looked at all of this data and concurred with this conclusion. That's one of the reasons he's here. Otherwise, this very, very [indiscernible] would have been very difficult to bring in from his so-called retirement at a young age. So, I'm going to pass it on to Dr. Buell now to make comments about Phase 3, because of course we're making plans for Phase 3, but the question becomes what indication and what types of Phase 3 trials we're pursuing. Dr. Buell?

Thanks very much Garo. I'm just going to reiterate a couple of points here, Emily. You're quite aware of the work that we've done, and I think it's an important time. We're grateful for the agency's partnership as we concluded our July meeting last year and now we're -- as they've requested, we're coming back with additional data and Steven just mentioned we have more than 40% additional patients, more patients on the Phase 1 with very mature follow-up. And then of course an additional year of follow up on the randomized Phase 2, which did include a standard of care arm. We expect to present data on these data sets at a major upcoming conference that will be near term, so you'll have a sense of the depth and durability of the responses. But as Garo mentioned, previously the FDA had mentioned to us again this was a year ago that they advised submission of the results, and this is specifically an outcome of the meeting. Due to the modest overall response rates and the fact of the ability of the response rates to reasonably predict a meaningful benefit for patients. Now, the reason that this response is really quite surprising to us was that given the clinical outcomes that we submitted at the time, we demonstrated more than 4 to 5-fold improvement in tumor shrinkage or response rates and a more than doubling of overall survival and it's very hard to treat cancer and since then, now nearly a year later, our data have further matured, reinforcing and extending the clinical impact in which in fact we've got some patients out beyond 4 years with no progression. So, we're really quite excited to bring the data back to the agency, and I think with this new evolving administration we share the urgency to bring new medicines to patients, particularly in this growing prevalent disease right now that's impacting the young as well. As far as next steps, we'll also talk with the agency about our randomized design. We're presenting 2 different approaches to the agency, because we have, quite frankly, as Garo mentioned, parties who are really interested in helping us accelerate the development of these for patients with the highest unmet needs for which there are currently no available therapies, and for patients, building on what you observe from the ASCO GI data, and Myriam Chalabi's data in patients in the earliest disease, neoadjuvant disease.

Thank you Jen. So, as we all know, besides the important box checking regulations, rules and regulations, drugs have to be demonstrated to be efficacious, in other words, they're active and they're safe. I mean, safety is of course relative to the patient population that we're going after. And one of the most striking features of BOT/BAL is that in the neoadjuvant setting, the efficacy is black and white, because we're not aware of very many agents out there, let alone IO agents, that within a span of 4 to 8 weeks, result in complete resolution of the tumor. And this is what we've seen visually and in terms of pathologic complete responses in the neoadjuvant setting. As Jen talked about in the late-line setting, I think she was being modest by calling the response rate modest. Of course, she also mentioned that it is 3 to 4 times better than anything out there because as you know, in late-line setting, response rates of approved products out there range from 1% to a maximum of 7%. And depending on the patient population, we're at least twice that, in most cases, 3 times that, with a longevity of the durable responses, which should translate to survival benefit. So, that's the specific nuance here.

Thank you.

Your next question comes from a line of Mayank Mamtani from B. Riley Securities. Your line is open.

Yes, good morning team. Thanks for taking my questions and pleased to see Dr. Goldberg join the team here. Are you able to discuss any development plan changes or update in light of the recent ACR update, thinking, your NEOASIS trial did have some non-CRC patients like TNBC and also obviously you have the late-line SCC cohort update, so was just curious how as you go into a type B meeting, some of these non-CRC [tumor] [ph] types kind of play a role in your longer term development strategy, or are you just very focused on CRC to get this meeting very, very focused on CRC if you could clarify that and then I have a follow up.

So, we believe that the shortest distance between presentation and approval is in the colorectal cancer setting, and there are 2 settings where we believe that this is important. One is in refractory disease, either third or fourth line therapy, and one of the interesting observations from the emerging data is that the response rate looks the same in third-line and in fourth-line, so that I think makes it clear that the mechanism of action of these drugs is divergent from the other drugs that patients have been exposed to. And the other area that we're excited about is in the neoadjuvant setting. As you may be aware, there was a recent presentation from the team at Memorial Sloan Kettering, on their MSI-high patients are showing activity in both MSI-high colon cancer and MSI-high non-colorectal cancers. And we believe that our approach is going to expand that indication to the much larger subset of patients who are microsatellite stable, who are not MSI-high, but the path that they have blazed in the MSI-high group is a path that we hope to follow in the neoadjuvant setting, both in rectal cancer and potentially in colon cancer, where the potential to avoid all of the toxicities of surgery, radiation, and chemotherapy would be welcomed by patients.

Does that address your question Mayank?

Yes, I guess the type B meeting focus. I heard that it's going to be primarily CRC focused is that fair and having those 2 indications late-line and neoadjuvant, yeah, that's clear. I guess, are you able to comment on when do you expect the type B meeting to occur and get all the strategic discussions that you alluded to, I believe would need to have those minutes in hand before you're able to move forward in a meaningful way. Is that fair?

Okay, I'll let Jen answer this very important question.

Hi, Mayank. We actually have quite a bit of data and information from the FDA, which has satisfied the discussions that you're referring to the strategic discussion. So, the path forward from our perspective is really quite clear. The opportunity is what we want to speak with the agency, which is the fastest path to get these products available to patients. That's independent of the strategic discussions.

I think that's very important [indiscernible].

And lastly, if you're able to comment on the European counterparts also, as that obviously has been a separate engagement, so any update there.

Sure, Jen will tell you what our history has been with Europe, because right after the unsatisfactory meeting with the FDA last June, we engaged with CHMP and the European authorities, and the outcome of those meetings I'll let Jen comment.

Thanks, Mayank. We have not previously disclosed this, so this is really the first that we're disclosing. The interactions with CHMP and the scientific advisory group last year was incredibly productive. The team was very prepared, impressively so. They agreed with us on our selected dose. They've agreed that we had achieved contribution of components, and they agreed with the two-arm randomized trial for registration. Now, the conditional approval pathway is a possibility for us that we're going to go ahead and pursue. We're talking with the U.S. FDA and we plan to talk with the European, the EMA, and essentially in parallel, the initial interactions with the FDA will occur first though.

Understood. Thank you for taking our questions.

Your next question comes from a line of Matthew Phipps from William Blair. Your line is open.

Good morning. Thanks for all the detail here on the updates. Garo, I think before you've provided some valuation framework for the Emeryville facility, and I'm wondering if that value has increased given the focus on kind of on-shoring pharmaceutical manufacturing over the past few months.

I think this is a very, very good question. And when I say good, I'm not dodging the question, Matt. I believe that the totality of the value we will derive out of the Emeryville facility will reflect that premium. Of course, if we had the luxury to wait another 6 to 12 months, I think that we could get a lot more for it. But right now, it is a relatively inexpensive access to capital. And hence we are pursuing that route, even though we believe the value will continue to go up.

Yeah, that's fair. And then I'm sure you can't give us too much more details on some of these agreements beyond what you already gave, but the licensing agreement, can you just say if that is geographic -- geography specific or if it is broader worldwide?

So, the 2 agreements, which have been submitted to us in writing, proposals, are global. Two additional agreements that we are potentially looking at as an important option for us are geography specific. So, depending on our coastal capital considerations and immediate needs, of course, the global licensing agreements would contemplate third parties underwriting the entire cost of additional trials and registration for BOT/BAL. So -- that appeal, because it will further drive our operating burn rate down. And but let us sort through these, because the sequence with which we consummate some of these agreements, and bring in cash and create value will be critical in determining our next steps.

Okay, great, thanks Garo.

Your next question comes from a line of Colleen Kusy from Baird. Your line is open.

Great, good morning. Thanks for taking our questions. Have you had any interactions yet with the new FDA at this point ahead of the Part B meeting? And can you provide a little more color on the publication that you mentioned that led the FDA to its conclusion last summer and why you think that might be a different situation this summer?

Okay, so I will answer the second question first. The publication we're talking about, I believe Dr. Buell correct me if I'm wrong, was a New England Journal of Medicine article by doctors Richard Pazdur and Julia Beaver. And this article, made a point that IO in combination with other agents, where the response rates are at a certain threshold do not necessarily result in long-term survival. However, there's a big however. Number one, these protocols discussed by and large were not IO only protocols. There was IO, mainly PD1 plus something else. And so that doesn't really reflect the power of the lasting durable responses generated by CTLA-4 agents. That is a very important point, very, very important point. And secondly, this article excluded a number of cases, we can think about 4 or 5 cases where low response rates, and when I say lower response rates, I'm not talking about single digits, I'm talking about 15% to 20% response rates, did indeed translate to longer term survival. So, it was somewhat partial in depicting the facts. And of course, that's one issue. Now, the second question that you asked, have we engaged with the new FDA? The answer is no, we have not, because the new FDA is comprised of leadership like Dr. Marty Makary, and a lot of the senior people at the FDA, and I'm not talking about Cancer division, but a lot of the senior people, and even in the Cancer division, a lot of the senior people have left. And so we're looking at our Type B meeting as an opportunity to re-engage the agency. However, the first step for us is to present the totality of the data. And when I talk about totality of the data, remember Dr. Goldberg made the point that our sharpshooting strategy will be colorectal cancer. However, the totality of data comprising our trials across 9 different cancers, and of those 9 different cancers, about 5 of them, both in numbers and in terms of durability of responses have matured to a point where we can proudly demonstrate the consistency of data from one cancer to another to another to another. So, that's what we will be presenting as well.

Great, that's helpful, thank you. And Dr. Goldberg, congrats on the new role. I wanted to ask, how much of your time do you anticipate being focused on metastatic CRC versus neoadjuvant CRC versus all the other tumor types that BOT/BAL shown activity in?

Well, so I think BOT/BAL has demonstrated activity really in virtually every setting it's been tried. The main reason to focus on colorectal cancer is that there's such a strong need expressed by patients and physicians to have an IO intervention that realizes some of the benefits that have been enjoyed by MSI-high patients in the much larger subset of colorectal cancer patients that are MSS and the data for activity of the pre-approved drugs in late-line metastatic colorectal cancer is quite modest and while the oncology community has embraced those drugs, the patient community is disappointed by what they bring and is looking for something better. So, we believe that the comparators in the setting of advanced disease, third and fourth-line disease are favorable comparator arms to the activity that Agenus has observed in the early trials. Now, from my perspective, the most potential is probably in the neoadjuvant setting. The groundbreaking study by Andrea Cercek and her colleagues at Sloan Kettering in MSI-high tumors where patients avoided chemotherapy, radiation, and surgery, is really startling and benefits patients in ways that we couldn't have imagined, even 5 years ago. We believe that that's translatable to rectal cancer patients with MSS tumors using this intervention. And to colon cancer patients, tumors above the rectum, where potentially we could come up with a surgery-free world for managing stage 3 colon cancer.

Thank you, Richard.

That's great, thank you. And one last one, if I may, could you talk about your strategy of sharing the Phase 2 data with the street, whether that would be in conjunction with the FDA meeting or after?

Sure, I think that's doable, and I just want to draw your attention to the neoadjuvant protocol that was presented at AACR whereby Myriam Chalabi presented data on patients with a fantastically acceptable safety profile. In fact, there were no real showstoppers in the safety of the drug. And of course this is in the earlier disease setting with lower doses, 25 and 50, but nonetheless, there were no real safety signals of any sort, including colitis, to really worry about. So, we believe that depending on the disease setting, as Richard said, neoadjuvant offers the largest potential and earlier the better intervention philosophy, of course, particularly with immunotherapy and in that setting we think we're going to be based on all of the studies that had taken place, we're going to be dealing with a safety profile that will be very, very acceptable to patients.

Great, thanks for taking our questions.

And there are no further questions at this time. I will now turn the call back over to Garo Armen for closing remarks.

Thank you very much everyone. We are very grateful for your attention and for your persistence with what we're doing for the benefit of patients and all stakeholders as I mentioned. We're also very grateful to our extended team, Dr. Richard Goldberg adds a deeper level of expertise in a disease that is the focus of our attention right now. And this particular disease is becoming a major problem in the young and the kinds of morbidities generated by existing treatments, chemotherapy, radiation, and surgery could be eliminated, potentially eliminated, and this is a very important issue, because as I said before, both with the young and the old, of course these are important, but with somebody having to live with these morbidities for the rest of their lives, we're getting patients as young as 8 years old with metastatic colon cancer, which is something remarkable. And so for a young person to live with these difficulties for the rest of their lives is a big issue. So, we're very grateful for all of your attention, and we've been on a path to do what is in the best interest of these patients, and as I said with our stakeholders, and we very much appreciate your support. Thank you.