Good afternoon, and welcome to Agenus investor briefing 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 turn the call over to Zack Armen, Head of Investor Relations.
Thank you, Operator. Welcome to Agenus' investor briefing call. Earlier today, we issued a press release announcing a strategic collaboration between Agenus and Zydus Lifesciences, which we are here to review in more detail with you today. 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, Chairman and CEO, and Dr. Steven O'Day, Chief Medical Officer. I'll now turn the call over to Garo Armen.
Thank you, Zack, and good afternoon, everyone. Thank you for joining us. On today's call, we will be discussing an exciting new partnership between Agenus and Zydus. It's an exciting opportunity for both companies and for trade between two great nations, the world's oldest democracy and the world's largest democracy. Before I get into the details, I want to start with why this is so important. As you've been hearing lately, colorectal cancer is on the rise, particularly among younger people under the age of 50. Colorectal cancer, which is known as CRC, incidences have doubled in the U.S. adults under 55 from 1995 to present. By 2030, colorectal cancer is projected to become the leading cause of cancer-related death in men under 50, that is, in the U.S.A. These younger patients especially need treatments other than chemotherapy, radiation, and life-altering surgeries.
They deserve an alternative with life-changing side effects. This was, by the way, a major topic of discussion at the ASCO meeting, which I attended, along with 75 meetings-80 meetings that we had with KOLs and investigators who came to meet with us without getting paid a penny. I must stress the importance of that. The new leadership at HHS and the FDA recognize what I just said. One of the President's first actions with Secretary Kennedy was to set up the Make America Healthy Again Commission, which is focused on investigating the causes of America's worsening health trends. The Commission issued its report last month, and one major area of focus was the rise in cancer incidences among younger people. This is alarming. Secretary Kennedy has pledged to root out conflicts of interest, and the FDA Commissioner, Dr.
Marty Makary has repeatedly stressed the need to accelerate approval of meaningful treatments. I underline meaningful treatments in this context. This shifting regulatory environment is deeply encouraging to us and for the entire research community who is discovering and developing novel and effective therapies, not incremental therapies that extend life by marginal timelines, a few weeks to a few months, with horrible side effects. It is an exciting time at Agenus. We have new data. We have added to our leadership, and now we have a new partnership and a new environment at the FDA. We'll talk about these one by one. Let's talk about new data.
For both botensilimab and balstilimab, which we call BOT/BAL, and by the way, the entire community now has started calling it BOT/BAL, we are generating consistent and compelling data across different lines of treatment, both in the neoadjuvant setting all the way down to later lines of treatment for patients that have exhausted every single available therapy. This is happening across multiple cold tumors that have historically defied standard immunotherapy treatments. These include MSS colorectal cancer, which, by the way, accounts for more than 85% of the colorectal cancer cases; certain hard-to-treat breast cancers like—I'm sorry, triple-negative breast cancer; sarcomas, which have been a traditionally difficult target for patients; and hepatocellular carcinoma, among others.
As I mentioned, I just got back from ASCO in Chicago, where we presented translational data showing that BOT/BAL elicited a response in MSS tumors, which, as I said, historically have not responded to any immunotherapy to speak of. Now, all of this builds off of Dr. Myriam Chalabi's presentation at AACR in late April of this year. Dr. Chalabi presented results from investigator-sponsored NEOASIS pan-c ancer study trial in the neoadjuvant setting. This study showed pathologic complete responses across multiple cancers and, importantly, no dose-limiting toxicities, and all patients proceeded to our next level of treatment, like surgery, on schedule. As Dr. Chalabi stated, these findings substantiate the importance of this immunotherapy in early treatment settings and highlight the broad potential utility of this combination, as she was talking about BOT/BAL. Let me spend a second on new leadership that we've added.
To support this next phase of development, we recently welcomed Dr. Richard Goldberg, a world-renowned GI oncology expert, as our Chief Development Officer. He was with us at ASCO as well. His leadership will be pivotal as we advance towards re-engaging the FDA for metastatic CRC and down the road for other tumor types as well. Now, let's come to new partnerships and new opportunities. Of course, today is about our new partnership and new opportunities. It is expected that the United States will reach a trade agreement with India any day now. In both countries, there is renewed sense of confidence in Indian-American relations and trade. Leaders in the U.S. recognize the need to secure America's biopharma supply chain, a very important part of the agenda here. For all these reasons, now is a great time for this particular agreement that we entered into today.
That is why we decided it's now. It's now that's the right time to move on to this kind of agreement. I believe this agreement and our relationship will benefit Agenus and Zydus, but also our two great countries, which are already great trading partners. Let me go to slide two, if I may. Slide two talks about the strategic collaboration uniting Agenus' pioneering research and development capabilities with Zydus' worldwide manufacturing and operating strengths.
Now, if you sort of take a step back and look at the reasons why we consummated our Emeryville strategy to make commercial-grade product, I might add, state-of-the-art facility that will make this commercial-grade product, it has to do with the fact that we want today reliable, consistent means of supplying in the event that our expectations and patients' expectations came true, that BOT/BAL became a standard for the treatment of many difficult-to-treat cancers. That was the original reason why we did this, because at that time, we realized that it would have been too risky for us to just depend on traditional CDMOs.
Now, what I'm delighted to announce with this agreement is that even though this transaction transferred the ownership to Zydus, we have the same drivers of integrity, reliability, efficiency, and quality in Zydus in a facility that we built and with a team that has played a major role in building this facility and running it right now. That is one of the reasons why having this partnership with Zydus makes our relationship not just in the context of generating additional funds for our own company, but also looking at the future and anticipating that future with a reliable partner. Okay. Now, this partnership and the divestiture of our non-core assets mark a new chapter for us for the reasons that I've told you.
Agenus 2.0, that's sort of a good way of conceptualizing our next chapter, a focused innovation engine with a clear path to value generation through streamlined execution and smart partnering. That is the desired outcome, and this is what we expect to execute on. For those of you joining that may not be as familiar with Zydus Lifesciences, they're a leading global pharmaceutical company with a fantastic reputation in India and beyond. With an $11 billion market cap, it is headquartered in India, employs over 27,000 people across 55 countries, including the United States. They bring deep expertise in manufacturing, clinical development, and regional care delivery, with $2.6 billion in 2024 revenues and an expanding chain of multidisciplinary hospitals and trial infrastructure across Southeast Asia. Now, with this, Agenus is positioned for substantial value creation through a layered approach that integrates scientific advancements with commercial foresight and fortitude.
Now, this is an interesting charge that tells you what our first phase of execution is, which is BOT/BAL approval in the U.S. being our focus. Next, of course, will be Europe shortly thereafter. After that, we have huge opportunities in indication expansion, other market approvals, and also, very importantly, and this was highlighted, by the way, at a number of our meetings at ASCO by some of the world's leaders in immuno-oncology who understand how immuno-oncology works. Their mandate is to help the system understand how immuno-oncology works and how the endpoints should be evaluated in the context of immunological effect on the tumor. We are positioned today for substantial value creation through a layered approach that integrates scientific advancements with commercial foresight.
Together, we're combining scientific innovation and global operational strength to unlock the full potential of BOT/BAL and expand our research and to expand our patients worldwide. Strengthening financial foundations, of course, is key. Our focused strategy of capital infusion to power Agenus plays a major role in that. Having a like-minded partner is one of the best ways of accomplishing this. With this transaction, we are divesting our non-core assets, which are hard assets. Manufacturing is not our sweet spot, but it happens to be Zydus' sweet spot. That does not mean we have not excelled in manufacturing. It simply means that we have very important agendas to execute on with innovation and bringing these products to patients as soon as possible. Zydus will be a very important part of that execution.
Looking at the deal structure, in addition to the $75 million upfront and the $50 million in contingent payments, we're also planning the divestment of land asset valued at $40 million-$50 million in the second half of this year. Of course, these types of transactions can be delayed. With that qualification, our intent is to monetize on our real estate assets in California that are not part of this deal. Of course, together, we also have the $16 million equity investment from Zydus, which is also a very big vote of confidence in us at $750 a share. We're reinforcing our balance sheet, reducing our cash burn, and focusing our capital with what derives the most value for us and our shareholders, and also, very importantly, for our patients. Our patients are in need of an innovative and potentially curative product.
Our vision is centered on bold, science-driven innovation. BOT/BAL is the lead in this, but we have a whole bunch of clinical-stage products behind BOT/BAL. That innovation only delivers impact if it reaches patients efficiently. That is why we are concentrating our resources on U.S. and U.S. registrational trials for BOT/BAL, with an understanding that our moral responsibility is to go beyond the U.S. as soon as possible. India is one of those territories. While integrating Zydus' advanced analytics to streamline our development, improve trial design, and optimize patient selection will be critical. Remember, Zydus is a company that is not just in pharmaceutical manufacturing, but they own a number of hospitals in India, including a cancer-dedicated hospital, as well as a CRO that advances clinical trials not just in India, but also other countries.
I had the pleasure of visiting India several weeks ago and visiting three of their hospitals and also visiting with their CRO. This is a meeting of the minds that has emerged to consummate this transaction. Our vision is centered on bold, again, science-driven innovation. That innovation only delivers impact if it reaches patients efficiently. That is why we are concentrating our resources on U.S. registration, as I said before. The key is in our clinical trial development, reducing timelines, lowering costs, and ultimately accelerating our path to regulatory approval. That is key. Having the ability to integrate with some of the subsidiaries or related companies of Zydus and execute clinical trials at record pace and allowing that to inform what clinical trials and what combinations and what indications should be pursued in the U.S.
is a very substantial advantage that will add value to Agenus and, very importantly, value to Zydus. Through this partnership, as I said before, we gain access to Zydus' extensive clinical trial networks across India and beyond. Of course, this accelerates our ability to bring BOT/BAL to more patients and more indications, leveraging their operational scale alongside our scientific leadership. We also see significant strategic value in combining BOT with upcoming PD-L1 biosimilars, PD-1 and PD-L1, I might say, that Zydus will be manufacturing. They're already well ahead of their competition in this area. This will give us an opportunity that could help unlock the current $60 billion global market segment in immunotherapy by adding BOT/BAL's strengths to the current state of affairs in immunotherapy, which reaches less than one-third of the eligible patients.
Our expectation is that with Bot infusion into these combinations, we can significantly expand that market, significantly expand that market. With this partnership, Agenus is executing a dual pathway to strategy for BOT/BAL, prioritizing U.S. registration trials while simultaneously leveraging Zydus' extensive infrastructure to advance development in emerging markets. This, by the way, allows us to accelerate approvals. It is a model that pairs scientific innovation with operational scale to maximize patient impact and shareholder value. Patient impact must be the driver for shareholder value, not the other way around. In conclusion, with new data coming at ESMO in July, continued regulatory engagement, both in the U.S. and in Europe, and now through Zydus, we expect that to be with India as well. With new regional partnership discussions underway, Agenus is positioned not just for progress, but for transformation.
That is the Agenus 2.0 vision in action: science-led, partner-enabled, and patient-focused strategy. Now, in conclusion, I just want to divert your attention to one thing. That is the team that worked tirelessly over the past months and continues to work tirelessly for potential additional transactions is the team that we would like to reward. That is the subject of our ask at our shareholder meeting for resolutions. As a final note, we will have our 2025 shareholder meeting on June 17. It is critically important that all shareholders of Agenus, as of April 24, 2025, record date, vote, very important. Agenus' proxy solicitor, Alliance Advisors, who's been with us for over 10 years, is available to assist you with your voting of shares, even if you do not have access to your proxy card. This could be done on the phone.
Their phone number is 844-202-6561. You can also email them at agent@allianceadvisors.com. Please do this as soon as possible to ensure that the team who delivered on this transaction is motivated and continues to work to deliver and expand on this transaction and more. Thank you very much for your continued support. Operator Tiffany, we are ready for questions.
At this time, if you would like to ask a question, press star, then the number one on your telephone keypad. To withdraw your question, simply press star one again. For today's call, we kindly ask that you limit your questions to one and one follow-up. We will pause for just a moment to compile the Q&A roster. Your first question comes from Colleen Kusy with Baird. Please go ahead.
Hi. Good afternoon and congrats on the deal, and thanks for taking our questions.
You referenced future clinical trials. Any more color on what indications those might be and whether that'd be funded by Agenus or Zydus or both? I have a follow-up, please.
Colleen, thank you for that question. When we were in India several weeks ago, Zydus brought together eight of India's absolutely top-notch oncologists. They flew them from all over India. As you know, India is not a small country. It takes effort to travel to the city of Ahmedabad, where Zydus is headquartered. We had the opportunity to connect with them in person, by the way, no Zoom connections or team connections. It was all in person. We presented data from all the trials, which include certainly colorectal cancer because that's where we have the largest database, but also cancers in earlier stage setting.
Most recently, the AACR presentation by Dr. Myriam Chalabi. Also, in our interactions with Zydus-owned or affiliated hospitals, we had the opportunity to meet with the head of the hospital that is specialized in cancer. I believe it is a 1,000-bed hospital just dedicated to cancer. The head of that hospital is a breast cancer surgeon. In our conversations, it became clear that there was very high interest in pursuing the triple-negative breast cancer. Based on the data, I admit that the data is small, but it is very compelling. I mean, if you have neoadjuvant patients with triple-negative breast cancer that respond to your treatment in six weeks and a number of them respond with complete pathologic responses, that is an eye-opener. When we went through that data, there is definitely high interest in pursuing indications like triple-negative breast cancer.
In India, by the way, it's much less competitive. It's much less competitive in terms of competing with existing standards of care or upcoming standards of care. We have, I think, a terrific opportunity there to pursue this, to pursue other neoadjuvant trials like sarcoma and also specialty cancers that come in small numbers in the U.S., but those numbers are a bit more in India. There will be a very high level of interest for Zydus to pursue and expand things in India. Of course, with our resources, we will be focusing on CRC, no question about that, including starting our registration trials in CRC this year with a group that is specialized in conducting these trials at a fraction of the cost.
We've referred to this before, at a fraction of the cost as regular CROs because they're a nonprofit and they've had a fantastic record with other products, both in terms of rapid enrollment and registration. This is not an unknown entity. We will have more on this to come in the second half of this year. This is a very high priority for us. Yeah.
Great. Thank you. Yeah, our follow-up is on CRC. Any update on the timing of your FDA meeting? Can you talk about what you plan to discuss at that meeting and talk about your level of confidence that the FDA will agree to an accelerated approval pathway? Thank you.
When dealing with the traditional FDA, I cannot make any unequivocal statements about their position.
However, what I can tell you is that we have expanded our dataset from last year's meeting to this year's meeting. How so? We have more patients, and we have more mature data. One of the questions of the FDA last year was based on their publication. They had some doubts about whether or not 20% response rates would translate to long-term benefit. Now we have more than one year additional data, and the results have been absolutely consistent and persistent. Of course, they need to make that judgment in conscience for us to encourage for accelerated approval go ahead.
Your next question comes from Joseph [Brueske] with H.C. Wainwright.
Hi. This is Joey on for Emily Bodnar. Briefly, you mentioned about the triple-negative breast cancer and the interest from Zydus.
Do you believe they're going to initiate any clinical trials evaluating BOT/BAL in the near term, and what might the regulatory process look like in India?
In terms of the regulatory process in India, of course, we will defer all of that to Zydus because they're the experts. They're a very well-established and very well-respected company by Indian authorities. We have not yet worked out the details of the exact next steps for clinical trials in triple-negative breast cancer and other indications. That is part of our work plan coming up in the next months.
Okay. Thank you. Just one follow-up. When can we expect the $50 million contingent payments to be made, and how do you plan to recognize the $75 million upfront payment in your financial statements?
I think is Christine with us about the recognition of the $75 million in our financial statements? We'll get back to you on that. I just want you to know that there are no tax consequences to that. There's zero tax consequence. We'll reflect that transaction appropriately in our financial statements with the realization that there's no tax consequence. That's number one. Number two, with regard to contingent payments, it is a function of how quickly we put in our orders for manufacturing in the Emeryville facility. I'm confident that those will come very quickly. I'm talking about no later than the next 18 months, starting in the next few months.
I see. All right. Thank you so much. Again, congratulations on the news partnership.
Thank you. Your next question comes from Mayank Mamtani with B. Riley Securities. Please go ahead.
Hey, good afternoon, team. Congrats on the deal. Thanks for taking your question. With $91 million coming in and you're getting close to a $50 million operating burn, now these non-core assets are off your P&L. Any color on impact on your cash runway you could provide and whether the phase III U.S. study, assuming that remains on track to initiate later this year, is that part of your operating burn? I have a follow-up.
As I indicated in our last call, we expect that our operating burn will be annualized $50 million going forward. That is what we anticipate. In terms of how we will fit in our plans for phase III trials designed for full approval, full approval.
I will tell you this year, if we initiate these trials, which I expect to initiate this year, our total expenditure for these trials this year will be approximately, I'm talking about a very large randomized two-arm trial. Our expenditures for this year will be no more than $5 million. Our expenditures next year will be no more than $12 million. And our expenditures the following year, which will be the conclusion of the trial, will be no more than approximately $8 million for a total of approximately $25 million over three years, over three years.
Wow. I guess I have to ask a follow-up to that. Is that because the product, the arrangement that you have with Zydus on product supply, so that $50 million will basically net out as contingent payments will net out as the cost for that drug? Is that essentially the cost savings?
These costs that you're talking about are the CRO-related costs?
Okay. Let me answer this in two ways. We are not including any Zydus-related data management cost savings or anything else. This is if we were to do this trial on our own without Zydus, the numbers that I've given you would be the numbers. Why is that such a cost saving? The outfit—this is on their website—that we're going to be working with is called CCTG. Okay? This outfit is specializing. First of all, it's a nonprofit agency. It does clinical trials in Canada, in France, in Australia, and New Zealand. Only a small population comes from New Zealand. The major populations are Canada, France, and Australia. All reference countries, all reference countries.
A part of the big cost savings is related to the fact that the standard of care treatment is covered in its entirety by those countries, in its entirety. Secondly, another big cost saving is that because this is a nonprofit, there are substantial cost savings associated with their CRO function of the trial. They're very excited about this. They've already teed up centers, and we expect them to execute at record pace. We met with them at ASCO a couple of days ago, and their level of enthusiasm is very, very high. By the way, just for clarity, it's Canadian Cancer Trials Group. It's CCTG. I may have pronounced the sequence wrongly. CCTG, Canadian Cancer Trials Group. They have already vetted with this program.
Understood. My follow-up to a prior question was around this data that you have accumulated for the Part B meeting.
Appreciate there's been incremental survival data, more patients. I think the total of 250 patients, if you add the phase I expanded cohort and then the phase II BOT/BAL, two arms, I get about 250 subjects. Are you able to comment on whether we'll get data on all of this at ESMO GI, or would we get data on a specific phase I expanded cohort at ESMO GI? I'm just trying to understand when the street would be able to see that entire package that would be presented to the FDA. Thanks for taking the question.
The very best Dr. O'Day is with us, and I'm going to defer to him to answer this question. Yeah.
Mayank, we haven't released, obviously, all the details, but we plan to update our—and it's been accepted—the extended phase I data, which includes an additional year of follow-up and a significant additional number of patients at ESMO GI, not the phase II data at that time.
We are tentatively—we can answer—we're tentatively scheduled to have an investigator forum at ESMO GI where we will be discussing everything, not just in the context of what will be presented.
Would that be released as part of some corporate deck update, the phase II active comparative control data?
Of course, we will share the phase II data with the investigators.
With investors, would that be shared around ESMO GI?
Yeah. Mayank, we've said since ASCO GI, we've reported the response data, which was the primary endpoint of the study. We continue to wait for follow-up and time-sensitive endpoints.
Hopefully, by the second half of the year, those will be mature enough to present or convey data in the phase II trial.
Steven
Thank you for that clarification.
Go ahead.
Steven, is it fair to say that so far the response rate data in phase I first cohort, phase I second cohort, and phase II has been consistent across the board?
Absolutely. Yeah.
That is the most important thing. Mayank, one thing that you need to factor into this is that these three different cohorts are maturing sequentially.
So far, the response rate is consistent. In the phase I first cohort and second cohort, the survival and the tail of the curve is consistent. In the phase II, we need to have a little bit more time to demonstrate what I just said in the first cohort and the second cohort.
I just got this question coming in. When do you think, base case that you should be in a position to file and any planning as you think about the scenarios for this FDA meeting? What are in your mind the scenarios that you're preparing for?
I think it'd be inappropriate for me to presume what the FDA will say or will do, but I'd say stay tuned.
Got it. Thank you.
Your next question comes from Matt Phipps with William Blair. Please go ahead.
Hi. Great. This is Madeline on for Matt Phipps. Thanks for taking the question and congrats on the update. In terms of the next steps for BOT/BAL in CRC, are you just prioritizing registrational trials in late-stage CRC at this time, or are you considering pursuing a potential path in neoadjuvant setting as well?
Based on our current plans, we're going to sprint with a randomized trial for registration in the late line setting. That's the trial that I spoke about, CCTG. We plan on executing that trial on our own by the end of this year. Now, with regard to neoadjuvant, your question is very pertinent because neoadjuvant data that we have published is unequivocal. I mean, when you see the results, and you have from the first trial, which was NEST at Cornell, a second trial, UNICORN, which was across 11 centers with more than double the number of patients, we observed absolute consistency. What is that consistency? We're talking about 100% pathological responses in a significant number of patients in record time. We're talking about in four to eight weeks.
Then subsequently, the NEOASIS trial, which is the one that was presented at AACR, and there will be updates on that trial because that trial continues to accrue at a very fast pace across multiple cancers, including CRC, have also shown absolutely consistent outcomes across the board. It is sort of a no-brainer to go after that market because the earlier you treat patients, the better the outcomes. These trials confirm that. There is no question about whether there is a contribution for another product that is being used because we are not using this in combination with chemo or radiation or anything else. With that, the market opportunity is very large. Of course, patient opportunity is profound. What that means is that the quality of life for these patients, should they undergo chemotherapy, radiation, and mutilating surgery, is horrible.
If we can replace that over time, it will mean a great deal for the patients and a great deal for the market opportunity as well. What do we do with that? I'd say stay tuned. We have plans for funding that trial through innovative mechanisms, and that's one of the things that we're working on as the next phase.
That will conclude our question and answer session. I will now turn the call back over to Garo Armen for closing remarks.
Thank you very much for everyone participating in this call. Like all good things, things take a little time. We have been working on this transaction and eight other transactions simultaneously over the last six months. Over the last six months.
We're grateful that we brought the most important elements of our next phase with Zydus to life today. We continue to explore opportunities along the lines of what I just mentioned, for example, for the neoadjuvant setting trial. I apologize for how much this takes. Thanks to lawyers, regulators, and others. I think we are destined to deliver only because we have a product. We're blessed by a product that has profound activity. We've demonstrated this now in well over 1,200 patients and counting. I'm very grateful to our team for making this a reality for us, for working hard, and to generate some superb clinical data as well as executing on transactions that we're talking about simultaneously.
This is a big feat, and that's one of the reasons I drew your attention to working with us, with our proxy solicitors, to make sure that our team is appropriately recognized. Thank you very much.
Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.