Agenus - Q3 2023

Transcript

Operator (participant)

Good morning. My name is Jeannie, and I will be your conference operator today. At this time, I would like to welcome everyone to the Agenus Q3 2023 Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. Thank you. Zack Armen, you may begin your conference.

Zack Armen (Head of Investor Relations and Corporate Development)

Thank you, operator, 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, Dr. Todd Yancey, Chief Strategic Advisor, and Christine Klaskin, Vice President of Finance. Dr. Robin Taylor, Chief Commercial Officer, will be participating in the Q&A session.

Now, I'd like to turn the call over to Garo to highlight our progress and speak to our outlooks for the remainder of the year. Garo?

Garo Armen (Chairman and CEO)

Thank you, Zack. Ladies and gentlemen, as we gather today for the earnings call, let's reflect on the remarkable patient outcomes from our botensilimab trials. As underscored by our leading experts and researchers, we're witnessing sustained benefits in treating some of the most challenging cancers. Based on these observations, and for the sake of cancer patients, our urgent mission is to set a new benchmark in cancer care, providing patients with longer-term, potentially curative benefit, with some patients experiencing treatable toxicities. Our BOT therapy is showing promise across various cancer stages and types, with benefits seen in some of the most treatment-resistant, so-called cold tumors. In addition, recent data presented at our corporate event in Madrid during ESMO revealed BOT potential in earlier stages of cancer, where remarkable rapid responses were observed, with the possibility to prevent significant treatment-related morbidities, including the potential need for colostomy.

Moving forward, we're concentrating on three key priorities: submitting our first biologics license application for colorectal cancer, prioritizing other clinical programs with the potential for rapid approval, and importantly, smartly allocating resources to achieve our goals. Accordingly, we're gearing up our first BOT/BAL BLA submission in mid-2024, with a focus on late-stage colorectal cancer. Dr. Yancey will delve deeper into this topic shortly. The cancer community's enthusiasm and rapid enrollment in our phase II clinical trial in MSS CRC highlights an urgent unmet need. To address this, we've started a compassionate use program with the aim of broadening it into an expanded access program next year. With very limited options to treat patients with advanced colorectal cancer, the positive trends and lasting responses in our studies strengthen our conviction in BOT/BAL's potential.

Our top priority is obtaining BOT/BAL's approval in MSS CRC in order to allow patients access to this important IO treatment, offering them new hope, which does not exist today. Our second area of focus is advancing our prioritized clinical programs, which include refractory pancreatic cancer and neoadjuvant setting in CRC. Dr. O'Day will detail the exciting data that showcases BOT's potential in these cold, solid tumors. In addressing our financial capabilities to drive our objectives, we're already taking and continue to take steps to contain costs. These steps are important, particularly given the current challenging environment in the biotech sector. Our immediate prospects for additional cash infusion that does not involve stock issuance includes a milestone payment from one of our partnered programs expected by the end of December 2023. That's this year....

In addition to this expected milestone, we are in the process of the sale of two non-strategic assets and pursuing the partial sale of milestones and royalties due to Agenus from our partner programs. These three sales are expected to close by the end of the first quarter half of 2024. The potential proceeds from these four transactions are estimated at approximately $200 million in total. With our cash balance at the end of Q3, along with these four planned transactions, we believe we are sufficiently funded through the end of 2024. In addition to these planned transactions, we're also in advanced discussions for a potential structured financing for BOT/BAL, as well as a potential corporate collaboration with a large pharma or biotech company. That ends my formal remarks, introductory remarks, and now I'll be handing it over to Dr.

O’Day to shed light on our latest findings and data updates. Steven?

Steven O'Day (Chief Medical Officer)

Thank you, Garo. Together with our investigators and key opinion leaders, we presented updates from the BOT/BAL development program at a corporate event hosted during the Madrid ESMO Congress in October. I'll now briefly describe these data updates, beginning with colorectal cancer. We updated our phase Ib cohort of 70 evaluable patients with bot and bal in refractory MSS-stable colorectal cancer without active liver metastasis. This is the target population for our fully enrolled Phase II study and the population in which we've received Fast Track designation from the FDA. The RECIST-confirmed overall response rate was 24%. The duration of response was not reached, with 59% of responses ongoing, and now a median follow-up updated to 12.3 months. These patients showed a 12-month overall survival rate of 74%, approximately twice that reported for standard of care.

With longer follow-up, the median OS, previously reported at 20.9 months, is now no longer reached. Importantly, the OS curve plateau continues to emerge and strengthen as the data matures, with the longest patient now alive at three and half years and three other patients who are alive beyond 21 months. We plan to file our initial BLA in this indication in mid-2024. Next, we presented data from an investigator-sponsored trial at the Window of Opportunity setting. Surgery was performed on average only four weeks after the initiation of immunotherapy. All three MSI-H colorectal patients had complete or near-complete pathologic responses. And even more importantly, six out of nine patients with MSS colorectal cancer had pathologic responses of 50% or greater, including two complete pathologic responses.

None of the 12 patients had tumor growth during the treatment interval, and no surgeries were delayed due to immune-related toxicities. These results represent an important opportunity to move into earlier lines of therapy with curative intent and change the treatment paradigm for MSS stable colorectal cancer, potentially avoiding the morbidity of late-line therapies. In second-line pancreatic cancer, we have treated six patients with a combination of botensilimab, Gemzar, and Abraxane triplet. All six patients had progressed following first-line metastatic FOLFIRINOX therapy, and all six had liver metastasis. Four of the six patients have achieved marked and sustained tumor marker reductions. Two of the four patients have already achieved partial responses at 16 weeks, with target lesion reduction of -47%, which has been confirmed, and -37%, which is pending confirmation scans, and both responses are ongoing.

Two other patients showed stable disease at their first eight-week scans, with tumor reduction of -20% and -13%, and they remain on study awaiting 16-week scans. A randomized Phase II study is currently enrolling, and a data update is anticipated in the first half of 2024. Our other Phase II trial is in refractory metastatic melanoma, including PD-1 refractory as well as PD-1 CTLA-4 refractory disease.... In a Phase Ib expansion cohort of 10 patients, botensilimab alone showed a 30% objective response rate and 60% disease control rate in these refractory patients. In the Phase II study, the botensilimab monotherapy cohort is now fully enrolled, and the botensilimab balstilimab combination cohort is enrolled with approximately 30 patients. A data update is anticipated in the second half of 2024.

In PD-L1 refractory and non-small cell lung cancer, we've reported on nine patients who were treated with a combination of BOT and BAL. Five of the nine patients in the combination achieved RECIST-confirmed partial responses for an ORR of 56% and a disease control rate of 89%. Approximately 50 patients have now been enrolled in two expansion cohorts, including PD-1 refractory, as well as TKI driver mutation refractory disease. A data update is anticipated in mid-2024. Dr. Breelyn Wilky, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research at the University of Colorado Cancer Center, presented an update of botensilimab program in sarcomas at ESMO 2023.

In 41 evaluable, heavily pretreated sarcoma patients, the combination of BOT and BAL demonstrated an overall response rate of 20%, a median duration of response of 19.4 months, and a six-month progression-free survival of 40%. There were differential responses observed by dose level, with 29% response rate in the 2 mg/kg BOT cohort, compared to 15% in the 1 mg/kg BOT cohort. In addition, we observed promising activity in difficult to treat subtypes of sarcoma, such as leiomyosarcoma and visceral angiosarcoma. The results we've achieved in cold tumors, in both the refractory setting and more recently in early disease, offers hope for patients and families where current standards of care are inadequate or limited in benefit. The robustness of our data broadly across tumor types, resulting in deep and durable responses, showcases a potential groundbreaking advancement in oncology for botensilimab.

We remain committed to improving patient outcomes and are grateful for the support of our team, trial participants, and stakeholders. I am confident in the positive impact we are making, and I'm excited about the future. Now I'll turn the call over to Todd to discuss our regulatory strategy.

Todd Yancey (Chief Strategic Advisor)

Thank you, Steven. The landscape for MSS CRC patients who've received one-two prior lines of therapy is challenging. There are limited effective options available, so our focus in our development and regulatory path is to bridge that gap. At present, the available therapies in this setting, including monotherapy with regorafenib, monotherapy with Lonsurf, and the newly introduced combination of Avastin and Lonsurf, offer only marginal reported improvements in survival, and response rates are low, with survival curves going to zero. Recognizing this, we've developed a differentiated investigational agent with botensilimab that has already demonstrated significant benefit over reported results for these standard-of-care therapies, with survival curve plateaus consistent with substantial long-term benefit.

In our studies, patients with a median of four prior lines of therapy, a quarter of whom had received prior immunotherapy, experienced a 24% RECIST response rate compared to the standard of care's reported rate of only 3%. Importantly, our median overall survival is currently exceeding 21 months, a significant leap from standard of care at 12.9 months, as reported in the ARCAD database. Our regulatory process is well underway, and we, as we have stated, plan to submit our first BLA, as characterized in our Fast Track designation, in the middle of 2024. This application is robust. It's targeted to include data from approximately 400 patients at two different doses, both 1 mg/kg and 2 mg/kg, and will be supported by safety data from several hundred additional patients across multiple indications where we have observed broad activity.

In this process, we're not leaving any stone unturned. We're conducting a comprehensive and full exploration of dose and schedule, ranging from the lowest dose of 0.1 milligrams per kilogram to 3 milligrams per kilogram in our phase I and phase II studies. Additionally, we're investigating the contribution of components of the two experimental agents, BOT and BAL, in a randomized fashion within our now fully enrolled phase II study. As we move forward, we are and will continue to proactively engage with regulatory authorities. While we await complete feedback from the FDA and EMEA, we have taken scientific advice from key European countries and are in the process of scheduling meetings with the CHMP and FDA representatives. These discussions are crucial as they will guard our path forward toward approval.

Our goal is clear: we aim to submit this package for potential approval by 2024 mid-year, and we're optimistic about the opportunity for an accelerated review, which would allow us to bring this innovative solution to patients in need as soon as we can. Now I'd like to turn the call over to Christine to discuss the financials.

Christine Klaskin (VP of Finance)

Thank you, Todd. We ended our third quarter of 2023 with a consolidated cash, cash equivalent, and short-term investment balance of $106.3 million. This compares to $193.4 million at the end of last year. For the three and nine months ended September 30, 2023, we recognized revenue, which includes non-cash revenue, of $24.3 million and $72.5 million, respectively. Including non-cash expenses of $28.1 million, we incurred a net loss of $64.5 million for the third quarter. For the nine months of 2023, we incurred a net loss of $208.9 million, which includes non-cash expenses of $82 million. I'll now turn the call back to Garo.

Thank you, Christine. I want to express my gratitude for your support during this pivotal phase of Agenus. Our strides in cancer research, highlighted by botensilimab, signify a potential new era in cancer care. I also want to express my gratitude to our employees. I am confident in our team's dedication and our ability to achieve our milestones. The success of botensilimab remains our top priority, and I assure you that our diligently managed finances will ensure the necessity for resources to be allocated for this very important endeavor. With your continued support, we expect to meet and exceed our goals with the prospect of bringing hope and healing to those affected by cancer. Thank you for your support once again. Together, we are destined for remarkable achievements for the benefit of cancer patients, which will in turn create significant value for all of our stakeholders.

With that, I will now open the call for questions. Thank you very much.

Operator (participant)

At this time, I would like to remind everyone, in order to ask a question, press Star, then the number one on your telephone keypad. Your first question comes from the line of Emily Bodnar with H.C. Wainwright. Your line is open.

Emily Bodnar (VP of Equity Research)

Hi, good morning. Thanks for taking the questions. First one, just briefly, if you can comment on when we may expect to see initial phase II data for the MSS CRC study. Then secondly, if you could talk about how you're thinking about strategy in neoadjuvant CRC. Are you kind of looking to evaluate broadly in CRC or just focus on MSS patients, and maybe just discuss the regulatory pathway to potentially getting BOT/BAL approved in that setting? Thank you.

Garo Armen (Chairman and CEO)

Thank you, Emily. So let me answer the question broadly, and I'll ask if Dr. O'Day has any additional comments. But so what I've said publicly is the fact that we have clearly disclosed the data on the first 70 patients, not because the rest of the data isn't satisfactory, but the rest of the data needs to be cleaned up and we need a little bit of work to do. But our look at the data, both in the second cohort and in our phase II studies, indicate that we should have a sustainable response rate, perhaps even an improving response rate, as we disclose and analyze these data for regulatory and beyond purposes.

So, that is more of a regulatory decision, when to disclose it, and the ideal circumstance for us will be certainly to publish data at around the time of a potential BLA submission to publish the data in a peer-reviewed journal. That would be part of our plan. Now, with regard to the neoadjuvant plans, we haven't quite crystallized it yet. Of course, the typical response for neoadjuvant studies is the fact that they are large studies, and they take time. But we believe that depending on what patient populations we go after, we may be able to look at a subset of patients that would be the subject of high morbidity with standards of care.

As you know, in these patients, even though the treatments are largely curative, they're not 100% curative. Standards of care are not 100% curative, but they cure a quite substantial number of patients. But those cures come at a very high cost to the patients, and that includes the potential use of colostomy bags. It involves sexual dysfunction. It also involves the loss of muscle function in the area of the abdomen. And particularly if you are a patient in your thirties, forties, you don't want to be subject to these morbidities.

So, we're going to take a little bit of time, not too much time, to determine exactly what the patient population and the trial design would be, with the aim of a very rapid trial execution and potentially rapid filing and approval. So, I think we'll disclose some of these details in the first half of next year.

Emily Bodnar (VP of Equity Research)

Okay, great. Thank you.

Operator (participant)

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

Colleen Kusy (Senior Research Analyst)

Great. Good morning. Thanks for taking our questions, and congrats on the progress. For the randomized CRC study that's fully enrolled, can you just give us a sense of the regulatory bar there? Does the combination need to be better than the individual drug arms and standard of care, and by what margin?

Garo Armen (Chairman and CEO)

If I may ask Tad to answer that question. Thank you.

Todd Yancey (Chief Strategic Advisor)

Hi, Colleen. I think there are really two questions there. One is, what do we expect in terms of performance versus standard of care? And the second is really, what do we expect to see in terms of incremental contribution in the doublet? So just to remind everybody about the design of the trial, there are five arms, of which one is standard of care, and of course, patients are randomized across these arms. The other four arms all have botensilimab, which, as monotherapy, we know to be active from the phase I dose escalation. And two of those arms have botensilimab in combination with balstilimab. And as we've been observing in the data set that we've been presenting, for the MSS-CRC patients on active liver mets since, well, for the last almost 18 months, there is a substantial benefit in the combination.

And so as it relates to the first question versus standard of care, standard of care, for patients with one-two prior lines of therapy, is offering a 3% overall response rate and an expected median overall survival of 12.9 months. That's coming from the RCAD database of over 18,000 patients. And currently, we're showing 24% versus 3% for response and over 21 months for median overall survival. So, we need to be obviously meaningfully better than currently available standards of care. So looking at 3% versus 24% or 12.9 months versus over 21 months, I think it's clear to everyone that you could drive a truck through that.

Now, as it relates to the incremental contribution of balstilimab to botensilimab, given our mechanism of action, which is really multifactorial, first of all, we have obviously our optimized engagement with CTLA-4 in a receptor ligand interaction. But the back-end engineering that's resulting in suddenly an activation of both innate and adaptive immune response, has created a hot milieu, and we expect to see a substantial improvement in the combination, certainly at least a doubling of response, when we add balstilimab. And so I think that's what we want to be able to discern. Just for comprehensiveness, we'll also remind everyone that in that same, clinical trial, we are looking at two, active doses, 1 milligram per kilogram and 2 milligrams per kilogram.

At the time of regulatory submission, we anticipate having approximately 175 patients in each of those two doses. So we'll be able to have a robust perspective on the activity of the doses one and two, and also on the tolerability of those two.

Colleen Kusy (Senior Research Analyst)

That's super helpful. Thank you. At the time of BLA submission, would you expect to have any sort of overall survival early data from, from this study?

Todd Yancey (Chief Strategic Advisor)

I think we would have certainly evident trends for patient benefit. What we've observed pretty consistently in the phase I database, which is not small, remembering we've got 101 patients in total there for safety, and we have 70 patients in the MSS-CRC non-active liver metastatic patient population for efficacy adjudication. We are obviously seeing that responses for patients and that response can be stable disease or better is translating to not only durable response but, you know, very substantial overall survival. So I certainly expect that we'd be able to demonstrate appointment estimates for response, durability of response for patients with stable disease or better, and that that is trending toward a survival benefit.

Remember also that, the time of submission is not a moment in time that's frozen, because we will be required to provide updates on safety and efficacy during agency review, and that will allow time for additional maturation of the dataset. And again, as has been consistent since we began to show data, in June of 2022, the longer, the study goes, the more mature the observations have been around the durability of response and its translation to survival. So I think we have a very, very robust set of data to present to the agencies for their review.

Colleen Kusy (Senior Research Analyst)

Got it. That makes sense. And on the cash guidance, can you maybe just provide a little bit more color on what's included in that in terms of the ongoing and planned studies?

Garo Armen (Chairman and CEO)

... if you can repeat the question on the latter part of your question?

Colleen Kusy (Senior Research Analyst)

Yeah, just on the updated cash guidance.

Garo Armen (Chairman and CEO)

I got it, I think. Okay.

Colleen Kusy (Senior Research Analyst)

Okay.

Garo Armen (Chairman and CEO)

So, as you know, we finished the quarter with a little over $100 million. My guidance for the fourth quarter burn is approximately $40 million. Now, beyond that, as we've said earlier, we will have a milestone payment that is due to us by the end of this year, and we will sell two assets that are non-strategic assets. We expect that to be completed in the first half of next year. And then a third-party royalty transaction. Now, of course, the first two are entirely in our control, meaning the milestone payment and the asset sales. And the royalty transaction will require external investors for that kind of a transaction. We have done that before some years ago.

In fact, about five years ago, we consummated a transaction for third-party royalties when we had a much skinnier royalty portfolio at the time, and we did this with XOMA Corporation. So we're talking about a transaction that will be multiples of that transaction for a much larger and much more attractive portfolio that has had some very encouraging comments from our partners. So with those, we expect to bring in approximately $200 million of cash between now and the middle of next year. That is through non-stock issuance transactions. Without any stock issuance, we expect to bring in approximately $200 million, and with that, it will take us well beyond the end of next year.

Colleen Kusy (Senior Research Analyst)

Got it. Thank you.

Garo Armen (Chairman and CEO)

Any other questions?

Operator (participant)

Mayank Mamtani, your line is open.

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

Good morning. Thanks for taking our questions and helpful recap of the ESMO event data. So maybe just to clarify on the second-line plus CRC-accelerated approval, you know, could—are you able to talk to the specific guidance you may have on the design of the phase III confirmatory study and maybe timing of initiation to just kind of round out the other updates you provided? And then I have a follow-up.

Garo Armen (Chairman and CEO)

So I'll just make a broad comment on the confirmatory studies, and then I'll ask Tad to provide additional color. But with regard to confirmatory studies, we have two choices. One is to do a confirmatory study in the second or third-line setting. The other one is to do a confirmatory study in the first line. We have not made that decision yet. We've had discussions with the FDA on the latter line, confirmatory study. We have not yet had discussions on the first line because we're awaiting data from an IST study which is ongoing right now, which studies botensilimab on top of FOLFIRINOX. And we expect that data to be available in the first quarter of next year, and that will inform us better which way to go, whether we go with first line or third line.

Todd, would you like to add any additional color on this?

Todd Yancey (Chief Strategic Advisor)

Yeah, I just add a couple of points to that. We already, Mayank, now that we have a clear understanding of how to preemptively manage or to intervene early on GI toxicity, we already have a higher level of comfort with regard to our ability to combine in the front line with 5-FU and oxaliplatin-based regimens, of course, which have associated GI toxicity. So that level of comfort is rising. But at City of Hope, we are conducting a study to determine what the best management paradigm would be for the combination. In addition to that, I think we have greater strength of evidence for incremental benefit in earlier lines of therapy derived from the preliminary data set we're seeing in the neoadjuvant setting.

So I think our objective will be to optimize the development program to accelerate access for patients to a broader patient population. So there's a lot of regulatory precedent for doing a confirmatory trial in either a broader patient population than the accelerated approval indication or, and/or in an earlier line. Again, at the end of the day, the decision with regard to the design of the confirmatory trial will require alignment with both the U.S. and the European authorities, and we're basically looking at two potential options at least that we would present for their review.

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

... very helpful. Thank you. And then on the new pancreatic cancer, BOT chemo data, could you just clarify what number of patients you are targeting in the randomized control cohort? And if you are seeing any uptake in enrollment, you know, similar to what occurred in the colorectal cancer expansion cohort last year. And for the relatively warmer tumors, you know, in lung and melanoma, it seems like you have both mono and combo BOT/BAL combination data. So, you know, there is a ton here of mono BOT data and combination BOT/BAL data. So how are you sort of thinking across tumor types, where you may pursue, you know, BOT standalone versus maybe combination? If there's a view on that you could share.

I have one more financial question after this.

Garo Armen (Chairman and CEO)

Thank you. Dr. O'Day, would you like to take that first part, the first multi-part question?

Steven O'Day (Chief Medical Officer)

Yeah. Mayank, can you repeat the very first part of it? I have the melanoma part, but.

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

The pancreatic cancer BOT chemo data, number of patients that you're targeting in the randomized control cohort, and if you've seen any uptick in enrollment?

Steven O'Day (Chief Medical Officer)

Yeah

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

... like what happened with Correct.

Steven O'Day (Chief Medical Officer)

We have a lot of enthusiasm around the data so far with both our PIs on the pancreas study, but more broadly, KOLs. We are expanding that, and it is accruing, and we plan on treating another 60 patients in randomization in the coming months.

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

Got it.

Garo Armen (Chairman and CEO)

In terms of melanoma-

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

Melanoma.

Steven O'Day (Chief Medical Officer)

In terms of melanoma, obviously, we have single agent activity in melanoma in a PD-1 and PD-1 CTLA-4 refractory that we've reported in our 1b trial. We've now accrued a large number of patients to monotherapy in both the PD-1 refractory and PD-1 CTLA-4 refractory at two different doses. As I said today, we're combining it with BAL, and that data will be maturing, and we look forward to presenting it in 2024.

Mayank Mamtani (Senior Analyst, Group Head of Healthcare Research)

Got it. And maybe for Garo, you know, this concept of structured financing or even corporate partnerships, I was just curious if there's any sort of segmentation you're thinking by indication or geographies. You know, are there any sort of constructs in deal term sheets that are more preferred versus less? If you could provide some color there, that would be helpful. And thanks all for taking my questions.

Garo Armen (Chairman and CEO)

So, the kinds of discussions that we're having, and some of them are in advanced stages, as I said before, really encompass both a global collaboration, across all indications, as well as specific indication collaboration, for which, infrastructure exists at some companies, to be able to segregate product by indication. That's new technology, and we've been proposed the potential, optional segregating certain indications that are of greater interest, to certain partners. So we're looking at all of these options simultaneously, and, I think a good deal for us would be driven by several things. Number one, the appropriateness of the collaborator, their conviction that our product could be a significant, player in the immuno-oncology and broader oncology field.

So, that's number one, because we believe that botensilimab plus balstilimab offers performance advantages that we have not seen at any immuno-oncology and oncology treatment setting. So for example, when we talk about patients that have either failed all other therapies or do not respond to other therapies, not just immunotherapy, but beyond immunotherapy, these are patients that are in dire need of a product that offers them a potentially curative option with toxicity that is transient. I think that there is an enormous need in the field for such a product, and I think botensilimab offers that treatment option for patients. Now, so given this, the partner must have high conviction that this product could be a huge win for patients and a huge win commercially as a result. That's number one.

Number two, the partner needs to make the appropriate financial commitments, not just for compensating us in terms of upfront and milestones, but also a substantial financial commitment for the development of this product. And the development has to be rapid because, as we've said before, we have seen clear clinical activity in, so far, nine different cancers. Now, you can't lie about that. It's real. It's been presented at major conferences, and so... Of course, there are regulatory and other questions about, do overall response rates translate to longer-term benefits? We know they do. We need to demonstrate that with numbers. But with CTLA-4 binding antibodies, and ours is a multifunctional, broad functioning, molecule that binds the CTLA-4 as one of its 5 different activities, not just the center stage activity, but one of five different activities.

All of that means that this product needs to be rapidly developed across all indications. If you pay attention to my quadrant slide, you will see that the opportunity for cancer patients is enormous there. A partnership has to be based on a commitment, financial commitment for rapid development. Of course, other cultural compatibilities that will allow our A team to work with a partner's A team to bring this into a harmonious conclusion.

Yeah, that makes a lot of sense. Thanks for taking our questions.

Operator (participant)

Your last question comes from the line of Kelly Shi with Jefferies. Your line is open.

Kelly Shi (SVP and Senior Research Analyst)

Hi, this is Claire on for Kelly. Thanks for taking our questions. So just one question for the plan for CRC. So can you remind us what's your plan for those CRC patients with liver mets at the phase III confirmatory study, specifically in patients without liver mets, or if there is an option to look at all comer patients as well? Thank you.

Garo Armen (Chairman and CEO)

So I will, I will take a little crack at it, and then I'll ask Dr. O'Day to also comment on this. So as you know, liver mets is a sort of a black box right now for everybody. There's no clear answer as to why liver mets patients don't respond. There is speculation about why they may not respond. And of course, liver is a privileged organ with a lot of immunosuppressive components to it. Now, we are looking at a number of ways of overcoming it. For example, if you look at our pancreatic data, all patients in the small number of patients that have been treated have had liver mets, and all patients that have responded have had their liver, liver mets respond.

Now, we don't know if any of the other chemotherapy components are contributing to this. For example, there's some speculation that gemcitabine may play a role in this. We don't know that, but I think in the next coming months we will have a very deliberate action plan in trying to answer this question with small trials, possibly ISDs, that will be undertaken to see if we can translate some of what we observed in pancreatic cancer can be also actualized in CRC. But right now, we're working with limited knowledge. But I think, as you said, this is an area that needs to be explored very diligently. Dr. O'Day?

Steven O'Day (Chief Medical Officer)

Yeah. So, obviously, in the refractory colorectal patient population, the IO co-- IO combination of BOT/BAL has its, most profound signal to date in the non-active liver met patients. These are patients who've never had liver metastases or have had treated liver metastases. But depending on alignment of the phase III trial, as Tad said, if we do move to first line, obviously we would treat all comers, and, so we will be aligning our phase III trial with, in the coming, weeks and months.

Kelly Shi (SVP and Senior Research Analyst)

Thank you.

Operator (participant)

There are no further questions at this time. Garo Armen, I turn the call back over to you.

Garo Armen (Chairman and CEO)

Thank you very much, everyone, for your attentiveness to our developments. This is a very exciting time, I believe, for cancer patients. Certainly, patients that are in desperate need of effective therapies, but not, not just therapies that extend their life by a month or two at a very high cost of quality of life, but potentially extend life much longer with potential curative outcomes in some patients, and with a much, much more acceptable, more dignified quality of life, with some gastrointestinal side effects that are typical to overactivation of the immune system. But they are reversible, and I think if you look at our record, our physicians have learned that reversibility is a function of rapid intervention.

As our trials progress from earlier stage, phase I trials for expanded cohorts of patients to phase II trials, we will be seeing a significant improvement in the way how transient toxicities are managed. So it's a very exciting time for patients. Other than the obligations that we need to fulfill in order to bring these products to patients very rapidly, I think the future looks brighter than it has ever looked in our company's history and in my career as an observer and an operator in this business. So thank you very much.

Operator (participant)

This concludes today's conference call. You may now disconnect.