Agenus Inc
NASDAQ:AGEN
Agenus Inc
NASDAQ:AGEN
Price:
10.86 USD
3.43%
Market Closed
Updated:
May 19, 2024
Section:
Earnings Call Analysis
Summary
Q3-2023
Q3-2023
Clinical Progress and Financial Overview
The company is developing botensilimab, showing promise to set new cancer care benchmarks with potential long-term, curable benefits, notably in challenging 'cold tumors' and colorectal cancer. A first biologics license application submission is planned for mid-2024, supported by comprehensive dosing data. Financially, Q3 ended with $100.63 million, down from last year’s $193.4 million. The burn rate for Q4 is projected around $40 million with additional funds expected from milestones and asset sales. Strategic partnerships are sought with a commitment to rapid development, emphasizing botensilimab's unique efficacy in immuno-oncology.
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Good morning. My name is Jeannie, I will be your conference operator today. At this time, I would like to welcome everyone to the Agenus Q3 2023 earnings conference call. [Operator Instructions]
Thank you. Zack Armen, you may begin your conference.
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 time lines as well as time lines 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 Feet Adviser; 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 outlook for the remainder of the year. Garo?
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 [indiscernible] therapy is showing promise across various cancer stages and [ tops ] 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 but potential in earlier stage drill 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 3 key priorities: submitting our first biologics license application for colorectal cancer, prioritizing other clinical programs with the potential for rapid approval and importantly, to mark reallocating 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 and urgent unmet need. To address this, we have started a compassionate use program with the AMO 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 potential. Our cap priority is obtaining BOT/BAL 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 includes refractory pancreatic cancer and new [indiscernible] setting in CRC. Dr. O’'Day will detail the exciting data that showcases BOT potential in these cold dollar 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, include the 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 2 nonstrategic assets and pursuing the partial sale of milestones and royalties due to Agenus from our partner programs. These 3 sales are expected to close by the end of the first quarter half of 2024. The potential proceeds from these 4 transactions are estimated at approximately $200 million in total. With our cash balance at the end of Q3, along with the 4 plan 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 structure 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?
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 MF 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 3.5 years and 3 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 WOW Cornell, in which 12 patients with CRC were treated with 1 dose of BOT and 2 doses of BAL in the neoadjuvant therapy window of opportunity setting. Surgery was performed on average, only 4 weeks after the initiation of immunotherapy. All 3 MSI high colorectal patients had complete or near complete pathologic responses. And even more importantly, 6 out of 9 patients with MS stable colorectal cancer had pathologic responses of 50% or greater, including 2 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 MS stable colorectal cancer, potentially avoiding the morbidity of late-line therapies. In second-line pancreatic cancer, we have treated 6 patients with the combination of botensilimab, Gemzar and Abraxane triplet. All 6 patients had progressed following first-line metastatic [ fulfuronox ] therapy, and all 6 have 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 minus 47%, which has been confirmed and minus 37%, which is pending confirmation scans and both responses are ongoing. Two other patients showed stable disease at their first 8-week scans with tumor reduction of minus 20% and minus 13%, and they remain on study awaiting 16-week scan. 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 CTLA4 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 BAL combination cohort is enrolled with approximately 30 patients. A data update is anticipated in the second half of 2024. In PD-L1 refractory non-small cell lung cancer, we reported on 9 patients who were treated with the 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 2 expansion cohorts including PD-1 refractory as well as TKI driver mutation refractory disease. A data update is anticipated in mid-2024. The Dr. Bree Wilky, Director of the Sarcoma Medical Oncology Deputy Associate Director for Clinical Research at the University of Colorado Cancer Center presented an update of botensilimab program in sarcoma at ESMO 2023. In 41 evaluable heavily pretreated sarcoma patients, the combination of BOT/BAL demonstrated an overall response rate of 20%, a median duration of response of 19.4 months and a 6-month progression-free survival of 40%. There were differential responses observed by dose level with 29% response rate in the 2-milligram per kilo BOT cohort compared to 15% a in the 1 milligram per kilo BOT cohort. In addition, we observed promising activity and difficult to treat subtypes of sarcoma, such as lyomyosarcoma 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 an adequate or limited 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.
Thank you, Steven. The landscape for MSS CRC patients who received 1 to 2 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 [indiscernible] serve 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 0. Recognizing this, we've developed a differentiated investigational agent with botensilimab that has already demonstrated significant benefit over reported results for the standard of care therapies. With survival curve plateaus consistent with substantial long-term benefit. In our studies, patients with a median of 4 prior lines of therapy, 1/4 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 2 different doses, both 1 milligram per kilogram and 2 milligrams per kilogram and will be supported by safety data from several hundred additional patients across multiple indications where we have observed broad activity. And in this process, we're not leaving any stone unturned. We're conducting a comprehensive and full exploration of dosing 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 2 experimental agents BOT and BAL in a randomized fashion within our now fully enrolled Phase II study. As we move forward, we are and we'll continue to proactively engage with regulatory authorities. While we await complete feedback from the FDA in 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 regard our path forward toward approval. Our goal is clear. We aim to submit this package for potential approval by 2024 midyear 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.
Thank you, Todd. We ended our third quarter of 2023 with a consolidated cash, cash equivalent and short-term investment balance of $100.63 million. This compares to $193.4 million at the end of last year. For the 3 and 9 months ended September 30, 2023, we recognized revenue, which includes noncash revenue of $24.3 million and $72.5 million, respectively, including noncash expenses of $28.1 million, we incurred a net loss of $64.5 million for the third quarter. For the 9 months of 2023, we incurred a net loss of $208.9 million, which includes noncash 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 the clinical phase of Agenus. Our strive in cancer research highlighted by botensilimab signify a potential new airline in cancer care. I also want to express my gratitude to our employees. I am confident in our team dedication and our ability to achieve our milestones. The success of [indiscernible] 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 Instructions] Your first question comes from the line of Emily Bodnar with H.C. Wainright.
First one, just briefly, if you can comment on when we may expect to see initial Phase II data for the MSS CRC study. And then secondly, if you could talk about how you're thinking about strategy in the adjuvant CRC. Are you kind of looking to evaluate broadly in CRC or just focus on patients and maybe just discuss the regulatory pathway to potentially getting BOT/BAL in that setting.
Thank you, Emily. So let me answer the question broadly, and I'll ask if Dr. [indiscernible] 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 call and in our Phase II studies indicate that we should have a sustainable response rate, perhaps even an improving risk pose rate as we disclose and analyze these data for regulatory and beyond purposes. So that is going to be more of a regulatory decision, when to disclose it and the ideal circumstance for us will be certainly to publish the data at around the time of a potential BLA submission. To publish the data in [indiscernible] would be part of our plan. Now with regard to the neoadjuvant plans, we haven't quite crystallized it. Of course, the typical risk plans for new [indiscernible] studies is the fact that the large studies, 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 mobility with standards of care. And as you know, in these patients, even though the treatments are largely curative. They're not 100% curative standard of care, I'm not 100%, 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 cholastapy bags. It involves sexual disfunction and also involves the loss of muscle function in the area of the avenue. And particularly, if you are a patient in your 30s, 40s, you don't want to be subject to these mobility. 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.
Your next question comes from the line of Colleen Kusy from Baird.
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?
If I may ask Todd to answer that question.
I think there are really 2 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, the 5 arms of which 1 is standard of care. And of course, patients are randomized across these arms. The other 4 arms all have votenfilumab, which as monotherapy, we know to be active from the Phase I dose escalation. And 2 of those arms have [ votepilomeb ] in combination with BAL [indiscernible]. And as we've been observing in the data set that we've been presenting for the MSS CRC patients on active liver met 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 is for patients with 1 to 2 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 Arcad 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 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 and a receptor ligand interaction. But the back-end engineering is resulting in suddenly in activation of both innate and adaptive immune response has created a hot meal hue, and we have -- 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 2 active doses, 1 milligram per kilogram and 2-milligram per kilogram. And at the time of regulatory submission, we anticipate having approximately 175 patients in each of those 2 doses. So we'll be able to have a robust perspective on the activity of the doses, 1 and 2 and also on the tolerability of those two.
That's super helpful. And at the time of BLA submission, would you expect to have any sort of overall survival early data from this study?
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 on active liver metastatic patient population for efficacy adjudication. We are obviously seeing that responses for patients and that response can be stable [indiscernible] or better is translating to not only durable response, but very substantial overall survival. So I certainly expect that we'd be able to demonstrate a point 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 data set. 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.
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?
If you can repeat the question on the latter part of your question?
Yes. Just on the updated cash guidance?
I got it. I think. So as you know, we finished the quarter with a little over $100 million. My guidance for the fourth quarter burn is approximately GBP 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 2 assets that are nonstrategic assets. We expect that to be completed in the first half of this next year. And then a third-party royalty transaction. Now of course, the first 2 are entirely now control, meaning the milestone payment and the asset sales. And the royalty transaction will require external investors for that kind of transaction. We had done that before some years ago, in fact, about 5 years ago. We consummated a transaction for third-party royalties when we had a much skinnier loyalty portfolio at the time. And we did this with [indiscernible] So we're talking about a transaction, there 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 called cash between now and the middle of next year. That is through nonstock issuance transactions. Without any stock issuance we expect begin approximately $200 million. And with that, it will take us where we are at the end of next year. Any other questions?
Mayank Mamtani your line is open.
Helpful recap of the SMO even data. So maybe just to clarify on the second line plus CRC accredited approval, 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.
So I'll just make a gross comment on the confirmatory studies, and then I'll ask Todd to provide additional color. But -- with regard to confirmatory studies, we have 2 choices. One is to do a confirmatory study in the segment 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 later 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 with studies bought about [indiscernible]. 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 the first line or third line. Todd, would you like to add any additional color on this?
Yes. I just had 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. You already have a higher level of comfort with regard to our ability to combine in the frontline with 5FU and oxaliplatin-based regimens, of course, which have associated GI toxicity. So that level of comfort is rising. But as 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 that 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. And 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. And 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 2 potential options at least that we would present for their review.
Very helpful. 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 uptick in enrollment similar to what occurred in the colorectal cancer expansion cohort last year? And for the relatively warmer tumors in lung and melanoma, it seems like you have both mono and BOT/BAL combination data. So there is a theme here of Mona BOT data and combination BOT/BAL. So how are you sort of thinking across tumor types where you may pursue BOT stand-alone versus maybe combination, if there's a view on that you could share? And I have one more finance question after this.
Thank you. Dr. O'’Day, would you like to take that first part, the first multi part question.
Yes. Mayank, can you repeat the very first part of it, I have the melanoma part. But...
The pancreatic cancer bought chemo data, number of patients that you're targeting in the randomized control cohort? And if you've seen any uptick in enrollment like what happened with [indiscernible]
So we have a lot of enthusiasm around the data so far with both our PIs on the pancrea study, but more broadly KOLs. So we are expanding that and it is accruing, and we plan on treating another 60 patients in randomization in the coming months. In terms of melanoma, obviously, we have single-agent activity in melanoma in PD-1 and PD-1 CTLA-4 refractory that we've reported in our Ib 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 2 different doses. And as I said today, we're combining it with BA, and that data will be maturing, and we look forward to presenting it in 2024.
Got it. And maybe for Gary, 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? Are there any sort of constructs and town sheets that are more preferred versus less? If you could provide some color there, that would be helpful.
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 indicators as well as specific indication collaboration for which infrastructure exists at some companies to be able to segregate products by indication. That's new technology, and we've been proposed the potential option of segregating certain indications that are of greater interest to ship 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 burger oncology field. So that's number one, because we believe that botensilimab plus [indiscernible] offers performance advantages that we 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 product that offers them a potentially curative option with toxicity that is transit. I think that there is a an enormous need in the field for such a program. 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. Thats. number one. Number two, the [indiscernible] 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 plant. And the development has to be rapid because, as we've said before, we have seen clear clinical activity. And so far, 9 different cancers. 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 benefit. 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 1 of its 5 different activities, not just the center stage activity, but 1 of 5 different activities. So all of that means that this product needs to be rapidly developed across all indications. And if you pay attention to my [indiscernible] slide, you will see that the opportunity for cancer, cancer patients is enormous. So the partnership has to be based on a commitment financial commitment for rapid development. And of course, other cultural compatibilities that will allow our team to work with and partners a team to bring this into a harmonious conclusion.
Your last question comes from the line of Kelly Shi with Jefferies.
This is Claire on for Kelly. So just one question for the plan for CRC. So can you remind us what's your plan for those CRT patients with [indiscernible] at the Phase III confirmatory study, specifically in patients with [indiscernible] is there is an option to look at all-comer patients as well?
SP1 So I will take a little crack at it, and 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 livermed 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 what we're coming in. For example, if you look at our pancreatic data, all patients in the small number of patients that have been treated that had liver [indiscernible] and all patients that have responded have had liver [indiscernible] response. 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 at all in this. We don't know that. But I think in the next coming months, we will have a very deliberate action plan and trying to answer this question with small trials, possibly ISPs that will be undertaken. So see if we can translate some of what we were observed in [indiscernible] 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?
Yes. So obviously, in the refractory colorectal patient population, the I-O combination of BOT/BAL has its most profound signal to date in the nonactive [indiscernible] patients. These are patients who've never had liver retests or have had treated liver metastas. But depending on alignment of the Phase III trial, as Todd said, if we do move to first line, obviously, we would treat all comers. And so we will be aligning our Phase III trial in the coming weeks and months.
There are no further questions at this time, Garo Armen. I turn the call back over to you.
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, not just therapies that extend their life by a month or 2 at a very high cost of quality of life, but potentially expand life much longer with potential creative 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 into venture. And as our trials progress from earlier stage Phase I trials for extended onto patients to Phase II trials, we will be seeing a significant improvement in the way our transient toxicities are managed. So it's a very exciting time for patients. And 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 my career as an observant and an operator in this business. So thank you very much.
This concludes today's conference call. You may now disconnect.