Agenus Q1 2023 Earnings Call Transcript

Quartr
Provided by Quartr
May 9, 2023

There are 9 speakers on the call.

Operator

Day, and welcome to the Agenus First Quarter 2023 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. And finally, I would like to advise all participants that this call is being recorded. I'd now like to welcome Mr.

Operator

Zach Arman to begin the conference. Zack, over to you.

Speaker 1

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. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. Joining me today are Doctor.

Speaker 1

Garo Armen, Chairman and Chief Executive Officer Doctor. Stephen O'Dea, Chief Medical Officer And Christine Klaskin, Vice President of Finance. 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.

Speaker 2

Good morning, everyone, and thank you for joining us for our Q1 2023 update. Today, we'll primarily focus on the significant progress we've made with our groundbreaking motensilumab program And its potential to transform cancer treatment across 9 different solid tumor types that we've reported on so far. Over the past 10 months, we've presented data At the plenary or late breaking sessions of 5 major conferences, including ESO GI, Titsi, ASCO GI, SGO and CITAS. We look forward to sharing further insights at upcoming conferences such as ASCO in June And Esbo GI in July. Motencilimab, our innovative And multifunctional CTLA for anybody aims to revolutionize cancer treatment by extending clinical benefit To whole tumors, which have historically been unresponsive to standard of care and other immunotherapy agents, including Other CTLA-four antibodies.

Speaker 2

And impressively, odevansilumab has demonstrated clinical responses in both cold and hot tumors. In a diverse patient population of nearly 400 individuals Across 9 solid tumor types, all of them had exhausted prior treatment options, otencilimab has made significant strides in eliciting responses, Offering renewed hope for those who have failed all other available treatments. Let's take a closer look at response rates achieved with otenzilumab. Across all 9 solid tumors, we will observe remarkable response rates of up to 50% in highly refractory cancers. This is truly an impressive accomplishment considering the patient population involved.

Speaker 2

Notably, many of these responses have proven to be durable responses. This is a critical factor in Evaluating a treatment's potential to transform patients' lives in a meaningful way. But the story doesn't end there. Preliminarily, data suggests that potenolimab may be exceptionally effective in colorectal cancer Patients with whole tumors that have historically been unresponsive to immunotherapy. Even in hot tumors that have failed standard of care, including immunotherapy, of course, with or without chemotherapy, We are witnessing unprecedented response.

Speaker 2

Similarly, deep responses For such patients who have exhausted all available therapies, potencilimab holds the potential To be a game changer. Moreover, early clinical data indicates that Important responses may be achievable in the neoadjuvant setting, possibly Introducing an entirely new treatment approach and enhancing patient outcomes. The clinical data generated with potencilimab is truly inspiring, and we're thrilled with the progress we've made thus far. We firmly believe that potenselimab has the potential to reshape how we approach treating solid tumors, And we eagerly look forward to further advancements in this crucial program. With our more advanced programs As well as on the regulatory front, we're also making significant strides.

Speaker 2

Our Phase II ACTIVATE studies in colorectal, Melanoma and pancreatic cancers are set to conclude enrollment in 2023. And we are expediting enrollment into our refractory non small cell lung cancer cohort Where we have previously reported 50% response rates in patients who have failed prior PD-one and chemotherapy. We plan to launch a randomized Phase III study if the observed response rates persist in the extended cohort in Not small cell lung cancer. We're also proud to announce the fact that BotVal combination has generated Orbit has been granted fast track designation by the FDA for treating non MSI high colorectal patients Without active liver metastases. This acknowledgment of our potential to fulfill a significant unmet medical need Could accelerate the development and review of our application for approval.

Speaker 2

In conclusion, our unwavering commitment to advancing Our clinical pipeline and delivering innovative treatment for cancer patients remains stronger than ever. We are enthusiastic about Potenalemap's progress and its potential to profoundly impact the lives of patients with solid tumors. I will now hand it over to Doctor. Stephen O'Dea, who will provide further details on the latest data and then I will be coming back

Speaker 3

Thank you, Garo. Together with our investigators, We presented updates from the Bowel Development Program at 2 major medical meetings last quarter, Including a late breaking oral session at the American Society of Clinical Oncology Gastrointestinal cancer symposium in January in San Francisco at an oral plenary session at the Society of Gynecologic Oncology Annual Meeting in Tampa in March. I'll now briefly describe these data updates beginning with colorectal cancer. As Garo said, metastatic non MS high colorectal cancer patients treated with standard of care Have a reported 12 month survival rate of only 25% And an overall reported response rate to 3rd line treatments of 1% to 2%. Immunotherapy treatments of combinations PD-one and CTLA-four have similarly reported Poor response rates of only 1% to 5% in comparable populations.

Speaker 3

Doctor. Anthony El Khohuri, Associate Director for Clinical Research at the USC Norris Comprehensive Cancer Center And the Keck School of Medicine at USC presented our latest update of botanilumab program in colorectal cancer at ASCO GI. The cohort of 70 evaluable patients had a medium of 4 prior lines of therapy and a third of the patients Patients who received the bot bowel combination Showed a 12 month overall survival rate of 63%, more than twice the reported rate of 25% for standard of care. In the subgroup without active liver mets, the 12 month overall survival was 81%. This is the targeted population for our Phase 2 study where we recently received Fast track designation from the FDA.

Speaker 3

Even in patients with active liver The 12 month overall survival was 40%, indicating a survival advantage over standard of care for all patients Regardless of the presence of liver metastasis. The overall response rate for the 70 patients was 23% With 69% of the objective responses ongoing at the time of the data cut. The disease control rate, which is inclusive of complete responses, partial responses and stable disease was 70 Next, moving on to ovarian cancer. The reported response rate for standard of care in recurrent platinum Resistant refractory ovarian cancer with chemotherapy is only approximately 10%. PD-one and CTLA-four combinations have reported response rates of 3% to 10% in comparable patient populations.

Speaker 3

Doctor. Bruno Baccorne, Assistant Professor, Harvard Medical School, Presented the update of the botanselimab program in ovarian cancer at SGO's annual meeting in Tampa in March. 24 valuable patients were presented who had a median of 4 prior lines of therapy And 21% had already failed immunotherapy. The majority of patients, Almost 80% were high grade serous histology, which is the most common and most aggressive form of advanced Ovarian cancer. The overall response rate was 33% in this poor risk group And the disease control rate was 67%.

Speaker 3

Responses were durable like colorectal cancer With median duration of response not reached. This cohort continues to Expand and enroll in our Phase 1b study. While our primary focus remains advancing the A focused number of additional programs and combinations to further expand the therapeutic potential of boaten and unlock the full potential of our portfolio. Several of these programs have been selected for presentations At the upcoming ASCO conference in June in Chicago.

Speaker 2

AGEN2373

Speaker 3

Is our CD137 agonist designed to stimulate the activation of both cytotoxic T cells and NK cells while mitigating the liver toxicities, which are common to the first Generation target class. Complete results from the 1st in human dose escalation study of AGEN2373 Monotherapy in patients with advanced solid tumors will be presented during an ASCO poster discussion session On Saturday, June 3. We expect to complete enrollment of the Phase 1b study of AGEN2373 In combination with boatensilumab in PD-one relapsed refractory melanoma in the first half of 2023. Doctor. Brelin Wilke, Director of the Sarcoma Medical Oncology At the University of Colorado School of Medicine, we'll deliver an oral presentation on a single arm open label Phase 2 study of balsalumab with zalafrelumab, our first generation CTLA-four antibody plus doxorubicin in patients with advanced sarcomas at ASCO on Monday, June 5.

Speaker 3

Finally, Incyte will be presenting 3 poster presentations of our clinical partnered programs during the ASCO conference. Now I'll turn the call over to Christine for the financial update.

Speaker 4

Thank you, Steven. We ended our Q1 2023 with a cash, Cash equivalent and short term investment balance of $189,200,000 this compares to $193,400,000 at December 31, 2022. This quarter end, we have raised $13,600,000 Sales under our aftermarket issuance sales agreement. For the Q1 ended March 31, 2023,

Speaker 5

We recognized revenue of $22,900,000

Speaker 4

and incurred a net loss of $70,900,000 which includes non cash expenses of $24,900,000 I now turn the call back to Garo.

Speaker 2

Thank you, both Steven and Christine. In conclusion, we're very, very excited about the progress that we've made in our clinical programs As demonstrated by the updates that Steven and I shared with you earlier, our bowel combination therapy has At the ASCO GI Conference, we reported that this benefit has translated into improved survival in our metastatic colorectal patients. And we're very encouraged that it will also translate to improve survival in many and all of the cancers that we've studied so far. Our continued innovations and progress highlights our unwavering commitment to advancing cancer care. As Steven reported earlier, this progress also includes our ongoing exploration of our diverse portfolio, including A very exciting molecule, our anti CD137 molecule.

Speaker 2

This is an agonistic antibody. ILT-two on the other hand is now in clinical combinations and of course the combinations of our checkpoint antibodies with MINX Our genetic INK T cell therapies. A moment about MYC. MINK's latest update at the AACR conference reported clinical responses in solid tumor cancers With their lead candidate, Agent 797, an off the shelf INKT cell therapy. These data underscore the launch of a clinical trial in metastatic gastric cancer Led by Doctor.

Speaker 2

Elena Jangjigyan, who is the Chief of GI Cancer at Memorial Sloan Kettering. And this is externally funded by non diluted grant financing. Mink will supply the trial with its in house Factor in capability, which today can produce 5,000 doses per year with rapidly expanding capacity. To enable access to this exciting portfolio, we've issued a dividend of mixed shares to our Agenus Shareholders, in order for them to have the opportunity to participate in the upside of mix directly. As we recognize our Q1 achievements, we're grateful for the incredible support and momentum we've built with clinical experts and patients.

Speaker 2

Our determination to bring innovative treatments for cancer patients remains We're actively exploring discussions with potential partners and collaborators To maximize the potential of botanselimab and the rest of our pipeline, our focus is not only on managing these assets prudently and also on building our internal capabilities. In conclusion, as an organization, we're deeply committed to revolutionizing cancer treatment By making access to high quality medicines, our very top priority, We aim to create a simple progressive model that ensures patients receive the best possible treatments available to them. Drawing inspiration from value based care, patient centric care And integrated care systems, we focus on delivering efficient, personalized and top notch care For everyone who can benefit from it. Together, we strive to transform the cancer treatment landscape By putting patients first and making state of the art medicines accessible to all, all who need it. You will be hearing more about these strategy and how our initiatives will integrate into these strategies in our coming communications.

Speaker 2

With that, we'd like to now open the call for any questions you may have. And thank you everybody for joining us today once again. Anna?

Operator

Thank you, speakers. Your first question comes from the line of Emily Bodner of Wainwright. Emily, please go ahead.

Speaker 4

Hi, good morning and thanks for taking the questions. Maybe could you expand a bit more on what we should be expecting you To present on at ASCO for AGEN2373 and how you kind of think about what would be positive data in that study considering it's monotherapy. And then maybe can you just discuss if there's any other Phase 2 or Phase 3 studies that

Speaker 2

So let me make a couple of broad comments Then I'll turn it over to Stephen. As you know Emily, 2,173 is a very important Product, very important product because it adds some very complementary attributes To patient care and patient treatment. For example, with bodesilumab, we're activating T cells. Wireless, we're also generating memory and depleting regulatory T cells, But activating T cells better than the 1st generation CTLA Forrester. Now what 2,373 does in addition is really concentrate on the memory Which becomes critically important in the durability of immune response and durability of patient benefit.

Speaker 2

So that's one bucket and I think Doctor. O'Dea can expand on it. But secondly, we'll ask about other Phase 2 trials. Now we haven't really publicly announced any of our plans with regard to additional Phase 2 trials or Data from other programs. But just as we do very properly, until for example we get the abstracts Except at major conferences, we won't talk about it because it jeopardizes obviously the Acceptability of an abstract if we publicly discuss these things.

Speaker 2

So that's what we do. But what's very encouraging also to us Remember, as we said during our call today, since late June of last year, We have presented data at oral plenary opening sessions at so many major conferences, which is really unprecedented For a single product, if you look at it. So very encouraged, but stay tuned for the rest of it. But Stephen, would you like to add any comments about

Speaker 3

So our CD137, we're incredibly excited about. And as you said, we will be updating the Phase 1 monotherapy trial at ASCO And a poster discussion session in the coming weeks. The IO world has been focused on inhibitory Checkpoints, obviously, for good reason for a long time with CTLA-four, PD-one and the other. The agonists have struggled mightily with toxicity issues, particularly around liver toxicity with 1st generation. And there was great promise that by pushing the accelerator, in addition to blocking the break of the T cell, more extraordinary things could happen.

Speaker 3

So we've designed a next gen CD137 that really will hopefully be an Important combinational partner in our arsenal and obviously for patients. So what we're looking for, just from my perspective Obviously, we want to see safety with this new drug design. And obviously, single agent activity would be great and is very important, I think, In any IO asset and we'll be updating our data in a few weeks. So stay tuned.

Speaker 4

Great. Thank you very much.

Operator

Our next question comes from the line of Mike King of E. F. Hutton. Please go ahead.

Speaker 6

Hi, guys. Good morning and thanks for taking the questions. Congrats on the progress. Just real quick, Two things. Garo, you had said you made a comment about your inclination to move forward with a randomized trial Non small cell lung cancer based on the results of the single arm study, but I didn't catch quite what you had said and If you had said some kind of a bar for response rates or some other criteria that would motivate you to move into a randomized trial in non small cell?

Speaker 2

Sure. Very good question, Mike. Thank you. So as you know, lung cancer is a hot Cancer, relatively hot cancer. And so while botezolumab has shown profound activity in cold tumors like cold rainfall, Warm tumors also are a target.

Speaker 2

And in lung cancer, We've shown that in PD-one resistant as well as PD-one Plus chemo unresponsible resistant tumors. We're showing with a small denominator admittedly, But we're showing about 50% response rates, which is really a very, very major improvement for the Now as I said, the denominator is slow. And so what we're doing is really expanding the cohort on lung cancer patients so that in a relatively short period of time, we can move the denominator up to 40, 50 patients. And of course, if we can maintain the kind of response rates, which you've seen in about 10 patients prior. In 4,050, You will see a huge level of game changer interest in this.

Speaker 2

Now with the early data, A few outside groups have shown significant interest in doing randomized trials With Voronav, these will be multiple arm trials with standard of care in the earlier stage setting. So stay tuned. We have not yet announced the specific plans, but these plans are well underway for a randomized Phase 3 trial That will include botencilimab plus a current standard of care The versus the other arms that we haven't disclosed yet, Right. That trial should be initiated sometime this year.

Speaker 6

Sometime this year. Okay. All right. Superb. I mean, I got a ton of questions, but I guess On ASCO, I'm sorry, the ESMO GI, I think the last time you Show data at ASCO GI in colorectal was 70 patients And you had the 1 year response at 63%.

Speaker 6

Are we going to get those updated? Is the end going to change? Maybe qualitatively, Can you tell us what the data is going to look like, what the complexion will be at the ESMO GI meeting?

Speaker 2

I'll turn this to Steven.

Speaker 3

Yes. Thanks again for the question. Yes, so we did report 70 patients at ASCO GI and obviously that trial Was it continuing to enroll at the time? It has since completed enrollment as we've launched our Phase 2 Pivotal trial. So you can expect more patients and longer follow-up with the next update at ESMO GI.

Speaker 6

Okay, great. All right. Thanks. I'll jump back in queue.

Operator

Our next question comes from the line of Mayank Mamtani of B. Riley. Please go ahead.

Speaker 7

Good morning, team. Thanks for taking our questions and congrats on the progress. So just a couple of quick follow ups, two questions being asked Sure. And then I have a couple more. So, it was curious to see your Fast Track designation come in line with how this CRC data is maturing.

Speaker 7

Could you comment or specify that this updated data was Submitted as part of requesting the agency for Fast Track and if there are any other Mechanisms like breakthrough therapy or others that are being explored, as you get close to getting randomized control data From the Phase 2 study.

Speaker 2

So, Fayan, I think I'd be wise not to elaborate on Your question, because of the sensitivity at many levels. But suffice it to say that We are obviously keeping not just the FDA, but other agencies abreast of Developments with CRC and some of the other indications as well. Now one thing that is sure That I think needs to be stressed over and over again. When we treat patients, which are not just metastatic patients, for example, in CRC, but also other indications. But these patients are typically 3rd, 4th, 5th line patients.

Speaker 2

They have been Treated with pretty much everything that's available and either haven't responded Or failed after they have responded to these other treatments. So these are pretty sick patients. And the kinds of responses that we're seeing, which are in the neighborhood of 20% to 50% depending on the indication, It's really something very meaningful for the patients. And of course, from a regulatory perspective, you may say, well, response is not enough, But please explain that to the patient that the response is not a good thing. So we are diligently pursuing, of course, the next steps.

Speaker 2

Response is a very important criteria for Axit that has exhausted all options, particularly to the kind of durable responses we're All the magnitude that I just talked about, they're very meaningful, but we're also diligently pursuing that these responses will translate to longer term benefit to patients and of course the data that we showed at ASCO GI with survival curves Indicates, and of course, mind you, this is not a randomized trial, but the differentiation In this patient population in terms of overall survival is such that we are confident That the responses are going to translate to longer term benefit including survival. And I may add that With CTLA-four, typically, you do see response rates correlate Very well with other benefits. The same is not necessarily true with other IO treatments or other cancer treatments. But with CTLA-four targeting agents, generally and Doctor. O'Day can elaborate on this That it would be impossible to think about a trial where response rates will not translate to survival.

Speaker 2

Stephen, would you like to bring in your experience with that?

Speaker 3

Sure, Garo. Obviously, yes, I would agree CTLA-four as a Target because of the durability of responses and the fact that RECIST 1.1 underestimates Clinical benefit because minor responses and stable disease could be significantly durable has Correlated well with overall survival. And just I would redirect people to the initial ipilimumab study in melanoma, of course, only had a 10% percent sort of classic Rhesus 1.1 response and yet the survival curve showed a hazard ratio of 0 point So about 1 in 3 melanoma patients were having significant clinical benefit, which is double what the response rate was and it mimicked The plateau of the survival curve at 20% to 25%. So I think in general, CTLA-four based therapies, Whether alone or in combination with PD-1s have correlated well with survival and we based on our duration of Spons across bonecilumab are very hopeful it will continue to do that as we look at survival curves in our different solid tumor Clinical

Speaker 2

trials. Very

Speaker 7

helpful. Thank you. And secondly on the non small cell lung cancer cohort, Interesting to hear you are thinking of a randomized Phase 3 there. Could you talk to what sample size you need to see here Confirm this 50% response rate over time and we get a lot of questions about confirmed, unconfirmed Responses, so could you just clarify there was one unconfirmed PR when you last reported, has that been confirmed with the recent scans?

Speaker 2

Right. So I'll just give you a little bit of a hint, which is factual. As you know, Daxitaxel is the only approved therapy for patients in non small cell lung cancer who have failed chemo and PD-one. And so this is a low bar with 9% response rate right now. So the early indications of responses that we're seeing Our far in excess of that.

Speaker 2

And the only risk here is, are we preferentially putting patients that are best prognosis? And the answer is categorically to that question, no. So the 50% response rates, if Continued, in a larger denominator, we'll demonstrate a very significant benefit For patients who have failed chemo plus PD-one And who are otherwise going to be treated with docetaxel, which as I said shows a variable bar of 9% response So far and those non present responses are likely not to really show a major benefit for patients. So That's the bottom line. And of course, we haven't released all the details on this and we will.

Speaker 2

We are seeing responses in the worst patients with low TMB and low PD L1 expression, which Gives you a sense of what mechanism of obesilumab is in terms of both Lighting up tumors, making tumors harder. So if you can take low TMB patients and treat them with modesilimab to make them harder, which we Seem to be doing in our trial and you're dealing with patients that typically don't respond The one with low PD L1 expressions, those are 2 very important indicators as to the status of the patients Being a very correct full prognosis patient. So we're very encouraged with this outcome actually. And clearly outside groups that we're working with who would be at least partially or entirely sponsoring The trial are also very encouraged with the data. That's why we're proceeding in this direction.

Speaker 7

Did you say what denominator you might be targeting here? And then just my final Sorry, go ahead.

Speaker 2

We haven't disclosed those numbers yet, Mayank. I think we're in the process of Going back and forth and trying to finalize these details, but be rest assured it's not going to be a 1,000 patients.

Speaker 7

Understood. Thank you. And my final question on the 2,373 BOD combination study that is Approaching enrollment completion in melanoma, PD L1 refractory. Could you comment on what Appropriate benchmarks are Doctor. O'Day, since this is your arena and what might you be looking to deliver.

Speaker 7

And if I heard you right, the Timeline for that data is within first half twenty twenty three or is it just enrollment completion you said?

Speaker 3

So the accrual to the cohort will we expect to complete in the first half of the year. We won't have data Until later in the year at the earliest. But in terms of that cohort, obviously, these are very extensively treated melanoma patients that Or very refractory to IO and BRAF if they're mutant. So obviously any responses in This group would be of note and we look forward to observing this data as it evolves. So heavily pretreated melanoma patients The vast majority have had both CTLA-four and PD-one and in BRAF mutants have already exhausted

Operator

Our next question comes from the line of Matthew Phipps from William Blair. Please go ahead.

Speaker 8

Thanks for taking my question. I know the Phase 2 in CRC has done a good job of Showing contribution to components through different arms. But I'm wondering as you move into more indications such as if you launched a Phase 3 in non cell lung cancer, would you have to show contribution of components in those additional arms with the bone cell and that monotherapy arm?

Speaker 2

So the answer is no. We do not have to show that all over again in each and every indication, Matthew.

Speaker 8

Great. Thanks, Gail. Can you remind us on the timing of any Gilead opt in decision? Is it completion of this Phase 1? Or does it also The next study in combo with bonizumab and melanoma.

Speaker 2

Okay. So I think it's reason for a couple of things here. One is, Will our interests and Gilead's interest converge here? And we don't know the answer to that question From their perspective, but we regard 2,173 as a critical and cost program for us. We also believe that we need to have freedom to operate with 2,373 For the best interest of Agenus portfolio.

Speaker 2

So it will be a question of negotiation. And stay tuned Towards the end of the year, there will be more clarity as to how and if this option will proceed.

Speaker 8

Great. Thanks Garrett. Last one, I know we're going to get the Bowel's sarcoma data at ASCO. Is there any Steps forward for that combination, I know that focus has rightly switched to boncilumab, but just curious.

Speaker 3

Matt, obviously, our focus is on the next generation CTLA-four. Having said that, we think we have An excellent first generation CTLA-four that's been in combination in cervical and now this will be the first Real data in sarcoma. So again, let's watch the data as it gets presented and obviously we'll make decisions. But we certainly won't distract from our primary focus, which is boatensilumab and getting to market.

Speaker 8

Yes, that makes sense. Thanks, Doctor. Dae.

Operator

There are no further questions at this time. I turn the call back over to Mr. Garo Arben for closing

Speaker 2

Thank you very much everybody. Thanks again for joining us today. Clearly, there's So a lot going on and we are very eager to communicate things to all of our constituencies, which include Certainly our shareholders, but also very importantly investigators, KOLs who are major stakeholders in this because of Their interest with their patients to either participate in these trials and or To have these products available to them with the allowances that are there prior to approval And certainly posted Google as well. So we're very, very grateful to all of your support. The biotech markets have been challenging in the last year or so, but we're proceeding in a way that Really supersedes any of these challenges because what we've got in our portfolio is something very important for the benefit of these patients Certainly patients that have exhausted all options, but even patients that are in the earlier stages of disease and can benefit from our compounds in ways that will provide them with an option, which is typically not being addressed properly or effectively with current treatments.

Speaker 2

So thank you again And stay tuned. We'll see you at these upcoming conferences as well as in our next earnings

Operator

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

Remove Ads
Powered by Quartr
Earnings Conference Call
Agenus Q1 2023
00:00 / 00:00
Remove Ads