Agenus Inc. (NASDAQ:AGEN) Q4 2022 Earnings Call Transcript March 14, 2023

Operator: Thank you for holding and welcome, everyone, to the Agenus Fourth Quarter and Full Year 2022 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. Thank you. I will now turn the call over to Zack, Head of Investor Relations. Zack, please go ahead.

Zack Armen: Thank you, Jack, 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. 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 Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Steven O'Day, 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. Garo?

Dr. Garo Armen: Good morning, everyone, and thank you for joining us this morning. We are absolutely thrilled to share the progress we've made at Agenus in advancing our deep immuno-oncology pipeline. Our portfolio is designed to address areas of high patient need and to unlock the large untapped market opportunity in cold and treatment-resistant cancers. And on top of that, to provide benefit beyond what is currently available with I-O treatments in other tumors, including hot tumors. At the forefront of our pipeline is botensilimab a clinical stage multifunctional Fc-enhanced CTLA-4 antibody with potentially blockbuster capabilities. Over the last 12 months, we've made substantive progress addressing the ongoing botensilimab development program, including having dosed over 300 heavily pretreated patients with advanced solid tumors as part of our Phase 1b trial.

That's a very large trial in account. And we've done this with as monotherapy and in combination with our PD-L1 -- I'm sorry, PD-1 antibody balstilimab. Botensilimab has produced durable objective responses in nine cold and/or treatment resistant cancers, including MSS colorectal cancer and MSS stands for microsatellite stable cancers that are particularly challenging to treat with immunotherapy. So, we've seen results in MSS colorectal cancer, MSS endometrial cancer, platinum-resistant refractory ovarian cancer, PD-1 resistant refractory non-small cell lung cancer, PD-1 and CTLA-4 resistant refractory melanoma, a particularly challenging patient population. PD-1 resistant refractory hepatocellular carcinoma, PD-1 resistant refractory cervical cancer, angiosarcoma and liposarcoma, this is a very extensive list of difficult-to-treat cancers that had been treated and failed prior treatments.

Based on the unprecedented clinical responses in these patients, we have initiated three global randomized Phase 2 trial, evaluating the efficacy and safety of botensilimab monotherapy or combination therapy with balstilimab in MSS colorectal cancer, melanoma, and pancreatic cancer. We aim to initiate a Phase 3 study in MSS colorectal cancer later on this year in the hope that the cumulative data that we've generated between Phase 1, the Phase 2 randomized trials and the initiation of our Phase 3 trials will lead to a rapid approval path for the benefit of the patients. We are thrilled by the clinical results we have seen with botensilimab and are excited about its potential to positively impact the treatment landscape for patients obviously suffering for cancer, all kinds of cancers.

We remain committed to advancing our pipeline of innovative therapeutic therapeutics and believe that our portfolio of programs in the immuno-oncology space is robust with multiple programs in development, including, very importantly, our ILT2 program, which is codenamed AGEN1571 and our CD137 program, otherwise also known as 41BB agonist antibody, which is codenamed AGEN2373. Both of these molecules are progressing in the clinic. We look forward to sharing more updates on our progress during various conferences throughout this year and our other communications means as well again throughout this year. Thank you for your attention. And now I will turn the call over to Steven O'Day to highlight the recent clinical data presented on botensilimab.

Dr. O'Day has a very extensive section today because there's a lot to talk about. And so we'll ask him to go through it very, very orderly, slowly because I think the content is something that is not to be rushed, Dr. O'Day.

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Dr. Steven O'Day: Thank you, Garo. Together with our investigators, we were pleased to have had the opportunity to present data updates from the botensilimab and balstilimab development program at five medical meetings over a nine-month period, including plenary sessions at ESMO World Congress on Gastrointestinal Cancer, the Society for Immunotherapy of Cancer, otherwise known as SITC, the Connective Tissue Oncology Society, known as CTOS along with a late-breaking oral session at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium this past January, and finally, an oral plenary session at the upcoming Society of Gynecologic Oncology Annual Meeting. These presentations highlighted the durable responses and meaningful clinical benefits of the botensilimab, balstilimab combination compared to what has been reported with standard of care and other investigational therapies in patients with MS stable colorectal cancer, non-small cell lung cancer, ovarian cancer and sarcoma.

I'll now briefly describe these data updates, beginning with our MS stable colorectal cancer program. In metastatic MS stable colorectal cancer after failure of first and second line therapies, the current standard of care is a 12-month overall survival rate of approximately 25% and an overall response rate of only 1% to 2%. Other PD-1 or PD-L1 CTLA-4 combinations evaluated in this comparable patient population supported response rates of only 1% to 5%. Our latest update of botensilimab program in metastatic MS-stable colorectal cancer was from an expanded cohort of 70 evaluable patients presented at ASCO GI by Dr. Anthony El-Khoueiry, Associate Director for Clinical Research at USC Norris Comprehensive Cancer Center and the Keck School of Medicine at USC.

This presentation showed that treatment with botensilimab, balstilimab combination resulted in a 12-month survival rate of 63% and including a 12-month survival rate of 81% in patients with no active liver metastasis and a 40% 12-month survival rate in patients with active liver metastasis, suggesting a favorable overall survival in each of these patient subpopulations. Median overall survival in the overall population and the subset without active liver met disease has not yet been reached. The overall response rate of the 70 evaluable patients was 23%, and 69% of these objective responses were still ongoing at the time of the data cut. The disease control rate, which is inclusive of complete responses partial responses and stable disease was 76%.

These patients had a median number of four prior lines of therapy. Turning to anti-PD-1, PD-L1 relapsed refractory non-small cell lung cancer. At SITC, we reported our first four evaluable patients with two objective responses or 50% response rate and three out of the four responses with disease control for a 75% disease control rate. Since SITC, we have four responders out of a total of eight patients now with four additional patients treated, confirming the response rate reported at SITC in a larger patient population. Other PD-1 or PD-1 CTLA-4 combination in the second or third-line PD-1 refractory non-small cell lung cancer population have reported response rates of 6% to 13%. Based on these early clinical signals, we are aggressively expanding enrollment in this non-small cell lung cancer cohort and plan additional non-small cell lung cancer studies.

In 19 evaluable patients with platinum relapsed refractory ovarian cancer, we observed high responses for an overall response rate of 26% and a disease control rate of 63%. Other PD-1 or PD-L1 CTLA-4 combinations have reported response rates of 3% to 10% in comparable patient populations. An update of this cohort will be presented at an oral plenary session at Society of Gynecologic Oncology 2023 Annual Meeting in Women's Cancer on March 27 in just a couple of weeks. At CTOS, last November and presented by Dr. Bree Wilky at the University of Colorado, data was presented on a cohort of heavily pretreated metastatic sarcoma patients of mixed histology. Of the 13 evaluable patients, the 12-month overall survival rate was 77%, and the median overall survival had not yet been reached.

The overall response rate was 46% with 67% of the objective response is still ongoing at the time of the data cutoff. Other PD-1, PD-L1 CTLA-4 combinations have reported response rates of 12% to 16% in comparable patient populations. Reflecting the high unmet patient need in each of these cancer types, we have been encouraged by the consistently positive feedback we have received on these data from key opinion leaders in the field across diseases, what often describes the results we have reserved in these cold or PD-1 refractory settings as unprecedented. Now I'll summarize our plans for ongoing clinical activities, starting with MS stable colorectal cancer. We have launched a randomized Phase 2 trial of botensilimab and the botensilimab, balstilimab combination therapy in patients without active liver metastasis who have received one or two prior lines of standard of care therapy.

This study is actively enrolling at sites around the world. Importantly, we have designed this study to satisfy key regulatory requirements, including exploration of two known active fixed doses of botensilimab. In addition, we are evaluating both botensilimab as monotherapy and as combination with balstilimab and to establish the contribution of respective component of the study. Finally, we have randomized to fifth control arm that is a standard of care, either regorafenib or long serve at their approved doses and schedules. We intend to submit a regulatory review of MS stable colorectal cancer in 2024, a data package with this randomized Phase 2 study, along with data for more than 300 patients in the Phase 1b study. This package will include overall response rate, duration of response, progression-free survival and overall survival.

We also expect to launch a Phase 3 confirmatory study in MS stable colorectal cancer in 2023 that will be powered to demonstrate statistically significant and clinically meaningful overall survival. We expect this study to be considerably or fully enrolled by the time of our potential regulatory submission in 2024. Now, let's turn to melanoma. In melanoma, as part of the Phase 1b expansion, we reported responses with botensilimab monotherapy in patients who are refractory to PD-1 and patients refractory to both PD-1 and CTLA-4. This is an area of significant unmet need. We currently have an active -- a Phase 2 study evaluating botensilimab monotherapy in these cohorts of PD-1 refractory and PD-1 CTLA-4 refractory disease and plan to explore a rapid registration path, if the observed signal remains robust.

In metastatic pancreas cancer, we are evaluating a second line patients in a Phase 2 randomized study comparing standard of care gem-abraxane to gem-abraxane in combination with botensilimab therapy. We continue to enroll patients in our ongoing Phase 1b expansion cohorts with a focus on PD-1 or PD-L1 refractory non-small cell lung cancer patients. Like our approach with melanoma, we plan to explore a rapid registration path in non-small cell lung cancer, if the observed signal continues to remain robust. Botensilimab clinical activity in late-stage refractory cancers has generated substantial interest from leaders in the field worldwide, including requests for cooperative and investigator-sponsored trials. As we progress trials to support potential registration in colorectal cancer, melanoma and lung cancer, we plan to leverage these important partnerships to expand development in indications such as sarcoma and ovarian cancer as well as other areas where botensilimab has already demonstrated promising potential clinical benefit.

While advancing the clinical development of botensilimab and balstilimab remains our top priority, we also continue, as Garo said, to progress a focused number of additional programs combining botensilimab with other agents in our pipeline to further expand the therapeutic potential of botensilimab and unlock the full potential of our portfolio. Let me tell you a little bit about those programs. We expect to complete enrollment of our Phase 1 study of botensilimab in combination with AGEN2373, a CD137 agonist in PD-1 relapsed refractory melanoma in the first half of 2023. AGEN2373 is a conditionally active CD137 agonist designed to stimulate the activation of cytotoxic T and NK cells while mitigating the liver toxicities common to this target class.

The advancement of this study triggered a $5 million payment from our partner Gilead last year. We also dosed the first patient in the Phase 1 study of AGEN1571 at the end of last year as a monotherapy and continued dose escalation of monotherapy this year. In addition, we will be combining our AGEN1571 in combination with botensilimab and balstilimab in advanced solid tumors this year. AGEN-1571 is an ILT2 agonist antibody designed to modulate tumor-associated macrophages, T cells NK cells and NK T cells to overcome resistance to checkpoint blockade. This clinical study was initiated based on pre-clinical data we reported at the 2022 American Association for Cancer Research Annual Meeting which showed superior potency and functional activity of AGEN1571 compared to the only otherwise known clinical stage asset as well as enhanced immune cell activation when combined with botensilimab or balstilimab.

Now, I'll turn the call back over to Garo to discuss our strategic partnerships.

Dr. Garo Armen: Thank you, Stephen. As you can see, it has been a very, very busy year with a lot of impressive data that has been generated and the validation that we have received in making presentations, podium presentations, plenary presentations four of them within a six-month window at major conferences, and a substantial number of KOLs that have been engaged in discussions about the data and about our next steps with the data for expansion of our trials and a potential registrational pathway. So progress with me with our truly differentiated R&D engine and strategic partnerships has been impressive by all accounts. And as you know, we have generated $825 million in cash already received through our partnerships with the potential to deliver an additional $2.7 billion in future milestone payments, and on top of that, royalties when these products are commercialized.

So that's the side of our business, which doesn't drain any resources, including cash resources from the Company. This is in addition to us advancing our own portfolio which may result in a significant upside, a financial upside for the Company. And of course, this is a testament to the strength of our pipeline and the innovative capabilities of our R&D platforms. And thank you for that team, Agenus Research. In 2022 alone, our partnership with Merck, BMS, Incyte, UroGen have resulted in the launch of nine new additional clinical trials of our partnered assets. What's even more impressive is that these trials are all evaluating molecules discovered here by Agenus, including some exciting ones like MK-4830, an ILT4 antagonist now led by Merck and BMS-986442, antigen bispecific antibody now with by BMS.

We're also seeing very great progress with molecules targeting GITR, LAG-3, TIM-3 now led by Incyte. Looking ahead at 2020 -- I'm sorry, 2023 is this year, we have some major clinical milestones inside, as Dr. O'Day mentioned. We're expecting to complete enrollment of our global randomized Phase 2 activate studies of botensilimab in MSS colorectal cancer, melanoma and pancreatic cancer plus we expect to initiate a Phase 3 study of botensilimab with balstilimab in MSS colorectal cancer complete enrollment of our Phase 1b study of botensilimab and AGEN2373. That's our CD137 molecule. In melanoma, and initiate botensilimab and balstilimab combination cohorts in a Phase 1 study of AGN1571, a very exciting molecule that targets the myeloid arm of the immune system.

We're also advancing seven clinical collaborations evaluating combinations of external agents with our PD-1 and CTLA-4 antibodies, sponsored and executed by our partners. All in all, we are incredibly excited about the future potential of our pipeline and our partnerships. We're thrilled, of course, to share these updates with you all. With that, I'll turn the call over to Christine for a financial update, and I'll come back for closing remarks. Christine?

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