Welcome to Agenus' First Quarter 2022 Financial Results conference call. My name is James, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. During the Q&A session, if you have a question, please press zero one on your touchtone phone. I'd now like to turn the call over to Ethan Lovell, Chief External Affairs and Communications Officer. Mr. Lovell, you may begin. Thank you, James, 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 contain 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 on the call are Dr. Garo Armen, Chairman and Chief Executive Officer, Dr. Steven O'Day, Chief Medical Officer, Dr. Dhan Chand, Head of Drug Discovery, Christine Klaskin, Vice President of Finance, and Dr. Jennifer Buell, Chief Executive Officer of MiNK Therapeutics. 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. Dr. Garo? Thank you, Ethan, and thank you all for being with us today. As we all have witnessed, the biotech sentiment is the most negative we've seen in decades. Given the current climate, I'd like to begin today's call by indicating that we are aware of this reality and are putting on hold all programs which are not critical for near-term value generation. While, and importantly, we are marching ahead with programs which we believe have the prospects of generating significant near-term value. Overall, we expect these steps will result in significant cost reduction for the balance of this year. Ironically, despite recent trends, scientific and medical innovation is at an all-time peak. However, it appears that irrational exuberance coupled with recent regulatory uncertainty, I'm mumbling my words here by even talking about regulatory uncertainty, but particularly this is happening in the U.S. of course, has made it more difficult for investors to differentiate between the good, the bad, and the ugly. Still, some companies will continue to innovate and achieve success. Several, like us, have already started restructuring their operations and curtailing their ambitions to adjust to current realities. While this shifting environment has led to a discouraging financial climate for biotech, we believe companies like Agenus with integrated capabilities, and importantly, platforms which can drive continuous innovation will emerge at the forefront. A few will be able to build significant value while advancing profoundly effective treatments and cures. At Agenus, we expect that our portfolio of innovative discoveries and our steadfast commitment will trump all hurdles and deliver life-changing medicines to patients, while creating significant value for all stakeholders. Thus, Agenus' strategy is to continue to drive innovation in today's shifting environment. Now, I will outline our highest priority programs. Starting with botensilimab, our most advanced fully owned program represents the highest potential in our portfolio. This is, by the way, based on the fact that the compound, botensilimab, is the most advanced in the clinic among the novel compounds that we have in our portfolio. Our expectations of botensilimab as a potential blockbuster IO agent are supported with additional clinical data, which we expect to present at an upcoming cancer conference. Botensilimab is an activator of both innate and adaptive arms of the immune system. Data from our proprietary VISION platform continues to support its broad and unique activity, including responses in patients with so-called cold tumors, which typically do not respond to immune therapy. We have expanded patient enrollment in our existing clinical trials, in specific cohorts of patients, which will form the basis of our phase II studies in colorectal cancer, melanoma, and pancreatic cancer. Our efforts to initiate these studies are currently in high gear. Our clinical development strategy of botensilimab is to demonstrate clear superiority to existing checkpoint immunotherapies and/or other standards of care. This is based on strong signals we have observed in our phase I study in patients who were heavily pretreated. These observations led to our prioritization of relapse-refractory melanoma, MSS colorectal cancer, and pancreatic cancer as our target indications for potential approval. Now, for a minute, for context, colorectal cancer is the third leading cause of cancer-related deaths in the United States, with over 50,000 Americans dying each year. Immunotherapy treatments in colorectal cancer have been largely unsuccessful, partly because most colorectal cancers are cold tumors, and for those with metastatic disease, five-year survival rates are in the low teens. Also, for context, current standards of care for patients which are represented in our trials deliver approximately a 2% response rate, with significant side effects and minor improvement in survival. In contrast, botensilimab in combination with our anti-PD-1 balstilimab has delivered significantly higher response rates, which will be discussed soon. Botensilimab also holds significant potential in melanoma, where despite treatment advances, there remains few effective therapies for those who fail frontline regimens, particularly with immunotherapies as well. In addition to these indications, we presented data at last year's SITC demonstrating that botensilimab benefits in several other cold tumors, including endometrial, cervical, and pancreatic cancers. Over 50% of patients treated with botensilimab had received at least three prior lines of therapy. Botensilimab produced objective responses in these difficult to treat patient settings. Hence, we're preliminarily exploring development strategies across these indications, to bring therapy options to patients who have limited or no options today. The unique attributes of botensilimab have been the result of the deliberate efforts of our team, who engineered this molecule based on their understanding of tumor biology and the immune system. These translated into a unique mechanism of action, which results in the activity of botensilimab across a variety of tumors. At SITC, we presented botensilimab's activity in nine different tumors. While botensilimab binds to CTLA-4, it has a much broader activity by targeting both the adaptive and the innate immune arms of the system. We're working closely with scientific and regulatory experts to advance botensilimab in hard-to-treat cancers, which I mentioned include cancers characterized by cold tumor types. We're hopeful that the unique attributes of this molecule will lead to life-changing outcomes for underserved patients, including potential treatments for pediatric cancers. While advancing our portfolio with our high-priority programs, we're also pursuing our business development plans with potential collaborators. In addition, we're actively looking at innovative financing mechanisms, which we have excelled in delivering previously. Adapting our business model in consideration of the current industry landscape is, for us, a critical extension of our innovation and strategic thinking. Agenus has had an impressive track record of BD transactions and innovative financings, with more than $800 million raised in just the past six years, and potential to realize significant milestone on royalty payments from six different companies involving eight product candidates currently in clinical development. As Agenus moves with speed and innovation to execute our scientific discovery and clinical research, we're committed to taking the steps which will ensure our medical advances will be widely available to patients all over the world. Investing in integrated discovery, development, and manufacturing capabilities, and emphasizing on international approaches to clinical development and commercialization are critical to achieving our objectives in this regard. We're putting these strategies into practice. For example, with [balstilimab], as we strive to make this combination available in ex-US territories and as we continue to prioritize industry partnerships which allow Agenus to retain elements of independence and control over the development of our molecules. It is also noteworthy to mention that Agenus' science has already advanced 16 discoveries into clinical development. With a very exciting cell therapy company represented today by the CEO, Dr. Jennifer Buell. That's MiNK Therapeutics, created as a separate company and another SaponiQx potentially in the making. Our ability to discover and innovate best-in-class molecules and treatments has been the basis for a significant number of productive industry partnerships. Our company values and the high worth we place on science has been instrumental in industry breakthrough therapies such as GSK's Shingrix vaccine, with current analyst estimates of approaching $3 billion in annualized revenues this year. As I mentioned earlier, we're also sharpening our focus around expense management to extend our runway to continue with our discoveries uninterrupted. Every aspect of this process matters to us. We have initiated a comprehensive review to eliminate non-discretionary spending and implement highly efficient practices. While we believe Agenus is in a strong financial position with over $260 million in cash, our view is to exercise a conservative fiscal policy, particularly in times of uncertainty in financial markets and drug regulation. Our focus also includes our technology advancements, which drive efficiencies in product discovery and innovation. This is highlighted by our unique discovery platform, VISION, which has led to, among others, our emerging work on myeloid checkpoint targets. At AACR in April, we presented data on our anti-ILT2 antibody, AGEN1571, which represents our first fully owned clinical-stage myeloid targeting agent. In preclinical studies, AGEN1571 has already demonstrated several important advantages. We expect to enroll patients in our phase I studies of AGEN1571 shortly. Our plans are to evaluate this agent both as monotherapy, and in combination guided by readouts from our VISION platform. Last month, we also announced the receipt of a $5 million milestone payment from our partner, Gilead Sciences. While this is a tiny amount, it denotes the advancement of AGEN2373, our CD137 agonist, which has unique advantages over other molecules. CD137 is an important pathway for anti-tumor immunity due to its ability to enhance T-cell and NK cell proliferation, cytokine secretion, and cellular cytotoxicity. Importantly, AGEN2373 was designed to mitigate the liver toxicity that has limited the advancement of a 1st generation molecule. Gilead retains an exclusive option to license AGEN 2373, while Agenus has the ability to opt in for a 50/50 profit share and U.S. co-commercialization rights. Agenus stands to receive up to $570 million in future potential option fees and milestones from this product candidate alone. There'll be, of course, additional royalty payments, depending on the magnitude of a product like this upon successful launch. Development of AGEN 1777, our FC enhanced TIGIT bispecific antibody partnered with BMS, is also advancing in the clinic. We continue to believe AGEN1777 represents a best-in-class antibody, with an increasing body of evidence indicating that FC enhancement is required to achieve optimal results with a TIGIT targeting approach. The programs I highlighted today signify Agenus' unique ability to advance our own pipeline with our own combinations, which is also enabled by information and knowledge we gather from our proprietary VISION platform. Among others, VISION informs upstream target prioritization and downstream biomarker identification, as well as trial design. It is this ability to work rapidly with independence, and integrity driven by science, that positions Agenus to be a leader in biotech's currently shifting environment. Thank you very much, and I now turn it over to Christine, and I'll come back shortly after that. Thank you, Garo. We ended our first quarter 2022 with a cash and short-term investment balance of $263 million as compared to $307 million on December 31st, 2021. We recognized revenue of $26 million for the quarter ended March 31, 2022, which represents an increase of $14 million from the $12 million reported for the same quarter in 2021. Both amounts include revenue related to non-cash royalties earned, revenue recognized under our collaboration agreements, and in 2022 milestones received. Net loss for the quarter ended March 31, 2022 was $51 million, which includes non-cash expenses of $21 million compared to a net loss for the same period of 2021 of $54 million, which includes non-cash expenses of $20 million. Per share losses were $0.19 per share in the first quarter of 2022, as compared to per share losses of $0.27 in the first quarter of 2021. Cash used in operations for the three months ended March 31, 2022 was $52 million, up from the $43 million for the quarter ended March 31, 2021. As Garo mentioned, the company has initiated cost containment measures with expected reductions in operating expenses in the coming quarters. I now turn the call back to Garo. Thank you very much, Christine. To summarize, despite the stressful external landscape, we continue to make important advances in a field which is in need. We have a number of important developments, including near-term data disclosures, initiation of phase II botensilimab programs. We're delivering on our promise of building a company with a diverse pipeline and moving swiftly to address areas of high unmet patient need. By the end of 2022, we expect to have initiated several new clinical studies, including the three phase II studies for botensilimab that we spoke about. A phase I monotherapy study for AGEN1571. We also expect to complete enrollment in the relapsed refractory melanoma cohort of our combination study involving botensilimab and AGEN2373. In addition, there's of course, the potential of corporate collaborations and additional cash infusions from them during the course of this year. Thank you again for your attention, and we will now open the call for questions. Thank you. We can begin our question and answer session. If you have a question, please press zero one on your phone. If you wish to be removed from the question queue, you may press zero two. If you're using a speakerphone, you may need to pick up the handset first before pressing the numbers. Once again, if you have a question, please press zero one on your phone. Our first question comes from Mayank Mamtani, I apologize, from B. Riley Securities. Good morning. Thanks for taking my questions and helpful biotech sector-specific commentary there, Garo. Maybe just to kick start things with your recent prioritization of ILT2 as an important target and a myeloid checkpoint inhibitor. Was just curious what was the rationale for that and sort of your history in that space? Also if you could talk to how might Sanofi's development, and I think some data coming at ASCO, inform your development and sort of the basket of initial solid tumors you might prioritize. Then I have a follow-up. Let me first turn it to Dr. Dhan Chand to address at least a part of this question. Thank you, Garo. Mayank, thank you for that question. As you're aware, Agenus is well familiar with the ILT space. In fact, we built Merck's ILT4 antibody, MK-4830, which is progressing in the clinic, showing activity in patients that are refractory to PD-1 therapies, as by design by Agenus. With that knowledge and experience that we built in the space, we've also retained ILT2 and progressed ILT2 to the clinic where we have demonstrated, as you can see, at AACR, the potential for ILT2 activity in not only complementary to PD-1, but also extending activity to colder tumors where PD-1 is not active. We've also demonstrated broad activity of AGEN1571, which includes activity that goes beyond just myeloid activation, which includes T-cell, NK, and NKT activation. You'll also notice from our poster at AACR that we demonstrate best-in-class activity compared to other ILT2-targeting agents, which includes the most advanced clinical asset, the BioNTech asset. We have demonstrated, in head-to-head studies, that AGEN1571 has not only monotherapy potential, but it's a superior activator of both myeloid activation and T and NK activation. Great. Thank you for that helpful color. I think the second part of the question is what tumors will we study? I think maybe Dhan could start, and Dr. O'Day could finish... Sure. Thank you. I'll turn it over to Dr. O'Day shortly. As you saw from our poster, IO, we demonstrated that HLA-G, which is the main ligand for ILT2, are expressed in tumor types that are independent of PD-L1 expression, so we see this as complementary. Of course, we will be exploring this retrospectively in the clinic. We've also identified, as part of our preclinical development, potential biomarker of response to AGEN1571, which will also be applied to our trial. Steven? Yeah. Mayank, thank you for the question. Obviously, you can see our excitement around the ILT-2, ILT-4 field. Obviously, the myeloid space has been a challenge, but we really feel this is an important space. The ILT-2 that we have put forward with the AACR, as Dan said, has both myeloid as well as lymphoid feature activation features, which may bring it best in class. Obviously the ILT-4 that our molecule that Merck is advancing is showing some early promise. In terms of tumor types, I think, obviously we're gonna do the phase I broadly and look because obviously ovarian cancer, other tumors, even liver metastasis are, may very much be myeloid dependent, pancreas and others. What's really great about our pipeline right now is botensilimab obviously looks like as a next-generation CTLA-4, is really broader than CTLA-4 in terms of its innate adaptive synapse in the Fc-enhanced region. Really, we think bringing broader, you know, T-cell repertoire recognition of weak neoantigens. I think that innate adaptive space that botensilimab brings, and then bringing a myeloid-active drug that has lymphoid coverage also, may be very exciting. We couldn't be more excited about the areas of the pipeline that we're gonna bring forward and then have combination potential. Thank you. Understood. On botensilimab, how might you be thinking of second half or fall medical conferences for incremental data disclosures? If you are able to comment, you know, relative to what you've said before of, you know, obviously melanoma landscape very, very different than pancreatic and with CRC, you do have a specific trial design in place, a comparative study. Any incremental thoughts on, you know, melanoma and pancreatic for development and registration would be helpful. Sure. Well, I think. Let me just tell you, regarding the conference. We have not disclosed the conference that we're gonna be presenting at yet, but it is an important medical conference, cancer conference. Stay tuned and that disclosure will be made shortly. Now let me turn it to Dr. O'Day about the trial design. One of the reasons our phase II trials have taken a little bit of time to commence is, related to the fact that the regulatory environment has gotten to be somewhat all over the place, we've had to make sure that we consult with the appropriate parties, to design the kinds of trials that are going to be meaningful for the next steps in product registration. Now, with that, it's important to note, and Dr. O'Day will elaborate on this- ... that all of the trials in the phase II setting, particularly given the regulatory environment that we're in right now, will be randomized in one way or another. Okay. Randomized to either standard of care, or randomized within the drug that we're studying. Dr. O'Day, please, take it from here. What I would say is, as Garo has said, we are laser-focused on our botensilimab program because the phase I, which is now an extended phase I program, is showing really remarkable activity in a number of solid tumors, and the data continues to be encouraging. Because of this, we see it as a potential foundational partner, and the development plan, which has taken some time to really be very strategic, is really gonna ask three fundamental questions. One, as a single agent, is it differentiated and powerful? Obviously, melanoma is the disease to test that with a clear benchmark for ipilimumab, which we think we can beat. The second is, colorectal, where combination therapy with our PD-1 is showing significant activity. This will be an area where we can see how botensilimab combines with a PD-1. Finally, a very cold tumor like pancreas, given our preclinical data showing very powerful combinational potential of botensilimab with chemotherapy in a mouse model, and some early signal in the clinic with response to pancreas with botensilimab, we think this is an excellent experiment to look at botensilimab in combination with chemotherapy. The three registrational pathways, melanoma, colorectal, and pancreas, are really asking three fundamental scientific questions, single agent activity, combination with chemo, and combination with PD-1. We look forward to following that data and seeing if it can become a real new asset to the IO community in terms of target, and most importantly, clinical performance in unmet needs. Great. My final question was on the OpEx savings that you guys are working on. You know, obviously very astute and makes a lot of sense in this environment to, you know, prioritize as much as you can. Are you able to quantify any of that, or is that sort of work in progress? Maybe also comment on you know, since a majority of the work will be on the botensilimab development and, you know, potential combination regimens in the tumor types we talked about and beyond, how might you be thinking you know, of some of that P&L burden that's to come you know, starting next year? Okay. We haven't quantified the savings yet, but let me tell you that it's going to be 5%-10%. We are talking about significant savings associated with the measures that we're taking. As I said earlier, all these savings are taking place without compromising the delivery of our highest priority programs, which includes AGEN1181. There's no way we're gonna compromise the advancements of AGEN1181, because it is the most advanced, the most promising, potentially blockbuster compound in our portfolio. That doesn't mean we're not excited about the rest of the compounds in our portfolio. It's just the fact that this is the most advanced makes it much more compelling to support near term. As I talked about, some of the other compounds are also advancing. For example, the expenses associated with AGEN1571 through phase 1 clinical trials is relatively modest, and compounds such as our CD 137 are also advancing rapidly with the potential of the option holder exercising the option, which, when it happens, will bring in significant additional cash resources into the company. AGEN1777 on the other hand, is being advanced entirely with Bristol Myers Squibb's support. A lot of these compounds other than AGEN1181 are either representing minor expenditures going forward or are entirely underwritten by our collaborators. Great. Thanks for taking my question. Our next question comes from Qi Wen of Jefferies. Hi, this is Qi Wen at Jefferies. Thank you for taking my questions. I'm asking questions on behalf of Kelly Shi. I do have two quick questions. Number one, for the phase II trials for botensilimab, I just wanna clarify, you said the trials were about to launch. Is that most likely starting Q2 or Q3? Second, is that previously you said in colorectal cancer or cervical cancer, the response rate is very low. Could you maybe give a rough number, like what is likely the response rate that would clear the regulatory hurdle? That's question number one. For question number two, I just wanna follow up on the operating cash expenses. Now, besides the cost containment, is there any other measures you're currently considering that will potentially risk cash? Or, putting it another way, what is the expected milestone payments that you're likely to receive in the next few quarters? Thank you. Okay. Let me start out with the trials, timing of the trials. All three trials that we spoke about, phase two trials, are expected to commence starting in the third quarter of this year. As I mentioned, one of the reasons it's taken so long is for us to be able to confer with the appropriate advisors, authorities and so on and so forth, to make sure that we have considered everything. That's one of the reasons for each trial having multiple arms, including randomization in some cases to the standard of care. All of this means that trial design has been finalized. The only hurdle between now and initiation of these trials is simple operations. We are clear on the kinds of trials that are going to be the subject of our phase II undertakings. Now, with regard to expenses, I think your question, if I understand it correctly, is how. I think that's. Did you have a question on the expenses? Yeah. I'm sorry. Yeah, I just wanna understand, besides the cost containment, is there any other plans to raise cash and, you know. Oh, I see. Yeah. Right. You also wanted to know if there are any additional milestones that we will receive this year. The answer is yes, we expect additional milestones to be received for the balance of this year. We haven't disclosed what they are, but stay tuned. With regard to additional cash resources, as you know, we've been very, very resourceful in doing collaborations with companies and other creative transactions. We haven't tapped. I mean, this is the horrible time to do that. We have no plans of any marketed stock issuance, if that is the question that you're asking. It's a horrible environment to do that in any way. We've been very creative in transactions, and I don't wanna elaborate on what we have in active consideration right now. Everything you do is, of course, has some element of dilution, including partnerships, because you're giving up part of the upside of your compounds. What we plan on doing is to be as creative as possible, including potential royalty transactions that will support our needs in coming years. Thank you. Our next question comes from Matt Phipps of William Blair. Hi, good morning. Thanks for taking my call in advance. Dr. O'Day, I was wondering for your phase two melanoma trial and for relapsed refractory melanoma, obviously the first line market is changing a bit with the recent approval of the PD-1/LAG-3. Just wondering if you're going to enroll patients who have just failed PD-1 plus LAG-3, or would you even enroll patients who failed Opdivo/Yervoy? Yes. Hi, Matt. Yes, obviously the frontline setting in melanoma now involves three options, you know, single agent PD-1 combinations with CTLA-4, ipilimumab, and then obviously the new LAG-3 PD-1 combination. We will be looking at all of those groups. Obviously the space is sort of divided between ipilimumab frontline and then PD-1 monotherapy. We expect that some patients will now be failing. We know they will be failing the LAG-3 combination too, and we'll be looking at all three of those. We think we have not just a CTLA-4 drug, but potentially a broader, you know, drug with AGEN1181, and we certainly wanna understand whether it can rescue any of those scenarios. Okay, great. Thank you for that. Just to help clarify for what to expect in the third quarter, is this just combination? Is there also additional monotherapy updates over what you guys showed at SITC? Is this all tumor types or was it focusing on some of these ones that you're going into phase two as far as additional patients beyond what we saw at SITC? Sorry, Matt, I guess I don't understand the question. You said some botensilimab updates coming in Q3, some additional clinical data. You know, you guys gotta show data at SITC. Is it the patients in cross both- No. ... The monotherapy and the combination? Oh, sorry. Is it just the combination? Yeah. As Garo said, we are continuing to expand the phase I trial in a number of different areas, particularly around the diseases like melanoma, colorectal, pancreas, that we plan to open phase II trials. We will be bringing data forward at important medical conferences later this year, and we haven't announced where, but the additional data around those diseases will be updated at conferences later this year. Matt, to be clear on that note, as you remarked, we had done a phase 1 study with over 100 patients enrolled, and then, we were getting set up to start our phase II studies late last year. For a while these phase \I1 enrollments had slowed down. Because of the longer timelines required for our initiation of phase II studies, we made a deliberate effort, and executed on it, in enrolling patients in specific cohorts that would be the subject of our phase II studies. Since that decision was made earlier on this year, enrollment in those cohorts that will be the subject of phase II studies has actually exploded. We have considerably more patients in those cohorts that have generated data, which will be the subject of our upcoming presentation with additional data disclosure. Does that? Yeah, no, that's great. Thanks for the additional clarity on that. Look forward to it. Thanks for taking my questions. Once again, if you have a question, please press zero one. We have no more questions. Thank you very much, everybody, and thank you very much for your attention in these very busy times. We look forward to fielding your questions and don't hesitate to contact us as required. Thank you, ladies and gentlemen. This concludes today's conference. Thank you for participating. You may now disconnect.