Good morning, ladies and gentlemen. Thank you for standing by and welcome to the Agenus Second Quarter 2020 Conference Call and Webcast. At this time, all participants are in a listen-only mode. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Dr. Jennifer Buell, President and Chief Operating Officer of Agenus. Dr. Buell, please go ahead.

Thank you very much. Thanks for joining us. Today’s call is being webcast and will be available on our website with our accompanying slide material for replay. Before we start, we’d like to remind you that this call will include forward-looking statement including statements regarding our clinical development, regulatory plan and timeline, 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. As a reminder, this call is being recorded for audio broadcast. I’m Jennifer Buell, President and Chief Operating Officer of Agenus and we are delighted to provide an update today on our business. Joining me are Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Dhan Chand, Head of Drug Discovery; Julie DeSander, Vice President and Head of Business Development; and special guest, Dr. Bree Wilky, Director of Sarcoma Translational Research Program at University of Colorado Cancer Center; and Dr. Chuck Drake, Professor and Co-Director of the Cancer Immunotherapy Programs at New York-Presbyterian and Columbia University. Dr. Wilky is one of the foremost experts in sarcoma and the first clinical investigator to dose patients with zalifrelimab, our anti-CTLA-4 antibody in a Phase 1 clinical trial, and she's a Senior Author on a 2019 publication to report on the curative benefits of zalifrelimab in patients with aggressive NGS sarcoma. And Dr. Drake is an internationally renowned expert in immune therapy, immune modulating antibodies, and tumor microenvironment conditioning agents. I'm thrilled to have them with us today. Now, I will turn the call over to Garo to highlight our key achievements in the first half of 2020.

Thank you, Jen and thank you all for your interest in Agenus and for joining us this morning. Our special thanks, as Jen mentioned, to our experts, Dr. Drake and Dr. Wilky for taking the time from their busy practice to review and interpret the latest data from our trials. Both Bree and Chuck have been extremely helpful with their guidance for rapid clinical development paths of our potentially lifesaving medicines. This year, we have advanced our extensive clinical as well as near-clinical pipeline of agents. We have generated important data updates, some of which we will share with you today. You can also expect additional updates on up to five of our programs in upcoming presentations at major conferences between now and year end. Before we go into some of the details, please keep in mind that Agenus should be considered as fundamentally a technology and biology company. This has allowed us to design our broad portfolio to address one simple thing, how to overcome the challenges posed by cancer, which is constantly trying to evade the body's immune system. This is cancer's big trick by the way. Disability for virus is what makes our company special and our portfolio of innovative products, very excited. Using this intrinsic understanding of the immune system and our portfolio of agents, we expect to transform Agenus into a U.S. commercial biotechnology company with a recurrent pipeline of innovative immune-oncology agents. We expect our first commercial products to be our anti-PD-1 we call bali and our anti-CTLA-4, zali antibodies. In addition to investing in innovation, early on, we made a strategic decision to develop our own PD-1, balstilimab. We consider PD-1 as being an essential component for use in cocktails with our pipeline of innovative agents. Although there are several commercially available PD-1s…

Thank you so much, Garo and Jen, for inviting me to speak today and it's wonderful to have the opportunity to speak with all of you about the work that has come out of these amazing molecules and our partnership with Agenus. And so I'm Bree Wilky. I am the Deputy Associate Director for Clinical Research at the University of Colorado and the Director of the Sarcoma program here. So, for those of you who may not know, sarcomas are a collectively rare group of over 100 different cancers of bone and soft tissues. And what they all have in common is that they're quite devastating in the metastatic setting. There are essentially no curative therapies. They tend to be refractory to treatment with overall less than 20% of patients surviving more than five years with metastatic disease. And so immunotherapy for sarcomas is really the next frontier and we've just begun to explore the activity of I/O in these sarcomas. And so during my early years in Miami, I was part of the zalifrelimab Phase 1 trial and I was able to observe for the first time, some absolutely unbelievable responses with CTLA-4, as well as PD-1 antibodies and this disease group. And this actually was so influential that it made me completely change my career and focus on how we can use immuno-oncology to create these amazing responses to all patients with sarcomas. And so that led me to the University of Colorado where now we have both a laboratory completely focused on sarcoma micro environment and immuno-oncology. So, I just want to tell you a little bit about angiosarcomas and I think we have some pictures to go along with this. But angiosarcoma is a blood vessel cancer and the typical story is that these tend to…

Thank you very much Bree. We congratulate you on your work for your patients, which is quite remarkable. Now, building value for our lead molecules, we will expand the benefit of CTLA-4 and PD-1 combinations across different tumors, but also very importantly across different geographies as well. And while we do not have today the capacity to be all over the world from a commercial perspective, it is critical for us to make sure that we have the right partners to be able to expand globally. A few weeks ago, we now announced a partnership with Betta Pharmaceuticals, a national level, high-tech pharmaceutical company based in China. Betta has a strong track record of advancing innovative products in China and a growing portfolio of complementary oncology therapies. They are an I partner to enable us to address significant patient needs in China, which by the way is a rapidly growing market, while also advancing global development of balstilimab and zalifrelimab. I will turn the call over to Julie DeSander, the head of all of our business development efforts to highlight the strategic value of this partnership. Julie?

Thank you, Garo. As Garo mentioned, a few weeks ago, we announced a new partnership with Betta Pharmaceuticals, granting rights to balstilimab and zalifrelimab in Greater China in exchange for $35 million upfront in cash and equity, a $100 million in milestones and tiered royalties up to the low 20s. We're still to expand the benefit of balstilimab and zalifrelimab to patients in this region. China represents an important geography for Agenus. The PD-1 market in China alone is projected to grow to over $14 billion over the next 10 years and the addition of CTLA-4 meaningfully improve the efficacy of PD-1 therapy. We expect balstilimab and zalifrelimab to be the first approved PD-1, CTLA-4 combination in cervical cancer. It was important for us to enter China with a strong local partner who has deep knowledge of the market, regulatory processes and clinical footprint in the region. We selected Betta as our ideal partner based on their success in launching the first innovative oncology product in China in lung cancer, their commercial footprint and their broad clinical portfolio that may benefit from combinations with PD-one or CTLA-4. Together we look forward to bringing the benefit of balstilimab and zalifrelimab to cervical cancer patients in China, which has been times the incidence compared to the U.S. We will also be exploring label expansion opportunities with Betta in areas of high unmet need, which could include indications such as lung, gastric or liver cancer. These indications account for nearly half of all cancer related deaths in China. And our indications with the addition of CTLA-4 significantly improves the efficacy of PD-1 therapy. Finally, we look forward to pursuing new synergistic combinations of these agents with both Agenus and Betta’s other pipeline programs. I will now turn the call over to Jennifer to provide an update on progress of our novel program and upcoming catalysts.

Thank you very much, Julie. And thank you again, Dr. Wilky that was an outstanding presentation. We're thrilled to be in a partnership with you and very exciting to see the maturity of the data from our current trial, our Phase 2 trial of zalifrelimab in refractory patients, patients refractory to PD-1 trials. And it's very early days, so we already have three responses. We have a clinical benefit rate of over 40% with 13 patients with durable disease stabilization, and we're looking forward to the continued maturity of that data. And we're thrilled to be launching a trial specifically in angiosarcoma. Those are really great results. And we're excited about what the future can look like for these patients with such a rare tumor. And I also want to highlight that angiosarcoma is relatively rare tumor, but it's more prevalent in Asians living in the U.S. of course, but also in China. We see a much higher prevalence of angiosarcoma. So we're looking forward to seeing what we can do for patients globally within our own hands and through our partnerships. Now when you focus on value creation, value is created. And in 2015, we set out on a plan to become a commercial company, set up for success. Today, we outlined our path to becoming a commercial company. Garo touched on our clinically validated assets. You've heard some of the data. You've seen data on these programs earlier this year and you will see more data at upcoming medical conferences later this year. We also presented the opportunity that Agenus has to drive differentiated value through combinations. At our core, we are technologists and biologists, we've designed the most innovative and productive research engine in our industry, with more than 21 assets advancing in preclinical and clinical development.…

Hi, Jen. Thank you. I'm very happy to be here. I've been working on immunotherapy since around 2000. Really kind of with not much success until about 2007 when I was fortunate to treat the first kidney cancer patient in the world ever with anti-PD-1 that was on a Phase 1 trial and that patient had a complete response, and remains in complete response to this day. But what I can tell you is seeing complete responses in Phase 1 trials is incredibly rare. And so seeing a PET CR in this setting is really quite interesting and quite unusual actually. As you know, Phase 1 trials are not designed to test activity frankly. They're designed to test safety and so far the data for 1181 points to a very reasonable safety profile with really no hypothesis or severe unexpected immune related adverse events reported. The other thing that I think wasn't quite highlighted from this trial is, sometimes the immune system doesn't quite eliminate the tumor, but enters into long-term disease stabilization and Garo mentioned that on this trial, there were a large number of patients with stable disease. And when people say stable disease, they usually just say it specifically. But if you remember, Garo said it perfectly, these patients had stable disease for greater than six months. So six months is not usually seen in Phase 1 trials, and that really does reflect early evidence of clinical activity for 1181. The other thing that you've listened to this call is the word synergistic actually. And I'm usually in a position to that word, but I can tell you because people won't do the math and prove it, but I can tell you that in kidney cancer, anti-PD-1 and anti-CTLA-4 are indeed synergistic, in terms of complete responses…

Dr. Drake, thank you so much. And you can certainly count on that and we're looking forward to expanding your collaboration without question. Thank you. Thank you again very much. We've got exciting plans for AGEN1181. We plan to commercialize this molecule in the U.S., and potentially will consider licensing ex-U.S. rights on this. In terms of the past to market and breath of development programs, we're going to prioritize indications that are relatively large that are eligible for accelerated approval in the U.S., a fast to market approach to get the molecule into the market for patients. This will be through a few different prioritized indications that include, but are not limited to PD-1 refractory melanoma. This could be the single arm study could form the basis for a first approval with this molecule and this would -- the design of the study could include a monotherapy as well as a combination as Chuck mentioned, the criticality of combinations here for durable curative responses is important and we have the molecules within our own portfolio to do so. We'll also further pursue combination approvals with PD-1 and cold tumors. These include microsatellite stable diseases like you've seen responding with endometrial cancer as well as colorectal cancer and of course, large tumors like non-small cell lung cancer and prostate cancer. Our expectation is Bali combination with AGEN1181 will offer significantly enhanced durability. Now turning to AGEN2373. This is our novel anti-CD-137 molecule. This molecule is designed with important safety and efficacy features as compared to competitor molecules. We've presented some of this publicly. AGEN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing CD-137 costimulatory signaling and activated immune cells, both adaptive T cells and innate and T cells. Dual targeting of both innate and adaptive immunity makes this molecule highly attractive target for cancer immune therapy. Today, I am very happy to report that AGEN2373 has dosed through the one mg per kg dose cohort with no observed liver toxicity, and previously liver toxicity was what has hampered or killed one of the competitor molecules. Furthermore, we've observed durable disease stabilization in patients with ovarian cancer, sarcoma, and non-small cell lung cancer on this early trial. We're advancing the combination as we're advancing the molecule into higher dose cohorts and in combination with balstilimab, while contemplating additional opportunistic combinations with complimentary therapies such as anti-CTLA-4 combinations. Now, I will turn the call over to Dr. Dhan Chand. Dhan will summarize important findings that illustrate the opportunity of novel combination approaches to drive durable and curative responses to cancer specifically, in PD-1 refractory cancers. I'll also ask Dhan to provide a brief update on our TIGIT molecules and the next steps for our allogeneic iNKT cell therapy program. Dhan?

Thank you, Jen. While PD-1 and PDL-1 antibodies have been a spectacular commercial success, only a small portion of patients have had sustainable long-term benefits. Therefore, there is a substantial need for therapies and patients who relapse for do not respond to PD-1 monotherapy. We have presented data on patients responding to our first on next generation CTLA-4 antibodies. We're also advancing some important new therapeutics that may also deliver benefit in selected patient populations. The first decision as you all know, TIGIT is shaping up to be a powerful combination partner with PD-1 antibodies, especially in tumors expressing TIGIT. We have designed two different approaches to ultimately target TIGIT those in corporate our technology innovation through Fc engineering. You'd have seen data at AACR from genetics to just that revealed that they have no monotherapy as suggested as Fc silence is a liability and Fc competence is important. TIGIT is overexpressed in multiple tumors and is known to be a key player in driving resistance to anti-PD-1 and as a result, tumors grow. Blocking TIGIT with antibodies like our monospecific TIGIT antibody AGEN1327, more our TIGIT bispecific AGEN1777 unleashes important immune cells, such as T-cells, and NK cells to killed many types of cancer Agenus was the first to discover and report in Cancer Cell and the ACR in 2019 that TIGIT antibodies require Fc code engagements to promote optimal T-cell activity against tumors. TIGIA AGEN1327 is engineer with this Fc enhancement and has outperformed all tested competitor antibodies and showed superior T cell activation when combined with PD-1 for LAG-3 antagonists or OX40, or CD137 agonists. Our TIGIT is an ideal combination partner for addressing non-resistance mechanism to current checkpoint therapy and with the potential to provide deeper responses. In addition to superior function demonstrated against tested competitors,…

Thank you very much Dhan. Very soon, we hope we expect to announce the initiation of a clinical trial using our allogeneic iNKT cells to treat patients with moderate to severe COVID-19. This trial will be conducted to start at New York, Presbyterian Hospital. We've already cleared the IND and are working with the institution now to launch the trial within the next very near term. iNKT cells or invariant natural killer T-cells are a unique cells type that combines the features of both arms of the immune system, the T cells and NK cells, both the adaptive and innate immunity data and animal models similar to SARS-CoV-2 infection show the increasing the frequency of iNKT cells reduce viral shedding, prevented inflammation driven lung injury, and demonstrated viral clearance. These are all particularly important attributes in the attempt to overcome COVID-19. Beyond COVID-19, these cells have great potential in mitigating cancer, and agenesis advancing clinical trials for patients with cancer planned for later this year. Again, those trials are also FDA cleared to launch the clinical trials. And now we're just working with the hospital on readiness and resource availability during the pandemic. So we expect that trial will start very quickly, certainly in the second half of this year. Importantly, scientists from Agenus presented data most recently Dhan highlighted some of this that Agenus, iNKT can penetrate tissues, they form to the important issues where the action is necessary, giving them a critical advantage to target solid tumors, not served by available cell therapies. iNKTs can kill cancer without requiring genetic manipulation this is really important. We can eliminate significant costs and capacity constraints that are required to modify typical cell therapies through genetic modification. We don't have that unmodified iNKT cells target a specific liquid antigen CD1D on tumors and tumor supporting cells. And iNKT cell activity can be augmented by a lipid ligand also known as alpha Galacto Ceramide. The combination of checkpoint antibodies and activated iNKT cell triggering therapy showed curative potential and PD-1 refractory models as Dan just reported to you now. That supports our clinical plans going forward to go beyond take cell therapies beyond hematologic tumors and move into solid tumors, specifically in combination with active checkpoint modulating antibodies. Agenus has a benefit of a very well designed portfolio of checkpoint antibodies, cell therapy and vaccines which gives us enormous flexibility to develop these novel combination with curative potential for patients with cancer and infectious disease at a significant cost advantage. I'm really excited to share with you as these trials continue to mature in the clinic. I'll now turn the call back over to Garo to summarize our near term catalysts.

Thank you, everyone, all the speakers, I think did a phenomenal job of outlining what we have ongoing. And I know that at times, the enormity of what we have, it gets a little confusing. It's a lot. And but don't be intimidated by the enormity of the immune system. And the complexity of cancer is such that it requires you to battle this disease properly. It requires an enormous army of capabilities and enormous military capabilities, if you will, immune military capabilities to be able to fat hold this properly. For those of you who are interested in digging into it a little bit more, we have an excellent, very well written book by Lorne Samporia that we inventory here. If you contact Amber Henson, you will get a copy of it. It will be a gift from us to you. Particularly the first lecture of that book outlines the way the immune system works beautifully. Getting back now. All of what you've heard so far today and what you haven't yet heard sets us up for an exciting second half of this year and beyond. Among critical path items for us is to initiate our BLA filing for balstilimab and conclude our discussions with the FDA on the confirmatory trial design, which will be our obligation to get full approval down the road for cervical cancer in an earlier disease setting. For balstilimab alone and for balstilimab plus zalifrelimab, I know that based on the outcome of the FDA discussions, we will be prepared for filing not just one, but the combination of a balstilimab and zalifrelimab in patients with refractory cervical cancer. In addition to these exciting plans, we will also present data as Jen spoke about, I mentioned earlier at upcoming medical conferences and scientific conferences,…

Thank you. We will now begin the question-and-answer session. [Operator Instructions] The first question comes from Mayank Mamtani from B Riley FBR.

Good morning. Thanks team for taking my question. Congrats on the progress across seems like several modalities you have in your portfolio. Just quickly on the 1181 way to see the partial response convert into PR. Jen, could you maybe talk about these nine pending scan do you have? What, just qualitative color on what tumor types? And is this going to be some data presented at ESMO in October?

Hi Mayank. Thanks very much for the question. So regarding independent scan, these are patients now we look patients are scanned every six weeks. And so therefore, we get a sense of what's happening with their tumor dynamics over that period of time and what our clinical team and Dr. Anna Wijatyk here with us as well, what they will present effectively is a series of these waterfall plots that allow us to watch the tumors now what we have seen over time, such as for this patient with durable ovarian, as durable response for over 18 months with ovarian cancer, when you're actually looking at the dynamics of that patient scan your -- you're seeing that the tumor is -- tumors. They're never -- not moving in one direction or another. They're either growing or shrinking. And what we're seeing is this continuous shrinking or a negative radiologic finding. And as we watch that, we see that there may be a point at which that could trigger requirements to meet the recessed 1.1 requirements for a consideration is a partial response or a complete response. So we're watching these scans of these patients to see where they are with respect to their tumor dynamics and conversion to responses. So there are a couple of upcoming medical conferences as most certainly one as you'd mentioned. There's also CITC and there are a few other conferences and we do plan to present data on our cervical cancer program, as well as on 1181, an upcoming medical conferences. Now, of course we can't disclose that conferences have yet abstracts are in review is, the process here. So we will inform you as soon as soon as we can, where that data will be presented. But yes, we you can expect clinical updates on our lead programs, and including 1181.

Great, thanks. Thanks for that clarification. And then on to Garo's comment about a lot going on, and especially with, zali and 1181. How do you strategically think about it? So just taking a step back? Is it -- is it stratification by a allele is it you know, matter versus broader tumor types? Like how are you thinking about the two given both are now demonstrating a very good clinical activity?

Thanks very much, Mayank. Very important question here. We are seeing now in the responses. And just to reiterate for AGEN1181. We have a complete response. So we've reported on and now a pet complete response. So two of those patients have responses here, as well as the long term durable stable disease stabilization that we've observed. Now in those responses, what we are seeing is that those patients have the mutation on the CD-16 allele and data presented from us as well as others have demonstrated that those patients are unable or unlikely to respond to a first generation therapy. This does allow us to leverage this particular genetic biomarker as a consideration for stratification. Now there are tumors and of course bali, zali are mature assets there in preparation for BLA filing. And, and we have generated hundreds of patients worth of data with these molecules. We have a significant opportunity to continue to expand the development of these molecules already these validated IO agents in tumors where we know that there is activity with the CLTA-4 and or PD-1. And these approaches these tumor indications expanding in these with bali, zali allows us a few things, generate data and larger market opportunities that that will support inclusion into NCCN guidelines that will allow physicians access to our agents to prescribe for their patients, as well as then, of course, further expanded data for approvals. Now, these are very quick indications, because we already have a path laid out for us, so we don't want to lose the opportunity to take advantage of bali, zali in indications where they know that will work. Now with respect to AGEN1181, we have PD-1 refractory cases in which we believe this molecule could have pronounced activity, particularly in patients with the polymorphism that allows for some enhancement, for identification of response. Our team's overall are critically looking at every patient in our trials. And of course, the goal is to identify patients most likely to respond and include them on the therapy that they are most likely to have a response to. And low hanging fruit for us, of course, is a CD-16 allele patient, it's opportunistic, and it allows us to differentiate and have lifecycle management of our first generation as well as our next generation therapies.

Very helpful. And if I can just squeeze in the final question around your partnered programs, and it's a two part question around you know, 2373, which has the collaboration with Gilead. And then also if you could comment on QS-21, including, I think some comments around, the AH-01 that GSK has been talking about the adjuvant which I think QS-21 has saponin in it. Just remind us the -- with some specificity the kind of work that is going on and what terms you have with your partners, as you progress this in terms of putting out more data?

Sure, I mean, as far as our partnerships are concerned, and as you said, Mayank, we have a Gilead and others you will be hearing some near-term developments, I think, milestones that we may reach with our existing partners. That's an ongoing thing. And going forward as our portfolio crystallizes in terms of generating data, for example, data that we're seeing on 1181, our next gen multi-purpose CTLA-4, that makes the data we're seeing makes it molecule very valuable. In fact, if you look at developments in the last five years, we believe Fc AGEN1181 is one of the most important breakthroughs in I/O, and we also believe, of course, then that's going to be followed with our TIGIT, 2373 and so on. I mean, all these molecules that share a very important engineering design components based on our knowledge of the field, knowledge of biology, knowledge of cancer, the immune system. All these things make our molecules, ones that have not come about by chance, but had been specifically designed to do certain things. And so that's very exciting for us. Now because we do not have a global reach as a company, we will concentrate our commercialization efforts in the U.S. So going forward, you can expect us to increasingly have a higher proportion of our portfolio retained for U.S. rights and license fee from ex-U.S. purposes. So that's going to be the path forward for us. And in our discussions with companies, generally everybody wants to have the U.S. component. But it's also clear, Mayank, as you know, that the ex U.S. cancer market is growing, led by China, but also other geographies. So hence, ex U.S. market in terms of the value that it will generate for our collaborator partners of the future will become much…

Yes. And what learned earlier this week, adjuvant vaccines are definitely, performing relatively better. So, absolutely looking forward to, more updates from you on that and then appreciate the broader color. Thank you so much. Appreciate you taking my question.

Thank you.

[Operator Instructions] Next question is from Matt Phipps from William Blair. Please go ahead.

Hi. This is a Hunter [ph] on for Matt. Thanks for taking my question. Just first, I wondered on 2373. You mentioned that there is no liver toxicity observed. I was wondering, if you could provide some color on sort of any other adverse event and the tolerability there?

Thanks very much for your question. The molecule is really quite tolerable. So we have not, no other deleterious adverse events. No adverse events have really emerged beyond, I might Anna Wijatyk is here as well. She could speak to this and a -- from your feedback and maybe just a little color on that the safety profile.

Yes. So far the safety profile has been pretty predictable and pretty mild. No unexpected events as consistent what -- with the mild and moderate events, immune mediators but not accounted for ordinary.

Thank you very much.

Anna, thank you. And then I was also wondering, I'm on the doxorubicin bali and zali study, I was wondering what the tolerability was looking like there. I know there's only five patients but with this theory?

So, I would like to see if Dr. Bree Wilky is still on the line. I know that she had a clinic requirements starting, Bree, are you still on the line?

Yes, I'm still here. Could you repeat the question though?

Yes. Asking on what the tolerability -- tolerability of the doxorubicin bali and zali study was looking like?

So again, it's a little early. We're actually this is our safety lead in period with the six patients. But I will say that at least today, we haven't seen any prohibitive DLTs that are limiting the combination.

Perfect. Thank you very much.

Sure.

There are no more questions in the queue. This concludes our question-and-answer session. I'd like to turn the conference back over to Dr. Garo Armen, for any closing remarks.

Thank you very much, Jason, and thank you very much for everybody for joining us on this occasion. We look forward to for further updates. And we'll keep you informed, so everyone could be at least as excited as we are. Thank you.

Thank you.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.