Agenus Inc.

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. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. To withdraw your question, please press star then two. 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 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. 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. Dan Chan, Head of Drug Discovery, Julie DeSander, Vice President and Head of Business Development, and special guests, Dr. Bree Wilke, Director of the 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. Wilke is one of the foremost experts in sarcoma and the first clinical investigator to dose patients with Xalfalimab, our anti-CTLA-4 antibody, in a phase one clinical trial. And she's a senior author on a 2019 publication to report on the curative benefits of Zolifrolimab in patients with aggressive angiosarcoma. 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. Wilkie, for taking the time from their busy practice to review and interpret the latest data from our trials. Both Bri 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. This ability of ours is what makes your company special and our portfolio of innovative products very exciting. 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 immuno-oncology agents. We expect our first two 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 of Filamat. 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 and others in development, There are significant advantages to having your own PD-1. The first of this is affordability and flexibility of developing combinations. I'm going to list for you our pipeline, our IO pipeline, which is synergistic with PD-1. And they're extensive. They include our other late stage agent, Zally, the agenus first-generation CTLA-4 that is. AGEN 1181, our multifunctional CTLA-4, which you'll hear about with some data later on from Chuck. Our FC-enhanced TIGIT monospecific antibody, AGEN 1327, with an IND expected to be filed within the next six months. Also, our FC-enhanced bispecific TIGIT antibody, Agen 1777, also expected IND filing in the next six months. Next, Agen 1223, a very exciting bispecific antibody in the clinic, which we have not disclosed the details on the bispecific composition of it just yet. Agent 2373, our CD137-4-1BB molecule, which is in the clinic, and you'll hear about some data from that molecule in a bit. And lastly, our allogeneic INKT cell therapy for cancer with an IND, which has been cleared already. So all this list of compounds that I talked about are Absolutely synergistic with our PD-1 molecule. Another huge advantage of having a PD-1 in-house is to control over pricing these combinations, which is critical because based on our meetings with over a dozen payer groups so far, there is an implied price ceiling if several novel IO combinations are required to be effectively treating cancer. And that, by the way, is a foregone conclusion that combinations will be required for effective treatment and control of cancer. In addition to the advantages offered by having our own PD-1 for our own portfolio, it is also becoming clear that other companies who need a PD-1 to combine with their own pipeline of agents or their own commercial products may prefer to use our PD-1, that is the agenus PD-1, versus others for the same reasons that I have cited which benefit us. Let me now reflect on a couple of other things. In order to move quickly and effectively in the rapidly moving and highly competitive field of immunoncology, we need to have in-house downstream capabilities. In-house, yes, downstream capabilities. These capabilities include development and manufacturing. Manufacturing, as many of you know, is becoming a bigger bottleneck for other companies as a result of the demands, particularly lately, imposed on the system due to a substantial number of COVID-19 products and development programs. Having our own CMC and manufacturing capabilities allows us to bypass these systemic bottlenecks. For example, we have already proactively produced commercial-grade Bali and Zali required for our CMC module expected to be submitted to the FDA in this quarter as part of our expected BLA filing this year. Second, PD-1 antibodies have already generated significant value for several companies. We believe there will be also a significant opportunity for us in a market that today exceeds 22 billion in annual revenues with projections which double those numbers in the next five years. That has become exceedingly clear and also very important, as I mentioned earlier, is that in order to penetrate this large market in a meaningful fashion, With a new PD-1, such as ours, one needs to offer a value proposition with combinations which can provide superior patient benefit. By the way, for those of you who have visual capabilities, we have a series of slides, as you can see on the screen, which are position appropriate, talk appropriate as I go through this. She's comments. In our clinical and neoclinical pipeline, we have several molecules with the potential to offer superior benefit to patients when combined with our PD1, as I discussed a bit ago. Hence, having our own PD1 is critically important for our own overall commercial success, including Very importantly, the optimization of the revenue potential of our own PD-1 Valley. Today there is only one commercially available PD-1 for a CTLA-4 combination. It is approved in six cancer indications with expected combined revenues of about $13 billion this year. Based on data available to date, The cancer target for PD-1 CTLA-4 combinations are in their commercial infancy as emerging data on this slide suggests curative benefit to patients in potentially more than 20 different types of cancer. We're advancing our PD-1 antibody, Bostilumab, as a monotherapy in combination with Zolifrolimab, our anti-CTLA-4 antibody. As you know, our first target is patients with relapsed refractory cervical cancer who have failed first and second line treatments. As you can see on this slide, Cervical cancer afflicts about 10,000 women in the U.S. every year. Currently, approved therapies have limited activity with response rates of 10 to 15% and with limited durability of responses. Based on the data we have seen so far in cervical cancer, our anti-PD-1 antibody may offer improved clinical benefit compared to other PD-1 antibodies. These results are expected to be presented shortly at an upcoming conference this year. When combined with the lefrolimab, we see improved and longer-term responses in cervical cancer patients. And when we look at clinical data on squamous cell carcinoma of the servings, patients, which about accounts for 70% of total cervical cancers, we see a doubling of these responses with our products. Combination, by the way. Agenus commercial plans include providing access, this is a very important point for us, to all patients with cervical cancer, regardless of their health coverage and affordability. I am confident we can reach this goal while simultaneously creating significant value for your company. The next slide shows the clinical facts of PD-1 beyond cervical cancer. The combination of anti-CTLA-4 and anti-PD-1 has improved response rates and very importantly durability of responses in more than 14 tumor types so far. While our first indication being pursued is cervical cancer with our combination as well, we are contemplating to develop our PD-1 CTLA-4 combos in indications like non-small cell lung cancer, melanoma, renal cell carcinoma, hepatocarcinoma and and a number of others. Today, I will be providing you with an update on our Phase 1-2 trial with XALI, Xalifurlimab. I know I'm switching between XALI and Xalifurlimab. I don't want to confuse you, but XALI is the short name for Xalifurlimab. So, today we will be providing you with an update on our Phase 1-2 trial of XALI as a monotherapy and in patients refractory to PD-1. This is an important and growing population of cancer patients. We have enrolled 39 patients into our Phase II study of Xelofrilumab in patients who have failed anti-PD-1 therapy. In this trial, we have achieved three partial responses in patients with angiosarcoma famous carcinoma of the head and neck, and neurocrine cancer. In addition, however, we have achieved durable disease stabilization, and that means beyond six months in 13 patients so far. That represents a 40% clinical benefit rate with our first generation anti-CTLA-4 antibody for patients for whom there's really no treatment at all. These data build on a growing body of evidence that the addition of CTLA-4 alone in PD-1 failures may provide us with a rapid registration opportunity for zoliferilumab as well as we can extrapolate this to our multifunctional next generation CTLA-4 antibody Agent 1181, in patients who have no treatment options today at all. Also importantly, we continue to see complete and partial responses with zolifluamab in angiosarcoma, a rare tumor for which there are no approved therapies. We have invited Dr. Brie Wilkie, who is an absolutely world-renowned sarcoma expert who has led the clinical trial initiative at Colorado University to discuss our data. Bri was the first physician to treat a patient without phase one study with zoliferilumab and to report on an early observation of the curative potential of zoliferilumab with or without balistilumab. in Patients with Angiosarcoma. Thank you for being with us today, Brie, and I turn it over to you. Thank you.