Agenus Inc.

Good day and thank you for standing by. Welcome to the Agenis Third Quarter 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to Divya Vasudevan. Thank you. Please go ahead.

Thank you, Tamiya, 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. As another reminder, this call is being recorded for audio broadcast. Joining me today are Dr. Gerald Armand, Chairman and Chief Executive Officer, Dr. Jennifer Buell, Chief Executive Officer of Ming Therapeutics, Dr. Stephen O'Day, Chief Medical Officer of Agenis, and Christine Klaskin, Vice President of Finance. Now, I'll turn the call over to Gero to highlight the progress we have made to date this year. Gero?

Thank you very much, Divya, and thank you all for your participation and your interest in Agenis as well as Mink Therapeutics. As we have shared previously, our business model is comprised of four pillars. Now, for today's discussion, I will redefine what those four pillars are, and we will primarily talk about pillar number one, two, and three, and I'll make some broad comments about pillar number four. The first pillar is what we describe as our significant value creators. We believe these compounds and opportunities could be significant. And they represent certainly our next generation compounds. And one primary example of that, which we will talk about in some detail today, is our next generation CTLA-4 inhibitor, HN1181. The second pillar is represented by our partner programs and recently launched affiliated businesses, including Mink Therapeutics and Saponix. The third pillar we describe as supportive programs, such as Bostilumab and Zoliferilumab, and I will define what we mean by supportive programs in just a bit. And our fourth pillar, which is a silent component of our business, we don't talk very much about it, but a very important component because without it, we wouldn't be able to accomplish the kind of things, innovations and advancements as we have. And that is represented by our vertically integrated structures comprised of key operational capabilities for the company, including our commercial manufacturing, including our vision technology, which is our response prediction platform designed to facilitate the development of our pipeline by targeting patients who are likely to respond to therapy. Now, I would like to begin the call by addressing the first pillar, which is driven by our flagship program, AGEN 1181. Now, as you know, we have a CITC presentation coming up. This morning, we announced the CITC publication of an abstract summarizing data from a dose escalation study of over 100 patients treated with our next-generation CTLA-4 inhibitor, AGEN1181, as both monotherapy and in combination with our PD-1 inhibitor, Bostelamab. More details will be presented this Friday. I will provide a top-line summary here. AGEN 1181 is the first reported CTLA-4 inhibitor to demonstrate clinical activity in nine cold or treatment-resistant tumors as monotherapy and in combination with bostilumab. Secondly, AGN1181 monotherapy and in combination with falcilumab has shown compelling clinical activity and durable responses across a number of cold tumors such as colorectal, endometrial, pancreatic cancer, and they have been, as I said, in treatment-resistant settings such as PD-1 relapsed and refractory melanoma, non-small cell lung cancer, and cervical cancer. Importantly, we are seeing evidence of more favorable safety profile relative to first-generation CTLA-4 molecules. Also, AGEN 1181 is performing as designed. We designed this model for a specific performance. And so far in the clinic, it is indicating that it's delivering that performance. And that is to expend the benefit of immune therapies to a broader patient population with deeper, more durable responses than what is available to them today. Dr. Steven Roday will share additional comments along with our plans to accelerate development of 1181 alone and in combination with Maltulamab. As I mentioned earlier, full details of this will not be released until the poster is released this Friday at the CITC conference. That's Friday, November 12th. Next, I would like to address our second pillar of our business model, which include our recently launched affiliates and partner programs. As you know, amongst our accomplishments with regard to our second pillar is the launch of these businesses. To start with, on October 15th, we announced the successful IPO of Ming Therapeutics, which has raised over $40 million and a valuation of $400 million. We are pleased that Mink has been one of the best performing IPOs recently, having appreciated 58% as of the closing price race yesterday. Dr. Jennifer Buell, the newly appointed CEO of Mink Therapeutics, will tell you more about Mink programs and share a preview of the three abstracts where we announced recently, which will be presented at CITC this week. Now separately, in September, we also announced the launching of Saponix. Saponix is our subsidiary working on building an integrated vaccine platform based on scalable and secure manufacturing of saponin-based adjuvant. This premise behind Saponix business model is captured in the following, and I'll outline this in four different categories. Firstly, the need for vaccines offering long-lasting efficacy and efficient production has become amplified because of the needs as described by the current reality, which is the pandemic. The durability offered by QS21 Stimulant, which is our flagship adjuvant, has been validated by Shingrix, which offers protection exceeding nine years. And this is particularly important in the current climate where we know the current vaccines are waning in activity after three, six months. and whereas POS21 Stivalan is largely responsible in Schengrix for this long-lasting efficacy. But, on the other hand, the supply is limited due to the reliance on a complicated and expensive extraction process from the Chilean soapbark tree. So, to this end, we're working with two companies, Phytan Biotech and Ginkgo Bioworks, to optimize the plant cell culture process, which we have developed for the purposes of manufacturing QS21 stimulant and next-generation saponin-based adjuvants. This is very important because some of our next-generation saponin-based adjuvants are particularly relevant to respiratory viral infections. Among our objectives is to also establish a platform for developing next-generation adjuvants, effective and scalable vaccine formulations with optimized antigen and adjuvant pairing. And in the future, we'll talk about what we mean by that. Now, in addition to this, also part of our second pillar is the driver of our certainly past and also, importantly, future partnerships. In October, we announced the first patient dose with agent 1-777, our FC-enhanced TIGIT by specific antibody license to BMS recently. This achievement triggered a $20 million milestone payment from BMS and BMS intends to advance AGEN-1777 in high priority indications such as non-small cell lung cancer. We are very excited about the prospects of AGEN-1777. Our clinical stage, AGEN-2373, is a differentiated CD137 molecule. It's a CD137 agonist. Otherwise, in the past it was known as 4-1-BB as well. It is designed to selectively enhance tumor immunity while avoiding toxicity associated with systemic CD137 activation. We presented clinical data at ASCO this year showing that Agen 2373 led to prolonged disease stabilization in heavily pretreated cancer patients with good tolerability, no evidence of liver toxicity, which has been one of the issues with other CD137s. Associated, of course, with this is the fact that this has been done in a monotherapy setting. And we are, of course, starting combination trials with this. AGEN 2377, with our AGEN 1181, which is our next-generation CTLA-4, in PD-1 relapsed and refractory melanoma this year. Another program involves our clinical collaboration partner, NELIM, which has recently dosed the first patient in a combination study of our first-generation CTLA-4 with Nelum's hedgehog inhibitor and chemotherapy in first-line pancreatic cancer patients. Now, next is our third pillar, which is our supportive programs, and they constitute the third pillar of our business model and our strategy. Now, what do we mean by this? Our supportive programs include Boxolimab, our PD-1 anybody, and Zolifrolimab, our first-generation CTLA-4 anybody. These are programs which, on their own, do not represent blockbuster opportunities for us. However, in combination with other novel agents in our portfolio or in combination with agents in other companies' portfolio, they represent important opportunities. So when people ask us, why does the world need another PD-1 antibody, it isn't that the world needs another PD-1 antibody, but we need it because we have an extensive portfolio of agents, and in the context of developing combinations, our PD-1 antibody will make that job a lot easier, a lot more efficient, and at the end, deliver much more prudent economics to the healthcare system and to patients. Among important achievements of our supportive programs was this year, we reported at ESMO back in August that the combination of bostilumab and zolotrilumab resulted in near doubling of responses, that is 33% responses versus what has been reported for pembrolizumab, in PD-L1-positive cervical cancer patients. Now let me touch upon some of the recent announcements that we made and the potential implications of those developments for our company, for our portfolio going forward. As you may have noted, we recently withdrew the BLA for Bostelumab monotherapy due to a technicality associated with the accelerated approval window closing for us, following, of course, the technicality associated of the accelerated window closing, followed the full approval of pembrolizumab in second-line cervical cancer, which the FDA granted the approval of four months ahead of the FDA goal date. Now of note is the fact that this BLA withdrawal was not related to Balsillimab's performance. In fact, our agent met and exceeded predefined clinical milestones for this indication, for this trial. Our agent achieved trial endpoints with 20% response rates in PD-L1 positive patients versus 14% reported in Pembrolizumab labeled. And of course, in single arm trials, it's very difficult to compare these types of numbers to each other, but we are still heartened very much that we showed 20% responses versus 14% responses, as opposed to the other way around, for example. Now, we also completed successfully three FDA-approved inspections for our PDUFA date of October 16th, 2021, with no 483 cited, which is a very big achievement for our company, our organization, and we're very proud of that. Given the clinical benefit demonstrated by Bacillamab, we are planning to launch expanded access programs to give patients and doctors access to both Bacillamab in several countries, perhaps including the U.S., pending the regulatory process associated with expanded access. As a result of our BLA withdrawal, we also announced this continuation of our phosphilimab confirmatory trial, BRAVA, which is expected to reduce our R&D expenses by over $100 million over the next couple of years. Now, with these developments, we expect to end the year with approximately $250 million in cash to execute on our combination development programs for Asia and 1181 and beyond. Now, let me pause here and address two frequently asked questions that have been put to us. One is the fact that we withdrew the BLA for Does that impact our development programs going forward that involve Bostilumab? For example, Bostilumab plus 1181. Does it impact it? Now, before I answer that question, let me address the fact that we have amassed an enormous amount of safety information in over 400 patients treated with Bostilumab. And As I mentioned, we have shown clear activity of Bustelimab, certainly in cervical cancer where we've treated a substantial number of patients, but also in other indications. So we have a highly active PD-1 antibody. Now, with regard to how will this withdrawal of the BLA affect our next steps going forward with combinations, We're certainly going to use the data, both the efficacy data that shows the activity of PD-L1, I mean PD-1 anybody, as well as the safety of it. We're going to use this going forward in our justification of combinations. And given the way we have designed our trials, we do not expect at this stage, we do not expect this to be a hurdle for our expeditious development of combinations. So that's number one. The second question that gets asked is, because of what has happened with the FDA having requested us to withdraw the VLA, a question such as, are we blacklisted by the FDA now? That's going to make our lives difficult going forward. Well, we certainly don't think so, and we certainly hope that that's not the case. If we, provided that we show high activity with our compounds going forward, which we expect to do, which compounds like 1181 alone and in combination with busulinab, provided that we show profound activity, of course, anyone stopping to get in the way of an expeditious approval to bring access to patients would have to be questioned. So we do not expect that our honorable agency will blacklist us or any other company for that matter for reasons that relate to what we have experienced. But having said all of that, we plan on proceeding in a pristine fashion with data that will be generated that could justify the next steps associated with our portfolio of novel agents reaching patients. So with that, I would now like to turn the call over to our chief medical officer, Dr. Stephen O'Day, to discuss the Agile 1181 clinical update shared today in our SITC abstract. And just to remind you that on Friday, there will be more details associated with the release of our poster that will have more data. So we will hold back on some of the details today to respect the confidentiality with the CIDC rules. Steven.