Agenus Inc. (AGEN) Q1 2019 Earnings Report, Transcript and Summary

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Agenus First Quarter 2019 Conference Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Dr. Jennifer Buell, Chief Operating Officer of Agenus. Dr. Buell, Please go ahead.

Thank you, operator. Today’s call is being webcast and will be available on our website for replay. Before we start, we would like to remind you that this call will include forward-looking statements, including statements regarding our clinical development plans and time lines, partnership opportunities and time lines and our financial position. 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 am Jennifer Buell, Chief Operating Officer of Agenus. Joining me today are Dr. Garo Armen, Chairman and Chief Executive Officer; Mr. Bruno Lucidi, the CEO of our AgenTus, Cell Therapy Business Entity; and Fr. Dhan Chand; a key member of innovation team; and Christine Klaskin, our Vice President of Finance. I will begin by stating that 2019 is off to a strong start. Enrollment in our two trials, which are designed to support a BLA filing has been faster than our earlier projections. Hence clinical data from these trials may come before the end of this year, which means we may be able to file our first BLA earlier than anticipated in 2020. As you know, we have two registration trials underway; either trial or both could support BLA filings. The first of these trials is our PD-1 monotherapy trial in second-line cervical cancer. The second is a combination of PD-1 and CTLA-4, also in second-line cervical cancer. I would like to state that our combination trial strategy can provide us with an important competitive advantage in this cancer type and in others. Secondly, enrollment in our second-generation CTLA-4, our AGEN1181 trial is also proceeding. We believe our second-generation CTLA-4 could be a best-in-class molecule. And it has the potential to expand the commercial potential of our PD-1 beyond what our first-gen CTLA-4 combination offers. We anticipate early clinical readouts of our next-gen CTLA-4 also by the end of this year. We plan to commence combination trials of our second generation CTLA-4 with our own PD-1 in the next several months. Clinical data from our second-generation CTLA-4 could represent a very important value inflection point for us for defining our own U.S. commercial opportunity as well as for our ability to monetize on the ex-U.S. right for this molecule. Our product discovery and product development focus is on achieving high responses and durable responses. This means we are focused on shorter trials, lower costs trial and more rapid product development registrations as well as combination product registrations. Our opportunities for combinations also includes combinations with our checkpoint antibodies, our bispecifics, our cell therapies and our vaccines. Our access to these combination agents is a major advantage, which helps our ability to rapidly deliver on our high impact strategy. We define high impact products as products with durable high responses and/or strategies that address tumor types or cancers for which there are no currently effective treatment options. Generally, these attributes translate to shorter, less costly trials designed for accelerated FDA approval. Our integrated capabilities from antibody discovery to cell line development to GMP manufacturing are key to our ability to build a pipeline of products quickly and at lower costs as well. These advantages allow us to manage a larger portfolio of discoveries and development programs at a much more efficient costs and with higher quality than would be possible without these internal capabilities. Our innovation and our speed in drug discovery has enabled us to deliver the largest preclinical collaboration in oncology in 2018, the Gilead transaction with $120 million upfront cash, $30 million in equity investment and potentially $1.7 billion in additional payments plus royalties. Today we will highlight two of our most exciting novel antibodies. One has already entered the clinic, the other is expected to enter the clinic in the coming months. Our second-generation CTLA-4, AGEN1181 and our novel anti-CD137 molecule, AGEN2373 have unique advantages over other antibodies targeting the same receptors. A key contributor to these potential best-in-class antibodies, Dr. Dhan Chand, is going to tell you more about these molecules and their unique attributes shortly. Additionally, we are advancing our second-generation, currently undisclosed bispecific programs towards IND. AgenTus, our cell therapy subsidiary, has made significant progress as well. Last year at this time, the company was building a team, and advancing a single lead candidate. Today, AgenTus has 39 employees, a robust pipeline of five TCR candidates and two CAR-T candidates and are on track to file INDs for a proprietary – our proprietary allogeneic cell format and an autologous TCR for patients with cancer this year. Bruno, the CEO of AgenTus, is with us for this call and will provide an update on the progress of AgenTus. Lastly, our earlier innovations have been important catalysts for at least one blockbuster product for our partners. Sales of GSK’s Shingrix vaccine powered with our QS-21 has achieved over $1 billion in revenues in its first year of launch, it’s expected to reach $1.3 billion in revenues this year. Also, this year, GSK announced the launch of a large trial with the QS-21 containing vaccine, Mosquirix, the first ever malaria vaccine. The global burden of malaria is immense, and more than 400,000 people dies each year. We are excited to contribute to the potential eradication of this deadly disease. Finally, the Bill & Melinda Gates Foundation provided us with a grant of about $1 million to enable development of an alternative manufacturing process of QS-21 to ensure the continuous future supply of this important adjuvant. I will now turn the call over to Garo.

Thank you, Jen. As Jen mentioned, our highly productive discovery capabilities have resulted in our broad pipeline of immuno-oncology agents, which we intend to use for establishing our own commercial presence in North America. This productive discovery capability has also resulted in the largest upfront payment for a preclinical collaboration last year. This collaboration with Gilead was an important defining point for us, which among other things served as an important external validation of our innovations over the last five years. As you know with the 4 antibody acquisition about five years ago, we transformed Agenus into a broad based immuno-oncology engine covering antibodies, cell therapy, vaccines and adjuvants for very critical components of the army that is required to fight a disease like cancer. We consider individual elements of our portfolio and the ability to generate smart combinations to be key to developing second-generation immuno-oncology therapies for patients who need effective and importantly durable treatments. We are a company with the capacity to create. We invent and advance novel products at Agenus. We have the foundation – the tree, not just the fruit. We nourish our creativity, we cultivate our innovation and we harvest our productivity. We make important advancements for the benefit of all of our stakeholders, including patients, the healthcare system, our shareholders and our team. We have delivered and continue to deliver with a high sense of urgency, because we know lives are at stake. In the past three years we have delivered 11 INDs with additional INDs planned for the first half of this year, setting records in the immuno-oncology industry. We filed six INDs in 2018 and among these include our proprietary second-generation CTLA-4. This is a very exciting molecule, which we plan to generate meaningful data this year and engage a partner to commercialize in the rest of the world, while we retain the U.S. commercial rights for ourselves. In addition to our second-generation CTLA-4, we’re also on track to file an IND for our CD137 agonist an off-the shelf phosphorylated neoantigen vaccine in addition to that. In a few minutes you will hear from Dr. Chand speak about our second-generation CTLA-4 and our anti-CD137 molecules and specifically what makes them so powerful. These are just two in our pipeline of novel molecules that we will specifically showcase during this call. And I must add that any one or combination of these molecules has the potential to be blockbuster products. Our operational successes have put us in a powerful position this year. We have enrolled as Jen mentioned, our PD-1 and CTLA-4 trials faster than our original projections. And we could potentially file our BLAs earlier than anticipated in 2020. We plan to develop, register and launch our PD-1 and CTLA-4 in the U.S. with a first indication in second-line cervical cancer. We will explore rest of world partnerships to expand our footprint and allow access to patients outside of the U.S. Cervical cancer as you heard is a formidable disease and the best available molecules delivers up to 15% responses with current PD-1s. We believe, we have an opportunity to improve these response rates with our combination strategy. We also plan on pursuing opportunities beyond cervical cancer. Our second-generation CTLA-4 can potentially provide us with the opportunity to significantly expand the utility of our PD-1 into other cancers. The genius of Agenus lies in the intelligent design of our molecules and intelligent design of our clinical trials. As you heard from Jen, our objective is to develop high impact therapies designed to achieve high response rates and long durability of responses. Having our own discovery, our own manufacturing and our own combination development agents is key to achieving this objective. This is core to our advantage. Last year, one of the Nobel Prizes for medicine was awarded for work done to block CTLA-4 in order to stimulate the immune system to attack cancer. First-generation agents, including our own CTLA-4 blocking agent, AGEN1884, have shown curative benefit in a small portion of otherwise incurable cancer patients. We believe we can expand the benefit to more patients by improving on the first-generation CTLA-4 blockers. We believe we have achieved this with our second-generation CTLA-4, AGEN1181. I will invite one of our lead innovators, Dr. Dhan Chand, to discuss why CTLA-4 is so important and why we believe our second-generation CTLA-4, AGEN1181, has best in class features and will be so important for treating patients. Dr. Chand will also discuss our novel CD137 blocker expected to be in clinical development this year. Dr. Chand?

Thank you, Garo. I am delighted to discuss two key assets in our novel second-generation pipeline. Why they are important? And how we believe they will change the treatment paradigm? First, I will discuss CTLA-4 and emphasis why it is so important. CTLA-4 blocks the ability of the immune system to kill cancer. It prevents the initial T cell response to cancer and furthermore, it augments the immune suppressive function of regulatory T cells. Together, CTLA-4 inhibits the ability of the immune system to effectively fight cancer. Blocking CTLA-4 with antibodies like AGEN1884 or AGEN1181 unleashes the ability of the immune system to kill cancer. Importantly, blocking CTLA-4 also improves the durability of the anti-cancer response. These are critically important pathways in our efforts to conquer cancer. Durability of response is one of the hallmarks of anti-CTLA-4 therapy. When we block CTLA-4, like in metastatic melanoma, we see durable anti-tumor immunity. In fact, it was the work by Nobel laureate Jim Allison on CTLA-4 and anti-CTLA-4 therapy that allowed us to start putting the words cure and cancer in the same sentence. In multiple cancer types, where PD-1 brings clinical benefit, adding a CTLA-4 blocking molecule, increases the response rates and durability of responses. We have observed this in metastatic melanoma, MSI high colorectal cancer, and renal cell cancer, to name a few. Today, the combination of CTLA-4 and PD-1 are the only clinically validated immune oncology combinations. As remarkable as anti-CTLA-4 therapy is at promoting durable anti-tumor responses, only a small subset of patients today benefits from anti-CTLA-4 therapy, highlighting the need for better anti-CTLA-4 agents and/or combination therapy. Early data on CTLA-4, in patients treated with a higher dose, revealed some immune related toxicities and therefore CTLA-4 was perceived as toxic. Moreover, early clinical data involving anti-PD-1 therapy demonstrates similar response rates as anti-CTLA-4 therapy with a more favorable toxicity profile. As such, we saw a shift away from the use of CTLA-4 in favor of PD-1 antibodies. As a matter of fact, there are a scarcity of first generation CTLA-4 molecules and even fewer next generation molecules. Today we believe that we have the most advanced clinical stage antibodies in both categories. I will now briefly discuss why AGEN1181 expands the criticality of the benefit of this target. AGEN1181 or second-generation anti-CTLA-4 antibody, leverages a breakthrough discovery made by Agenus scientists, which was published in the journal Cancer Cell in June 2018. It represents a significant advancement in anti-CTLA-4 therapy with the potential for deeper clinical responses and better combination potential. We discovered that one of the key factors that influence the therapeutic activity of anti-CTLA-4 antibodies is their ability to interact with cancer-fighting T cells and a subset of immune cells known as antigen presenting cells. This interaction is accomplished in parts by the Fc-region, an important section of the antibody that binds to Fc gamma receptors on antigen-presenting cells. Optimizing this interaction through engineering of the Fc-region of the antibody to better engage a specific Fc-receptor, Fc gamma RIIIA, on antigen presenting cells, significantly enhanced the therapeutic potential of anti-CTLA-4 therapy. AGEN1181 was designed to block CTLA-4 and harness this novel Fc gamma-related mechanism that is not captured by the first generation anti-CTLA-4 therapies. Compared to the current generation, AGEN1181 has an enhanced ability to promote superior T cell priming and T cell activation. T cell priming is a crucial step in launching potent immune responses against cancer. Moreover, AGEN1181 is better designed to promote the depletion of intratumoral regulatory T cells as compared to the current generation of anti-CTLA-4 antibodies. Intratumoral regulatory T cells represent a significant barrier to successful anti-cancer immune responses. In addition to improved single agent activity, AGEN1181 has shown superior combination potential in preclinical tumor models with other cancer therapies such as immune modulatory antibodies, including anti-PD-1 therapy, and vaccine therapies. We are advancing our second generation CTLA-4 molecule, AGEN1181, as a monotherapy and in combination with our anti-PD-1 molecule and anticipate data readouts as early as the second-half of this year. Now, very briefly on AGEN2373, our anti-CD137 molecule. AGEN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells, both adaptive T cells and innate NK cells. The potential to dually target innate and adaptive immunity makes CD137, a highly attractive target for cancer immunotherapy. Additionally, the unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.

Thank you, Dhan. What Dhan just described is literally a small size of the very exciting innovation that are ongoing at Agenus. I will now switch briefly to a very exciting new paradigm represented by our second generation bispecific checkpoint antibodies. Our emphasis is new discoveries that can have high impact in the treatment of patients with cancer. What I mean by this, our products that can move to market faster, and with this provide benefit all our stakeholders. Hence, our objective is to emphasize high impact therapies, as you heard before, which lead to small, shorter trials, in our efforts to achieve patient benefit and eventual regulatory approval and subsequently commercial launch (25:17) all rapidly. And this capacity allows us to be able to manage a broad portfolio simultaneously with that incurring the high expenses that would be typically associated with the management of such large portfolios. Our first-generation bispecific molecules targeting important tumor escape mechanisms were the subject of our recent collaboration with Gilead. Our second-generation bi-specific molecules are rapidly progressing towards IND filings, and these second generation bispecific antibodies address additional important mechanisms such as co-inhibitory pathways in natural killer cells and T cell biology, targeting tumor associated macrophages, tumor/stromal-targeted neutralization, and multispecific cytokine targeting agents. I realize that all of this sounds like a mouthful, but the biology and our understanding of cancer immunology has advanced for us to have validated the importance of these mechanisms. Our capabilities and pipeline have been key to our ability to enter into very important partnerships such as Gilead and prior that with Incyte and Merck and GSK. We expect additional partnership transactions to be an important part of our strategy going forward including this year. Given the productivity of our discovery engine, we also expect our pipeline of innovation to be driving our own commercial strategy. Our strategy is to balance between monetizing a portion of our discoveries every year, while keeping rights to North America. We expect to generate meaningful clinical data this year in our efforts to monetize on ex-U.S. rights with significant value consideration. This strategy will be tested with our second generation CTLA-4 antibody currently in clinical development with prospects of generating clinical data by year end both in a monotherapy setting and in combinations. We possess key components as I said earlier of immuno-oncology requirements is included checkpoint modulating antibodies, neoantigen vaccines, adjuvants, and adoptive cell therapy approaches, both with TCR and CAR-T therapies all of which exists in-house. Cancer is a complex disease and we believe that combinations will be necessary to deliver optimal benefit in patients in a second generation treatment paradigm setting. Our cell therapy business, AgenTus has made important progress on the advancement of the pipeline to IND filings this year, as well as progress towards our first round of private financing ahead of a potential IPO. I am delighted to invite the CEO of AgenTus, Bruno Lucidi, next to provide you with the progress we have made at AgenTus. Bruno, the floor is yours.

Thank you, Garo and thank you for the opportunity to provide an update on our exciting cell therapy company AgenTus. As you all know, Agenus had the foresight to separate its cell therapy efforts from the parent company 18 months ago. And you heard recently, our collaborator Gilead decided to do the same with its pioneering cell therapy company Kite. Separation of cell therapy from rest of immuno-oncology is a prudent strategy based on business model considerations. Let me start by stating that as Jen alluded to earlier, AgenTus has made very important progress in building a team, expanding our cell therapy construct capabilities, substantially expanding our pipeline of TCRs and CAR candidates, and very importantly, advancing our novel and proprietary allogeneic cell format. As you all know, allogeneic format is critical to broadening the applications of cell therapy from the limited market served by cell therapy today. Despite the remarkable success and clinical benefit demonstrated by, what we call, first generation cell therapies to date, current approaches have their own limitations. This include, the very limited cancers indications today’s cell therapy serves, long lead times for manufacturing, complicated logistics and very high costs. Our technologies, assets and capabilities are designed to address every one of these issues. In addition, because of our ability to piggyback on our discovery capabilities at Agenus, AgenTus has a significant advantage in delivering high impact cell therapy products and consistent with our overall strategy do it fast. A number of our lead cell therapy candidates which are in the category of what we call second or third generation cell therapy products, are targeting solid tumors which account for more than 90% of today’s cancers. In the past year alone, at AgenTus, we have built a proprietary discovery platform for CARs and TCR, which is based on our clinical validated and highly productive antibody drug discovery platform. Our core capabilities in bioinformatics, structural and computational biology, molecular and cell biology, and importantly, our access to Agenus pipeline of rational immuno-oncology antibodies which constitute intelligent cell therapy combinations provides AgenTus with a unique advantage not common in the cell therapy universe. I will provide you with some highlights of our capabilities and accomplishments. First, in the past year, we have built and perfected a high throughput drug discovery engine that is unique to us. This engine can generate high quality TCRs and CAR therapies. TCRs are critical for targeting solid tumors and our TCR drug discovery capabilities provides us with very unique advantages over most others. Another important critical success factor is our proprietary allogeneic platform and I’m happy to say, we are on track for our first IND filing of our allogeneic cell format by year end. Our ability to have access to Agenus antibodies for optimal combinations is yet another major advantage for us. Immediate priorities for combination agents for our portfolio of cell therapies include our PD-1, CTLA-4 first and second generation and CD137. Also something unique is our novel and proprietary phosphorylated antigen targeting platform, which we call PTTs that provides us yet with another unique technology advantage. Agenus has developed a library of over 2,000 phosphopeptide targets and we, at AgenTus, are the only cell therapy company with access to TCRs to some of these phosphopeptide targets. As you can see the progress we have made in such a short period of time is a tribute to our stepped up immuno-oncology efforts at Agenus over the past five years as well as the advances made by our team at AgenTus. In the past months, we have also secured a substantial grant-based funding from the Belgian Wallonia Government to advance our cell therapy manufacturing capabilities. Currently, we are advancing – in advanced stage discussions for a private round of financing which we are aggressively targeting to close over the next few months. Now I will turn the call back to Garo.

Thank you very much, Bruno for articulating the exciting developments at AgenTus. Before turning the call over to Christine for recapping our quarterly financial report, I wanted to summarize a few key points. One, we have developed and have been successfully practicing a complete set of capabilities and immuno-oncology agents in our efforts to rapidly deliver high impact products. Two, we have an outstanding pipeline of novel and second generation immuno-oncology agents that we expect will deliver substantial benefit to patients with cancer. Three, our operational excellence has put us on a path to a BLA filing that not only remains on track but could even be ahead of schedule. And four, we are emphasizing smaller, focused trials to achieve high response rates specifically targeting patients who are not being effectively served by today’s first generation immuno-oncology agents. To appreciate the full value of our portfolio and protect the interests of our shareholders, we recently launched an innovative first of its kind financial mechanism which we call BEST Biotech Electronic Security Token. BEST is designed to preserve maximal value for our existing shareholders while providing funding for the expanded development of our PD-1 antibody beyond cervical cancer. BEST is a digital security, which provides the opportunity for investors to invest in a single, late-stage asset. And to be clear, BEST is not a cryptocurrency, BEST is a financial instrument designed to have minimal dilution to our shareholders. Given our decision to limit the money raise through this innovative financing mechanism, we expect BEST will only impact a small portion of the initial PD-1 income. As you know, the quicker and broader the – we expand the opportunities for our PD-1 antibody, the greater the leverage and value for our current shareholder as well as BEST holders. I know that a lot of you are wondering about the status of our BEST offering. We are taking our time, besides the fact that we are not in a rush to do this and we would like to make sure that it is done properly. It is after all a first of its kind biotech financing instrument. Its structure must be perfected, and the potential audience must be properly selected and qualified. For those of you who may think BEST is a gimmick, we would like to encourage you to read more about it and approach us with your questions that surely deserve clarification. In addition to BEST being an innovative biotech instrument, financing instrument that is, we believe it has the potential to streamline health care commerce down the road. That’s for much more expensive decisions but not the first phase of our intent. There are some lingering questions out there, for example, will BEST investors sell their Agenus stock and buy this digital security? Based on everyone we have spoken to so far, this is clearly not the case and we don’t expect this concern to be an issue as it often is in the case when companies issue convertible securities, which allows for arbitrage. So for clarity, we will take our time to test BEST and expect to complete the offering before the end of the year. Now I will turn it over to Christine Klaskin to provide financial highlights. Christine?

Thank you, Garo. We ended the first quarter of 2019 with a cash balance of $158 million. This compares to a $53 million balance at December 31, 2018. For the first quarter ended March 31, 2019, we reported net income of $17 million or $0.14 per share compared to a net loss for same period in 2018 of $54 million, or $0.53 per share. In this first quarter, we recognized revenue of $80 million which includes revenue from our transaction with Gilead and non-cash royalties earned. I’ll now turn the call back to Garo.

Thank you, again, Christine. In closing, we expect the following key catalysts for 2019. One, completing accrual of PD-1 and CTLA-4 trials by year end, both of these are designed to lead to product approval in the U.S., based on of course the outcome of the data from the trials. Two, upon a successful outcome of these trials, we expect to file our first BLA in 2020. Three, initiate first-in-class combinations with our second generation CTLA-4 and our proprietary PD-1 molecule. Four, advance additional breakthrough discoveries and file at least three additional INDs in 2019. Five, advance our next generation best-in-class molecules into the clinic, including our selective Treg depleting bispecific, AGEN1223. Six, advance our cell therapy programs and have AgenTus funded independently in anticipation of a potential public offering. Seven, complete our BEST offering. And lastly, but not least, very importantly, we expect to complete one or more business development/partnership collaboration transactions in 2019. We are committed to our mission of delivering for our patients and for all our stakeholders. Our efforts and staying power over the last 25 years speaks to this commitment. We thank you for your staying the course and joining us on this journey. Now we would be happy to entertain your questions.

We will now begin the question-and-answer session. [Operator Instructions] We’ll take our first question from Harshita Polishetty with B. Riley FBR.

Hey, guys. Good morning. Congrats on the progress and thank you for taking my questions. So two quick ones from me. The first one is on your next-generation CTLA-4 trials. Could you talk a little more about what we should expect in the data later this year with regard to the number of patients? And any other details you can provide there on the trial? And then how you’re thinking about combination? Of course your PD-1 is one, but what are some other combinations you’re thinking about? And then my second one is on the cell therapy platform. What are the 2019 INDs in the pipeline? And any additional color on the financing decisions would be helpful. I apologize if I missed this in the prepared remarks. Thank you.

Sure. Let me just take a crack at the first question in terms of our CTLA-4. As you know, we started our dose-escalation trial recently. And so far, we have accrued patients at the prescribed date – rate that is allowed for us. And at the end of each dose, we expect to introduce a combination. So we are expecting our first combination to start in the next two to three months, with the lowest dose that is. And by the end of the year, we expect to see an early glimpse at the clinical trial, certainly safety as well as perhaps some elements of efficacy with this compound and with combinations. In terms of your second question, if I understand it correctly, you are asking for our financing plans. So as much as and…

AgenTus.

AgenTus financing plans. So AgenTus financing plans include a private offering, which will be our first round of private financing that we expect to complete in the next several months. And beyond that, we will entertain the possibility, and we are in the process of evaluating right now where this will be, whether it will be done overseas or domestically or both, to do a public offering sometime next year. Does that answer your question, Harshita?

Yes, yes, it does. Thank you, Garo.

[Operator Instructions]

I suspect, operator, that we have been very complete in our description of our business and our plans. So if there are no further questions, we can conclude our call. And I must say, we appreciate your attentiveness, appreciating the fact that clearly cancer and immunology of cancer are complicated high science, and – but we have basically persevered over the last 25 years and built a phenomenal team and phenomenal capabilities to tackle this challenge of complicated high science that constitutes cancer and immuno-oncology. So with that, we invite you to continue your communications with us. As you know, we are upgrading our communication capabilities with a newsletter that is published every two weeks on Mondays. And those publications are topical, so they include different facets of our science and our strategy, the outcomes. We will continue to do that. We haven’t missed a beat, I believe, from the start of this process. And we will also engage in additional communication formats and forums, including Science Days that will go into the reality of our science in some detail, and that will be organized sometime this year as well. So I think all of this is being recorded so we cannot hide from it, and we welcome all of that. So with that, I will conclude our call.

This conference has now concluded. Thank you for attending today’s presentation. You may now disconnect.