Agenus Inc. (AGEN) Q2 2016 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen, and welcome to Agenus Second Quarter 2016 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference is being recorded. I would like to introduce your host for today’s conference Ms. Michelle Linn. Ma’am, please begin.

Thank you. Welcome to the Agenus second quarter 2016 conference call. Before I continue, I would like to remind you that this conference call will contain forward-looking statements, including statements regarding the Company’s potential income stream, research and development, and clinical trial activities, the publication of data and potential application of the Company’s technologies, and product candidates toward the prevention and treatment of diseases. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. Reference to these risks and uncertainties is made in today’s press release and they are disclosed in more detail in our most recent filings with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this call and Agenus undertakes no obligation to update or revise these statements. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. When evaluating Agenus’ business and securities, investors should give careful consideration to these risks and uncertainties. As a reminder, this call is being recorded for audio broadcast. With me today are Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Robert Stein, President of R&D; Dr. Jennifer Buell, Vice President, Development Operations and Program Management and Christine Klaskin, Our Vice President of Finance. During this call, Garo will provide a corporate update, Bob and Jen will provide an R&D update, and then Christine will review our financial results. We will then open up the call for questions. With that let me turn the call over to Garo.

Thank you, Michelle, and thank you all for joining us this morning. I’m delighted to report that during the past quarter, the progress we made with our immune-oncology programs has gained additional momentum. We are in line with the major theme at this year’s ASCO, both with our overall immune-oncology strategy as well as the breadth of our immune-oncology programs which includes our combinations strategies. During the quarter, we also continued to advance our checkpoint antibody programs, both in the clinics and in research. Our VP of Development Operations, Dr. Jennifer Buell, and our President of R&D, Dr. Stein, will update you further on these topics in just a bit. First, I will summarize the advances we made since the beginning of the second quarter and highlight our near term plans and milestones. To start, we delivered antibody candidates to Merck. This event triggered the first milestone in our agreement. Under this agreement, we can receive up to $100 million in total milestones as well as [royalties] (Ph). We strengthened our clinical development team with the addition of Dr. Jean-Marie Cuillerot, who was appointed as the Head of our Global Clinical Development. Jean-Marie has played key roles in regulatory filings of two of three known validated antibody targets, including CLTA-4 and PD-L1 antibodies. Most recently, he served as the Global Head of Clinical Development Immuno-Oncology at Merck Serono, where he advanced Merck Serono’s PD-L1 antibody, avelumab from pre-IND to regulatory filing. He was also responsible for delivering the data set leading to the co-development deal with Pfizer, which involves an upfront payment of $850 million, milestone payments of 2 billion and a 50/50 partnership for ipilimumab. Needless to say, Jean-Marie's experience will be critically relevant to all of our immuno-oncology developer strategies. Including our own CTLA-4 and our own PD-1 programs. Thirdly we added fourth member to our Board of Directors, lf brings more than 30 years of valuable pharmaceutical industry experience in leadership roles having most recently served as Chief Executive Officer of Lundbeck. lf previously served as President of Wyeth, Europe, Africa and Middle East and most recently serves under Board's of several biopharmaceutical companies including UCB and Nestle Health Sciences. On the clinical front we advanced our proprietary programs, our CTLA-4 antibody now is in the clinic. We believe our molecule is the only clinical stage CTLA-4 antibody in development other than Bristol-Myers ipilimumab and Astrazeneca’s [tralokinumab] (Ph). We expect to initiate combination trials with our CTLA-4 antibody in the first half of 2017. Since this year's ASCO we have received significant interest from companies with regard to our CTLA-4 program. If we do partner this program we anticipate retaining certain rights and we choose a partner who shares our strategic vision for how it fits into the evolving immuno-oncology ecosystem. Next our collaboration with Incyte continues to progress successfully as we advance our anti-GITR agonist antibody 1876 in the clinic. In addition we expect Incyte to begin clinical studies with our OX40 agonist antibody in the second half of this year. We expect to initiate several clinical programs with our additional immuno-oncology candidates within the next six months. It is also important to point out that we had a broad portfolio of over a dozen antibody programs including - inclusive of those two undisclosed targets and additionally we have three neoantigen vaccines, which are in various stages of development. On the operational side, we have taken important steps to become vertically integrated. What this means is that we can take immuno-oncology molecules particularly including antibodies from discovery to cell line development and [two] (Ph) GMP manufacturing in-house. In this regard we upgraded our recently acquired antibody manufacturing facilities and expanded our capacity. These steps allow us to bring our cell line development and manufacturing capabilities in-house which we regard as an important advantage in an environment of increasingly tighter third party manufacturing capacities. We expect to be able to produce development material to support our pipelines starting in early 2017. It is important to also note that our cell line development capabilities have already produced generous yields making our first cell lines compatible with commercial productions. With regard to streamlining our operations, we expect to complete the consolidation of our European research facilities at the end of this month with the closing of our Jena, Germany site. The consolidation should help us with efficiency as well as productivity. Lastly, we are now positioned to have our Prophage autologous vaccine advanced into randomized studies in combination with checkpoint inhibitor in newly diagnosed glioblastoma. We expect this trial to commence by the end of 2016. In addition we also expect to initiate as a one study of our AutoSynVax for ASV vaccine this is our second generation synthetic autologeous vaccine targeting cancer and neoantigens. This trial is expected to commence within the next nine months. On the financial front, while we are judicially allocating our resources to our proprietary programs designed to bring commercial revenue within the next five years, we are also actively pursuing creative non-dilutive funding strategies. These include strategic alliances and partnerships, all with the intent of helping us build a leadership position in the field of immuno-oncology. I would like to now turn the discussion to Dr. Jennifer Buell, who heads up our Development Operations and is a veteran of Agenus. Jennifer.

Thank you, Garo. I would like to comment briefly on recent important developments in the immuno-oncology field including the important development at this year’s ASCO. Dr. Stein will further elaborate on these topics. As you are undoubtedly aware, the future of immuno-oncology is in combination these include combinations not only with checkpoint antibodies, but also combinations involving neoantigen vaccines with checkpoint molecules. This year at ASCO, we witnessed a dramatic validation of these combination approaches, most specifically the importance of targeting CTLA-4 as the backbone of these combination strategies with prominence. Regimens involving lower and less frequent dosing of CTLA-4 antibody like [Aervoe] (Ph) in combination with PD-L1 inhibitors yielded a more pronounced clinical efficacy than either agent alone. And also importantly this was achieved without the added toxicity. Most experts now believe that the combination of CTLA-4 antibodies with PD-L1 blockade using a tolerable dosing regimen is going to remain as a foundational immuno-oncology regimen that it was originally thought to be. Because of our conviction, we aggressively advanced our lead CTLA-4 antagonist agent 1884 into the clinic. We have also continued the development of our second CTLA-4 antibody agent 2041. We anticipate initiating combination studies with our first candidate in the first half of 2017. Dr. Stein will elaborate further on these programs shortly. In January of 2016, we received clearance from the FDA to advance our CTLA-4 and our [indiscernible] antibodies into the clinic. We are very happy to report that we dosed our first patient with agent 1884 in April. We have completed the dosing of our first cohort of patients and we are initiating the dosing of our second cohort shortly. We are also delighted to report that our colleagues at insight dosed the first patient with our GITR agonist at the end of June. At ASCO clinical data on next generation checkpoint antibodies such as OX40 and 41BB agonist was reported the preliminary translation of biology readouts support the validation of these targets with signals of efficacy and no one expected toxicity. We believe that the real value of these targets will be demonstrated in combinations. Importantly, combinations of CTLA-4 and perhaps also PD-1 antagonist. As I have already mentioned our GITR agonist partnered with Incyte is in the clinic and our OX40 agonist also partnered with Incyte is expected to be in the clinic in the second half of this year. As mentioned earlier we also continued to advance our portfolio of undisclosed checkpoint antibodies against novel T Cell targets as well as other immune cell targets. To sum, we have already commenced clinical development with two of our checkpoint molecules this year and we expect to bring additional to the clinic within the next six months. Lastly at ASCO neoantigens were emphasized as key determinants necessary to shape an effective immune response against cancer. Specifically too much considered cold or less response at the checkpoint antibodies, the use of neoantigen vaccines can be leveraged to convert the tumor to a heart tumor thereby rendering them vulnerable to the effective at the checkpoint blockade. .: Putting all of this together we believe that Agenus is well positioned to bring effective achievements to patients of cancer and additionally having assembled all three of the critical parts and that will likely be the future of the immuno-oncology ecosystem. These include a broad portfolio of checkpoint antibodies, neoantigen vaccines and adjuvant [Technical Difficulty] our President of R&D for an update on our programs.

Thank you Garo and Jen. I'm very pleased to further update you on the important progress we have made over the last quarter advancing our immuno-oncology pipeline. As Jen and Garo indicated two of our lead checkpoint modulator antibodies have entered into clinical trials so far this year. Clinical trials have been initiated with our CTLA-4 antagonist, AGEN1884 and our GITR agonist INCAGN1876, the latter partnered with Incyte. We are looking forward to initiating combination trials with these antibodies as well as advancing additional checkpoint modulator antibodies and vaccines into the clinic over the next 12 months. We also made important progress in our partnership with Merck to discover and develop antibodies against novel checkpoint targets. This involved the discovery of a lead antibody candidate as similar backups to an undisclosed novel target. Merck is moving the lead candidate into IND enabling studies this year. We received the $2 million milestone payment for this accomplishment and are excited to see this program targeting a novel and exciting checkpoint target moving into the clinic. I would like to add a few additional comments on the very encouraging results emerging from ASCO this year. One of the biggest shifts in immuno-oncology following this year’s ASCO is that CTLA-4 antagonist have risen to real prominence again. This has been a very important part of our strategy and has been widely have progressively pursued both of our CTLA-4 antibody molecules toward the clinical development. We believe AGEN1884 is the third clinical stage anti CTLA-4 antagonist behind only aervoe and tremelimumab and that both of our CTLA-4 agents will combining powerfully with Agenus’ PD-1 antagonist, the first of which is also slated under Phase I in Q1 2017. Having antibodies within our product portfolio that target both CTLA-4 and PD-1 as well as our other immuno-oncology programs could present Agenus with a significant opportunity including first in class and second in class opportunities. With the addition of Jean-Marie Cuillerot to our team, we are evaluating the best strategic approach for the development of these two programs to determine a rapid registration path. We also believe that these targets will pare powerfully with our various vaccine programs to elicit effective immune responses against cancers not yet recognized as non-self by patient’s immune system. We have previously shown preclinical evidence of enhanced anti-tumor responses combining CTLA-4 or PD-1 blockade with our vaccines in animal models. Additionally, we think that the other major immuno-oncology theme emerging from ASCO was the growing recognition of neoantigens presented by cancers as the effective basis for their immune destruction. This recognition the importance of neoantigens has been parent to us at Agenus for a long time. In fact our Prophage vaccine which is an autologous vaccine loaded with patient’s own tumor neoantigens represents what we think is one of the most clinically advanced and promising cancer vaccines based on Phase II data in newly diagnosed glioblastoma which were presented at ASCO last year. We expect to begin a controlled clinical trial examining the effects of Prophage combined with the PD-1 blockade in patients with newly diagnosed glioblastoma this year. In addition to Prophage we believe we have built best in class capabilities for neoantigen prediction based on bioinformatic analysis of next generation DNA sequencing of tumors to identify mutant proteins that can be the basis for immune recognition and destruction of tumors. This combined with our clinically validated heat shock protein-70 peptide vaccine platform enhanced with our proprietary QS-21 stimulon adjuvant have allowed us to create AutoSynVax, a fully synthetic personalized neoantigen vaccine which we recently introduced and which we expect will enter into Phase I in the next nine months. We are also very excited about an entirely new class of neoantigens, which are now part of the Agenus portfolio. These new types of neoantigens were discovered by the founders of PhosImmune, a privately held company, which we acquired at the end of last year. Cancer cells are known to have this regulated biochemical function and as a consequence neoantigens arise with cancer cells abnormally phosphorylated non-mutant proteins, which can lead to the production of neoantigens even though the protein sequences aren’t immune. These abnormally phosphorylated proteins can present neoantigen to trigger immune recognition, which then could lead to the structure of the tumor cells by the immune system. Unlike most neoantigens arising from mutant proteins the phosphopeptides neoantigens are found in many patients with similar tumor types. We are developing various methods of generating immune responses to get a selected proprietary phosphoryl peptide neoantigens. This is being used to generate an advanced PhosphoSynVax and broadly applicable set of off-the-shelf neoantigen cancer vaccines. In closing we are very pleased to have recruited Dr. Jean-Marie Cuillerot as VP Global Clinical Development. Jean-Marie was previously at Bristol-Myers Squibb where he contributed importantly to the development of aervoe and most recently at EMD Merck Serono where he led the clinical development of avelumab, the PD-L1 antagonist partner with Pfizer. This program which he led from pre-IND to filing and progressed from first demand to BLA filing and under three year underscores Jean-Marie's creativity and drive. We are very excited to have him as part of our team at Agenus where he will help us to design to and develop best in class combination immuno-oncology treatment regimens. Thank you for your attention. I'd now like to turn the call over to Christine Klaskin, our VP of finance who will review our financial performance.

Thank you, Bob. I will now review our second quarter 2016 financial results. For the second quarter ended June 30, 2016 Agenus reported a net loss attributable to common stockholders of $28.4 million, which includes $7.6 million of non cash expenses. This compares to a net loss attributable to common stockholders for the second quarter of 2015 of $40.5 million, which included $17.3 million of non cash expenses. Net loss was $0.33 per share and $0.53 per share basic and diluted for the three months ended June 30, 2016 and 2015 respectively. The decrease in net loss attributable to common stockholders for the three months ended June 30, 2016 compared to the net loss attributable to common stockholders for the same period in 2015 was, primarily due to the $13.2 million charge for the purchase of our SECANT yeast display platform in 2015 and a non cash expense from fair value adjustments of our contingent obligations partially offset by the advancement of our checkpoint antibody program. For the six months ended June 30, 2016, the company reported a net loss attributable to common stockholders of $60.2 million, which includes $17.2 million in non cash expenses, compared with a net loss attributable to common stockholders of $59.3 million, which includes $26.5 million in non cash expenses, for the six months ended June 30, 2015. Net loss was $0.69 per share and $0.83 per share, basic and diluted for the six months ended June 30, 2016 and 2015, respectively. Cash, cash equivalents and short-term investments were $123.3 million as of June 30, 2016. This concludes the financial portion of the call. I will now turn it over to Garo for closing comments.

Thank you everyone. In closing, we are very pleased with the tremendous progress we made at Agenus over the last 30 months. During this period we have significantly broadened our portfolio of immuno-oncology capabilities through both in-house inventions as well as acquisitions. We have put into place integrated capabilities including substantial vertical integration to allow us to advance our programs rapidly and efficiently. And also critically importantly we have advanced our immuno-oncology programs across the board with two checkpoint antibodies having entered the clinic this year and at least two more later to do so over the next six months. With that, I would like to thank you for all joining us on this call today. We look forward to providing you with additional updates on our next quarterly call and I will turn the call back over to Michelle. Michelle.

Thank you, Garo. Operator, you can now open the call for questions.

[Operator Instructions] Our first question will come from the line of Jason McCarthy from Maxim Group. Your line is open.

Hi all, congratulations on the progress. We continue to see multiple checkpoints now moving into the clinic, so we are excited for the company. Bob, I had a question I just picked it out, 41BB agonist wasn’t talked about too much, I think it's really interesting. And could you comment on the potential of 41BB agonist in the Agenus pipeline? And are you thinking about using something like that with a vaccine versus the [indiscernible] you are using 41BB stimulatory domain it’s really interesting comparison that we are trying to make?

If I may, first of all as you know, Jason, we have not disclosed anything outside of the six antibody targets that we have made public. But having said that, perhaps Bob can comment generically based on his knowledge on how does 41BB factor into the equation. Bob, would you do that?

I think one of the things that came out of ASCO is very clearly is that 41BB is emerging as a very interesting checkpoint target we are not insensitive to that point of view. And you might imagine we might have anticipated some of that. I do think it's a very interesting opportunity, it has the number of effects, it can help activate T-cells, but it can also up-regulate the activity of any K-cells inside tumors. It can combine well with antibody approaches that are intended to deplete into tumoral Tregs through antigen potent cytotoxicity. And it is interesting in the setting of cell therapy 41BB internal signal transduction domain seem to stimulate perhaps cell for memory production. So we think that it's a very interesting adjunct and we are as Garo mentioned have many undisclosed programs and some of them are for interesting targets.

And just a follow up or additional question, at what point will Merck announce what the targets are, so we can get a better sense of clinical programs that they might be running and to get a sense of what that value could be to Agenus?

I think that’s entirely up to Merck, Merck will control that. However, they are I think very interesting they are a little bit off the beat in past, but have very strong rationale and I think they will perform well in Merck’s portfolio and we are excited about them. We are very glad that we are able to generate development candidate backups and it wasn't - Merck did a somewhat unusual deal and that they gave us complete R&D support, [indiscernible] booked to $100 million of milestones for a successful compound and also mid single digit growth which is pretty unusual deal given that they came to us with the targets. So, we are very excited about it, I think this is entirely within their purview to decide when they're going to review what the targets are.

Thank you. Our next question will come from the line of Mike King from JMP Securities. Your line is open.

May be just, a quick follow-up on Jason's question. The thought that ran through my mind as you guys were speaking is that this portfolio of yours and your partners is I would say spring loaded for a lot of data. So, I'm just wondering what are your thoughts are about disclosure, when and where do you think we might start to see the first evidence of the actual activity of some of these assets, so we can understand better how you guys are creating value from your R&D?

Mike I mean this is obviously a very prudent question. Let me answer it in the following way. And I don't like to be ambiguous about it but there are first of all as you know the product development timelines Bob alluded to it in the context of Jean-Marie record, product development timelines are getting more and more compressed because of higher efficacy and presumably better looking toxicity or side effect profile. And in the context of that, clinical plans and data generation becomes a very-very important confidential asset to keep, particularly given the fact that the field is also getting very-very competitive. So, we will be disclosing things that we are legally required to do but outside of that of course in the context of scientific meetings as well it will be a responsible thing for us to disclose what needs to be disclosed. But outside of that you can expect us to be airing on the side of confidentiality because we don't want our competitive positions to be revealed. And so that's what I can say on this question. Bob would you like to add anything.

Thank you, Garo. I think that we are advancing our compounds as aggressively as it's possible given the slightly conservative position the FDA is taking on starting doses with that and be expect to be a meaningful pharmacodynamic doses sometime probably first half of next year. and we are working to develop those translational evidence that our compounds are working and clinical response data will of course lag behind that. Probably I would think that things won't hold over the next year with several of these compounds but we don't really want to be articulating extremely specific timelines at this point.

The other question I wanted to ask you guys is, when rightly state that the space is very competitive and you are in many instances creating fast follower molecules. When you think about that from a strategic point of view how do you balance getting in battles with the Merck’s and the Bristol’s of the world versus creating molecules that have slightly enhanced or improved properties relative to what’s out there? And is that even possible and knowable?

So a couple of things Mike. One is that we are not at all daunted by that and I would like to just elaborate little bit on the last question you asked. We are quite confident based on the preclinical characteristics of our molecules, tested against human cells and results were achieved in non-human primates with our molecules but these will have requisite activities, something that PK needs to still be demonstrated in people that that should also be fine. So we think that what is going to be crucial here is they have the right combinations to combine in the right ingredients to put together to create best combination regimens. And for that we think you’re going to need a CTLA-4 compound, you’re going to need a PD-1 compound and then you’re going to want to explore combinations with some of these other agents like GITR and OX-40 which are emerging as probably very important but maybe not powerful single agent antigens compounds in some settings. So we think that for some of these components of these regimens you need to have very high quality well performing agents, but they don’t necessarily have to be extremely differentiated from the other agents out there. For some of them we do think we have novel characteristics in our compounds that makes them potentially best in class. But the key here is to create best in class regimens and test them in the right clinical settings. And even though the big companies that are somewhat in front of us have occupied a fair amount of space. There is a lot that’s not been effectively exploited and there are opportunities to do better on dosing regimens even in the things where there are some registrations and you could look at that very clearly by looking at the benefits of dialing back the tones of CTLA-4 blockade on top of PD-1. So we think there is going to be a very large amount of addressable space. And as Jen had alluded to earlier in the discussion we think that the addition of vaccines to activate the immune system and then to shape the immune response of checkpoint modulating antibodies is a very large and largely unexploited opportunity where we are well positioned to lead the pack.

Thank you [Operator Instructions]. Our next question will come from the line of Swayampakula Ramakanth from H.C. Wainwright. Please go ahead.

Thank you. This is [RK] (Ph). Good morning Garo and Bob. A couple of quick questions. Just following up on some of the conversations we have had this morning. Looking into your CTLA-4 program, and also looking at some of the marketing data, which we are receiving from the Big Pharma, compounds like aervoe seemed to be hitting a platter in the market. So, when we look at your program, should we assume that the way you are seeing your CTLA-4 programs as an initial steps to make sure their efficacy in certain chambers, which are not being looked at other folks already in front of you. And also to use them as in combinations because it looks like that's something which your team is professing quite a bit this morning?

So, we have I think some very good strategies for going to meaningful indications and tumor types that haven't been blanketed by the larger companies yet. We also have ideas about how to make rapid progress towards registration. And we are in exploration with larger potential partners as to how to capture some of the real blockbuster potential that our CTLA-4 and [indiscernible] PD-1 programs have when combined together. So, we do think that there's lots of fresh space that the evident supports likely utility but having been covered by the competitors yet. And we are very comfortable that we are developing high power strategies to exploit that. And as I mentioned having Jean-Marie Cuillerot in the mix has already had a significant impact even though his first day with us was July 5th.

And actually that was kind to be my next question and certainly Agenus has made some very good hires in the recent past especially who have made major clinical and R&D development contributions. And by these hires what is it that you want to investors to understand, how your corporate strategy is changing especially getting past the initial stages of development, more into the mid-to late stage development of the programs?

So, RK has any strategies there is quite simple, as you know the combination of quality and completeness of assets especially in an environment where combinations are going to be paramount for success, for achieving efficacy and cures. The quality of the assets and also very importantly quality of the people will be major drivers of success and if you combine that with the appropriate strategy and the resources we can get there. Now the question then becomes what are the objectives? As a company our objective is to be able to generate revenues from multiple revenue sources within the next five years. And if we are on track with the achievements over that then we can look forward to building a very-very meaningful very unique company longer term. So, that's the objective and we need to balance certainly at given time, priorities, resources and bringing in the kind of resources that we talked about earlier in order to be able to execute. But we feel that we have the raw materials both in the context of a portfolio technologies by enlarge the value in place and general capabilities that include vertical integration as well as people to be able to do this way.

And maybe as good for adding that our strategy has been to create a fully professionalized organization all the way from discovery through IND enabling studies through early development and now we are building out the late stage development capabilities Jean-Marie and the mix which we are very glad about. And what we have tried to do all along is recruit for talents expertise and experience. And in the case of the development strategies here, this is a space where the paradigm is evolving very rapidly and improving remarkably. And so Jean-Marie was able to take the PD-L1 antagonist that EMD Serono had from first in man to BLA filing and under three years. He was heavily experienced in the development of aervoe, he played a major role in seeing up the EMD Serono PD-L1 for the Pfizer partnership which is a very good partnership and then was able to drive it through to registration filing very rapidly. And so what we wanted people who know what’s in the box but aren’t afraid think out of box.

And talking about partnerships I know you don’t want another question on Merck partnership. But I am just trying to understand beyond the initial process of providing Merck with a preclinical product, what additional responsibilities or inputs do you have in further development of the product and now with some key personnel. Can that help?

In that particular program the responsibility for advancing through IND enabling studies and through clinical development resides with Merck. There are some ongoing discussions about other ways we might interact but that program is under their hospices.

Thank you. At this time, I am showing no further questions. I would like to turn the conference back over to Ms. Michelle Linn for any closing remarks.

Thank you, operator. I would like to remind listeners that the call will be accessible from the Company’s Web site at www.agenusbio.com. On behalf of the management team at Agenus, we’d like to thank everyone for joining us on today’s call. We will be available to receive any further inquiries following the call. With that, operator, please conclude the call.

Ladies and gentlemen, thank you for participating in today’s conference. This concludes the program. You may now disconnect. Everyone, have a great day.