Q3 2019 Earnings Call

As a reminder, today's conference is being recorded no I would like to turn the conference over to Dr., Jennifer Kneale, Chief operating officer of a genus. Please go ahead Dr. appeal.

Operator: After today's conference is recorded, now I would like to turn the conference over to Dr. Jennifer Buell, Chief Operating Officer of Agenus. Please go ahead, Dr. Buell.

Dr. Jennifer Buell: Thank you, Operator. Today's call is being webcast and will be available on our website with our accompanying slide material for replay. Just a reminder, the slides are now live on our webcast, and if you have access to a computer, you'll be able to view them manually. Before we start, we would like to remind you that this call will include forward-looking statements, including statements regarding our clinical development and regulatory 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. Joining me today are Dr. Garo Armen, Chairman and Chief Executive Officer, Dr. Anna Vyatek, Head of Clinical Development and Operations, and Christine Klaskin, our Vice President of Finance. I'm going to start this call today by first asking Garo to provide you with the reality of Agenus operationally and in The Marketplace. I accept these facts as they are, and what we have achieved will be eye-opening to you all. Daryl

Thank you operator for today's call is being webcast will be available on our website with our accompanying slide material for replay just a reminder, the slides are now lives on our webcast and access to a computer you'll be able to view that.

Manually.

Before we start we would like to remind you that this call will include forward looking statements.

Statements regarding our clinical development, a regulatory plans and timeline.

Well, that's timeline for data released and partnership opportunity. They stay with are subject to risks and uncertainties. We refer you to our LTAC filings for more details on these risks as a reminder, this call is being recorded for audio broadcast.

Joining me today are Dr., Carl Armen, Chairman and Chief Executive Officer, Dr. <unk>, the attack head of clinical development and operations and Christine Klaskin Vice President of Fine Yes.

I'm going to start this call today by first asking Dara to provide you with the reality of agenda operationally.

In the marketplace.

Expect these bad as they are and what we have achieved well be eye opening you walk.

Garo H. Armen: Thank you, Jen. During our last quarterly call, I shared a visual with you. That's the very first slide that you have in your possession. This one speaks to our R&D productivity and the fact that, over the last four years, in I&D filing, we have outpaced other immuno-oncology companies, large and small. Also important is the fact that all the INDs that we have filed, all 13 of them so far, represent inventions of Agenus. During this call, we will update you on the progress we've made with our most advanced program. RCTOA for anybody: zolfirilimab and our PD-1 antibody Balthetilimab. I know these are mouthfuls, and I'm just getting used to using them myself.

Girl.

Thank you Johnny.

[noise] during our last quarterly call I shared their visual which you. That's the very first slide that you have in New York session.

It's one speaks to our R&D productivity and the fact that over the last four years, he and I Indeed filings.

We have outpaced either you mean oncology companies large and small.

Oh, sorry, or is the fact that all the I am pleased that we have filed all 13 of them so far.

Represent in ventures, Oh agenda.

[noise] during this call we will update you on the progress we made with our most advanced programs.

Oh studio away for anybody.

It's really about.

And our PD, one antibody Bob to him I know these are mob falls down I'm, just getting used to using their myself.

Garo H. Armen: We are targeting commercializing both agents in the first half of 2021, which means we will be filing our BLA or BLAs in 2020. Our first indication will be a second line cervical cast. But, importantly, we are developing these two antibodies because they are critically important agents to be used in combination with many of our own next-generation antibodies, including by specific, in combination with our allogeneic cell therapy for which our first IND is on track to be filed this year, and also in combination with our cancer vaccines, which include our off-the-shelf phosphorylated antigen vaccines where we have a highly proprietary position. As you can see from our IND chart, we have generated 13 immuno-oncology agents which are all in clinical development.

We are targeting commercializing <unk> agents in the first half of 2021.

Which means we won't be filing our be away or B.L.A.'s and 2020 .

Our first indication will be second line cervical cancer.

Bob and importantly, we are developing these two anybodys because they are critically important age tends to be used in combination with many of our order next generation antibodies, including bi specifics.

In combination with our powergen ache cell therapy for which our first I N. D is on track to be filed this year.

And also in combination with our cancer vaccines, which include our off the shelf for far away [laughter] antigen vaccine.

Where we have a highly proprietary position.

And you can't see from Brian de chart, we haven't generated 13, immuno oncology agents, which are all in clinical development is presently.

Garo H. Armen: We expect that some of the next-generation agents in our pipeline can help expand the market opportunity for our PD-1 and our CTLA for anybody. For example, to the extent that the combination of our next-gen CTLA-4 antibody plus our PD-1 antibody performs better than those in the market today, we believe our PD-1 commercial opportunity could be substantial. And on that note, we plan to start our combination trials for our next-gen CTLA-4 and our own PD-1 antibodies this month. In addition to the leverage our PD-1 and CTLA-4 antibodies provide us with for our development strategy. We have been approached by several companies who have expressed their interest in accessing our agents to develop their own proprietary products. And this has, of course, many advantages that we can discuss for them and, of course, for us as well. The first of these transactions is expected to be finalized in the next few weeks. Each of these transactions will involve a modest upfront payment.

We expect that some over the next generation agents in our pipeline can help expand the market opportunity for our PD, one and our CTO way for anybody.

For example.

So do you expect that the combination of our Nexgen CTO away for anybody plus our PD, one antibody performs better than those in the market today, we believe our PD one commercial opportunity could be substantial.

And on that note we plan to start out combination trials for our next tranche you take away for and our own PD one antibodies this month.

In addition to leverage our PD, one and city away for anybody's provide us with.

For our development strategy, we have been approached by several companies who have expressed their interest to access our agents to develop with their own proprietary products.

And this has of course, many advantages that we can discuss for them.

Of course for us as well.

The first of all these transactions is expected to be finalized in the next few weeks.

Each of these transactions will involve a modest upfront.

Garo H. Armen: Cash Milestones, and Double Digit Royal. I will now provide you with some insights into our ongoing cervical cancer trial. As promised, we have completed the required enrollment in our PD-1 CTLA-4 combination trial in cervical cancer, and we expect to complete enrollment in our monotherapy trial, the PD-1 trial, by year end. We have completed the planned interim analysis of our combination trial and expect to complete the planned interim analysis of our monotherapy trial soon. We have shared the results generated from our interim analysis of our combination trial with our data safety and monitoring board. And based on both safety and efficacy signals, they issued a recommendation to proceed to completion.

Cash milestones and double digit royalties.

I will now provide you with some insights into our ongoing cervical cancer trial.

We have as we have promised we have completed the required and wrong on Cobar PD, one PD L.A. for combination trial in cervical cancer.

And we expect to complete enrollment of our monotherapy trial, the PD one trial by yearend.

We have completed the planned interim analysis about combination trial and expect to complete the planned interim analysis of our monotherapy trials true.

We have shared the results generated from our interim analysis of our combo trial with our data safety monitoring board and based on both safety and efficacy signals they issued a recommendation for precede to completion.

Garo H. Armen: I should also point out that in preparation for our potential BLA filing next year, we have produced commercial-grade material for both of our antibodies. I will now switch to some visuals, additional visuals, and address questions we are asked frequently. The next visual... represents the evolution of our pipeline in the past four years. Our pipeline for 2015 is in the second visual you have, and includes seven products. Since that time, we have created an extensive portfolio of Check Point Anybody's, if you can switch to the next visual, Check Point Anybody, allogeneic cell therapy, and neoantigen vaccine.

I should also point out that in preparation for our potential BLE filing next year, we have produced commercial grade material for both of our antibodies.

[noise] I will now switched to some visuals additional visuals and address questions were asked frequently.

The next visual represents the evolution of our pipeline in the past four years.

Our pipeline in 2015 is in the second visual you have.

Included seven product since that time, we have created an extensive portfolio.

Oh checkpoint antibodies, if you can switch to the next visual.

Portfolio of Anybodys.

Our generic cell therapy, and Neoantigen vaccines.

Garo H. Armen: I believe our pipeline represents one of the most comprehensive portfolios in immuno-oncology today. It also allows us and our partners to explore optimal combinations without having to compromise based on limitations to access, which we experienced, by the way, many years ago when we were trying to do combination trials with vaccines and checkpoints. And unfortunately, at that time, we did not have access to checkpoints the way we have today.

I believe our pipeline represents one of the most comprehensive portfolios in Immunoncology today.

It also allows us in our partners to explore optimal combinations without having to kind of a compromise based on limitations to access which we experienced by the way many years ago. When we were trying to do a combination trials with vaccines and checkpoints and unfortunately.

At that time, we did not have access to checkpoints the way we have today.

Garo H. Armen: Another question we get asked related to how we are able to manage so many programs given our limited monetary and human resources. First, regarding human resources, I humbly believe that we have built one of the best teams in the industry. They are inventive, smart, highly knowledgeable, very passionate about their work, and very hard workers. Without them, we would not be able to achieve all of this.

[noise]. Another question, we get asked related to how are we able to manage so many programs given our limited monetary and human resources.

First regarding human resources I humbly believed that we have built one of the best teams in the industry.

Our inventive smart highly knowledgeable very passionate about their work and very hard working.

Without them, we would not be able to have achieved all of this we expect our team to be the key drivers are a lot continuing innovation and success.

Garo H. Armen: We expect our team to be the key drivers of our continuing innovation and success. Regarding monetary resources, if I can ask you to switch to the slide showing our partnerships over the last four years, that slide number five, I would like to draw your attention to the following visual. This speaks to our resourcefulness in having raised a significant amount of money, which has been in excess of $500 million in the past four years alone. And we have not done a public stock offering for the last four and a half years. Of course, that has positives and negatives, but we hope that our shareholders will view most of it as positive. We aim to continue to fund our future operations largely through these types of creative mechanisms until we achieve profitability. Another question we get often is... Have we sold all rights to our pipeline? And slide number six answers that question. The answer is, of course, no.

[noise] regarding monetary resources, you're tracking asks you to switch to the slide that has our partnerships in the last four years that slide number five.

I would like to draw your attention to the following visual.

This speaks to our resourceful, mostly in having raised a significant amount of money, which has been in excess of $500 million in the past four years along.

And we haven't done you have not done and market that stock offering for the last four and a half years.

Of course that has.

As it is and negatives, but we hope that our shareholders would be well view most of it as positives.

[noise], we aim to continue to fund our future operations largely through these types so created mechanisms.

Until we achieve profitability.

[noise] and other question. We got often is have we sold the all rights to our pipeline.

And slide number six answers that question.

The answer is of course no. This pipeline chart shows that we have partnered and what we have retained.

Garo H. Armen: This pipeline chart shows that we have partnered with and what we have retained. All magenta-colored products represented in this pipeline, or in the agents, rather, belong to us 100 percent. Importantly, we'll also retain the rights to generate specific molecules with all of our proprietary targets. And as we demonstrate the clinical activity of some of our clinical stage immuno-oncology agents, we plan to keep more and more North American rights for ourselves and license ex-North American rights to others.

All Magento killer products represented in this pipeline and the agents rider.

Belong to ask 100% importantly, we're also retained the rights to generate by specific molecules with all of our proprietary targets.

And as we demonstrate clinical activity on some of our clinical stage immuno oncology agents, we plan to keep more and more north American rights for ourselves and license ex North American rights for others.

Lastly, I would like to assure you three recent stock chart speeds, our 12 month performance chart.

Garo H. Armen: Lastly, I would like to show you three recent stock charts. These are 12-month performance charts. And they show our performance, which is in bright green, relative to, number one, the large and medium size of the technology company. Secondly... It shows our performance, again in bright green, relative to 28 immuno-oncology companies. And the third chart shows our performance relative to the drug index and biotechnology. As you can see, the performance of our company is substantially better than essentially all others. However, our absolute staff performance has been dragged down by the sector, and of course, we're not satisfied with our absolute performance in terms of staff rises.

Charts.

[noise] and they show our performance, which is in full bright green relative to number one the large and medium size.

Biotechnology companies.

Secondly.

It shows our performance again, right green relative to 28.

In college you companies.

And the third chart shows our performance relative to the drug index and the biotechnology. Thanks.

[noise] and you can see the performance of our company substantially better than essentially all others.

Our absolute stock performance has been dragged down by the sector and of course, we're not satisfied with our absolute performance stock price.

Garo H. Armen: In addition to our continuing efforts to improve our communications and education, we have recently hired an investor relations professional who will be known to at least some of you. And we look forward to her interacting with investors and analysts at a high level of frequency so that we are able to provide you with additional data and education on our portfolio, and, for that matter, on the sector as well. In spite of the fact that the sector has experienced unprecedented and explosive revenue growth in the last five years, in the form of, for example, the two PD1s and CTLA for Anybody, expected to top 20 billion in revenues this year, recent trends have shed some doubt about the sector's ability to continue with its past momentum.

In addition to our continued efforts to improve our communications and education, we have recently hired and Investor Relations professional.

All be known trade at least some overview.

And we look forward to hurry interacting with investors and analyst with a high level of frequency for us to be able to provide you with additional data and education on our portfolio.

For that matter for the sector as well.

[noise] inspired told the fact that the sector has experienced unprecedented then explosive revenue growth and the last five years and a formal for example, the to PD ones.

In the city away for anybody expected to top 20 billion in revenues this year.

Recent trends have shed some doubts about the sectors ability to continue with the past momentum.

Garo H. Armen: Now, this is an important section, and I draw your attention to it. We aspire to return confidence to the high hopes for the sector with our performance in the near and long term. And on that note, during 2020, we expect to generate clinical data on the following immuno-oncology agents and trials. And I specifically draw your attention to the fact that there are six.

Oh this is an important section and and I draw your attention to it.

We aspire to return confidence the high hopes for the sector with our performance near and long term.

And on that note.

During 2020 , we expect to generate clinical data on our following immuno oncology agents and trials and I, specifically draw your attention and the fact that there is six agents.

Garo H. Armen: agent that we expect clinical data from next year, and I will go over them one by one, in seven different programs. The first one is clinical data on our PD-1 CTLA-4 combo trial in cervical. Second one, clinical data on our PD-1 monotherapy trial in cervical cancer. Now, beyond these first two, we are going to talk about new agents. So these are highly innovative new products. The third one is clinical data on our next-gen CTLA-4 dose escalation trial for clinical data on our next-gen CTLA-4 combination trial with our own PD-1. Five, clinical data from our tumor conditioning by specific GS1423, which is now in the hands of Gilead, licensed to Gilead fully.

We expect clinical data out of next year and I will go over them one by one.

In seven different programs.

First one.

His clinical data on our PD one she till April combo trial in cervical cancer.

Second one clinical data on our PD, one monotherapy trial in cervical cancer.

Beyond this first too we are are going to talk about new agents. So these are highly innovative new products the third one.

Clinical data on our next shipments to Chile or dose escalation trial.

For clinical data on our next Gen City away for combination trial with our own PD one.

Five clinical data from out schumer conditioning by specific.

She as one to four to three which is now in the Haynesville Gilliat license feel guilty absolutely.

Dr. Jennifer Buell: Clinical data on our own bispecific agent, 1223, designed to deplete intratumoral T-regs, and seven, clinical data on our differentiated CD137 antibody, agent 2373. So all these developments are slated for the upcoming year. And we're very, very pleased with the fact that we will have clinical data on multiple programs from six different immuno-oncology agents that have been in our portfolio and in the hands of our partners. Finally, before I turn this to Jen Buhl, I want to let you know that on November 15. That is the following Friday, by the way. We are hosting an R&D day in New York. The event will include an update on the field of immuno-oncology by experts Dr. Steven ODay and Dr. Manuel Hidalgo, as well as presentations from the company on our lead CTLA-4 and PD-1 programs, our next generation agents, including the CTLA-4 molecule, our next gen CTLA-4, and our discovery engine and capability. It will be informative, and I hope that some of you will be able to attend it, but nonetheless, it will be available via webcast. By the way, we also plan on having research days in other cities and in Europe in the coming months. Now, Dr. Jen Buell, our Chief Operating Officer.

Six.

Clinical data on our own by specific agent 12, 23 design to deplete intra Tumoral T regs and seven clinical data on our differentiated CD 137 anybody age and 20 373.

So all these developments are slated for the upcoming year and and and were very very pleased with the fact that we will have clinical data.

Multiple programs from six different immuno oncology agents that have been in our portfolio and in their hands of our partners.

Finally, before I turn it is for Gen view I want to let you know that on November 15.

That is the following Friday right away, we are hosting at R&D day in New York.

Event will include an update on the field argument oncology by experts Dr., Stephen or day, and Dr. manual hit the algo.

As well as presented patients from the company I now leads to delay for PD one programs. Our next generation agents, including CLA for molecule. Our next gens utility for an hour discovery engine and capabilities.

It will be informative.

And I hope.

That some of you will be able to attended but nonetheless, it will be available via webcast by the way. We also plan on having research days in other cities and in Europe in the next coming much now Dr. Jan view, our Chief operating officer.

Dr. Jennifer Buell: Thank you very much, Garo. As Garo mentioned, this is indeed a very exciting time for us. While the transformation of the company occurred only within the last four years, we're operating with the integration, agility, and flexibility of a team that's been together for decades. This is largely due to our shared passion to deliver high-impact therapies and small, fast clinical trials designed for rapid regulatory and commercial success with products that are accessible to all patients who need them. We share a commitment to transform the experience that a diagnosis of cancer means for patients, and I'm very excited to have Dr. Ana Biatek share details about the progress we're making in the clinic. Before doing so, I want to summarize a few highlights of our progress in 2019 with details on some of our critical catalysts. This year, we've made remarkable progress in our trials, which includes the completion of accrual into one trial and approaching completion of accrual into our second. The interim analyses, which were preplanned based on independent core lab reviews, are underway.

Thank you very much guy as Guy mentioned this is indeed, a very exciting time frame.

Well the chance amazed how the company occurred only within the last four years or operating with the integration agility and flexibility of a team that's been together for a decade. This is largely due to our shared passion to deliver high impact therapies and small sats clinical trials designed for rapid regulatory and camera.

Initial success, it's probably that.

Our accessible to all patients who need them.

We share a commitment to transform the experience the diagnosis of cancer means that patients.

Very excited to have that data attach or details about the progress were making and.

Before doing so I want to summarize a few highlights on our progress in 2019 with detailed themselves are critical catalyst.

This year, we've made remarkable progress our child.

That concludes the completion of a cool into one trial and approaching completion of accrual into our second interim analyses, which were pre plan based on independent quite elaborate views are underway.

Dr. Jennifer Buell: To date, our available investigator-reported data underscore the clinical benefit of our PD-1, Agent 2034, belacetilumab as a monotherapy for patients with refractory cervical cancer, and furthermore, the benefit of the addition of CTLA-4, which is Agent 1884.

Today, our available investigative appointed either underscore the clinical benefit of our PD. One page 10, 2030 select balance still about all the monotherapy for patients with refractory cervical cancer.

Furthermore, the benefit of the addition of CTO playful and this is our age and 18 84.

Dr. Jennifer Buell: [inaudible] to PD-1 in combination with PD-1 to expand response rates and potentially the durability of these responses. Anna will tell you more about these programs shortly. We advanced four novel discoveries to IND this year, and these discoveries are now progressing in the clinic, generating validating data on the differentiated proof-of-mechanism of our potentially first or best-in-class agents. These discoveries include our next-generation CTLA-4, agent 1181, our differentiated CD137 agonist, agent 2373, our first-in-class Treg-depleting bispecific antibody, agent 1223, and, of In summary...

Well the fill in that.

Anyone in combination with people want to extend response rate and potentially the durability of these responses.

I'll tell you why about these program shortly.

We advanced board novel discoveries Die Andina here I need discoveries are now advancing in the clinic generating validating data on a differentiated proof of mechanism of dollar potentially first our best in class H.

These discoveries included.

Next generation sequencing for age and 11 anyone.

Our differentiated CD 137, agonists HM 20 373.

Our first in class Keybanc depleting by specific antibody engine 12 23.

And of course, G.S. 14, 23, a biofunctionals molecule now exclusively licensed it gilliat and being developed by them.

[noise] [noise] in summary.

Dr. Jennifer Buell: This year, we've generated data on more than 250 patients with our LEAD CTLA-4 MPD-1 program. We've completed enrollment and the interim analysis for one late-stage trial designed to support approval, and we're on track to complete enrollment and the interim analysis for the second trial this year. We've advanced our next generation CTLA-4 agent 1181 through several dose escalation cohorts and will start combinations imminently. Additionally, we have advanced our differentiated CD137 agonist into early dose evaluation. We've activated the clinical trial for our Treg depleting agent, 1223. Furthermore, we've advanced our allogeneic cell therapy into IND enabling for a filing this year and engaged regulators to enable rapid combinations of our allogeneic cell therapy and our antibodies. In addition to these clinical milestones, we've also announced three cash milestones in our Gilead collaboration, approximating $23 million. We have also entered into an agreement to manufacture GS-1423 for Gilead at undisclosed financial terms. Finally, due to the blockbuster sales of GSK Shingrix vaccine, which contains our proprietary QS21 adjuvant, now exceeding $1.6 billion in the first nine months on the market, we have extinguished our contingent financial obligation of $25.9 million to health care royalties.

This year, we've generated data on more than 250 patients with RBC Kelly or on PD One program.

We completed enrollment and the interim analysis. So one late stage trial design disappoint approval and we're on track to complete a wrong enrollment in the interim analysis by the second child this year.

We've advanced our next generation see tailing for age and 11 81 through several dose escalation cohorts and we'll start combination imminently.

We have in advanced our differentiated Sydney 137 agonists into early dose evaluation.

We activated the clinical trial for our T. way depleting by specific agent 12 23.

Furthermore, we've advanced our allogeneic cell therapy into I, Andy enabling for a filing this year and engage regulators to want to enable rapid combination of our allogeneic cell therapy and our antibodies.

In addition to these clinical milestones. We've also announced three cash milestones that are good we had collaboration approximating $23 million.

We've also entered into an agreement to manufacture and she has 14 23 werent gilliat for undisclosed financial.

Finally, due to the blockbuster sales GSK shingrix vaccines containing our proprietary Qs 21, Japan now exceeding $1.6 billion in the first nine month in the markets, we have extinguished our contingent financial obligation.

That's $25.9 million healthcare royalty.

As a reminder, agenuss remains eligible to receive sales milestones of shingrix up to $40 million, which are likely to come next year based on current trends of Shingrix revenues.

Dr. Jennifer Buell: As a reminder, Agenus remains eligible to receive sales milestones of Shingrix of up to $40 million, which are likely to come next year based on current trends of Shingrix revenue. Now I'll take just a couple of minutes to zoom in on our next-gen CTLA-4, our differentiated CD137 agonist, and our agenta cell therapy company. To reiterate Garo's earlier points, all of these next-generation agents show important added benefit with PD-1 in our preclinical investigation and, in some cases, with CTLA-4 or the combination of both. Given the preponderance of data we've generated with our lead molecule, we are able to accelerate the combination with our novel agent quickly. These include combinations with our allogeneic cell therapy.

Now I'll take just a couple of minutes a zoom into our next gen. CBLI for our differentiated see any 137 agonist and our agenda cell therapy company can reiterate guidance earlier point all of these next generation agent chilling Orient added benefit with PD, one and I preclinical interrogation in some cases what seem to.

Selling for or the combination of bone.

Given the preponderance of data we generated with our lead molecule, we are able to accelerate the combination with our novel agents quickly.

These include combinations with our allogeneic cell therapy.

So far as to extend our as introduction of our next Gen see Kelly for age and 11 anyone as a reminder, it's designed to address the shortcomings of the first generation CBLI for and to expand benefit to the majority of patients who otherwise experienced low responses. This first generation ideally Boyd easily.

Dr. Jennifer Buell: So first, to expand on Garo's introduction of our next-gen CTLA-4, Agent 1181. As a reminder, it's designed to address the shortcomings of the first-generation CTLA-4 and to expand benefit to the majority of patients who otherwise experience low responses to first-generation CTLA-4s due to a genetic polymorphism. We've shared early clinical readouts of this molecule with our scientific advisors. And we plan to share these data more broadly as they mature and as combinations with our PD-1 Agents 2034 commence.

Genetic polymorphism [noise].

We've shared early clinical Readouts of this molecule with our scientific advisor.

Well, we plan to share these data more broadly as they mature and as combinations with our PD one agents like 2034 come at.

Dr. Jennifer Buell: As Garo alluded to earlier, if Agent 1181, our next-gen CTLA-4, in combination with our PD-1 or others, outperforms currently available first-gen CTLA-4 PD-1 combinations, it will be an extraordinary outcome for patients and all of our stakeholders. Now I'll turn to our differentiated anti-CD137 molecule, Agent 2373. It's in the clinic.

As Carol alert alluded to earlier.

Hey, John 11 anyone our next Gen Sealy for in combination with our PD, one or others.

Performs currently available first chance detailing for PD one combination.

We'll be an extraordinary outcomes for patients and all of our stakeholders.

Now I'll turn to our differentiated anti CD 137 molecule in 10 20 373, it's in the clinic.

Dr. Jennifer Buell: This molecule was designed with important safety and efficacy advantages over competing molecules. HN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing a specific CD137 co-stimulatory signaling in activated immune cells. This is both the adaptive T-cells and innate NK cells, parts of the immune system. This makes it a very attractive target for cancer immune therapy. Importantly, these unique properties of Agent 2373 are designed to enhance efficacy while limiting the systemic toxicity that has hampered the development of competitor molecules.

This molecule was designed with important safety and efficacy advantage as older competitor molecule.

Hey, Jim 20, 373 is a fully human monoclonal antibody that bush the immune response to cancer cells by enhancing specific CD 137, co stimulatory signaling and activated immune cells.

This is both the adoptive T cells and me NK cell parts of the immune system.

This makes it a very highly very attractive targets for cancer immunotherapy.

Importantly, these unique finding properties of age and 20 373 are designed to enhance efficacy by eliminating the systemic toxicity that has hampered the development of competitor molecules.

Dr. Jennifer Buell: Before I turn the call over to Anna, I'd like to give you a brief update on Agentus, our cell therapy subsidiary. Agentus continues to build on the progress we shared during our last call. Our proprietary allogeneic cell format is advancing to IND, and the company's highest priority and focus is to deliver allogeneic cell therapy approaches with proprietary targets and combinations with Agenus antibodies to patients with solid tumors as well as those with hematologic cancers. To accelerate our efforts, we've appointed an industry veteran, physician, and financing expert, Dr. Walter Flammenbaum, as CEO. One of Welter's highest priorities is to bring our discussions on financing to a positive conclusion. I will now turn the call over to Anna to give you a brief update on our most advanced programs.

[noise] before I turn the call over to Anna I'd like to give you a brief update on a gentle our cell therapy subsidiary.

Agendas continues to build on the progress we shared during our last call. Our proprietary allogeneic cells format is advancing dieting and the company's highest priority and focus is to deliver allogeneic cell therapy approach as well proprietary targets and combinations with agenuss antibodies to pay.

Patients with solid tumors as well as those hematologic cancers.

Two weeks celebrate our efforts we've appointed an industry veteran physician and financing expert Dr. Walter Simon Dom as CEO .

What about the highest priority is to bring our discussions on financing to a positive conclusion.

I will now turn the call over to add on to getting a brief update our most advanced programs.

Dr. Anna Vyatek: Thank you Jen and Garo. This year has indeed been very productive and exciting, as Jen and Garo described. I have had the pleasure of working with an extraordinary team to deliver real breakthrough outcomes in timing to complete enrollment in our trials designed to support BLA as well as, in parallel, advance four novel molecules to the clinic this year, at the same accelerated pace. As a matter of fact, similar to our accelerated pace shared in discovery and manufacturing, our clinical operations team is innovating to do the same in the clinic. In that regard, we have advanced from IND clearance to first in man trial in a matter of weeks and exactly 69 days to first patient after the IND clearance. As Jen and Garo already mentioned, the progress on our lead molecules is very important to enable us to start the combination with our next generation molecules. The first combination with our next-generation CTLA-4, Agent 1191, is expected to start this month, and our PK and PD data that we are acquiring in an ongoing manner are informing optimal dosing in this study. Now, our lead programs.

Thank you attend and saw though.

This year.

You can be engine products is an exciting as genon got all described.

I have had the pleasure to work with a nice extraordinary team to deliver real breakthrough outcomes and timing to complete enrollment knowledge trials designed to support the allay as well as in parallel advanced form molecules. The clinics. This year the same accelerated space.

As a matter of fact similar to what accelerated pace shut in discovery and manufacturing our clinical operations team is innovating to do the same into clinic.

That's what God do we have as bombs from I M. D. P lens. So first in man trial in a method off weeks and exactly six to nine days to first patient and after that I N D player.

As Jeff Garro already mentioned the progress on our lead molecules. It's very important I'm just trying to enable us to stop the combination with our next generation molecules. The first combinations with our next generation to delay for age and 11 age you its expected to start this month and our peak.

P. did they thought that we are acquiring cannot not going come I know our informing optimal dosing can this study.

No I wanted to programs Oh are proprietary city like four and PD, one antibodies suddenly friendly mopping and bonds to them up on advancing towards a plan b alike filing and 21.

Dr. Anna Vyatek: Our proprietary CTLA-4 and PD-1 antibodies, Xalifrelimab and Valstilimab, are advancing towards a planned BLA filing in 2020. At the upcoming Society of Immunotherapy and Cancer Conference this year, we'll present clinical data from our phase one dose escalation and expansion cohort, showing that Balsillimab is well-tolerated and reveals immunologic and clinical activity in recurrent As Garo and Jen reminded us, we are pursuing balstelumab as monotherapy and in combination with salifrelimab in patients with relapsed cervical cancer. In the combination trial, we have completed our accrual required for a potential BLA filing as well as interim analysis. Our data continues to support our conviction that this validated I.O.

At the upcoming society for immunotherapy income so called for US this year well the present clinical data from our phase one dose escalation and bolt ons showing stop but still the mob is well tolerated and reviews project and many color maybe dig into the cotton, Ohio concepts.

It's more impressive then what was previously reported in this population went the other PD one antibodies.

As gone Gen remind that we are pursuing the boss to them up as a monotherapy and in combination with sun friendly mob in patients with relapsed that's not free up.

So I'd be called concept.

In the combination trial, we have completed our accrual will require that floor and potential killing filing as well as inventory monopolies.

Our they thought continues to support our conviction that this body of data that are you a combination may important meaningful benefit including improvement in response rates and durability of response beyond what is available today to this patient.

Dr. Anna Vyatek: Combinations may impart meaningful benefits, including improvement in response rates and durability of response beyond what is available today to this patient. As a reminder, this is a disease that affects young women. These women have failed earlier lines of therapy, which in some cases included surgery, radiation, chemotherapy, and other agents, often multiple combinations. When they progress, there are very limited to no treatment options for this patient.

And as a reminder, this is so disease that affects young women. This woman have cited earlier lines of therapy, which in some cases included some generated by the nation's chemotherapies and other agents often multiple combinations.

When they progress there are very limited no treatment options for this space.

Dr. Anna Vyatek: We are working with a sense of urgency to deliver meaningful treatment to this vulnerable population. We believe that our first generation agents, both alone and in combination, can do that. We are working with our clinical advisors and the FDA in our efforts to advance this product quickly. This is why, while we plan to publicly disclose data on our interim analysis this year, we have been advised to do otherwise in order to protect the integrity of our ongoing trials and succeed with the BLA filing as quickly as we can in 2020. I look forward to providing additional information at our upcoming R&D day on November 3rd. Thank you, and now I will turn it back to Garo.

We are working with the sense of urgency to deliver meaningful treatment. So there's vulnerable population. We believe that's our first generation agents bulk alone and in combination can do that.

We are working with our clinical and I suppose and then yeah, you know what enforcement deposits product quick thing.

This is why why that we plan to publicly disclosed they thought I went into my mum. Nowadays is this year, we have been advised to do otherwise north of two broke that they integrate U haul are ongoing trials and succeed to what the B.L.A. Highland as quickly as we can and 22 inch.

I look forward to provide additional information a dollar upcoming R&D day on November sustained.

Thank you and not I want to turn this back to battle.

[noise]. Thank you very much on and your team.

Garo H. Armen: Thank you very much, Anna and your team, for moving our clinical programs at such a record pace. As I mentioned in our strategy, our strategy is to balance monetizing a portion of our discoveries every year while increasingly keeping rice in North America for some of our very valuable assets. Earlier, I indicated that we expect to generate meaningful clinical data in the next 12 months on a significant number of both partnered and wholly owned programs. This we expect to help our efforts to monetize on our ex-U.S. rights with significant value consideration.

Before moving to our clinical programs essentially record pace [noise].

As I mentioned in our strategy.

Our strategy is to balance between.

Monetizing a portion of our discoveries every year.

While increasingly keeping rice for North America for some of our very valuable assets.

Earlier, I indicated that we expect to generate meaningful clinical data and the next 12 months and a significant number of course partnered and wholly on programs.

This we expect to help our efforts to monetize on our X your west rights with significant value consideration.

Garo H. Armen: This strategy will be tested with our second generation CTLA4Anybody, currently in clinical development, as Jenna and I talked about, with prospects of generating early but potentially meaningful clinical data in the next month. Our ability to control key components of immuno-oncology combinations under one roof, specifically checkpoint antibodies, cell therapy, new antigen vaccines, and our QS21 adjuvant, we believe is a key advantage in our ability to develop the right combination drugs and in our ability to price them affordably, all for the purpose of benefiting patients. Before turning the call over to Christine... for recapping our quarterly financial report, I wanted to summarize a few key points.

This strategy will be tested with our second generation CTO a for anybody current being clinical development as Jennifer and I talked about with prospects, so generating early but potentially meaningful clinical data in the next month.

Our ability to control key components, so humid oncology combinations under one roof, specifically checkpoint antibodies cell therapy, neoantigen vaccines and out Qs 21, agile bench. We believe it is a key advantage in our ability to develop too right.

The nation drugs and in our ability to price them affordably.

Oh for the purpose are benefiting patients.

Before turning the call over to Christine.

For.

Recapping, our quarterly financial report I wanted to summarize if you keep orange.

We have.

Garo H. Armen: We have an outstanding pipeline of novel and second-generation immuno-oncology agents designed to deliver a substantial benefit to patients with cancer. We expect to become a commercial stage company without PD-1 and CTLA for anybody, first in cervical cancer, with strategies to rapidly expand to other cancers, particularly with our combination agents. 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. In addition to the clinical readouts, which I outlined earlier, targeted for the year 2020. Here's what we expect to accomplish by year's end. 2019 and into 2020. One, complete our monotherapy, as we talked about, PD-1 trial, accrual, and conduct our planned interim analysis for this trial on a BLA file.

And outstanding pipeline <unk> novel, and second generation immuno oncology agents designed to deliver substantial benefit to patients with cancer.

We expect to become a commercial stage company without PD, one and see too late for Anybodys first in cervical cancer with strategies to rapidly expand.

Other cancers, particularly without combination age.

We are emphasizing smaller focus trials to achieve high response rates, specifically targeting patients what not being effectively serve by today's first generation immuno oncology agents.

In addition to the clinical Readouts, which I outlined earlier targeted for the year 2020 .

Here's what we expect to accomplish by year's end.

29 team and into 2020 .

One complete our monotherapy as we talked about PD, one trial accrual and conduct our planned interim analysis for this trial for it'd be already finally.

Both our monotherapy and combination trials are designed to lead to be L.A. filings for salaries and approvals.

Garo H. Armen: Both our monotherapy and combination trials are designed to lead to BLA filings for accelerated improvement, to complete dose escalation, and to commence combination trials for our second generation CTLA-4 with our proprietary PD-1 molecule. Three, as I mentioned earlier, advance our differentiated best-in-class molecules in the clinic, including advancing and generating clinical readouts with our differentiated CD137 molecule, Agen 2373, and our selected Treg depleted by specific Agen 1223, advance additional breakthrough discoveries and file at least two additional INDs in 2020, advance our genetic cell therapy program, and have Agentus funded independently, as Jen mentioned. And importantly, we expect to complete additional business development transactions in 2019 and in 2020. Now, I will turn it over to Christine Klaskin to provide financial highlights. Christine

True complete dose escalation and commands combination trials for our second generation she delay for with our proprietary PD one molecule.

Three.

Mentioned earlier advance our differentiated best in class molecules into clinic, including advancing and generating clinical readouts without differentiated CD 137 molecule age and 20 373, and our selective T regs depleted by specific.

Asian 12 23.

[laughter] advancing additional breakthrough discoveries in file it leads to additional lie Andy's in 2020 .

[noise] advance our allogeneic cell therapy program and have a gentle find interesting annually as Jim mentioned.

And importantly, we expect to complete additional business development transactions and trying to 19 and in 2020 .

Now I will turn it over to Christine Klaskin to provide financial highlights Christine.

Christine M. Klaskin: Thank you, Garo. We ended the third quarter of 2019 with a cash balance of $93 million, as compared to $53 million at December 31, 2018. Our cash used in operations for the quarter ended September 2019 was $28 million, compared to $25 million for the same period in 2018. Cash provided by operations for the nine months ended September 2019 was $13 million, which compares to cash used in operations of $95 million for the same period in 2018. For the third quarter ended September 30, 2019, we reported a net loss of $46 million, or $0.33 per share, compared to a net loss for the same period in 2018 of $34 million, or $0.29 per share. For the nine months ended September 30, 2019, we reported a net loss of $81 million, or $0.58 per share, compared to a net loss for the same period in 2018 of $113 million, or $1.04 per share.

Thank you Dara.

We ended the third quarter 2019, with a cash balance of $93 million as compared to 53 million at December 31st 2018.

Cash used in operations for the quarter ended September 2019 was $28 million compared to 25 million for the same period in 2018 [noise].

Cash provided by operations for the nine month ended September 2019 was 13 million, which compares to cash used in operations of 95 million for the same period in 2018.

For the third quarter ended Septemberthirty 2019, we reported net loss of $46 million for 33 cents per share compared to a net loss for the same period in 2018.

$34 million were 29 cents per share.

For the nine months ended September 32019, we reported a net loss $81 million were 58 cents per share compared to a net loss for the same period in 2018 of $113 million free dollar four cents per share.

Christine M. Klaskin: During the nine months ended September 2019, we recognized revenue of $116 million, which included revenue from our transaction with Gilead and non-cash royalties earned. This compares to revenue of $30 million for the nine months ended September 2018. Through the third quarter of 2019, we also recorded $30 million of non-cash interest expense due to our transaction with Healthcare Royalty related to the sale of future royalties. I now turn the call back to Garo.

During the nine month ended September 2019, we recognized revenue of $116 million, which includes revenue from our transaction with Gilliat and noncash royalties earned.

This compares to revenue of $30 million for the nine months ended September 2018.

Through the third quarter 2019, we also recorded $30 million of noncash interest expense due to our transaction with health care royalty related to the sale a future royalties.

I now turn the call back to go.

Garo H. Armen: Thank you all. Thank you Jen, Christine, and Hannah. And thank you all for your attention. Now we'll turn the call over to chat to field questions. Yes, sir, we will now begin the question and answer session. To ask a question, you may press star then 1 on your touch-tone phone. If you are using a speakerphone, please pick up your handset before pressing the...

Thank you Oh, Thank you Jane Christine.

Thank you all for your attention now, we'll turn the call over to truck to a few questions.

Yes, Sir we will now begin the question and answer session to actually question. You May Press Star then one all your Touchtone phone if you're using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then to at this time, we'll pause momentarily to assemble our roster.

Operator: To withdraw your question, please press star then 2. At this time, we'll pause momentarily to assemble our roster, and our first question will...

[noise] and our first question will come from Byron arm in of Jefferies. Please go ahead.

Operator: This question will come from Byron Armen of Jefferies. Please go ahead. Yeah, hi guys, thanks for taking my call.

Garo H. Armen: Thank you for taking my questions. Garo, can you maybe talk about the 2034 monotherapy and combo trial with 1884? I think, you know, that trial has arm one, which is the monotherapy component, and arm two, which is the combo component. Which of these arms was the interim analysis conducted for? And can you just talk about the thresholds that you would need to hit in order to stop the study on Enron for each arm?

Yeah, Hi, guys. Thanks for taking my questions.

Carl can you just maybe talk about the 2034 monotherapy and combo trial with 18 84 I.

I think you know that trial has one which as monotherapy component arm to which is a combo component which of these ours was was the interim analysis conducted for.

Can you just talk about the thresholds that you would need to hit.

In order to stop the study enrolled for each arm.

Garo H. Armen: Okay, Biren, just a reminder, I did mention during my talk that the one that we conducted an interim analysis for is the combination trial. And I must also emphasize that these are planned interim analyses. So they're pre-planned into the trial. The other pre-planned interim analysis for the monotherapy trial will happen soon. And we will also, of course, make that available to our DSMB. With regard to our regulatory strategy. I will turn it over to my colleagues here, Jen and Anna, to comment on that.

Okay very addressed just a reminder, I didnt mention during my talk.

One that we conducted an interim analysis for is the combination trial.

And I must also emphasize that fees are playing the interim analyses.

Preplanned into the trial.

The other Preplanned interim analysis for the monotherapy trial will happen soon.

And we will also force make that available to RMBS ever be.

With regard to our regulatory strategy I will turn it over to my colleagues here genon out to comment on that.

Dr. Jennifer Buell: Thanks so much, Barron. So just to be very clear, these trials are being conducted as two single-arm trials to support VLA approval, both of them pre-discussed with the agency and otherwise. Now, the monotherapy trial with PD-1 is in relapse-refractory cervical cancer, and that trial accrual is ongoing and planned to be completed by the end of the year. To support accelerated approval, which is our regulatory strategy with this particular product in this indication, we effectively need to demonstrate what PEMBRO has done, comparable to PEMBRO, which is, as you know, between 12 and 14 percent response rate. We have not completed the interim analysis yet, the planned interim analysis for the monotherapy trial, but we're on track to do so before year-end for the combination trial, where we believe that we're going to deliver expanded response rates and durability of response given the mechanism of action of the addition of CTLA-4 to an indication that is largely based on a virally induced tumor, such as the cervical.

Thanks, so much Barron so just to be very clear. These child [noise] are being conducted.

Two single arm trial to support the L.A. improve both of them pre discussed with the agency and otherwise now the monotherapy trial with PD, one isn't relapse refractory cervical cancer.

And that that trial accrual is ongoing plan to be completed by end of year.

To support accelerated approval, which is our regulatory strategy with this particular product in this indication we effectively need to demonstrate what pembro has done comparable to Pembro, which is as you now between 12 and 14% response rates.

We have not completed the interim analysis, yet the planned interim analysis by the monotherapy trial, but we're on track to do so before yearend.

With a combination trial, where we believe that we're going to deliver expanded response rate.

And durability of response, given the mechanism of action at the addition of C.T. only four to an indication that is largely based on a viable induced tumor such a cervical and just just comparatively we've seen that addition of ceiling for in a number of different cancer types has done that and RCC and some days.

Dr. Jennifer Buell: And just comparably, we've seen that adding CTLA-4 to a number of different cancer types has done this in RCC, and some data presented at ESMO in cervical cancer and otherwise. We believe that we will do the same with our own combination program. Similarly, combination CTLA-4 and PD-1 is being pursued as a single-end trial to support accelerated approval in second-line cervical cancer, with accrual completed and the planned interim analysis also completed. While we would very much like the opportunity to share the data publicly, in our most recent discussions with our regulatory advisors, the agency, and our scientific advisors, it is likely in the best interest of the company and the integrity of the trials not to do so However, we do plan to provide you with a good clinical review, and Anna will do so at Investor Day, where you'll have a sense of how the activity of monotherapy and the combination of our agents is working in cervical cancer and a number of other different cancer types. Anna, do you want to add anything to that?

Not presented at ESMO and cervical cancer and otherwise.

We believe that we will do the same with our own combination program. Similarly combination seen Kelly for in PD one.

Being pursued as a single arm trial, just a sport accelerated approval in second line cervical cancer.

With accrual completed and the planned interim analysis also completed.

Well, we would very much like the opportunity to share the date at publicly and our most recent discussions with our regulatory advisors. The agency and our scientific advisor is it is likely in the best interest at the company and the integrity of the trials not to do so at this time, however, we do plan to pro.

By two with Oh, I, good clinical review and animal do sell at the Investor day, well, you'll have a set a sense of how the activity as a monotherapy and the combination of our agents are working and cervical cancer and a number of other different cancer types and I do want to add anything to that no I fully agree one.

Dr. Anna Vyatek: No, I fully agree with what you said, Jen. I think, you know, we are underway with completing enrollment for the monotherapy study. We completed the combination therapy, and the durability obviously requires more time to be followed on. So, I think we just keep going, and we stay on track for our filing in 2020.

That was a watch as such and I think you know we are on the away all plus completing enrollment for the monotherapy study completed the combination therapy and that the durability is sufficiently requires more time to be followed on a month. So I think we are well justified.

It's too and we stay on track for our filing 2020 fantastic. Thanks, Anna and I'll make one more point bearing we will continue to ascertain data from these agents in total for a number of different reasons for own pipeline development as well as for some of the collaborative and clinical collaborations that.

Garo H. Armen: Fantastic. Thanks, Anna.

Dr. Jennifer Buell: And I'll make one more point, Barron. We will continue to ascertain data from these agents in total for a number of different reasons, for our own pipeline development as well as for some of the collaborative and clinical collaborations that we're contemplating. And so, what you will see is that accrual will be open, and it's at our discretion. We've completed our obligations to meet trial enrollment, but we have the discretion and opportunity to continue to accumulate data in these indications. So I don't want there to be any confusion.

Contemplating and say what you will see is that they'd be accrual well be well be open and it to our discretion, we completed our obligation to meet that trial.

Enrollment, but we have the discretion and opportunity to continue to accumulate data and the syndication so.

I don't want there to be any confusion.

Dr. Jennifer Buell: So let me, let me, ask some follow-up questions on your comment on the combination arm for the interarm. Do you believe you've hit the necessary threshold that you needed to hit in that analysis? I'm going to assume ORR was the primary endpoint that you used for that analysis. And second, I guess, you know, as it relates to dosing on the combination arms, can you just review that for us? And then I guess the third question is for the combination cohort, were these specifically PD-1 positive patients at baseline that you enrolled in the study? Okay, so maybe Anna, we might do this in a bit of a different order, we'll start with dosing, we'll talk about the endpoints, and PD-L1, the patient's selectivity, and then an impression of where we are with the data, Anna.

So let me let me if I could ask some follow ups on your comments.

On the combination arm for the interim.

Do you believe you hit the necessary threshold, but that you needed to head on that analysis.

And this or or was the primary endpoint that you've done.

For that analysis.

And second I guess, you know as it relates to dose, saying on the combination ours can you just review that for US and then I guess third question.

As for the combination cohort, where these specifically PD one positive patients that baseline that you've enrolled in this study.

Okay, So maybe and I will wait we might do this in a bit of a different border well start with dosing well talk about the endpoints.

And and PDL, one the patient selectivity uh-huh.

And then and then impression of where we are with the data Hana. So in terms of love. Both saw this approach. One example, all patients regardless of their PDL one stoppel I'm. So they are not selected specifically, we obviously are often saying to the PDL one assertions status, but.

Dr. Anna Vyatek: In terms of both studies, actually, we have enrolled patients regardless of their PD-L1 status, so they are not selected specifically. We obviously are assessing the PD-L1 expression status, but selection has not happened at study enrollment. In terms of the availability and the promise of the data from the interim analysis, as you know very well, interim analysis is done on a small number of patients, and it only gives you a preliminary glimpse of what the totality of the data will look like. They are done mostly for the assessment of futility and then any safety signals. As such, this has been evaluated by our data safety monitoring board, and as Garo mentioned, the committee recommended continuing the study without modifications. At this point, I don't believe we can disclose any more data based on the recommendation from regulators and advisors and the importance of keeping the data integrity for the filing. Gorsuch.

The the selection has not happened at the end the study enrollment.

In terms of the availability and that the promise of that they stuff from the interim analysis as you all know very well interim analysis are places on the small number of patients and they only kids into a preliminary glimpse of what the totality of that they thought well look like.

Slices most before the assessment of that a few Chile. He and then the any safety signal sets as such the sentiment that's all the way by our they'd that safety monitoring board them. That's got all mentioned.

The common she was I commented to continue the study without modification so at.

This point I don't even if we can that would kind of that has a this close anymore. They taught by some of the recommendation from regulate dose and advisors and the and that and the importance of keeping that they tightened technology for the filing.

Dr. Anna Vyatek: Which dosage should be used? There was a question about which dosage.

Dosage.

Used it was a good question about which dosage.

Dr. Anna Vyatek: So, in terms of combination therapy, the dosage we used for CTLA-4 is one milligram per kilogram every six weeks, so it's a much lower dose than in a monotherapy setting for this agent, so that also gives you a potential good safety profile, and that is on top of the PG-1 agents used every two weeks, one milligram per kilogram, sorry, three milligrams per kilogram in this population.

So in terms of the combination therapy and the deleverage we use a point the.

Like or is one that means I'm per kilo grom.

The six weeks, so it's a much lower adult than than.

In the in a mono therapy, so things unfold. This agent. So that's all I'll give you a potential good safety safety profile and doctors on top of the of the you on the and the agents you as the every ER and talk to link so one milligram per kilogram.

So some of its remains on spoke you look in this.

Population.

Dr. Jennifer Buell: And Barron, I'm going to add a couple of points here. On dosing, we have the opportunity and have done the comparability to have flexibility in how we want to dose these products. So the trial is designed to interrogate, as Anna mentioned, biweekly dosing of PD-1, agent 2034 at 3 mg per kg, and agent 1884 at 1 mg per kg. And none of the patients have come off due to intolerability, and that was the reason for selection.

And there and I'm going to add a couple of points here on the on the dosing we have the opportunity and have done that compare ability to have flexibility in how we want to dosing products. So the trial designed to interrogate as Adam mentioned by weekly dosing at PD. One in 10 2030 43 makes for King.

And agent 18, 84, and one make for cake and no none of the patients have come off due to in Tolerability and that was the reason why it sounds like you know selection to get the real value of CP Lakeport dosing, we want to ensure a proper exposure.

Dr. Jennifer Buell: To get the real value of CTLA-4 dosing, we want to ensure proper exposure. Additionally, the PD-1 selection biomarker Now, as you can imagine, Pembro is approved in a selected population, patients who are positive for PD-L1, and we are pursuing, while we'll analyze these data, we believe that when you add CTLA-4 on top of PD-1, it may be able to bring benefits regardless of this particular biomarker selection. And that's an important point, and our data support our hypothesis in this regard. With respect to outcomes, as Anna mentioned, and we're very thoughtful and conservative about the presentation of these data, but I'll say that based on the preponderance of evidence that you're seeing in this indication with this combination, we're very confident in the results that we're seeing as of now.

Additionally, the PD one selection biomarker now as you can imagine we know so pembro is approved in a selected population patients who were positive for PDL one.

And we are pursuing while we'll analyze these data we believe that when you ask the killing fly on top of PD, one it maybe able to bring the benefit regardless of this particular biomarkers selection and that's an important point and our data to support our hypothesis in this regard with respect to the outcome.

Sounds as Adam mentioned, and where we're very thoughtful and conservative about the presentation of these data, but I'll say that based on the preponderance of evidenced that you're seeing in this indication with the combination we're very confident in the results that were seeing as of now.

Okay. Thank you.

Dr. Jennifer Buell: Okay, thank you. And our next question will come from Matt Phipps of William Blair. Please go ahead.

And our next question will come from Matt Sips of William Blair. Please go ahead.

Operator: Go ahead. Go ahead. Good morning.

Good morning, Thanks for taking my question so.

Operator: Thanks for taking my question. So, I was just wondering if you could maybe firm up the timelines a little bit for the second line cervical filings now that you've completed enrollment in one and are soon to complete enrollment in the other. And I assume, you know, response rate with a certain duration of therapy is what will be needed. Is it six months of duration that you have to report on for expiratory approval, or can you give any clarification there? So Matt, very good questions.

I was just wondering if you could maybe from up the timeline for a little but for the second one is sort of go filings now that youve completed enrollment in one and soon to complete enrollment in the other.

And I assume you know response rate with a certain duration of therapy is what will be needed as it is a six month duration that you have to report on a fruitful for approval or can you give any.

Clarification there.

[noise]. So so not very good questions with respect to the time the timing, while we have a advance these programs and with add on her exceptional team. We are certainly ahead of our earlier projections, but what I will say is that we have not we will serve.

Dr. Jennifer Buell: With respect to the timing, while we have advanced these programs and with Anna and her exceptional team, we are certainly ahead of our earlier projections, but what I will say is that we have not, we will certainly, well, we feel very strongly that we'll hit our VLA filing in 2020. We believe that we are earlier than prior projections, but we have not yet given an actual timeline for that filing. So if you'll just bear with us, we'll continue to keep you informed as much as we can as we advance through this process. We're in the process of now building out the submission package. And ideally, with the extension or with activity, we can see responses and continue to follow patients beyond 6 and, ideally, to 12 and longer, 12 months and longer. But we will know in a few months after dosing what the activity looks like. I hope that helps. Great, yeah, thanks. And then do these have to be filed together, or can they be filed separately? Just, um...

Only a one we feel very strongly that will hit I really filing in 2020, we believe that we are earlier than prior projections, but we have not yet given an actual timeline for that filing and so so if you want just bear with US we'll continue to keep you informed as much as we can as lean as we advance through this process where in the.

Process of now building out the I'm submission package. So on the last point for follow up right now as you know what these patients that diseases really uniformly think they'd all there are no.

No no highly beneficial products for these patients any progress very quickly they progress and eight to 12 weeks.

So that would be the minimum amount of time that we would be following these patients and ideally went that extension or a with activity. We can see responses and continue to follow patients be on six and ideally to 12 in longer until much longer but the we will now in in a few months.

After dosing starts with the activity looks like I hope that helps.

Great. Thanks, and then did they supposed to be filed together or can they be filed.

Separately just [noise].

Dr. Jennifer Buell: These are two independent BLA paths, so they don't need to be filed together.

[laughter] this sounds until end up and and be a life pot. So they don't need to be filed so that the.

Dr. Jennifer Buell: Okay. And then as far as the 1181 development strategy is concerned, I'm just curious if you think you can maybe go after... kind of an accelerated initial pathway, and maybe melanoma patients who don't have that high affinity CD16 allele, or... Did you try to go after other tumor types where maybe TLA-4 hasn't been as effective? Just kind of curious what your current thoughts are on the next steps forward for that program. Matt, thank you very much.

Okay.

And then as far as the 11 81 development strategy. It's just curious if you think too and maybe go after.

I'm kind of an accelerated initial pathway and maybe melanoma patients who don't have that a high affinity CD sixteena Leo or.

If you try to go after other tumor types, where maybe to look for other than as effective just kind of curious what's your current thoughts are on the.

That's for for that program.

[noise] mapping. Thank you very much I'll tell you. We just are coming off of a couple of days ago, We held and advisory Board meeting with our key scientific advisors, who are I'm incredibly experienced in this space and many of their names will be known take two you we've spoken about this opportunity.

Dr. Jennifer Buell: I'll tell you, we just are coming off of a couple of days ago, we held an advisory board meeting with our key scientific advisors who are incredibly experienced in this space, and many of their names will be known to you. We spoke about this opportunity, and based on the data available to us to date, we are pursuing development pathways that will leverage accelerated approvals via the U.S. FDA. We do think that there's a large unmet need in some of these tumors, such as melanoma, as you've mentioned, as well as other tumors where first-generation CTLA-4s are approved, and this next generation may actually expand the benefit to the patients, as you've mentioned. We will be, and Anna can speak to this, collecting data, particularly on this biomarker-selected population as well, but right now It should address all of the mechanisms for a first-generation CTLA-4, plus the added benefit in those patients with the polymorphism. Anna?

And based on that the data available to us to date, we are pursuing development pathways that will leverage accelerated approvals to via the U.S.S.T.J.

Oh, we do think that there's a large unmet need and some of these tumors such as melanoma as he mentioned as well as other tumors, where first generation see tally for their approved.

This next generation may actually expand the benefit to the patients as you've mentioned, we will be in and I can speak to that's collecting data, particularly on this biomarker selected population as well, but right now where we've opened the trials to a broad group because our next gen seasonally for covers the gamut it will.

It should address all of the mechanisms represented recency feeling for policy I didn't benefit in those patients with the polymorphism Anna yes on the I've talked about I think so Oh, you know early in the into development. That's as we say since we are planning to open combination cohorts that as well.

Dr. Anna Vyatek: Yes, and to add to that, I think it's still early in the development, as we stated, we are planning to open combination cohorts, as well as data gathering for different doses for the dose escalation phases. We are contemplating opening those expansion cohorts in a number of indications that could be of interest, such as refractory melanoma indications. So that's definitively in our plans.

Yes, we are pursuing they have got the wincor their friends all his for the dose escalation phase as well I'm contemplating a opening cost adult expansion cohorts in in a number of indications that that self interest such as Ah that's absolutely melanoma indication so well that's.

Definitively you know our plan.

Okay, that's mostly on a gentle so just.

Dr. Jennifer Buell: Okay, lastly on Agentus. So, you know, this has been kind of around in the background for a while, and we talked about spinning off its own entity and getting its own funding. I mean, how confident are you that you can make that happen now? And, you know, I think there's definitely some interest from investors, and I'm trying to reduce the burn rate a little bit, and maybe this is one way where that can happen.

You know this then something that's been kind of around in the background for awhile and talked about spinning off in stone is the P is getting its own funding I mean, how confident are you didn't make that happen, though and.

I think there's stuff with.

And interest for investors and I'm trying to reduce the burn rate a little bit maybe this is one way or will that can happen I guess.

Yeah.

Let me I mean, you hear me [laughter] I'm very good points here or there are several drivers one is that.

Garo H. Armen: Yeah, Matt, let me, I mean, you make some very good points here. There are several drivers.

After the acquisition, so too high profile cell therapy companies.

Garo H. Armen: One is that after the acquisitions of two high-profile cell therapy companies, interest in the field sort of cooled down, and that has had a slightly negative effect on our timelines for funding Agentus independently. However, Agentus has been spun out. It is a separate company in terms of legal, financial, and other considerations. We are getting closer to filing an IND, which I think will be a very important value inflection point for us. We're slated for that IND filing this month, whereas previously we were pursuing autologous and halogeneic formats. Now there is a focus on the halogeneic format. So we will no longer be pursuing the autologous format, which puts us in a much more focused strategy. And so once we file our IND and the operations become clarified for investors, we feel very confident that we will be able to fund this company separately in the next few months.

The interest in the field sort of a cool down and that has had a slightly negative effects in our timelines Oh funding and battery. However.

Agenda to has been spent out.

It is a separate.

Company interim show legal financial and other considerations.

We are getting closer to filing at I.M.D., which I think we'll be a very important value inflection point for us with slated for that I'd be filing this month.

Whereas previously we were pursuing balls.

Autologous and allogeneic formats now there is focused on the I would you make format. So we will no longer be pursuing autologous format, which is what's actually that much more focused strategy and ER and show one.

We file our I N D.

And the operations become clarified for investors, we feel very confident that we will be able to fund. This company separately in the next few months.

Garo H. Armen: All right, thank you very much. Our next question will come from Harshida Polishetty, an investor. Please go ahead. Hi, good morning. Congratulations on the quarter, and thank you for providing the updates this morning. Just one question on my end. With regard to the Gilead collaboration,

All right. Thank you very much.

Our next question will come from heart Szeto, Polish Eddie and Investor. Please go ahead.

Hi, good morning, Congrats on the quarter and thank you for providing the update this morning Ah. That's one question on my end.

With regard to the Gilliat collaboration I noticed that they fight off you know filed to offer up to 11.1 million up agenda shares on October 20 said the says the entire goliat stake in agenda as if I remember correctly. So I was hoping you could provide some color on what's happening there and perhaps a brief update on topic.

Harshida Polishetty: I noticed that they filed to offer up to $11.1 million in Agenus shares on October 26.

Harshida Polishetty: This is the entire Gilead stake in Agenus, if I remember correctly. So I was hoping you could provide some color on what's happening there and perhaps a brief update on how the collaboration is progressing.

Collaboration is ongoing.

Garo H. Armen: is ongoing.

Sure.

Garo H. Armen: Sure. As you know, Harshita, we have...

And as you know our sheet Oh, we have.

Fulfilled.

Garo H. Armen: Fulfill all of our 2019 milestone obligations with Gilead. And our collaboration is proceeding on a very, very positive path. And so there are additional opportunities in the coming years in terms of additional milestone payments and so on that we're very hopeful will materialize, including in 2020.

All of our 2019 milestone obligations with Ah Gilliat.

And our collaboration is proceeding on a very very positive Pat.

And so our additional opportunities in coming years interim show additional milestone payments and so on that was very hopeful will materialize, including in 2020 .

Garo H. Armen: With regard to the filing that you're referencing, unfortunately, because of legal requirements, sometimes disclosures are misleading. I mean, you'd expect that the SEC and the legal profession would make language disclosures that would be crystal clear, but that's not the case, unfortunately. And so this filing of 11 million shares is simply a registration step. As per contractual obligation, and we've done this previously with other companies where there is a share exchange, we are obligated to register the shares. It has nothing to do whatsoever with Gilead's interest in selling shares. In fact, to the best of our knowledge, Gilead has absolutely no plans to sell any of the shares, as we have seen no such sales from our previous partnerships. So it's a combination of language that, unfortunately, is not as clear as it should be, and perhaps investors are not indulged in reading beyond the first paragraph.

With regard to the filing that you're referencing.

Unfortunately beef because all.

Legal requirements, sometimes disclosures.

Our misleading I mean, you would expect that the FCC and the legal profession would.

Make this.

Language disclosures that would be crystal clear, but that's not the case Unfortunately and so this filing on 11 million shares is is simply a registration statement Cheryl as current contractual obligation and we've done this previously.

With other companies, where these a share exchange.

We are obligated to register the shares it has nothing to do whatsoever with deal we had interest to sell shares in fact for the best for about an hour give you had had absolutely no plans to share. So any other shares as we have seen no such sales.

From our previous partnerships so.

It's a combination of.

Or language that unfortunately is not as clear as it should be and perhaps investors not indulging in reading be on the first paragraph.

[noise] right. That's really helpful. Thank you so much for the color Garo.

Garo H. Armen: Great. That's really helpful. Thank you so much for the call, Garo.

It's a pleasure.

Operator: It's our pleasure. Again, if you have a question, please press star.

Again, if you have a question. Please press Star then one.

Operator: Again, if you have a question, please press star, then 1. This concludes our question and answer session. I would like to turn the conference back over to Dr. Garo Armen for any closing remarks.

[noise].

This concludes our question and answer session I will like to turn the conference back over to Dr. Garo Armen for any closing remarks. Please go ahead. Thank you very much Chuck how she does question has sort of evoked are there.

Garo H. Armen: Remarks. Please go ahead.

Garo H. Armen: Thank you very much, Chuck. Harshita's question has sort of evoked other sorts of misperceptions. One misperception is that we have a significant amount of debt on our balance sheet. And once again, this is an accounting mishap in the way things are disclosed. So we have no substantial debt on our balance sheet. What that is is representative of the royalty arrangement that we did with HCR about a couple years ago, or less, which obligates us to put a number on our balance sheet that has nothing to do with our debt obligation. In fact, under no circumstances could that debt obligation be triggered.

Sorry, I missed perceptions.

One of these perception is that we have a significant.

In mountrail debt on our balance sheet.

And once again this is an accounting.

Mishap in the way things are disclosed so we have no substantial debt on our balance sheet, what what that is is.

Representative all the royalty arrangement that we did with H.C.R.

A body couple of years ago, or less which I'll get access to put a number on our balance sheet that has nothing to do without debt obligation in fact under no circumstances that that obligation could be triggered.

Garo H. Armen: And, in fact, as Jen mentioned earlier, our only debt obligation, which was $27.5 million, has already been extinguished because of the success of Shingrix. Shingrix sales have exceeded a certain amount, which is a billion dollars in net revenues that have extinguished that obligation. And moreover, if you look at the publicly disclosed Shingrix revenues and annualize that number... We will meet the next two milestones in the course of 2020 for payment of an additional $40 million to Agenus. So next year, we expect to have reasonable milestones, including this one, that will augment our cash position. And when we make a public disclosure in our financial statements that we have enough cash for this second quarter of next year, it does not include all of these additional milestones that are due to us.

And in fact is as John mentioned earlier.

Our only that obligation, which was 27 and a half a million dollars has already been extinguished because of the success of Shingrix Shingrix sales have exceeded a certain amount a wishes <unk> billion dollars in net revenues that extinguishes.

Right.

And and Moreover, if you'll look at the publicly disclose shingrix revenues.

And annualize that number.

We won't meet the Knicks, two milestones and of course are 2024 payment or additional $40 million go Agenuss. So next year, we expect to have.

Reasonable milestones, including this one.

That will augment our cash position.

And when we make a public disclosure in our financial statements that we have enough cash.

Into this second quarter off next year. It does not include all over these additional milestones that are due to us. So just bear with us well make things a lot more clearer going forward and at the expense. So simplicity, a we will add simple comp.

Garo H. Armen: So just bear with us. We'll make things a lot clearer going forward. And at the expense of simplicity, we will add simple comments that make these disclosures more digestible and less confusing. So, thank you very much for your attention. We look forward to keeping you abreast of additional progress. And we're heading into a very exciting 2020 in terms of both data and other accomplishments, and we look forward to communicating all of that to you. Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Means that make these disclosures more digestible and less confusing. So thank you very much for your attention. We look forward to keeping you abreast of additional progress and we're heading into a very exciting 2020 Oh in terms of <unk> data and other accomplishments.

And we look forward to communicate well look back to you. Thank you.

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