Q3 2020 Agenus Inc Earnings Call

[music].

Operator: Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Agenus third quarter 2020 conference call and webcast. At this time, all participants are in a listen-only mode.

Good morning, ladies and gentlemen, thank you for standing by and welcome to the Janice third quarter 2020 conference calls and Webcasts at this time all participants are in a listen only mode should you need assistance. Please.

Operator: Should you need assistance, please signal a conference specialist by pressing the star key, followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press the star key, then one on your touch-tone phone.

Signal a conference specialist by pressing the Starkey followed by zero. After today's presentation, there would be an opportunity to ask questions to ask a question. You May Press Star then one aren't get Touchtone phone to withdraw your question press the pound key. Please note. This event it's being recorded.

Operator: To withdraw your question, press the pound key. Please note, this event is being recorded. I would now like to turn the conference over to Dr. Jennifer Buell, president and chief operating officer of Agenus. Dr. Buell, please go ahead.

It I would now I'd like to turn the conference over to Doctor, Jennifer view, President and Chief operating officer of a genus Dr. Bill. Please go ahead.

Dr. Jennifer Buell: Thank you very much, Cheryl. And thank you all for joining us today. Today's call is being webcast. It will be available on our website with our accompanying slide material for replay.

Thank you very much Cheryl.

And thank you all for joining US today, today's coughing webcast it won't be available on their website with our accompanying slide material for replay.

Dr. Jennifer Buell: Before we start, we'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans and timelines, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filing for more details on these risks. As a reminder, this call is being recorded for audio broadcast.

Before we start we'd like to remind you that this Halloween food forward looking statements, including statements regarding a clinical development regulatory commercial plans and timelines as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties and we refer you to a SEC filing for more details on these rhett.

As a reminder, this call is being recorded for audio broadcast.

Dr. Jennifer Buell: I'm Jennifer Buhl, President and Chief Operating Officer of Agenus. We're really delighted to provide an update today on our business. Joining me are Dr. Garo Armen, Chairman and Chief Executive Officer, and Christine Klaskin, Vice President of Finance. Now I'll turn the call over to Garo to highlight our key accomplishments and plans. Thank you, Jen, and thank you all for your participation in this call.

I'm, Jennifer beautiful, President and Chief operating officer of a Janice, we're really delighted to provide an update today on our business.

Joining me, our Doctor thorough Armen, Chairman and Chief Executive Officer, and Christine class skin Vice President.

Finance.

No I'll turn the call over to go out to highlight are key accomplishments and plants.

Thank you and thank you all for your participation in this call.

Garo H. Armen: Today, I will begin with a recognition of our team's resolve and commitment to deliver for our patients and their families. We have made excellent progress in advancing our LEAD programs, Bustelumab and Zoliferumab, to BLA filing and made important advancements with our next wave of innovations, which are in the clinic. This wave of innovations includes Agent 1181, our ST Enhanced Next Generation Anti-CTLA-4 Antibody, our differentiated CD137 agonist, agent 2373; agent 1223, our intracumeral Treg depleting antibody by specificity, and our allogeneic INKT cell therapy for patients with cancer and COVID-19. These achievements have set us up for potentially transformative advances in the treatment and cure of cancer. At the beginning of this year, we hosted an R&D day in New York.

It's a very I will begin with a recognition of our team's resolve and commitment to deliver for our patients and their families.

We have made excellent progress in advancing I'll leave programs.

Map map could BLA filings and made important advancements with our next wave will be no ratios, which are in the clinic.

This way well renovation.

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Aging 11 81.

If see enhanced next generation Mtc Kelly for antibody.

Our differentiated C. D 137 agonist agent 23 73.

Adrienne 12, 23, Oh intra tomorrow T rig depleting by specific.

And our our generic I N K T cell therapy for patients with cancer and COVID-19.

These achievements have set us up for potentially transformative advances in the treatment and cure of cancers.

In the beginning of this year, we hosted in R&D day in New York, We outline friends that would bring us to our first PRA filing for I'll leave molecules. While also advancing are novel pipeline of differentiated first or best in class molecules.

Garo H. Armen: We outlined plans that would bring us to our first PLA filing for our lead molecules, while also advancing our novel pipeline of differentiated first or best in class molecules. We committed to share data readouts from six clinical programs this year. As promised... First, having generated positive clinical data from the Bali monotherapy trial of 160 patients, we have initiated a rolling BLA filing with the FDA and paid the filing fee of approximately $2.9 million in the third quarter of this year. Second, we presented impressive data from our Bally plus Zally 155 patient combination trial. We are in discussions with the agency regarding a potential VLA filing. Third, we have generated clinical response data in our AGEN 1181 Phase 1 trial. Additional clinical response data will be presented by Dr. Steven ODay at CIDC on November 14. We are particularly excited about this program. Fourth, clinical data from our AGEN 2373 dose escalation trial is maturing. We will provide an overview of these data at CIDSE and expect to present additional data at upcoming conferences.

We committed to share data readouts from six clinical programs this year.

As promised.

First having generated positive clinical data from valley monotherapy trial over hundred 60 patients we have initiated the rolling BLA filing with the FDA and paid the filing fee over approximately $2.9 million in the third quarter of this year.

Second we presented impressive data from our valley, plus Sally 155 patient combination trial.

We are in discussions with the agency regarding your potential will be already filing on this one.

There we have generated critical response data in our age.

Adrienne 11, 81 phase one trial.

Additional clinical response data will be presented by Dr. Stephen All day. It's 50 on November 14th we are particularly excited about this program.

Fourth clinical data from our agent $23 73 dose escalation trial is maturing.

We will provide an overview of these data at 50 and expect to present additional data at upcoming conferences. In addition, we expect to start combination trials of Asia and $23 73 will without stiller Mab soon.

Garo H. Armen: In addition, we expect to start combination trials of Agent 2373 with our Bacillimab soon. Data from our bispecific antibody, Agen 1223, is also maturing. And we expect to present clinical data at upcoming clinical conferences. We are delayed in generating clinical data from our very exciting allogeneic INK T-cell program due to COVID-19, but we are now screening patients for imminent enrollment. We are particularly excited about this program because, one, the ability of INKT cells to kill cancer cells directly as well as by recruiting other components of the immune army, and also two, the ability of INKT cells to kill cells that are infected with viruses such as COVID-19, while also they regulate or modulate immune overactivation. This is a very important property of INKT cells beyond activating the immune response.

Fifth.

Data from our by specific antibody Adrienne 12, 23 is also maturity.

And we expect to present clinical data it also upcoming clinical conferences.

Sixth.

We are delayed in generating critical data from our very exciting our genetic iron case yourself program.

Due to COVID-19.

But we are now screening patients for imminent enrollment.

We are particularly excited about this program because one.

The ability of iron K T cells to kill cancer cells.

Correct, Lee as well as by recruiting other components of the immune army.

And also to the ability o'brian K T cells to kill cells that are infected with viruses such as COVID-19.

Whoa also they regulate or modulate immune over activation. This is a very important property of I N K T cells beyond.

Debating immune response.

Garo H. Armen: And unlike many other cell therapies, we expect to deliver a potential benefit to both cancer patients and patients with serious viral infections, at a much lower cost. It is also important to note that 13 Agenus-discovered clinical-stage compounds have cleared initial safety at multiple doses. Our next steps will be the rapid advancement of a number of these programs to combination treatment, with our own agents such as Bally and our next-gen CTLA-4 antibody, agent 1181. Next, while we are advancing our clinical programs, our innovation engines continue to yield new and exciting products which are rapidly progressing toward the clinic. This year... We submitted seven abstracts to six, and all seven were accepted for presentation.

And unlike many other cell therapies, we expect to deliver potential benefit to both cancer patients and patients with serious viral infections.

At a much lower cost.

It is also important to note that 13 agenda is discovered clinical stage compounds clear through initial safety at multiple doses.

Our next steps will be rapid advancement of and number of these programs to combination treatments with our agents such as valley and our next Gen. <unk> for antibody AGN 11 81.

Next.

While we are advancing are clinical programs are innovation and Jones continue to yield new and exciting products, which are rapidly advancing towards the clinic.

This year, we submitted seven abstracts to city.

And Oh seven were accepted for presentation.

Garo H. Armen: Our CT presentations include four clinical and three preclinical programs. CITSI, as you know, has become one of the most notable immune oncology conferences in the world. And we look forward to our presentations between November 11 and November 14. In a few moments, Jen will provide you with detailed highlights of these presentations. However, please be mindful that the full details from these presentations will only be discussed and disclosed at CITSI in compliance with CITSI disclosure rules.

Our system Presentation's include for clinical and three preclinical programs.

C. As you know has become one of the most notable oncology car prices in the world.

And we look forward to our presentations between November 11th and November 14th.

In a few moments Jen will provide you with detailed highlights of these presentations. However, please be mindful that the full details from these present patients will only be discussed and disclosed at city and compliance with C disclosure rules.

Garo H. Armen: Now, let me briefly discuss an important driver of our innovation. It is the Agenus Proprietary Vision Platform, which is one of our seven presentations at CityDistrict. A week ago, I took half a day to work in our vision laboratories, where we do state-of-the-art research with state-of-the-art equipment and with our exceptional team of scientists. Here is vision's value for us and also what it does. Agenus' vision can investigate the stages of various types of immune cells, including T-cells. It allows us to study these T-cells in a simulated human tumor microenvironment. Typically, T cells go from their naive state, to their activated state, and then to their efficacious state, otherwise known as the Tumor Co-Killing State, and ultimately to their non-efficacious or exhausted state.

Now let me.

Discuss briefly and important driver of our innovation.

It is the agenda as proprietary vision platform, which is one of our seven presentations at 50 this year.

A week ago I took a half a day to work in our vision laboratories, where we do state of the art research, which state of the art equipment and with our exceptional chemo scientists.

Here is visions value for us and also what it does.

Hey, Janice vision can investigate stages of various types of immune cells, including T cells.

Vision allows us to study these T cells in a simulated human tumor microenvironment.

Typically T cells go from there and naive state.

They are activated state and then to their efficacious state.

Otherwise known as tumor chewing state and.

And ultimately to their none efficacious or exhausted state you.

Garo H. Armen: You may have heard the term T cell exhaustion; that is what this refers to. The VISION platform enables the investigation of the effect of therapeutic drugs and genetic interventions to determine how they can enhance the efficacious state of T-cells. So the objective here is to keep T-cells in an efficacious state as long as possible or to drive them into that efficacious state. The platform recapitulates known markers of pathology in the tumor microenvironment and helps discover new relevant markers. With all of this, we can investigate new hypotheses in immune oncology. Agenus Vision is an in vitro translational model of multicellular interaction seen in the in vivo tumor microenvironment and therefore has the potential to direct patient-specific therapy by mimicking the tumor biology seen in patient biopsies.

You may have heard the term tissot exhaustion.

That is what this refers to.

The vision platform unable to the investigation bowlby effect or therapeutic drugs and genetic interventions.

And how they can enhance the efficacious state of T cells. So the the objective here is to keep T cells, and an efficacious state as long as possible or to drive them into that application state.

The platform recapitulates known markers of apology and the tumor microenvironment and helps discovered new relevant markers with all of this we can investigate new hypotheses immune oncology.

Janice vision is an in vitro translational motto or multi cellular interactions seen in the in vivo tumor microenvironment, and therefore has potential to direct patient specific therapy by mimicking the tumor biology seen in pay.

Mission biopsies.

Garo H. Armen: In brief, we have designed a proprietary platform where, at any given point in time, we can intervene with our molecules and other molecules to modulate a model human system to determine the best therapy option for patients. We believe that our vision platform has the potential to transform cumbersome and lengthy clinical trials into an agile trial matching platform to meaningfully benefit cancer patients. The platform also has potential utility in studying the immune response to infections. Also, among recent exciting developments are data presentations by companies to whom we have licensed our molecules. For example, at ESMO last month, Merck provided an update on MK4830, an anti-ILT4 antibody that Agenus discovered and licensed to Merck several years ago. The data with this myeloid targeting molecule generated quite a bit of attention with 11 objective responses, including two complete responses and nine partial responses in heavily pre-treated patients with advanced thalate tumors. Agenus is entitled to an additional $85 million in milestone payments plus royalties from commercial sales of this agent.

In brief we have designed a proprietary platform.

At any given point in time, we can intervene with our molecules and other molecules to modulate a model human system.

To determine the best therapy option for patients.

We believe that our vision platform has the potential to transform cumbersome and lengthy clinical trials into an agile trial matching platform, who meaningfully benefit cancer patients. The platform also has potential utility and studying the immune response.

To infections.

Also among recent exciting developments are data presentation's by companies, who we have our license molecules too.

For example, it is more last month.

Provided an update on M. K four 830.

This is an anti ILP for antibody that agenda discovered and lie system Mirc several years ago.

The data with this myeloma targeting molecule generate that quite a bit of attention.

11 objective responses, including to complete responses and nine partial responses in heavily pre treated patients.

Advanced solid tumors.

Janice is entitled to an additional 85 million and milestone payments plus royalties from commercial sales of this agent.

Garo H. Armen: It is also important to note that we have also advanced our own unencumbered myeloid cell targeting program. We have an undisclosed myeloid cell targeting program of our own, which we're targeting to file an IND-4 next year. In the second quarter of this year, we filed two separate cell therapy INDs, both of which were cleared to proceed to the clinic. We made a strategic decision at the time to prioritize our COVID patient enrollment program, and having cleared all institutional requirements, we're in the process of screening patients and expect to dose our first patient imminently. INK T-cells are invariant natural killer T-cells.

Also important to note that we have also advanced our own unencumbered myeloid itself targeting programs.

We have an undisclosed my Lord so targeting anybody who are are long, which we're targeting to file an hi, Andy for next year.

And the second quarter of this year, we filed two separate cell therapy and these both of which were cleared to proceed to the clinic.

We made a strategic decision at that time to prioritize our covert patient enrollment program and having cleared all institutional requirements. We're in the process of screening patients and expect to dose our first patient imminently.

I N K T cells are invariant natural killer T cells remember these R T cells.

Garo H. Armen: Remember, these are T-cells, a unique cell type that combines the features of both innate and adaptive immunity. These lipid ligand binding cells have tumor targeting capability without the need for engineering, and they also have a natural ability to suppress graft versus host. Together, these features underscore the attractive development attributes of INKTs with the benefit of scalability since they are allogeneic. Finally, we turn to our most powerful adjuvant asset in our pipeline.

Or a unique sometime.

Combines the features of inmate and adaptive immunity.

Is lipid ligand binding samples have tumor targeting capabilities without the need for engineering and they also have a natural ability to suppress graft versus host disease.

Together. These features underscore attractive development attributes of land.

With the benefit of scalability since they are our generic.

Finally.

Turning to our most powerful adjuvant acid in our pipeline.

Garo H. Armen: QS21 Stimulon Agilus, is in GSK's Shingrix vaccine, the most effective shingles vaccine with over 90% efficacy and which has achieved blockbuster sales status in its first two years after launch. Although there was an interruption in its sales momentum related to COVID-19 this year, sales seem to be on track and rising, and if they continue with this current trend...

<unk> 21, similar adjuvant.

Is in Gsk's shingles vaccine the.

The most effective shingles vaccine with over 90% efficacy and wishes achieved blockbuster sales that is in his first two years after launch.

Although there was an interruption in its sales momentum related to call at 19 this year.

Sales team to be on track and rising and if they continue with this current trend.

Garo H. Armen: It will trigger a milestone payment of $25 million, which could be in 2021. QS21 is clearly the most powerful adjuvant that we know. However, its supply is capped because of the limited supply of its raw material, which comes from a Chilean soapbark tree.

It will trigger.

Millstone payment of $25 million, which could be in 2021.

Two of 21 is clearly the most powerful adjuvant that we know.

However.

Why is kept because of the limited supply raw material, which comes from a Chilean soapbark tree.

Garo H. Armen: Agenus has been working on a more sustainable supply of feedstock for QS21 Stimulon since 2015. We have addressed this by developing a proprietary renewable source. And recently, we have validated 2S21 Stimulon quality and biological activity from this source. Further, we entered a contract this month to scale up the production of QS21 similan from this source material with phyton biotin. And now, a few words about our manufacturing and supply chain. Now, to some of you, manufacturing supply may be in the background, but it is critically important in advancing programs. Without it, we certainly could not have achieved the number of IND filings and the advancements in the clinic. On the topic of sustainable supply, this pandemic has heightened everyone's awareness of the importance of access to materials. We have now seen firsthand the value of independence in manufacturing and supply.

<unk> has been working on a more sustainable supply of feedstock for 221 still Milan.

2015.

We have addressed this by developing a proprietary renewable source and recently, we have validated choice 21, similar in quality and biologic activity from this source.

Further we enter that contract this month to scale up the production of curious 21 similar from this source material with Phyton biotech.

And now a few words about our manufacturing and supply chain now to some of you manufacturing supply may be in the background, but it is critically important in advancing programs without it we certainly could not have achieve.

The number of Randy filings and the advancements in the clinic.

And the topic of sustainable supply. This pandemic has heightening the everyone's awareness on the importance of access to material.

We have now seen first hand, the value of independence in manufacturing and supply.

Garo H. Armen: While we didn't anticipate this pandemic, we did anticipate the need for fully integrated capabilities for a sustainable supply of goods and materials to complement our innovation, all for the purpose of benefiting patients with a sense of urgency that requires speed and innovation. Our research, productivity, and pipeline have yielded more than 20 novel programs, with 15 INDs filed in four years. This productivity would not have been possible without our manufacturing and supply team at Agenus West, especially in this world when access to manufacturing slots is getting scarcer, timelines are being delayed, and material is more difficult to access. Our internal manufacturing and CNC capabilities give us the freedom and flexibility to accelerate our development programs as well as provide access for our current and future partners. And we have done some of this in the past couple of years.

While we didn't anticipate this pandemic, we did anticipate the need for fully integrated capabilities for a sustainable supply of goods and materials to complement our innovations.

All for the purpose of benefiting patients with a sense of urgency which requires speed and innovation.

Research productivity and pipeline has yielded more than 20 novel programs with 15 Ind's filed in four years.

This productivity would not have been possible with our men without our manufacturing and supply team at the agenda is west.

Especially in this world when access to manufacturing slots is getting scarcer.

Timelines are being delayed and material is more difficult to access our internal manufacturing and C&C capabilities give us the freedom and flexibility to accelerate our development programs as well as provide access for our current.

And future partners and we have done solve this in the past couple of years that is manufactured product for our partners.

Garo H. Armen: That is the product manufactured for our partners. Our Agenus West team has delivered more than 11 GMP batches for our own use and for partners in just the last few years alone. And lastly, an update on our partnership. As I mentioned earlier, our innovation engine has given rise to 15 clinical stage programs, with seven of those advancing through strategic collaborations with Merck. Gilead, Eurogen, Insight, and most recently with Beta Pharmaceuticals. Beta is a China-based pharmaceutical company to whom we have licensed greater China rights for our PD-1 and our first generation CTLA-4. That's Val Enzo.

Our agenda West team has delivered more than 11, GMP bachelors for our own use and four partners in just the last few years alone.

And lastly, an update on our partnerships.

As I mentioned earlier.

Our innovation engine has given rise to 15 clinical space programs with seven of those advancing through strategic collaborations with Merck.

Gilead Euro Jen inside and most recently with better pharmaceuticals.

Better is a China based pharmaceutical company to whom we have licenses greater China rights four hour PD one and.

And our first generation CTO April.

Let's bow Enzo.

Garo H. Armen: These partnerships have generated substantial financial value for us, with the additional value extending access to our innovations to patients at an accelerated pace, which would not have been possible with our own capabilities alone. This strategy has allowed us to nearly double the number of molecules advancing in clinical development by leveraging the support and infrastructure of our collaborators. While we ultimately endeavor to retain all rights to our innovations, in the near term, balancing between retaining rights to some of our agents, with an emphasis on the U.S. right, and out-licensing others with an emphasis on ex-U.S. rights, is prudent for us fiscally as well as responsible for advancing our innovations into the clinic. Thus, partnering collaborations and innovative transactions are core to our strategy. This strategy has generated more than $575 million of income in the past five years to help fund our operation, as part of this strategy, to maximize the value of our own I.O. portfolio going forward.

These partnerships have generated substantial financial value for us with the additional value expanding access to our innovations to patients at an accelerated pace, which would not have been possible without phone capabilities alone.

This strategy has allowed us to nearly double the number of molecules advancing in clinical development.

By leveraging the support and infrastructure our collaborators.

Collaborators.

While we ultimately endeavor to retain all rights to our innovations in the near term balancing between retaining rights to some of our agents with an emphasis on U S rates.

And our licensing others with an emphasis on X U S rates is prudent for us physically as well as it's responsible for advancing innovations into the clinic.

Thus partnering collaborations and innovative transactions are core to our strategy.

This strategy has generated more than $575 million of income to us in the past five years, who have fallen into our operations.

As part of this strategy.

Garo H. Armen: We will also provide access to others who can advance clinical programs in combination with some of their own agents with our products, such as PD-1 and CTLA-4, while we retain full rights to the commercialization of our products. This will help accelerate the pace of market expansion for our molecules. In addition to IO-IO combinations, we also have non-immuno-oncology agents, which is a very substantial market. Today, we announce the first of these collaborations with Brother Farm.

To maximize the value of our own Iowa portfolio going forward. We will also provide access to others, who can advanced clinical programs in combination with some of their own agents with our products such as speeding one NCT away for <unk>.

While we retain full rights please commercialization of our products.

This will help accelerate the pace of market expansion of our molecules.

In addition to Iowa, Idaho combinations with also nausea.

On college agents, which is a very substantial market.

Garo H. Armen: Rutherfarm is a leading innovative Italian biotech company dedicated to drug discovery and development with a pipeline of new chemical entities, that is, small molecules, as well as biotherapeutics... Through this collaboration, Rutter Farm will evaluate the safety and efficacy of CR 6068, Rotter Farm's Portland EP4 receptor antagonist with Bulfilimab in patients with advanced mismatch repair, proficient, and microcephalized stable metastatic colorec

Today, we announce first though these collaborations would ratify biotech rather farm is a leading innovative Italian biotech company dedicated to drug discovery and development with a pipeline of new chemical entities that is small molecules as well as biotherapeutic.

<unk>.

Throw this collaboration rather farm will evaluate the safety and efficacy of C. R 6068.

A lot of farms important for receptor in packages.

Garo H. Armen: I realize that's a mouthful, but it's an accurate description of the reality for these cancers, a development area of high unmet need, that is, and where immune therapies alone have not demonstrated significant clinical benefits so far.

Both still the math in patients with advanced mismatch repair proficient and Michael centralized stable metastatic colorectal cancer I realized as a mouthful, but it's an accurate description of the reality for these cancers.

Garo H. Armen: Lastly, as of today... We are in active CDA discussions with nine major pharma and biotech companies for potential out-licensing transactions. This is the most, by the way, breadth of companies that we have had ongoing active discussions with. These could result in the infusion of significant amounts of cash.

And development area of high unmet need that is and we're immune therapy as alone have not demonstrated significant clinical benefit so far the.

The trial is expected to commence this year.

Lastly.

As of today.

We are in active.

Discussions under CDA with nine major pharma and biotech companies.

Garo H. Armen: We will update you appropriately if and when some of these transactions come to fruition. And now, I will turn the call over to Jen to provide you with a summary of data from ESMO, our Commercial Launch Readiness Plans, and the upcoming data from SIDS, without violating the disclosure rules, of course. Gen.

For potential out licensing transactions. This is the most by the way.

Most breath of companies that we have had ongoing active discussions with.

These could result in the infusion of significant amounts of cash.

We will update you appropriately if and when some of these transactions come to fruition.

Dr. Jennifer Buell: Thank you, Garo. As Garo shared, the productivity of our research and development engine is really profound. We're incredibly proud of what we've accomplished and what our teams continue to accomplish.

And now I will turn the call over to adjourn to provide you with a summary of data from as more commercial launch readiness plans and the upcoming data from <unk> without violating the disclosure of course Jen.

Dr. Jennifer Buell: If you look at our pipeline, you'll see more than 20 discoveries targeting very novel biology. You'll see that we've brought 15 of those to IND and now into the clinic. These are being advanced now in our own hands and in the hands of our partners, giving us an opportunity to actually expand the breadth and reach of our science and our innovation. Here at Agenus, we're advancing eight of these programs. And I should highlight that this efficiency is coming out of a company that has just over 200 employees, which is incredibly efficient. And the number of INDs, we've shared this with you before, the number of INDs that we filed in the past four years has rivaled our largest competitors, Bristol, Merck, Novartis, and others. So again, just to emphasize all of the capabilities that we have in-house with a very efficient team. And now we're advancing eight of these programs in our own hands.

Thank you and Kyle.

As Gary shared.

Of activity of our research and development engine, it's really profound are incredibly proud of what we've accomplished of our teams continue to accomplish if you're looking at pipeline nothing more than 20 discoveries unlisted with targeting very novel Biology.

See that we've brought 15 of <unk>.

<unk> and now into the clinic.

These are being advanced now in our own hands and in the hands of our partners gives us an opportunity to actually expand the press and reach of our science and innovation.

Hurry to Janice were advancing eight of these programs that I had highlights that this efficiency is coming out of our company. That's just over 200 employee which is incredibly efficient and the number of <unk>. We share. This with you before the number of <unk> that we filed in the past four years, hence Reinhardt, our largest competitors based on Mac, Nevada.

Dr. Jennifer Buell: We've already provided clinical updates to you on the first three of these programs so far this year, most recently at ESMO. Those updates included data on Balsilumab, our PD-1, Zalifelumab, our anti-CTLA-4, AGEN-1181, our FC-engineered, next-gen CTLA-4. And during the upcoming CITSE, in the next couple of weeks, we're going to present an update on an additional four clinical programs and three very novel programs and platforms. I'm going to turn to Esmo and summarize some of the data that many of you may be aware of, but others may not.

Others.

So again just to emphasize all of the capabilities that we have in house with a very efficient team and now we're advancing eight of these programs in our own hands.

Already provided clinical updates to you on the first three of these programs. So far this year most recently at as now.

There are updates included data and filling up our PD one talon selamat are anti <unk> four.

Eliminating one hour FC engineered Nextgen <unk> four.

And during the upcoming city in the next couple of weeks, we're going to present, an update on an additional or clinical programs and three very novel programs and and platforms.

I'm going to Kansas to ask Merlon summarized some of the data that many of you may be aware, but others may not.

Dr. Jennifer Buell: At the recent European Society for Medical Oncology, this is the ESMO meeting, Dr. Dave O'Malley, he's a professor of obstetrics and gynecology at the Ohio State University College of Medicine. He's also the director of the Division of Gynecologic Oncology. He presented results from the largest data set of patients with relapsed refractory or metastatic cervical cancer treated with anti-PD-1, Arbalstilamab, alone or in combination with our anti-CPLA-4, Xeloprelamab. The more than 300 patients' worth of data will support our BLA filing, which is now well underway. In fact, we've received confirmation that the FDA has commenced the review of our BLA starting with our CMC module. The ESMO presentation is available in the events and presentation section of our website. I encourage you to have a good look at it.

At the recent European Society Medical oncology. This is the asthma meeting Dr. Dave O'malley, He's a professor of obstetrics and gynecology at the Ohio State University College of Medicine. He is also the director of the division of Gynecologic oncology.

He presented results from the largest data set of patient with relapsed refractory or metastatic cervical cancer treated with anti ped, one or bastogne app alone or in combination with our anti <unk> four download fellowman.

The more than 300 patients worth of data will support our BLA filing which is now well underway. In fact, we have received confirmation that the FTA has commenced they review of our BLA, starting with our CMC mild Manuel.

The ethanol presentations available on our events and presentations section of our website I encourage you to have a good look at that and I'm going to highlight a few resounding messages and James presentation now.

Dr. Jennifer Buell: But I'm going to highlight a few resounding messages from Dave's presentation. Notably, Keytruda is approved in PD-L1 positive tumors only, and in the data for cervical cancer from Merck, Keytruda has shown no clinical responses in PD-L1 negative tumors. This suggests Valstilumab may be a differentiated anti-PD-1 antibody, and 160 patients treated with belacelamab or PD-1 as monotherapy.

I'll still amount has shown activity and both PDL, one part of the test and PDL one negative tumors.

Notably Keytruda is approved and PD outlet positive tumors only.

And then the data and cervical cancer framework Keytruda has shown no clinical responses and PDL one negative tumors.

This suggests bilestone that may be a differentiated anti ped one.

And 160 patients treated with pastel, an app or P. D. One as a mono therapy, we reported response rate of 19% and PDI, one positive patient and 10% and PBR one negative patient.

Dr. Jennifer Buell: We reported response rates of 19% in PD-L1 positive patients and 10% in PD-L1 negative patients. This compares to the commercial PD-1 inhibitor, Keytruda, with 14% response rates in PD-L1 positive tumors and no response rates in PD-L1 negative tumors. The durability of this trial and of these responses is quite impressive, exceeding 15 months, and patient follow-up continues. When we add xalifrolumab to belastilumab in the same population of refractory metastatic cervical cancer patients, we see an important expansion in response rates to a near doubling in PD-L1 positive tumors of 27%. This represents a benefit that has not yet been observed with any available therapy for patients with cervical cancer. Importantly, we also see an extension in the durability of these responses, where the median duration of response has not yet been achieved after 16 months.

This compares to commercial PD, one keytruda with 14% response rates and PDL, one positive tumors and no response rates NPD one negative tumors.

The durability of this child. These end up these responses is quite impressive exceeding 15 months and patient follow up continues.

When we add solid fell amount to balance telecom and the same population refractory metastatic cervical cancer patients. We see an important expansion in response rates into a near doubling and PDL one positive tumors of 27%.

This represents.

Benefit that has not yet been observed with any available therapies for patients with cervical cancer.

Importantly, we also see an extension and the durability of these responses where the median duration of response has not yet been achieved after 16 months.

Dr. Jennifer Buell: These data underscore not only the clinical activity of our molecules and the meaningful potential for patients with cervical cancer, including those who have no effective options, such as patients with PD-L1-negative tumors, but they also showcase the details supporting our robust BLA filing for balacelamab, which, as Garo mentioned, is already underway. We consider PD-1 to be an essential component for use with our own pipeline, as well as with the pipeline of others. Although there are several commercially available PD-1s and others in development, there are significant advantages to having our own PD-1. The first consideration is, of course, affordability and flexibility in developing combinations.

These data underscore not only the clinical activity of our molecules in a meaningful potential for patients with cervical cancer.

Including those who have no effective options such as patients with PDL one negative tumor.

But it also showcases the details supporting our robust BLA filing for Bastille, a map, which as Carol mentioned is already underway.

We consider PD, one as being an essential component for you.

With our own pipeline as well as with the pipeline of others.

Although there are several commercially available PD, one and others in development.

A significant advantages to having your own PD one the first is of course affordability and flexibility and developing combination.

Dr. Jennifer Buell: Our own I-O pipeline is highly synergistic with PD-1. This pipeline includes agents such as our first-generation Xelophelemab and anti-CTLA-4 agents, such as Agen 1181, our next generation FC Enhanced Multifunctional Anti-CTLA-4 Antibody.

Our own I owe pipeline is highly synergistic with PD one.

This pipeline includes agents such as our first generation xylophone have an anti <unk> for an agent.

Adrienne 11 81.

Our next generation SCN hand, multi functional anti detailing for antibody.

Dr. Jennifer Buell: Our FC-enhanced, body-specific, PIDGET antibody, HN1777; this is expected to be in the clinic next year. Our differentiated CD137 antibody, Agent 2373, and our very exciting intra-tumoral Treg depleting antibody, Agent 1223, also in the clinic, and our allogeneic INKT cell therapy for patients with cancer, which will be in the clinic this year. This list of compounds is synergistic with our PD-1, and we've presented data at AACR, ESMO, and ASCO demonstrating the value of the combination of these agents with our PD-1. Another huge advantage of having PD-1 in-house is to control pricing of our combinations.

Our asking enhanced five specific pincheck antibody HN 17, 77. This is expected to be in the clinic next year.

Our differentiated CD 137 antibody 823 73.

And now are very exciting entered tomorrow T ranked depleting <unk> specific antibody agent 12 23 also in the clinic.

And our allogeneic I N K T cell therapy for patients with cancer, which will be in the clinic this year.

This list of compounds are synergistic with our PD, one and we present the data.

Alright, asthma would ask out demonstrating the value of the combination of these agents with our P. D. One.

Another huge advantage of having a P. D. One in house is to control pricing of our combinations combinations will be required for effective treatment and control of cancer.

Dr. Jennifer Buell: Combinations will be required for effective treatment and control of cancer, and pricing will be an important component of access to these molecules. The advantages offered by having our own PD-1 for our own purposes are becoming clear, and also that other companies who need a PD-1 to combine with their own pipeline of agents or their own commercial products may prefer to use our PD-1, that is, Faustina Mab, versus others, for all the reasons that I've cited above. We plan to follow the BLA filing for Bell Stilomab.

And pricing will be an important component of the access to these molecule.

The advantages offered by having our own P. D. One for our own purposes, it's becoming clear and also that other companies who need a P. D. One two combined with their own pipeline of agent or their own commercial products may prefer to use our PD one.

That is I'll spell them out versus others for all the reasons that I've stated above.

We plan to follow the the BLA filing about selling them.

Dr. Jennifer Buell: With the combination BLA in the same population, so adding xalophralumab to balacelumab in patients with cervical cancer, within a few months of our filing, we're preparing for an upcoming pre-BLA meeting with the FDA this year to finalize our plan. We see Valstilumab as an important addition to therapies for patients with cervical cancer who have clinical responses and broadly in both positive and negative tumors, and we believe that the combination has the potential to be the first checkpoint combination in cervical cancer with the potential to bring practice-changing benefits to patients with high response rates that are durable. The second-line cervical cancer market includes approximately 4,000 patients, as you know, and about half of them seek treatment. And we're positioning ourselves to capture a good proportion of this market.

With the combination BLA and the same population, so adding zeller fell on them about filling that in patients with cervical cancer within a few months of our filing we're preparing for an upcoming prevail a meeting with the FDA this year to finalize our plans.

We see Bilestone that is an important addition to therapy for patients with cervical cancer with clinical responses and broadly in both positive and negative tumors and we believe that the combination has the potential to be the first checkpoint combination and cervical cancer with the potential to bring practice changing benefit.

Patients with high response rates that are durable.

The second line cervical cancer market includes approximately 4000 patients as you know.

And about half of which seek treatment and we're positioning to capture a good proportion of this of this market of this market.

Dr. Jennifer Buell: Our commercial and medical plans incorporate a multifaceted approach with three major pillars involving Data Generation and Publication, building awareness of our therapies, and educating the market on the unmet need for patients with cervical cancer. Awareness is a critical component of rapid adoption, and this is a key area of focus for our teams. We've taken several steps to address this in recent months, including detailed presentation of data at ESMO for both monotherapy and the combination, and preparation of this data for rapid publication in high-impact journals. We've already deployed a team of experienced medical science liaisons, or MSLs, to engage in the community and scientific exchange. Based on our analyses, we plan to hire a nimble and efficient sales force focused on targeting higher volume gynecologic oncology accounts.

A commercial and medical plans incorporate a multifaceted approach with three major pillars involving.

Generation in publication.

Building awareness of our therapies and educating the market.

That need for patients with cervical cancer awareness is a critical component of rapid adoption and this is a key area of focus for our teams. We've taken several steps to address this in recent months, including detailed presentation of data as Mal for both monotherapy and the combination and preparation of this data for rapid publication and high impact.

Journals.

We've already deployed a team of experienced medical science liaisons or MSL to engage in the community and scientific exchange based on our analyses we plan to hire a nimble and efficient salesforce focused on targeting higher volume gynecologic oncology account are fit for purpose commercial launch effort.

Dr. Jennifer Buell: Our fit-for-purpose commercial launch effort is being managed by an experienced launch team who have led the successful commercial launches for several products in oncology and rare diseases at large pharmaceutical companies, such as BMS. Our launch preparations will lay the foundation for the innovation to follow. Our pipeline is built for stacking, for bringing together optimal combinations for patients in ways that no one else can and delivering robust value reproducibly. As the limitations of PD-1 therapies become more obvious, and the obsolescence rates of current therapies increase, we are prepared to meet the growing needs of patients and providers with new therapies that can be combined affordably and accessibly. Now this is a good time to discuss the innovations that are following the launch of Balsillumab and Xalophrelumab. Agent 1181 Agent 1181 is our next-generation FC-enhanced anti-CTLA-4 antibody. It's poised to be a transformative CTLA-4 asset. It's rationally designed with FC engineering to optimize its action and overcome the shortcomings of first-generation assets.

Is being managed by inexperienced launch team who have led the successful commercial launches for several products in oncology and rare diseases at large pharmaceutical companies such as BMS.

I launch preparations will lay the foundation for the innovation to follow.

Our pipeline is built for stacking for bringing together optimal combination for patients and ways that no one else can and delivering robust value reproduceably as.

As the limitations of PD, one therapies become more obvious and the obsolescence rates of current therapies increase.

We are prepared to meet the growing needs of patients and providers with new therapies that can be combined affordably and excessively.

Now this is a good time to discuss the innovations that are following the launch a bow.

I'll still amount in Dallas Allomap.

First.

Agent 11 81.

811, 81 is our next generation as the enhanced anti <unk> for antibody.

It's poised to be a transformative futilely for asset it's rationally designed with FC engineering to optimize it's action and overcome the shortcomings of first generation assets.

Dr. Jennifer Buell: 1181 has the potential to increase the therapeutic benefit of anti-CTLA-4 therapies and expand responses to a broader population of patients. We've previously reported very promising data that we're seeing with this agent, and we will continue to present additional data. Complete responses are often rare in phase one studies.

11, 81 has the potential to increase the therapeutic benefit of anti <unk> therapies and expand responses to a broader population of patients.

We've previously reported very promising data that we're seeing with this agent and we will continue to present additional data.

Complete responses are often rare in phase one study.

Dr. Jennifer Buell: For Agent 1181, we've already seen two reported complete responses, one of those by a complete response by PET scanning. And these patients both have microsatellite-stable endometrial cancer, very hard-to-treat endometrial cancer, PD-L1-negative tumors. They also both have a genetic polymorphism in their CD16 allele.

The agent I'll have an 81, we've already seen two reported complete responses one of those by a complete response by pet scanning and.

And these patients of both have microsatellite stable endometrial cancer very hard to treat endometrial cancer PDL, one negative tumors. They.

They also both have a genetic polymorphism and their CD 16 LDL.

Dr. Jennifer Buell: These characteristics make them unlikely responders to anti-CTLA-4 therapy or most IOtherapies, but they have seen complete responses to Agen 1181. And we are thrilled to have Dr. Steven ODay to present the updates on these additional data and clinical responses, as well as some exciting mechanistic findings that have not been observed with first-generation anti-CTLA-4 molecules. Dr. ODay has deep experience with CTLA-4. As a matter of fact, he was the first to dose a patient with ipilimumab.

These characteristics make them unlikely responders to anti <unk> for therapy.

Or most Iowa therapies, but they have seen complete responses from HN 11 81.

And we are thrilled to have Doctor, Stephen though day to present the updates on these additional data and clinical responses as well as some exciting mechanistic findings that has not been observed with first generation anti <unk> four molecule Dr.

Dr. Jose has deep experience with seating for as a matter of fact, he was the first to dose the patient with a dilemma Nab. He presented his seminal finding that a plenary session at ask out in 2009, which exemplify the curative power of anti <unk>, four and ignited a field we now call.

Dr. Jennifer Buell: He presented his seminal findings at a plenary session at ASCO in 2009, which exemplified the curative power of anti-CTLA-4 and ignited a field we now call immune oncology. Twenty years later, Dr. ODay was the first to dose a patient with our optimized anti-CTLA-4 agent, Agent 1181, a molecule that we believe will be the next major breakthrough in this field. We're looking forward to his presentation. Now, our allogeneic cell therapies, our INKT. Dr. Birju Yigit is an expert in the biology of INKT cells. She's going to be presenting updated data on our program. INKT cells, or invariant natural killer cells, are a unique cell type that combines the features of both arms of the immune system, the T cells and the NK cells, both adaptive and innate immunity.

Immune oncology 20 years later that Joe day was the first to dose a patient with our optimize anti <unk> for agent agent 11, 81, a molecule that we believe will be the next major breakthrough in this field, we're looking forward to his presentation.

Now are allenton Nag cell therapies R. I N K T.

Dr. <unk> get it is an expert in the biology of I N K T cells.

She is going to be presenting updated data.

On our program I N K T cells or invariance natural killer cells are unique cell type that combines the features of both arms of the immune system. The T cells and the NK cells, both the adaptive and innate immunity. We believe these cells will have an important role in the elimination of tumors and the elimination of viruses such.

Dr. Jennifer Buell: We believe these cells will have an important role in the elimination of tumors and the elimination of viruses such as COVID-19. We've previously reported that our clinical trials for INKT cells in cancer and in COVID-19 were cleared by the FDA. We successfully opened our first site earlier this year at Cornell, and we were just notified that screening has commenced, and we expect to announce the dosing of our patients with allogeneic INKPs imminently. The timing of this trial starting, of course, is in parallel to another uptick in the spread of the virus, and New York is being hit yet again.

COVID-19, we've previously reported that are clinical trials for iron K T cells, and cancer and and Covid were cleared by the FDA.

We've successfully opened our first site earlier this year at Cornell and we were just notified that screening has commenced and we expect to announce the dosing of our patients with valid to Nag <unk> imminently.

The timing of this child's starting of course is in parallel to know another uptick in the spread of the virus in New York as being hit yet again, we're hoping that we can bring benefit to these stations with covid.

Dr. Jennifer Buell: We're hoping that we can bring benefit to these patients with COVID. Beyond COVID-19, these cells have great potential for mitigating cancer, and Agenus is also advancing clinical trials for patients with cancer planned to start dosing also this year. Those trials are also FDA-cleared to launch and will be initiated at Dana-Farber. Turning to our differentiated CD137 anti-CD137 molecule, HN2373, Dr. Claire Galland will be presenting data at CITSE. This molecule is designed with important safety and efficacy features as compared to other molecules. HN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells, both adaptive T cells and innate NK cells. Dual targeting of both innate and adaptive immunity makes this molecule a highly attractive target for cancer immune therapy.

Beyond COVID-19, these sounds have great potential in mitigating cancer and agenda is also advancing clinical trials for patients with cancer plan to start dosing also this year.

Those trials are also FTA clear to lunch and will be initiated Athena fiber.

Turning to our differentiated C D 137.

<unk> C D 137 molecule agent 23 73.

Did clear Golan, who will be presenting data at this molecule is designed with important safety and efficacy features as compared to other molecules.

820, 373, the fully human monoclonal antibody that boost the immune response to cancer cells by enhancing C. D 137, co stimulatory signaling and activated immune cells, both adaptive 2008, and K T cells in case us.

Dual targeting of both the name and adaptive immunity makes us molecule highly attractive target for cancer immune therapy.

I'm very happy to report that 20 373 has dose beyond now the one make for cake dose cohort with no observed liver toxicity previously liver toxicity was what hampered or killed one of the competitor molecule.

Are there more we've observed terrible disease stabilization in patients with ovarian cancer sarcoma announced small cell lung cancer and this early trial tactical on will provide an update on the preclinical and clinical progress and our upcoming combination plans with this molecule.

Dr. Jennifer Buell: I'm very happy to report that 2373 has dosed, beyond now, the 1 mg per kg dose cohort with no observed liver toxicity. Previously, liver toxicity was what hampered, or killed, one of the competing molecules. Furthermore, we've observed durable disease stabilization in patients with ovarian cancer, sarcoma, and non-small cell lung cancer in this early trial. Dr. Galland will provide an update on the preclinical and clinical progress and our upcoming combination plans with this molecule. Turning to TIDGET, which will also be presented at CITSE, it's shaping up, of course, to be the next breakthrough therapy for I.O. But we've seen this.

Turning to ticket, which will also be presented asset theme, it's shaping up of course to be the next breakthrough therapy for I O. We've seen that says conviction supported by the launch of multiple late stage clinical trials by erosion, Mark and others and some recent strategic collaboration we've learned from data presented ASKO from genentech's to jet.

That revealed no monotherapy activity.

And suggested that FC silence as a liability and FC competence at a minimum is necessary now there are a couple of component components to think about this with respect to the FC engineering of an antibody. There is an empty silence, there's an FC competent and then there's an FC enhance which is the engineering that we've been.

Dr. Jennifer Buell: This conviction is supported by the launch of multiple late-stage clinical trials by Roche and Merck and others and some recent strategic collaboration. We've learned from data presented at ASCO from Genentech's TIDGET that revealed no monotherapy activity. It's suggested that FC silence is a liability, and FC competence, at a minimum, is necessary.

Floyd into our agent 11, 81, we have a lot of experience with this enhancement. We've also employed the same technology and technique into our attention molecules, which include our motto specific antibody as well as our Bispecific, we've published that FC enhancements necessary.

To optimally target ticket just to reiterate FC competence nfc's silent molecules are not enough to optimally target ticket biology, you need the FC engineering. The FC enhancement, we've applied our science of the design of two different approaches. This is agent 13, 27 are mono specific ticket antibody and our.

Dr. Jennifer Buell: Now, there are a couple of components to think about this with respect to the FC engineering of an antibody. There is an FC silent, there's an FC competent, and then there's an FC enhanced, which is the engineering that we've employed in our HN1181. We have a lot of experience with this enhancement. We've also employed the same technology and technique in our TIGIT molecules, which include our monospecific antibody as well as our bispecific. We've published that FC enhancement is necessary to optimally target TIGIT. Just to reiterate, FC competence and FC silent molecules are not enough to optimally target TIGIT biology. You need FC engineering, FC enhancement.

By specific agent 17, 77, these molecules unleash T cells NK cells and have demonstrated superior tumor, killing ability compared to other available to join antibodies. We've shown you that data earlier, and we will share more at <unk>.

We have the potential to combine these agents effectively with other agents such as file still amount of our P. D. One.

Now are by specific molecules 17, 77 has some interesting individual promise. This molecule has shown traumatic tumor control in a P. D. One refractory colon cancer mouse model and we've designed it to be used as a monotherapy.

At 50, Dr. Rebecca Award will share important data that underscores the importance of these features for potential best in class biologic activity and in vivo model.

We remain on track to advanced novelty novelty jet molecule to the clinic in 2021.

[noise] Zelman follow ups are first generation <unk>, four and showing important activity, both as a mono therapy as well as in combination with pastel I'm, having patients with cervical cancer. We've continued to interrogate a population of patients that are growing geezer population of patients who have failed PD, one and have nothing else.

Dr. Jennifer Buell: We've applied our science to the design of two different approaches. This is Agent 1327, our monospecific TIGIT antibody, and our bispecific, Agent 1777. These molecules unleash T cells and NK cells and have demonstrated superior tumor-killing abilities compared to other available TIGIT antibodies. We've shown you that data earlier, and we'll share more at CITSE. We have the potential to combine these agents effectively with other I.O. agents such as Balsillumab or PD-1.

We have seen activity with solid Fellowman. We've also seen activity with this molecule and rare tumors such as angiosarcoma, we presented that data and Dr pretty well get our last earnings call highlighted a couple of key findings related to our anti <unk> four zealous Allomap and angiosarcoma. We're also.

Seeing this this activity and other PD one refractory tumors.

And is the growing population of PD Winter factory, Kansas expand <unk> is a follow up on therapy may provide the immune catalyst for a gerbil responses. We've previously reported on two responses and angiosarcoma wholesales PD, one and we look forward at 50 to be following up on these promising responders with new reports of single agent.

Dr. Jennifer Buell: Now, our bi-specific molecule, 1777, has some interesting individual promise. This molecule has shown dramatic tumor control in a PD-1 refractory colon-cancer mouse model, and we've designed it to be used as a monotherapy. At CITSE, Dr. Rebecca Ward will share important data that underscores the importance of these features for potential best-in-class biologic activity in in vivo models. We remain on track to advance a novel tiget molecule to the clinic in 2021. Xelophthalimab is our first-generation CTLA-4 antibody.

<unk> and rare tumors.

And finally, adding to our vast body of knowledge about film App in Dallas fell amount and refractory metastatic cervical cancer is new data demonstrating that suda progression, which is is somewhat come in and immune therapy essentially it occurs in patients.

When there's inflammation around the tomb right actually appears as disease progression, but in fact, it's actually immune attack on the tumor in many cases, sometimes patients are prematurely discontinued from therapy because of the perception that they're tumor may have progressed.

Dr. Jennifer Buell: It's showing important activity, both as monotherapy and in combination with valsthalimab in patients with cervical cancer. We've continued to interrogate a population of patients that is growing. These are populations of patients who have failed PD-1 and have nothing else. And we have seen activity with xalophthalimab.

We are the first to demonstrate in patients with cervical cancer.

See the progression this phenomenon of radiological growth and tumors and tumor size is not due to the spread of cancer patients being treated with immune therapy may discontinue prematurely exist progression R. Tsuda progression is not properly identified and delineated stopping treatment too early it can be detrimental to these peace to.

Dr. Jennifer Buell: We've also seen activity with this molecule in rare tumors such as angiosarcoma. We presented that data, and Dr. Bree Wilk, in our last earnings call, highlighted a couple of key findings related to our anti-CTLA-4 xalophthalimab and angiosarcoma. We're also seeing this activity in other PD-1 refractory tumors. And as the growing population of PD-1 refractory cancers expands, zoliferolamab as a follow-on therapy may provide the immune catalyst for durable responses. We've previously reported on two responses in angiosarcoma who failed PD-1, and we look forward at CITSE to following up on these promising responders with new reports of single-agent activity in rare tumors. And finally, adding to our vast body of knowledge on valstilumab and zalafrelumab and refractory metastatic cervical cancer is new data demonstrating that pseudoprogression, which is somewhat common in immune therapy, essentially occurs in patients when there's inflammation around the tumor.

These patients.

Using our knowledge.

And identification of Cedar progression patterns, and recurrent metastatic cervical cancer, we plan to optimize treatment and care for these patients.

And finishing up with our vision platform is Carl has mentioned earlier or vision platform. It's a proprietary platform designed to recapitulate the human tumor microenvironment in our system that allows us or enables us to to interrupt.

With or intervene with therapeutic intervention and reinvigorate T cells to fight cancer.

Our data set of responding and non refunding patients have given rise to improve matching of patients to our clinical trial and dosing protocols, whether it's combination or sequential and information on molecule designed to optimally address tumor escape mechanisms or revive immune fighting cells.

Since he will be presenting data on how we use the system to identify novel PD one biomarkers the expression of PDL. One on tumors has been used as a standard predictive biomarker for anti PD one therapies, we've utilized our vision system by driving T cell dysfunction in vitro to identify a biomarker that may call into question the <unk>.

Dr. Jennifer Buell: It actually appears as disease progression, but in fact, it's actually an immune attack on the tumor in many cases. Sometimes patients are prematurely discontinued from therapy because of the perception that their tumor may have progressed. We are the first to demonstrate in patients with cervical cancer that pseudoprogression, this phenomenon of radiologic growth in tumor size, is not due to the spread of cancer.

Liability of PDL, one expression and identify other more reliable predictor response predictive molecules.

We're looking forward to a very exciting city program with our seven programs that will be presented there and I am now going to turn the call over to Christine class skin to review our financials Christine.

Thank you Tim.

We ended the third quarter of 2020, with a cash balance of $114 million as compared to $62 million at December 31st 2019.

Dr. Jennifer Buell: Patients being treated with immune therapy may discontinue prematurely if this progression, or pseudoprogression, is not properly identified and delineated. Stopping treatment too early can be detrimental to these patients. Using our knowledge, we plan to optimize treatment and care for these patients.

This compares to a cash balance of $79 million at the end of the second quarter of this year.

For the third quarter ended September 30th 2020 hour cash used inaugurations was $32 million.

That loss for this quarter was $52 million or 28 cents per share and include certain non-cash expenses $18 million.

Dr. Jennifer Buell: And finishing up with our vision platform. As Garo mentioned earlier, our vision platform is a proprietary platform designed to recapitulate the human tumor microenvironment in a system that allows us or enables us to interrupt, intervene with therapeutic interventions, and reinvigorate T-cells to fight cancer. Our dataset of responding and non-responding patients has given rise to improved matching of patients through our clinical trials and dosing protocols, whether it's combination or sequential, and information on molecule design to optimally address tumor escape mechanisms or revive immune-fighting cells. At CITSE, we'll be presenting data on how we use the system to identify novel PD-1 biomarkers. The expression of PD-L1 on tumors has been used as a standard predictive biomarker for anti-PD-1 therapy.

This compares to catch used an operation for the same period in 2019 of $28 million and a net loss of $46 million or 33 cents per share, which included $9 million a non cash expenses.

Our cash used in operations for the nine months ended September 30th 2020, with $104 million with a net loss of 145 million or 88 cents per share compared to cash provided by operations of $13 million in a net loss for the same period in 2019 of $81 million or.

58 cents per share.

For the nine month period ended September 30th 2020, we recognize revenue a $57 million, which includes revenue related to be upfront license fee from our transaction with better in addition to non-cash royalties earned.

Dr. Jennifer Buell: We've utilized our vision system by driving T-cell dysfunction in vitro to identify a biomarker that may call into question the reliability of PD-L1 expression and identify other more reliable response predictive molecules. We're looking forward to a very exciting FTSE program with our seven programs that will be presented there. And I'm now going to turn the call over to Christine Klaskin to review our financials.

For the same period in 2019, we recorded revenue of 116 million, which includes revenue related to the upfront license fee from every transaction with Gilead. In addition to non-cash royalties earned.

Christine M. Klaskin: Thank you, Jen. We ended the third quarter of 2020 with a cash balance of $114 million, as compared to $62 million at December 31, 2019. This compares to a cash balance of $79 million at the end of the second quarter of this year. For the third quarter ended September 30, 2020, our cash used in operations was $32 million. The net loss for this quarter was $52 million, or $0.28 per share, and it includes certain non-cash expenses of $18 million.

I know throws a call back to go for his concluding remarks.

Thank you Kristin country Jam.

So.

There is a lot as I've said in my last call.

And you are wondering how one will make money with all of this and.

And we of course are determined to embark on our strategy to build.

A highly highly successful company.

Our industry and beyond.

And that's based on five important pillars.

And I will go.

Through them one by one very briefly.

Thriller number one is to manage to continue to manage our cash position.

Relative to our cash requirements.

Christine M. Klaskin: This compares to cash used in operations for the same period in 2019 of $28 million and a net loss of $46 million, or $0.33 per share, which included $9 million of non-cash expenditures. Our cash used in operations for the nine months ended September 30, 2020, was $104 million, with a net loss of $145 million, or $0.88 per share, compared to cash provided by operations of $13 million and a net loss for the same period in 2019 of $81 million, or $0.58 per share. For the nine-month period ended September 30, 2020, we recognized revenue of $57 million, which includes revenue related to the upfront license fee from our transaction with VEDA, in addition to non-cash royalties earned. For the same period, in 2019, we recorded revenue of $116 million, which includes revenue related to the upfront license fee from our transaction with Gilead, in addition to non-cash royalties earned. I now turn the call back to Garo for his concluding remarks. Thank you, Christine. And thank you, Jen.

As you can see from this quarter's report and our performance over the last few years, we have done this well.

That is until.

We can bridge to an infusion of significant amount of cash.

Either one or more transactions and that's what we're working on diligently.

So that's number one number two very important.

Position are first generation products.

With building over commercial presence in order to optimize the revenues of these products and I'm talking about specifically Bali and Valerie and how do we do that by bringing in a very competent first class launch and commercial.

Team, which we have brought in a team from outside now that has provided us with a turnkey operation and are in the process installed building our own team for our needs going forward now once we launch our first generation products, we will optimise their red.

Prepare show for the proven indications, but most importantly beyond approved indications in combination with our products and as I explained before in combination with other products, including non Io agents.

Garo H. Armen: So, there's a lot, as I said in my last call, and you are wondering how one will make money with a... And we, of course, are determined to embark on our strategy to build a highly, highly successful company in our industry and beyond. And that's based on five important pillars, and I will go through them one by one very briefly.

Surgery.

Embark on our strategy of sprinting towards her approval for our pipeline of clinical products that in our opinion has very very.

Exciting potential in fact blockbuster protection among those included in that category is Jerome described <unk>.

Garo H. Armen: Pillar number one is to continue to manage our cash position relative to our cash requirements. As you can see from this quarter's report and our performance over the last few years, we have done this well. That is, until we can bridge to an infusion of a significant amount of cash from either one or more transactions. And that's what we're working on diligently. So that's number one. Number two, very importantly, position our first generation product, with the building of a commercial presence, in order to optimize the revenues of these products. And I'm talking specifically about Bally and Zally.

181 or Mixtion.

<unk> four molecule and also importantly are 23 73 or C. D 137 antibody that we're starting to see some data on this that we believe will be particularly exciting when we start our combination trials with 23.

73, and also very importantly.

R I N K T cells.

We believe.

Iron Katie cells work the way, we expect them to work so commercial potential of this.

Mortality is quite significant.

Fourthly.

Garo H. Armen: And how do we do that? By bringing in a very competent first-class launch and commercial team. We have brought in a team from outside now that has provided us with a turnkey operation, and we are in the process of building our own team for our needs going forward. Now, once we launch our first generation products, we will optimize their revenue potential for the approved indications, but most importantly, beyond approved indications, in combination with our products and, as I explained before, in combination with other products, including non-IOH. Thirdly, embark on our strategy of sprinting towards approval for our pipeline of clinical products, which, in our opinion, have very, very... exciting potential, in fact, blockbuster potential. Among those included in that category, as Jen described, 1,181 are Next Gen. CTLA-4 molecules, and also, importantly, our 2373, our CD137 antibody, that we're starting to see some data on this that we believe will be particularly exciting when we start And also, very importantly, our INKT cell. We believe if INKT cells work the way we expect them to work, the commercial potential of this modality is quite significant. Fourthly, we will continue to innovate with our pipeline, soon to be in the clinic. They include Agen-1777, our tigit by specific molecule, and are also undisclosed.

We will continue to innovate.

With our pipeline soon to be in the clinic.

Include Adrian one triple seven.

Sure.

My specific molecule.

And are also undisclosed.

My Lord so targeting antibody.

The we expect offer these molecules could be in the clinic next year.

And lastly, we believe given the breath of transactions and the retro molecules that we're partners. We're partners through third parties, we believe by helping them optimize their potential for products that we have license them.

We believe we can generate over time, a cash annuity to fund our business.

So with that I will stop and try out for the operator to see if there are any questions weakness.

Laurel.

Ladies and gentlemen, if you would like to ask a question. Please press Star then the number one on your telephone keypad will pass, but just a moment to compile but Q&A roster.

Your first question is from the line of my neck and one Tommy.

Thanks for taking Leguizamon redo his so much progress across the by blood, including audio on them and button and program them. Congrats on the into six Donnelly do it in from the left to get a community, let's see and hopefully from your food. Your partners. So I have a few questions on this a lot going on.

So blue values lead combination filing.

Garo H. Armen: Myeloid cell targeting... We expect both of these molecules to be in the clinic next year. And lastly, we believe, given the breadth of transactions and the breadth of molecules that we have partnered with third parties, we believe by helping them optimize their potential for products that we have licensed them, we can generate, over time, a cash annuity to fund our business. So with that, I will stop and turn it to the operator to see if there are any questions we can answer. Cheryl.

But again.

Again could you could you just need to what.

So I'm reading the numbers.

<unk> so the mood.

<unk> ended up to a beautiful island.

Hi, Matt I wasn't able to use that we waiting for a duration of response and we don't yet have the median duration of response achieved but we this may take quite a bit of time patients are brick.

Peculiarly with the combination are staying on therapy, and they're having really quite lengthy and durable responses.

Operator: Ladies and gentlemen, if you would like to ask a question, please press star, then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A list. Your first question is from Myank Mamtani. Thanks for taking my question and great to hear so much progress across the pipeline, including wholly owned and partner programs, and congratulations on the interest externally, including from the investigator community at CIDSE and hopefully from your future partners. So I have a few questions; obviously, you have a lot going on.

So that won't hold us up from any of our regulatory issues with the combination.

That's just something that will follow and continue to report on.

Theoretically.

And practically the longer it takes for us to reach duration of response, the better the patients are doing great.

Right right. Okay. So what would you say then is Ah Ah.

<unk>.

Is it.

Just digging it sequentially given agency has a lot going on on oncology Goldman specific stuff. So you're just digging it sequentially Dubia live filings that please.

Mayank Mamtani: So for Valley-Valley combination filings, again, could you speak to what we are sort of waiting there for, is it duration of response, or is it, you know, longer-term safety tolerability data in regards to your NDA filing? Mark, I wasn't able to, you said, are we waiting for a duration of response? So we don't yet have the median duration of response achieved, but this may take quite a bit of time. Patients are, particularly with the combination, staying on therapy, and they're having really quite lengthy and durable responses. So that won't hold us up from any of our regulatory issues with the combinations. That's just something that we'll follow and continue to report on. I mean, theoretically and practically, the longer it takes for us to reach durational response, the better the patients are doing. Right, right?

The success rate there are a few reasons for that my arm can we have as we've mentioned we have some partnership activity with with access to Bali.

It's a very straightforward filing and just technically there was there was there was an opportunity to engage the agency develop our relationship with them through the monotherapy filing.

The trials were run in parallel the data were collected essentially in parallel and the submission will be semi parallel. So we're still in the preparation phase for the combination there are some advantages to just pushing the the bowels till about filing in this year as a mono therapy and and follow.

Weighing in but we expect and we're in the process of speaking with the agency and the total package requirements et cetera that the combination will be just a couple of months behind the monotherapy.

Right.

Great. Thanks, so much for that information to my next question kind of got the garage.

Dr. Jennifer Buell: Okay, so what would you say then is the gating step here? Is it that you just are taking it sequentially, given, you know, the agency has a lot going on, you know, non-oncology, you know, COVID specific stuff. So are you just taking it sequentially, the two BLA filings? Is that basically?

Your multiple checkpoint programs for aged M. N C. B a LIBOR also so the importance of engineering as you highlighted you know the F. C. <unk> a visit for example.

The look that bill yet and I was so then it goes decided there'll be three study today like you said Morgan Rose have UFC comprehend. So maybe you know just.

Dr. Jennifer Buell: That's right. There are a few reasons for that, Mayank, and we have, you know, as we've mentioned, we have some partnership activity with Access to Bali. It's a very straightforward filing.

Talk to me about how you think about you know 1181 M.

Let me see that when they go data homeless either skiing. It is do you know other other programs that you have and.

And you know this entire concept of S B N and.

Dr. Jennifer Buell: And just technically, there was an opportunity to engage the agency, develop our relationship with them through the monotherapy filing. The trials were run in parallel, and the data were collected essentially in parallel.

Again guns actually makes a lot of sandwiches and the gimmick.

<unk>.

Highlighted different approaches a different company with a good day.

Ah let me just make a couple general comments allow veteran answer the the rest of the question but.

Dr. Jennifer Buell: And the submission will be semi-parallel. So we're still in the preparation phase for the combination. There are some advantages to just pushing the BAL-SILIMAP filing in this year as a monotherapy and following it up, but we expect, and we're in the process of speaking with the agency on the total package requirements, et cetera, that the combination will be just a couple of months behind the monotherapy. Right. Great. Thanks so much for that explanation!

One thing that I think is important for everyone to realize is that there is very defined strategy or pursuing leads and programs that have an advantage over anybody else's agents in other words.

If we have a puget molecule.

Only way, we justify advancing that molecule is if we can clearly demonstrate superiority over other molecules that we either internally generate that is we generate other molecules true test hours of the games or.

Mayank Mamtani: So my next question kind of cuts across, you know, your multiple checkpoint programs for TIGIT and CTLA-4 also. So the importance of FC engineering, as you highlighted, the FC depleted version of TIGIT, for example, is being looked at. Gilead and AstraZeneca also started their phase three studies today.

We procured to test our molecules again, so long list, we can demonstrate bed.

Rigorously, we don't take programs forward and so when we come up with lead such as 23 70 threes or one Triple February. These are have been validated by our systems, including the usual.

A vision technology went applicable in order to justify our further investment to take it forward, we don't do it because target is fashionable.

Dr. Jennifer Buell: Like you said, Merck and Roche have the FC competent. So maybe, you know, just talk to me about how you think about, you know, 1181, when we see that clinical data, how much de-risking it is to, you know, other programs that you have and, you know, this entire concept of FC enhanced, again, conceptually makes a lot of sense, but just in the clinic, as you highlighted, there are, you know, different approaches at different companies. Let me just make a couple of general comments, and I'll let Jen answer the rest of the question. But one thing that I think is important for everyone to realize is that there is a defined strategy of pursuing leads and programs that have an advantage over anybody else's agents.

Jen.

And maybe a few Pointsman 11, 81, why don't we choose the route that we chose and we presented these data publish them in Kansas 2018, and it was really.

It it feels shaking and that we're getting we have quite a bit of interest, particularly in this molecule. In the features have played out in the clinic quite well and the differentiating features of doing the F. C enhancement versus other approaches like the AC constantly that approach.

Few phone then I'm just going to highlight the most important and is that through the FC engineering. The enhancement. We avoid complement mediated toxicities. These are the hypothesised us narrow endocrine disorders that actually have hampered these are irreversible toxicity, we see them in about 15% of patients to retreat.

With first generation Ccls for us and we very much wanted to be able to take advantage of all of the value of <unk> for which we now and it's the data are out there. It was that it's really the only molecule where we see the tail of the current phenomenon. These long durable caritive responses. So we want it to be able to expand and brought in the population too.

Dr. Jennifer Buell: In other words, if we have a tiget molecule, the only way we justify advancing that molecule is if we can clearly demonstrate superiority over other molecules that we either internally generate, that is, we generate other molecules to test ours against, or we procure them to test our molecules against. So unless we can demonstrate that. Rigorously, we don't take programs forward. And so, when we come up with leads, such as 2373 or 1777, these have been validated by our systems, including the use of vision technology when applicable, in order to justify our further investment in taking it forward. We don't do it because the target is fashion.

Could have that experience without some of these irreversible toxicities.

The enhancement has allowed us to do that and and we have not seen any narrow endocrine disorders are toxicities and our trial to date. The other features of course, so are to broaden the population of responders to those who may have Ah polymorphism in their CD 16, allele and that's more than 40% of the population those patients do.

Not respond the first generation Ccls for these are data presented by us and others and we are seeing responses with those patients on our trial patients who have these mutations so it's acting as designed and then finally of course and we've presented Sns's mechanistically.

Driven it's the enhanced immunogenicity that we see and we've shown that date those data with 11 81 was 11 81 in combination with Val <unk> as well as with our ticket molecule on these data are all available publicly on our website and just two days ago, Dr. Dan Chan head of our discovery group here presented it.

Garo H. Armen: So, Jen, after you. And maybe a few points, Mayank. So, 1181, why did we choose the route that we chose? And we presented these data, published them in CancerCell in 2018, and it was really sort of field-shaking in that we're getting, you know, we've had quite a bit of interest, particularly in this molecule, and the features have played out in the clinic quite well. And the differentiating features of doing the FC enhancement versus other approaches, like the AFU-cosylated approach, are a few-fold, and I'm just going to highlight the most important one is that through FC engineering, the enhancement, we avoid complement-mediated toxicities. These are the hypophysitis and neuroendocrine disorders that actually have hampered, these are irreversible toxicities.

The ticket conference we've made that publication presentation available for you on our website and it will showcase at the features that we've leveraged into our 11 81, that's given us the benefit that we're seeing right now in patients we've engineered into ticket the difference and the difference in the approaches that we've te.

And I believe maybe because of the timing of development. Some of these earlier ticket molecule were designed a few years ago and did not benefit from some of the science that we know today in that we've published on as well now.

We're all just waiting to see how some of these data will play out and IRA mehlman from genetic in his own words believes that FC competence is critical FC Ssilence is going to be problematic.

And now we believe that it's one step more than that but FC engineering or enhancements will be even even better than FC competence alone.

Dr. Jennifer Buell: We see them in about 15% of patients who are treated with first-generation CTLA-4s. And we very much wanted to be able to take advantage of all of the value of CTLA-4, which we know, and the data are out there. It's really the only molecule where we see the tail of the curve phenomenon, these long, durable, curative responses. So we wanted to be able to expand and broaden the populations who could have that experience without some of these irreversible toxicities. SC Enhancement has allowed us to do that, and we have not seen any neuroendocrine disorders or toxicities in our trial to date. The other features, of course, though, are to broaden the population of responders to those who may have a polymorphism in their CD16 allele, and that's more than 40% of the population. Those patients do not respond to first-generation CTLA-4. These are data presented by us and others, and we are seeing responses with those patients on our trial who have these mutations. So it's acting as designed.

So that so that's why we pursued the approach that we've pursued.

We're following the science here and and the data will continue to play out, but I think that the ticket conference is very informative and I think dan's contributions to that will help to better elucidate why we've chosen the path that we've chosen.

That's great I really appreciate the detailed explanation. So my last question. If I may on do 373 as you know you. You said you were thinking about combination the could.

Could you.

Just kind of share your thoughts based on what you see and whether it's going to be a more traditional b D. One combination or are you also a big CBL at four and my second part to that question is do you also.

Got a payment drunk like.

Like you had from mug <unk> before.

This goes onto the next stage of development Ah. Thanks, so much for taking my questions.

Okay. So maybe I'll, so first with respect to the to the Ah combination approach and.

You you hit them very important points and there's some science this less well adopted by the community, but that we believe it's really opportunistic and that is that includes combinations beyond PV one now that's.

Dr. Jennifer Buell: And then finally, of course, and we've presented this, and this is mechanistically driven; it's the enhanced immunogenicity that we see. And we've shown that those data with 1181, with 1181 in combination with valstilumab, as well as with our TIGIT molecule, and these data are all available publicly on our website. And just two days ago, Dr. Dan Chan, head of our discovery group here, presented at the TIGIT conference. We've made that publication presentation available for you on our website, and it will showcase the features that we've leveraged into our 1181 that's given us the benefit that we're seeing right now in patients, we've engineered into TIGIT. The difference in the approaches that we've taken, I believe, may be because of the timing of development. Some of these earlier TIGIT molecules were designed a few years ago and did not benefit from some of the science that we know today, and that we've published on as well.

What we know is C. D 137 molecules that we've seen in the clinic and tumors like melanoma, and Ah lung cancer and others. We have seen the combinations with city 137, Agnes NPD, one have great value for patients. The problem has been the liver toxicity that we've seen with those other molecule also the inability to safely dose tolerably dose.

These molecules in combination the design of ICT 137 molecule allows us to get around that we have not seen hepatic toxicity, so, but we're not averse to a traditional more traditional combination to started we have a lot of data on both film App and there's a strong rationale for the combination with PD one that.

That said those combinations will essentially be traditional and base case in your words and I agree with you we will add on other very novel compounds that we can deliver and others cannot <unk> is one really important and complementary agent to Staticity 137, Agonism, we've got.

Really impressive preclinical data to support some of the plans that we have for the for this molecule and will be more public about it as we continue to expand this trial. The protocol amendment is underway. So you'll start to see the updates on what are clinical plants are with city 137, just in the next couple of weeks.

Dr. Jennifer Buell: Now, you know, the world is waiting to see how some of these data will play out, and Ira Melman from Genentech, in his own words, believes that FC competence is critical; FC silence is going to be problematic. Now we believe that it's one step more than that, that FC engineering or enhancement will be even better than FC competence alone. So that's why we've pursued the approach that we've pursued. We're following the science here, and the data will continue to play out, but I think that the Tidget Conference was very informative, and I think Dan's contributions to that will help to better elucidate why we've chosen the path that we have chosen. That's great. I really appreciate the detailed explanation.

With respect to the the option programs. These I have prenegotiated financials with with with Gilead and I'll turn it over to Garrett the highlight a couple of those points. So.

Would regard true milestones for the balance of this year next year and beyond you can expect perhaps one milestone we would term that is very minor milestone this year from.

One of our partners.

There will be the most significant milestone expect before next year will be there <unk> 25 million dollar.

Mayank Mamtani: So my last question, if I may, on 2373, as you know, you said you were thinking about combinations there. Could you just kind of share your thoughts based on, you know, what you've seen, whether it's going to be a more traditional PD-1 combination, or are you also thinking CDLA-4? And the second part to that question is, do you also record a payment from Gilead like you did from Merck for the ILT-4 if this goes on to the next stage of development? Thanks so much for taking my question. Okay, so maybe I'll, first, with respect to the combination approach, and, and, you hit some very important points, and there's some science that's less well adopted by the community, but that we believe is really opportunistic. And that is, that includes combinations beyond PD-1.

Really milestone.

But in terms of transaction income.

Forward your balance of this year or next year.

Those will come from medium or large transactions.

Will be characterized as new transactions.

Through from existing milestones those will be the more meaningful components of income.

For next year.

Fantastic abuse it'd be updated thanks for taking my question.

Thanks Man.

Your next question is from the line of match steps with William Blair.

Pay my grocery just kind of one for me.

Just curious.

In conjunction with this at the meeting if you'll be able to give me some more concrete plans for 11 81, you guys with North Dakota leather thing ways. You can go with the next steps to a molecule whether it's.

Dr. Jennifer Buell: Now, that said, what we know with CD137 molecules that we've seen in the clinic in tumors like melanoma and lung cancer, and others, we have seen that combinations with CD137 agonists and PD-1 have great value for patients. However, the problem has been the liver toxicity that we've seen with those other molecules, so the inability to safely dose or tolerably dose these molecules in combination. The design of our CD137 molecule allows us to get around that. In fact, we have not seen hepatotoxicity.

Spirits individual.

And the current trial or kicked me off with those two trials Linda Covid Kodachrome gruesome.

The business Valley, which I know you guys just posted a neutral angiosarcoma. So good to do the you.

You know just go with the Bill moving those too.

<unk> please.

Hi, Matt. Thanks, Thanks, very much for your for your question 11, Yes. The answer is yes, we will give more clarity and I'll tell you a few reasons.

Dr. Jennifer Buell: So a more, but we're not averse to a traditional combination to start. We have a lot of data on valstilumab, and there's a strong rationale for the combination with PD-1. That said, those combinations will essentially be traditional and base case, in your words, and I agree with you.

We very recently met with our scientific Advisory Board and just to reiterate there on our website, but these are and really astute group of scientists that were thrilled to be working with and it includes Mario snow encourage self are in Palo Rousseau and done about half and while Hidalgo, Stephen though day real experts in drug development.

And specifically an immune therapy development and we went through all of the date of the preponderance of data that we have to see and we've actually agreed on the fact that we have a very active dose and a very active combination dose that we will now proceed with the child that that we believe will be design.

Dr. Jennifer Buell: We will add other very novel compounds that we can deliver and others cannot. And CTLA-4 is one really important complementary agent to CD137 agonism. And we've got some really impressive preclinical data to support some of the plans that we have for this molecule, and we'll be more public about it as we continue to expand this trial. The protocol amendment is underway, so you'll start to see updates on what our clinical plans are with CD137 in just the next couple of weeks. With respect to the option programs, I have pre-negotiated financials with Gilead, and I'll turn it over to Garo to highlight a couple of those points. So with regard to milestones, for the balance of this year, next year, and beyond, you can expect perhaps one milestone this year from one of our partners.

<unk> to support a very rapid.

BLA filings our next wave.

Rx clinical expansion for 11, 81 will be very very important for us and will be designed for to interrogate activity in a few different target tumors of interest where we believe that we have differentiated and superior approach and.

In March market opportunities. So we will be disclosing these plans with you this year.

Okay.

As one spread to have a few items.

All the questions. So we can properly and Nicole.

R.

Nine minutes over.

Dr. Jennifer Buell: There will be the most significant milestone expected for next year will be the GSK $25 million royalty milestone. But in terms of transaction income, for either the balance of this year or next year, those will come from medium or large transactions that will be characterized as new transactions as opposed to from existing milestones. Those will be the more meaningful components of income for X.

There are no further questions at this time, Sir are there any closing remarks.

Thank you very much everybody I think we've covered quite a bit.

And we look forward to communicating all the excitement in coming weeks months in a year.

Okay.

Ladies and gentlemen. This concludes today's teleconference. Thank you for your participation you may now disconnect.

Mayank Mamtani: Fantastic. Appreciate the update. Thanks for taking my call. Thanks, ma'am. Your next question is from the line of Matt Phipps with William Blair.

[music].

Matthew Phipps: Morning, thanks for taking my question; it's just kind of one for me. Just curious if, in conjunction with this CISI meeting, you'll be able to start giving some more concrete plans for 1181. You guys have talked about a lot of different ways you can go with the next steps for that molecule, whether it's expanding into individual tumor types in the current trial or kicking off some phase two trials, and then just again, kind of balancing that versus Advancing the Valley, which I know you guys just posted a trial on angiosarcoma, so good to see that. But, you know, just kind of the balance of moving those two assets forward.

Dr. Jennifer Buell: Thanks. Hi Matt, thanks very much for your question. Yes, the answer is yes. We will give more clarity, and I'll tell you a few reasons.

Dr. Jennifer Buell: We very recently met with our scientific advisory board. And just to reiterate, they're on our website. But this is a really astute group of scientists that we're thrilled to be working with. And it includes Mario Snoll and Kurt Schelper and Pat LaRusso and Don Van Hoff, Manuel Hidalgo, and Steven ODay, real experts in drug development and specifically in immune therapy development. And we went through all of the data, the preponderance of data that we have to date, and we actually agreed on the fact that we have a very active dose and a very active combination dose that we will now pursue with the trial that we believe will be designed to support a very rapid VLA filing. Our clinical expansion for 1181 will be very important for us and will be designed to investigate activity in a few different target tumors of interest where we believe that we have a differentiated and superior approach to large market opportunities.

Dr. Jennifer Buell: So we will be disclosing these plans with you this year. As a special thanks for all the questions, Cheryl, we can promptly end the call. We are about nine minutes over. There are no further questions at this time, sir. Are there any closing remarks? Thank you very much, everybody. I think we've covered quite a bit, and we look forward to communicating all the excitement in the coming weeks, months, and years. Ladies and gentlemen, this concludes today's teleconference. Thank you for your participation. You may now disconnect.