Welcome to the twenty twenty annual meeting for Agenus. Our host for today's call is doctor Garo Armen, chair and CEO. At this time, all participants will be in a listen only mode. I will now turn the call over to your host, Doctor. Armen.
You may begin.
Good afternoon, everyone. I'd like to call to order the Genesis twenty twenty Virtual Annual Meeting of Stockholders. I am Garo Armen, Chairman and CEO of Agenus. With me today are Doctor. Jennifer Buell, our President and COO Evan Kearns, our Vice President and General Counsel and Secretary and the following members of our Board of Directors, Brian Corvese, here in person, Doctor.
Allison James Ellis, Bill Jordan, Ulf Wimber, and Kim Wright virtually. I'd like to thank them all and each one of you, whether participating by proxy in advance of meeting or online today, for your time and commitment to Agenus. And now, I'd like to turn things over to Evan Kearns to conduct the formal portion of our meeting. After completion of the formal portion, I will come back with a few remarks and answer any questions in a slightly more creative format that we have adapted our this year's annual meeting and we will end it after remarks by Doctor. Buell with a roundtable discussion and we'll inform you about the participants of that discussion in just a bit.
Doctor. Kearns?
Good afternoon. Thank you, Garo, and welcome to all of our stockholders. We will now begin the formal portion of the annual meeting. This meeting was called by our Board of Directors on 04/23/2020. I have received an affidavit of distribution from Broadridge Financial Services that notice of this meeting was furnished by the company on or about 04/29/2020 to every holder of record of common stock as of the close of business on 04/24/2020, the record date The for this Board of Directors has appointed Christine Klaskin as the Inspector of Elections for this meeting.
Ms. Klaskin has signed the oath of office, which will be filed with the records of this meeting, and she has prepared a report stating that the holders of majority of the outstanding shares of common stock of the company as of the close of business on the record date are present or represented by proxy at this meeting. Therefore, I declare that a quorum is present. The list of stockholders as of the record date is available for inspection by stockholders using the link entitled Registered Shareholder List at the bottom right hand side of your screen. During the meeting, stockholders may ask questions by typing them into the Ask a Question field and clicking Submit.
Questions pertinent to meeting matters will be answered at the end of the meeting subject to time constraints. We are now ready to proceed with the business of the meeting. The matters to be voted on in today's meeting are as set forth in the company's proxy statement. Let me briefly describe the voting procedures. You may vote your shares during the meeting through the web portal by following the instructions listed.
If you have previously voted by proxy, you do not need to vote again unless you wish to change your vote. If you have not already voted or you wish to change your vote, please follow the instructions on the web portal for how to submit your vote. No votes, ballots, proxies, or revocation or changes to votes, ballots, or proxies will be accepted after the polls are closed. I now declare the polls open for each matter to be voted on at this annual meeting. Proposal number one.
The first item on the agenda is to elect Doctor. Garo Armen and Ulf Windberg as Class II directors, each for a term of three years expiring at the twenty twenty three annual meeting. Their qualifications are described on pages eight to nine of the proxy statement, and the Board unanimously recommends that stockholders vote in favor of their elections. Proposal number two. The second item on the agenda is the proposal to approve an amendment to our amended and restated directors' deferred compensation plan to increase the number of shares of common stock authorized for issuance thereunder from 425,000 shares to 575,000 shares.
A detailed description of the proposal can be found on pages 35 to 37 of the proxy statement, and the Board unanimously recommends that stockholders vote in favor of this proposal. Proposal number three. The third item on the agenda is a proposal to approve the company's twenty nineteen employee stock purchase plan. The detailed description of the proposal can be found on pages 38 to 42 of the proxy statement, and the Board unanimously recommends that stockholders vote in favor of this proposal. Proposal number four.
The fourth item on the agenda is a proposal to ratify the appointment of KPMG as the company's independent registered public accounting firm for the fiscal year ending 12/31/2020. The detailed description of the proposal can be found on pages 43 to 44 of the proxy statement, and the Board unanimously recommends that stockholders vote in favor of this proposal. The final proposal, proposal number five. The fifth item in the agenda is a proposal to approve in a nonbinding advisory vote the compensation of the company's named executive officers. A detailed description of the proposal can be found on page 45 of the proxy statement.
And while the vote is advisory, the Board and the compensation committee will consider the outcome of the vote when considering future executive compensation arrangements. I will now keep the voting open for a few moments before closing the polls. The polls are now closed. Inspector of Elections, please deliver your report on the results of the vote.
Thank you, Evan. I have completed a preliminary count of the shares voted at today's annual meeting. There were sufficient votes to first elect Garo Armen and Ulf Windberg as Class II Directors of the company. Second, amend the company's amended and restated directors' deferred compensation plan to increase the number of shares of common stock authorized for issuance thereunder to 575,000 shares. Third, approve the company's twenty nineteen employee stock purchase plan.
Fourth, ratify the appointment of KPMG LLP as the company's independent registered public accounting firm for the year ending 12/31/2020. And fifth, approve in a nonbinding advisory vote the compensation of the company's named executive officers. I, as the Inspector of Elections, will prepare and deliver a final report on the results of the voting to be included in the records of this meeting. Additionally, the final voting results will also be included in the company's current report to be filed with the Securities and Exchange Commission following this meeting.
Thank you, Christine. That concludes the formal portion of the meeting. Before I turn things back over to Garo, I'd like to note that the remainder of this meeting will include forward looking statements, including statements regarding clinical development and regulatory plans and timelines. These statements are subject to risks and uncertainties. We refer you to our SEC filings for more details on these risks.
Joe? Thank you, Evan, Christine and all of you. Just to reiterate what Evan said, before I start my update, once again, please note that all remarks today may contain forward looking statements that are subject to risks, risks and risks. We refer you to our public filings for more details. Joining Jen and I here today virtually are two very special guests, Doctor.
Larry Norton and Doctor. Peter Jones. Doctor. Norton is the Senior Vice President and Saratham Chair at the Memorial Sloan Kettering Center, Cancer Center rather. And Doctor.
Peter Jones will represent the voice of our shareholders. Today, we present to you at a time when the world is in a state of disharmony, which unfortunately collides with the challenges of dealing with a major global pandemic. At Agenus, we are committed to doing all we can to address these issues with our initiatives, our policies, as well as our overall capabilities. And very importantly, while we keep our focus unwaveringly on our critically important cancer programs. I would be remiss if I did not specifically mention the dedication of our teams at all three of our sites.
They have been diligently forging ahead with all of their responsibilities. As you may know, we are classified as an essential business and hence we never shut down. But we did allow those who could function remotely to work from home starting on March 3. In the last week, we have begun the gradual process of fully reopening. Through the collective efforts of our dedicated team, our committed clinical sites and clinical investigators and patients, we have continued to make important progress with enrolling in all of our trials and importantly also monitoring clinical results.
At our company, we take pride in our innovation and efficiencies. We are in an era where the pace of therapeutic discoveries must keep pace with the exponential growth of scientific advances. We have demonstrated our ability to do this with 15 of our programs advancing into the clinic in the past five years. Our innovation and productivity have been possible because we have the key machineries to advance an idea into a product candidate and then into the clinic. We have done this with antibody discovery platforms, our mono specific and bi specific design capabilities, our Fc engineering capabilities, our cell line development and our GMP manufacturing, all in house.
These capabilities are coupled with just over two fifty employees at three sites Lexington, Massachusetts Berkeley, California and Cambridge, UK. Today, our employees, our team members are the formidable force behind all of these advances that we will be talking about today. As many of you are aware, today our extensive clinical stage portfolio includes 12 of the key foundations of immuno oncology. Our first generation CTLA-four and our PD-one antibodies. We are racing to file our very first BLA in the coming months based on the progress we've made with these programs.
Recent advances in the development of PD-one in combination with CTLA-four validates our strategy for both our first and second generation CTLA-four targeting antibodies. We intend to fully exploit these combination opportunities with both of our CTLA-four targeting antibodies. Jen will give you more details on that in just a bit. Having our own PD-one gives us significant flexibility in providing the best affordable combination option for patients. Our target opportunity extends far beyond cervical cancer into more than 26 indications where the combination of these antibodies has either shown benefit or is being actively pursued in clinical development.
These include lung cancer, colorectal cancer, melanoma, renal cell carcinoma, and many, many others. A critical part of our success has been our manufacturing capabilities, which are and will continue to be key to our speed and innovation success. We purchased Zoma's antibody manufacturing capabilities five years ago. And today, manufacturing space is at a premium. And our internal capabilities gives us the freedom and flexibility to accelerate our development programs and to provide the same for our current and future corporate collaborations.
Our manufacturing team has delivered more than 11 GMP batches since our acquisition. Of course, we're bragging about this. This is in addition to the more than 80 antibodies that they have delivered during their tenure as a team before our acquisition of them. This record underscores our ability to continue to deliver innovative molecules in the future. I will give you a few examples of our innovation now.
Our Cambridge based antibody designers became experts at Fc engineering before Fc engineering became fashionable. They designed a first in class Fc engineered next generation CTLA-four, AGEN1181, which I believe is one of the most exciting developments in next gen immuno oncology antibodies, period. We're very excited with the way this molecule is trending in the clinic, both as monotherapy and in combination with our own PD-one. These data were most recently presented by Doctor. Steven O'Dea at ASCO and Jen will tell you more about them shortly.
Our second and third generation programs target TIGIT. As you're aware, TIGIT is also shaping up as an exciting target. To fully address the biology of this target, we have designed and developed potential first and best in class Fc engineered monospecific and bispecific digit molecules, both soon expected to enter the clinic. By the way, it's important for me to mention that these two molecules, even though they target TIGIT, the monospecific and the bispecific, do different things. So they're not substitutable.
Finally, we have our allogeneic cell therapy platform. Our iNKT cells are now advancing to the clinic for patients with cancer and separately for patients with COVID-nineteen. We are very excited about the unique target killing and importantly anti inflammatory properties of our allogeneic NKT cells. Taken together, Agenus stands in a position to deliver combination therapies designed to be accessible to all patients, regardless of their financial circumstances, their race, or their background. To drive the power of this statement, I should mention that in the last four years, we have created more than 20 discoveries, most of which are already in the clinic.
We have also forged productive partnerships with Gilead, UroGen, Insight and Merck. And we have further monetized on our existing licensing agreement with GSK. Altogether, these have resulted in excess of $540,000,000 in payments to us over the last five years. These are not bio dollar payments. These are actual cash payments that have come into the company.
Our licensing, just a word about QS-twenty one because I think the time is very appropriate for it. Our licensing arrangement with GSK involves our QS-twenty one saponin adjuvant, which is in GSK's Shingrix vaccine, the most effective shingles vaccine, which has over ninety percent efficacy and which has achieved blockbuster sales potential in the first three years of launch. We believe the key driver of this success of Shingrix is our QS-twenty one saponin adjuvant. Given the scarcity of the raw materials for QS-twenty one, we have made important advances with an alternative source of a raw material, which we believe will have very important advantages, particularly in our efforts to provide large amounts, very large amounts of highly effective adjuvants to make future vaccines possible, including vaccines to prevent pandemics such as COVID-nineteen. Today's QS-twenty one supply could not produce sufficient quantities to make that possible.
But we believe that our advances with this alternative supply will be key to making this possible, both from a quantity and from a cost perspective. I will now turn the call over to Jen to provide you an update on our clinical stage programs and what you can expect in the course of the next year. Doctor. Jane Buoh.
Thank you, Garo. As Garo noted, our core capabilities have given rise to more than 20 discoveries with 15 INDs already filed. Those are products in the clinic or just about to enter the clinic, which I'll highlight in just a few moments. I'm thrilled to say that every single one of our innovations continue to advance in development in our own sponsored trials and through our partnered programs. At Agenus, we are advancing six of these molecules in the clinic on our own.
We've shared clinical data already on the first three of these programs so far this year. That includes Zalifrelimab, our anti CTLA-four molecule, Zalstilimab, our PD-one, and AGEN1181, our multifunctional T cell engager which also binds CTLA-four. All three of these programs represent important advances for patients with cancer. First, our combination of Zalprelimab and Valsdilimab appear to nearly double the response rates of approved therapy for patients with refractory cervical cancer. This is an important advancement.
As for more than the last two decades, the best available therapies revealed about eight to fourteen percent response rates. And until recently, those responses were not durable. Second, our PD-one balsilimab shows fourteen percent response rates in refractory cervical cancer, and these response rates are durable. This shows clinical comparability to the performance of commercially available Keytruda in this indication. Thirdly, AGEN1181 is designed to deepen the antitumor immune response for patients with cancer.
It's also designed to hamper tumor escape mechanisms, as well as to broaden the patient population of responders from the current twenty percent to more than sixty percent of patients. This is a result of the design of the molecule to benefit patients with a genetic mutation in their CD16 allele. These patients currently do not respond to a first generation CTLA-four. Data already presented at ASCO has demonstrated that the molecule is active, showing partial and complete responses in patients who have a mutation in their CD16 allele status. This is very exciting for us.
So what's next for these programs? We're in the process of filing two BLAs this year for balstilimab alone and in combination with salifrelimab. Our filings come at a time when CTLA-four is experiencing a renaissance. We recently participated in a panel with the world experts on CTLA-four, Doctor. Steven O'Dea and Doctor.
Chuck Drake. They've highlighted the learnings that we have had with the development of CTLA-four in general and the opportunity with our next generation CTLA-four molecule. Importantly, CTLA-four continues to emerge as a really critical component in IO therapeutic regimen. And as a matter of fact, just in the past week, there are now six approved indications for the combination of CTLA-four and PD-one. Those include melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and two different indications for lung cancer.
And there are more than 20 new indications in development with Bristol's products. We are filing our first BLAs in cervical cancer. Cervical cancer is a horrifying disease, particularly for young women who come from disadvantaged backgrounds and have limited healthcare coverage. Typically, patients with cervical cancer are treated with toxic chemotherapy upon first diagnosis. And unfortunately for patients with metastatic disease, these treatments have little clinical benefit and a lot of difficult side effects.
Patients ultimately progress with few treatment options. We are committed to changing this reality. And as I mentioned earlier, balstilimab, our PD-one shows fourteen percent response rates in refractory cervical cancer independent of PD L1 status. Importantly, in our second trial testing the combination of our PD-one balstilimab with our CTLA-four, zalifrelimab, for advanced cervical cancer patients, we saw durable responses of over twenty six percent based on a pre planned analysis of over 55 patients. And these data were based on the independent radiology review, which is the gold standard in assessing cancer progression.
As we progress with the success of our programs, increasingly we plan to develop, register, and launch our lead program in The US and partner in the ex US geographies. We believe this strategy will enhance the value of our more advanced assets while we continue to innovate. Turning to our innovation, I'll say a few words about AGEN1181. This is our CTLA-four multipurpose next generation antibody. It's an Fc enhanced antibody.
AGEN1181 is in the clinic, and the clinical data on the first couple of dozen patients in a dose escalation study are exciting. In addition to the responses we've seen, the data suggests this molecule can be administered safely and holds great promise for patients both as monotherapy and in combination with our PD-one antibody balstilimab. The data were recently presented by Doctor. Steven O'Dea at ASCO. Doctor.
O'Dea presented complete response, partial response, and long term stability of patients who had previously failed all other therapies. As the trial matures, additional clinical data is expected to be presented at upcoming conferences in the second half of this year. Eleven eighty one was deliberately designed to improve the efficacy and safety of first generation CTLA-four. And what we're seeing specifically and data that had been generated with the first generation CTLA-four Yervoy outside of melanoma in more than one thousand patients treated, we saw only four complete responses. Those were in prostate cancer, and they were with high doses of Yervoy.
We are seeing a complete response in a patient with endometrial cancer, a partial response also in endometrial cancer with more than seventy percent tumor burden reduction in her target lesions, and a complete response in the patient's non target lesions. The data are now available on our website and presented at ASCO by Doctor. O'Day. Importantly, Doctor. O'Day also presented on a patient with ovarian cancer who at our lowest dose of monotherapy AGEN1181, point one mgs per kg, the patient has had durable disease stabilization now for over a year.
Given the promising early data, we are contemplating accelerated development pathways in indications such as PD-one refractory lung cancer, melanoma, and importantly MSS tumors such as colorectal and endometrial cancers. Both of the patients who had observed responses in our trial were microsatellite stable patients and PD L1 negative patients. These patients had the poorest prognosis and responded, and the responses to date are durable. Now I'm going to wrap up by highlighting two additional very exciting programs and our upcoming catalysts. As Garo mentioned, TIGIT is shaping up as a powerful combination partner with PD-one antibodies, especially in tumors expressing PD L1.
We've designed two different approaches to optimally target TIGIT. Our team is amongst the pioneers in Fc engineering. As I mentioned earlier, our CTLA-four AGEN1181 is Fc engineered to provide enhanced benefits over first generation molecules. Our TIGIT molecules, both the mono specific as well as our bispecific molecule are also Fc engineered. Our Fc enhanced anti TIGIT antibody has outperformed all tested competitor antibodies.
And it showed superior T cell activation when combined with PD-one or LAG-three antagonists. Also, our TIGIT bispecific molecule, AGEN1777, has demonstrated potent tumor killing as a monotherapy in difficult to treat cancers where PD-one antibodies alone are ineffective. You can expect to see additional data on these molecules over the course of the upcoming months. Our upcoming catalysts include two BLA filings for our lead CTLA-four and PD-one. These molecules already received FDA Fast Track designation.
They're eligible for priority review, and we are on track to file these BLAs this year. You can expect additional data on eleven eighty one, particularly in selected cohorts of patients with targeted indications that we're pursuing such as lung cancer, melanoma, colorectal, endometrial, and other tumors in indications that are eligible for accelerated approval and represent meaningful commercial markets for us. We will also plan on providing updates on three additional important programs. These include our novel Treg depleting bispecific AGEN1223, which is in the clinic. Our differentiated anti CD137 antibody AGEN2373.
This molecule is designed to selectively enhance T and NK cells with unique finding characteristics to eliminate the liver toxicity that has hampered the development of competitor compounds. And as a matter of fact, our team now has advanced the program through the clinic to the dose where Urelimab, Bristol's four-1BB molecule, has seen hampering liver toxicity. To date, our molecule appears to be acting as designed without tampering liver tox. So additional data will be forthcoming on that molecule. Finally, our allogeneic INKT cells.
These cells have unique properties. Now this includes the ability to combat cancer and viral infections such as COVID-nineteen. One of the potential advantages of our allogeneic iNKTs is the fact that they are potentially agnostic to what type of cancer or virus is being targeted. They're a core part of our immune system. We've designed the manufacturing process to take one donor, isolate these rare cells, these rare immune cells, and generate enough material that's scalable to treat over one thousand patients.
And that's with our early phase manufacturing process without the expert process development work that's currently underway. These INKTs are potentially additionally helpful in COVID-nineteen in which they can dampen harmful inflammation and promote protection from viral reinfection. These are particularly important features in our battle to treat COVID-nineteen. We recently reported that the FDA has cleared our INKT INDs to treat patients with cancer and separately to treat patients with COVID-nineteen. We expect to begin the trial soon.
As Darrell mentioned, a distinct advantage for Agenus in our efforts to combat cancer is our arsenal of novel checkpoint antibodies, bispecifics, allogeneic cell therapy, and QS 21 adjuvant. This gives Agenus a significant advantage in controlling the clinical development of optimal combinations as well as optimal commercial price flexibility. Now we're going to conclude the meeting with a roundtable discussion. It's my pleasure to invite Drs. Larry Norton and Doctor.
Peter Jones to join myself, Daro, Doctor. Dan Chan, our Head of Drug Discovery, Doctor. Anna Viatek, our Head of Clinical Development to the line. Before opening the discussion up, I'll just share a bit more detailed introduction to our invited guests. Doctor.
Peter Jones is representing our shareholders today. Doctor. Jones is a retired physician surgeon from UCLA and formerly a cancer researcher in immuno oncology at John Wayne Cancer Center. He's co authored numerous scholarly articles about immune therapy and immuno oncology. Doctor.
Larry Norton is the Senior Vice President in the Office of the President of Memorial Sloan Kettering Cancer Center. He served as the President of ASCO and was appointed by President Clinton to serve on the National Cancer Advisory Board. He's authored more than three fifty peer reviewed publications. Doctor. Norton is an expert in tumor metabolism and is a key scientific advisor on our portfolio as a whole.
And most recently is advising us on interrogating the pronounced responses that we've observed in an early phase clinical trial of AGEN1181. And I should mention, we have the distinct privilege to work with an exemplary scientific advisory board, and these include Doctor. Norton, as I've just introduced to you, and some others who you have met in prior calls or at our R and D days, and that includes Doctor. Chuck Drake, Doctor. Steven O'Day, Doctor.
Dan Van Hoff, Doctor. Mario Snowll is the president of SITC, Doctor. Pat LaRusso at Yale. These contributors have been deeply embedded with our team here to interrogate our science and help us design optimal clinical and translational protocols to continue to accelerate our clinical programs by identifying which patients are most likely to respond to some of these very novel and innovative therapies. And the work of Doctor.
Norton and his laboratory, it has been outstanding and very supportive of helping us to better understand some of the profound responses that we're seeing with eleven eighty one that may help to further accelerate our development planning efforts. So this roundtable is designed to be interactive, and we're gonna go ahead and open it up for some questions.
Absolutely. And welcome, doctor Norton and doctor Jones. We're delighted to have you today.
Happy to be here. Very happy to be here. Thank you.
Thank you.
Thank you. Perhaps I'll go ahead and just get us started with a question to you, Doctor. Norton. You have been in this field for many, many years, and you've identified and defined ways in which you can solve the problem of breast cancer for many patients, and your reputation precedes you. As you look at where we are, the state of the world, in your perspective, what is needed to be successful in immuno oncology?
You know, it's all about innovation. It always has been. And the whole history of development of cancer drugs has always been about convergence, putting together pieces that may not be necessarily logically connected before you find that logical connection and you have it as a synergy between various ideas. And and I think that we're really at that point now with immuno oncology where we know enough about the various components of the immune response, the way way cancers protect themselves from from from the immune system, and potential combinations with other medications that may interfere with the way cancers may protect themselves from immunotherapy that we are on the verge I think of really a dramatic revolution in the way we take care of cancer, the way we think about cancer. And when these changes do occur historically, when these changes occur, once the pieces come together they change very quickly.
And I think that's where we are. I think we're ready for a dramatic change in our approaches to cancer based on the convergence from many different angles.
Excellent. And I think a tribute to what has your advisement has helped us to develop the depth and breadth of the portfolio to actually provide that level of combinations. And Garo will often say obsolescence rates are continuing to shorten that, you know, the products move through the clinic so quickly, and then they're obsolete, leaded by other more innovative programs. And that's why we have set up what I believe to be one of the most productive research engines given the number of programs that we're advancing so quickly to continue to fill that void.
And And that's join you on that just before we pass it over to Doctor. Jones is that one of the really exciting things about working with you so far is that you do have many different products and developments and many different ideas that are happening simultaneously, all of which could potentially work together. And seeing that happen all within one company is very exciting because you can move much faster that way in terms of developing new therapeutic ideas combining different approaches.
Thank you. Thank you for that, Barry. There used to be a time where innovation in this exciting field of medical sciences was so slow that any time you had a new product, you basically had a monopoly for ten to twenty years even after patent expiry because there was not much to compete with. But as you say, things are really taking off now and we're almost approaching the pace at which technology companies innovate and progress their business. And so hence the importance of having multiple shots at that goal.
And to this point, I'll just have Doctor. Dan Chen give you, in as much as we can publicly disclose to date, a glimpse of some of our science that is helping to elucidate how to best bring these combinations forward. And so I'll ask Dan just to highlight a few components of our upcoming AACR presentation.
Thank you, Jen. And Doctor. Norton, you touched on a very good point about bringing components together and leveraging those components to bring curative responses to patients. And next week at AACR, we will be presenting data on how we can leverage our own inventions with respect to CTLA-four therapy, PD-one, and other components within our pipeline to treat heart indications that are typically refractory or resistant to current therapies. And this includes leveraging multiple aspects and arms of the immune system to fight cancer.
Thank you.
Excellent. Thank you, Dan. And Doctor. Jones, I'll turn it to you for a few moments to talk about from the shareholder perspective, how do you see the value of the portfolio given your background in oncology and immuno oncology and now on the side of a shareholder.
Yeah, thanks for asking me to participate in the call. I think like most investors here, I was attracted by the Check Point molecule pipeline. It was actually the best I could find for any small company. And the other programs seem to complement the Check Point program. And like Doctor.
Norton said, it's a combination of all of them that make things really attractive here all in a small company. So that makes for a very interesting riskreward for an investor. Obviously, there are major risks, but the reward side is pretty high if any of these combinations work, especially given the size of the company.
Thank you. Thank you, Peter.
Thank you very much, Peter. So let me open up the table for any questions that any of the participants may have.
Including our
roundtable. Absolutely, including our roundtable.
I'll ask
a I
think the number one from an investor standpoint, the number one factor that will move the Agenus share price in a major way near term it was clarity that $11.81 is beating ipilimumab. And could you just go into the strategy a little bit more for achieving that quickly? I gather the move into the major cancers with PD-one failures would get us there. I think that's probably a very good strategy. Is there any consideration of more monotherapy $11.81 at higher doses?
Okay. So very important questions, and I'll just I'll highlight a couple of important components, and some of which is what we're collaborating with Doctor. Norton and others on is, first, we have a first generation CTLA-four, and we have our Fc engineered eleven eighty one. And we have clinical data on both of these molecules, both alone and as monotherapy as well as in PD-one refractory patients, as well as in combination with balsilimab. So a very deep and rich population to draw some information from.
So our scientists have been interrogating a number of really important components to differentiate these molecules immunologically, biologically, and some of the biomarkers. And those include response in CD16 in patients who have genetic polymorphisms in their CD16 allele. It includes gene expression analyses. It includes interrogation of important markers of response such as TCR clonality and diversity. And so the teams are working very heavily in that space.
It also includes some very important metabolic considerations that we've been haven't yet disclosed, but we've been working closely with Doctor. Norton on. And so those are happening because we believe that in order to really be able to quickly differentiate responders from nonresponders, we need to understand some of these response factors. On the front, based on what we're seeing, we know a few things. And I'll refresh what I said earlier that when we've interrogated Yervoy activity outside of melanoma, we've seen in over one thousand patients treated there were four complete responses.
These were in prostate cancer. There have been no responses outside of prostate cancer. And this is over one thousand patients treated. And we've spoken with PIs who published, PIs who did not publish, but who led trials. We have a good sense of what that data looked like, what those data looked like.
In our own trial now with eleven eighty one, we are already seeing outside of prostate cancer, we're seeing patients with endometrial cancer that has all of the poorest prognostic measures microsatellite stable disease, PD L1 negative patients, and they're responding. We see that in endometrial, and we see strong disease stabilization in over seventy percent of patients treated. And those include patients with ovarian cancer, and some of the other patients have not yet been presented publicly. So I'll refrain now from sharing some of that data. Given what we are seeing, when we met with our advisory board, they said two important things.
Number one, you must find a development path for monotherapy eleven eighty one. On the recent call I reflected on with Chuck Drake and Doctor. Steven O'Dea, Chuck said what we're seeing with eleven eighty one is far beyond anything with Yervoy. And that call is publicly available on our website, and I'm happy to share out that link. And he said that what we're seeing is very unique, and we need to think about it differently.
And there is a monotherapy path. Additionally, the combination to show superiority that we've seen in preclinical models PD-one in combination with eleven eighty one demonstrates superiority. We would like to recapitulate that in the clinic, particularly in tumors that allow us a fast to market approach and a meaningful commercial market. And those include non small cell lung cancer, and we're seeking the PD-one refractory population there for two reasons. One, both in lung and PD-one refractory melanoma, this will allow us to interrogate monotherapy cuclide eleven eighty one activity.
It also will allow us to interrogate combination activity in the cases where patients continue on PD-one. And those are very meaningful markets, and that will give us a sense of superiority because we have so much data on how Yervoy performed in those populations. There's a lot of published literature there as well. This would allow us to move the product very quickly through development while then in parallel we could contemplate superiority trials. But it's not something that we feel that we need to do immediately.
We believe we could demonstrate superiority by taking the preponderance of evidence that's clinically available to us now and strategically applying our clinical practices to interrogate the PD-one refractory population with the monotherapy as well as with the combination approach.
I have a question for Doctor. Knox. Larry, you have trained and continue to mentor some of the most brilliant medical researchers in the field.
Thank you.
And if you can thank you for that, by the way. We're benefiting from it as well. If you can tell us what is driving these cancer researchers today in terms of the fields of their interest and how they participate in this sort of revolution that we talked about.
Yeah. That's a very good question. Excellent. No. That's an excellent question.
I think in general, researchers have been consistent since my experience, a driving need to make a difference in the world, to help people that are ill, to make them better. There's a deep altruism. But that altruism is coupled with also an extraordinary degree of deep scientific knowledge now, much more so than I've ever seen before. The people that we're seeing going into medicine now are extremely well schooled in biological science, chemistry, even mathematics and physics, certainly computer science, and the technical fields related to artificial intelligence. We're seeing an extraordinary group of hypereducated individuals who are coupling that with the desire to use those tools to make a concrete difference.
And I think the fact that industry such as pharmaceutical industry and other industries, technology industry, really taken advantage of those individuals in terms of working, together with academic institutions, with government support in the form of grants, is another example really of convergence. And we're seeing a cross exchange between the various academic institutions and industry government in ways that I think are extraordinarily productive. I chair some activities in the National Cancer Institute, for example, that are very good illustrations of that phenomenon. The other characteristic in terms of their deep education and their altruism, their dedication, is that and I don't know the reasons why, and I think many people on the call could probably have a better hypothesis than I can have. They're very good at navigating interpersonal systems, working together with people in constructive ways.
They discussed our educational system for a long time now has emphasized team working together, know, what they call co creation, you know, rather than as individual silos. And I remember, you know, in in my youth where, you know, there were dominant scientists who wouldn't collaborate with others and and want their whole world of ideas themselves, and that's not what's happening there. We're seeing great growth across civilization, largely driven by the by the younger people in the field who really enjoy working together collaboratively with other people for commendable goals. So I I think the human resource there is is quite extraordinary. And then you couple that with the scientific advances that we've been talking about all along, the knowledge of what make cancers work and why they're cancers, the knowledge of how the immune system works and how that can be manipulated to our advantage, you know, the enormous amount of scientific tools that are available to us, the future looks very bright indeed.
So part of what I'm hearing from you is that a whole bunch of advances in cross functional disciplines are now converging in these brilliant scientists and are being utilized to develop tools that we didn't even dream of ten, fifteen years ago. And that's pretty exciting actually. And thank you very much for helping us identify some of the pathways that may be very helpful in terms of biomarkers and also hooking up with some of the progressive researchers to work with us and Yeah. Advancing our
mean, honestly, think that you've got a really good example here with your eleven eighty one, which is obviously a very active molecule that you already heard in terms of having a single agent response rate that that dwarfed what we've seen with other agents, you know, of this type. But one of the projects that I'm very excited about involves that is coupling three separate fields that normally would not be connected. One of my colleagues discovered molecular abnormalities that change the metabolism of cancer cells. A brilliant young investigator that I worked with, Morris and Kettering, has found that not knowing necessarily that of of those, you know, the etiology of those molecular abnormalities, etiology of those metabolic abnormalities and molecules, the fact that metabolic abnormalities like that can actually arrest the immune system and stop it from working optimally to kill cancer. And then my knowledge of your work that basically shows a very active agent that could actually make white cells functional despite those metabolic abnormalities.
So you've the field of metabolism, the field of immunobiology, and the field of drug development all converging together in a really exciting project. It's probably one of the most exciting projects I've been involved with in a long time because it not only can help eleven eighty one work better, but also it may be applicable to many different types of cancer that have those molecular abnormalities. We call those basket trials now where instead of zeroing in on the organ the cancer comes from, we can zero in on the molecules that make the cancer cell tick. And it turns out that these metabolic abnormalities I'm talking about are found commonly in some cancers like endometrial cancer, but also in a significant or small number of other cancers including breast cancer, which I'm predominantly involved with. So I think I could foresee basket trials where a whole lot of different kinds of cancer types are being treated with this type of approach.
So it really is kind of cool in this example really of convergence and involving people of different disciplines you know, sparking off each other and creating something new and exciting and we think could really help people with cancer.
Thank you. Thank you very much. There's a question from the field which I will repeat thanks to the technologies post COVID now or hopefully it's post COVID. We have the ability to interact more intimately with the questions from the field. So question is, are there any updates on the existing partnerships with Gilead, INSIGHT, or Merck?
And any updates on additional partnerships that may ensue? And the short answer to that question is, as far as we know, and we know quite a bit because we interact with all of our partners on a regular basis, we have committee meetings with them. So all of the programs so far in all of our partnerships are progressing. And we expect to get some milestones from some of them in coming months and beyond. Now with regard to new partnerships, as you questioner knows, the only thing we can say is when there's a deal, there'll be an announcement.
Unfortunately, we cannot make any comments ahead of time. And so you will have to wait, and I think the progress is as expected. The second question from the field. I understand that right that the patients receiving eleven eighty one failed Yervoy first, then we had a seventy percent complete response.
70% clinical benefit.
Clinical benefit, right. So I think if I heard Jen right, and based on my knowledge of what's going on, we never said they failed Yervoy first, never said that. We did say they failed PD-one. And so hence, became candidates having failed PD-one and other therapies for November. Now, what Jen said was that we will pursue eleven eighty one both as monotherapy and combination therapy in patients who have failed everything, including potentially GEARBORT as well.
But that will be in future development programs.
And yes, we did have we reported it at ASCO, we did have a clinical benefit rate of about seventy percent that includes complete response, partial response, and disease stabilization.
By the way, on that note, as our advisors will attest to, in immuno oncology, to track the history of immuno oncology since Geroid and many patients that have been treated. And in our trials, not in all patients, but in some patients, disease stabilization after a few months, after many months could convert to responses. This is a very important data point. And in fact, I might tell you that there is a very famous patient who was treated with Yervoy many years ago who had stable disease for eight years, eight years, and then converted to partial response. Of course, this doesn't happen often after eight years, but there are case studies like this.
So the interesting thing about immuno oncology is that at least in some patients, you have this state of equilibrium going on. Patient living with its immune system battling the disease on an ongoing basis. And then at some point, the balance tips in favor of beating the disease. In other cases, it tips over in favor of the disease taking. But this is a very interesting phenomenon and speaks to the power of the immune system.
And some of which we're seeing, and Anna can speak to this, we've seen this in our monotherapy PD-one trial as well as our combination. Yes, absolutely,
we have cases that converted from stable disease into partial or complete response after a period of time.
Thank you, Anna. Peter, you're always chuck full of wonderful questions. If you'd like to ask additional questions and our roundtable participant, please do so.
Sure, I'll just make one comment. I was very excited to see you moving into the high tumor burden cancers with eleven eighty one that are PD-one failures. And I think the number one reason is really what Dan Chan presented at I believe it was R and D Day where he showed that the slide from the Vargas paper I subsequently read that paper it shows really the benefit from the FC engineering would be expected maximally in tumors with high tumor mutational burden. So I think this move into non small cell lung cancer and melanoma, I think, makes a lot of sense to get us to where we know that eleven eighty one is a confirmed superior molecule. We have some strong hints so far, but we don't have absolute confirmation.
Let's see. Would ask one question of Doctor. Norton. We've seen in the last couple of years a number of papers that have come out that show an impressive obesity paradox wherein patients treated with checkpoint molecules, if they're overweight or moderately obese, they experience enhanced benefit. From a metabolism standpoint, what do you think is going on there?
There's two hypotheses that I've been thinking about. One of them is that obesity is a pro inflammatory state. There are a lot of circulating cytokines, IO six, IO one beta, and a whole collection of pro inflammatory molecules. The patients are basically primed to have an immune response and unleashing that with molecules that take the break off in the system if the conditions are right in terms of the tumor, maybe a deep growth inhibiting for the tumor cells. In other words, the white cells are ready to kill the cancer and they're all primed.
The inflammatory cytokines have made them hyperactive, but they're being blocked and you have to release that blockade with drugs like anti CTLA-four. And that's one hypothesis. The second hypothesis is that obesity, people tend not to be obese just because they overeat. Their metabolic abnormality is called metabolic syndrome. There are biochemical reasons why people are prone to obesity, and that's why you see obesity growing in families.
They've done twin studies, for example, where twins separated at a very early age and raised by totally separate families, and and yet, you know, or have a tendency for obesity. So there's a certain there's a certain predisposition, which means that there are metabolic abnormalities, and those metabolic abnormalities may be just the kind of metabolic abnormalities I was talking about earlier that may impede the immune response. And when you give a drug like an anti CTLA-four and you make the T cells work better, again because what I'm talking about these metabolic abnormalities is called T cell exhaustion. The T cells are there. They want to kill the cancer, but they become exhausted.
They're no longer functional because of the metabolic abnormalities caused by the tumor or perhaps caused by the obesity. And that if you unleash them by a drug like anti CTLA-four, a classy drug like anti CTLA-four, then they can work better and do their job better. So I think we're pursuing both of those right now, actually looking at them and the metabolic abnormalities I mentioned earlier, which I think is a very, very exciting research project, but also the pro inflammatory actions of obesity and how that may work against you under many circumstances, increase risk of heart disease and stroke and other degenerative diseases, but may actually make immune checkpoint inhibitors work better because the immune system is really primed to be hyperactive and really ready to go when you take the break off. I don't know which one. It might be both.
It might be different ones in different patients. But it's something we're actively pursuing.
Thanks.
So should Agenus focus its trials in the Northern States where people tend to winter well, as they say, and put on weight.
Very well said. Well, we're going to go ahead now and close this call. I want to send a very special thank you to Doctor. Norris, Doctor. Jones for joining us today.
I want to, of course, thank our team for their outstanding performance and thank our shareholders for your continued support and dedication. Looking forward to speaking with you again soon.
Thank you.
You. Pleasure.