Q4 2020 Agenus Inc Earnings Call
Good morning, ladies and gentlemen, thank you for standing by and welcome to the agenda.
Operator: Good morning, ladies and gentlemen. Thank you for standing by.
Operator: And welcome to the Agenus Fourth Quarter 2020 conference call and webcast. At this time, all participants are in a listen-only mode. If you require operator assistance, please press star, then zero. After today's presentation, there will be an opportunity to ask questions. To ask a question during the Q&A session, you will need to press star, then 1.
And as fourth quarter 2020 conference call and webcast.
At this time all participants are in a listen only mode.
If you require operator assistance. Please press Star then zero.
After todays presentation, there will be and opportunity to ask questions to ask a question. During the Q&A session you will need to press Star then one.
Please note.
Operator: Please note that this event is being recorded and may be used in future Agenus promotional material. I would now like to turn the conference over to John Medina, Director of Investor Relations. John, please go ahead.
And is being recorded and may be used and future of genus promotional material.
I would now like to turn the conference over to John Medina Director of Investor Relations. Please go ahead.
John Medina: Thanks, Liz, and thank you all for joining us today. Today's call is being webcast, and it will be available on our website for replay.
And thank you all for joining us today this.
Total is being webcast and we will be available on our web site for replay.
John Medina: Before we start, I just want to quickly introduce myself. I know I've spoken with a number of you already over the last month or so, but I started here at Agenus back in February to help lead the investor relations efforts. Certainly, it's a very promising time for the company, and I'm looking forward to being part of the conversations we have with the investment community. With that said, I just want 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 filings for more details on these risks. As a reminder, this call is being recorded for audio broadcast.
Before we start just wanted to quickly introduce.
This is find out and spoken with a number of you already over the last month or so and I started here and a genocide back in February and to help lead the Investor Relations efforts certainly it's a very promising time for the company and I'm looking forward to being part of the conversations we're having with the investment community and wood.
And I just want to remind you that this call will include.
And myself 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 filings for more details on these risks.
As a reminder, this call.
<unk> reported for audio broadcast.
John Medina: Joining me today are Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Jennifer Buell, President and Chief Operating Officer; Andy Early, Chief Commercial Officer; and Christine Klaskin, Vice President of Finance. Also available during the question and answer session will be Dr. Steven ODay, our chief medical officer. Dr. ODay joined Agenus earlier this year as well, along with a number of other key hires, and brings clinical development expertise to Agenus at this pivotal time. Now, I'll turn the call over to Garo to highlight our key accomplishments and our goals for 2021. Garo?
Joining me today and about the Garo, Armen, Chairman and Chief Executive Officer, Dr. Jennifer Buell, President and Chief Operating Officer, Andy early and Chief Commercial Officer, and Kristine Classic and Vice President and finance.
Also available during the question and answer session will be Dr. Stephen Though day, our Chief Medical Officer.
And as being a doctor a day joined <unk> earlier this year as well along with a number of other key hires and brings clinical development expertise to a genesis at this pivotal time.
And now I'll turn the call over to Garo to highlight our key accomplishments and our goals for 2021 Garo.
Garo H. Armen: Good morning. Thank you very much. In 2020, our pipeline continued to grow with an arsenal of agents designed to activate the immune system across different types of patients and cancers on the one hand, while also addressing immunotherapy resistance pathways across many tumor types on the other. We expect these advances will contribute to the I.O. field on multiple fronts.
Good morning, Thank you very much.
In 2020.
Pipeline continues to grow within the arts and remove agents designed to activate the immune system across different types of patients and cancers on one hand, while also addressing immunotherapy resistance pathways and of course, many tumor types and the other.
We expect.
And our advances will contribute to the I O field on multiple fronts.
For instance.
Garo H. Armen: For instance... We are advancing Agent 1181's clinical development and generating responses in patients who are unlikely to otherwise respond to immunotherapy. We expect to advance Agent 1181 to registrational studies this year. We've also made substantial advances with our Tidget program, demonstrating the unique attributes of our platform, which is IND-ready.
We are advancing a gen 11, and 81 clinical development and generating responses in patients who are unlikely to otherwise respond.
These and immunotherapy.
We expect to advance a Jan 11, and 81, two Registrational studies this year.
We've also made substantial advances with our ticket programs.
<unk> the unique attributes.
And to our bi specific antibody, which is I N D ready.
One of our notable achievements during 2020 was the completion of patient enrollment and data analysis of our two most clinically.
Garo H. Armen: One of our notable achievements during 2020 was the completion of patient enrollment and data analysis for our two most clinically advanced agents, Valstilumab, which is our PD-1 antibody, and Zoliferumab, which is our first-generation CTLA-4 antibody. We call these BOW and ZOW for short.
Past agents, while still a map, which is our PD one antibody.
And so it's really map, which is our first generation <unk> four antibody.
We call these bowel and Zhao for short.
Garo H. Armen: We are progressing with the completion of our BLA filing for BAL and will proceed with our strategy regarding a potential BAL plus ZAL filing once BAL's BLA filing has been accepted. It is our aim to use Balsillimab as the foundation for several of our pipelines, as well as offer our bell for use with therapies from other companies, which require combination with a PD one blocker. Our objective is to rapidly enable synergistic combinations to advance the field.
We are progressing with the completion of our BLA.
L a filing for Bal.
And we'll proceed with our strategy regarding a potential bounce plus south filing.
<unk> thousand and BLA filing has been accepted.
It is our aim to use both bill and Matt is the foundation for several of our pipeline agents.
As well as all four of our Val for use with therapies from other companies, which require combination with a PD one blocker.
Our objective is to rapidly enable synergistic combinations to advance the field.
Garo H. Armen: Synergistic combinations for our agents include cell therapy through our subsidiary, Agentus. While we are continuing our allogeneic intelligent INKT cell therapy in patients with COVID-19, we will be advancing these intelligent cells into CASA trials with combinations around mid-year, separately. At a time when the world's need for higher quantities of vaccine production grows, we are advancing our plans for producing high quantities of QS21 adjuvant, an antigen-sparing adjuvant, from a renewable source. What that means is that a vaccine formulation with QS21 may require as little as 100-fold less antigen to achieve the same immune response.
Synergistic combinations for our agency includes cell therapies through our subsidiary Egencia is.
While we are continuing our allogeneic intelligent I NK and T cell therapy and patients with COVID-19, we will be advancing these intelligence.
And it sells into cancer trials with combinations around mid year.
Separately and.
At a time when the world's need for higher quantities of vaccine production grows.
We are advancing our plans for producing high.
And the quantities of Qs 21, and adjuvant from a renewable source.
Towards 'twenty, one is and MTGE sparing adjuvant.
That means.
And vaccine formulation with Qs 21 may require as little as one.
104, less antigen to achieve the same immune response.
If this proves to be the case for some or most COVID-19 vaccines you can appreciate the potential implications over <unk> 21 to be able to significantly increase global COVID-19 and manufacturing.
Garo H. Armen: If this proves to be the case for some or most COVID-19 vaccines, you can appreciate the potential implications of QS21 to be able to significantly increase global COVID-19 manufacturing capacity, that is, vaccine manufacturing capacity, without the need to add additional antigen production capabilities, which is one of the major bottlenecks of today. Several of these advancements I touched upon represent important milestones. We expect some of those to result in cash-accretive corporate transactions starting in the second quarter of this year.
Moving capacity that is vaccine manufacturing capacity without the need to add additional MTGE and production capabilities, which is one of the major bottlenecks of today.
Several of these advancements I touched upon represent important milestones.
We expect some of those to result in cash accretive corporate transactions.
Our team and the second quarter of this year.
In 2020.
Garo H. Armen: In 2020, we built on a Genesis Foundation of Innovation and Integration. These, that is, innovation and integration, are the key pillars of our business model. While COVID has posed challenges for many, including Agenus, we were early to anticipate and adjust to life in the very early stages of the pandemic.
We built on a Genesis foundation of innovation.
Asian and integration.
These are that is innovation and integration are the key pillars of our business model.
While COVID-19 has posed challenges for many including agendas, we were early to anticipate and adjust to life and the very.
Early stages of the pandemic.
Garo H. Armen: We've also rapidly adjusted to address new needs, such as INKT cell therapy in patients with the most severe infections of COVID-19 who are dependent on life support. We published early data from the trial and expect to share more as our trial matures. Our teams are also preparing for the scenario of a rapid or emergency use path for INKT cell therapy should the trial data look encouraging. But with all these adjustments, our core mission is unchanged.
We are also rapidly adjusted to address new needs, such as I and K T cell therapy and patients with more severe infections of COVID-19, while dependent on life support.
We published early data from the trial and expect to share more as our trial matures.
And are also preparing for the scenario of a rapid or emergency use pad four I and K T cell therapy should the trial data and look encouraging.
But with all these adjustments our core mission is unchanged, we will continue to innovate and advance our program.
Garo H. Armen: We will continue to innovate and advance our programs with speed. This requires integrated capabilities to reduce our dependence on outsiders on the one hand, but also, very importantly, retaining and continuing to acquire top talent. High talent density is key to our ability to deliver innovation. Recently, we welcomed stunning talent into our leadership team, and I will start with Dr. Steven ODay, our Chief Medical Officer, and our Chief Commercial Officer, Andy Hurley. These two professionals are among some of the most respected names in the field.
Our teams would be this requires integrated capabilities to reduce our dependence and outsiders on one hand, but also very importantly, retaining and continuing to acquire high talent.
Hi talent density is key to our ability.
Program over and innovation.
Recently, we welcomed stunning talent into our leadership team and I will start with that because even though a day, our chief Medical officer, and our Chief Commercial Officer, Andy Hurley.
And these two professionals are amongst some of the most respected names in the field.
Garo H. Armen: Dr. Oday is a pioneer in immuno-oncology, and as a clinical investigator, he has been an important contributor to the success we've seen so far with HN 1181. As we advance in the discovery and development of high-performing immune therapies and, particularly combinations, we need to have formidable players like Dr. Oday on our team. Dr. Oday played a key role in the successful development of Yervoy and Optivo, CTLA-4 and PD-180, as well as several other cancer therapies.
And today is a pioneer and immuno oncology and.
And as a clinical investigator has been and important contributors to the success, we've seen so far with age and 11 81.
As we advance and the discovery and development of high performing immune therapies and particularly combinations.
And therefore, we need to have formidable players back back total day and our team.
And they played a key role and the successful development and over year void.
And Opdivo and <unk>.
<unk> four and PD one agents.
As well as several other cancer therapies, he has the knowledge and expertise.
Garo H. Armen: He has the knowledge and expertise to build on our work with 1181, cemented in place in the IO landscape, and fully maximize the compound's potential as a blockbuster therapy for cancer patients. We have big plans for Asia in 1181 and will pursue accelerated pathways to advance the molecules of the market. Andy Hurley will be a key driver of our aspirations to do this. In his role as chief commercial officer, Andy joined us after three decades of building teams and commercializing products in biopharma. With a Balfour-Limat BLA filing expected in the first half of this year, Andi will help establish Agenus as a commercial company with Balfour-Limat as a key actor in our plans for our ambitious combination strategy.
<unk> and our work with 11 and 81 cemented in place and the Io landscape and fully maximize the compounds potential as a blockbuster therapy for cancer patients.
We have big plans for Asia, and 11, and 81 and will pursue accelerated pathways. So advanced the molecule to the market.
To Bill Andy Hurley will be a key driver of our aspirations to do this.
In Israel as Chief commercial officer.
And they joined US after three decades of building teams and commercializing product and Biopharma.
And they're both still the Mab BLA filing expected in the first half of this year.
And they will help establish a generous as a commercial company with barstool and map as a key actor and our plans for our ambitious combination strategies.
Okay.
Given our mission to develop impactful combinations for patients.
Garo H. Armen: Given our mission to develop impactful combinations for patients, Agenus requires clinical scientists with extensive and established expertise. Dr. Joe Grossman joined our team as head of exploratory medicine from Harvard and Beth Israel. His specialty includes colorectal and pancreatic cancer.
And Genesis requires clinical scientists with extensive and established expertise that's been true Grossman joined our team as head of exploratory medicine.
From Harvard and Beth Israel.
His specialty includes colorectal and pancreatic cancers Dr.
Garo H. Armen: Dr. Grossman will drive our translational medicine strategy, which is a key aspect of Agenus' clinical development strategy. Dr. Jason Paragas, another recent addition to our team, is an expert in data analysis and artificial intelligence. He formerly served with TARPAD, working on threat detection for the U.S. government and Associated Defense Department. Jason joined us as Vice President of Strategic Initiatives. Jason will also be working with our team to industrialize and broaden the applications of our vision response prediction technology.
It's one will drive our translational medicine strategy, which is a key aspect of Genesis clinical development strategy.
Doctor, Jason progress and other recent addition to our team as an expert and data analysis and artificial intelligence and.
And formally share.
Growth DARPA working on threat detection for the U S government and associated defense departments.
Jason joined Us as vice President of strategic initiatives.
Jason will also be working with our team to industrialize and broaden the applications.
And our vision response prediction technology.
Next Adam crowds joined as Chief legal and compliance officer to ensure our commercial readiness and.
Garo H. Armen: Next, Adam Kraus joined as Chief Legal and Compliance Officer to ensure our commercial readiness, and Mark Wiles joined as Vice President of Regulatory Affairs. It is a transformative period for Agenus, and the value each of these team members brings will help drive a new level of success for the company. We understand the ambitious scale of our mission as we seek to disrupt an industry that has been challenged by disruptive demands. We believe that marshalling the best people and resources is paramount to achieving success. I would now like to turn the call over to our President and Chief Operating Officer, Dr. Jennifer Buell.
And Mark Wilde's joined as Vice President and regulatory Affairs.
It is and transformative period for.
For a generous and the value each of these team members bring will help drive and new level of success for the company.
We understand the ambitious scale of our mission as we seek to disrupt and industry that has been challenged with disruptive and demands we believe marshaling.
And as people and resources is paramount to achieving success.
I would now like to turn the call over to our President and Chief operating Officer, Dr. Jennifer Buell.
Yeah.
Yeah.
Thank you.
Dr. Jennifer Buell: As Garo indicated, our R&D engine has been enormously productive, with numerous discoveries, I&D filings, and product candidates advancing in late-stage trials. As a result, 2020 was a period of significant data flow.
Moving the Sky indicated our R&D engine has been enormously productive with numerous discoveries and filing and product candidates advancing and late stage trials.
As a result, 2020 was a period of significant data flow.
Dr. Jennifer Buell: We presented data updates on our programs at all of the leading oncology conferences last year. At CITSE, AACR, and ASCA, we presented data on clinical responses with 1181, as well as differentiation of our five lead molecules. And finally, we also presented data on our response prediction platform, VISION.
We presented data updates on our programs and.
And a leading oncology conferences last year.
And sitting ACR and ask and we presented data and clinical responses with 11 and 81.
As well as the differentiation of our five lead molecules and.
And finally, we also presented data on our.
And all of <unk> predictive prediction platform vision.
And with our tissue specific age and 17 77, we presented data revealing the potential to brought and the activity beyond the first generation of anti antigen antibodies.
Dr. Jennifer Buell: With our TIGIT BISPECIFIC, Agen 1777, we presented data revealing the potential to broaden the activity beyond the first generation of anti-TIGIT antibodies. We engineered an important region of the molecule, the FC region, to improve responses, expand the population of responders, and generate monotherapy activity, which is not currently seen with PIDGET monospecific antibodies available today. More recently, at ASMO just a few months ago, we presented preliminary data from the BAL Stilomab Monotherapy and BAL-Xel combination studies showing breakthrough activity in PD-L1 positive and PD-L1 negative cervical cancer patients.
Engineering and important.
Our response region of the molecule the FC region to improve responses and expand the population of responders and generate monotherapy activity, which is not currently seen with ticket mono specific antibodies available today.
More recently.
And at ESMO, just a few months ago, we presented preliminary data from the bowel still them at monotherapy and <unk> combination studies, showing breakthrough activity and PDL, one positive and PDL, one negative cervical cancer patients.
Dr. Jennifer Buell: As we look into 2021, including AACR next month, we will continue our aggressive approach to data presentation, providing clinical updates on our lead compounds, including Agent 1181, in our BLA filing. Our rolling BLA filing for bowel-stilomib monotherapy and second-line cervical cancer is underway. Initiated in September, we expect to complete the filing during the first half of this year.
As we look into 2020 one including.
<unk> C R and next month, we will continue our aggressive approach to data presentation.
Providing clinical updates on our lead compounds, including age and 11 and 81.
On our BLA filings.
Our rolling BLA filing for Bell still enough monotherapy.
And a in second line cervical cancer is underway.
Initiated in September we expect to complete the filing during the first half of this year and as we disclosed in September this timeline of comedies and two additional late confirmed responders seen and our pivotal trial will provide the FDA with six months of follow.
Dr. Jennifer Buell: And as we disclosed in September, this timeline accommodates two additional late confirmed responders seen in our pivotal trial. We'll provide the FDA with six months of follow-up on those patients, as well as 12 months of median follow-up on all trial participants. We believe Balsilumab's approval would represent a meaningful new option for the cervical cancer community. However, we note that Pembrolizumab, Keytruda, is approved in the PD-L1 positive population only and shows no clinical responses in PD-L1 negative tumors and in the largest I.O. clinical trial in this population to date in over 160 patients treated with balacelamab alone. We reported response rates of 19% in PD-L1 positive patients and 10% in PD-L1 negative patients.
Therapy on those patients as well as 12 months median follow up on all trial participants.
We believe both Phil and I have the approval would represent a meaningful new option for the cervical cancer community.
We note that pember lithium atoms Keytruda is approved and the PDL one positive population only.
<unk> chose no clinical responses and PDL one negative tumors.
And then the largest Io clinical trial in this population to date and over 160 patients.
Treated with valves telematic alone, we reported response rates of 19% and PD lone positive patients and 10.
And then and PDL one negative patients.
Dr. Jennifer Buell: This compares favorably to Keytruda, which has 14% responses in PD-L1 positive tumors and no responses in PD-L1 negative tumors. In addition, the durability of response in our pivotal trial was impressive, lasting approximately 15.4 months. This is not observed with chemotherapeutic options currently available for these patients. The duration of response is a hallmark of effective IO agents, and ours far exceeds the limited duration of response observed with chemotherapy in these patients. We believe these clinical data reveal emerging differential features of balaclava.
This compares favorably to Keytruda, which is 14 per cent responses and PDL, one positive tumors and no responses and PDL, one negative tumors and.
In addition, the durability of response and our pivotal trial was impressive lasting approximately 15 point.
Per say months. This is not observed with came up therapeutic options currently available for these patients.
The duration of response is a hallmark and effective Io agents and ours far exceeds the limited duration of response observed with chemotherapy.
These patients.
Yeah.
And for them.
Yeah.
Yes.
Yeah.
We believe these clinical data reveal emerging differentiate differential features of bell still them up.
Dr. Jennifer Buell: We plan to publish the full clinical data set of BAL Stilomab in Refractory Cervical Cancer in a high-profile journal. Additionally, we will publish preclinical data from our vision platform that further elucidates BAL's superior tumor cell-killing capabilities compared to the leading commercially available PD-1 antibodies. Regarding our plans for the balustelomab plus alofilamab BLA filing, we've been in ongoing discussions with the FDA. The trial has completed enrollment. The patients have concluded a median of 12 months of follow-up.
We plan to publish.
The full clinical dataset of bell still and map and refractory cervical cancer and a high profile journals. Additionally, we will publish preclinical data from our vision platform that further elucidate bells superior tumor cell killing capabilities.
Compared to the leading commercially available.
Anyone antibodies.
Regarding our plans for the bowel still amount plus Ela fellowman BLA filing we've been and ongoing discussions with the FDA. The trial has completed enrollment of patients have concluded. The median of 12 months of follow up.
Dr. Jennifer Buell: And we're collecting data on late responses in this trial as well. The data continues to improve as it matures with response rates and, most importantly, duration of those responses. Agenus will continue to keep the agency informed of additional data advancements.
And we're collecting data on late responses and this.
<unk> P as well the data continues to improve as it matures with response rates and most importantly duration of those responses.
Genesis will continue to keep the agency informed of additional data advancements and as Garo just discussed we plan to disclose the timing and strategy regarding.
Dr. Jennifer Buell: And as Garo just discussed, we plan to disclose the timing and strategy regarding BAL and ZAL once BAL's FDA filing has been accepted. Our first approval with balacelamab would mark a strategic milestone for Agenus. Having our own approved PD-1 inhibitor would allow us the freedom and flexibility for the development and commercial pricing of our combination regimens with our own IO compounds, including CTLA-4, TGITS, and novel molecules targeting myeloid pathways and beyond. In addition, we see a significant opportunity with our PD-1 inhibitor in combination with potential partner programs.
Chile, and zol, one spouse FTA filing has been accepted.
Our first approval at the hostile and map with Mark and strategic milestone for genus having our own approved PD, one inhibitor and would allow us to freedom and flexibility for the development and commercial pricing of our combination regimens.
And with our own Io compounds, including C. T L. A four digits and novel molecules targeting myeloid pathways and beyond.
In addition, we see a significant opportunity with our PD one.
In combination with potentials partnered programs.
And.
Regarding 11 and 81.
Dr. Jennifer Buell: Regarding 1181, to the emerging clinical profile of 1181. Again, this is also an engineered antibody. We've engineered the FC region of the antibody to improve its features.
To the emerging clinical profile of 11, eight and one again. This is also and engineered antibody we've engineered the FC region of the antibody to improve its features and we.
Dr. Jennifer Buell: We designed 1181 for superior efficacy, with improved T cell priming and the capability to deplete suppressive intratemoral regulatory T cells. We've also designed the molecule for better safety, avoiding complement-mediated toxicities, and broadening the patient population who can benefit from CTLA-4. That's because of improved binding to CD16, and we're seeing activity in patients with both the low affinity and the high affinity CD16 allele. We believe Agent 1181 continues to show nothing less than extraordinary promise as a differentiated anti-CTLA-4. This potential is upheld by the new data Agenus announced early in February that describes new confirmed responses.
We designed 11 81 for superior efficacy.
Gesine with improved T cell priming.
And the capability to deplete suppressive interest tomorrow and regulatory T cells.
We've also designed the molecule for better safety, avoiding complement mediated toxicities and brought and the patient population who can benefit.
Benefit from C T L a four and.
And that's because of improved binding to see day, 16, and we're seeing activity and patients with both the low affinity and the high affinity cities and 16 allele.
We believe age and 11 81 continues to show nothing less and extraordinary promise and the differentiated anti.
And I see T. L. A for this potential is upheld and the new data Genesis announced early in February that describes new confirmed responses.
Dr. Jennifer Buell: As of February, a total of 6 confirmed responses with 1181 monotherapy and 1181 plus BAL have been reported in colon, ovarian, and endometrial cancers, including two complete responses. Furthermore, we've seen responses in cold tumors. These are tumors that have a low tumor mutational burden, microsatellite-stable disease, and PD-L1-negative tumors, as well as BRCA-negative tumors, and tumors with a low-affinity CD16 allele. This is what makes 1181 unique.
As of February a total of six confirmed responses with 11, and 81 mono therapy, and 11 and 81 plus value have been recorded reported and colon.
Ovarian.
Varian and.
And endometrial cancers, including two complete responses.
Further we've seen responses and cold tumors. These are tumors that have low tumor mutational burden.
Microsatellite stable disease, and PDL, one negative tumors as well as bracken negative tumors and tumors with a low affinity.
2016 allele.
This is what makes 11 and 81 unique these are tumors, where current Io therapy is largely ineffective and addition, no debilitating neuro endocrine toxicities or liver toxicities have been observed unlike what we see and patients treated with your boy experiencing 10% to 15% taxes.
Dr. Jennifer Buell: These are tumors where current iotherapy is largely ineffective. In addition, no debilitating neuroendocrine toxicities or liver toxicities have been observed, unlike what we see in patients treated with Yervoy who experience 10-15% toxicity. Looking ahead with 1181, currently in phase 2 development, our goal is a fast-to-market strategy, targeting indications that currently have few effective treatments and patients who have failed prior to standard therapies. Trials are continuing with 1181 alone and in combination with balacelamab in expanded cohorts and microsatellite-stable colorectal cancer, microsatellite-stable endometrial cancer, non-small cell lung cancer With continued positive clinical data, a registrational program is expected to be in by the end of this year.
And he sees.
Looking ahead with 11 and 81 currently in phase two development.
Our goal is a fast to market strategy targeting indications that currently have few effective treatment and in patients who have failed prior to standard therapies.
Trials are continuing.
And this would have and 81 alone and in combination with bell still them out with.
And with expanded cohorts and microsatellite stable colorectal cancer.
Microsatellite stable endometrial cancer, non small cell lung cancer and melanoma.
With continued positive clinical data a registrational program expect it to be.
And by the end of this year.
And it's with great excitement that we brought on board, Dr. Stephen Oh day, and expert and delivering effective io agents to patients with cancer.
Dr. Jennifer Buell: And it's with great excitement that we brought on board Dr. Steven ODay, an expert in delivering effective bioagents to patients with cancer. AGEN 1181 alone, and as the backbone of high-impact combinations, could be a foundational therapy if approved, driving the next wave of biotherapies. Our initial registration plan will focus on indications for rapid launch through the accelerated approval pathway, either as a monotherapy or on top of our PD-1 or any approved PD-1.
H and 11, and 81 alone and as the backbone of high impact combinations could be a foundational therapy if approved.
Proved driving the next wave of I O treatment. Our initial Registrational plan will focus on indications for a rapid launch through the accelerated approval pathway.
As a monotherapy or on top of our PD, one or any approved PD one.
Dr. Jennifer Buell: Based on our preclinical and clinical data to date, our ambitions with 1181 plus PD-1 are to be the dominant I.O. combination with the potential to overtake Irvoy and Aptivo or Kimo and Keytruda as the market leader. We're actively seeking the right partner to execute this strategy and dominate in this sector.
Based on our preclinical and clinical data to date.
Our ambitions with 11, and 81 plus PD one arm.
Or to be the dominant I O combination with the potential to overtake your voice and opdivo or chemo and keytruda as the market leader.
And we're actively seeking the right partner to execute this strategy and dominate in the sector.
At the upcoming ACR conference in April will present, two abstracts, featuring age and 11 81 alone and in combination with other Io mechanisms such as our anti PD, one therapy, they'll still and map will showcase how the unique design of this molecule is expanding the benefit of this important target to try and drive responses.
Dr. Jennifer Buell: At the upcoming AACR conference in April, we'll present two abstracts featuring HN1181 alone and in combination with other IO mechanisms, such as our anti-PD-1 therapy, Valstilumab. We will showcase how the unique design of this molecule is expanding the benefit of this important target to drive responses in all polymorphic variants and the ability to provide clinical benefit in previously unresponsive tumors. We'll also show the benefit of adding 1181 to other checkpoint inhibitors such as anti-PD-1, anti-TIGIT, INKT Activating Therapy, and Adoptive T-Cell Therapy. Novel I.O.
<unk> and all polymorphic variants.
And the ability to provide clinical benefit and previously unresponsive tumors.
We'll also show the benefit of adding 11 and 81, two other checkpoint inhibitors, such as anti PD one.
Anti ticket.
I N K T activating therapy.
And adoptive T cell.
All therapy novel I O combinations will drive the next wave of I O therapy, and a Genesis believe that 11, and 81 alone and in combination with other mechanisms is the foundation of this next wave.
Dr. Jennifer Buell: Combinations will drive the next wave of I.O. therapy, and Agenus believes that 1181 alone, and in combination with other mechanisms, is the foundation of this next wave. Let's turn now for a moment to work on PIDGET.
And.
Let's turn now for a moment to work on ticket.
Dr. Jennifer Buell: Not unlike CTLA-4 and PD-1, TIGID is one of the key components in our immune system. It's found on T-cells, and by suppressing unnecessary activity, like the activation of T-cells, it helps keep the immune system properly balanced. Usually, Tidgit is invaluable to good health, but in cancer patients, its suppression of the immune system allows tumors to grow. An important finding is that treatment with PD-1 actually up-regulates TIGIT, consequently curbing its activity. Using antibodies has become an area of intense R&D efforts, and anti-TIGIT therapy is set to be another breakthrough in I.O. Agenus has two anti-tissue antibodies.
Not unlike C T L. A four and PD one tissue is one of the key components and our immune system is found on T cells and by suppressing unnecessary activity like the activation of T cells and helps keep the immune system properly balanced.
Usually pitch it is invaluable to good health, but and.
Cancer patients tissue suppression of the immune system allows tumors to grow.
And important finding is that treatment with PD, one actually up regulates ticket consequence, consequently, curbing the activity.
And pichet, often using antibodies has become an area.
A intense R&D effort and anti ticket therapy is set to be another breakthrough and I O.
A genesis two anti antigen antibody such as age and 13 twenty-seven of mono specific antibody. That's also engineered like Asia, and 11 and 81 to improve performance.
Dr. Jennifer Buell: This is Agen 1327, a monospecific antibody that's also engineered, like Agen 1181, to improve performance, and Agen 1777, a bi-specific antibody that includes a tiget arm that has also been engineered for FC enhancement. As a potentially best-in-class agent, we're prioritizing agent 1777 for advancement into the clinic, and expect to begin human studies this year. What makes Agens 1777 potential the best in class?
And Asia and 17th.
<unk> and 77, our bio specific antibody that includes a digit arm that has also been engineered for FC enhancement.
As a potentially best in class agent, we're prioritizing agents 17, and 77 for advancement into the clinic and big and expect to begin human studies this year.
What makes agents 17, and 77 potential best in class similar to 11 and 81, we've designed the front end of 17 and 77 for strong receptor binding and this case to digit we've also engineered the FC backend for improved T cell and NK cell.
Dr. Jennifer Buell: Similar to 1181, we've designed the front end of 1777 for strong receptor binding, in this case, to TIGIT. We've also engineered the FC back end for improved T cell and NK cell activation, in order to more effectively unleash the immune system. We've gone one step further with 1777 by engineering it as a bi-specific antibody, co-targeting a second tumor escape mechanism to create a double blockade against cancer escape. This dual blockade is designed to address a potential alternate escape mechanism to tiget therapy.
And activation.
In order to more effectively unleash the immune system.
We've gone one step further with 17 and 77 by engineering. It is a bispecific antibody co targeting a second tumor escape mechanism to create a double blockade against cancer escape.
This dual blockade is designed to address the potential alternate escape mechanism to tissue therapy.
Dr. Jennifer Buell: Overall, we believe the combination of our FC-enhanced and co-targeting with our Agent 1777 Bi-specific gives it best-in-class potential and, as Garo mentioned, potentially provides strong efficacy not just in combination with other I.O. mechanisms but also uniquely as a single agent.
Overall, we believe the combination of our FC enhanced and co targeting with our agents 17, and 77 by specific gives it a best in class potential and as Garo.
[noise] mentioned potentially provides strong efficacy not just in combination with other io mechanism, but also uniquely as a single agent.
Dr. Jennifer Buell: Some of this has already been demonstrated in preclinical tumor models, and we eagerly anticipate clinical trial initiation this year. Our Tidget Strategy was also recently featured in our first episode of Agenus Insights, our new R&D mini-series that provides insight into impactful areas of research and Agenus' contribution to immune oncology. We encourage you to watch the replay and to stay tuned for more episodes in the coming months.
Some of this has already been demonstrated in preclinical tumor models and we eagerly anticipate clinical trial initiation this year.
Our ticket strategy was also recently.
And these features and our first episode of a genus insights. This is our new R&D mini series that provides insight into impactful areas of research and a genesis contribution to immune oncology. We encourage you to watch the replay and stay tuned for more episodes and the coming months.
Through our agenda is subsidiary we've developed a platform to produce and variant natural killer T cells or I N K T's.
Dr. Jennifer Buell: Through our Agentus subsidiary, we've developed a platform to produce invariant natural killer T-cells, or INKTs. INKTs are a type of self-directed, intelligent immune cells capable of producing responses from both the innate and the adaptive arms of the immune system. I think if youth can combat multiple disease threats in an autonomous manner.
I N T Ts or a type of self directed.
Intelligent immune cells capable of producing responses.
Chances from both the innate and the adaptive arms of the immune system.
I think if he's can combat multiple disease threats and our autonomous manner and.
Dr. Jennifer Buell: In inflammatory disorders, INKTs help to restore the balance of the immune system, correcting conditions like the cytokine storm that we see in patients with severe cases of COVID-19. Earlier this year, we announced preliminary Phase 1 data from our COVID-19 trial, currently ongoing. Dose escalation for an initiation into a Phase 2 trial is on track for the first half of this year, and data readouts are expected in the fourth quarter. Now, in cancer, INKTs home in on tissues and direct the killing of tumor cells. They have an invariant TCR receptor, so it doesn't need to be engineered to them.
And inflammatory disorders, I NK and T has helped to restore the balance of the immune system drafting conditions like the cytokine storm that we see and patients.
And with the severe cases of COVID-19 earlier this year, we announced preliminary phase one data from our Covid trials currently ongoing.
Dose escalation for and initiation into a phase two trial is on track for the first half of this year and data Readouts are expected in the fourth quarter.
Now in terms.
Cancer I N K T's home in on tissues, and direct the killing of tumor cells, they have and and variant TCR receptor it doesn't need to be engineered to them.
This will counter immune suppressor cells and block tumor escape mechanisms you can imagine the benefit of.
Dr. Jennifer Buell: This will counter immune suppressor cells and block... tumor escape mechanisms. You can imagine the benefit of this homing feature we observe in lung tissue in the infectious disease setting to be very impactful in diseases like lung cancer. And do the cell therapy INKTs have the potential to be used on their own? and in combination with additional anti-cancer therapies such as those already in our pipeline. Agentis' first INKT Phase 1 trial in cancer is anticipated to start dosing during the first half of this year, and we're targeting human studies to be initiated in solid tumors soon thereafter.
This homing feature we observe and lung tissue and the infectious disease setting to be very impactful and diseases like lung cancer.
And as a cell therapy I N K T has the potential to be used on their own.
And in combination with additional anti cancer therapies, such as those already and our pipeline.
So Genesis is first I N K T phase one trial and cancer is anticipated to start dosing during the first half of this year and we're targeting human studies to be initiated and solid tumors. Soon thereafter.
And lastly, while we often discuss our I O pipeline compounds and isolation, there's clearly.
Dr. Jennifer Buell: Lastly, while we often discuss our IO pipeline compounds in isolation, there's clearly tremendous value in the combination potential for the cancer pathways we're targeting, PD-1, CTLA-4, TIGIT, INKT therapy, and other promising mechanisms and programs we have not yet discussed on this call. Stay tuned for more on these exciting developments in the balance of this year. I'll now turn the call over to our Chief Commercial Officer, Andy Hurley, to elaborate on our excitement regarding Agent 1181.
Tremendous value and the combination potential for the cancer pathways, we're targeting PD one C. P. L. A four digit I and K T therapy, and other promising mechanisms and programs we have not yet discussed on this call.
Stay tuned for more and these exciting developments and the balance of this year.
Now.
The call over to our Chief commercial officer, Andy Hurley to elaborate on our excitement regarding agent 11 and 81.
Andy Hurley: Thank you, Jen. My decision to join the Agenus team was driven...
Jim My decision to join the agenda and was driven by the excitement we all feel and the opportunities we have here under one roof I'm.
Andy Hurley: I'm driven by the excitement we all feel and the opportunities we have here under one roof. I'm also driven by our near-term prospects, which I believe could create substantial value.
And I'm also driven by our near term prospects, which I believe.
To create substantial value.
Andy Hurley: which I believe could create substantial value. I'm particularly excited by how we can take our PD-1 Balcephalumab and potentially grow it into a major franchise with superior combination potential with Agent 1181. I believe 1181 will significantly expand the commercial opportunity of our anti-PD-1 antibody with the potential to outperform current IO combinations. The clinical results to date have been very exciting, both as a monotherapy and in combinations across a wide array of tumor types.
I'm, particularly excited about how we can take our PD, one belt and fill them out and potentially grow it into a major franchise with a superior combination potential with age and eliminated one volume.
Believe 11 81 wells.
Significantly expand the commercial opportunity.
Anti PD, one with a potential to outperform current and Io combinations and the clinical results to date have been very excited over as a monotherapy and in combinations across a wider array of tumor types, specifically as Jan said cold tumors, such as microsatellite stable.
Andy Hurley: Specifically, as Jen said, cold tumors, such as microsatellite stable tumors, represent a significant portion of colorectal and endometrial cancers, and traditional PD-1 anti-CTLA-4 inhibitor therapies have not been as effective here. These are tumors that don't generally respond to cancer immunotherapy, and yet we are seeing responses with agent 1181.
Tumors represent a significant portion within colorectal and endometrial cancers, and traditional PD, one antagonist and <unk> four inhibitor therapies have not been as effective here.
And are tumors, which don't generally respond to cancer immunotherapy and yet we're seeing responses with age and 11.
And everyone.
Andy Hurley: Practically and conceptually, we're not limited to any tumor type if the current response trends we are seeing continue. It's really a function of choosing patients and indications, which can get us to the finish line quickly and leverage this to expand on our broader opportunities. Having our own PD-1 to pair with our superior CTLA-4 and then having our own unique CTLA-4, which can add significant value to our PD-1, are advantages which are very exciting for us to pursue.
Practically and conceptually, we're not limited to any tumor type if a car and response trends we are seeing from changyou.
Really a function of picking patients and indications, which can get us to the finish line quickly and leverage this to expand on our broader opportunities.
And your way and PD one to pair.
With our superior situated for.
And then having our own unique see Julie for which can add significant value to our PD, one and our vintages, which are very exciting for us to pursue and.
Andy Hurley: And then there's the rest of our pipeline, including our intelligent cell therapy program, our vaccines, and an exciting pipeline of antibodies with compelling early data. I feel the privilege of working with an exceptional team of people across all disciplines. I have worked at highly successful companies, but what we have here is very, very unique and exciting. I hope to interact with you more frequently and do a deeper dive on our commercial strategy to create something exceptional. I appreciate the opportunity to express my plans, and I'll now turn the call over to Christine Klaskin to review our financials.
And then there's the rest of our pipeline, including our intelligent and cell therapy program, our vaccines and exciting type.
And our bodies with compelling early data.
I feel the privilege of working with an exceptional team of people across all disciplines.
I've worked at highly successful companies, but what we have here is very very unique and exciting I hope to interact with you more frequently and do a deeper.
And one of if on our commercial strategy to create something exceptional I.
I appreciate the opportunity to express my plans and I'll now turn the call over to per screen and classroom to review our financials.
Thank you Andy.
Christine M. Klaskin: For the year ended December 31, 2020, we recognized revenue of $88 million, which included revenue related to the upfront license fee from our transaction with VEDA, in addition to non-cash royalties and milestones earned. For the year ended 2019, we recorded revenue of $150 million, which included revenue related to the upfront license fee from our transaction with Gilead and milestones earned in addition to non-cash royalties. The net loss for the fourth quarter was $38 million, or $0.20 per share, compared to a net loss for the same period in 2019 of $31 million, or $0.22 per share.
For the year ended December 31 2020.
Di managed revenue of $88 million, which includes revenue related to the upfront license fee from our transaction with better in addition to non cash royalties and milestones earned.
For the year ended 2019, we recorded revenue of $150 million, which included revenue related to the upfront.
License fee from our transaction with Gilead and milestones earned in addition to noncash royalties earned.
Net loss for the fourth quarter was $38 million or <unk> 20 per share compared to a net loss for the same period in 2019 of $31 million or 22 cents per share.
Net loss for 2020 was $183 million per $1.05 per share compared to a net loss for 2019 of $112 million or <unk> 80 per share.
Christine M. Klaskin: The net loss for 2020 was $183 million, or $1.05 per share, compared to a net loss for 2019 of $112 million, or $0.80 per share. We ended 2020 with a cash balance of $100 million, as compared to $62 million on December 31, 2019. I will now turn the call back to Garo for his concluding remarks.
We ended 2020 with a cash balance of $100 million.
As compared to $62 million on December 31, 2019.
I will now turn the call back to Garo for concluding remarks.
[noise] and causing.
Garo H. Armen: In closing, the progress Agenus has made in the past year has set the stage for an exciting 2021. We expect to achieve value driving corporate events, clinical and preclinical pipeline events starting in the second quarter of this year, and they will include, Completing our BLA filing for vascular monotherapy in second-line cervical cancer, preparing for commercial launch in the second line cervical cancer market, defining our BLA filing strategy for BALSAL, clinical and preclinical data presentations at conferences, including for Valzao, 1181, PIDGET, INKT cell therapy, and other Agenus and partner programs.
And the progress and Janus has made in the past year has set the stage for and exciting 2021.
We expect to achieve value driving corporate events.
Clinical and preclinical pipeline events, starting in the second quarter of this year and they will include.
Completing our BLA filing for both skilled and map monotherapy in second line cervical cancer.
Cancer.
Preparing for commercial launch and the second line cervical cancer market.
Defining our BLA filing strategy for valves out.
Clinical and preclinical data presentation's at conferences, including.
Pals out.
11 and 81.
And I.
And K T cell therapy, and other agendas and partnered programs.
Initiating clinical studies without ticket program.
Garo H. Armen: Initiating clinical studies with our PIDGET program, with the prioritization of Agen 1777. Continuing with our phase two development for agent 1181, Plus, while still on the map, with a goal of transitioning into registrational studies, continuing enrollment in the ongoing phase one studies of INKTs in COVID and in cancer, expanding Agenus' West capacity for internal and partnered manufacturing support, and producing a sustainable supply of QS
With the prioritization of a gen one triple seven.
Continue.
And with our phase II development for Asia, and 11 and 81.
Plus barstool and map.
With a goal of transitioning into Registrational studies.
Continuing enrollment in the ongoing phase one studies, all I and K T's in Covid.
And and cancer.
Expanding the Genesis west capacity for internal and partnered manufacturing support.
Producing a sustainable supply of Qs 21, and four partnered programs.
Garo H. Armen: And lastly, delivering cash-aggretive corporate transactions starting in the second quarter of this year. Thank you very much again for your interest. And now we're ready to open up for questions with myself, Dr. Buell, Andy Hurley, and Dr. Steven ODay present. (Inaudible) Maybe it's the, uh, our... Liz, if you could get the Q&A going, please? Ladies and gentlemen, if you'd like to ask a question at this time, please press the star, then the number one key on your touchtone telephone. Again, that is star, then one. If you'd like to ask a question at this,
And lastly.
And we delivering cash accretive corporate transactions, starting and the second quarter of this year.
Thank you very much again for your interest.
And now we're ready to open up for questions wed myself book to Bill and the.
Early and Dr. Stephen All day present.
Jonathan.
And maybe it's the our lives if he could get them.
Oh, and please ladies and gentlemen, if you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone telephone.
And again that is star.
And then one if you'd like to ask a question at this time.
Our first question comes from the line up here and a man with Jefferies.
Operator: Our first question comes from Line Out Beer, and I'm in with Jeffrey's.
Yeah, Hey, guys. This is jeet on for Darren and thanks for taking my questions. Congratulations on the progress.
Jeet: Yeah. Hey, guys. This is Jeet on for Barron.
Jeet: Thanks for taking my questions. Congratulations on the progress to date, and I'm looking forward to updates this year. Could you just maybe walk me through the timing, perhaps, between the BAL BLA filing and when you actually anticipate submitting the combo, and perhaps when ultimate approval is perhaps expected there? And then second, just if you could talk through perhaps some of your go-to-market efforts to this point and any goals for the remainder of this year. And if there's any color on discussions with payers or thoughts on pricing, that would be great. Thank you.
A day and looking forward to update this year.
Could you.
Just maybe walk me through the timing, perhaps between the bow and BLA filing and when you actually anticipate submitting the combo and perhaps one ultimate approval with perhaps expected there and then second and just if you could talk to perhaps some of your go to market efforts to this point and any goals.
<unk> for the remainder of this year and if there's any color on discussions with payers and thoughts on pricing that would be great. Thank you.
Garo H. Armen: Thank you, Vera, and let me start out addressing the BALZEL question. As you know, and as we sort of alluded to, as data matures, looking at our past performance with data disclosures, we're delighted to see that the data is getting better. And I think, you know, given the size of our company and given the enormous demands on us from the Regulatory Undertaking, we made a decision several months ago, which we articulated to the investment community, that our first priority is to file our BLA with Balstodomat.
Thank you Barry let me start out addressing the.
Bells out question.
As you know and as we sort of alluded true.
The data matures.
Yeah.
Looking at our past performance with data disclosures.
And we're delighted to see that the data is getting better.
And I think you know given the size of our company and given the enormous dim.
Demands on us for regulatory undertake.
And we made a decision and several months ago, which we articulated to the investment community that our first priority is to file our BLA with barstool and map.
Garo H. Armen: And once that's done, we will provide additional guidance for our timelines associated with our BALZAL filing. And, of course, that will include disclosure of more mature data, which we're in the process of addressing, both from a public disclosure perspective, as well as disclosing it to the agent, got it, go to market strategy. I'm assuming you're talking about going to the product market strategy. And with that, I think Andy, are you prepared to give us some initial remarks?
And once that's done we.
We will provide additional guidance for our timelines and associated.
And our valves valve finally and.
And of course that will include disclosure of more mature data, which were and the process of.
Addressing.
Both from a public disclosure perspective, as well as disclosing it to the agency.
Got it.
<unk> go to market strategy I'm, assuming you're you're talking about go through product market strategy and with that I think Andy are you prepared to give us. Some initial remarks sure yes, it's a good question.
Andy Hurley: I've been here for a limited amount of time.
And here and a limited amount of time, but I can tell you that the launch planning is underway, we're really evaluating how we're going to really address the unmet needs and the marketplace and position this product and a way that addresses those unmet needs bolt and a physician level as well as on a patient level and at the patient level you bring up the question.
Andy Hurley: I can tell you that the launch planning is underway. We're really evaluating how we're going to address the unmet needs in the marketplace and position this product in a way that addresses those needs.
Andy Hurley: addresses those unmet needs, both at a physician level as well as at a patient level. And at the patient level, you bring up the question of pricing and access.
And on pricing and access that's going to be one of our absolute Paramount priorities is to ensure unencumbered access to bell <unk> as we look at the landscape that's going to follow we look at this as a pivotal part and our relationship with payers because we don't believe this is going to be of.
Andy Hurley: That's going to be one of our absolute paramount priorities, just to...
Andy Hurley: Unencumbered Access to Valsilumab as we look at the landscape that's going to follow. You know, we look at this as a pivotal part in our relationship with payers because we don't believe this is going to be, of course, our first and only entry into the marketplace. We want to be able to follow on with other products, and establishing those relationships and making sure that they understand our goals, which is unencumbered patient access, is going to be really key.
Our first and only into the marketplace, we want to be able to follow on with other products and establishing those relationships and making sure that they understand our goals, which is unencumbered patient access is going to be really key so we're going to be starting those discussions with payers. We've done a lot of market research to understand really what are the drivers to.
Andy Hurley: So we're going to be starting those discussions with payers. We've done a lot of market research to understand really what the drivers are for positioning our product, and we're really encouraged by what we're hearing to be able to offer that in a setting both at the physician and patient level. So I can tell you that, you know, I'm week four into the role, and, you know, ultimately, I'm very encouraged by the level of effort that's already been put in and our planning moving forward.
Of course, and our product and we're really encouraged by what we're hearing to be able to offer that and.
And a setting both at the physician and patient level. So.
So I can tell you that.
Weak for into the role and ultimately I'm very encouraged by the level of effort that's ours.
Position and are planning moving forward.
Andy Hurley: Got it. And if I could just ask one more follow-up question. On 1181, it seems like the AACR presentations will be fairly preclinical in nature. Just wanted to know if we can anticipate perhaps, you know, a robust clinical update on that, perhaps later this year, and if we'll maybe get a look at that phase two data in colorectal.
Got it and if I could just ask one more follow up question on $11 81. It seems like the ACR presentation will be fairly preclinical in nature and just wanted to know if we can anticipate perhaps.
Robust clinical update on that.
Perhaps later this year and it will maybe get a look at that phase two data in colorectal.
Andy Hurley: Hi Jeet. Thanks for...
Dr. Jennifer Buell: Hi Jeet. Thanks for the question. Actually, AACR will certainly include some preclinical information, but we will also provide a clinical update on where we are with the programs. So stay tuned for more on that.
Thanks.
Hi, Thanks for the thanks for the question actually ACR and certainly will include and preclinical information but of course, we will also provide a clinical update on where we are with the programs and so.
Stay tuned for more on that.
Our next question comes from my Assam, Tony with B Riley Securities.
Operator: Our next question comes from Mayank Mamtani with Be Riley Securities.
Mayank Mamtani: Good morning team, I appreciate the comprehensive update and thanks for taking our questions. It's great to have Dr. Oday and Andy be part of the discussion. So maybe just piggybacking on the previous question on the upcoming 1181 clinical data at ACR, would you also have a more updated cutoff relative to February 9th? Could you just clarify that? And maybe, Dr. Oday, could you comment on why MSS colorectal indication kind of makes the first to pursue as you think about the path to market? Could we just talk about the dynamics of that indication?
Good morning, Deane appreciate the comprehensive update and thanks for taking my question and to have Dr. Dee and Andy will be part of the discussion.
So maybe just piggybacking on the previous question on the.
And the upcoming 1181 clinical data at ACR.
Would you also have a more updated got off relative to February nine could you just got it by that and maybe maybe Doctor a day, if you could comment on why and that's S.
Escalate and colorectal indication and a mix of clause do price you as you think about Boston.
And you just talk about the dynamics of that indication.
Dr. Jennifer Buell: So before I turn it over to Dr. Oday, Mayank, thanks for your question. At AACR, yes, we will have more mature data than what we've previously disclosed, and this will include more information on duration as well as potential new responses in the program too. Now I'll turn it over to Dr. Oday to give you his thinking on MSS colorectal cancer.
So before I turn it over and stature and a day and Leon. Thanks for your question at ACR, Yes, we will have a more mature.
Data volume.
And then what we've previously disclosed and this will include.
More information and duration as well as a potential new responses and the program to now I'll turn it over to Doctor on data and give me and him thinking on MSS colorectal cancer. Thank you Mark.
Steven J. ODay: Thank you, Myron. Well, as Andy said, I'm new to the company in recent months, but I have had the unique opportunity to be involved with 1181 over the course of the last several years, both in learning about its exciting clinical drug design, as well as preclinical data, and then obviously being involved as the principal investigator in the 1181 Phase 1 trial. What's exciting to me is that the preclinical data of more activity and Treg depletion, as well as more potential access to low affinity CD16 alleles, all seem to be playing out so far in the clinic with our Phase 1 trial.
And then he said.
New to the company in recent months, but I have had the unique opportunity to be involved with eliminating one over the course of the last several years, both and learning about it and exciting clinical and drug design as well as preclinical data and then obviously been involved but the principal investigator and the.
Eliminating one phase one trial.
What's exciting to me is the preclinical data of more activity and.
T Reg depletion as well as more.
Our potential access to low affinity CD <unk>, all seems to be playing out.
So far and the clinic with our phase one trial as you can imagine.
Steven J. ODay: As you can imagine, with the competitive nature and approvals across IO indications and solid tumors, Phase 1 trials attract fairly cold tumors that are MS-stable, and it's no surprise that our trial has attracted those patients, particularly colorectal, endometrial, MS-stable, ovarian, and others. And what's exciting to me is to see objective responses, obviously, in both 1181 monotherapy and immunocompromises in these cold tumors that are predominantly PD-L1-negative, MS-stable, low tumor burden, and interestingly, in CD16 lower heterozygous affinity polymorphisms, which is all consistent with preclinical data.
With the competitive nature and approvals across Io indications in solid tumors phase one trials.
Attractor fairly cold tumors that are stable and.
And I was surprised that our trial has attracted those patients, particularly colorectal endometrial MF stable ovarian and others and what's exciting to me is to see objective responses, obviously and bulb, eliminating one monotherapy and combinations in these cold tumors that are.
And Theres only PDL, one negative MF payable low tumor burden and interestingly and <unk> 16, lower heterozygous affinity polymorphism, which is all consistent with preclinical data. So given that fact, obviously I'm excited to be part of the development of this drug.
Steven J. ODay: So given that fact, obviously, I'm excited to be part of the development of this drug as we go forward. And colorectal MS-stable cohorts are clearly a huge unmet need with a low bar in the second and third line settings. So we're going to follow the data and expand these cohorts in cold tumors, as well as look at our warm to hot tumors, both lung and then cutaneous tumors, melanoma and non-melanoma cutaneous skin tumors, are real opportunities for us to look both at this agent and single agent as well as combination. So it's going to be an exciting year for me and my clinical team to develop this very exciting drug.
Predominantly as we go forward and colorectal MF stable cohorts are clearly a huge unmet need with a low bar in the second and third line settings. So we're going to follow the data and expand these cohorts and cold tumors as well as look at our warm to hot tumors.
Both lung and then cutaneous tumors melanoma non melanoma cutaneous skin tumors are real opportunities for us to look both at this agent and assimilate Gen as well as combination. So it's gonna be excited and coming year from me and my clinical team to develop this very exciting drug.
<unk>.
Last day.
Mayank Mamtani: Fantastic! That's very helpful.
And.
And then on Duke wake ones, but Jan and I have one more.
Mayank Mamtani: And then on two quick ones for Jen, and I have one more for Garo to close. Jen, what would be the path for QS21, just from a clinical development standpoint and also on the TIGIT bi-specific? When do you expect to announce the other target you're working on?
Jim what would be the bond book you guys to anyone just from that.
And any great development standpoint, and also on the Bispecific.
When do you expect disclosing the other.
And you are working on.
So my I'm done here. So let me start with what should you just closing as you can imagine this is an incredibly competitive space we have.
Dr. Jennifer Buell: So Mayank, on to you. So let me start by disclosing that, as you can imagine, this is an incredibly competitive space.
Five specific that is a first of its kind, we believe and it's designed really.
Dr. Jennifer Buell: We have a bi-specific that is the first of its kind, we believe, and it's designed really to address an entirely new area. So we will not be disclosing that anytime soon, but we'll certainly keep you informed as the data continues to progress both pre-clinically and then clinically, and that may drive our decision about disclosures. For QS21, the development is really straightforward. So, as you know, the Bill and Melinda Gates Foundation have invested in our initiative to advance a sustainable supply of QS21.
Got you.
To address.
Entirely new area. So we will not be disclosing that anytime soon.
Certainly keep you informed and.
The data continue to.
Progress, both pre clinically and then clinically and.
And that May drive our decision.
And disclosures.
And for Qs 21, the development is really straight forward. So as you know Bill and Melinda Gates Foundation had invested in and our initiative.
Advance a sustainable supply.
And the supply of Qs 21, we've done so well and in the process.
Dr. Jennifer Buell: We've done so, or we're in the process of doing so, but we've already generated early data and demonstrated the biocomparability of this new supply compared to the previous clinic version, which is now in the approved Shingrix vaccine, as you know. So, the development is straightforward.
And if doing so but we've already generated early data and demonstrated the bio comparability.
This new supply compared to the.
And the previous clinic version, which is now and the approved Xing Greg's vaccine as you know.
So the development and straight forward its preclinical comparability and then.
Dr. Jennifer Buell: It's preclinical comparability, and then the clinical program will be very abbreviated to bring this product into the market with a number of vaccine products underway, and particularly at this time when we see the criticality of effective vaccines. We know that historical vaccines no longer cut it. Flu vaccines at 30% efficacy just won't do it. So, we need to improve our ability to take antigens, allow for mass global production of those, and this is where QS21 is really critical, at antigen sparing, allowing a fewer number or a lower amount of antigens to actually be quite effective. As you see with Shingrix, it's over 90%, up to 97% effective in adults, and it gets better with age.
And on a go program will be very abbreviated to bring this product into market with a number of our vaccine products underway and particularly at this time, when we see the criticality and.
Effective vaccines, we know of that historical vaccines and no longer cut it.
Vaccines at 30.
And the Clintons efficacy just won't do it.
So we need to improve.
And our ability to take antigens allow for mass global production of those and this is where our Qs 21 is really critical and antigen sparing, allowing a fewer number and lower amounts.
Britta Gen to actually be quite effective as you see with <unk> with over 90% up to 97% effective and adults and gets better with age and these are the kinds of findings that we're gonna need across the board as we deal with these mutating viruses repeatedly.
Dr. Jennifer Buell: These are the kinds of findings that we're going to need across the board as we deal with these.
Okay.
Mayank Mamtani: Okay, very helpful. So, I think there are a number of different disease indications that you may consider, including flu, COVID, and Shingrix.
And he has.
And so.
And a number.
A number of different.
Disease and the.
The patients that you'll make them today, including flu, including Covid even share.
Understood.
Mayank Mamtani: Okay. Then lastly for Garo, as you think about these cash accretive transactions, can you just give a high-level talk about the framework that you guys are kind of evaluating internally? Because when you think about prosecuting these opportunities, you know, across the board, more advanced late-stage versus earlier-stage programs, kind of how do you think about, you know, a lot of push and pull that might be associated with these transactions?
And then lastly.
You think about these accrued cash with either transaction.
Can you just high level.
And after the framework that you guys are kind.
And if evaluating and Ben and leave Us and when you think about prosecuting these opportunities.
Across the board more mid stage voice is earlier stage programs.
How do you think about.
A lot of push and pull that might be associated with these transactions.
Right. So Oh I can tell you right now is stay tuned as I said in the a and b.
Garo H. Armen: So all I can tell you right now is to stay tuned. As I said in the second quarter, starting in the second quarter, we will see cash accretive transactions, including corporate. Unfortunately, I cannot disclose anything more than that right now.
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Second quarter, starting in the second quarter, we will see a cash accretive transactions.
Including.
<unk> corporate transactions.
So unfortunately, I cannot disclose anything more than that right now.
Mayank Mamtani: Okay, thanks for the email question.
Okay, great. Thanks for taking my question.
Operator: As a reminder, ladies and gentlemen, that is star then one if you'd like to ask a question. Our next question comes from the line of Matt Phipps with William Blair.
As a reminder, ladies and gentlemen that is star then one if you'd like to ask a question.
Our next question comes from the line of Matt Phipps with William.
Okay.
Matthew Phipps: Good morning, thanks for taking my question. So this morning, Sanofi and Regeneron announced positive phase three results for Moteo in treating cervical cancer. I know you guys had previously kind of hinted at needing to get that accelerated approval BLA in before a full approval was there. I assume, given you guys are close to finishing the bowel BLA, that the phase three positive results aren't gonna affect that at this point, but just wanted to confirm.
Yes.
Good morning, Thanks for taking my question and so this morning, Sanofi and Regeneron announced positive phase three results from the town and cervical cancer.
No you guys had previously kind of hinted at needing to get that accelerated approval BLA and before you know a full approval.
There is.
I assume you know given you guys are close to finishing the ball B L. A that the phase III positive results aren't going to affect that.
Dr. Jennifer Buell: Hi Matt. Thanks for the question. Yeah, I agree with you. So, the accelerated approval pathway remains open until full approval is granted in the same indication. Based on where we are with our filing, we don't believe this will impact our plan.
At this point, but just wanted to confirm.
Hi, Matt. Thanks for the question, Yeah, I agree with you and so that accelerated approval pathway remains open and helpful.
Approval is granted and the same indication based on where we are with our filing and.
We don't believe this will impact our plans.
Dr. Jennifer Buell: And similarly, obviously, since the Val-Val is a combination, that accelerated pathway should still be there as well.
And similarly, obviously since the bounce out of a combo that but it's only a popular should still be there as well.
For for a bounce all combo, absolutely others actually.
Dr. Jennifer Buell: for Balzac Combo. Absolutely. Yeah, there's actually, we're the frontrunner there. Yeah.
And where the front and whether there.
Yeah.
Alright, great. Thanks for taking the question.
Thanks, Matt.
I'm showing no further questions in queue at this time I'd like to turn the call back to garner Armen for closing remarks.
Matthew Phipps: Alright, great. Thanks for taking the time to ask the question.
Thank you very much everybody and I think we have covered and some of the really important to highlight.
Operator: I'm showing no further questions in queue at this time. I'd like to turn the call back to Garo Armen for closing remarks. Thank you very much, everybody.
I know that there is considerable amount and.
And our <unk>.
Rusty here, we do prioritize some of the most important near.
Garo H. Armen: Thank you very much, everybody. I think we have covered some really important highlights. I know that there is a considerable amount on our roster here, but we do prioritize some of the most important near-term priorities for us. And so bear with us, and I think with our new star team or the added star team, I'm confident that we will be taking a number of these programs to the finish line expeditiously. Thank you very much, and we'll see you next time.
Near term priorities for us and.
And so bear with us and I think with our new star.
Team or added star team I'm confident that we will be taking and number of these programs to the finish line expeditiously. Thank you very much and we'll see you next time.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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Yes.
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Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating.
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