Q2 2022 Agenus Inc Earnings Call
Operator: Good morning.
Good morning.
Operator: My name is Abby, and I will be your conference operator today.
My name is Abby and I will be your conference operator today.
Operator: At this time, I would like to welcome everyone to the Agenus Second Quarter 2022 Financial Results Conference Call.
At this time I would like to welcome everyone to the agenda second quarter 2020 financial results Conference call.
Operator: All lines have been placed on mute to prevent any background noise.
Ethan Lovell: Good morning, everyone, and welcome to our Second Quarter Earnings Results Conference Call.
All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time.
Please press star followed by the number one on your telephone keypad.
If you would like to withdraw your question again press the star and the number one on your telephone keypad.
Operator: After the speaker's remarks, there will be a question and answer session.
Ethan Lovell: I'm Ethan Lovell, Agenus' Chief External Affairs and Communications Officer, and I have with me today on the call Agenus' Chairman and CEO, Garo Armen, and the company's Vice President of Finance, Christine Klaskin.
<unk>.
Mr Ethan level chief.
External affairs and Communications Officer, you May begin your conference.
Operator: If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad.
Thank you and good morning, everyone and welcome to our second quarter earnings results Conference call I need some level of Genesis Chief External Affairs, and Communications officer, and I have with me today on the call agenda, Chairman and CEO Darryl.
Operator: If you would like to withdraw your question, again, press the star and the number one on your telephone keypad.
Ethan Lovell: Also joining us today is Agenus' Chief Medical Officer, Dr. Steven O'Day, who will be available during the Q&A portion of this call.
And the company's Vice President of Finance Christy Blackstone.
Also joining us today's agenda, Chief Medical Officer, Dr. Stephen though day will be available during the Q&A portion of this call.
Operator: Thank you.
Ethan Lovell: Before I turn the call over to Garo for his prepared remarks, I would like to read our forward-looking statement disclosure. This call will include forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans and timelines, including timelines for data release and partnership opportunities.
Before I turn the call over to Garo for prepared remarks, I would like to read our forward looking statement disclosure.
This call will include forward looking statements, including statements regarding our clinical development regulatory and commercial plans and timelines, including timelines for data release and partnership opportunities.
Ethan Lovell: Such statements are subject to risks and uncertainties and speak only as of the date they are made.
Let's statements are subject to risks and uncertainties and speak only as of the date. They are made agenda is under no obligation to update any of these forward looking statements and we refer you to our SEC filings for more details on these risks.
Ethan Lovell: Agenus is under no obligation to update any of these forward-looking statements, and we refer you to our SAP filings for more details on these risks.
Operator: Mr. Ethan Lovell, Chief of External Affairs and Communications Officer, you may begin your conference.
Ethan Lovell: With that, I'd like to turn the call over to Garo Armen.
With that I'd like to turn the call over to Garo Armen Garo.
Garo Armen: Garo?
Ethan Lovell: Thank you.
Garo Armen: Thank you very much, Ethan, and thank you for joining us today.
Thank you very much.
And thank you for joining us today.
We will concentrate.
Garo Armen: We will concentrate, to start, on our priority clinical programs, which have demonstrated highly exciting activity.
And our priority clinical program, which has demonstrated highly exciting activity.
Garo Armen: We will also provide updates on our earlier stage programs, which we expect to deliver successful outcomes in the clinic based on the robust research and preclinical data that's been generated so far.
We will also provide updates on our earlier stage programs, which we expect to deliver successful outcomes in the clinic based on the robust research and preclinical data that's been generated so far.
Yeah.
Genesis had a successful second quarter capped by groundbreaking presentation at the World Congress on gastrointestinal cancer in Barcelona.
Garo Armen: Agenus had a successful second quarter, capped by a groundbreaking presentation at the World Congress on Gastrointestinal Cancer in Barcelona. Our leap-breaking submission was offered prime of place at the conference's opening session, and Dr. Anthony Alcohuri presented on heavily pretreated MSS colorectal patients, who were treated with our novel adaptive innate immune activator, called Botansilamab, in combination with our anti-PD-1 antibody, Balsilamab. We will call these BotBal for short, but this combination delivered 24% overall response rates and 73% disease control rates, with a substantial number of these patients showing responses at data cut-off. No grade 4 or 5 events were reported, and the combination was generally well-tolerated. What makes these responses unique is the fact that these patients had cold tumors.
Our late breaking submission was offered triangle place at the conference is opening session.
And Anthony I'll cohort presented a heavily pre treated MSS colorectal patients who were treated with novel adaptive and innate immune activator called potential of that.
In combination with our anti PD one antibody.
Stuart.
Okay.
We will call these bought back.
For sure.
But this combination delivered 24% overall response rates.
73% disease control rate.
With a substantial number of these patients showing.
Responses at data pattern.
No grade four or five events were reported.
And the combination was generally well tolerated.
Garo Armen: And cold tumors are historically not responsive to immunotherapy. In addition, these patients had tumors which were PD-L1 negative with low tumor mutational burden.
What makes these responses unique is the fact that these patients had cold tumors and.
In cold tumors are historically not responsive to immunotherapy.
In addition, these patients had tumors, which were PD lone negative.
With low tumor mutational burden.
Garo Armen: Responsive patients included those who had failed prior IO therapies.
Responsive patients, including those who had failed prior io therapies.
Garo Armen: All of these make the patients treated in our trial highly unlikely to respond to immunotherapy or conventional immunotherapy, and certainly not other treatments either.
Although these make the patients treated in our trial.
Hi, Lee unlikely to respond to.
Immunotherapy.
Conventional immunotherapy.
And certainly not other treatments either.
Garo Armen: While this trial was not randomized, experts in the field were satisfied with our criteria for selecting patients, who were heavily pretreated and that were not confounding factors which would subjectively favor outcomes achieved in the study. We observed 24% objective response rates when compared to 1-2% responses in similar patients are achieved with current standards of care.
While this trial was not randomize experts in the field, we're satisfied with our criteria for selecting patients who are heavily pre treated.
And that we're not confounding factors, which would subjectively favor outcomes achieved in this study.
We will observe 24% objective response rates when compared to 122% responses and in similar patients already.
With current standards of care.
Garo Armen: This is a clear demonstration of a potentially groundbreaking therapy by the account of the experts in the field.
This is a clear demonstration of it potentially groundbreaking therapy by the account of the experts in the field.
Garo Armen: For those of you who were unable to attend the conference, we provided a video link to the full presentation on our website.
For those of you who are unable to attend the conference with <unk> provided the video link to the full presentation on our website.
Garo Armen: We're also pleased with the enthusiastic response of the ESMO GI leadership.
We're also pleased with the enthusiastic response of the ESMO Gi leadership.
Garo Armen: And in our subsequent meetings with IO leaders in the field who regard the outcomes as potentially paradigm changing.
And in our subsequent meetings.
I owe leaders in the field, who regard the outcomes as potentially.
Paradigm change.
Garo Armen: This data has translated into significant interest in our upcoming clinical trials with Bonensulimab, and we have received a substantial number of unsolicited inquiries from leaders in the field to participate in our upcoming CRC melanoma and pancreatic cancer trials.
This data has translated into significant interest in our upcoming clinical trials with both <unk> and we have received a substantial number of unsolicited inquiries from leaders in the field to participate in our upcoming CRC melanoma and pancreatic cancer trial.
Garo Armen: The unique attributes of Bonensulimab and the unprecedented responses that it achieved in patients with cold tumors, has also generated significant interest in future trials of other cold tumor cancers, such as gynecological cancers, gliomas, breast cancer, and pediatric cancers.
House.
The unique attributes of <unk>.
And Matt and the unprecedented response.
Change in patients with cold tumors has also generated significant interest in future trials of other cold tumor cancers, such as gynecological cancers.
<unk> breast cancer and pediatric cancers.
Garo Armen: We're currently working with the FDA and other global regulatory agencies to start randomized phase 2 clinical trials, which we hope will begin very shortly.
We're currently working with the FDA and other global regulatory agencies to start randomized phase two clinical trials, which we hope will begin very shortly.
Garo Armen: Our strategy is to pursue the expeditious development of approval of our promising pipeline in as many markets geographically as possible. This includes botansilamab as a monotherapy and in combination with bostilamab, xylosilamab, in combination with bostilamab, and others in clinical development.
Our strategy.
Is to pursue the <unk>.
The dishes development of it.
Ruble of our promising pipeline.
In as many markets geographically as practicable.
This includes potentially map.
As a monotherapy.
And in combination with barstool at that.
We're thrilled that in combination with us and others in clinical development.
Garo Armen: All of our pipeline products have been designed, and this is a very important point to note, to perform in unique ways as combination or monotherapies.
All of our pipeline products have been designed and this is very important point to note.
Perform in unique ways as combination.
Orlando therapies.
Garo Armen: And all of our programs are designed to address the limitations of current I.O. treatments, to deliver improved and differentiated patient benefits.
And all of our programs are designed to address the limitations of current I O treatment.
To deliver improved and differentiated patient benefit.
Garo Armen: We do not take a mean-to approach in any of our development strategies.
We do not.
Take a lead to approach in any of our development strategies.
With podcast you remap, we're very encouraged to see.
Garo Armen: With botansilamab, we're very encouraged to see the design performance of this molecule, play out in what clinicians describe to be the unprecedented clinical benefit in heavily pretreated co-tumor cancers.
The design performance of this molecule play out in what clinicians.
Right to be the unprecedented clinical benefit and heavily pre treated cold tumor cancers and this of course is beyond the next three cancers that we.
Garo Armen: And this, of course, is beyond the next three cancers that we have defined, in our Phase II clinical protocols to commence shortly.
Defined as our phase II clinical protocols to commence shortly.
Garo Armen: Botansilamab was designed to deliver multiple functions in a single antibody. T-cell priming, T-cell activation, suppression of regulatory T-cells, and avoidance of complement-related toxicities, among others.
<unk> was designed to deliver multiple functions in a single antibody.
T cell priming T cell activation.
Suppression of regulatory T cells.
And avoidance of complement related toxicities among others.
Garo Armen: Among the attributes of botansilamab is consistent activity we're seeing across nine solid tumors, including, as we've talked about earlier, gynecological cancers, sarcomas, which have not responded to available I.O.
Among the attributes of Boston about.
This consistent activity, we're seeing across nine solid tumors.
Garo Armen: treatments.
Including as we've talked about earlier gynecological cancers, so core mines, which have not responded to available treatments.
Yeah.
We have several other pipeline candidates that I would like to and should now for which we employed a similar approach.
Garo Armen: We have several other pipeline candidates that I'd like to mention now, in which we've employed a similar approach.
Garo Armen: Powered by our sophisticated discovery, antibody engineering, and vision platforms, we've designed, for example, our CD137 agonist, agent 2373, to retain or enhance the efficacy of first-generation CD137 agonists while avoiding liver toxicity that derailed the development of other such molecules. Thus far, we've seen early signals of activity with no liver toxicity in the clinic, and are moving to complete our enrollment in a combination study of agent 2373 and botansilamab in relapsed refractory melanoma to start.
Powered by our sophisticated discovery antibody engineering envisioned platforms with design for example, our CD 137 agonist AGN 2373.
To retain or enhance the efficacy of <unk>.
First generation of CD 137 agonist.
While avoiding liver toxicity that derail the development of whether such molecules.
Thus far we've seen early signals of activity with no liver toxicity in the clinic and are moving to complete our enrollment in a combination study of age and $23 73.
And both Haynesville and map.
In relapsed refractory melanoma to start.
Garo Armen: We also recently announced that we've begun dosing patients in our Phase I study, of our own novel anti-ILT2 antibody. This is agent 1571. Agen 1571 is a potent inhibitor of IL-T2, a broadly expressed receptor that suppresses, myeloid and lymphoid responses, and which is believed to contribute to PD-1 and CTLF-4 resistance. That is, suppression of myeloid and lymphoid responses we believe are responsible partly for PD-1 and CTLA-4 resistance.
We also recently announced that we've begun dosing patients in our phase one study of novel our own novel <unk>.
Anti <unk> two antibody this is a gen $15 71.
Asia 15, 71 is a potent inhibitor of Iot Chu.
Broadly expressed receptor.
That should presses myeloid and lymphoid response.
And which is believed to contribute to PD, one and CTO or resistance.
That is suppression or myeloid and lymphoid responses. We believe are responsible partly for PD, one and <unk> four resistance.
Garo Armen: We're very optimistic about Agen 1571, given our competitive positioning in the marketplace and the encouraging activity of a similar antibody we discovered and licensed to Merck. The Merck antibody, codename MK4830, targets among members of the LIL-RB family, shown as IL-T4. Merck has published data demonstrating strong activity in heavily pretreated patients with solid tumors when combined with anti-PD-1 therapy, including a 45% response rate in patients who had progressed on prior PD-1 therapy alone.
We're very optimistic about <unk> 71.
Even our competitive positioning.
Andy encouraging activity or a similar antibody discovery.
Discovery and license to Merck.
The Merck antibody.
Core team and K 48 30.
Targets among members of the <unk> family, Sean S. I L T four.
Merck has published data demonstrating strong activity in heavily pretreated patients with solid tumors when combined with anti PD one therapy.
Including a 45% response rate in patients who had progressed on prior PD one therapy alone.
Garo Armen: Naturally, the question of access to ample resources to make these programs, to take these programs, to the finish line, has come up from time to time in both internal and strategic planning and external discussions. Throughout our company history, we have managed and balanced our ambitions and our ability to tap resources.
Yeah.
Actually the question of access to ample resources to make these programs to take these programs to the finish line has come up from time to time.
In both internal and strategic planning and external discussions.
Throughout our company history.
We have managed and balanced our ambitions and our ability to tap resources.
Garo Armen: Tactics we've used included prioritization of key near-term value drivers, building internal, capabilities to reduce dependence on outside vendors, including soup-to-nuts commercial manufacturing of our products, clinical trial management and execution through our own CROs, and, of course, our own internal discovery engine and development.
Tactics, we've used included prioritization of key near term value drivers.
Building internal capabilities to reduce dependence on outside vendors.
Including soup to nuts commercial manufacturer and go buy our products.
Clinical trial management and execution through our own Cro's and of course.
Our own internal discovery and development.
We have balanced the need to properly resource.
Garo Armen: We have balanced the need to properly resource our priorities with prudent efficiency measures and cost-cutting.
Alrighty.
Prudent efficiency measures and cost cutting.
Garo Armen: You've seen this in our spending trends from the first quarter of this year, to the second quarter of this year. We expect these trends to continue.
You have seen this in our spending trends from the first quarter of this year to the second quarter of this year.
We expect these trends to continue.
Garo Armen: We have also been resourceful with inputs of cash resources. Our largest cash resources, over the past half a dozen years have been corporate transactions, which have netted us over $800 million.
We have also been resourceful with inputs of cash resources.
Our largest cash resources over the past half a dozen years had been corporate transactions, which have nevertheless.
Garo Armen: We've also selectively utilized ATM sales designed to keep dilution to a minimum.
Over $800 million.
We are also selectively utilized ATM sale design.
Designed to keep dilution crew and minimum.
Garo Armen: We expect corporate transactions to continue to be the dominant source of our cash until we have a sustainable cash flow from our products and our revenues from products to finance our operations going forward sustainably.
We expect corporate transactions to continue to be the dominant source of our cash until we have a sustainable cash flow from our products and our revenues from products to finance our operations going forward sustainably.
Garo Armen: Regarding our partnered antibodies in active development, in addition to the earlier mentioned, Merck-licensed antibody MK4830, the list includes our anti-TIGIT by Specific, Agent 1777, licensed to Bristol-Myers, along with our four immunotherapies licensed to Insight.
Yeah.
Regarding our partnered antibody is in active development. In addition to the earlier mentioned Merck licensed antibody MK four.
830.
The list includes our anti <unk> by specific a gen. One triple seven.
License to Bristol Myers, along with our four Immunotherapies license to insight.
Garo Armen: These are all advancing in the clinic, and as these programs successfully progress, they have the potential to trigger milestone, payments to Agenus, totaling close to $3 billion in addition to sales-based royalties for those molecules that reach commercial launch.
These are all advancing in the clinic and as these programs successfully progress they have the potential to trigger milestone payments to <unk> totaling close to $3 billion. In addition to sales.
Royalties for those molecules that reach commercial launch.
Garo Armen: In the past half a dozen years, Agenus has delivered exceptional productivity by advancing 15 antibodies and cell therapies.
In the half.
Half a dozen years.
Janus has delivered exceptional productivity by advancing 15 antibodies and cell therapies.
Garo Armen: Biopharmaceutical discovery and development is a high-risk, high-reward endeavor, and we believe we have a powerful set of capabilities, when it comes to choosing targets, combinations, and design elements for Io innovation and success.
Biopharmaceutical discovery and development as a high risk high reward endeavor.
And we believe we have a powerful set of capabilities when it comes to choosing targets combinations and design elements for Io innovation and success.
All of the molecules in our pipeline were chosen based on their potential for unique advantages in clinical settings.
Garo Armen: All the molecules in our pipeline were chosen based on their potential for unique advantages in clinical setting, and elements of their, design have been carefully tailored with the intention of creating differentiated best or first-in-class molecules and cell therapies.
And elements of their design have been carefully tailored with the intention of creating differentiated.
First or first in class molecules and cell therapies.
Garo Armen: We are confident that our current and future partnerships will position the company to fund a substantial portion of our development activities, over the coming years, and that our discovery, antibody engineering, and vision platforms will fuel continued innovation and growth of our pipeline.
We are confident that our current and future partnerships will position.
The company to fund.
Substantial portion of our development activities over the coming years and that our discovery antibody engineering and vision platforms will fuel continued innovation and growth of our pipeline.
Garo Armen: We're excited to enter the third quarter from a place of strength and innovation, as we have seen with the remarkable results that have been achieved, with potencilumab and malfilumab combination in MSSCRC patients, and more to come on that.
We're excited to enter the third quarter from a place of strength and innovation.
As we have seen with the remarkable results.
<unk> had some of that.
<unk> in that combination.
In.
MSS CRC patients and more to come on that.
Garo Armen: The future holds great things for the field of immunotherapy, and Agenus looks forward to contributing to the advancement of these life-changing medical developments.
The future holds great things for the field of immunotherapy and a generous looks forward to contributing to the advancement of these life changing medical develop.
Garo Armen: With all of that, I'll turn the call over to Christine to cover our financials.
With that I'll turn the call over to Christine to cover our financials Christine.
Thank you Darren.
Christine Klaskin: Christine?
We ended our second quarter 2022, with a cash and short term investment balance of $238 million. This compares to $263 million at the end of the first quarter and 307 million at year end.
We recognized revenue of $21 million in the second quarter ended June 2022, which represents an increase of $10 million from the $11 million reported for the same period in 2021.
Revenue for the six months ended June 2000, $20 million to $47 million, an increase of $25 million from the same period in 2021.
Amounts include revenue under our collaboration agreement in.
In 2022 milestones earned and revenue related to noncash royalties earned.
For the second quarter ended June 2022, our cash used in operations was $43 million compared to 56 million for the same period in 2021.
Our net loss for the quarter ended June 2022, with $49 million or 17 cents per share compared to a net loss of $84 million or <unk> 37 per share for the quarter ended June 2021.
Noncash operating expenses for the second quarter ended June 22.
$19 million compared to $30 million for the second quarter ended up 2021.
Our cash used in operations for the six months ended June 2022, with $96 million with a net loss of 100 million or <unk> 35 per share compared to cash used in operations of $98 million and a net loss for the same period in 2021 of $138 million or 65.
<unk> per share.
Christine Klaskin: Thank you, Gaurav.
I'll now turn the call back.
Christine Klaskin: We ended our second quarter, 2022, with a cash and short-term investment balance of $238 million. This compares to $263 million at the end of the first quarter and $307 million at year-end. We recognized revenue of $21 million for the second quarter ended June 2022, which represents an increase of $10 million from the $11 million reported for the same period in 2021.
Christine Klaskin: Revenue for the six months ended June 2022 with $47 million, an increase of $25 million from the same period in 2021. Amounts include revenue under our collaboration agreement, in 2022 milestones earned, and revenue related to non-cash royalties earned.
Q&A.
Thank you very much Christine and I think we're ready for any questions. They may have from the fields.
Yeah.
And at this time I would like to remind everyone in order to ask a question. Please press the star.
Christine Klaskin: For the second quarter ended June 2022, our cash used in operations was $43 million compared to $56 million for the same period in 2021. Our net loss for the quarter ended June 2022 with $49 million or $0.17 per share compared to a net loss of $84 million or $0.37 per share for the quarter ended June 2021. Non-cash operating expenses for the second quarter ended June 2022 were $19 million compared to $30 million for the second quarter ended of 2021.
Key followed by the number one on your telephone keypad and we'll pause for just a moment to compile the Q&A roster.
Christine Klaskin: Our cash used in operations for the six months ended June 2022 was $96 million with a net loss of $100 million or $0.35 per share compared to cash used in operations of $98 million and a net loss for the same period in 2021 of $138 million or $0.65 per share.
Your first question comes from <unk> <unk>.
Johnny with B Riley Securities. Your line is now open.
Garo Armen: I'll now turn the call back to Garo to handle our Q&A.
Good morning team thanks for taking our questions. So maybe first on the.
You too.
Program that just ended clinic, but could you just review with us the rationale for it.
Mining with both PD, one as well as your next Gen. <unk> four and also would love to hear what we already know and should look out for the one in the field.
These.
ILD drugs in the clinic.
All of those might be evolving.
Going forward.
Validation of use in a combination setting.
Garo Armen: Garo?
Sure Mark I think if your question is.
The rationale for combining Iot too with still a map and potentially Matt is that the question.
Garo Armen: Thank you very much, Christine.
Yes, the first part.
Garo Armen: And I think we're ready for any questions that you may have on the field.
Okay. So I wanted to ask a doctor or they and perhaps even vantran, who has joined US today for why we have.
Query this in preclinical models and the research rationale and perhaps a doctor or they can kind of elaborate on that more. Thank you darlin. Thank you my own for the question. So there are couple of evidence that support the combination of <unk> 71 with bookings still amount of milestone model. So first is that you will recall.
Garo Armen: And at this time, I would like to remind everyone in order to ask a question, please press the star key followed by the number one on your telephone keypad.
<unk> from our subsea or ACR poster actually earlier this year demonstrating the high expression of <unk> two <unk> two positive myeloid cells in patients that did not respond to <unk>.
Check point therapy checkpoints secondaries, Brian to PD, one or PD, one <unk> four combination.
The second is that we've demonstrated in preclinical disease relevant models that the combination of PD, one and <unk> 71 enhances T cell activation NK cell activation of NK T activation and the combination of <unk> and agents.
$50 71, potentially it's immune activation.
One of the reasons for this is about <unk> two is known to inhibit FC gamma or signaling, which is critical for therapies like book and fill them up on agent $15 71 believes that.
And then lastly, when you look at patient samples, particularly tumor infiltrating lymphocytes and tumor cells.
As shown in our ACR poster youll notice that PDL, one and <unk>. The ligand for allergy to are expressed on a different subset of tumor cells <unk>.
Same goes for Iot to anti PD one.
Suggest that the combination of both of them up and sell them.
With the age of 50, and 71 leverage different arms of immune system.
Tension anti tumor immunity.
Garo Armen: And we'll pause for just a moment to compile the Q&A roster.
I'll turn it over to Stephen to out a bit more color on our clinical Russia, yes.
Operator: Your first question comes from Mayank Mumtani with B. Riley Securities.
Thank you Manoj.
Yes, we're very excited about this IL two program is potentially first in class based on the preclinical data suggests that we have over myeloid and lymphoid checkpoint that could be quite synergistic.
Operator: Your line is now open.
Mayank Mamtani: Good morning, team.
And really build into some of the mechanism of resistance of PD, one and <unk> four and obviously the IL four program.
Mayank Mamtani: Thanks for taking our question.
Our antibody that Merck has is using is obviously advancing in the clinic with objective responses. So there's some proof of concept in this myeloid class, but we think we have a more broad myeloid and lymphoid checkpoint that may answer some of the resistance issues.
Mayank Mamtani: So maybe first on the ILD2 program that just entered clinic, could you just review with us the rationale for combining with both PD-1 as well as your next-gen CDLA-4?
First generation checkpoints, so and as you know we dose the first human patient with our Iot to several weeks ago.
Mayank Mamtani: And also would love to hear what we already know and should look out for in the field with these ILD drugs in the clinic and how those might be evolving going forward for validation of use in a combination setting.
What's exciting about this program and this week, we will be looking for model therapy single agent activity, but obviously, but the program is designed to fold in Bilbao.
Garo Armen: Sure, Mayank.
Garo Armen: I think if your question is the rationale for combining ILD2 with balacelamab and botansilamab, is that the question?
<unk> combinations.
A boat and sell about combination. So we have the flexibility to move more quickly with combinations as well as model therapy. So more to come by the very exciting program. That's now in the club adapter some tremendous.
Mayank Mamtani: Yes, the first part of that.
Clinical work in drug design.
Garo Armen: Okay.
Garo Armen: So I'm going to ask Dr. O'Day and perhaps even Dan Chen, who has joined us today, for why we have queried this in preclinical models and the research rationale.
Okay.
Thank you so much for that.
Comprehensive overview and then just maybe a follow up more focused on <unk>.
Garo Armen: And perhaps Dr. O'Day can elaborate on that more.
Could you just give us an update on how far along you are with the melanoma cohort.
Garo Armen: Thank you, Gaurav.
<unk>.
<unk> progress to date.
Bombing.
Thinking for our future development plan.
It is looking like.
Working towards.
Some sort of a base too.
Trial.
<unk> later this year and next year.
So the.
The question is to be answered at an upcoming major conference.
The release date has not just for the additional patients.
Enrolled and studied in the CRC cohort, but.
Some of the major cohorts as well so unfortunately, we cannot publicly disclose the specifics but.
It will be during the course of this year.
Got it and my final question on financials.
Could you just.
Remind us what.
Outstanding non dilutive milestones remain.
But the.
We ended up the year.
Just comment on that or even into early next year.
So.
Once again, given the sensitivity of this.
Very subject.
We will not comment on.
Any specifics.
Deal structures or.
Or.
Yeah.
I should say the numerical relevant so anything such as that now as far as any particular milestones.
As we've said publicly and I think we've alluded to this during the course of our.
A press release that we expect this year to receive a total of approximately $25 million from.
The payment that's due to us as part of the transaction that we consummated with HCR for Qs 21.
So that will happen during the course of this year and that's of course, it non dilutive component.
But but additional partnership discussions and consummation of these discussions to take them to conclusion.
We'll wait for more specifics.
Announcements for that.
Yeah.
Garo Armen: And thank you, Mayank, for the question.
Thank you Pavel.
Yeah.
Garo Armen: So there are a couple of evidence that support the combination of Agent 1571 with botansilamab and balacelamab.
Yeah.
Hum.
And your next question comes from the line of Matt.
William Blair. Your line is now open.
Garo Armen: The first is that you will recall from our AACR poster, actually, earlier this year, demonstrating the high expression of ILD2 and ILD2-positive myeloid cells in patients that did not respond to checkpoint therapy.
Garo Armen: And by checkpoint therapy, I'm referring to PD-1 or PD-1 and CDLA-4 combinations.
Good morning, Thanks for taking my question.
Just curious when we might get some more details on the design.
Nine of these pending.
It is true that when.
Can you comment on the MSS CRC arm will recur.
Require a mono therapy or arm.
Maybe any thoughts on competitors.
Sure.
Sure I think in terms of the specific design of the trials as you know Matt we have said specifically that we expect to start three randomized phase II trials.
Those will commence soon.
The first cohort of details will be disclosed.
During the week of ethanol coming out.
Hmm.
Okay, I guess as far as the <unk>.
And cohort.
Coming up later this year or is there any.
Details you can give on maybe how many patients do you expect total wind expansion cohorts that are.
Okay.
So the plan is for us to present.
A number of cohorts of this study at Ash.
Another major conference coming up, which we have not announced yet.
Okay.
Great.
Well look forward to a big thing.
Thank you very much Matt.
Yeah.
Again, if you would like to ask a question. Please press <unk>.
Turkey and the number one your telephone keypad.
Next question.
My apologies.
Question.
Jumped out of queue.
Okay here, we go Kelly shy with Jefferies. Your line is now open.
Hi, Thank you for taking our question. This is Dave on Alicia and my question is.
Could you talk about potential impact of Tyler.
Knievel approval in melanoma.
Phase II trial design in melanoma.
Yeah.
So.
Yes.
Yeah.
I think that there are they.
Ill tackle that question Steve is always the question is what is the impact of.
Nemo lag three in the melanoma space with our trial design.
Is that the question.
Yes.
Through one off that you have a needle how does it impact.
Designed for melanoma.
Well I think that the exhaustion checkpoint slight lag three Tim three and obviously PD, one obviously very different targets on <unk> four so obviously with first line melanoma now Theres three potline options <unk> four with PD, one PD one monotherapy.
PD one lag three so we'll be addressing all of those cohorts with our design of our about and sell them out which we think is.
Is obviously, a very unique different checkpoint exhaustion checkpoints, but we will address it.
Look forward to getting data around all of those subgroups.
Alright, great. Thank you.
And there are no further questions at this time, Mr. Amin I turn the call back over to you.
So very much for your attention and interest in our company in closing I'd like to just reiterate the point that.
Garo Armen: The second is that we've demonstrated in preclinical disease-relevant models that the combination, of PD-1 and Agent 1571 enhances T-cell activation, NK-cell activation, and NKT activation, and the combination of both Stilimab and Agent 1571 potentiates immune activation.
Garo Armen: One of the reasons for this is that IL-T2 is known to inhibit FC-gamma-R signaling, which is critical for therapies like both Stilimab, and Agent 1571 relieves that.
Garo Armen: And then, lastly, when you look at patient samples, particularly tumor-infiltrating lymphocytes, and tumor cells, as shown in our ACR poster, you'll notice that PD-L1 and HLA-G, the ligand for IL-T2, are expressed on different subsets of tumor cells and immune cells.
Garo Armen: The same goes for IL-T2 and PD-1.
Garo Armen: This suggests that the combination of both Stilimab with Agent 1571 will leverage different, arms of the immune system to potentiate anti-tumor immunity.
Garo Armen: I'll turn it over to Stephen to add a bit more color in our clinical rationale.
Garo Armen: Yeah, thank you, Mark, and, yeah, we're very excited about this IL-T2 program as potentially, best first-in-class, based on, Dan said, the preclinical data suggests that we have both a myeloid and a lymphoid checkpoint that could be quite synergistic and really build into some of the mechanism of resistance of PD-1 and CTLA-4, and obviously the IL-T4 program that we, our antibody that Merck is using, is obviously advancing in the clinic with objective responses, so there's some proof in concept in this myeloid class, but we think we have a more broad myeloid-lymphoid checkpoint that may answer some of the resistance issues to first-generation checkpoints, so, and as you know, we dosed the first human patient with our IL-T2 several weeks ago, and what's exciting about this program is we will be looking for monotherapy single-agent activity, but obviously the program is designed to fold in both VAL, IL-T2 combinations, and a botancilumab combination, so we have the flexibility to move forward quickly with combinations as well as monotherapy, so more to come, but a very exciting program that's now in the clinic after some tremendous preclinical work and drug design.
With the data disclosure of potential adverse Trustbuster man.
We have received.
Many accolades about.
Garo Armen: Thank you.
T.
Robustness of the responses that we've seen in fact.
Many of the long term experts in the field.
<unk> certainly CRC experts have commented on the fact that they have not seen such responses with conventional immunotherapy. So clearly this is a very exciting period for the next steps of immunotherapy.
Garo Armen: Thank you so much for that, you know, comprehensive overview, and then just maybe a follow-up, you know, more focused on botancilumab, could you just give us an update on how far along you are with the melanoma cohort, and how much of your progress to date is informing your thinking for a future development plan, which, you know, is looking like you are working towards, you know, some sort of a Phase II trial starting later this year or next year?
Garo Armen: So the question is to be answered at an upcoming major conference that's going to release data, not just for the additional patients that have been enrolled and studied in the CRC cohort, but some of the major cohorts as well.
Garo Armen: So unfortunately we cannot publicly disclose the specifics, but it will be during the course, And my final question on financials, could you just remind us what outstanding non-dilutive milestones remain for the remainder of the year, could you just comment on that, or even into early next year?
Garo Armen: So, once again, given the sensitivity of this very subject, we will not comment on any specific, deal structures or, I should say, the numerical relevance of anything such as that.
Garo Armen: As far as any particular milestones, as we've said publicly, and I think we've alluded to this, during the course of our press release, that we expect this year to receive a total of approximately $25 million from the payment that's due to us as part of the transaction that we consummated with HCR for QS21.
Garo Armen: So, that will happen during the course of this year, and that's, of course, a non-dilutive, component, but additional partnership discussions and consummation of these discussions to take them to conclusion, we'll wait for more specific deal announcements for that.
And we're delighted to have work until the Max lead that effort.
Garo Armen: Thank you, Garo, for that helpful interview.
Operator: And your next question comes from the line of Matt Fitts with William Blair.
For the future of these patients and there will be so with that.
Operator: Your line is now open.
Stay tuned for additional information that we will be disclosing.
Matt Phipps: Good morning, Garo.
Matt Phipps: Thanks for taking the question.
Matt Phipps: Just curious, when we might get some more details on the design of these impending Phase, II studies for blood cell maps, can you comment on if the MSS TRC arm will require a monoclonal therapy bowel or butt arm, and maybe any thoughts on comparators for that trial?
Garo Armen: So, I think in terms of the specific design of the trials, I mean, as you know, Matt, we have said specifically that we expect to start three randomized Phase II trials.
Garo Armen: Those will commence soon.
Garo Armen: I think the first cohort of details will be disclosed during the week of ESMO coming up.
We now and the end of the year.
Garo Armen: Interesting.
Operator: Kelly Shi with Jefferies.
Garo Armen: Okay.
And that will set the stage for us to be able to do our next set of trials randomized trials with the hope that we will get to the finish line with the collaboration or many of the experts in the field as well as regulatory agencies around the world. So I'll end, Mike commented if you have any additional questions.
Garo Armen: And I guess as far as the expansion cohorts coming up later this year, is there any details, you can give on maybe how many patients you expect total in the expansion cohorts that are for the blood cell map update?
Garo Armen: So, the plan is for us to present a number of cohorts of the study at another major conference, coming up, which we have not announced yet.
Garo Armen: Okay, all right.
Garo Armen: Great.
Garo Armen: Well, look forward to updates.
Garo Armen: Thanks, Matt.
Operator: Your line is now open.
Garo Armen: Thank you very much, Matt.
Operator: Hi.
Operator: Again, if you would like to ask a question, please press the star key and the number one, on your telephone keypad.
Operator: Thank you for taking our question.
Operator: Your next question, my apologies, the question has jumped out of queue.
Operator: This is Dev on for Kelly Shi.
Operator: Okay, here we go.
Operator: And my question is, could you talk about potential impact of RetaliMAP plus, NEVO approval in melanoma on your phase two trial design in melanoma?
Operator: So, I think Dr. O'Day will tackle that question.
Operator: The question is, what is the impact of NEVO LAG-3 in the melanoma space with our trial design?
Operator: Is that the question?
Operator: Yes.
Operator: So, the approval of RetaliMAP and NEVO, how does it impact your design for melanoma?
Operator: Yeah.
Operator: Well, I think that the exhaustion checkpoints like LAG-3 and PIM-3 and obviously, PD-1 are obviously very different targets than CTLA-4.
Operator: So, obviously, with first-line melanoma, now there's three frontline options, CTLA-4 with PD-1, PD-1 monotherapy, and then PD-1 LAG-3.
Garo Armen: So, I'll end my comments, and if you have any additional questions and queries, please don't hesitate to get in touch with us.
Operator: So, we'll be addressing all those cohorts with our design of our Abbot and Sillimap, which we think is obviously a very unique, different checkpoint than the exhaustion checkpoints.
Garo Armen: Thank you very much.
Operator: But we will address it and look forward to getting data around all those subgroups.
Operator: All right.
And inquiries, please don't hesitate to get in touch with us. Thank you very much.
Operator: Great.
Operator: Thank you.
Operator: Thank you.
Operator: This concludes today's conference call. You may now disconnect.
Operator: And there are no further questions at this time.
Garo Armen: Mr. Armin, I will turn the call, back over to you.
Sure.
Garo Armen: Thank you very much for your attention and interest in our company.
This concludes today's conference call you may now disconnect.
Garo Armen: In closing, I'd like to just reiterate the point that with the data disclosure of Botan Sillimap plus Pulse Sillimap, we have received many accolades about the robustness of the responses that we've seen.
Garo Armen: In fact, many of the long-term experts in the field, including certainly CRC experts, have commented on the fact that they have not seen such responses with conventional immunotherapy.
Garo Armen: So, clearly, this is a very exciting period for the next steps on immunotherapy, and we're delighted to have Botan Sillimap lead that effort for the future of these patients and their well-being.
Garo Armen: So, with that, please stay tuned for additional information that we will be disclosing between now and the end of the year, and that will set the stage for us to be able to do our next set of trials, randomized trials, with the hope that we will get to the finish line with the collaboration of many of the experts in the field, as well as regulatory agencies around the world.
Okay.
[music].
Okay.
Okay.
Yes.
Yes.