Q1 2024 Corvus Pharmaceuticals Inc Earnings Call
Operator: Good afternoon, ladies and gentlemen, and welcome to the Corvus Pharmaceuticals business update and reports first quarter 2024 financial results conference call. At this time, all lines are in a listen only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Monday, May 6, 2024. I would now like to turn the conference over to Zack Kubow, Your Real Chemistry. Please go ahead.
Good afternoon, ladies and gentlemen, and welcome to the Corvus Pharmaceuticals business update and reports first quarter, it's what he'd wanted before if they national results conference call.
At this time all lines are in a listen only mode. Following the presentation. We will conduct a question and answer session. If at any time during this call you're required to get this just since these spreads far and zero for the operator.
This call is being recorded on Monday May 6214.
I would now like the third the Cod for ancillary Sakel Bowl your real chemistry. Please go ahead.
Zack Kubow: Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals First Quarter 2024 Business Update and Financial Results Conference call. On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer; Leif Lee, Chief Financial Officer; Jeff Arterra, Chief Business Officer; Jim Rosenbaum, Senior Vice President of Research; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences.
Speaker Change: Thank you operator, and good afternoon, everyone.
Speaker Change: Thanks for joining us for the Corvus Pharmaceuticals first quarter 2020 for a business update and financial results Conference call.
Speaker Change: On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer.
Speaker Change: Lastly, Chief Financial Officer.
Speaker Change: Jeff Archera Chief business Officer.
Jim Rosenbaum Senior Vice President of research and Ben Jones, Senior Vice President of regulatory and pharmaceutical Sciences.
Zack Kubow: The executive team will open the call with some prepared remarks, followed by a question and answer period. I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus's annual report on Form 10-K and other filings the company makes with the FCC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements except as required by law. With that said, I'd like to turn the call over to Leif Lea. Leif?
Speaker Change: The executive team will open the call with some prepared remarks, followed by a question and answer period.
Speaker Change: I would like to remind everyone that comments made by management today and answers to questions will include forward looking statements.
Speaker Change: Forward looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements.
Speaker Change: The risks and uncertainties described in Corpus. This annual report on Form 10-K, and other filings the company makes with the SEC from time to time.
Speaker Change: The company undertakes no obligation to publicly update or revise any forward looking statements, except as required by law.
I'd like to turn the call over to Leif week late.
Leiv Lea: Thank you, Zack. I'll begin with a quick overview of our first quarter 2024 financials and then turn the call over to Richard for a business update. Research and development expenses in the first quarter of 2024 totaled $4.1 million compared to $4.6 million for the same period in 2023. The net loss for the first quarter of 2024 was $5.7 million, including non-cash income of $0.2 million related to Angel Pharmaceuticals, our partner in China.
Thank you Zach I'll begin with a quick overview of our first quarter 2020 for financials, and then turn the call over to Richard for a business update.
Leiv Lea: This compares to a net loss of $7.9 million for the same period in 2023, which included a $1.7 million non-cash loss related to Angel Pharmaceuticals. Total stock compensation expense for the first quarter of 2024 was $0.7 million compared to $0.5 million for the same period in 2023. As of March 31, 2024, Corvus had cash, cash equivalents, and marketable securities totaling $22.1 million as compared to $27.1 million at December 31, 2023. Today, we closed a $30.6 million financing that included a premier group of biotech investors, as well as some members of the Corvus leadership team.
Leif: Research and development expenses in the first quarter of 2024 totaled $4 $1 million compared to $4 6 million for the same period in 2023.
Leif: Net loss for the first quarter 2024 was $5 $7 million, including noncash income of <unk> 2 million related to Angel Pharmaceuticals, our partner in China.
Leif: This compares to a net loss of $7 9 million for the same period in 2023, which included a $1 $7 million noncash loss related to Angel pharmaceuticals.
Leif: Total stock compensation expense for the first quarter 2024 was $7 million compared to <unk> 5 million for the same period in 2023.
Leif: As of March 31, 2024 quarters of cash cash equivalents in marketable securities totaling $22 1 million as compared to $27 $1 million at December 31, 2023.
Leif: Today, we closed a $36 million financing that included a premier group of biotech investors as well as some members of the cordless leadership leadership team.
Including the proceeds from this financing pro forma cash at March 31, 2024 was approximately 52 million up $52 $7 million.
Leif: Extending our cash runway into Q4 of 2025.
Leif: I will now turn the call over to Richard who will discuss our clinical progress and elaborate on our strategy and plans.
Richard A. Miller: Thank you life and good afternoon, everyone. Thank you for joining us today for our business update call.
Leiv Lea: Including the proceeds from this financing, pro forma cash at March 31, 2024 was approximately 52 point million, up $52.7 million, extending our cash runway into Q4 of 2025. I will now turn the call over to Richard, who will discuss our clinical progress and elaborate on our strategy and plan.
Leiv Lea: Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today on our business update call. Since our Q4 update in mid-March, we have continued to make progress against two key value drivers that we are focused on for 2024. First, for our planned registrational phase three trial of Soquelitinib for patients with relapsed peripheral T-cell lymphoma, we remain on track to begin enrollment in the third quarter. And our confidence in this trial continues to grow as two additional patients in our Phase 1, 1B trial recently achieved objective responses at first follow-up.
Richard A. Miller: Since our Q4 update in mid March we have continued to make progress against two key value drivers that we are focused on for 2024 first for our planned Registrational phase III trial, the so called <unk> for patients with relapsed peripheral T cell lymphoma, we remain on track.
Richard A. Miller: To begin enrollment in the third quarter.
Richard A. Miller: And our confidence in this trial continues to grow as two additional patients in our phase one one b trial recently achieved objective responses at first follow up.
Richard A. Miller: Second our placebo controlled phase one trial of Socal at nib for patients with moderate to severe atopic dermatitis, we began patient enrollment in April which keeps us on track to report early data from the trial before the end of the year.
Richard A. Miller: We began patient enrollment in April, which keeps us on track to report early data from the trial before the end of the year. In addition to these two priorities with Socolitinib, today we are reporting encouraging initial data from our phase 1b2 trial of ciferadenant, our adenosine A2A receptor antagonist, in frontline metastatic renal cell cancer. Based on the significant deep response rate seen in the initial set of patients, the protocol pre-specified statistical criteria for expanding the study have been met, and the Kidney Cancer Research Consortium, or KCRC, is enrolling additional patients.
Richard A. Miller: In addition to these two priorities with Socal isn't it today, we are reporting encouraging initial data from our phase one b two trial if sephora.
Richard A. Miller: For a dent our adenosine <unk> receptor antagonist in frontline metastatic renal cell cancer or RCC.
Richard A. Miller: Based on the significant deep response rate seen in the initial set of patients. The protocol Prespecified statistical criteria for expanding this study has been met and the kidney cancer Research consortium or case CRC is enrolling additional patients.
Richard A. Miller: Combined with our ongoing business development efforts aimed at further unlocking the potential of ITK inhibition in a broad range of oncology and autoimmune indications, we believe Corvus is positioned to continue building value and advancing our unique pipeline to help improve clinical outcomes for patients.
Richard A. Miller: Combined with our ongoing business development efforts aimed at further unlocking the potential of ITK inhibition in a broad range of oncology and autoimmune indications. We believe corvus is positioned to continue building value and advancing our unique pipeline to help improve clinical outcomes for patients.
Richard A. Miller: Now I will provide more detail on our progress, starting with socolitinib for PTCL. While we are no longer enrolling new patients in our phase one trial, the data continues to evolve as patients on therapy complete their scheduled follow-up assessments. In the most recent data cutoff from May 3, 2024, we had two additional patients that achieved an objective response at their first follow-up visit. The first was a complete response confirmed by PET-CT scan, and the second was a partial response with over 80% tumor volume reduction. These patients both had multiple sites of disease and had failed two prior therapies. Both of these patients are continuing treatment. With these additional valuable patients,
Richard A. Miller: Now I will provide more detail on our progress starting with Socal at Nib for P. T C L.
Richard A. Miller: Well, we are no longer enrolling new patients in our phase one trial. The data continues to evolve as patients on therapy complete their scheduled follow up assessments.
Richard A. Miller: In the most recent data cut off from May three 2024, we had two additional patients that achieved an objective response at their first follow up visit.
Richard A. Miller: The first was a complete response confirmed by pet scan and the second was a partial response with over 80% tumor volume reduction.
Richard A. Miller: These patients both had multiple sites of disease and had failed two prior therapies.
Richard A. Miller: Both of these patients are continuing on therapy.
Richard A. Miller: With these additional evaluable patients the objective response rate or or or for the phase III eligible patients is now nine out of 23 or 39%, including five complete responses and four partial responses.
Richard A. Miller: The objective response rate, or ORR, for the phase three eligible patients is now nine out of 23, or 39%, including five complete responses and four partial responses. Although not studied head to head, the complete response rate for Soquelitinib at 22% is approximately double that seen with Belinostat or Pralatrexate, the standard chemotherapies for PTCL that we will be comparing to in our phase three trial. Similarly, the ORR, disease control rate, progression-free survival, and overall survival for this group compare favorably to the results seen with Belenostat or Pralatrexone.
Richard A. Miller: Though not studied head to head the complete response rate for Socal isn't there that 22% is approximately double that seen with Belinda stat or Prowler Trek Seth the standard chemotherapy for PTC L that we will be comparing to in our phase III trials.
Richard A. Miller: Similarly, the O R. R disease control rate progression free survival and overall survival for this group compares favorably to the results seen with Belinda stat or prelate Trek state.
Richard A. Miller: The median PFS for our patients, which is the primary endpoint for the phase 3 trial, is 6.2 months. This is substantially better than reported results for the standard agents, which are 1.6 and 3.5 months for bilinostat and pralotrexate, respectively.
Richard A. Miller: The median PFS for patients, which is the primary endpoint for the phase III trial is $6. Two months. This is substantially better than reported results for the standard agents, which is one 6% and three five months for Brilinta stat, and <unk> <unk>, respectively.
Richard A. Miller: The durability of our responses is impressive, with some of the earlier enrolled patients maintaining their responses for more than 24 months. We plan to begin patient enrollment in our Socolitinib Registrational Phase III Clinical Trial in relapsed PTCL in the third quarter of 2024. We are working with or are in advanced discussions with a number of leading centers in the United States and Canada. We anticipate that about 40 centers will participate in the trial. The vast majority will be in the United States.
Richard A. Miller: The durability of our responses is impressive with some of the earlier enrolled patients maintaining their responses for more than 24 months.
Richard A. Miller: We plan to begin patient enrollment in our so-called Registrational phase III clinical trial in relapsed P. T C. L. In the third quarter of 2024. We are working with are we are working with or are in advanced discussions with a number of leading centers in the United States and Canada, we anticipate about <unk>.
Richard A. Miller: These centers will participate in the trial the vast majority will be in the United States.
Richard A. Miller: Now for an update on Socolitinib for atopic dermatitis, the first immune disease indication we are evaluating. In April, we initiated patient enrollment in the first patient cohort of the trial. There is high interest in our trial from physicians due to several attractive features of Socolitinib. First, it is a first-in-class drug with a novel mechanism of action. Socolitinib acts upstream by blocking Th2 and Th17 cells and thereby results in the inhibition of many different cytokines involved in the disease.
Richard A. Miller: Now for an update on so-called Aetna for atopic dermatitis, the first immune disease indication we are evaluating.
Richard A. Miller: In April we initiated patient enrollment in the first patient cohort of the trial.
Richard A. Miller: There is high interest in our trial from physicians due to several attractive features of so-called isn't it first this is a first in class drug with a novel mechanism of action. So pullet nib acts upstream by blocking th two in th 17 cells and thereby resulted in inhibition of many different cytokines.
Richard A. Miller: Second, it is an oral therapy, and in our cancer studies, it has been shown to have a very good safety profile. And third, it may have broad utility across many different autoimmune and inflammatory diseases, and this trial may provide proof of concept for the treatment of other immune diseases. The trial was designed to enroll 64 patients with moderate to severe atopic dermatitis that have progressed on at least one prior therapy. The study is randomized, placebo-controlled, and blinded to patients and treating physicians.
Richard A. Miller: <unk> involved in disease.
Richard A. Miller: Second it is an oral therapy and in our cancer studies has been shown to have very good safety profile.
Richard A. Miller: And third it may have broad utility across many different autoimmune and inflammatory diseases and this trial may preferred provide proof of concept for the treatment of other immune diseases.
Richard A. Miller: The trial was designed to enroll 64 patients with moderate to severe atopic dermatitis that have progressed on at least one prior therapy. This.
Richard A. Miller: This study is randomized placebo controlled and blinded to patients and treating physicians.
Richard A. Miller: There will be four sequentially enrolled cohorts of 16 patients, with patients in each cohort being randomized 3 to 1 to different dosing regimens of socolitinib or placebo given for 28 days. The primary endpoint is safety and tolerability, and efficacy is measured using the Investigator Global Assessment and the Clinically Validated Measurement of Improvement in Eczema Area and Severity Index Score, also known as EZS. It should be noted that while the trial is double-blind, the company is not blind.
Richard A. Miller: It will be four sequentially enroll cohorts of 16 patients.
With patients in each cohort being randomized three to one two different dosing regimens of socal at nib or placebo for 28 days.
Primary endpoint is safety and Tolerability and efficacy as measured using investigator global assessment and the clinically validated measurement of improvement in eczema area and severity index score also known as easy.
Richard A. Miller: It should be noted that while the trial is double blind. The company is not blinded we plan to evaluate the data in an ongoing manner as successive cohorts complete enrollment.
Richard A. Miller: We plan to evaluate the data in an ongoing manner as successive cohorts complete enrollment. We will also measure the levels of various serum cytokines at baseline and on treatment. These measurements may provide useful biomarkers. Based on current enrollment trends, anticipated site activations, and follow-up timelines, we believe data from the initial cohorts will be available before the end of 2024, with study completion in early 2025. Outside of our PTCL and atopic dermatitis trials, we are still planning a socolitinib solid tumor trial as a single agent and in combination with nivolumab in relapsed RCC, and we remain active in our corporate partnering discussions.
Richard A. Miller: We also will be measuring the levels of various serum cytokines at baseline and on treatment.
Richard A. Miller: These measurements may provide useful biomarkers.
Richard A. Miller: Based on current enrollment trends anticipated site Activations and follow up timelines, we believe data from the initial cohorts will be available before the end of 2024 with study completion in early 2025.
Richard A. Miller: Outside of our P. T C L. In atopic dermatitis trials, we're still planning a socal it nips solid tumor trial as a single agent and in combination with Novo Nomad in relapsed RCC and we remain active with our corporate partnering discussions our business development strategy.
Richard A. Miller: Our business development strategy is to find partners with development and commercialization expertise in immune diseases, as well as to seek regional partnerships in oncology that would be complementary to our focus and expertise in cancer. I'm excited to update you on the progress with Cifradenin or Adenosine A2A Receptor Antacid. We have been one of the leaders in the development of adenosine A2A receptor antagonism for the treatment of cancer. Over the past few years, published preclinical and clinical studies have demonstrated the anti-tumor activity of ciferadenant as monotherapy and when given in combination with checkpoint inhibitors.
She is to find partners with development and commercialization expertise in immune diseases as well as seek regional partnerships in oncology.
Richard A. Miller: That would be complementary to our focus and expertise in cancer.
Richard A. Miller: I'm excited to update you on the progress with CIT for a dentist or a dentist <unk> receptor antagonist.
Richard A. Miller: We have been one of the leaders in the development of the dentist DNA to a receptor antagonism for the treatment of cancer.
Richard A. Miller: Over the past few years published preclinical and clinical studies have demonstrated the antitumor activity of Sephora, Janet as a mono therapy and when given in combination with checkpoint inhibitors in particular in our preclinical studies published in 2018, we found that anti.
Richard A. Miller: In particular, in our preclinical studies published in 2018, we found that anti-CTLA-4 antibody combination with siforadenate produces striking anti-tumor efficacy in several animal models. Further research has revealed the probable mechanism for this synergy, which involves modulation of the tumor microenvironment, specifically the blocking of myeloid-derived suppressor cells.
Richard A. Miller: <unk> four antibody combination with Sephora dennett produces striking antitumor efficacy in several animal models.
Richard A. Miller: Further research has revealed the probable mechanism for this synergy which involves modulation of the tumor microenvironment.
Specifically, the blocking of myeloid derived suppressor cells.
Richard A. Miller: In other words, we believe that anti-CTLA-4 antibodies are a much better combination partner for A2A antagonists than anti-PD-1. These findings led to our collaboration with the Kidney Cancer Research Consortium. This group of institutions brings together the leading physicians and researchers in kidney cancer, whose goal is to discover improved therapies for patients with renal cancer. Our Phase 1B2 clinical trial, which is led by Dr. Katie Beckerman from Vanderbilt University Medical Center, is evaluating sifredinib as a potential first-line therapy for metastatic renal cell cancer in combination with ipilimumab and nivolumab.
Richard A. Miller: In other words, we believe that anti C. T. L. A for antibodies are a much better combination partner for <unk> antagonists that anti PD ones.
Richard A. Miller: These findings later led to our collaboration with the kidney cancer Research consortium.
Richard A. Miller: This group of institutions brings the leading physicians and researchers in kidney cancer, whose goal is to discover improved therapies for patients with renal cancer.
Richard A. Miller: Our phase <unk> clinical trial, which is led by Dr. Katy Beckerman from Vanderbilt University Medical Center is evaluating sit for it than it is a potential first line therapy for metastatic renal cell cancer in combination with Illumina Mad and naval the map.
Richard A. Miller: The study is now open at MD Anderson, Vanderbilt, Duke, and the University of Pennsylvania. The clinical trial is currently in the phase two portion and overall is designed to enroll up to 60 patients. There are currently over 27 patients in the trial. The trial employs a stringent efficacy endpoint, the deep response rate.
The study is now open at MD, Anderson, Vanderbilt, Duke and the University of Pennsylvania.
The clinical trial is currently in the phase II portion and overall is designed to enroll up to 60 patients.
Richard A. Miller: There are currently over 27 patients enrolled the trial.
Employs a stringent efficacy endpoint deep response rate deep response rate is the CR rate plus the PR rate only counting prs that achieved greater than 50% tumor volume reduction.
Richard A. Miller: A deep response rate is the CR rate plus the PR rate, only counting PRs that achieve greater than 50% tumor volume reduction. Note that the usual criterion for PRs is 30% tumor reduction. Data from the KCRC have shown that deep response rate correlates with long-term progression-free survival and overall survival, and in their previous studies, it was 32% with ipilimumab and nivolumab. In an interim analysis, our protocol-defined, pre-specified statistical threshold for efficacy is the demonstration of at least a 50% increase above the 32% deep response rate seen with previous ipinevo combination This means we need to exceed a deep response rate of 48%.
Speaker Change: Nope the usual criteria for P ours is 30% tumor reduction.
Speaker Change: Data from the case CRC has shown that deep response rate correlates with long term progression free survival and overall survival and in their previous studies is 32% with it being luminaire then Nolan map.
Speaker Change: In an interim analysis, our protocol defined Prespecified statistical threshold for efficacy is the demonstration of at least a 50% increase above the 32% deep response rate seen with previous Evo combination.
Speaker Change: Trials in renal cell cancer conducted by the kidney cancer Research consortium.
Speaker Change: This means we need to exceed a deep response rate of 48%.
Richard A. Miller: As of May 2, 2024, the interim analysis that was conducted indicates that we have met the statistical threshold for efficacy, so the trial continues to enroll patients. We are excited about these results, given the positive clinical implications for patients. In addition, they are consistent with our laboratory and preclinical findings and we believe may represent a novel immunotherapy approach. Summarizing the outlook for the remainder of 2024 with our recent financing, our current cash gives us runway into late 2025, allowing us to achieve several near-term milestones, including
Speaker Change: As of May <unk> 2020 for the interim analysis that was conducted indicates that we have met the statistical threshold for efficacy. So the trial continues to enroll patients.
Speaker Change: We are excited about these results given the positive clinical implications for patients. In addition, they are consistent with our laboratory and preclinical findings and we believe may represent a novel immunotherapy approach.
Speaker Change: Summarizing the outlook for the remainder of 2024 with our recent financing our current cash gives us runway into late 2025, allowing us to achieve several near term milestones including.
Richard A. Miller: We will start our Registrational Phase III Clinical Trial of Socolitinib and PTCL in the third quarter. Generating interim results from our Socolitinib Phase 1 atopic dermatitis trial before year end, followed by final data in early 2025, reporting additional data from the Sephora Denon Phase 1B2 clinical trial later this year, and initiating a phase two clinical trial with socolitinib and solid tumors in the fourth quarter, with initial data anticipated in the second half of 2025.
Speaker Change: Starting our Registrational phase III clinical trial of so-called isn't it in PTC L. In the third quarter.
Speaker Change: Generating interim results from our so-called Lytton in phase one atopic dermatitis trial before year end followed by final data in early 2025.
Speaker Change: Reporting additional data from the sephora than in Phase <unk> clinical trial later this year.
Speaker Change: And initiating a phase II clinical trial with so-called isn't it in solid tumors in the fourth quarter with initial data anticipated in the second half of 2025.
Richard A. Miller: We look forward to providing updates on our programs in the coming quarters. I will now turn the call over to the operator for a questions and answer period. Operator? Thank you.
Speaker Change: We look forward to providing updates on our programs in the coming quarters I will now turn the call over to the operator for a question and answer period operator.
Operator: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number. If you are using a speakerphone, please lift the handset before pressing the One moment please for your first question. Your first question comes from the line of Aydin Huseynov from Leidenberg. Your line is now open.
Speaker Change: Thank you.
Speaker Change: Oh man, we will now begin the question and answer session should you have a question. Please press the star followed by the number one on your thoughts going forward you will hear about from that you have had has been rates should you wish to decline from the polling process. Thus.
Speaker Change: And as far as followed by denim breakthrough if you are using a speaker phone. Please lift the handset before pressing that.
Speaker Change: One moment for your first question.
Speaker Change: Your first question comes from the line of ebay and hard to know from Ladenburg. Your line is now open.
Okay.
Aydin Huseynov: Good afternoon, everyone. Congratulations on the progress and, most importantly, with two additional responses to PR and CR. They're quite unexpected from phase 1B. So regarding circolipinib in PTCL, you got 23 patients, DCR 61%, 5 CRs, 4 PRs. Could you remind us what the standard is for KCRs in other PTCL trials?
Ebay: Good afternoon, everyone.
Speaker Change: Congratulations with the progress on most of the part of live with two additional responses from TR NCR.
Ebay: Quite unexpected from things won't be so so regarding so called Loopnet.
Ebay: In P. T C. L. So you've got 23 patients this year or 61% CR or PR. So could you remind us what is the standard of care CRC. Another PTC L trials, the leanest projects eight or any other agents.
Richard A. Miller: Thank you, Aydin, for the question. So, the approval studies for both bolinostat and pralotrexate were single-arm studies. Those drugs received accelerated approval about 15 years ago. They each had CR rates of about 10 percent and overall response rates of about 25 to 30 percent. They had PFSs, progression-free survivals, of about one and a half to three and a half months.
Richard A. Miller: Thank you, Aydin.
Speaker Change: Thank you Adrian.
Speaker Change: For the question.
Speaker Change: The the.
Speaker Change: The approval studies for both Belinda Stat and prelate treks eight were single arm studies those drugs received accelerated approval about 15 years ago. They each had CR rates of about 10%.
Speaker Change: And overall response rates of about 25% to 30%.
PFS is progression free survival of about one 5% to three five months.
Speaker Change: Sure.
Aydin Huseynov: Okay, that's helpful. And with the new responses, how much is this going to increase your sort of preliminary PFS and OAS? I know you reported previously 6.2 months in PFS, 28 months in OAS. So is it going to increase significantly?
Okay, that's helpful and with the new responses.
Speaker Change: How much this is going to increase your sort of.
Speaker Change: Preliminary PFS on the Oreo I know you reported previously at two months PFS 28 miles away. So is it going to increase significantly.
Richard A. Miller: So, the current ORR now, overall response rate, is 39 percent, just to remind you that. And by the way, in lymphoma, we use the Lugano criteria, which is 50 percent for a PR. And I should add that the PR that I just mentioned had about an 87 percent reduction in tumor. One tumor was totally gone. I suspect he could be on his way to a CR very soon. The PFS, we expect the PFS to improve as these last few patients move through the median.
Speaker Change: So the current or are now overall response rate is 39% just to remind you that in by the way in lymphoma, we use the Lugano criteria, which is 50% for our PR and I should add that the PR that I just mentioned.
Speaker Change: Has about 87% reduction of tumor one tumor was totally gone I suspect he could be on his way to a CR very soon.
Speaker Change: The PSS, we expect the PFS to improve as these last few patients move through the median.
Aydin Huseynov: Okay. And regarding the data from the Phase 3 trial, when do you think we will have a first glimpse of the readout? I know this is a randomized trial, a blinded trial, but when do you think we'll have the first look at it?
Speaker Change: Okay.
Speaker Change: Understood.
Speaker Change: And regarding the data from the.
Speaker Change: The phase III trial.
Speaker Change: When do you think we will have a first glimpse on the on the.
Speaker Change: The readout any.
I know this is a randomized trial blinded trial, but what do you think we will have the first look at it.
Richard A. Miller: Well, it is a randomized trial, but it is not a blinded trial. I mean, we know who gets chemotherapy and who gets our drug. It's hard to disguise that in an oncology trial since these drugs, the chemotherapy drugs, have side effects. The median PFS is, as I mentioned, for prolatrexate and bolinostat is short, only a few months. Therefore, the study is not that long. It's 150 patients.
Speaker Change: Well it is a randomized trial it is not a blinded trial.
I mean, we know who gets chemotherapy and who gets our drug.
Speaker Change: It's hard to disguise that in an oncology trial since these strokes at the chemotherapy drugs have side effects.
Speaker Change: The.
Speaker Change: The median PFS is as I mentioned for <unk> and balloon is that our short only a few months.
Speaker Change: I therefore.
Speaker Change: That is not that long its 150 patients we think we could probably enroll that thing fully in about 18 months.
Richard A. Miller: We think we could probably enroll that thing fully in about 18 months, and then you'd need some follow-up after that to get to the final data. There is a point that we conduct an interim analysis, which is when half of the events occur, the events being the PFS events. But that occurs so late in the study that we would probably wait for the end of the study to make a final determination. Now, having said that, we do have an outside data monitoring committee. And I guess if the results were so persuasive or compelling, you would possibly have an ethical reason to.
Speaker Change: Then you'd need some follow up after that to get to the final data there is an interim.
Speaker Change: There is a point that we conduct an interim analysis.
Speaker Change: Which is one half of the events occur the events being the PFS events.
Speaker Change: But that occurred so late in the study that we would probably wait for the end of the study too.
To make a final determination now having said that we do have an outside data monitoring committee and I guess, if the results were so persuasive were compelling.
Speaker Change: You would.
Speaker Change: Possibly have an ethical reason to discontinue the study.
Speaker Change: Okay makes sense and the last one if I may.
Aydin Huseynov: Okay, he makes it. And the last one, if I may. So, Ed, let me just say.
Speaker Change: Let me just so I think you have data from those trials.
Richard A. Miller: So I think you have data from this trial in 24 months. Okay, so about 26, 26. Okay, so I'm trying to understand, you know, these drugs seem to be working, but there are 40% who don't respond, essentially, right, 39%, you know, based on DCR. So is there any way to come up with some other potential biomarkers to screen patients who would be more likely to respond or somehow choose patients? Yeah.
Speaker Change: 24 months.
Speaker Change: Okay. So like 26.
Speaker Change: 2006.
Speaker Change: Okay.
Speaker Change: So I'm trying to understand this.
Speaker Change: The trucks are seem to essentially we're working in.
Speaker Change: There is 40% who don't respond essentially right, 39% based on PCR. So is there any way to come up with some other potential biomarkers to screen patients, who would be more likely to respond or.
Speaker Change: Choose patients yes.
Richard A. Miller: Well, we are working on that. You know, we're looking all the time for, you know, mutations and baseline immune status, etc. But you'll remember that several months ago we implemented, and on conference calls I talked about, the immune status at baseline, the absolute lymphocyte count, then using a number of prior therapies. I'm happy to report that since we implemented those eligibility criteria, we have seen, I would say, not only more responses, but I would say the kinetics of the responses also have been faster. So I think that those moves that we made several months ago, or maybe a year ago now, really have made a difference. And those moves were based on our better understanding of the mechanism of action.
Speaker Change: We are working on that.
Speaker Change: We're looking all the time for <unk>.
Speaker Change: Mutations in baseline immune status et cetera, but you'll remember that several months ago, we implemented and on conference calls I talked about.
The immune status at baseline the absolute lymphocyte count.
Speaker Change: And then using a number of prior therapies.
Speaker Change: Happy to report that since we've implemented those eligibility criteria we have seen.
Speaker Change: I would say not only more responses, but I would say the kinetics of the responses also has been faster.
So I think that those moves that we made several months ago or maybe a year ago now.
Speaker Change: Really have made a difference in those moves were based on our better understanding of the mechanism of action.
Aydin Huseynov: So I expect that in a phase three trial, we already know this, we're gonna get better patients. They're gonna have a better immune status to start with. Phase one trials usually get sicker patients just by nature of the fact that they've exhausted all other, any other therapies that are available. So I would expect that, you know, our results could get better. And we are continuing to look at different markers. But so far, I don't know, other than the baseline immune status, I don't know if we have a specific molecular marker.
Speaker Change: So I expect that in a phase III trial, we already know this.
Speaker Change: <unk> III trial, we're going to get better patients theyre going to have better immune status to start with phase. One trials you usually get sicker patients just by by nature of the fact that they've exhausted the other any other therapies that are available.
Speaker Change: So.
Speaker Change: I would expect that.
Speaker Change: Our results.
Speaker Change: Could get better.
Speaker Change: And we are continuing to look at different markers, but so far I don't know other than the baseline immune status.
Speaker Change: No if we have the specific molecular marker.
Richard A. Miller: Understood. Thank you. Thank you so much and congratulations on the progress.
Speaker Change: Understood. Thank you. Thank you so much and congratulations with the progress.
Speaker Change: Oh.
Jeffrey Michael Jones: Your next question comes from the line of Jeff Jones from Oppenheimer. Your line is now open.
Speaker Change: Your next question comes from the line of Jeff <unk> from Oppenheimer. Your line is now open.
Jeffrey Michael Jones: Thank you, operator. And congrats on the news guys, that's great, and congratulations on the financing as well. One question on the so-called lit nib. There were a number of responders in phase one that were cutaneous T cell lymphoma patients. Can you remind me if cutaneous T-cell lymphoma patients are going to be included in phase 3 and what impact that might have on the PFS?
Jeff Archer: Thank you operator.
Jeff Archer: That's on the news guys Thats, great and congrats on the financing as well.
Jeff Archer: One question on so call it.
Jeff Archer: Yes.
Jeff Archer: There are a number of responders in the phase one that were cutaneous T cell lymphoma patients.
You remind me.
Jeff Archer: Cutaneous T cell lymphoma patients are endpoint to be included in the phase three and what impact that might have on the PFS.
Richard A. Miller: There are a couple of patients who are included in R23 that had cutaneous T-cell lymphoma. Both of those patients had transformed cutaneous T-cell lymphoma. That portends a very bad prognosis when you get what's called large cell transformation. That's not your typical CTCL, my point is.
Jeff Archer: There are a couple of patients who are included in our 23 that had cutaneous T cell lymphoma. Both of those patients had transformed cutaneous T cell lymphoma that portends, a very bad prognosis. When you get what's called large cell transformation, that's not your typical <unk>.
Richard A. Miller: CTCL patients are not going to be enrolled in our phase three trial because it really is a different disease. It's treated with different drugs. And it can be a chronic disease early. People who have just skin disease can have it for many years. That's not the patients we're talking about in this trial. But Jeff, I think you raise a good point which I forgot to mention.
Jeff Archer: Is my point CTC L patients are not going to be enrolled in our phase III trial, because it really is a different disease, it's treated with different drugs and it can be a chronic disease early people, who have just skin disease.
Jeff Archer: And have disease for many years, that's not the patients we're talking about in this trial, but Jeff I think you raise a good point, which I forgot to mention we see responses in cutaneous lymphomas anaplastic lymphoma.
Richard A. Miller: We see responses in cutaneous lymphomas, anaplastic lymphoma, peripheral T-cell lymphomas, something called angio-aminoblastic or now known as T-follicular helper cell lymphoma. These are very different histologies under the microscope. They have different patterns of spread in the body. And they have different mutations, genetic mutations.
Jeff Archer: Peripheral T cell lymphomas.
Jeff Archer: Something called the NGL immunoblastic or now known as T. Follicular helper cell lymphoma. These are very histology.
Jeff Archer: Different histology is under the microscope, they have different patterns of spread.
Jeff Archer: In the body and and they have different mutations genetic mutations the <unk>.
Jeffrey Michael Jones: The fact that we see activity in this very diverse group of lymphomas, of T-cell lymphomas, is really, again, consistent with our mechanism, which is to induce a host anti-tumor response. And one of the motivating factors that we think we can extend this to solid tumors is that, that was the reason we started doing preclinical work with solid tumors. That data has been presented and confirmed by others. And this is the reason why we're all so excited about looking at this drug in solid cancer.
Jeff Archer: Fact that we see activity in this very diverse group of lymphomas of T cell lymphomas.
Jeff Archer: Is really again consistent with our mechanism, which is to induce a host anti tumor response and one of the motivating factors that we think we can extend this into solid tumors that was the reason we started doing preclinical work with solid tumors that data has been presented and confirmed by others and this is the reason why we're also excited about.
Jeff Archer: Looking at this drug in solid cancers.
Richard A. Miller: Did I hit you?
Speaker Change: Did I answer your question.
Jeffrey Michael Jones: Yeah, you did. That was really helpful. I appreciate it.
Speaker Change: Yes, you did that was really helpful. I appreciate it.
Speaker Change: I've always wondered about a little about those cutaneous responses, which are obviously getting really good responses.
Richard A. Miller: I've always wondered a little about those cutaneous responses, which are obviously generally good responses. Jeff, hold on. The responses that we see in these cutaneous patients, it's not fair to call them that. They have cutaneous disease. They have circulating tumor cells. They have lymphadenopathy. Sometimes they have visceral disease. The responses that we've seen in the responding patients are not just cutaneous. It's throughout the body.
Speaker Change: Oh.
Jeffrey Michael Jones: Okay. Fair. Sorry. That was a poor language choice on my part. In the atopic dermatitis study, you mentioned, I believe, patients had been on two prior lines of therapy. Are you including patients who have previously had dupilumab and failed, or are you not being that specific?
Speaker Change: Yeah, Oh told on the responses that we see in these cutaneous patients well, it's not fair to call them that they have cutaneous disease. They are circulating tumor cells. They have lymphadenopathy, sometimes they have visceral disease. The responses that we've seen in the responding patients is not just cutaneous it's.
Speaker Change: Throughout the body.
Speaker Change: Okay Fair sorry.
Speaker Change: Poor language choice on my part.
Speaker Change: In the atopic dermatitis study.
Speaker Change: You mentioned I believe patients had been on two prior lines of therapy or they're going to be.
Speaker Change: Are you, including patients who have previously had to pull them out and failed or does that argue not being that specific.
Richard A. Miller: We're not being that specific. And they have to have failed at least one prior therapy, one prior to either systemic or topical therapy. Some of the patients, we assume that some of the patients that come into our trial will have failed DUPI, but it's not required. They will also have failed others.
Speaker Change: We're not being that specific and that they have to have failed at least one prior therapy.
Speaker Change: One prior.
Either systemic or topical therapy some of the patients we assume that some of the patients that come in our trial will have failed dupee, but it's not required.
Speaker Change: We'll have also failed others.
Jeffrey Michael Jones: I think we got a recent patient who failed a JAK inhibitor, for example. So this trial was really intended to show, of course, that the drug is well-tolerated in a patient population like this. And we're looking for activity. Obviously, subsequently, we'll be trying to figure out how it stacks up against some of these other agents. But right now, we're confirming mechanisms, safety, and, yes, we are measuring efficacy against a placebo.
Speaker Change: I think we got a recent patient who failed the JAK inhibitor for example.
Jeffrey Michael Jones: Got it. No, I appreciate the clarity. And then last question on SIFO, I know that you said 27 patients were enrolled, but you didn't specify how many were included in that interim efficacy analysis.
So really.
Speaker Change: We have to put this this trial was really intended to show of course that that era is well tolerated in a patient population like this and we're looking for activity.
Richard A. Miller: I think there are 18 patients in that group. You're right because some of them haven't come back for their first visit yet.
Speaker Change: Obviously subsequently we'll be trying to figure out is it how does it stack up against some of these other agents.
But right now we're confirming mechanism safety and yes, we are measuring efficacy against the placebo.
Speaker Change: Got it no I appreciate the clarity.
Speaker Change: And then last question on it though I know that you had said 27 patients were enrolled.
Speaker Change: But you didn't.
Speaker Change: Specify how many were included in that interim efficacy analysis.
Speaker Change: I think there is 18 patients in that.
Speaker Change: Youre right because some of them to have some of them haven't come back for their first visit yet. So so this protocol by the way was prepared by the case CRC.
Richard A. Miller: So this protocol, by the way, was prepared by the KCRC. And they have, there are sort of blocks of, I forget how many patients each block is, eight or nine patients each. And there's a criteria efficacy threshold that you have to pass to continue. And the results so far are really pretty good. And in fact, we're organizing a meeting at ASCO to think about, oh, discussing things like adding a control arm or, you know, where do we go from here? Obviously, at some point, you want to have a control arm.
Speaker Change: And.
Speaker Change: They have there are sort of blocks of.
Speaker Change: I forget how many patients each eight or nine patients each and there is a criteria efficacy threshold that you have to pass to continue.
Speaker Change: The results. So far are really are really pretty good and in fact.
Speaker Change: We're organizing.
Speaker Change: Meeting at <unk>.
Speaker Change: To think about Oh discussing things like adding a control arm or where do we go from here obviously at some point you want to have a control arm in there.
Richard A. Miller: By the way, the deep response rate of 32 percent for ipi-nevo, I know people are always critical of historical controls, as they should be, but that's based on a 900 patient checkmate to... What was it? The checkmate study with ipi-nevo versus Sutent was over 900 patients, and then there was a nevo-cabo versus Sutent. That was... 700 pages.
Speaker Change: Sure by the way the deep response rate of 32% <unk> I know people always critical of historical controls and as they should be but that's based on our 900 patient checkmate two what was it the checkmate study with Opdivo versus <unk> was over 900 patients and then there was neither cabo versus.
<unk> that was 700 patients. So this is.
Speaker Change: This is based on.
Speaker Change: Pretty good.
Speaker Change: A good foundation of data.
Jeffrey Michael Jones: Just one clarification. You mentioned in your remarks that you think 27 patients enrolled and then going over this threshold of deep responses to expand that trial. Did you mean just up to 60 patients, expand further up to the 60 planned, or is there a potential expansion beyond those 60 patients?
Speaker Change: Got it.
Speaker Change: Just one clarification.
Speaker Change: You had mentioned in your remarks, I think 27% enrolled and then going over that threshold of deep responses to expand that trial.
Speaker Change: Did you mean, just up to the 16th.
Ill expand further up to the 60 plan doors there.
A potential expansion beyond those 60 patients.
Richard A. Miller: No, there's no expansion beyond the 60. What I talked about, when I mentioned expanding, I think at some point it would be nice to add a control arm, you know, maybe ipinevo alone, ipinevo placebo. But that probably raises the whole question of, do you want to do a randomized phase 2 or do you want to go right to phase 2?
Speaker Change: No Theres no expansion beyond the 60.
Speaker Change: What I talked when I, when I mentioned, expanding I think at some point.
Speaker Change: It would be nice to add a control arm, maybe it be knievel alone <unk> placebo.
Speaker Change: But probably that raises that raises the whole question of do you want to do a randomized phase two or do you want to go right to a phase III.
Jeffrey Michael Jones: Yeah, understood. All right. Thank you very much, guys. That's it for me.
Speaker Change: Yes.
Speaker Change: Understood Alright, thank you very much guys.
Speaker Change: It for me thanks.
Greg Sovanovic: Your next question comes from the line of Greg Sovanovic. Your line is now open.
Speaker Change: Your next question comes from the line of Greg Some burden of that your line is now open.
Greg Sovanovic: Good afternoon. Thanks for taking my questions. I have two in particular. One, maybe I'll start with your 2nd asset. I know you mentioned that you were able to pass the bar for success for moving forward. I don't know if you've missed this, but if you quantified how much better beyond that bar that you had seen from, I guess you're 18, a valuable patient. So, I'm wondering if you can perhaps shed more light on that. And then, secondly, just on your current cash, and congrats on the recent raise, but if you could clarify whether that cash gets you through phase 3 for in.
Greg: Good afternoon, Thanks for taking my questions.
Greg: I have two in particular.
Greg: One.
Maybe I'll start with the.
Greg: Your second asset I know you mentioned that you were able to pass like the.
Greg: As far for success for moving forward.
Greg: I don't know if you I might've missed this if you quantified how much better beyond that bar that you would seen from I guess your 18 evaluable patients.
Greg: I'm wondering if you can perhaps shed more color on that and then secondly, just on your current cash and congrats on the recent.
Greg: Raise but if you could clarify whether that cash gets you through.
Greg: The phase three.
Greg: For so-called at Nib.
<unk>.
PTC: PTC all thanks.
Okay.
Richard A. Miller: Okay, Craig, let me take the first one first. So the statistical threshold was a 50% increase. So the statistician's 50% increase above the 32%, which is obviously 48%. If you meet that, you have... Oh, you have a difference with a p-value of 0.1 in only 18 patients. That's a pretty stiff hurdle. A 50% increase is a big hurdle. And so we exceeded that. I can't give you the exact number because the KCRC doesn't really want to disclose that yet.
PTC: Okay, Craig let me take the first one first so the statistical threshold was a 50% increase so the statisticians.
PTC: 50% increase above the 32%, which is obviously, 48% if you meet that you have.
PTC: Oh, you have a difference of.
PTC: With a P value of 0.1, and only 18 patients that's a pretty stiff hurdle, 50% increases that they've hurdle.
PTC: And so we exceeded that I can't give you the exact number because the K CRC doesn't really want to disclose that yet and I understand why because these numbers jump around a lot and a small study.
Richard A. Miller: And I understand why, because these numbers jump around a lot in a small study. But we're better, then 48% deep response rate, okay? And again, I want to emphasize 50% improvement in deep response rate; that's a stiff hurdle. And the reason we wanted that is we didn't want to waste time on something that didn't have a significant probability of working, so we made it, and neither did they. So we've deliberately made these hurdles pretty strict. Now, your second question. I'll let Leif answer that question.
PTC: But we're better than 48% deep response rate okay.
PTC: And again I want to emphasize 50% improvement in deep response rate is that just deferral and the reason we wanted that is we didn't want to waste time on something that they didn't have a significant probability of working so we made it nor does day.
PTC: So we deliberately made these hurdles pretty strict.
Speaker Change: Now your second question.
I'll, let Lisa answer.
Leiv Lea: So Craig, associated with our financing, we also sold warrants. Now these warrants, first of all, have an exercise price of $3.50, but more importantly, maybe, they expire on June 30th, 2025, so a little over a year from now. So if all those warrants were exercised, we'd raise about $60 million. So the $30 million plus the $60 million, should those warrants be exercised, would get us through the phase three trial.
So craig associated with our financing.
Lisa: We also sold Laurence that is Warren's first of all have an exercise price of $3 50.
Greg Sovanovic: Okay, thank you for that clarification. Thanks again.
Lisa: But but.
Lisa: More importantly, maybe.
Lisa: They expire June 30 of 2025.
Lisa: A little over a year from now.
Lisa: So if all of those warrants were exercised we would raise about $60 million, so the $30 million plus the $60 million.
Lisa: Should those warrants to be exercised.
Lisa: Would get us through the phase III trial.
Speaker Change: Okay. Thank you for that clarification. Thanks again.
Speaker Change: Yeah.
Roger Song: Your next question comes from the line of Roger Song from Jeffreys. Your line is now open.
Roger Song: Your next question comes from the line of Roger song from Jefferies. Your line is now open.
Roger Song: Yeah.
Jiayuan Gong: Good afternoon, this is Liangchen Wang on behalf of Roger Song. So thank you for taking our questions. I guess we have a few. First one's about the modified inclusion criteria, so about the absolute lymphocyte count, about 900. So if I remember correctly, there is a big overlap between this 900 plus ALC count and the patient population. So, could you clarify what's, you know, in general, this population?
Roger Song: Good afternoon adjacent to downtown core Roger So so thank you for taking our questions. Just a few questions from US first one about.
Roger Song: Collegium.
Roger Song: The modified inclusion criteria and it's all about the absolute lymphocyte count.
Roger Song: 900 so.
Roger Song: If im remembering correctly there are big overlap.
Roger Song: 990.
Roger Song: Yeah.
Roger Song: 900, plus ALC comps between the patient population so could you clarify whats in general.
Roger Song: These population looks like.
So.
Richard A. Miller: So... The 900th absolute lymphocyte count was determined based on the early part of the trial where we were taking anybody who failed, you know, any number of prior therapies. And we recognized that those patients above 900 did better, much better. And then we realized that those were the patients who had no more than three prior therapies, less than or equal to three prior therapies. And so that's the criteria that we're using because they're less immunocompromised.
Roger Song: The 900 absolute lymphocyte count.
Roger Song: <unk>.
We determined based on the early part of the trial, where we were taking anybody who failed.
Roger Song: Any number of prior therapies, and we recognize that those patients above 900.
Roger Song: Did better much better.
Roger Song: And then we recognize that those were the patients who had no more than three prior therapies less than or equal to three prior therapies.
Roger Song: And so that's the criteria that we're using because.
Roger Song: They're less immuno compromised.
Richard A. Miller: Those are what's been used on the patients that have been reported in today's press release. It's the number of prior therapies greater than is equal to one, less than is equal to three. I don't recall. I'm sorry.
Roger Song: Those are the those are what's been used on the patients that have been reported in today's press release, it's the number of prior therapies greater than or equal to one less than or equal to three.
Speaker Change: Now no I don't I don't recall that I'm sorry.
Jiayuan Gong: Do we know in general how many patients have this, you know, meet this criteria? Oh, if we, in our trial, the percentage of patients that will meet this criteria is very high. Again, in a phase three trial, we're already hearing from doctors that we're going to get patients right after they fail their first line therapy, maybe a second line therapy. I would expect the number of eligible patients to be nearly 100%.
Speaker Change: Do we know.
Speaker Change: How many patients are have the meet these criteria.
Richard A. Miller: Got it. Thank you.
Speaker Change: Oh, if we in our trial the percentage of patients that will meet this criteria.
Speaker Change: Very high.
Speaker Change: Again in a phase III trial, we're already hearing from doctors, we're going to get we're going to get patients right. After they file their first line therapy may be a second line therapy I would expect the number of eligible patients to be nearly 100%.
Jiayuan Gong: So, our second question is about the AD study. It mentions there that we could expect some early data by year end. So, you know, just in general, how much data should we expect from there?
Speaker Change: Got it thank you.
Speaker Change: So our second question is about a deep that install it maintenance or what could we expect some early data read out.
Speaker Change: By year end so how.
Speaker Change: So just in general how much data should we expect from there.
Richard A. Miller: I think you can expect data from the first couple of cohorts. And as you recall, our first dose is 100 mg BID, which is a pretty good dose. It's a dose that we know occupies the target maybe 50% or so, give or take. It's not the best dose, but it's a pretty good dose.
Speaker Change: I think you can expect data from the first couple of cohorts.
Speaker Change: And as you recall, we are where.
Speaker Change: Our first dose is 100 milligrams b I D, which is a pretty good dose. It's a dose that we know occupies the target maybe 50% or so give or take.
Speaker Change: Not the best dose, but it's a pretty good dose. The second cohort gets 200 milligrams and then we had a 200 PID so I think that.
Jiayuan Gong: The second cohort gets 200 mg, and then we do 200 BID. So I think that we may very well may see some signs of efficacy in the first cohort. I would expect that in the second cohort we would see it. Obviously, I think it would be better in subsequent cohorts than the first cohort, but we're also looking at these biomarkers, the serum cytokines, that we know we affect and how they'll change. So I'm hoping that sometime by the end of the summer, we'll start to get a feel for the clinical activity of the drug and also its effect on circulating cytokines.
Speaker Change: We very well may see some signs of efficacy in the first cohort I would expect in the second cohort we would see it.
Speaker Change: Obviously.
Speaker Change: I think it would be better in subsequent cohorts in the first cohort, but we're also looking at these biomarkers the serum cytokines that we know we affect and how and how they'll change so I'm, hoping that sometime by the end of the summer we will start to get a feel for the clinical activity of the drug and also its effect on circulating <unk>.
Speaker Change: Cytokine.
Richard A. Miller: Got it. So, you know, since you talked about the dosing regimens, just in general, how should we think about circulating and dosing regimens in AD, you know, considering
Speaker Change: Got it so thank.
Speaker Change: Can you talk about the dosing regimens.
Speaker Change: In general how should we think about circulating in dosing regiments in a D. Continuing with it's a different indication compared to.
Speaker Change: The dosing in.
Speaker Change: T cell lymphoma.
Richard A. Miller: Okay, so we know, and we've tested this not only in lymphoma patients, T-cell lymphoma patients, but in other normal people in vitro. We know what it takes to saturate the T-cell ITK in the T-cell. So, as you recall, it's a covalent drug, similar to the way ibrutinib worked, but this is to a different target, so that once the drug binds to the target, it doesn't come off. So, we know what it takes.
Speaker Change: Okay.
Speaker Change: So so we know.
And we've tested this not only in in lymphoma patients T cell lymphoma patients but in in.
Speaker Change: In other in normal people in vitro, we know what it takes to saturate the T cell ITK and the T cells.
Speaker Change: So as you recall, it's a covalent drug similar to the way Ibrutinib work, but except this to a different target so that once the drug binds to the target it doesn't come off so we know what it takes we have a really good pharmacodynamic marker to know that we're blocking the T cells.
Richard A. Miller: We have a really good pharmacodynamic marker to know that we're blocking the T-cells, or at least occupying the T-cells. Pharmacodynamics will apply in AD, as it does in lymphoma. I mean, the occupancy will be the same, but what it takes to affect your immune response is something we don't know. And that's why we're looking at different doses. Aydin Huseynov, Roger Song, Leiv Lea, Zack Kubow, Corvus Pharmaceuticals Inc., Yep.
Speaker Change: Or at least are occupying the T cells.
Speaker Change: Now, we don't know for sure that the same.
The same.
Speaker Change: Pharmacodynamics will apply in Adas and in lymphoma, I mean, the occupancy will be the same but what it takes to affect your immune response that we don't know and that's why we're looking at different doses.
Speaker Change: In this study the reason to look at different doses is what does it take to affect the immunology in these patients and also of course.
Speaker Change: We're looking for as low as possible to lower the dose the one would think the safer it would be.
Richard A. Miller: So that's why that's why this is phase one study. But I mean, this is basic chemistry. Socolitinib reacts with the ATP binding pocket of ITK. And that's the truth. That's what happens. And once that's occupied, that enzyme isn't going to work unless until a new one is made. So, and of course, as you know, the rationale is that atopic dermatitis patients have an intense Th2 helper T cell component in their disease, and we think if the drug gets there and it binds covalently to ITK, we know that we block Th2 cells, we know we block Th2 cytokines, we think that will have an impact on the disease. But the purpose of the trial is to show that.
Speaker Change: Yes. So that's why that's why this is that's why there's a phase one study but.
Speaker Change: I mean this is basic chemistry.
Speaker Change: So call it reacts with the ATP binding pocket of ITK and Thats.
Speaker Change: That's the fact, that's what happens.
Speaker Change: And once that's occupied that that ensign isn't going to work unless and until the new one is made.
Speaker Change: Sure.
Speaker Change: So and of course as you know the rationale is that.
Speaker Change: Atopic dermatitis patients have an intense.
Speaker Change: Th two helper T cell component in their disease, and we think as the drug gets there and it binds covalently to ITK, we know that we block THQ cells. We know we bought tht cytokines, we think that will have an impact on the disease, but the purpose of the trial is to us too.
To show that.
Jiayuan Gong: Sure, maybe I can squeeze another question in here. So regarding the ITK inhibitors, I know you have a couple more coming up in the pipeline. So what are some key differences between this one, colitinib, and the other candidate?
Speaker Change: Sure maybe.
Speaker Change: Maybe I'll squeeze one other questions here regarding the ITK inhibitor energy I know you have a couple more coming up in the pipeline. So what are some key differences between this one.
Speaker Change: So quality names.
Speaker Change: Other Kennedy.
Richard A. Miller: So first of all, we have over a dozen other ITK inhibitors that we've been evaluating. Some are completely different chemical structures, some are covalent, some are non-covalent, but the interesting biological features are that some seem to affect T cells more than others, and we find that to be quite interesting, quite novel, and provides for, I think, some very strong intellectual property.
So first of all we have over a dozen other ITK inhibitors that we've been evaluating.
Speaker Change: Some are a completely different chemical structures some are covalent summer non covalent.
Speaker Change: But the interesting biological features as some seem to affect us.
T cells <unk> T cell subsets more than others, and we find that to be quite interesting quite novel.
Speaker Change: And provides for I think some very strong intellectual property.
Jiayuan Gong: Thank you. That's all from us.
Got it. Thank you that's all from us Thank you.
Speaker Change: Again.
Li Wang Watsek: Your next question comes from the line of Li Watsek from Kantar Fitzgerald. Your line is now open.
Speaker Change: Your next question comes from the line of Lee <unk> from Cantor Fitzgerald. Your line is now open.
Speaker Change: Yeah.
Rosemary Li: Hi, this is Rosemary Ansely. Thank you so much for taking our questions and coming out. So just two quick ones from us.
Lee: Hi, This is <unk>. Thank you so much for taking our questions and congrats.
Rosemary Li: For atypical dermatitis, do you have a benchmark in terms of improvement in eczema area and severity index?
Lee: Just two quick ones from us for atopic dermatitis, there isn't a benchmark in terms of improvement in eczema area and severity index.
Richard A. Miller: No, we don't have a benchmark.
Speaker Change: No we don't have a benchmark.
Rosemary Li: Okay. Okay. Thank you. And then for a second question, for your next-gen ITK inhibitors, do you plan to generate any human data for business development discussions or just like the clinical trials? I'm sorry.
Speaker Change: Okay. Okay. Thank you and then.
Speaker Change: Second question for your neck and ITK inhibitor.
Speaker Change: And you probably generate any human data for BBB, especially I guess like preclinical I'm, sorry, I couldn't understand the question can you repeat it.
Rosemary Li: I'm sorry, I couldn't understand the question. Can you repeat it?
Rosemary Li: Oh, sorry. So for your next-gen ITK inhibitors, do you plan on generating any human data before going for BD discussions? Well, we're
Speaker Change: Alright.
Speaker Change: For your next Gen. ITK inhibitor do you plan on generating any human data before going for BD discussion.
Richard A. Miller: Well, we're doing both in parallel. We're now selecting some of these backup or second-generation ITK inhibitors, and they're in their IND enabling studies.
Speaker Change: Well, we're doing both in parallel.
Speaker Change: We are now selecting some of these backup for a second generation ITK inhibitors, there than they are in their IND, enabling studies, we're scaling them up.
Richard A. Miller: We're scaling them up. You know, we're moving down parallel tracks. Okay, thank you. Okay. Operator, I think that exhausts our questions here for now. I want to thank you.
Speaker Change:
Speaker Change: We're moving down.
Speaker Change: Parallel tracks.
Speaker Change: Okay. Thank you.
Speaker Change: Okay.
Speaker Change: Operator.
Speaker Change: Okay.
Speaker Change: Exhausted our questions here for now.
Speaker Change: I want to thank Hello, any other questions that I Miss.
Operator: There are no further questions at this time. I will hand the call over to Richard Miller, CEO of Corvus. Please continue.
Speaker Change: There are no further questions at this time.
Speaker Change: Had the call over to Richard Miller CEO of <unk>. Please continue.
Richard A. Miller: Thank you, operator. I want to thank everyone for participating in today's conference call. We look forward to updating you on subsequent calls and appreciate your interest. Take care.
Richard A. Miller: Thank you operator, I want to thank everyone for participating in today's conference call. We look forward to updating you on subsequent calls and.
Appreciate your interest take care.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
Richard A. Miller: Yes.