Good morning, everyone. Thank you for standing by, and welcome to the Corvus Pharmaceuticals Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. It is now my pleasure to turn the call over to Zack Kubow of Real Chemistry. Please go ahead, sir.
Thank you, operator, and good morning, everyone. Thanks for joining us for the Corvus Pharmaceuticals soquelitinib FDA Meeting and phase III Clinical Trial update conference call. On the call are Richard Miller, Chief Executive Officer, and Leiv Lea, Chief Financial Officer. 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' most recent quarterly report on Form 10-Q and other filings the company makes with the SEC 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, I'd like to turn the call over to Dr. Richard Miller. Richard?
Thank you, Zack, and good morning, everyone. Thank you for joining us today for our call. We are very excited about soquelitinib and the potential of selective ITK inhibition as a platform opportunity across hematological cancers, solid tumors, and autoimmune and allergic diseases. We are now advancing on each of these fronts, and combined with our other pipeline programs, Corvus has significant opportunities to improve clinical outcomes for a range of indications for patients with unmet needs. First, in lymphoma, we are pleased to report that following an end-of-phase pre-phase III meeting with the FDA in late August, just last week, we achieved alignment on our plans for a phase III registration clinical trial of soquelitinib in patients with relapsed peripheral T-cell lymphoma, or PTCL.
We have previously outlined our expectations for the design of this phase III trial, and I am happy to confirm that following the meeting, there are no significant changes to the key aspects of the trial, including sample size, dosing regimen, eligibility, comparator arm, endpoints, and statistics. I would like to thank the FDA team for their guidance, which included helpful feedback that we are integrating into both the study design and overall registration strategy. With alignment with the FDA on the trial design in hand, we believe we can initiate the trial early in 2024. Second, in solid tumors, we plan to initiate a phase I-B/II clinical trial of monotherapy soquelitinib in patients with relapsed metastatic renal cell cancer. This is an indication that could greatly expand soquelitinib's impact and open the opportunity to potential use in a broad range of other solid tumors.
Now I will share more details on our FDA meeting and the phase III clinical trial plan for soquelitinib. Last week, we completed the end of phase, pre-phase III meeting with FDA to discuss our submitted briefing documents containing detailed data on soquelitinib's safety, efficacy, pharmacokinetics, pharmacology, dosing, and a range of preclinical information, as well as our proposed phase III registration clinical trial for the treatment of relapsed refractory PTCL. I should add that our package contained data on about 58 patients across all dose levels and diseases. Based on the meeting and FDA's feedback, there are no substantial changes from what we proposed in the design of the trial or our registration strategy and plans. We are now working on finalizing the study protocol. The key aspects of the trial include the following.
The trial is planned to enroll a total of 150 patients with relapsed PTCL, 75 patients per arm, that have received one to less than or equal to three prior therapies. The restriction on number of prior therapies is important because it also identifies immunocompetent patients, which are those with absolute lymphocyte counts above 900. This eligibility feature captures about 90% of the patients with ALC greater than 900. Patients will be randomized to receive soquelitinib, 200 milligrams, two times a day, or the standard of care chemotherapy agents. The standard of care agents will be physician's choice between pralatrexate, belinostat, or gemcitabine. The primary endpoint will be progression-free survival, determined by an independent review committee. Secondary endpoints will include objective response rate and overall survival. The study also will include an interim analysis.
Our planned trial should support FDA approval if statistical significance is achieved and the study is well conducted. PTCL is a bad disease with a very poor prognosis, and there is a significant need for new therapies. The common treatments are various chemotherapy regimens, which are inconvenient and poorly tolerated. For relapsed patients, which is the population we are targeting in our trial, the outlook is extremely grave. These patients have a 6.5-month median overall survival after first relapse, with many patients dying within the first few months. They have limited treatment options, and in fact, in the National Comprehensive Cancer Network treatment guidelines for PTCL patients following first relapse, the recommended option for second-line therapy is enrollment in a clinical trial of an experimental therapy, even though there are three approved agents for this setting.
So we are excited to be bringing a potential new treatment option for these patients. In addition to finalizing the protocol, we will continue recruiting investigators for the study, executing site contracts, securing IRB approvals, and the other usual steps needed to initiate the study. As noted on our Q2 update call, we had already begun recruiting U.S. and international investigators, and we anticipate that up to 40 leading academic and private medical centers with significant experience in PTCL lymphoma research will participate in the trial. This includes our principal investigator, who is a leader in the field and has published and conducted other phase III studies in T-cell lymphoma. We are making good progress on all fronts and anticipate that we can initiate the soquelitinib phase III trial early in the first quarter of 2024.
Selective ITK inhibition with soquelitinib also has been shown to enhance immune responses to solid tumors in preclinical studies. Soquelitinib's unique mechanism of action is characterized by activation of cytotoxic killer cells, increased infiltration of these cells into tumors, and reduction and reversal of T cell exhaustion, resulting in a more potent and prolonged immune response. We have developed a protocol for a phase I-B/II trial of soquelitinib monotherapy in renal cell cancer patients in first or second relapse following frontline checkpoint inhibitor therapy. The primary objective of this study will be to evaluate antitumor activity. We have several reasons for starting with renal cell cancer to establish proof of principle, and we are planning for other solid tumor clinical trials as well. The Kidney Cancer Research Consortium will lead this trial. We anticipate that the trial will be initiated in early 2024.
Outside of cancer, we are excited to continue the development of soquelitinib in autoimmune and allergic diseases, starting with atopic dermatitis. There is a strong scientific rationale for selective ITK inhibition for this indication, including results in companion dogs with spontaneous, naturally occurring atopic dermatitis, where soquelitinib has shown preliminary signs of activity. This approach represents a new idea in the treatment of immune diseases, and the results from our studies with soquelitinib in atopic dermatitis, and other autoimmune disease models could extrapolate to Th2 and Th17-mediated diseases like asthma, fibrosis, psoriasis, and a range of other immune-mediated diseases. We are optimistic about our novel ITK inhibitor as a platform technology with broad applications in oncology and autoimmunity. We will continue to build value by prudently and efficiently pursuing our multiple development opportunities.
Our main focus is soquelitinib for relapsed PTCL, where we have a clear pathway to initiate a phase III registration clinical trial in early 2024. This is complemented by new trials planned in solid tumors, and we are continuing development in autoimmunity, expanding the opportunity for soquelitinib and our other ITK inhibitors in development. Taken altogether, we have multiple upcoming catalysts across our pipeline, led by our foundational work on ITK inhibition and its myriad of biologic activities in the immune system.
Over the remainder of the year and into 2024, our upcoming milestones include ongoing updates from the phase I/I-B clinical trial of soquelitinib in T-cell lymphoma, including a potential presentation at the ASH meeting in December. Interim data from ciforadenant phase I-B/II trial in frontline metastatic RCC before year-end. The initiation of the soquelitinib phase III registration clinical trial in early 2024, and the initiation of a phase I-B/II solid tumor monotherapy trial of soquelitinib in relapsed renal cell in early 2024. These programs provide us with multiple opportunities to address significant patient needs and the potential to efficiently build value for our shareholders. In closing, we look forward to providing updates on our programs in the coming quarters. I will now turn the call over to the operator for questions and answer period. Operator?
Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question today, please press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for questions. Thank you. Our first question is from the line of Aydin Huseynov with Ladenburg Thalmann. Please proceed with your questions.
Good morning, everyone. Good morning, Richard, Leiv . Congratulations on the FDA clearance on the phase III. A couple of questions. So, does the FDA still want to see additional data from the phase I-based study of soquelitinib?
No, no additional data is required.
Oh, okay. Understood. And are you—I, I think you mentioned that you plan to present more data at ASH this year?
Correct. We've submitted an abstract to ASH, and we do plan to present data there.
Yeah. Okay, understood. So, so the other previously approved PTCL agents, they were all approved via accelerated path, and it was monotherapy, single arm, pralatrexate, romidepsin, belinostat. But given that regulatory environment change and you, you have to run a longer phase III study, do you think the FDA may still suggest, some sort of, you know, better, approval process, some fast track priority review, anything that would facilitate the, the process?
Well, I actually think that we are in a better shape because of recent guidelines from FDA, where now for accelerated approval, they're going to require randomized trials. I personally think that's a great idea because without a concurrent random control arm, you really don't know what these results mean. So, I believe the trial we now have actually gets us a better answer faster. We have an interim analysis where we can look at futility, we can look at response rate, we can look at PFS at that time, and we can determine whether or not the results are profound enough to seek accelerated approval, or we can continue the trial to the end and get a full approval, definitive approval. So having the random not.
The randomized trial and having a control arm is really what the FDA wanted. Actually, the number of patients, as you can see for this study, 150, is not a large study, and yet that gives us a really great opportunity to prove efficacy. Let me add that there is never, there is no approved agent for relapsed T-cell lymphoma that is based on a randomized trial. Let me repeat that. There is, to my knowledge, and I'm pretty sure this is true, if you speak to anyone, there is no approved agent for relapsed peripheral T-cell lymphoma that has been based on a randomized trial. Now, I'm an oncologist, and I can tell you randomized trials are gold. Single-arm trials are good.
They're better than no trial, but again, without having a concurrent control arm, randomized control arm, it is very difficult to compare results from one trial to another, because patients are just different at different places and in different times. Is that clear, Aydin?
Oh, absolutely. It makes a lot of sense. Appreciate that. And how long do you think it will take to enroll these 150 patients? And when do you think you will be able to read out some interim data from this study?
I think we can read out this trial in two years, interim analysis, 18 months. Obviously, a lot depends on rates of enrollment and event rates. So the PFS endpoint, to be clear about that, is an event-driven endpoint, not a time-driven endpoint. 150 patients enrolled, our statistical calculations show that, we can look at the data after 130 PFS events.
Thank you, Richard. Very, very helpful. Congrats again on the FDA green light.
Our next question is from the line of Jeff Jones with Oppenheimer. Please proceed with your question.
Thanks, guys. Good morning and congratulations. Just quickly, could you speak in a little bit more depth about the use for patient selection of less than three lines of prior therapy versus the ALC count that you were using to sort of discriminate likely responders and non-responders, and how you've reported data previously? Thanks.
Okay. Yeah, thanks for that question. The phase I/I-B trial that we've been conducting had no restriction, initially had no restriction on ALC or number of prior therapies. In fact, the range of prior therapies in our trial ranged all the way from one to 18. Even in our 200 mg dose, it ranged from about one to 12. When we learned about the mechanism of action of the drug, we recognized pretty quickly that this is dependent on immunocompetence, on having normal lymphocytes that could mediate the killing. We then restricted the study to ALC of 900. Doing that pretty much restricts the number of prior therapies to three.
By the way, three is a commonly used cutoff for a lot of these trials. So with the criteria of 900 or three prior therapies, you achieve the same enrichment. When we look at our data, if you take patients with less than or equal to three prior therapies, 90% of them have ALCs above 900. So prior therapies is a very standard way to enroll patients. And although we're collecting the data on ALC, in fact, we're doing more than that, we're not only collecting data on ALCs, we're gonna be looking at the subsets and so forth from the blood, T cell subsets. We think we don't need to make that a strict eligibility criteria. Numbers of prior therapies is much more standard.
It doesn't change the enrichment, it doesn't change the strategy.
Great.
Does that make sense?
Appreciate the additional color. Yeah. Thanks, guys.
Our next question is from the line of Li Watsek with Cantor Fitzgerald. Please proceed with your questions.
Hey, good morning. Thank you for taking our questions. I guess just first, wondering if you can just share more detail around, you know, powering assumptions for the phase III. What is the effect size that, you know, this trial is powered to show us specifically for PFS? And you mentioned that there will be an interim analysis, maybe around 18 months or so. Maybe talk a little bit about the expectation there, any possibility to maybe hit the efficacy hurdle early and maybe get an AA approval there?
Okay, let's start with the power assumptions. Our trial has, I believe it's an 87% power to see a prolongation of survival from an expected 3.8 to 6.2, I believe it is, a little less than three months. That number is picked because that's what we feel is clinically meaningful, and we think we can hit that. P-value has to be 0.025, 0.05, two-sided test. The interim analysis is primarily a futility analysis. However, the blinded review committee, data monitoring committee, will have unblinded data, will be able to look at data for PFS and response rate.
We do have power calculations for those endpoints, but there's really no, you know, guidance or hurdle that makes you wanna do that. We haven't been so much pushing that because the events are so quick, between relapsing and death, that you don't really have to wait that much longer to get the end of the trial, to get to your full number of events. You're, you know, obviously, if median PFSs here are three to four months, I mean, think about that, three to four months is one or two visits to the doctor, if you have two or three monthly return visits. So it's not a long time between when you would do that interim analysis and when you would do the definitive analysis.
I'm not even sure it would be worth doing it, because it takes work, it takes also some risk in terms of compromising the trial. So, I think we should plan that we're gonna do, we're gonna go to the full endpoint, the definitive endpoint, which, by the way, gives you full approval, not a, not an accelerated approval.
Okay, got it. That makes sense. And the second question is: Now you have this, you know, phase III trial design aligned with FDA. Just wondering, you also mentioned, right, you are also planning to go into other indications. So is there a plan to maybe consider, you know, leverage resources from a potential partner here?
Sure. We always consider partnerships. And you know, when the right transaction comes, right arrangement potentially comes along, we would consider it. We obviously... We believe that the ITK target is a platform technology. I don't talk about this, but we have second, third generation ITK inhibitors with very unique features geared towards autoimmunity, allergy. We think those, that's an area that's very partnerable. Obviously, we'd like to move along on our cancer indications, especially now with the phase III starting, that will build value much faster for us with our lead program. Perhaps the autoimmunity becomes something that we focus our partnering possibilities on. Does that make sense?
Yes. Thank you very much.
Just to, just to add a little bit more on that, cause I haven't talked about this in, in a while. I should note that the soquelitinib composition of matter patents have issued in major territories now, U.S., Europe, China, Japan, really all the major countries. We've also have what I think is a very rich portfolio of IP protecting various methods of treatment, functions, monitoring, both for cancer and autoimmunity. So I think that what is special about our position now is that we believe this is a really important target. And at the moment, we have a strong leadership position, a lot of expertise, a lot of chemistry and bioassays that we've developed that will take years for other people to duplicate.
I'm sure they're already working on it, 'cause they're reading our patents as well. So I think we're really in good shape here, really being the leader in this area. Very similar to what my team did in drugs called rituximab and ibrutinib.
Our next question is from the line of Mara Goldstein with Mizuho Securities. Please proceed with your questions.
Great. Thanks so much for taking the question. I just had a question on subtypes for PTCL and whether or not that will be a stratification factor at all in the trial?
The what? The-
Subtypes.
Oh, subtypes.
Yeah.
Our trial is focusing on the three major subtypes, which comprise 85%-90% of peripheral T-cell lymphomas. That is not a stratification factor. There are three stratification factors. We considered all of these, Mara. Number one is age above or below 60. Number two is region of the world. And number three is how long you were on your prior therapy before you progressed. That's a very important stratification factor, maybe one of the most important ones. Let me be clear on that. If you progress, let's just say you got CHOP chemotherapy, and you progressed-
Mm-hmm.
in less than six months, or if you went more than six months before you progressed, that's the stratification feature.
Okay.
Greater than or less than a six-month progression. And that turns out to be a really powerful stratification feature.
Okay.
Okay?
That's great. Mm-hmm. And is there any, I mean, I'm thinking the use of stem cell transplant is limited in this indication, but I think it, right? Is there some use of it, and is that at all-
Is what limited? I didn't hear you.
On stem cell transplant,
Oh, stem cell transplant. Stem cell transplant, autologous or allogeneic, is really limited to a small number of patients. You have to be young.
Mm-hmm.
You have to get into remission to CR, pretty much, in your second remission. I mean, that's a really small number of patients.
Okay. All right. Thank you. Appreciate it.
Our next question is from the line of Roger Song with Jefferies. Please proceed with your question.
Great. Thanks for taking the question, and congrats for the alignment with the FDA. Maybe just a few quick clarification, which you mentioned the power and another assumption is around three months versus six, 6.2. Just curious, do you have different expectations for the standard of care for those patients with one, two, all the way to three prior lines? How does 3.8 fit into different prior line of therapy? I have a follow-up. Thank you.
Yeah. So if you look at the PTCL studies with belinostat, pralatrexate, I don't care where, where you look. In general, the median PFSs will fall three to four months. Okay? That's a pretty consistent number. All right? And most of these studies don't break out whether you have one prior, two, or three. They sort of, you know, take a whole collection of that, but I don't think that that's gonna matter. three to four months is very commonly seen. Do you have another question, Roger?
Got it. Yeah, that's helpful. Yes, and so for the interim, you mentioned the PFS number is around 130 events. Just to clarify if that's for the final event or the interim-
Right.
-event. And also, for the interim data readout, would you report some other data points like ORR and some others? And the last portion of the question is, in terms of the potential accelerated approval, will that be supported by your interim analysis using PFS or some other data points or time points you can potentially to support accelerated approval? Thank you.
All right. All right, let me see if I can remember all those, Roger. But the first question, let me review the number of events again. The final analysis is done when you have 130 PFS events. So we enroll 150 patients. You have... When you get to 130 events, you can look at the data. That's your final analysis. The interim is done, also driven by events, and it's half the event, 65 events, okay? So that's when you do your interim analysis. Now, the company is not looking at that data. We have an independent data monitoring committee that you know can make the determination of futility, or it can make the determination that, hey, this is a really spectacular result, maybe you wanna go talk to the FDA.
But even if, I mean, unless obviously, the results are incredibly spectacular, you'd have, I guess, an ethical dilemma. You'd wanna go to the FDA, because you wanna make it available. I don't think that's actually realistic. I think more likely, and we've always been planning to do the entire study, because again, the timing, because the events are, the PFS is so quick, that to get to the... We'd almost have the trial fully enrolled when we do the interim analysis. Understand?
Yep, got it. Mm-hmm.
So just waiting a few more months gives you the full approval potential or definitive. And, you know, doing these analysis takes a lot of work and so forth and costs money, et cetera. And you don't wanna compromise the final endpoint, so that has to be done very delicately. Okay? I mean, basically, when you do the interim analysis, you're probably already fully enrolled in the trial. Now, of course, it depends on enrollment rates and things like that. Is that clear?
Yeah, that's clear.
Okay. Now... yeah, I think I've answered your questions. Any other questions in the-
Uh-
Okay. Well, I think that concludes the questions. So I appreciate everybody's participation in this call, especially for people on the West Coast, since it's so early in the morning here. We really look forward to keeping you updated on our progress on this trial and the other activities at the company. Thank you very much.
This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.