Hi, everyone. Welcome to day two of the Cantor Fitzgerald Global Healthcare Conference. My name's Li Watsek, a biotech analyst here at Cantor Fitzgerald. I'm very pleased to welcome our next company, Corvus Pharmaceuticals, for a fireside chat. With me today is Jeff, our Chief Business Officer from the company. Jeff, how about we turn it over to you to walk us through the story?
Sure. Maybe we'll start with who's Corvus.
Yeah.
We're a clinical stage company. We're focused on developing novel immune modulators for the treatment of cancer and immune diseases. Our lead program, soquelitinib, is a novel oral ITK inhibitor.
It's in a registrational phase III trial for peripheral T-cell lymphoma. In addition, we're in a phase II trial called the SIERRA-1 trial for moderate to severe atopic dermatitis. Our partner, Angel Pharmaceuticals, is also studying soquelitinib in an AD trial as well. Soquelitinib represents a pipeline and a product opportunity for us. We have a number of studies planned, including asthma and HS, that will start this year. We have strong composition of matter patents that go through November of 2037, and with pharmaceutical extensions, 2042. The ITK is a platform technology for us, so we have a number of next generations and backups in development.
Okay, great. Maybe let's start with ITK. I think this is a little bit of a novel biology for a lot investors, and you guys have shown some pretty nice data in atopic dermatitis, and we're still learning about how the drug works. I wonder if you can just tell us a little bit about the ITK inhibition and how that differentiates from the other classes that we have seen in the space, for example, like STAT6.
Sure. How are we different? I would say three things. We're an oral tablet, the mechanism of action, as you mentioned, and also the selectivity and safety of the drug. We're an oral tablet, which is important to note because obviously in atopic dermatitis, the primary therapies are injectables, so there's an unmet need for a novel and safe product. In terms of the mechanism of action, ITK stands for interleukin-2-inducible T-cell kinase. It's involved in T-cell receptor signaling and differentiation.
Essentially how we work is that we block Th2 and Th17 and those respective cytokines. Think IL-4, 5, 13, like Dupixent, think IL-17 like Taltz. In addition, what we've shown is that we can shift or switch Th17 cells to become Treg cells. So we feel like we are actually rebalancing the immune system, not suppressing it. In addition, in terms of differentiation, ITK has very limited tissue distribution. It's found only on T-cells and NK cells.
We are highly selective just for ITK, so we expect limited off-target effects, and we've seen that to date in our clinical data. We've had a very good safety profile.
Mm-hmm. I want to follow up on some of the biomarker data that you guys shared, which I think provided pretty interesting insights into how ITK inhibition works in autoimmune diseases.
I wonder if we can just share a little bit about the findings there, the recent data, and how do we match that with the clinical outcomes?
Sure. Well, maybe to start with the clinical outcomes because we've had very strong data to date. Our safety profile is similar to placebo in atopic dermatitis. Our efficacy profile is similar to a JAK or a biologic. It depends whether you're looking at EASI 75 or IGA 0/1.
Relating to the biomarker data, it does support the clinical profile. We showed at the SID data, we had data showing a dose response effect in reducing Th2 cells-
and those respective cytokines, so we reduced IL-4, 5, 13, and TARC. In terms of Th17, we actually showed a reduction in RORγt, which is a transcription factor for IL-17. And we showed an increase in Tregs both on therapy and off therapy, and we saw an increase as well in Bach2, which supports Treg survival. So we think now this biomarker data is supporting our clinical data.
Mm-hmm. I think, Jeff, you mentioned Treg upregulation is a pretty unique aspect of ITK inhibition because that contributes to sort of immune rebalance. Tell us about in your own study, do you see the upregulation just from absolute number perspective or percentage perspective? After you discontinue the drug, do you still see the elevated Treg-
Yeah
upregulation?
It is both.
Yeah.
We see an absolute increase as well as a percentage increase.
But also, we also see no change in the CD8 T cells, so we see no immune suppression. In terms of the durability effect, in our biomarker data, we've seen that increase in Tregs off of therapy throughout the 30 days. And in our clinical data, we've seen clinical effect maintained out to 90 days
And so obviously in the Sierra-1 phase II trial
we'll be studying that by looking at, we have a 90-day off-therapy period where we'll look at that durability of effect.
On the flip side, do you guys think there might be some potential infection risk just with the upregulated Treg?
Yeah. We have seen no immunosuppression or infection at all in our studies.
Keep in mind that soquelitinib is designed to block specifically ITK, and we spare RLK. RLK is resting lymphocyte kinase. It is a redundant pathway for T-cell receptor signaling.
Again, think immune balance, not immune suppression.
Yeah. Okay.
Excuse me. I think that the mechanism is designed really to be very targeted.
Mm-hmm. By the end of the year, you guys are going to share some data from Angel Pharmaceuticals. Can you just walk us through what we should expect to see from that data set? And what would be a good outcome for you guys?
Sure. The Angel data that we'll share in December is cohort one, right?
Which is our low dose.
Right. That study actually mirrors very similar to the Sierra-1 study that we have going on right now. You will see data on 12 weeks of treatment, you will see data on the low dose, and you will also see data on QD and BID. We actually are looking forward to that data because we think it will be supportive of what we might see in the Sierra-1 trial.
My understanding is it is a China study,
meaning you are only enrolling Chinese patients, but your phase II is global. How should we think about putting the China data in the context of your global study?
Yeah.
Any differences that we should keep in mind?
Well, again, the Sierra-1 study is very similar. Sierra-1 is a global study, to your point, but in terms of trial design, inclusion criteria, exclusion criteria, they are all very similar. They are both 12-week studies. They are both looking at 90 days off of therapy.
To your point, it is a different geography. It is a different patient population. There is potentially some different biology there. We do think, again, it would be supportive of what we might see in the Sierra-1 trial.
Mm-hmm. Then in terms of the cohort 1 data, it is going to be a 12-week treatment.
That is going to be a little bit longer. What is your expectation for the efficacy? Just, EASI score-
EASI 75. Should we expect sort of deepening of response relative to the four-week and eight-week treatment duration?
Well, to your point, based on the kinetics that we've shown to date, which is at four and eight weeks, we do see those curves continuing to point down.
It would make sense that we would hopefully see a deepening of response at 12 weeks.
Again, this is the first time we're studying in this long duration, so it'll be very helpful to see that data.
Mm-hmm. Okay. For the Asian patients, I believe there is more of a Th17 component to it. So what do we know about how these patients might respond to an ITK inhibition versus the U.S. patients? Is there any difference that we should keep in mind?
Sure. Yeah, I think with Asian patients, the Th17 biology is a little more prevalent.
That has been published in the literature.
You see more Th17 activation on top of the core Th2 biology.
Otherwise, we do block both Th2 and Th17, so we think it makes sense in terms of the phenotype to study these patients.
Mm-hmm. You don't necessarily expect that there might be some differential response, just from an ITK inhibition perspective in more Th17 driven versus Th2?
We don't know. I mean, that's why we're doing-
Yeah
This is the first time we're studying soquelitinib in Asian patients with AD, so that's something-
we'll look to learn.
Mm-hmm. Will you share biomarker data on Th17? What kind of biomarker data would you share from cohort 1?
Yeah, we will. We'll share probably very similar to what we've already shared.
We'll look at Th2, we'll look at Th17 and the respective cytokines, we'll look at Treg data as well.
But that data will come in 2027.
Okay. But for this year, we will not see biomarker data?
No.
Just the clinical data?
Yeah, just the clinical data.
Okay. Any differences in the patient baseline characteristics between the China trial and your phase I U.S. trial that we should keep in mind when we try to put the data into perspective?
Yeah. Again, I think the trials are very similar in terms of trial design, inclusion criteria, exclusion criteria. Obviously in a Chinese study, the standard of care may be a little different.
The availability of systemics and use of systemics may be less.
Yeah.
It could be that you end up seeing maybe sicker patients with higher baseline EASI scores. But we'll just have to see.
Okay. For your ongoing phase II study, what kind of efficacy and safety profile do you have to show to be able to have a viable product in atopic dermatitis?
Well, I think, again, the unmet need is for a novel oral safe product, and the data we've shown to date, I think is pretty compelling in terms of safety and efficacy.
With that, we do primary market research and talk to physicians. Obviously, showing an effect similar to a biologic is a significant opportunity for us.
But look at the psoriasis market, and you look at Otezla, right?
That is a less effective drug, very safe drug. It does over a couple billion dollars in sales.
Our expectation is that we should be able to reproduce the results we've seen to date, which would be similar to a biologic.
You expect your phase II study will have a similar or comparable outcome as the biologics, like DUPIXENT?
Well, that's what we've shown to date.
Yeah.
Right?
Okay.
If you look at EASI 75, that's more comparable to the JAK in terms of
Yeah
our response. IGA 0/1 was more comparable to a biologic.
As the oral therapy, do you think you need to match biologics in terms of efficacy, or because there's convenience to it, potentially you don't have to aim as high as DUPIXENT?
Well, I think the data we've shown is strong.
I think we're hoping to reproduce what we've shown.
Yeah
You point to an Otezla.
Yeah
In the market, it just needs novel oral safe.
Exactly.
Look at J&J just came into the psoriasis market with icotrokinra, right?
That's going to be a very successful drug, and that's a fairly crowded market. I think it just shows you the demand for oral therapies.
Mm-hmm. Can you update us on the enrollment status of the phase II?
Sure. The trial's on target. We're enrolling as we speak, and we're going to read out that data in Q3 2027, about a year from now.
Okay. We know in atopic dermatitis, placebo effect could be a challenge, and there's variability amongst patients. In the trial, how do you mitigate the placebo response to make sure that it's not going to outperform? What is your assumption for the EASI 75 for the control arm?
Sure. I think three things for controlling for placebo. One is the patient selection, two is the site selection, and three is enrolling more sicker patients. In terms of patient selection, in addition to the PI, we have an independent dermatologist that is also reviewing these patients before they go into the trial, and we are also taking photos, and we are looking at those photos. You want to make sure you have sick enough patients, true moderate to severe patients, going into the trial because the mild patients are what can mess up, especially the placebo response, because it can respond fairly well in there.
In terms of site selection, we are going with sites that have already done these trials. They know how to accurately assess patients' disease status. Third, as a reminder, in our phase I data, we had 35% of patients that were on a prior systemic therapy. In the Sierra-1 trial, we can have up to 40% of patients on a prior systemic therapy.
Okay.
These sicker patients do not respond as well to placebo, so that should help control that as well.
Can you talk a little bit about intermittent dosing?
Sure. I think the durability of effect is a very exciting and interesting part of the soquelitinib story. With that, I will come back to the immediate need is for novel oral safe.
Our plan with soquelitinib is to bring the product to market as quickly as possible. That will mean standard, continuous chronic daily dosing, just like what J&J did with icotrokinra, right? One pill once a day.
With that, in the Sierra-1 trial, we do have that 90-day period where we're looking off therapy. If we see that continued durable effect, we are going to study that in future trials, likely lifecycle management, and that will be part of the follow-on program.
In terms of competition, some companies working on ITK-based molecules, and several companies are working on long-acting biologics. How do you see soquelitinib position against these therapies?
Sure. The long-actings are interesting. AbbVie just paid $11 billion for
Yes
Apogee, right? I think what you see what happens with long-acting is that they actually can grow the market, which is what's happened
in psoriasis.
I expect that the same to happen in the atopic dermatitis market. Being an oral tablet, safe oral tablet, you mentioned positioning. Physicians are telling us that they would likely want to use it in frontline therapy, which would make sense. With that, the psoriasis or the AD market is going to grow two to three times the size of the psoriasis market. Each 1% share is $1 billion in sales. There's actually plenty of room for both orals and long-actings.
Do you have any comments on the other ITK inhibitors in development?
Sure. For the most part, we are the only selective ITK inhibitor in the clinic. Aclaris has an ITK/JAK3 that they're developing.
They've already stated that they're not going forward in.
Yeah
Atopic dermatitis. In terms of just novels and pipeline there, it isn't that busy in terms of the number of novel products. You've got ITK, us, you've got STAT6, and there's probably 10 or 12 of those in development, and you've got IRAK4, but they've actually had some setbacks.
Yeah
in terms of that data. It's not that crowded of a pipeline in terms of novel oral therapies.
Then just beyond atopic dermatitis, you guys are also looking at asthma and HS. Why are these the right indications
Sure
in terms of the expansion?
Well, I think there's a high unmet need in both asthma and HS for an oral product. Second, we follow the science, right?
Asthma is a Th2 driven disease.
We blocked Th2 and Th17, and their respective cytokines, so IL-4, 5 and 13, like DUPIXENT. Well, IL-5 is like FASENRA and NUCALA, right, which are a couple billion USD each drugs. The biology makes sense for asthma. In addition, the overlap with asthma and AD is significant, right? About 25% of adults and 40% of children have both. Of course, DUPIXENT has in their label, both an asthma indication as well as an AD indication.
For HS is primary a Th17 driven disease.
Obviously, you look at BIMZELX, and that drug blocks IL-17A and F. Again, we've shown in preclinical models and clinical models that we can reduce Th17 and IL-17, so that also made sense to us.
Mm-hmm. Jeff, you mentioned there is a good overlap between AD and asthma. In your study, do you have any patients that have both?
Not that I know of. I don't think we have had in the past, and we don't know if we'll have that, of course, in the Sierra-1 trial.
Mm-hmm. Okay.
I think Kymera has mentioned they had a few patients that had overlapped.
Okay.
Yeah.
In asthma, you guys are going to study both Th2 and non-Th2 disease. I think most existing biologics focus primarily on Th2 patients. What gives you the confidence that you can address both populations?
Right. Again, I think because of our mechanism of blocking both Th2 and Th17, it makes sense for us to look there.
Non-T2 or low T2 is primarily driven by a Th17. TEZSPIRE is approved there. There's a high unmet need in that space. It represents probably 30%-40% of the market. With that, the larger market, of course, is still the T2 asthma.
That's a significant opportunity on its own. Also, keep in mind, we've designed the asthma trial to be flexible, so if that non-T2 or low T2 arm is not performing, we can actually drop that arm.
When are we going to see data from the asthma trial?
That's 2028. We're going to start the trial right by the end of the year.
Yeah.
Likely 2028, right, in terms of that.
Okay. In terms of HS, what do you need to see in the initial proof of concept study to validate the Th17 set of story? Obviously, that works. It could open up a lot of opportunities beyond Th2 diseases.
Yeah. I'm sorry, was it HS you were asking?
HS, yes.
Yeah. In HS. Well, I think we haven't studied HS yet.
This will be our first Th17 disease that we're studying soquelitinib.
Yeah.
What we're doing is we've designed a true proof of concept study. It's a smaller study. There's no placebo. It's really looking at safety, of course. We're looking at activity, so we'll look at the HiSCR 50, 75, 90. We'll look at the biomarkers. We'll look at the impact on Th17. Based on that, the holistic of the data, the biomarkers and impact on Th17, we'll make a decision about how we move into phase II.
Is there a bar of success that you guys need to achieve for the HS study? Given it's a single arm, you guys are not going to be compared to a placebo.
Yeah. I think if we're comparable to existing therapies or pipeline therapies, for example, if you look at BIMZELX, non-placebo adjusted I think was a 35% improvement in the HiSCR 75.
It's probably comparable to what's on the market.
35%
Yeah
is what you guys are aiming for. We also know placebo effect is pretty challenging in HS as well. Do you have any thoughts on how you might mitigate this risk if you're going to maybe a phase III study?
Yeah, I think right now we'll have to see if we're active, right,
Yeah
in HS. I think we'll have to figure out that when we move into phase II.
Mm-hmm. Lastly, on your phase III study in PTCL, what would be the read through from the futility analysis in Q1?
Yeah. The futility analysis, as you know, we moved from December into Q1 because it is based on events, so we have to actually have patients progress. That is a good thing that we actually moved into Q1.
Look, it is a g o, no g o, Li. It is a futility analysis, so we take no statistical penalty. If the committee looks at it and says we are safe and we are non-futile, I think that is just a positive signal for the study going forward.
You would not be sharing any sort of safety data from the analysis?
No.
What is the timing of the phase III top line?
Probably Q4 of next year.
Q4.
Of 2028, yeah.
Okay.
Because it is based on events, we are rolling on target, but then you have to wait for these events to happen.
Mm-hmm. How are you guys thinking about the opportunity in PTCL versus in AD, in asthma, and HS? I understand the PTCL may read out earlier than your AD trial, but on the other hand, there is significant opportunity in the I&I indications. Just thinking about how do you approach capital allocation and how you are thinking about balancing different indications.
Sure. Yeah. PTCL has a very, very high unmet need. It is a very difficult disease, and standard care is inadequate, but it actually represents a very near-term commercial opportunity for us. That is actually an indication that we could commercialize ourselves. There is not a very large commercial footprint. With that said, to your point, we understand the size of the opportunity in atopic dermatitis and the total addressable market, so our development and commercial strategy will be to maximize the opportunity for soquelitinib. In terms of capital allocation, we know we raised a couple of hundred million dollars in January. As of June 30, I think we had about $214 million in cash. That gives us a runway through the middle of 2028.
What that does is that pays for the phase III trial PTCL study, it pays for the phase II trial SIERRA-1 , as well as HS, and at least a good chunk of the asthma study.
Of course, once we get the data, we will look at what makes sense to go forward from a commercial standpoint. We could consider partnering as well on the I&I side. At this point, we are really focused on execution and completing these studies and bringing this data to the market.
What would be a good time to have a more, I guess, substantial strategic discussion for you guys?
Post the phase II data, I think.
Post phase II.
Yeah
AD data.
Yeah.
For the HS study, are we going to see data next year or more of a 2027 event?
Target is 2027.
2027.
We're just starting to enroll a patient study now. It's a relatively small study, so target is 2027.
It sounds like 2027 is going to be a pretty big year for you guys.
Yeah.
Okay.
Well, if you look at our news flow rate, in December we have the Angel cohort 1 data.
In Q1 we will have the PTCL futility. In Q2, we would have the cohort 2 Angel data.
Q3, we would have the SIERRA-1 phase III data. So we have a number of key events coming up sequentially over the next few quarters.
Yeah, very good. We will have to wrap up here. Jeff, thank you very much for the time today.
Thank you.