Corvus Pharmaceuticals Inc (CRVS) 2022 Q3 法說會逐字稿

Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to the Corvus Pharmaceuticals Third Quarter 2022 Business Update and Financial Results Conference Call. (Operator Instructions) Later, we will conduct a question-and-answer session and instructions will follow at that time.

It is now my pleasure to turn the conference over to Zack Kubow of Real Chemistry. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals third quarter 2022 business update and financial results conference call. On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; and James Rosenbaum, Senior Vice President of Research.

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' quarterly report on Form 10-Q, which was filed today with the SEC 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 Leiv Lea. Leiv?

Thank you, Zack. I will begin with a quick overview of our third quarter 2022 financials and then turn the call over to Richard for a business update. At September 30, 2022, Corvus had cash, cash equivalents and marketable securities totaling $49.6 million as compared to $69.5 million at December 31, 2021. Based on the recent prioritization of our clinical stage pipeline plans, we believe our cash will provide runway into early 2024.

Research and development expenses in the third quarter of 2022 totaled $10.4 million compared to $7 million for the same period in 2021. The increase of $3.4 million was primarily related to a $5.5 million increase in drug manufacturing costs, which was partially offset by a $2.2 million reduction in clinical trial costs.

As you can see, we continue to prudently manage our cash burn rate while advancing our portfolio of product candidates. We were able to achieve this by careful utilization of experienced personnel, leveraging external resources and establishing collaborations that help support development of our products.

Examples of these collaborations are Angel Pharmaceuticals, our partner in China now involved in clinical trials with CPI-818 and mupadolimab, and the Kidney Cancer Consortium, which is conducting a first-line trial with ciforadenant in combination with ipilimumab and nivolumab for renal cell cancer.

The net loss for the third quarter of 2022 was $14.8 million compared to a net loss of $10.7 million for the same period in 2021. Total stock compensation expense for the third quarter of 2022 was $0.7 million compared to $1.1 million for the same period in 2021.

I'll now turn the call over to Richard, who will elaborate on our strategy and plans.

Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our third quarter 2022 business update. We are excited to share an update on our clinical programs, which aim to bring new therapeutic approaches to a range of diseases, including cancer and immune-mediated diseases. We intend to accomplish this by modulating the activity of immune cells utilizing our precisely targeted drugs.

As we approach the end of the year, we are positioned for a series of potential catalysts across our portfolio with the goal of expanding our ability to help more patients. Our lead program is CPI-818, our ITK inhibitor that we believe has diverse opportunities across oncology, autoimmunity, fibrotic diseases and allergic diseases.

CPI-818 is a covalent ITK inhibitor and binds to ITK similar to the way ibrutinib binds to BTK. We believe the opportunity with CPI-818 to target T cells is similar to that of BTK inhibitors and anti-CD20 antibodies that target B cells for the treatment of both B-cell lymphomas and autoimmune diseases.

Importantly, members of the Corvus team play crucial roles in the discovery and development of these agents. We are not aware of any other ITK inhibitors currently in clinical development. CPI-818 is currently being studied in a Phase I/Ib clinical trial in patients with relapsed T-cell lymphoma. We have identified an optimal dose of 200 milligrams oral twice per day, and Corvus, along with our partner in China, Angel Pharmaceuticals are expanding a cohort of patients focused on this dose.

We announced this morning that data from this study will be presented in a poster presentation at the American Society of Hematology Meeting on December 12. We previously reported that as of July 22, there were 8 evaluable patients treated at the 200 milligram BID dose. We had 1 complete response, 1 nodal complete response, 1 partial response and 5 patients with stable disease. We view these results positively given the severity of the disease.

These patients had a median of 4 prior therapies, and the published overall survival of first relapsed T-cell lymphoma is reported to be a median of 5.6 months, and the progression-free survival is less than 3 months in first relapse. Now our patients had 3 or 4 relapses. The update at ASH will include more mature safety and antitumor activity for patients in this 200 milligram cohort. In addition, the presentation will include analyses of CPI-818 immune modulation of normal T cells as measured by changes in Th1, Th2, Th17 cells and what are known as terminally differentiated T effector memory cells and various serum cytokines in blood samples from these patients.

These immunomodulatory effects has very important implications for therapy of autoimmune and allergic diseases. Advancing our strategy for CPI-818 in autoimmune and allergy is a major focus for the company being led by Dr. James Rosenbaum, who joined us in July. Based on our ongoing work, we are increasingly confident that we will initiate clinical trials in autoimmune and/or allergic diseases in the first half of 2023.

We also plan to initiate a Phase II trial of CPI-818 in T-cell lymphoma in 2023. Dr. Rosenbaum will elaborate on more of this during our Q&A if we have time. We plan to host a conference call and webcast on December 12 at the ASH meeting to discuss the CPI-818 data along with updates on our plans for CPI-818 in autoimmune disease and allergy. Initial details about this call are included in our ASH curtain raiser and third quarter results press releases today and more specifics will be announced closer to the time of the event.

Moving on to ciforadenant, our adenosine 2a receptor antagonist. In October, the Kidney Cancer Research Consortium initiated a Phase Ib/II clinical trial evaluating ciforadenant as a potential first-line therapy for metastatic renal cell cancer in a triplet combination with ipilimumab and nivolumab. The trial was being led by the University of Texas MD Anderson Cancer Center, which is one of the 7 partner institutions that make up the consortium.

All the members are premier institutions and others include Beth Israel Deaconess, Duke University, University of Michigan, University of Pennsylvania, UT Southwestern and Vanderbilt. The trial is based on our publication in 2018, showing synergy of ciforadenant with anti-CTLA-4 antibody in preclinical tumor models, and data from our Phase I studies demonstrating antitumor activity of cifo. The trial is planned to enroll up to 60 patients with newly diagnosed or recurrent Stage IV renal cell cancer that have not received any prior systemic therapy.

Patients will receive cifo 100 milligrams oral twice daily continuously in combination with ipi 1 milligram per kilogram once every 3 weeks for 4 doses and nivolumab 3 milligram -- 3 mgs/kg given every 3 weeks. These are fairly standard regimens for this disease.

The Phase Ib run-in portion will enroll 8 patients with primary end points of safety, tolerability and antitumor activity. In the Phase II portion, the primary endpoint is the percent of patients who achieve deep responses. This is defined as CRs, complete responses and partial responses that have greater than 50% reduction in tumor volume, reflecting our goal to raise the plateau on the progression-free survival and overall survival by adding cifo.

Historical data from these institutions I just mentioned has shown that deep responses correlate with prolonged progression-free survival and is seen in approximately 32% of patients receiving ipi/nivo. As a reminder, this is an open-label single-arm trial, so we anticipate that we will get a good feel for efficacy early in the trial.

Next is mupadolimab, our B cell activating anti-CD73 antibody. We believe mupadolimab is differentiated in the CD73 landscape as it binds to a unique epitope on the CD73 protein which on B cells results in their activation and differentiation into antibody-producing plasma cells and into memory B cells. We think that the immunomodulatory properties provide a unique mechanism of action in immunotherapy.

We anticipate that in the near term, our partner, Angel Pharmaceuticals will initiate a Phase I/Ib clinical trial in China with mupadolimab alone and together with pembrolizumab in patients with relapsed/refractory non-small cell lung cancer and patients with head and neck squamous cell cancers. In the U.S., we remain paused but ready to advance mupadolimab into a randomized controlled Phase II trial as we continue to focus our resources on the development of CPI-818.

In closing, we believe Corvus is well positioned with several potential catalysts for our programs in the next 12 months, combined with a cash runway into early 2024. Key upcoming milestones include new CPI-818 Phase I data will be presented at ASH in December. As a reminder, this study includes Angel Pharmaceuticals, who is responsible for that portion of the study in China, and we are planning a Phase II trial for T-cell lymphoma in 2023.

CPI-818 development in autoimmune and allergy is ongoing with the goal of initiating clinical trials in the first half of 2023. With ciforadenant, Phase Ib/II trial for first-line renal cell cancer, we have the potential for a read on clinical activity, response rate, early in enrollment since it is an open-label study. And the development of mupadolimab is continuing in China with the pending initiation of a Phase I trial by Angel Pharmaceuticals, which could yield new data next year. We look forward to providing updates on these key initiatives in the coming quarters.

I will now turn the call over to the operator for questions-and-answer period. Operator?

(Operator Instructions) Our first question today will come from Mara Goldstein of Mizuho.

This is Jerry Gong on for Mara Goldstein. Congratulations on the accepted abstract. For the ongoing CPI-818 trial, can you confirm if you are continuing to monitor any patients in higher dose cohorts? And can you provide any color as for the breakdown of CPI-818 patients on the trial in China via like U.S. or Australia?

We are done enrolling patients in the higher dose cohorts, that is the 400 and 600 milligram cohorts. What we will be primarily focused on at the ASH meeting is the ongoing enrollment and follow-up of our patients in the 200 milligram cohort. One thing to emphasize based on your question is that we have identified a very interesting dose response relationship for this drug.

And 200 milligrams is a dose, probably 200 milligrams to 400 milligrams is a dose that has, we think very important effects on T cell differentiation. This has never been described previously. We think we have interesting intellectual property around this, I might add. And we will be hitting that hard at the ASH meeting, not only in terms of the antitumor effects but also the effects on normal T cell biology. The second question was -- Jerry, what was your second question?

Yes. Sorry. So can you provide any color as for the breakdown CPI-818 patients on the trial in China via in the U.S. or Australia?

Most of the patients who've been treated on our trial are from the U.S., some from Australia and South Korea. More recently, enrollment has been coming significantly from China as well as here.

Got you. And can I ask one more follow-up? So China has recently reiterated that there's zero-COVID policy. So how might this affect current clinical trials in China, including CPI-818 and the Mupa trial that just recently got IND approval?

So we've been monitoring that very carefully. I don't believe that the zero-COVID policy had a substantial impact on our trial in China. We're only at what 4 or 5 centers now and some of those centers just opened up recently. And in the last few weeks, it appears that the zero-COVID policy or the COVID pandemic in China has subsided. So right now, we're not seeing any significant impact on that.

Our next question today will come from Roger [Song] of Jefferies.

Great. Congrats for the progress. Maybe, Rich, a couple of questions for the CPI-818. Since I'm looking at the press release and your prepared remarks, you're prioritizing the autoimmune or the allergic disease for CPI-818. Maybe just remind us what is the biology CPI-818 is trying to address for those disease? And also can you just confirm with us what will be the next step for CPI-818, particularly for the U.S. and global outside of China?

Okay. So, first of all, let me emphasize that T-cell lymphoma continues to be our main thrust. We still view T-cell lymphomas at the most efficient, most effective shortest path to approval for a bad disease, we think our drug can help patients with this disease. We continue to believe that we can have a significant effect in -- as a monotherapy in relapsed disease. Of course, over the longer-term, we would be looking to combine it in earlier-stage patients with lymphoma.

So I want to emphasize that T-cell lymphoma is still the main thrust of our activities. However, it is very, very difficult to ignore the profound effects we see in our lymphoma patients, very reminiscent of what myself and my team saw when we started treating lymphoma patients with things like Rituxan and ibrutinib, we started to notice that there were effects on other B cells in that case, in the case of ITK, it's T cells that could really be important for a bunch of other diseases.

So the effects that we see and that we'll talk about at ASH, and there's a lot of really cool stuff on our poster at ASH. What has to do with the effects of CPI-818 on the differentiation of what are called T helper cells. No question that this causes skewing or biasing to Th1 T cells. Th1 cells are important in killing cancer cells and killing virally infected cells. And there is no question, we have in vivo evidence of this. We have in vitro evidence of this that we can cause dramatic inhibition of Th2 and its resulting cytokines like IL-4, IL-5, IL-13.

These are cytokines that are pathologic in diseases like asthma, atopic dermatitis, scleroderma and many, many other diseases. So the strategy is to blast forward with T-cell lymphoma as best we can, but concomitantly, invest our resources in initiating autoimmune disease trials in 2023. And I think this might be a good point to turn it over to Dr. Rosenbaum, who can maybe provide a little bit more detail on the question you're asking.

So the key for us, given the large number of opportunities we have in autoimmunity, the key for us is, can we pick an autoimmune disease or allergic disease where we can get in the clinic quickly, get relatively short endpoints and get meaningful clinical data in 2023. And that's what we intend to do. Now we're going to give a lot more details on this at our ASH conference call. But Jim, maybe you want to add to that? (inaudible).

Thanks, Richard. Sure. My pleasure. As you said, CPI-818 binds covalently to ITK, and ITK is a T cell enzyme that is critical for the generation of so-called Th2 cells, the subset of T cells that are vital in allergic and atopic disease and fibrotic disease. And right now, we're leaning toward atopic dermatitis as our first clinical target because the scientific rationale that Th2 cells are involved in that disease is overwhelming.

In addition, it's an unmet clinical need with drugs that are only partly effective or sometimes effective and often drugs that need to be given by injection. CPI-818, of course, is oral. It has a unique mechanism of action. And attractively, we believe that we can find clinical efficacy within 28 days. So we intend to be in clinical trials in the spring of 2023, and we expect to have results that will shed light on efficacy before the end of 2023. And as you said, we'll provide more details at the ASH conference on December 12.

Thanks, Jim. So Roger, any follow-up questions on that?

Yes. I think that's great. I mean I look forward to the data from both lymphoma and autoimmune disease. So maybe just a follow-up for the Mupa, understanding you're prioritizing CPI-818, but also you are advancing the Mupa in China. So maybe just when in the [world] condition, we will see the update for the Mupa development in the U.S. or outside of China?

Okay. So we expect to start enrolling patients in China before the end of the year. IND has been approved in China. And Angel already has several very good clinical sites lined up with prominent lung cancer and head and neck cancer experts. Of course, those studies are non-randomized trials. But it will include Mupa alone and Mupa together with pembro.

Now in the U.S., as you know, we have put our randomized Phase II trial plans on hold. That was a study in frontline lung cancer. I don't have any definite plans as to when we would start -- restart that in the U.S. Again, we're highly focused now on CPI-818. Obviously, the situation could change, because we have a protocol, we have sites ready, we have a collaboration, we're ready to go with our Mupa Phase II trial, everything is in place, ready to go.

It's just that we paused that because we were, number one, trying to conserve some capital, and number two, really looking to get some results from others who are working in this field as well. We're -- we've always been suffering from being the pioneer. So in this case, we have been the pioneer, but now we're going to wait for some of these other things to play out.

Now as, of course, Roger, as you know, there's other lung cancer studies, TIGIT antibodies and other things that are being looked at. Those results will be coming along soon in the next several months. Those could also impact our plans.

Got it. Yes. So...

Okay. Now as long as we're talking about -- because that's a good question. You could ask the same thing about ciforadenant or ciforadenant, my team is always criticizing me for my pronounciation. In any event, cifo, cifo's use in frontline with ipi/nivo is a really interesting trial. The science behind that and the rationale is quite fascinating. And we have uncovered together with some of our collaborators a really novel mechanism of action.

That's going to make perfect sense once we lay it out for people. We're not willing to do that yet because we want to fortify our intellectual property, et cetera. But it turns out that there's really something special about that. And I'm really looking forward to that data. The other thing about that trial is that it's based on CR and what we call deep PRs. There have already been a couple of publications that deep PRs and CRs correlate with PFS and OS.

So most people who respond are going to respond in 3 months. So we would know very quickly, very early in the study, whether we're having an impact on this deep PR/CR rate, which I mentioned in my remarks is, in the literature is about 32%.

All right?

Awesome. Yes. Great. Thank you for the additional color for the cifo. That's great.

All right. (Operator Instructions) And our next question today will come from Li Watsek of Cantor Fitzgerald.

This is [Rosemary] on for Li. I just have 2 quick ones. So for CPI-818, how fast do you think you could move into Phase II? And have you had any discussions with the FDA on potential path to approval? And then one on cifo, ciforadenant. So with the combo with ipi and nivo and frontline renal cell, could you give us a sense of what would be good data in your view?

Okay. The first question on T-cell lymphoma. So again, our plans would be to go into patient's monotherapy, refractory peripheral T-cell lymphomas and cutaneous T-cell lymphomas. We have a protocol drafted already. It's circulating around 2 investigators. We have not yet reviewed that protocol with the FDA. We would intend to start that trial probably midyear.

And again, that would be a single-arm trial. We can talk more about that at the ASH meeting in terms of what our thoughts are on size. But you're probably looking at a trial of 100 patients, 150 patients, something like that. The second question, what would be success, that's a great question because we have that, I mentioned in my remarks that a couple of papers have shown that deep PR and CR is 32%. So I want to beat 32%. Very simple.

Anything above 32%?

Well, I mean, I'd rather beat 52%, but...

Right, of course.

But yes, I mean, 32% is your basically historical data, recent historical data.

Okay. Got it.

(Operator Instructions) -- go ahead.

Yes, just to add one thing that even though everybody is excited about immuno-oncology and immunotherapies, it's worth highlighting that -- and there's no question that PFS and OS in many cases and response rates has increased, especially in things like renal cell cancer. But interestingly, the complete remission rate, complete remission rate has not really increased that much.

And most good oncologists want CRs, because CRs can turn into cures, PRs never turn into cures, almost never. So that's what you'll be looking at is CR and deep PR rate, response rate. Okay. Sorry, operator, any other...

No, we have no further questions at this time.

Okay. All right.

So -- go ahead. I can turn back to you or Dr. Richard Miller for closing. Thank you.

Okay. Well, thank you, operator. First of all, thank you, everyone, for listening in on the call. Appreciate your interest. We look forward to our next call on December 12 from New Orleans. And hope to give you an update there, as well as the usual quarterly updates as we move through the end of the year and 2023. Thank you very much.

The conference has now concluded at this time. We do thank you for attending today's presentation. You may now disconnect.