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Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to the Corvus Pharmaceuticals First Quarter 2023 Business Update and Financial Results Conference Call. [Operator Instructions] It is now my pleasure to turn the call over to

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals first quarter 2023 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; James Rosenbaum, Senior Vice President of Research; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences. 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.

Thank you,

Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our business update call. We continue to focus on advancing CPI-818, our ITK inhibitor towards a potential registration Phase 3 randomized trial for T cell lymphoma. We believe this first-in-class drug not only has the potential to be an important new treatment option for patients with relapsed peripheral T cell lymphoma or PTCL, but may also represent a platform opportunity across a broad range of cancers and immune diseases. Recent findings with 818, an important upcoming catalysts are; first, we continue to see good enrollment in our ongoing Phase 1/1b trial now utilizing our recently incorporated biomarker based on absolute lymphocyte count or ALC. And the data generated continues to be encouraging with meaningful objective responses in refractory patients with PTCL. Second, we will present additional interim data from our Phase 1/1b clinical trial in T cell lymphoma at the International Conference on Malignant Lymphoma in Lugano, Switzerland in mid-June. At that meeting, we will also be presenting biopsy and blood data from patients, supporting our proposed novel mechanism of action, which we believe extends the potential clinical indications beyond T cell lymphoma to solid tumors. Third, we intend to meet with the FDA in the second half of the year, likely during the third quarter, to discuss a plan for a registration Phase 3 clinical trial of CPI-818 in relapsed T cell lymphoma. We currently anticipate this would be a randomized trial of approximately 150 patients comparing CPI-818 monotherapy to standard of care chemotherapy agents. The primary endpoint is planned to be progression-free survival. Fourth, assuming a constructive meeting with the FDA, we plan to be Phase 3 ready with 818, including the initiation of the trial before the end of the year. And fifth, recent data presented at AACR indicates that selective ITK blockade enhances immune responses to tumors, including solid tumors, and it achieves this through novel immune mechanisms. At the recent Whistler Global Summit on Hematologic Malignancies, Dr. John Reneau, a hematologist specializing in lymphoma at the Ohio State University Comprehensive Cancer Center and one of the investigators in our 818 clinical trial, presented interim data from the trial. This included response data as of February 15, 2023, which we highlighted on our fourth quarter call. To briefly recap, of 13 patients evaluable for tumor response, we saw durable responses in four patients. Dr. Reneau's presentation also highlighted new evidence, supporting the recently implemented minimum ALC biomarker that we believe will enrich for patients more likely to respond to 818 therapy. The new evidence showed that ALC predicted response to 818, but was not associated with response to chemotherapy treatments that the patients received prior to their therapy with 818. This indicated that the beneficial predictive value of the absolute lymphocyte count biomarker was not due to selection of more favorable patients. We have recently updated our clinical data from the Phase 1/1b trial. As of May 1st, 28 patients were enrolled at the optimum dose of 200 milligrams BID and 19 are evaluable for tumor response. There have been two complete responses, one nodal complete response and three partial responses. two of the patients with partial responses continue on therapy and are doing very well. A total of nine patients remain on therapy, including five that have not yet been evaluated for tumor response. For patients with ALC greater than 900, objective tumor responses were seen in six of 13 that includes complete responses and partial responses with disease control in 11 of 13 that includes CR, PR and stable disease. No responses were seen in six patients with ALC less than 900, 06. The median progression-free survival is 19.9 months versus 2.1 months for patients with ALC above 900 and below 900 respectively. Of course, all new patients being enrolled are required to have an absolute lymphocyte count above 900. The more favorable responses in patients with an ALC greater than 900 is consistent with our data that's stimulating the immune response against the tumor contributes to the activity of CPI-818. We are encouraged by these results and we will continue to enroll patients in order to confirm and extend the findings. I also want to say a word about safety. The 200 milligram BI dose is one-third of the top dose of 600 milligrams BID that we studied in the trial. We have shown that the 200-milligram dose achieved nearly complete ITK target occupancy. No dose-limiting toxicities were seen in any dose group, including 600 milligrams BID. We believe this drug is very well tolerated and it should be easy to combine with other types of cancer therapy. In April, our team presented new preclinical data at the American Association for Cancer Research annual meeting that supports targeting ITK as a new approach for cancer immunotherapy, including the potential to treat both solid and hematologic cancers. The data demonstrated that CPI-818 enhanced immune response to several murine tumors, including models of colon, renal, melanoma and T and B cell lymphomas. In addition, 818 was shown to increase T effector cell infiltration into the tumors and increase the cytolytic capacity of killer T cells. In other findings, 818 was shown to reduce T cell exhaustion, which occurs when T cells are chronically stimulated with antigen, causing them to become reprogrammed and leading to their ineffectiveness. More recent findings show that 818 can reverse already exhausted T cells which revert to active T effector cells with renewed killing capacity. I want to reiterate the key findings from our ongoing Phase 1 trial in T cell lymphoma and now our recent preclinical data because they suggest a significant broad opportunity with 818. We believe selective ITK inhibition may represent a new approach to cancer immunotherapy with a novel mechanism of action that includes; number one, induction of Th1 skewing. number two, increased infiltration of CD8 T effector cells into the tumor. Number three, increased cytolytic capacity of CD8 cells. And 4th, reduction and reversal of T cell exhaustion. We also continue to extend our intellectual property covering CPI-818 and methods of use for the treatment of cancers and autoimmune diseases. We believe we have a strong intellectual property position for 818 and are not aware of any other selective ITK inhibitors currently in clinical development. Composition-of-matter patents have issued in the U.S., Japan, Europe, China and other countries already. Turning briefly to our partner-led programs. The Kidney Cancer Research Consortium led by the University of Texas MD Anderson Cancer Center, is currently enrolling patients in a Phase 1b/2 clinical trial of ciforadenant as a potential first-line therapy for metastatic renal cell cancer in triplet combination with ipilimumab and nivolumab. 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. Based on current timelines, we believe initial data from this trial could be available before the end of 2023. For mupadolimab, our partner, Angel Pharmaceuticals, is enrolling patients in a Phase 1/1b clinical trial in China with mupadolimab alone and together with pembrolizumab in patients with relapsed/refractory non-small cell lung cancer and head and neck squamous cell cancers. In closing, we believe Corvus is uniquely positioned with the prioritization of CPI-818, the most advanced ITK inhibitor in development. We are laser-focused on 818 and are gaining increasing confidence regarding its activity in a broad range of diseases, including cancers and autoimmunity. Our work, together with recent publications from others, are confirming the crucial role that ITK plays in regulation of the immune system. Our initial indication, T cell lymphoma, represents a clear unmet need and a potential path to registration. We are establishing the importance of ITK as a valuable therapeutic target. The key upcoming milestones for our programs include; continued enrollment in our Phase 1/1b trial at the 200 milligram BI dose of CPI-818, including the use of our new biomarker, absolute lymphocyte count; updated data from our CPI-818 Phase 1 T cell lymphoma trial will be presented at Lugano in June; meeting with FDA to discuss a randomized Phase 3 trial in the third quarter; and from our partner-driven programs, we anticipate interim data from the ciforadenant trial before the end of 2023. 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 Instructions] Our first question comes from Aydin Huseynov with Ladenburg Thalmann.

Thank you. Good afternoon, everyone. Congratulations, Richard and team with the update. And it seems like you have -- I just want to confirm, you have two more responses, partial responses from the new batch of data?

We have, let's see, two more responses.

Compared to the prior update call that we had at the end of March, right?

Correct.

So let me ask you about progression-free survival. You mentioned 19.9 months. So based on how many patients with this calculation? Could you give us a little bit more clarity on this?

So that's based on 13 patients.

And regarding meeting with the FDA, I think that's a little bit more clarity. This time, you mentioned that this is going to happen within third quarter. So what do you expect from this meeting? So you're planning a 150-patient trial, randomized trial. Do you expect any new details other than what you planned? Meaning, 1:1 randomization or some other randomization and the PFS primary endpoint. Do you think anything -- any surprises will come out of this meeting?

I do not expect any surprises. I think our protocol is pretty straightforward. It's a randomized controlled trial. What we're looking for at this meeting is agreement that this trial is properly designed, and if positive, would support registration of the product for T cell lymphoma. I think things that we want to discuss with them are the choice of standard therapies in the control arm. So as I mentioned, it will be monotherapy with 818 versus a standard therapy for T cell lymphoma. We're thinking now that that would include about three drugs. Belinostat and Pralatrexate are approved for relapsed T cell lymphoma, as you know. And one other drug will probably add to the standard therapy list would be gemcitabine, which is widely used for -- in fact, more commonly used than the approved drugs for peripheral T cell lymphoma. So investigators, if their patient is randomized with the control arm, the investigator discretion would allow them to pick one of those three drugs. So Aydin, really I think it's just getting an agreement on the design and the standard therapy. But since two of the drugs are already approved for relapsed T cell lymphoma and gemcitabine is used by majority of people, at least in the United States, I don't think that there will be too much controversy there. Also, the median PFS for these kinds of trials, there have been a few done in the past, is usually around three or four months. So I think that we have a pretty good expectation of what the control group would look like.

So it's kind of historical three, four months versus 20 months that you showed so far. But on ORR side, so far, the back on the envelope calculation show that 46% or something around this on the ALC above 900 group for your drug. But what is the -- can you remind us what is the historical ORR on the chemotherapy and approved drug side?

25% and very short responses. One of the other -- yes, by the way, the 40%, 50% response we're seeing, the PRs, I feel confident those PRs are still responding, for example, as you saw some of that data the other day. So obviously, some of that can change with time. As I mentioned, the ORR with the standard agents is about 25%. That's pretty reproducible. It's short-lived. And one of the other things about these control agents is they're very difficult to give and they're very toxic. Belinostat, for example, one of the approved agents is an intravenous infusion, five days in a row, every three weeks. Pralatrexate is a weekly injection, I think six out of seven weeks, but you have to pay meticulous attention to vitamin B12 and folate metabolism, administer that 10 days before and 10 days after. It's quite a significant hassle. And those drugs have significant toxicity, bone marrow suppression -- being nausea, vomiting, bone marrow suppression and we really haven't seen any of that. I should add, quality of life will also be one of the endpoints that we'll be following. Obviously, PFS is our primary endpoint, but secondary endpoints are response rate, overall survival, duration of response and a quality of life assessment as well.

Richard, given the difficulty in enrollment and with administration of this chemotherapy drug, would you expect the FDA proposing 2:1 randomization?

I'm sorry. Could you repeat that?

To propose 2:1 randomization as opposed to 1:1?

No, I wouldn't expect that. I don't think that would be -- I doubt they would do that, because first of all, 1:1 statistically is a more powerful study and we're going to allow cross over. So in patients on the control arm, when they progress, they can cross over to the treatment.

Okay. All right. Okay Richard, congratulations with the update and congratulations with additional responses. Thank you so much.

Thank you. Our next question comes from Li Watsek with Cantor Fitzgerald.

Hi, this is Rosemary on for Li. Thanks for taking our questions. Just two from us. So for 818, you've mentioned potential in immune diseases as well. So is your plan to generate some initial data there or would you consider directly going to find a partner for those indications? And then for ciforadenant, it seems like the timeline has shifted a bit. So could you possibly give us some color around the reason? Whether it's due to enrollment or just wanting to have a longer follow-up or something?

First question was...

818 in immune diseases.

Yes. So we are very excited about 818's activity in cancer. The AACR data, if you haven't seen that, you should take a look at it because some really striking findings in there. We're also very impressed now that there's been another -- a couple of scientific groups in animal models that have shown that blocking ITK either genetically or using our drug can enhance anti-tumor responses. So we are laser-focused now on T cell lymphoma first and then solid tumors. I've already got a couple of medical centers who are really interested in getting 818 into a solid tumor study. So that's going to take priority over the immune diseases because I think that we have data there already obviously in the clinic. We know a lot about it. And I think cancer in terms of product approval and development pathway is something that is a little bit easier for us. Now in terms of immune diseases, we're still considering whether or not to move into immune diseases with 818 later this year. However, I think that's going to depend on the progress we make with the cancer in the cancer area. Now one of the things that I should also mention is that we have several back-up compounds or next-generation compounds to 818 that block ITK in slightly different ways. Some of them have similar chemical structure. Some of them have different chemical structures. But we've been doing some additional work on these ITK inhibitors and it's really turning out to be fascinating how we can adjust the biologic properties. And I think that we can probably in the future make even -- make drugs that are even better designed specifically for certain autoimmune diseases. Now your next question on the ciforadenant, no slowdown there. It's being done. I don't know what you're referring to, but MD Anderson is enrolling frontline kidney cancer patients. We have a meeting at ASCO to review all that stuff. Other institutions are getting on board. It's an open-label trial and the endpoint is CR, CR complete responses and what we call, deep PRs. And we can -- we'll get a feel, CRs and deep PRs are about 30% in the literature from MD Anderson actually. So we'd be looking to see more than 30% CR, deep PR. And by the way, CRs are only about 10%. So seeing a couple of CRs would also be highly encouraging. And then finally, a word on cifo and putting it together with ipi/nivo, that wasn't done just to add a drug. It was done based on a publication we had in 2018 which showed that the biology, the immunobiology was such that adenosine A2 antagonism really, really goes well with anti-CTLA-4 therapy. And I can go into the reasons for that another time, but I think that's also a new biology. In other words, it's not just one plus one equals two. It's one plus one equals three I think.

Got it. Thanks so much. Thank you.

Thank you. Our next question comes from Mara Goldstein with Mizuho.

Hi, this is Jerry Gong on for Mara Goldstein. Thanks for taking my questions and congrats on the updates. So first, for the 19 evaluable CPI-818 patients. Can you show the average number of scans patients have had? And if the additional six efficacy evaluable patients are all at the 200 milligram dose?

The number of scans? You mean the average number of scans? What are you talking about? Patients get scanned every two to three months.

I guess, like what is the -- I guess, median time, like the time patients have been on study for, for the 19 efficacy evaluable patients?

The median time of therapy, I don't have handy right now. But if you look back at our last conference call, there was a waterfall plot and a swimmer plot on there. If you go look at that, Jerry, you'll see detailed information on how long those people have been on therapy. If I had to guess now, again, I don't have that information handy. Six months or more, but we have several patients still on therapy, including PRs. Actually, I think -- it is coming back to me now. Hang on a second. The number of patients in our study who are on therapy more than six months is something like 65%. So that means the median would be more than that I guess. But look at our -- look at the data from our last call.

We'll do. I guess, are all patients -- are the additional six efficacy evaluable patients and all remaining patients, I guess, even on study still, are they all at the new 200 milligram dose?

Yes.

For the five remaining patients without initial scan, can you share what their ALC is?

I think they're all above 900. We started implementing -- yes, they're all above 900, because we started implementing that a few months ago, December I think.

And final question for me. So for the ongoing -- or I guess a follow-up to the ciforadenant question earlier. How many patients do you expect to be able to share data from by the end of the year?

With some follow-up, more than 10.

Got it. Awesome. Thanks for taking our questions. And congrats on the update again.

All right. Thank you - thank you Mara Goldstein equivalent, Jerry, I guess.

Thank you. Our next question comes from Roger Song with Jefferies.

All right. Great. Thanks for update and taking all question. A quick one. So for the Phase 3 818 in TCL, understanding you will do the PFS as the primary endpoint. Is that possible you will take some internal look at the ORR or some other endpoints potentially for early fighting or interim just that data look? And also for the solid tumor plan, so with this AACR data, do you have any timeline for the clinical plan there? Thank you.

So yes, we do have plans to do an interim look at the data and evaluate response rate consistent with recent guidelines that came from FDA on accelerated approval. I don't want to make any promises about that. And the reason is that the median time to progression in the controls is so short that I'm not sure there's a big time difference between when you would look early for response rate versus waiting for the final event-driven endpoint. You follow me?

Yes, I got you.

So I'm not sure it makes a big difference, but of course we would look at that. And that's another thing of course to be discussed with FDA. But I would say, in this particular disease, it almost doesn't matter so much because those -- the timing is not going to be that different. I mean, it's relative. It might be a few months difference. That could be -- I guess, that could be significant. And then your question on the solid tumors, right now, we don't have any definitive plans as to when we would start a solid tumor trial. But we've been talking with people about diseases like renal cancer, lung cancer, melanoma and looking at the drug in PD-1-resistant patients, for example. The good news is, there's a lot of patients who have received anti-PD-1, PD-L1 agents, thousands and thousands. The bad news is, there's a lot of resistant patients. Most patients eventually fail it, either don't respond or have a recurrence. And so one of the things we're particularly interested is in that mechanism of resistance. And so those are discussions still going on. Obviously, we're -- as I mentioned in my talk, we're laser-focused on the T cell lymphoma work right now and getting that going as quickly as possible.

Right, thank you. Thank you, Rich.

Thanks.

Thank you. This concludes our question and answer session. I would like to turn the conference back over to Richard Miller for any closing remarks.

Thank you, operator, and thank you everyone for participating in the call. We look forward to updating you in the future on the progress we make. Thanks again. Bye.