Earnings Call Transcript - CRVS Q1 2023

Operator, Operator

Good afternoon, everyone. Thank you for being here, and welcome to the Corvus Pharmaceuticals First Quarter 2023 Business Update and Financial Results Conference Call. I would now like to hand the call over to Zack Kubow of Real Chemistry.

Zack Kubow, Presenter

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.

Leiv Lea, CFO

Thank you, Zack. I will begin with a quick overview of our first quarter 2023 financials and then turn the call over to Richard for a business update. Research and development expenses in the first quarter 2023 totaled $4.6 million compared to $5.1 million for the same period in 2022. The decrease of $0.5 million was primarily related to lower clinical trial and drug manufacturing costs. The net loss for the first quarter of 2023 was $7.9 million, which included a $1.7 million non-cash loss related to Angel Pharmaceuticals compared to a net loss of $8.3 million, which included a $1.0 million non-cash loss related to Angel for the same period in 2022. Total stock compensation expense for the first quarter of 2023 was $0.5 million compared to $0.7 million in the same period in 2022. At March 31, 2023, Corvus had cash, cash equivalents and marketable securities totaling $34.5 million as compared to $42.3 million at December 31, 2022. Looking forward, we continue to expect full year 2023 net cash used in operating activities to be between $19 million and $22 million. At the midpoint, this is a 24% decrease from 2022, demonstrating our continued focus on prudently managing our cash burn rate by focusing on our most promising opportunities and establishing collaborations that help support development of our product candidates. Based upon this trend and our focus on CPI-818, we believe our cash will provide runway into 2024. I will now turn the call over to Richard, who will elaborate on our strategy and plans.

Richard Miller, CEO

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 catalyst 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. 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 BID 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 fourth, 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 BID 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 the questions and answer period.

Operator, Operator

Our first question comes from Aydin Huseynov with Ladenburg Thalmann.

Aydin Huseynov, Analyst

Thank you. Good afternoon, everyone. Congratulations, Richard and team on the update. I just want to confirm, do you have two more partial responses from the new batch of data?

Richard Miller, CEO

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

Aydin Huseynov, Analyst

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

Richard Miller, CEO

Correct.

Aydin Huseynov, Analyst

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?

Richard Miller, CEO

So that's based on 13 patients.

Aydin Huseynov, Analyst

Regarding the meeting with the FDA, there seems to be a bit more clarity this time, as you've mentioned it will occur in the third quarter. What are your expectations for this meeting? You're planning a 150-patient randomized trial. Do you anticipate any new information beyond your current plans, such as the randomization ratio or the primary endpoint of progression-free survival? Do you expect any surprises from this meeting?

Richard Miller, CEO

I do not expect any surprises. I believe our protocol is quite clear. It's a randomized controlled trial, and at this meeting, we seek agreement that the trial is well-designed and, if successful, would support the registration of the product for T cell lymphoma. We want to discuss the choice of standard therapies in the control arm. Currently, we are considering monotherapy with 818 compared to a standard therapy for T cell lymphoma, which will likely include about three drugs. As you know, Belinostat and Pralatrexate are approved for relapsed T cell lymphoma. We also plan to include gemcitabine, which is more commonly used for peripheral T cell lymphoma than the approved drugs. If a patient is randomized to the control arm, the investigator will have the discretion to select one of those three drugs. Essentially, we aim to achieve consensus on the trial design and standard therapies. Since two of the drugs are already approved for relapsed T cell lymphoma and gemcitabine is widely utilized, especially in the United States, I don't anticipate much controversy. Additionally, the median progression-free survival for similar trials in the past has typically been around three to four months, so we have a solid expectation of what the control group will resemble.

Aydin Huseynov, Analyst

So it's kind of a comparison of the last three to four months with the 20 months you've presented so far. On the ORR side, the rough calculations indicate around 46% in the ALC above 900 group for your drug. Can you remind us of the historical ORR for chemotherapy and approved drugs?

Richard Miller, CEO

The overall response rate with the standard agents is approximately 25%, which tends to be consistent but not long-lasting. Additionally, these control agents can be challenging to administer and often come with significant toxicity. For instance, Belinostat, an approved treatment, requires intravenous infusions for five consecutive days every three weeks, while Pralatrexate involves weekly injections for about six out of seven weeks, necessitating careful management of vitamin B12 and folate levels both before and after treatment. These drugs often lead to side effects such as nausea, vomiting, and bone marrow suppression, which we have not encountered with our approach. Quality of life will also be an important factor that we will monitor. While progression-free survival is our primary endpoint, we will also assess response rates, overall survival, duration of response, and quality of life as secondary endpoints.

Aydin Huseynov, Analyst

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

Richard Miller, CEO

I'm sorry. Could you repeat that?

Aydin Huseynov, Analyst

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

Richard Miller, CEO

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

Aydin Huseynov, Analyst

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

Operator, Operator

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

Rosemary Li, Analyst

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?

Richard Miller, CEO

First question was... 818 in immune diseases. Yes. We are quite enthusiastic about 818's developments in cancer. The AACR data is impressive and worth reviewing due to its compelling findings. We're encouraged that several scientific groups using animal models have shown that blocking ITK, either through genetic means or our drug, can improve anti-tumor responses. Our primary focus now is on T cell lymphoma, followed by solid tumors. I have already connected with several medical centers eager to include 818 in solid tumor studies, which will take precedence over immune diseases since we already have considerable data in that area. I believe pursuing cancer offers a clearer path for product approval and development. Regarding immune diseases, we are still contemplating whether to advance with 818 in that area later this year, depending on our progress in cancer. Additionally, we have several back-up or next-generation compounds that block ITK in various ways, with some sharing chemical structures and others differing. Our ongoing work on these ITK inhibitors is proving to be intriguing, and I believe we could potentially develop drugs better tailored to specific autoimmune diseases in the future. As for ciforadenant, there's no slowdown. MD Anderson is actively enrolling frontline kidney cancer patients, and we plan to discuss this at an upcoming ASCO meeting. Other institutions are also participating. It’s an open-label trial with endpoints focused on complete responses and what we refer to as deep partial responses. Literature from MD Anderson suggests CRs and deep PRs are approximately 30%, so we're aiming for results above that benchmark. Notably, CRs alone are around 10%, so observing a few would be very promising. Lastly, regarding the combination of cifo with ipi/nivo, this was not just to add another drug but was based on our 2018 publication highlighting that adenosine A2 antagonism works effectively with anti-CTLA-4 therapy. The interaction suggests a synergistic effect, where one plus one leads to more than just two.

Rosemary Li, Analyst

Got it. Thanks so much. Thank you.

Operator, Operator

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

Jerry Gong, Analyst

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?

Richard Miller, CEO

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

Jerry Gong, Analyst

What is the median time that patients have been on the study for the 19 efficacy evaluable patients?

Richard Miller, CEO

I don't have the median time of therapy available right now. However, if you refer to our last conference call, you'll find a waterfall plot and a swimmer plot that detail the duration of therapy for those patients. If I had to estimate, I would say it's six months or more, but several patients are still receiving therapy, including those with partial responses. Actually, I just remembered that around 65% of the patients in our study have been on therapy for more than six months. This suggests that the median time would be greater than that. Be sure to review the data from our last call.

Jerry Gong, Analyst

Are all the additional six efficacy evaluable patients and all remaining patients, even those still on the study, at the new 200 milligram dose?

Richard Miller, CEO

Yes.

Jerry Gong, Analyst

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

Richard Miller, CEO

I think they are all above 900. We started implementing that a few months ago, I believe in December.

Jerry Gong, Analyst

And final question for me. For the ongoing or 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?

Richard Miller, CEO

With some follow-up, more than 10.

Operator, Operator

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

Roger Song, Analyst

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.

Richard Miller, CEO

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?

Roger Song, Analyst

Yes, I got you.

Richard Miller, CEO

I’m not certain it significantly impacts our plans, but we will consider it. This topic will also need to be discussed with the FDA. In this specific disease, the timing isn't going to be very different; it may vary by just a few months, which could be important. Regarding solid tumors, we currently don't have a set timeline for starting a trial in that area. However, we have been in discussions about various cancers such as renal cancer, lung cancer, and melanoma, particularly looking at the drug for patients resistant to PD-1 therapies. The encouraging aspect is that there are many patients who have undergone treatment with anti-PD-1 and PD-L1 agents, numbering in the thousands. On the downside, there are a significant number of patients who are resistant, as most ultimately do not respond or have a recurrence. We are especially interested in understanding the mechanisms behind this resistance. These conversations are ongoing, but as I mentioned earlier, our primary focus is on advancing the T-cell lymphoma work as rapidly as possible.

Roger Song, Analyst

Right, thank you. Thank you, Rich.

Richard Miller, CEO

Thanks.

Operator, Operator

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.

Richard Miller, CEO

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.

Operator, Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.