On March 28, 2023 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported a business update and reported financial results for the fourth quarter and year ended December 31, 2022 (Press release, Corvus Pharmaceuticals, MAR 28, 2023, View Source [SID1234629435]).
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"Heading into 2023, we are building momentum for CPI-818, our ITK inhibitor, which we believe is well positioned to provide a platform opportunity across cancer and immune diseases," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "This includes a growing body of clinical and preclinical data supporting ITK inhibition across a range of indications. The most encouraging data is in oncology, where enrollment in our Phase 1/1b trial in T cell lymphoma has accelerated and has enabled us both to increase the number of patients treated at the optimum dose and to identify a predictive biomarker that we believe will enrich for patients most likely to benefit from treatment with CPI-818. Looking forward, we are focused on achieving value driving milestones for CPI-818 including interim T cell lymphoma clinical data at upcoming medical meetings and additional preclinical data with CPI-818 in solid tumors at the upcoming AACR (Free AACR Whitepaper) meeting in April. In addition, we have upside potential from ciforadenant and mupadolimab, the clinical development of which are primarily being advanced and funded by partners."
Business Update and Strategy
Prioritized Program: CPI-818 (selective ITK inhibitor)
CPI-818 for T Cell Lymphoma
CPI-818 Phase 1/1b clinical trial results presented at the 64TH American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in December 2022 provided clinical data and in vivo evidence supporting its ongoing development as a therapy for T cell lymphoma and its potential in autoimmune and allergic diseases. Key data from the presentation include:
As of September 2, 2022, there were 1 complete response (CR), 1 nodal CR and 2 partial responses (PR) in 11 evaluable patients in the 200 mg twice per day cohort (identified optimal dose). An additional PR was seen in a patient receiving the 600 mg twice per day dose. No dose limiting toxicities were observed in 43 patients enrolled across four dosing cohorts, and a maximally tolerated dose was not reached at doses as high as 600 mg twice per day.
The 200 mg dose was shown to induce Th1 skewing and both Th2 and Th17 blockade based on findings in peripheral blood samples from several patients and in vitro data demonstrated that it did so in a dose-dependent manner that supported the selection of the 200 mg twice per day optimum dose. The findings of the human and preclinical studies suggest that CPI-818 enhances anti-tumor immunity representing a potentially novel approach to immunotherapy.
Enrollment in the 200 mg cohort has accelerated and is ongoing. As of February 23, 2023, 20 patients were enrolled, including 13 evaluable for tumor response. There have been 1 CR of 24 months duration, 1 equivocal CR awaiting confirmatory PET scan of 13+ months duration (a previous PR), 1 nodal CR of 21 months duration and 1 PR of 7 months duration. Ten patients continue on therapy, including seven that have not yet been evaluated for tumor response. The swimmer and waterfall tumor plots for these patients are shown below.
New CPI-818 predictive biomarker: Corvus has identified a biomarker associated with response to CPI-818. CPI-818 induces a host anti-tumor cell mediated immune response that requires normal functioning T cells. Data from the 200 mg cohort in the Phase 1/1b clinical trial indicates that a minimum absolute lymphocyte count (ALC) above 900 per cubic milliliter of blood is required for tumor response and disease control. Four of eight patients with ALC above 900 have objective responses (those four patients are described above), all eight have disease control (stable disease, PR, CR) and the median progression free survival (PFS) is 28.1 months. No objective responses were seen in five patients (0 of 5) with ALC below 900 and the PFS is 2.1 months. The ALC biomarker is routinely measured, is consistent with CPI-818’s presumed mechanism of action and is present in about 70% of patients based on the Company’s experience to-date. This biomarker has been incorporated as an eligibility criterion in the ongoing Phase 1/1b clinical trial.
Figure 1: Swimmer Plot for Patients in the 200 mg Dose Cohort of the CPI-818 Phase 1/1b Clinical Trial for T Cell Lymphoma. The plot shows the tumor response and duration (months) for patients with various tumor histologies, which are shown on the chart and defined as follows: PTCL-NOS, peripheral T cell lymphoma not otherwise specified; CTCL-SS, cutaneous T cell lymphoma Sezary; CTCL-MF, cutaneous T cell lymphoma mycosis fungoides; AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic T cell lymphoma and NKTCL, natural killer T cell lymphoma. The tumor response evaluation are labeled on the chart and are defined as follows: CR, complete response; equivocal CR; PR, partial response; SD, stable disease; PD, progressive disease. Arrows indicate that treatment with CPI-818 is continuing as of the February 23, 2023 data cut-off.
The plot shows the tumor response and duration (months) for patients with various tumor histologies, which are shown on the chart and defined as follows: PTCL-NOS, peripheral T cell lymphoma not otherwise specified; CTCL-SS, cutaneous T cell lymphoma Sezary; CTCL-MF, cutaneous T cell lymphoma mycosis fungoides; AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic T cell lymphoma and NKTCL, natural killer T cell lymphoma. The tumor response evaluation are labeled on the chart and are defined as follows: CR, complete response; equivocal CR; PR, partial response; SD, stable disease; PD, progressive disease. Arrows indicate that treatment with CPI-818 is continuing as of the February 23, 2023 data cut-off.
Corvus recently received a communication from the U.S. Food and Drug Administration (FDA) regarding its clinical development plans for CPI-818. Based on the current enrollment rate of its ongoing Phase 1/1b clinical trial, the Company believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a registration Phase 3 randomized clinical trial. As recommended by the FDA, the Company plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place later this year.
Reprioritization of CPI -818 for Atopic Dermatitis
Based on recent progress and data supporting the ongoing development of CPI-818 for T cell lymphoma and other cancers, Corvus has decided to delay its plans to initiate a Phase 1 clinical trial in atopic dermatitis. This decision allows the Company to conserve cash and intensify its focus on T cell lymphoma, which could include conducting a potentially registrational, randomized Phase 3 trial. While Corvus is pausing development of CPI-818 for the treatment of atopic dermatitis, the Company will continue to investigate the potential role of CPI-818 in immune diseases through its ongoing and planned preclinical research and external collaborations.
CPI-818 for HIV
In February 2023, researchers from The University of California San Francisco-Bay Area Center for AIDS Research (UCSF) presented new data at the 30th Annual Conference on Retroviruses and Opportunistic Infections demonstrating the potential of CPI-818 to reduce the need for chronic human immunodeficiency virus (HIV) therapy. The data further highlights the broad therapeutic opportunity for ITK inhibition with CPI-818. Based on this positive data, the UCSF team plans to continue studying the potential for ITK inhibition to be developed within antiproliferative and "block-and-lock" HIV cure strategies.
Partner Led Programs: Ciforadenant (adenosine 2a receptor inhibitor) and Mupadolimab (anti-CD73)
The Kidney Cancer Research Consortium (KCRC) is enrolling a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The clinical trial is expected to enroll up to 60 patients and initial data is anticipated before the end of 2023.
Angel Pharmaceuticals, Corvus’ partner in China, is enrolling patients in a Phase 1/1b clinical trial of mupadolimab in patients with non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers. In this clinical trial, patients will receive mupadolimab monotherapy or in combination with pembrolizumab.
Financial Results
As of December 31, 2022, Corvus had cash, cash equivalents and marketable securities totaling $42.3 million. This compared to cash, cash equivalents and marketable securities of $69.5 million as of December 31, 2021. Corvus expects full year 2023 net cash used in operating activities to be between approximately $19 million and $22 million, resulting in a projected cash balance of between $20 million and $23 million as of December 31, 2023. Based on its current plans, Corvus expects its cash to fund operations into 2024.
Research and development expenses for the three months and full year ended December 31, 2022 totaled $4.1 million and $24.5 million, respectively, compared to $4.8 million and $29.1 million for the same periods in 2021. In the fourth quarter of 2022, the decrease of $0.7 million was primarily related to a decrease in personnel costs.
The net loss for the three months ended December 31, 2022 was $9.8 million compared to a net loss of $9.2 million for the same period in 2021. Total stock compensation expense for the three months ended December 31, 2022 was $0.6 million compared to $0.7 million for the same period in 2021 and the non-cash loss from the Company’s equity method investment in Angel Pharmaceuticals was $4.6 million for the three months ended December 31, 2022 compared to $2.6 million for the same period in 2021.
Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, March 28, 2023, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter and full year 2022 financial results. The conference call can be accessed by dialing 1-844-825-9789 (toll-free domestic) or 1-412-317-5180 (international) or by clicking on this link and requesting a return call and using the conference passcode 3154152. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.