CRVS Corvus Pharmaceuticals Inc

Corvus Pharmaceuticals, Inc. (Corvus or the Company) (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced updated results from its Phase 1/1b trial of CPI-818, the Company’s ITK inhibitor, which demonstrated its anti-tumor activity in patients with T cell lymphoma (TCL) and its therapeutic potential in Th2 and Th17-mediated autoimmune and allergic diseases. The data will be presented today in a poster at the 64th American Society of Hematology (ASH) Annual Meeting & Exposition, which is taking place in-person and virtually from December 10 to 13, 2022.

“ITK inhibition with CPI-818 has demonstrated monotherapy anti-tumor activity in highly refractory T cell lymphoma patients, a population with limited and often ineffective treatment options,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “We have seen durable objective tumor responses in four of eleven evaluable patients. Based on the clinical results to-date, we plan to advance CPI-818 into a global Phase 2 clinical trial in T cell lymphoma in mid-2023. The study will be conducted in partnership with Angel Pharmaceuticals, which is responsible for the trial in China, where there is a higher incidence and prevalence of T cell lymphoma. The Phase 1 data also provided in vivo evidence of CPI-818’s ability to modulate immune functions of T cells by blocking both Th2 and Th17 T cells and skewing toward Th1 cells. The effects are important for cancer therapy – Th1 cells are essential for elimination of tumor cells – as well as in autoimmune and allergic diseases given that Th2 and Th17 cells are involved in many of these diseases. The clinical and preclinical findings reported at ASH suggest that CPI-818 enhances anti-tumor immunity and represents a potential novel approach to immunotherapy. We are advancing CPI-818 across multiple therapeutic areas, starting with a Phase 1 clinical trial in atopic dermatitis, known to be a Th2 driven disease, planned for early 2023.”

Dr. Miller concluded, “Overall, we believe the data presented at ASH provides a strong foundation and rationale for ITK inhibition in lymphoma and certain immune diseases. CPI-818 is the most advanced ITK inhibitor we are aware of and has demonstrated high selectivity for ITK, which we believe has been crucial to achieving the immunomodulatory functions observed in our studies to date and represents a significant achievement of our research and development group. We look forward to providing updates on the development of CPI-818 and our other clinical programs – ciforadenant as a potential first line therapy for metastatic renal cell cancer and Angel Pharmaceutical’s study of mupadolimab in patients with relapsed refractory non-small cell lung cancer and head and neck squamous cell cancers – in the coming months and year.”

CPI-818 Phase 1/1b Clinical Trial Key Results Presented at ASH 2022CPI-818 is being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. As of September 2, 2022, 43 patients were enrolled in the trial across four escalating dosing cohorts: 100, 200, 400 and 600 mg, each being administered twice per day. The 200 mg dose was found to provide plasma drug concentrations that optimally affect T cell differentiation in vitro and correspondingly was found to lead to the most frequent and durable tumor responses in vivo. Accordingly, Corvus identified it as the optimal dose and additional patients are being enrolled in a 200 mg dose cohort of the clinical trial. The Phase 1/1b clinical trial endpoints are safety, pharmacokinetics (PK), immunologic effects and tumor response.

T Cell Lymphoma Interim Data Highlights

• 13 patients were enrolled in the 200 mg cohort and 11 were evaluable for response. Overall objective responses were seen in 4 of 11 patients. Enrolled patients were heavily pretreated receiving a median of 3 prior therapies. In this group, there was one complete response (CR) lasting 25 months in a patient with peripheral T cell lymphoma (PTCL); one nodal CR lasting 19 months in a patient with cutaneous T cell lymphoma; and two partial responses (PR) ongoing at six and eight months follow up, respectively, in patients with PTCL and anaplastic large cell lymphoma. An additional patient in the 600 mg cohort also had a PR.
• No dose limiting toxicities were observed, and a maximally tolerated dose was not reached at doses as high as 600 mg twice per day.
• All of the foregoing data was as of September 2, 2022.

Immunologic Effects Interim Data Highlights

• As of September 2, 2022, the 200 mg optimal dose was shown to induce Th1 skewing and both Th2 and Th17 blockade based on peripheral blood samples from several patients:
  • In one patient that had a significant reduction of a large tumor on the abdominal wall, a blood sample analysis demonstrated an increase in blood Th1, a decrease in blood Th17, and a reduction of eosinophil count and IL-5 consistent with Th1 skewing and Th2 blockade. Tumor samples in this patient were also analyzed and showed an increase in terminally differentiated T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells.
  • In four patients (two with PRs, one with stable disease (SD) and one with progressive disease (PD), the change in Th1 and CD8+ TEMRA cells was serially measured over time. The PR and SD patients showed an increase in both Th1 and CD8+ TEMRA cells. Of note, SD and PD patients were lymphopenic at baseline with absolute lymphocyte counts <1,000, highlighting the need for a minimal level of immune competence.
• In vitro data demonstrated that CPI-818 induced Th1 skewing and Th2 blockade in a dose-dependent manner that supported the selection of the 200 mg dose. This includes an analysis of peripheral blood samples from 12 healthy volunteers that were stimulated in the presence of various concentrations of CPI-818 and other studies that showed that CPI-818 inhibited Th2 cytokine production from normal CD4+ and Sezary cells.
• Other in vitro studies showed that CPI-818 inhibited the production of interleukin 4, 5 and 13 cytokines produced by Th2 cells.
• In vivo preclinical studies in mice with transplanted T cell lymphoma showed that CPI-818 led to an increase in infiltration of normal CD8+ T cells in the tumor and inhibition of tumor growth.
• The findings of the human and preclinical studies suggest that CPI-818 enhances anti-tumor immunity representing a potentially novel approach to immunotherapy.
• Separate from the ASH presentation, Corvus recently initiated a CPI-818 study in companion dogs with naturally occurring, refractory atopic dermatitis. Early results from this study demonstrated CPI-818’s potential activity in this disease with five out of five treated dogs responding to therapy within 14 days.  

Conference Call, Webcast and Presentation SlidesCorvus will host a conference call and webcast today, Monday, December 12, 2022 from 4:30 – 5:30 pm ET to provide an overview of the CPI-818 data that presented at the ASH meeting, along with providing an update on the Company’s development programs. The conference call can be accessed by dialing 1- 877-300-8521 (toll-free domestic) or 1- 412-317-6026 (international) and using the conference ID 10172958. The live webcast, which will include presentation slides, 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.

About Corvus PharmaceuticalsCorvus Pharmaceuticals is a clinical-stage biopharmaceutical company. Corvus’ lead product candidate is CPI-818, an investigational, oral, small molecule drug that selectively inhibited ITK in preclinical studies and is in a multicenter Phase 1/1b clinical trial in patients with several types of T cell lymphomas. The Company’s second clinical program, ciforadenant (CPI-444), is an oral, small molecule inhibitor of the A2A receptor that is in an open-label Phase 1b/2 clinical trial. Its third clinical program, mupadolimab (CPI-006), is a humanized monoclonal antibody directed against CD73 that has exhibited immunomodulatory activity and activation of immune cells in preclinical and clinical studies. For more information, visit www.corvuspharma.com.

About CPI-818CPI-818 is an investigational small molecule drug given orally that has selectively inhibited ITK (interleukin-2-inducible T cell kinase) in preclinical studies. It was designed to block malignant T cell growth and to modulate immune responses. ITK, an enzyme, is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. Recent clinical data in T cell lymphomas suggests that CPI-818 has the potential to control differentiation of T helper cells and enhance immune responses to tumors. Interference with ITK signaling also can modulate immune responses to various antigens. Optimal doses of CPI-818 have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of Th2 related cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The immunologic effects of CPI-818 lead to what is known as Th1 skewing and is made possible by the high selectivity of CPI-818 for ITK. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with T cell lymphomas and leukemias and in patients with autoimmune and allergic diseases. The Company is conducting a Phase 1/1b trial in patients with refractory T cell lymphomas that was designed to select the optimal dose of CPI-818 and evaluate its safety, PK, target occupancy, immunologic effects, biomarkers and efficacy. Interim data from the Phase 1/1b clinical trial of CPI-818 for T cell lymphoma demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, and identified a dose that maximally affects T helper cell differentiation.

Current Treatment for Peripheral T cell LymphomasPTCL comprise a heterogeneous group of diseases. Generally, they have a dismal prognosis with a 5-year survival of 11% in patients with high-risk disease. Patients in relapse have a median overall survival of approximately 6 months and a median progression free survival of under 3 months. Initial treatments involve combination chemotherapy regimens and sometimes use of bone marrow transplantation in younger, potentially more favorable patients. In relapsed disease, currently approved therapies are toxic and have low response rates of 25-30% with median progression free survival of 4-5 months. Because of these factors, the National Comprehensive Cancer Network (NCCN) Guidelines recommends enrolling patients with relapsed disease in clinical trials with experimental agents as the preferred management indicating the need for safer and more effective therapies.

About Angel PharmaceuticalsAngel Pharmaceuticals is a privately held biopharmaceutical company developing a pipeline of precisely targeted investigational medicines for cancer, autoimmune, infectious and other serious diseases in China. Angel Pharmaceuticals was launched through a collaboration with U.S.-based Corvus Pharmaceuticals and investments from investors in China. Angel Pharmaceuticals licensed the rights to develop and commercialize Corvus’ three clinical-stage candidates – CPI-818, ciforadenant and mupadolimab – in greater China and obtained global rights to Corvus’ BTK inhibitor preclinical programs. Under the collaboration, Corvus currently has a 49.7% equity stake in Angel Pharmaceuticals excluding 7% of Angel’s equity reserved for issuance under the Angel ESOP, and Corvus has designated three individuals on Angel’s five-person Board of Directors. For more information, visit www.angelpharma.com.

Forward-Looking Statements This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-818, ciforadenant and mupadolimab; the Company’s ability and its partners’ ability, as well as the timing thereof, to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company and Angel’s Phase 1/1b clinical trials of CPI-818 and the Company’s planned initiation of a Phase 2 clinical trial of CPI-818 for T cell lymphoma and a Phase 1 clinical trial of CPI-818 for atopic dermatitis, both in 2023; and the timing of the availability and announcement of clinical data and certain other product development milestones in the coming months and year.   All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, filed with the Securities and Exchange Commission on November 3, 2022, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of CPI-818, ciforadenant and mupadolimab; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

INVESTOR CONTACT:Leiv LeaChief Financial OfficerCorvus Pharmaceuticals, Inc.+1-650-900-4522llea@corvuspharma.com

MEDIA CONTACT:Sheryl SeapyReal Chemistry+1-949-903-4750sseapy@realchemistry.com