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Angel Pharmaceuticals Presents Latest Data from Phase I/Ib Clinical Trial of CPI-818 (ITK Inhibitor) at the 64th ASH Annual Meeting
Jiaxing, China and Burlingame, Calif., U.S.A. – December 13, 2022 – Angel Pharmaceuticals, a clinical-stage innovative drug company, today announced the latest results from the global Phase I/Ib clinical trial of CPI-818, a global first-in-class ITK inhibitor being co-developed with Corvus Pharmaceuticals, demonstrating its antitumor activity in patients with T-cell lymphomas (TCL) and its therapeutic potential in Th2- and Th17-mediated autoimmune and allergic diseases. The data were presented as a poster at the 64th American Society of Hematology (ASH) Annual Meeting, held in a hybrid format from December 10 to 13, 2022. A conference call and webcast held this morning at 5:30 AM Beijing Time (4:30–5:30 PM Eastern Time on Monday, December 12, 2022) provided an overview of the CPI-818 data presented at the ASH Annual Meeting.
"CPI-818, an ITK inhibitor, has demonstrated single-agent antitumor activity in patients with refractory T-cell lymphomas, a population with extremely limited treatment options and very low response rates," said Dr. Richard Miller, Co-founder and Chairman of Angel Pharmaceuticals. "We have seen durable objective responses in 4 of 11 evaluable patients at the 200 mg dose level. Based on the current clinical trial results, Angel Pharmaceuticals and Corvus Pharmaceuticals plan to advance CPI-818 into a global Phase II clinical trial in T-cell lymphomas in mid-2023. Given the relatively high incidence and prevalence of T-cell lymphomas in China, Angel Pharmaceuticals will conduct the Chinese portion of the clinical trial. The Phase I data also provide in vivo evidence that CPI-818 can modulate T-cell immune function by inducing Th1 skewing and blocking Th2 and Th17 cells. These effects are important not only for cancer therapy – Th1 cells are essential for eliminating tumor cells – but also for the many autoimmune and allergic diseases involving Th2 and Th17 cells. The clinical and preclinical findings reported at ASH suggest that CPI-818 enhances antitumor immunity and represents a potential novel immunotherapeutic approach."
Dr. Miller concluded, "Overall, we believe the data presented at ASH provide a solid scientific rationale for ITK inhibition in the treatment of lymphomas and certain immune disorders. CPI-818 is the world's first ITK inhibitor to enter clinical development, with high selectivity for ITK, which we believe is critical for achieving the immunomodulatory effects observed in the study and represents a significant achievement by our R&D team."
Dr. Wang Tiefei, Co-founder of Angel Pharmaceuticals, said: "The successful conduct of the global Phase I/Ib clinical trial of CPI-818 fully demonstrates the complementary strengths and resource sharing advantages of the collaborative development between Angel Pharmaceuticals and Corvus Pharmaceuticals. We look forward to continuing our efficient cooperation to advance the global development of CPI-818."
Professor Song Yuqin, the Chinese Lead Investigator for the CPI-818 Phase I/Ib clinical trial and from the Department of Lymphoma at Peking University Cancer Hospital, commented: "As the world's first ITK inhibitor to enter clinical development, CPI-818 has already demonstrated a favorable safety profile and promising single-agent antitumor activity based on the available Phase I/Ib data, along with in vivo evidence of T-cell immune modulation, showing great potential in tumor immunotherapy. We hope that the subsequent development of CPI-818 proceeds smoothly and brings benefits to T-cell lymphoma patients in China as soon as possible."
Key Results from the CPI-818 Phase I/Ib Clinical Trial Presented at ASH 2022:
CPI-818 is being evaluated as a monotherapy in a Phase I/Ib clinical trial in patients with relapsed TCL. As of September 2, 2022, a total of 43 patients had been enrolled in the trial across four dose-escalation cohorts at doses of 100, 200, 400, and 600 mg twice daily. The 200 mg dose was found to provide plasma drug concentrations that achieved optimal effects on T-cell differentiation in vitro and correspondingly induced the most frequent and durable tumor responses in vivo. This was therefore selected as the optimal dose, and additional patients are being enrolled in the 200 mg dose cohort. The study endpoints are safety, pharmacokinetics (PK), immune effects, and tumor response.
Interim Data Highlights in T-Cell Lymphomas
Thirteen patients were enrolled in the 200 mg cohort, of whom 11 were evaluable for response. All were heavily pretreated, with a median of 3 prior lines of therapy. Overall objective responses were observed in 4 of 11 evaluable patients. In this cohort, one patient with peripheral T-cell lymphoma (PTCL) achieved a complete response (CR) lasting 25 months; one patient with cutaneous T-cell lymphoma achieved a nodal CR lasting 19 months; and two durable partial responses (PR) were observed in patients with PTCL and anaplastic large cell lymphoma at 6-month and 8-month follow-ups, respectively. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached up to 600 mg twice daily. All data above are as of September 2, 2022.
Interim Data Highlights on Immune Effects
As of September 2, 2022, peripheral blood samples from several patients showed that the optimal dose of 200 mg induced Th1 skewing and Th2/Th17 blockade:
In a patient with significant regression of a large abdominal wall tumor, blood sample analysis showed increased blood Th1, decreased blood Th17, and reduced eosinophil counts and IL-5 secretion, consistent with Th1 skewing and Th2 blockade. Analysis of the patient's tumor sample revealed an increase in terminally differentiated T effector memory cells (TEMRA cells), which are T cells capable of antigen presentation and mediating effector functions such as tumor cell destruction.
In four additional patients (two with PR, one with stable disease [SD], and one with progressive disease [PD]), changes in Th1 and CD8+ TEMRA cells were measured over time. Patients with PR and SD showed increases in Th1 and CD8+ TEMRA cells. Notably, the SD and PD patients were lymphopenic at baseline, with absolute counts <1,000, suggesting that patients need at least a minimal level of immune competence.
In vitro dose-dependent data indicated that CPI-818 at 200 mg induces Th1 skewing and Th2 blockade. This included analysis of peripheral blood samples from 12 healthy volunteers at various concentrations of CPI-818, along with other studies showing that CPI-818 inhibits Th2 cytokine production by normal CD4+ and Sezary cells.
Additional in vitro studies showed that CPI-818 inhibits the production of interleukins 4, 5, and 13, cytokines produced by Th2 cells.
In vivo preclinical studies in mice transplanted with T-cell lymphomas showed that CPI-818 increased CD8+ T-cell infiltration into tumors and inhibited tumor growth.
The human and preclinical study findings suggest that CPI-818 enhances antitumor immunity and represents a potential novel immunotherapeutic approach.
About Angel Pharmaceuticals
Angel Pharmaceuticals is an innovative drug company dedicated to oncology and autoimmune diseases. With the mission of benefiting Chinese patients, Angel is committed to bringing globally top-tier innovative drugs for serious diseases such as cancer and autoimmune disorders to China. In October 2020, Angel Pharmaceuticals completed its Series A financing round, co-invested by Beta Fund, Hisun Pharmaceuticals, Tigermed, and Puhua Investment, and established a strategic partnership with Corvus Pharmaceuticals (CRVS) of the U.S. For more information, please visit www.angelpharma.com.
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company. Corvus's lead product candidate is CPI-818, an oral, selective ITK inhibitor currently being evaluated in a multicenter Phase 1/1b clinical trial in patients with various T-cell lymphomas. Its second clinical program is ciforadenant (CPI-444), an oral small molecule inhibitor of the A2A receptor. Its third clinical program, mupadolimab (CPI-006), is a humanized anti-CD73 monoclonal antibody that has demonstrated immunomodulatory activity and immune cell activation in preclinical studies. For more information, please visit www.corvuspharma.com.
