Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company, today announced new preclinical data demonstrating the potential of CPI-818, the company's ITK inhibitor, for the prevention and
Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company, today announced new preclinical data demonstrating the potential of CPI-818, the company's ITK inhibitor, for the prevention and therapy of acute graft versus host disease (aGVHD) in patients receiving allogeneic hematopoietic cell transplantation (bone marrow transplantation). The data will be presented today in a poster at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition.
Bone marrow transplantation is a potentially curative therapy for patients with a variety of blood disorders, including blood cancers, certain solid cancers, hemoglobinopathies such as sickle cell disease, and immune deficiencies. However, its use has been limited by the pre-conditioning required to prepare the host to receive the transplant and by post procedure complications such as aGVHD, which occurs when engrafted alloreactive T cells produce an inflammatory response in the skin, gastrointestinal tract and liver. Current therapies for aGVHD, which have limited effectiveness, include steroids, ruxolitinib and other immunosuppressive drugs.
CPI-818 is an investigational, orally bioavailable, covalent inhibitor of ITK designed to have low nanomolar affinity. In vitro studies have shown that it potently inhibited T cell receptor signal transduction.
Preclinical Data Presented at ASH
The study evaluated CPI-818 in two mouse models of aGVHD. Recipient mice were pre-conditioned by having their bone marrow ablated with high dose radiation, and then received an allogeneic bone marrow transplantation. One group of mice was treated with CPI-818 dosed at 300 mg/kg/day delivered orally throughout the study period (seven days prior to transplant and 90 days post-transplant) and one group was treated in the same manner with a placebo control. The results of the study demonstrated that mice receiving CPI-818 had:
- Statistically significant improvement in GVHD score and survival compared to the placebo group.
- Increased concentrations of anti-inflammatory cytokines.
- Increased numbers of T suppressor cells in their spleens.
Collectively, the data demonstrated that ITK inhibition with CPI-818 has potential as a targeted approach to prevent or treat aGVHD through the suppression of T cell activation and proliferation, reducing concentrations of pro-inflammatory cytokines and increasing the concentration of anti-inflammatory cytokines. The study authors concluded that CPI-818 was the most potent and selective ITK inhibitor reported to date and these data highlight its promise as potentially a novel agent for the prevention or treatment of aGVHD.
"Acute graft versus host disease is a significant barrier to expanding the curative potential of bone marrow transplantation," said Marcel van den Brink, MD, PhD, lead author of the study and Head, Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center in New York, NY. "This preclinical data suggests that ITK inhibition with CPI-818 has the potential to be a novel agent that could prevent or treat aGVHD.
Corvus is studying CPI-818 in a Phase 1/1b clinical trial that was designed to select the optimal dose of CPI-818 and evaluate its safety, pharmacokinetics, target occupancy, 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. Corvus' partner in China, Angel Pharmaceuticals, plans to initiate a Phase 1/1b clinical trial of CPI-818 for the treatment of refractory T cell lymphomas in early 2022, with the potential to expand into autoimmune diseases over time. Angel Pharmaceuticals will be responsible for all expenses related to executing the trial in China.
"This study broadens the potential applications of CPI-818 to include aGVHD, which is a significant complication of bone marrow transplant," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "The data presented in these studies further strengthen the scientific rationale of T cell modulation through inhibition of ITK signaling pathways and support the mechanism and role of ITK inhibition in human diseases such as T cell lymphoma and autoimmunity."
Details regarding the poster presentation, which will be available in the poster hall and via the virtual event platform, are as follows:
Monday, Dec. 13, 6:00 p.m. to 8:00 p.m. ET
Poster Session: Highly Selective Irreversible ITK Inhibitor CPI-818 Reduces Acute Graft-Versus Host Disease
Presenter: Sarah Lindner, MD, from Memorial Sloan Kettering Cancer Center in New York, NY