New Preclinical Data Highlights Potential for CPI-818 (ITK Inhibitor) as a Therapy for Acute Graft Versus Host Disease in Patients Receiving Bone Marrow Transplantation
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
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
“This study broadens the potential applications of CPI-818 to include aGVHD, which is a significant complication of bone marrow transplant,” said
Details regarding the poster presentation, which will be available in the poster hall and via the virtual event platform, are as follows:
Poster Session: Highly Selective Irreversible ITK Inhibitor CPI-818 Reduces Acute Graft-Versus Host Disease
CPI-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 possess dual properties: 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. Interference with ITK signaling can modulate immune responses to various antigens. 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 diseases. The Company is conducting a Phase 1/1b trial in patients with refractory T-cell lymphomas.
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of mupadolimab, CPI-818 and ciforadenant, such as CPI-818’s 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 Company’s ability and Angel Pharmaceutical’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including Angel’s plans to initiate a Phase 2 clinical trial of CPI-818; and the timing of the availability and announcement of clinical data and certain other product development milestones. 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
Chief Financial Officer
Source: Corvus Pharmaceuticals, Inc.