CRISPR Therapeutics AG (Nasdaq: CRSP) presented data at the 2024 American Society of Hematology (ASH) Annual Meeting showcasing the potential of CTX112, a next-generation CD19 allogeneic CAR T-cell therapy, in treating relapsed or refractory (R/R) CD19-positive B-cell malignancies. The company also announced that the U.S. Food and Drug Administration (FDA) has granted CTX112 a Regenerative Medicine Advanced Therapy (RMAT) designation for R/R follicular lymphoma and marginal zone lymphoma. The therapy is currently in Phase 1/2 clinical trials.
The early clinical data suggests that CTX112 could provide meaningful clinical benefits with a well-tolerated safety profile when used with a standard lymphodepletion protocol. CRISPR Therapeutics expects to provide a broader update across oncology and autoimmune indications in mid-2025.
Clinical Trial Data and Efficacy
The ongoing Phase 1/2 dose escalation clinical trial is evaluating the safety and efficacy of CTX112 in patients with R/R CD19-positive B-cell malignancies. Preliminary data presented at ASH demonstrated encouraging response rates and a manageable safety profile, suggesting the potential for CTX112 to become an effective off-the-shelf CAR T-cell therapy.
Armin Ghobadi, M.D., Professor of Medicine and Clinical Director, Center for Gene and Cellular Immunotherapy (CGCI), at Washington University School of Medicine, noted, "CTX112 has shown dose-dependent efficacy and response rates that are comparable to the early autologous CAR T trials. These early results highlight the potential for CTX112 to emerge as an effective, off-the-shelf CAR T therapy for patients with relapsed or refractory CD19-positive B-cell malignancies."
FDA RMAT Designation
The FDA's Regenerative Medicine Advanced Therapy (RMAT) designation is designed to expedite the development and review of regenerative medicine therapies intended to treat serious or life-threatening conditions. This designation provides several benefits, including increased interaction with the FDA during the development process and the potential for priority review.
The RMAT designation for CTX112 underscores the FDA's recognition of its potential to address unmet needs in patients with R/R follicular lymphoma and marginal zone lymphoma. The designation may allow for accelerated approval pathways based on early clinical data, with confirmatory trials conducted post-approval.
Off-the-Shelf CAR-T Therapy
CTX112 is designed as an "off-the-shelf" therapy, meaning it can be manufactured in advance and readily available for patients, unlike autologous CAR T-cell therapies that require a patient's own cells to be modified. This approach simplifies the logistics of cell therapy manufacturing and has the potential to reduce costs and improve accessibility.
Expansion into Autoimmune Diseases
In addition to its potential in oncology, CTX112 is also being investigated in a Phase 1 clinical trial for systemic lupus erythematosus (SLE). The company sees potential to expand its use into additional autoimmune indications in the future, broadening the therapeutic application of this allogeneic CAR T-cell therapy.
Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics, stated, "The data support a well-tolerated safety profile and the possibility to address the unmet need in this patient population with an off-the-shelf CAR T therapy. These results also support the potential treatment of certain autoimmune diseases by CTX112, and we are continuing to advance our SLE trial."
