Crispr Therapeutics presents data on CTX112 at ASH Meeting

CRISPR Therapeutics (CRSP) presented data from the Company’s ongoing Phase 1/2 dose escalation clinical trial evaluating the safety and efficacy of CTX112, a next-generation CD19 allogeneic CAR T cell therapy, in relapsed or refractory CD19-positive B-cell malignancies at the 2024 American Society of Hematology Annual Meeting. Additionally, the Company announced that the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy designation to CTX112 for the treatment of R/R follicular lymphoma and marginal zone lymphoma. The Phase 1/2 clinical trial is an open-label, multicenter study evaluating the safety and efficacy of CTX112 in relapsed or refractory B-cell malignancies. Eligible disease subtypes include large B-cell lymphoma, follicular lymphoma grade 1-3a, marginal zone lymphoma, and mantle cell lymphoma/ CTX112 was infused after a standard course of lymphodepleting chemotherapy. Data were presented from 12 subjects treated during the dose escalation with CTX112 doses ranging from 30 x 106 CAR+ T cells. The study population was enriched for patients with high-risk characteristics, including: primary refractory disease or early relapse to first-line therapy; high tumor burden; and high disease prognostic index score or elevated lactate dehydrogenase. CTX112 was well tolerated across all dose levels. There were no reported dose limiting toxicities and no reported Grade greater than or equal to3 infections. All grade 3 or 4 cytopenias following lymphodepleting chemotherapy resolved to Grade 2 or better within 1 month of CTX112 infusion. There were no reported cases of Graft versus Host Disease. All cases of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were Grade 1 or 2 per the American Society for Transplantation and Cellular Therapy criteria. Objective and complete responses were seen at all dose levels and in all treated NHL subtypes. Responses were also seen in patients with poor prognostic factors including primary refractory disease, early relapse, and high baseline tumor burden. Five patients have achieved responses lasting for more than 6 months, including one patient whose 6-month response was confirmed after the data cut-off date. One patient treated at DL1 remains in complete remission over a year after initial CTX112 infusion. The clinical efficacy of CTX112 is supported by a clearly differentiated pharmacokinetic profile for an allogeneic CAR T cell therapy. The mean peak concentration and total exposure were significantly higher at DL3 and DL4 vs. DL1 and DL2. This dose dependence suggests the possibility of deeper and more durable responses as the trial moves from dose escalation to dose optimization. Comparing DL3, the addition of Regnase-1 and TGFbetaR2 edits results in 7-fold higher peak concentration and 9.7-fold higher mean area under the curve for CTX112 relative to CTX110. Furthermore, at DL4, both Cmax and AUC are showing significantly more consistent and predictable increases. This suggests that the novel CRISPR/Cas9 potency edits are leading to higher CAR T cell expansion and functional persistence without enhanced or increased lymphodepleting chemotherapy doses. These preliminary data demonstrate that CTX112 has the potential to provide meaningful clinical benefit with a well-tolerated safety profile. Given the inherent difficulties of manufacturing a CAR T therapy from a patient’s own diseased cells, allogeneic cellular therapy approaches have greater potential to address the unmet need in this patient population.