CARsgen Presents First-in-human Results of GPRC5D Targeting CAR-T CT071 at EHA 2024

SHANGHAI, June 15, 2024

The preliminary results of Phase I of CT071 (NCT05838131) were presented as a poster at the 29th EHA Annual Congress on June 14, 18:00 - 19:00 CEST, which was titled "First-in-human study of GPRC5D-targeted CAR T cells (CT071) with an accelerated manufacturing process in patients with relapsed/ refractory multiple myeloma (RRMM)".^[1]

"Multiple myeloma is a common yet incurable hematologic malignancy with high unmet need. Despite the numerous recent advances, most patients relapse and become refractory to available therapies and therefore, novel therapies are needed. GPRC5D, a protein highly expressed on the surface of malignant plasma cells with limited expression on normal tissues, represents a promising target for treating multiple myeloma. CT071 is a fully human GPRC5D-targeting autologous second-generation CAR T-cell product manufactured using our expedited CARcelerate^TM platform that shortens the manufacturing time to around 30 hours, supporting a shorter vein-to-vein time and younger T cells. The preliminary results of the ongoing study presented at EHA shows that CT071 has the potential to be the best-in-class GPRC5D targeting CAR-T therapy," said Raffaele Baffa, M.D., Ph.D., Chief Medical Officer of CARsgen Therapeutics. "We are excited about advancing CT071 and look forward to sharing future updates with the medical community."

As of February 28, 2024, 10 patients were dosed with CT071—7 patients at 1.0×10⁵ cells/kg and 3 patients at 3.0×10⁵ cells/kg. Among them, 80% had high-risk cytogenetics, 30% had one or more extramedullary plasmacytomas (EMD), and 40% were at R-ISS stage III. This was a heavily pre-treated population with a median of 5 prior lines of therapy, including 90% double-class refractory, 70% triple-class refractory, 40% penta-drug refractory, 50% having received autologous stem cell transplantation, and 20% had previously been treated with BCMA/CD19 dual-targeting CAR T cells. None of the patients on the study required bridging therapy due to rapid manufacturing turnaround.

The median follow-up at the time of data cut-off was 4.07 months (range: 2.8-7.4). There were no Grade 3 or higher cytokine release syndrome (CRS) events. No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. No adverse events of special interest or dose limiting toxicity (DLT) occurred. Four patients experienced treatment-related SAE, including pneumonia (n=1), decreased appetite (n=1) and thrombocytopenia (n=2), and all recovered.

The overall response rate was 90%, including 5 patients (50%) with stringent complete response (sCR), 2 patients (20%) with very good partial response (VGPR), and 2 patients (20%) with partial response (PR). All the 9 patients with evaluable MRD assessment at Week 4 achieved MRD negativity (10^-6 threshold) ), including all 5 patients with sCR/CR. The pharmacokinetic analysis demonstrated robust cell expansion and persistence, with median T_max of 14 days (range: 12-28) and median C_max of 32280.5 copies/μg gDNA (range: 8372-106060).