From June 2018 to March 2021, 18 patients underwent leukapheresis, run-in with JSMD194, and treatment with BCMA CAR T cells. The median age was 65 years, and patients had received a median of 10 prior lines of therapy (range, 4-19). 67% of patients were refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, 72% had high-risk cytogenetic features, and 28% had extramedullary disease. 7/18 (39%) had prior BCMA targeted therapy; other BCMA targeted CAR T cell products had previously been administered to 4/18 patients (22%). All 18 treated patients completed the 5-day run-in with JSMD194. After three oral doses of GSI, increased from a median of 610 to 9563 receptors per cell, or a median of 12-fold (range, 0.2-fold to 157-fold; Figure 1). The only patient that did not demonstrate an increase in BCMA ABC after GSI run-in had previously received BCMA targeted therapy and BCMA expression at screening was virtually absent. 5 patients were treated at 5x107 CAR+ cells, 3 were treated at 15x107 CAR+ cells, 3 were treated at 30x107 CAR+ cells, and 7 were treated at 45x107 CAR+ cells dose levels. Treatment was consistent with other BCMA CAR T therapy, with manageable toxicities. One patient experienced a DLT. 95% of patients experienced cytokine release syndrome (CRS), mostly grade 1-2 (83%), and 66% of patients experienced ICANS, predominantly grades 1-2. The overall response rate was 89%, with 14 patients achieving ≥ VGPR, and 8 patients achieving CR (including 5 with sCR). Deep responses were observed at all dose levels; including the first patient treated on trial at (dose level 1) who has maintained a stringent CR (sCR) for over 35 months and 3 of 5 patients at dose level 1 had no evidence of progressive disease for >18 months. With a median follow-up of 20 months, the median PFS is 11 months (95% CI, 6 mos to not reached). Amongst patients without prior exposure to BCMA targeted therapy (n=11), the median PFS has not been reached, while amongst those previously exposed to BCMA targeted therapy (n=7), the median PFS was 2 months.

• Eight patients, with a median age of 64.5 (range, 50-70 years) and a median of 10 prior regimens (range, 4-23), were screened, and seven patients have been treated.
• High-risk features were present in 75% of patients
• Following 3 oral doses (run in) of JSMD194, the percent of plasma cells expressing BCMA increased from 75% to 99% (7.6 to 98% pre, 75 to 100% post), soluble BCMA decreased by 2.0 fold (range 1.6 to 2.6 fold) after 3 oral doses, and BCMA antigen binding capacity increased from a median of 718 receptors to 13355 receptors per cell, or a median of 20-fold (range, 7.55-fold to 156.68-fold).
• Among 6 assessable patients, the best overall response rate was 100% (5 VGPR, 1 PR), with 5/6 patients MRD negative by flow. At data cutoff of July 15, 2019, no patient has relapsed, with a median follow-up of 5 months (range 1-11 months).