Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim clinical data from the Company's FT516 and FT596 programs for patients with relapsed / refractory B-cell lymphoma. FT516 is the Company's universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The Company's FT596 program incorporates both the hnCD16 Fc receptor and a chimeric antigen receptor (CAR) targeting CD19, which is designed to enable multi-antigen targeting of tumor cells, as well as an IL-15 receptor fusion (IL-15RF) to enhance NK cell activity and survival.

"We are very pleased with the interim safety, response rates, and durability of responses observed in our ongoing clinical studies of FT516 and FT596 for the treatment of patients with relapsed / refractory B-cell lymphomas. These data continue to demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates can uniquely deliver substantial therapeutic benefit and expand patient access to cell-based cancer immunotherapies," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "At this time, we are initiating multiple indication-specific, dose-expansion cohorts to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including in patients that have experienced disease progression following autologous CD19-targeted CAR T-cell therapy. In addition, early clinical data with the single-dose FT596 treatment schedule have shown robust 30-day response rates and we look forward to further assessing both single-dose and multi-dose treatment regimens to validate its potential best-in-class therapeutic profile."

FT596 Program

The ongoing clinical trial in relapsed / refractory B-cell lymphoma is assessing a single dose of FT596 as monotherapy (Monotherapy Arm) and in combination with a single dose of rituximab (375 mg/m2) (Combination Arm) following three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine). As of the data cutoff date of June 25, 2021, 10 patients in the Monotherapy Arm and 10 patients in the Combination Arm were evaluable for assessment of safety and efficacy in the first, second, and third dose cohorts of 30 million cells (n=3 each), 90 million cells (n=4 each), and 300 million cells (n=3 each), respectively (see Table 1). Patients had received a median of four prior lines of therapy and a median of 2.5 prior lines containing CD20-targeted therapy. Of the 20 patients, 12 patients (60%) had aggressive B-cell lymphoma, 10 patients (50%) were refractory to most recent prior therapy, and seven patients (35%) were previously treated with autologous CD19-targeted CAR T-cell therapy.

In the second and third single-dose cohorts of the Monotherapy and Combination Arms comprising a total of 14 patients, 10 of 14 patients (71%) achieved an objective response, including seven patients (50%) that achieved a complete response (CR), as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following FT596 dosing. Eight of 10 patients (80%) that had not previously received CD19-targeted CAR T-cell therapy achieved an objective response, including five patients (50%) that achieved CR. Two of four patients (50%) that had previously received CD19-targeted CAR T-cell therapy, both of whom were treated in the Combination Arm, achieved a CR. In the first single-dose cohorts of the Monotherapy and Combination Arms comprising a total of six patients, only one patient achieved an objective response, suggesting dose-response treatment effects for FT596. The ongoing dose-escalation study of FT596 is currently enrolling patients in the fourth single-dose cohort of 900 million cells in each arm.

FT516 Program

The clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2of fludarabine), a single dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting. Dose escalation is currently ongoing in the fourth multi-dose cohort of 900 million cells per dose.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting held in June, the Company highlighted positive interim clinical data for 11 patients treated in the second and third multi-dose cohorts of 90 million cells per dose (n=4) and 300 million cells per dose (n=7). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy. No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no TEAEs of any grade of CRS, ICANS, or GVHD were reported.