Interim Phase 1 Data of FT576 BCMA-targeted Product Candidate Show Clinical Activity in Initial Single-dose Escalation Cohorts as Monotherapy and in Combination with Daratumumab

Preclinical Data under Janssen Collaboration with FT555 GPRC5D-targeted Product Candidate Demonstrate Robust and Durable Tumor Clearance in Highly Aggressive Myeloma Model

SAN DIEGO, Dec. 10, 2022 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, today presented interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT576 for patients with relapsed / refractory multiple myeloma (r/r MM) at the 64th American Society of Hematology Annual Meeting and Exposition. The off-the-shelf product candidate, which is derived from a clonal master engineered induced pluripotent stem cell (iPSC) line, incorporates a chimeric antigen receptor (CAR) targeting B-cell maturation antigen (BCMA) as well as a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor to maximize antibody-dependent cellular cytotoxicity (ADCC) and enable dual-antigen targeting of myeloma cells through combination with monoclonal antibody (mAb) therapy. Preclinical data published last month in the journal Nature Communications (Cichocki et al. 2022, 13:7341) demonstrated that single-dose administration of FT576 was effective at controlling tumor growth in vivo, with deeper and more sustained anti-tumor activity observed through multi-dose administration of FT576 as well as in combination with the CD38-targeted monoclonal antibody daratumumab.

“The interim Phase 1 data from the low-dose cohorts of single-dose administration of FT576 in patients with relapsed / refractory disease provide encouraging clinical evidence of BCMA-targeted activity,” said Yu-Waye Chu, Chief Medical Officer of Fate Therapeutics. “In addition, initial safety observations of FT576 as monotherapy and in combination with daratumumab, with no reported events of cytokine release syndrome and ICANS as well as no study discontinuations due to treatment-emergent adverse events, indicate that the off-the-shelf product candidate has the potential to be safely administered in the outpatient setting. Dose escalation is currently ongoing with multi-dose regimens, and we look forward to evaluating the effect of increasing dose and dose frequency to define the product candidate’s therapeutic profile.”  

Interim Phase 1 Dose-escalation Efficacy Data
The multi-center Phase 1 clinical trial of FT576 is designed to assess its safety and clinical activity in adult patients with r/r MM, and to determine the recommended Phase 2 dose and schedule, as monotherapy (Regimen A) and in combination with daratumumab to simultaneously target BCMA and CD38 (Regimen B). As of the October 7, 2022 data cutoff date, 9 patients with r/r MM have been treated with a single dose of FT576, including 6 patients in Regimen A and 3 patients in Regimen B (see Table 1). Patients received standard conditioning chemotherapy consisting of cyclophosphamide (Cy) at 300 mg/m² and fludarabine (Flu) at 30 mg/m² for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 5 prior lines of therapy (range 3-10), including 6 patients (67%) that were refractory to last therapy.

• In Regimen A, 6 patients were treated with a single dose of FT576 as monotherapy in the first dose cohort at 100 million cells (n=3) and the second dose cohort at 300 million cells (n=3). In the second dose cohort, one patient, who had received 5 prior lines of therapy, was triple-refractory to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 mAb, and was refractory to last therapy (pomalidomide, daratumumab and dexamethasone), achieved a very good partial response (VGPR) with the other two patients showing stable disease (SD). Further evidence of FT576 activity was observed in the second dose cohort, with two patients for whom serum BCMA levels were evaluable showing a substantial treatment-induced decrease in soluble BCMA.
• In Regimen B, 3 patients were treated with a single dose of FT576 in combination with daratumumab in the first dose cohort at 100 million cells, with one patient achieving a partial response (PR) and one patient achieving a minor response (MR). All 3 patients showed a substantial treatment-induced decrease in soluble BCMA.

The Company has now initiated enrollment of two-dose escalation cohorts at 300 million cells per dose in both regimens.

Interim Phase 1 Dose-escalation Safety Data
No dose-limiting toxicities, and no events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD), were observed. Both FT576 treatment regimens were well tolerated. Two patients experienced Grade 3 or greater FT576-related adverse events (AEs), with one patient having Grade 3 diarrhea and one patient having two episodes of Grades 3 through 4 neutropenia and 3 episodes of Grade 3 anemia, all of which resolved. There were no serious AEs related to FT576. Grade 3 or greater treatment-emergent AEs (TEAEs) not related to FT576 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs.

FT555 GPRC5D-targeted CAR NK Cell Program
Under its collaboration with Janssen Biotech, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, the Company is currently conducting preclinical development of FT555, a multiplexed-engineered CAR NK cell product candidate derived from a clonal master engineered iPSC line incorporating four functional components: a proprietary CAR optimized for NK cell biology that targets GPRC5D, an orphan G-protein-coupled receptor expressed on myeloma cells with a distribution that is similar to but independent of BCMA; a novel hnCD16 Fc receptor for enhanced ADCC; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments.

At ASH, scientists from the companies jointly presented preclinical data demonstrating that single-dose administration of FT555 as monotherapy resulted in robust and durable antigen-mediated tumor regression in two independent disseminated tumor models of aggressive myeloma, which activity was further improved in combination with daratumumab to simultaneously target GPRC5D and CD38 antigens. Administration of three doses of FT555 as monotherapy further improved tumor clearance and showed superior activity compared to single-dose primary CAR T cells.

In May 2022, Janssen exercised its commercial option to FT555, pursuant to which the Company granted Janssen an exclusive license for development and commercialization of FT555. The Company is eligible to receive clinical, regulatory, and commercial milestones, plus double-digit royalties on worldwide commercial sales of the product candidate. In addition, the Company retains the right to elect to co-commercialize, and share equally in profits and losses, in the United States, subject to its payment of certain clinical development costs and adjustments in milestone and royalty payments.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT576
FT576 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Company’s immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.

Forward-Looking Statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the progress of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the therapeutic and market potential of the Company’s product candidates, the Company’s clinical development strategy, including for its FT576 and FT555 product candidates, the expected benefits of the Company's collaboration with Janssen and expectations regarding future potential research, milestone and royalty payments under the collaboration, and the objectives, plans and goals of the collaboration. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company’s product candidates may not demonstrate the requisite safety or efficacy to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company’s product candidates or in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT576 and/or FT555 may not be replicated in ongoing or future clinical trials, the risk that FT576 and/or FT555 may not produce therapeutic benefits or may cause other unanticipated adverse effects, the risk that the Company may not comply with its obligations under and otherwise maintain its collaboration agreement with Janssen on the agreed upon terms, and the risk that research funding and milestone payments received by the Company under the collaboration may be less than expected. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:
Christina Tartaglia
Stern Investor Relations, Inc.
212.362.1200
christina@sternir.com