Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-Cell Therapy

Off-the-Shelf CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate Three Dosing Regimens of FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, Aug. 02, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

“Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement.”

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

• Use of a clonal master engineered iPSC line as the starting cell source, which enables CAR T cells to be mass produced and delivered off-the-shelf for broad patient access;
• Incorporation of a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion as described in the journal Nature Medicine (https://doi.org/10.1038/s41591-018-0290-5);
• Insertion of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency as described in the journal Nature (https://doi.org/10.1038/nature21405); and
• Complete bi-allelic disruption of T-cell receptor (TCR) expression for the prevention of graft-versus-host disease (GvHD), a potentially life-threatening complication associated with allogeneic T-cell therapy.

The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24^th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

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 FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

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 advancement of, plans related to, and the therapeutic potential of the Company's product candidates, the Company’s clinical development and manufacturing strategies, and the Company’s plans for the clinical investigation and manufacture of its product candidates, including FT819. 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 results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay 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, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current 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), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. 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