27-year-old African American-Asian Woman with Active Lupus Nephritis Achieved DORIS Clinical Remission; Patient Remains On-study, in Clinical Remission, and Free of All Immunosuppressive Therapies

Patient Treated with Fludarabine-free Conditioning and Single-dose FT819; Favorable Safety Profile with No Grade ≥3 Adverse Events and No Events of CRS, ICANS, or GvHD

Reconstituted B Cell Compartment Predominantly Consists of Naïve, Non-class Switched B Cells with Deep Depletion of Aberrant B Cells and Plasmablasts, Indicative of Immune Reset

Second Treatment Arm Adding FT819 to Maintenance Therapy without Conditioning Chemotherapy Opened for Enrollment

SAN DIEGO, Nov. 18, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial clinical and translational data from the first patient treated in its FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. The patient, a 27-year-old African American-Asian woman diagnosed with lupus nephritis (LN) over ten years ago, received fludarabine-free conditioning followed by a single dose of FT819. The patient achieved DORIS (definition of remission in SLE) clinical remission and LLDAS (low lupus disease activity state) as of Month 6 follow-up. The patient continues on-study, in clinical remission, and free of all immunosuppressive therapies as of a data cutoff date of November 11, 2024. FT819 is the Company's off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking.

"These initial results are incredibly promising. Our patient not only went into drug-free clinical remission but also had resolution of fatigue, something that we as rheumatologists struggle to improve with our treatments," said Jennifer Medlin, M.D., and Principal Investigator at the University of Nebraska Medical Center. "If we continue to see similar results in other patients with an acceptable safety profile, off-the-shelf CAR T-cell therapy could be a complete game-changer for our sickest lupus patients. This gives me hope for a future where we can make a great impact on these patients with devastating disease."

Patient 1 Case Study

The patient presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. As of the data cutoff date, the patient has experienced no Grade ≥3 AEs, no serious adverse events (SAEs), and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. As of the data cutoff date, the patient continues in DORIS clinical remission and remains free of all immunosuppressive therapy.

Rapid elimination of CD19+ B cells in the periphery was observed following fludarabine-free conditioning and treatment with a single dose of FT819. B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. Notably, the unique double-negative (DN) B-cell subset, previously described and associated with severe SLE, was nearly eliminated.

"These seminal data with fludarabine-free conditioning and off-the-shelf CAR T-cell therapy in autoimmunity are exciting, and we are very pleased that the first patient with active lupus nephritis had a favorable clinical experience, achieved drug-free clinical remission, and continues on-study free of all immunosuppressive therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We believe our highly-differentiated therapeutic approach has the potential to transform outcomes for patients with autoimmune diseases without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization."

FT819 Phase 1 Autoimmunity Study

The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819 (NCT06308978). The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360 million cells. All three patients remain on-study, and there have been no dose-limiting toxicities (DLTs) and no events of any grade of CRS, ICANS, or GvHD. The Company plans to present clinical and translational data from the first three patients at the American Society of Hematology (ASH) Annual Meeting being held in San Diego, CA on December 7-10.

The Company is also enrolling a second treatment arm under the FT819 Phase 1 Autoimmunity study to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. This new arm is being conducted in parallel with the study's conditioning arm.

About Fate Therapeutics' iPSC Product Platform

Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company's proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company's platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics' iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.

About Fate Therapeutics, Inc.

Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company's pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit .

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 safety and therapeutic potential of the Company's iPSC-derived CAR T-cell product candidates, including FT819, the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Company's progress, plans and timelines for the clinical investigation of its product candidates, including the expected clinical development plans for FT819, the initiation and continuation of enrollment in the Company's clinical trials, the initiation of additional clinical trials and additional dose cohorts in ongoing clinical trials of the Company's product candidates, the timing and availability of data from the Company's clinical trials, the therapeutic and market potential of the Company's research and development programs and product candidates, the Company's clinical and product development strategy, and the Company's expectations regarding progress, plans, and timelines. 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 research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes 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 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 or delays in manufacturing or supplying the Company's product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, 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
Precision AQ
212.362.1200
christina.tartaglia@precisionaq.com

Source: Fate Therapeutics, Inc.