Fate Therapeutics Announces First Lupus Patient Treated in Phase 1 Autoimmunity Study of Off-the-shelf FT819 CAR T-cell Program
Pre-treatment Sample of Patient’s Blood Showed Rapid and Potent Depletion of CD19+ B Cells in Ex Vivo Cytotoxicity Assay with FT819
Translational Data from FT819 Phase 1 B Cell Malignancies Study Support Key Therapeutic Mechanisms of Activity for B Cell-mediated Autoimmune Diseases
Initial Clinical Observations of FT522 CAR NK Cell Program in Phase 1 B Cell Lymphoma Study Show Rapid, Deep, and Sustained B Cell Depletion and Enhanced Persistence in the Periphery
The multi-center, Phase 1 autoimmunity study of FT819 is designed to assess safety, pharmacokinetics, and anti-B cell activity for patients with moderate-to-severe SLE (NCT06308978). The first patient, a 27 year-old woman diagnosed with SLE over ten years ago who has refractory disease despite having been treated with multiple standard-of-care therapies, received conditioning chemotherapy followed by a single dose of FT819 at 360 million cells. The patient was discharged after a three-day hospital stay without any notable adverse events. In a "first-of-kind" translational assessment using a sample of the patient’s blood obtained prior to administration of conditioning chemotherapy, FT819 induced rapid and potent depletion of the patient’s CD19+ B cells in an ex vivo cytotoxicity assay.
“The seminal data with autologous CAR-T cell therapy demonstrating early and long-lasting remissions in patients with certain B cell-mediated autoimmune diseases is remarkable, and we are very excited to bring potentially novel therapeutic solutions with disease-modifying potential to our patients”, said
“We are excited to bring our iPSC product platform and our first product candidates to patients with autoimmune diseases, where preclinical and translational data from our off-the-shelf FT819 CAR T-cell program and our FT522 CAR NK cell program demonstrate key therapeutic mechanisms of activity for autoimmunity,” said
Translational Data for FT819 iPSC-derived CAR T-cell Program
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. Translational data presented today at ASGCT from the Company’s Phase 1 BCM study show that a single dose of FT819 exhibited multiple therapeutic mechanisms implicated in generating an immune reset in patients with B cell-mediated autoimmune disease. Clinical data highlighted today at ASGCT include:
- Blood samples taken from 23 patients treated for relapsed / refractory B cell lymphoma showed rapid and deep CD19+ B cell depletion, with sustained suppression of B cells, in the periphery during the initial 30-day period following administration of standard conditioning chemotherapy and FT819;
- Patient case studies demonstrating secondary and tertiary tissue trafficking, infiltration, and activity, with complete elimination of CD19+ cells in tissue; and
- Patient case studies of plasma cell depletion and B-cell reconstitution showing recovery of naïve and immature phenotypes, with little to no recovery of activated memory B cells or plasmablasts.
Notably, the Company also presented patient case studies demonstrating the capacity of FT819 to induce rapid, deep, and sustained B-cell depletion without the use of fludarabine as a conditioning agent. Collectively, these data support the potential of FT819 to reset the immune system of patients with autoimmune diseases, including as an add-on therapy to commonly-used treatment regimens. The presentation is available on the Company’s website here.
Preclinical and Initial Clinical Observations for FT522 iPSC-derived CAR NK Cell Program Data
FT522 is the Company’s off-the-shelf, CD19-targeted CAR NK cell product candidate and its first to incorporate a novel alloimmune defense receptor (ADR), which is designed to increase the potency of off-the-shelf cell therapy and enable effective treatment without administration of conditioning chemotherapy to patients. Data highlighted today at ASGCT include:
- In a novel re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, FT522 uniquely drove rapid and deep CD19+ B cell depletion, eliminated alloreactive T cells, and maintained functional persistence, indicating that FT522 can function effectively in the presence of an unmatched host immune system;
- In a preclinical in vivo biodistribution study, FT522 showed dose-dependent trafficking, infiltration, and residency in secondary and tertiary tissues without cytokine support at human dose equivalency levels of 250 million cells per dose and 1 billion cells per dose (based on 20 gram mouse and 65 kilogram human allometric conversion); and
- In initial clinical observations from the Company’s ongoing Phase 1 BCL study, the first two patients treated with FT522 showed rapid, deep, and sustained B-cell depletion in the periphery throughout the one-month treatment cycle. In addition, both patients showed enhanced persistence of FT522 in the periphery compared to clinical data observed with FT596, a prior-generation CD19-targeted CAR NK cell without ADR technology.
The Company intends to submit an Investigational New Drug (IND) application to the
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.
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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 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 initiation and continuation of enrollment in the Company’s clinical trials, 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, and the potential capabilities and benefits of the Company’s iPSC product platform. 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 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, 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
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Source: Fate Therapeutics, Inc.