FT825 / Fate Therap, Ono Pharma - LARVOL DELTA

Fate Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Business Updates (GlobeNewswire) - "FT825 / ONO-8250 iPSC-derived CAR T-cell Program:...Under its collaboration with Ono Pharmaceutical Co., Ltd. (Ono), the Company is conducting a multi-center, Phase 1 study to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250, a multiplexed-engineered CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2), in patients with advanced solid tumors (NCT06241456). Enrollment is currently ongoing at the third dose level of 900 million cells as monotherapy and at the second dose level of 300 million cells in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy."

Trial status • Solid Tumor

Preferential targeting of HER2-expressing cancer cells by FT825/ONO-8250, an off-the-shelf iPSC-derived CAR-T cell incorporating novel synthetic mechanisms for enhanced solid tumor activity (SITC 2024) - P1 | "Importantly, in these preclinical settings FT825/ONO-8250 displays limited cytolysis of HER2+ normal/non-tumorigenic cell lines, unlike trastuzumab-based primary CAR-T cells and ADCs such as trastuzumab-emtansine and trastuzumab-deruxtecan. Expression of high-affinity, non-cleavable CD16a by FT825/ONO-8250 also enables flexible complementation of CAR mediated tumor targeting when combined with therapeutic antibodies including EGFR (cetuximab), PDL1 (avelumab), and cMET (amivantamab) through antibody-dependent cellular cytotoxicity...Available clinical and translational updates will also be shared. Ethics Approval These studies were approved by Fate Therapeutics Institutional Animal Care and Use Committee and were carried out in accordance with the National Institutes of Health's Guide for the Care and Use of Laboratory Animals."

CAR T-Cell Therapy • IO biomarker • Oncology • Solid Tumor • EGFR • FCGR3A • HER-2 • PD-L1

Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting (GlobeNewswire) - "Preclinical Data:...At an oral presentation today at SITC...scientists...highlighted that FT825 / ONO-8250 demonstrated potent HER2-specific, anti-tumor activity in both in vitro and in vivo settings with limited cytolytic targeting of HER2+ normal cells....The scientists also presented preclinical data demonstrating that FT825 / ONO-8250 exhibits potent antibody-mediated cellular cytotoxicity (ADCC) through its high-affinity non-cleavable CD16 (hnCD16) Fc receptor, synergizing with trastuzumab to enhance clearance of HER2+ tumor cells and with cetuximab to enable multi-antigen targeting of HER2 and epidermal growth factor receptor (EGFR) expressed on cancer cells."

Preclinical • Solid Tumor

Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting (GlobeNewswire) - P1 | N=351 | NCT06241456 | Sponsor: Fate Therapeutics | "Initial Phase 1 Clinical Observations:...Three heavily pre-treated patients, all of whom were previously treated with at least five prior lines of therapy including HER2-targeted therapy, were administered conditioning chemotherapy and FT825 / ONO-8250 at the first dose level of 100 million cells as monotherapy. In all three patients, peak CAR T-cell expansion was observed at Day 8 following treatment. In addition, phenotyping of FT825 / ONO-8250 sourced from the patients’ peripheral blood on Day 8 was indicative of an activated state (as evidenced by high levels of Granzyme B expression and maintenance of CAR expression) with no evidence of exhaustion (as evidenced by low levels of PD-1 and TIM3 expression). As of a data cutoff date of October 25, 2024, FT825 / ONO-8250 was well-tolerated with no DLTs and no events of any grade of CRS, ICANS, or GvHD."

P1 data • Solid Tumor

Fate Therapeutics Reports Second Quarter 2024 Financial Results and Business Updates (GlobeNewswire) - "FT825 / ONO-8250 iPSC-derived CAR T-cell Program:...Three patients have been treated in the Phase 1 study with a single dose of FT825 / ONO-8250 as monotherapy at the first dose level of 100 million cells and, during the third quarter of 2024, the Company plans to initiate enrollment as monotherapy at the second dose level of 300 million cells and in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy at the first dose level of 100 million cells. The Company plans to present clinical and translational data from the Phase 1 study at a medical conference in the second half of 2024."

P1 data • Trial status • Solid Tumor

FT825/ONO-8250, an Off-the-Shelf, HER2 CAR-T, With or Without Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=351 | Recruiting | Sponsor: Fate Therapeutics

New P1 trial • Oncology • Solid Tumor

Fate Therapeutics Announces Initiation of Phase 1 Clinical Trial for FT825 / ONO-8250 in Patients with HER2-expressing Advanced Solid Tumors (GlobeNewswire) - "Fate Therapeutics...announced the initiation of enrollment for its Phase 1 clinical trial of FT825 / ONO-8250, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2)....The Phase 1 study of FT825 / ONO-8250 is being conducted under a strategic collaboration with Ono Pharmaceutical Co., Ltd. (Ono)....The Phase 1 study is designed to investigate a single dose of FT825 / ONO-8250 as monotherapy and in combination with monoclonal antibody therapy in previously-treated patients with advanced solid tumors. The dose escalation and dose expansion portions of the trial are expected to evaluate safety, tolerability, and pharmacokinetics as well as anti-tumor activity by overall response rate, duration of response and disease control rate."

Trial status • Solid Tumor

Fate Therapeutics Reports Third Quarter 2023 Financial Results and Business Updates (GlobeNewswire) - "The Company’s Investigational New Drug (IND) application for FT825/ONO-8250 was cleared by the U.S. Food and Drug Administration (FDA) in October for conduct of a Phase 1 study in patients with advanced solid tumors. The dose-escalation schema includes two treatment regimens: single-dose FT825/ONO-8250 as monotherapy; and FT825/ONO-8250 in combination with cetuximab....Preclinical data of FT825/ONO-8250, which was presented at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting, demonstrated that the antigen binding profile of H2CasMab-2 is unique and differentiated from that of trastuzumab, exhibiting similar potency with greater specificity for malignant HER2-expressing cells."

IND • New P1 trial • Preclinical • Solid Tumor

Development of FT825/ONO-8250: an off-the-shelf CAR-T cell with preferential HER2 targeting and engineered to enable multi-antigen targeting, improve trafficking, and overcome immunosuppression (SITC 2023) - "Unlike Herceptin-based primary CAR-T cells, FT825/ONO-8250 demonstrated limited cytotoxicity on multiple normal, non-tumorigenic cell lines, underscoring the preference of FT825/ONO-8250 for HER2 expressed by tumor cells (figure 1B). Finally, we observe robust anti-tumor efficacy in vivo in subcutaneous HER2+ xenograft models (figure 1C). Conclusions FT825/ONO-8250, engineered to (i) preferentially target tumor-expressed HER2 and (ii) overcome solid tumor heterogeneity, resist tumor microenvironment suppression, and enhance solid tumor trafficking, is scheduled for IND submission in 2H 2023."

CAR T-Cell Therapy • IO biomarker • Oncology • Solid Tumor • CXCR2 • FCGR3A • HER-2 • IL7 • IL7R

Fate Therapeutics Reports Second Quarter 2023 Financial Results and Business Updates (GlobeNewswire) - "The Company’s landmark Phase 1 clinical trial of FT819 is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master iPSC line....The Company is currently enrolling patients in single-dose treatment cohorts at 540 million cells in B-cell lymphoma and at 360 million cells in chronic lymphocytic leukemia....The Company is currently conducting IND-enabling activities and GMP manufacturing of FT825/ONO-8250, and plans to submit an IND application to the FDA in the second half of 2023 to jointly conduct a Phase 1 study for the treatment of patients with HER2-positive solid tumors."

Enrollment status • IND • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Fate Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Business Updates (GlobeNewswire) - "Mid-2023 IND Submission Planned for FT522 NK Cell Program in B-cell Lymphoma; IND Submission for FT825/ONO-8250 CAR T-cell Product Candidate for Solid Tumors Planned for 2023 under Ono Collaboration."

IND • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Fate Therapeutics Announces Termination of Collaboration Agreement with Janssen, Pipeline Prioritization, Next-Generation Programs, and Key 2023 Initiatives (GlobeNewswire) - "Fate Therapeutics...announced today that it has declined a proposal from Janssen Biotech, Inc. ('Janssen') for continuation of the collaboration and option agreement between the parties on revised terms and conditions and, as a result, the agreement has been terminated and all collaboration activities will be wound down in the first quarter of 2023....IND Submission Planned in Mid-2023 for NHL in Combination with CD20-targeted mAb; FT596 Product Candidate to be Discontinued....2023 IND Submission under Ono Collaboration Planned for FT825/ONO-8250 HER2-targeted CAR T-cell Product Candidate; Solid Tumor Program Incorporates Seven Novel Synthetic Controls Designed to Promote Effector Cell Function, Trafficking, and Resistance to Immunosuppressive Tumor Microenvironment."

Discontinued • IND • Licensing / partnership • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Fate Therapeutics Announces Exercise by ONO Pharmaceutical of Option to HER2-targeted CAR T-Cell Product Candidate for Solid Tumors (GlobeNewswire) - "Fate Therapeutics, Inc....announced that ONO Pharmaceutical Co., Ltd. (ONO) has exercised its option to FT825/ONO-8250...product candidate targeting human epidermal growth factor receptor 2 (HER2)-expressing solid tumors....Under the terms of the Collaboration and Option Agreement, Fate will receive a milestone payment in connection with ONO’s exercise of its option to FT825/ONO-8250. The parties will jointly develop and commercialize FT825/ONO-8250 in the U.S. and Europe, and ONO maintains exclusive development and commercialization rights for FT825/ONO-8250 in the rest of the world. Fate is eligible to receive clinical, regulatory and commercial milestone payments as well as tiered royalties on net sales outside of the United States and Europe by ONO. The parties recently expanded their collaboration to initiate preclinical development of an additional program targeting a second solid tumor antigen."

Licensing / partnership • Oncology • Solid Tumor

Fate Therapeutics Announces Exercise by ONO Pharmaceutical of Option to HER2-targeted CAR T-Cell Product Candidate for Solid Tumors (GlobeNewswire) - "'We are excited to initiate IND-enabling activities under our collaboration with ONO with the goal of submitting an IND application to FDA in 2023'....The Company’s multiplexed-engineered, iPSC-derived CAR T-cell product platform is designed to specifically address these challenges and enable the safe and effective treatment of solid tumors as monotherapy and in combination with monoclonal antibody therapy. At the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting to be held from November 8-12, 2022 in Boston, the Company is presenting a poster presentation of FT825/ONO-8250...which highlights the incorporation of a synthetic CXCR2 receptor to promote cell trafficking, a synthetic TGFβ receptor to redirect immunosuppressive signals in the tumor microenvironment, and a synthetic interleukin-7 receptor fusion protein to induce T-cell activation into its iPSC-derived CAR T-cell product platform."

IND • Preclinical • Oncology