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
Fate Therapeutics (NASDAQ: FATE) presented initial clinical and preclinical data for FT825/ONO-8250, a CAR T-cell therapy targeting HER2 in advanced solid tumors. The Phase 1 study's first low-dose cohort of three heavily pre-treated patients showed favorable safety outcomes with no dose-limiting toxicities or adverse events. The therapy demonstrated CAR T-cell expansion and maintained activation state at Day 8 post-treatment.
The product incorporates a novel H2CasMab-2 binding domain designed to overcome on-target, off-tumor toxicity. Preclinical data showed selective targeting of cancer cells while limiting effects on normal HER2+ cells. The study continues enrollment at higher doses and in combination with EGFR-targeted antibody therapy.
Fate Therapeutics (NASDAQ: FATE) ha presentato dati clinici e preclinici iniziali per FT825/ONO-8250, una terapia con cellule T CAR che mira a HER2 nei tumori solidi avanzati. La prima coorte a bassa dose dello studio di Fase 1, composta da tre pazienti pesantemente pretrattati, ha mostrato risultati di sicurezza favorevoli, senza tossicità limitanti da dose o eventi avversi. La terapia ha dimostrato un'espansione delle cellule T CAR e ha mantenuto uno stato di attivazione al giorno 8 dopo il trattamento.
Il prodotto incorpora un nuovo dominio di legame H2CasMab-2 progettato per superare la tossicità on-target ma off-tumore. I dati preclinici hanno mostrato un targeting selettivo delle cellule cancerose, limitando gli effetti sulle normali cellule HER2+. Lo studio continua con l'arruolamento a dosi più elevate e in combinazione con una terapia ad anticorpi mirata contro EGFR.
Fate Therapeutics (NASDAQ: FATE) presentó datos clínicos y preclínicos iniciales para FT825/ONO-8250, una terapia de células T CAR que se dirige a HER2 en tumores sólidos avanzados. La primera cohorte de baja dosis del estudio de Fase 1, compuesta por tres pacientes con un tratamiento previo intenso, mostró resultados de seguridad favorables sin toxicidades limitantes por dosis ni eventos adversos. La terapia demostró expansión de células T CAR y mantuvo el estado de activación en el día 8 después del tratamiento.
El producto incorpora un nuevo dominio de unión H2CasMab-2 diseñado para superar la toxicidad on-target pero off-tumor. Los datos preclínicos mostraron un objetivo selectivo de células cancerosas mientras se limitaban los efectos en las células normales HER2+. El estudio continúa reclutando a dosis más altas y en combinación con terapia de anticuerpos dirigida a EGFR.
Fate Therapeutics (NASDAQ: FATE)는 진행성 고형 종양에서 HER2를 타겟으로 하는 CAR T 세포 치료제인 FT825/ONO-8250의 초기 임상 및 비임상 데이터를 발표했습니다. 1상 연구의 첫 저용량 코호트인 세 명의 심한 선행 치료를 받은 환자들은 용량 한계 독성이나 부작용 없이 유리한 안전성 결과를 보였습니다. 치료법은 CAR T 세포 확장을 나타내고 치료 후 8일째에 활성화 상태를 유지했습니다.
이 제품은 표적 위치에서 비종양 독성을 극복하기 위해 설계된 새로운 H2CasMab-2 결합 도메인을 통합하고 있습니다. 비임상 데이터는 정상 HER2+ 세포에 미치는 영향을 제한하면서 암 세포를 선택적으로 표적하였음을 보여주었습니다. 이 연구는 더 높은 용량으로 계속하여 EGFR 표적 항체 치료와 병행됩니다.
Fate Therapeutics (NASDAQ: FATE) a présenté des données cliniques et précliniques initiales pour FT825/ONO-8250, une thérapie à base de cellules T CAR ciblant HER2 dans les tumeurs solides avancées. La première cohorte à faible dose de l'étude de Phase 1, composée de trois patients ayant subi des traitements lourds, a montré des résultats de sécurité favorables sans toxicité limitante de la dose ni événements indésirables. La thérapie a démontré une expansion des cellules T CAR et a maintenu son état d'activation au jour 8 après le traitement.
Le produit intègre un nouveau domaine de liaison H2CasMab-2 conçu pour surmonter la toxicité on-target, off-tumor. Les données précliniques ont montré un ciblage sélectif des cellules cancéreuses tout en limitant les effets sur les cellules normales HER2+. L'étude continue son recrutement à des doses plus élevées et en combinaison avec une thérapie anticorps ciblée contre l'EGFR.
Fate Therapeutics (NASDAQ: FATE) hat erste klinische und präklinische Daten für FT825/ONO-8250 präsentiert, eine CAR-T-Zelltherapie, die auf HER2 bei fortgeschrittenen soliden Tumoren abzielt. Die erste Niedrigdosisgruppe der Phase-1-Studie mit drei stark vorbehandelten Patienten zeigte günstige Sicherheitsdaten ohne dosislimitierende Toxizität oder unerwünschte Ereignisse. Die Therapie zeigte eine Expansion der CAR-T-Zellen und hielt den Aktivierungszustand am 8. Tag nach der Behandlung aufrecht.
Das Produkt enthält eine neuartige H2CasMab-2-Bindungsdomäne, die entwickelt wurde, um on-target, off-tumor Toxizität zu überwinden. Die präklinischen Daten zeigten eine selektive Zielgerichtetheit auf Krebszellen, während die Auswirkungen auf normale HER2+ Zellen begrenzt wurden. Die Studie setzt die Rekrutierung mit höheren Dosen und in Kombination mit einer EGFR-zielgerichteten Antikörpertherapie fort.
- Initial Phase 1 safety data shows no dose-limiting toxicities or adverse events
- Successful CAR T-cell expansion observed in all three treated patients
- Strategic collaboration with Ono Pharmaceutical for development and commercialization
- Preclinical data demonstrates selective targeting of cancer cells with impact on normal tissue
- Early-stage clinical trial with only three patients treated so far
- efficacy data available at this point
Insights
The initial Phase 1 data for FT825/ONO-8250 shows promising safety signals in treating advanced solid tumors. The key highlights include no dose-limiting toxicities and absence of common CAR-T side effects like cytokine release syndrome in the first three patients at the 100M cell dose. The CAR-T cells demonstrated desired expansion and maintained an activated state by Day 8, suggesting potential therapeutic activity.
The novel H2CasMab-2 binding domain appears to address a critical challenge in HER2-targeted therapy by preferentially binding to tumor-specific HER2 variants while sparing normal tissue expression. This could potentially reduce off-target toxicity compared to existing HER2 therapies like Herceptin. The dual targeting capability through ADCC with existing antibody treatments also presents an interesting combination strategy.
While early data is encouraging, larger patient numbers and longer follow-up are needed to validate efficacy. The ongoing dose escalation to 300M cells and combination cohorts will be important to watch.
Novel H2CasMab-2 Antigen Binding Domain Shown to Preferentially Target HER2 Expressed on Tumor Cells in Preclinical Studies
Initial Low-Dose Cohort of FT825 / ONO-8250 as Monotherapy Shows Favorable Safety Profile in Phase 1 Solid Tumor Study
Peripheral Blood from First Three Patients Demonstrates CAR T-cell Expansion with Maintenance of Activated State at Day 8 Following Treatment
SAN DIEGO, Nov. 09, 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 new preclinical data for FT825 / ONO-8250, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2), at the 2024 Society of Immunotherapy of Cancer (SITC) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024. FT825 / ONO-8250 incorporates a novel H2CasMab-2 binding domain targeting HER2 that is designed to overcome on-target, off-tumor toxicity and to recognize variants associated with poor clinical outcomes and tumor escape. In an ongoing Phase 1 study in advanced solid tumors, three patients were treated with FT825 / ONO-8250 in the first low-dose cohort as monotherapy, and no dose-limiting toxicities (DLTs) 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. The multi-center, Phase 1 study is currently being conducted under a strategic collaboration with Ono Pharmaceutical Co., Ltd. (Ono).
“FT825 / ONO-8250 integrates seven novel synthetic controls of CAR T-cell function designed to overcome multiple mechanisms that impede the safe and effective treatment of solid tumors. We are very pleased with initial Phase 1 clinical observations from the first low-dose cohort, which showed a favorable safety profile, product expansion, and maintenance of an activated CAR T-cell state,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “In addition, new preclinical data for FT825 / ONO-8250 presented today at SITC highlighted the cancer-selective recognition profile of its novel HER2 antigen binding domain, including its potential to target variants uniquely expressed on tumor cells. Under our collaboration with Ono, we are excited to further assess the potential of FT825 / ONO-8250 to benefit patients with hard-to-treat advanced solid tumors who currently have limited treatment options.”
Initial Phase 1 Clinical Observations
The Phase 1 study is designed to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250 as monotherapy and in combination with monoclonal antibody (mAb) therapy in patients with advanced solid tumors (NCT06241456). 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. Enrollment is currently ongoing at the second dose level of 300 million cells as monotherapy and at the first dose level of 100 million cells in combination with epidermal growth factor receptor (EGFR)-targeted mAb therapy.
Preclinical Data
While HER2-directed therapies, such as trastuzumab (Herceptin) and trastuzumab deruxtecan (Enhertu), are effective in treating HER2-positive cancers, widespread HER2 expression in normal epithelial tissue can lead to significant off-tumor, on-target toxicities. At an oral presentation today at SITC entitled “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”, scientists from the Company, Ono, Osaka University, and Tohoku University 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 on-tumor selectivity of FT825 / ONO-8250 was attributed to its incorporation of a novel HER2-targeted antigen binding domain, which was derived from a cancer-specific monoclonal antibody H2CasMab-2 (Kaneko et al., 2024), that was shown to differentially and preferentially recognize both locally misfolded HER2 and p95 truncation variants of HER2 as compared to trastuzumab. 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.
Under the terms of its partnership with Ono for FT825 / ONO-8250, Fate and Ono are jointly responsible for development and commercialization in the U.S. and Europe, and Ono maintains exclusive development and commercialization rights in the rest of the world. The parties are also conducting preclinical development of an additional solid tumor program targeting an undisclosed tumor-associated antigen.
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 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 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 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 and timelines, and the objectives, plans and goals of its collaboration with Ono. 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), the risk that its product candidates 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 Ono, and the risk that research funding and milestone payments received by the Company under its 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
Precision AQ
212.362.1200
christina.tartaglia@precisionaq.com
FAQ
What were the safety results of FT825/ONO-8250 in the Phase 1 trial?
How many patients were treated with FT825/ONO-8250 in the initial Phase 1 trial?
What is the target of Fate Therapeutics' FT825/ONO-8250 therapy?
