Fate Therapeutics Highlights FT522 Off-the-shelf, ADR-armed CAR NK Cell Product Candidate at 2024 ACR Convergence
Fate Therapeutics presented initial clinical data for FT522, its off-the-shelf, ADR-armed CAR NK cell product for B-cell lymphoma and autoimmune diseases. In the Phase 1 lymphoma study, FT522 showed a favorable safety profile with complete responses and demonstrated ability to persist and target CD19+ B cells without conditioning chemotherapy. The company is initiating a Phase 1 basket study for B cell-mediated autoimmune diseases as an add-on to standard treatments. Initial data showed no dose-limiting toxicities, with complete responses observed in indolent lymphoma patients and partial responses in other lymphoma types. The study revealed dose-dependent activity and successful B-cell depletion, supporting FT522's potential in treating autoimmune conditions.
Fate Therapeutics ha presentato dati clinici iniziali per FT522, il suo prodotto di cellule NK CAR armato ADR da utilizzare pronto all'uso, rivolto al linfoma a cellule B e alle malattie autoimmuni. Nello studio di fase 1 sul linfoma, FT522 ha mostrato un profilo di sicurezza favorevole con risposte complete e ha dimostrato la capacità di persistere e mirare alle cellule B CD19+ senza chemioterapia di condizionamento. L'azienda sta avviando uno studio pilota di fase 1 per le malattie autoimmuni mediate da cellule B come aggiunta ai trattamenti standard. I dati iniziali non hanno evidenziato tossicità limitanti alla dose, con risposte complete osservate nei pazienti con linfoma indolente e risposte parziali in altri tipi di linfoma. Lo studio ha rivelato un'attività dipendente dalla dose e un'efficace deplezione delle cellule B, a supporto del potenziale di FT522 nel trattamento delle condizioni autoimmuni.
Fate Therapeutics presentó datos clínicos iniciales para FT522, su producto de células NK CAR con armamento ADR de uso inmediato, para linfoma de células B y enfermedades autoinmunes. En el estudio de linfoma de fase 1, FT522 mostró un perfil de seguridad favorable con respuestas completas y demostró la capacidad de persistir y dirigirse a las células B CD19+ sin quimioterapia de acondicionamiento. La compañía está iniciando un estudio de fase 1 como cesta para enfermedades autoinmunes mediadas por células B como complemento a los tratamientos estándar. Los datos iniciales mostraron que no hubo toxicidades limitantes por dosis, con respuestas completas observadas en pacientes con linfoma indolente y respuestas parciales en otros tipos de linfoma. El estudio reveló actividad dependiente de la dosis y una exitosa depleción de células B, respaldando el potencial de FT522 en el tratamiento de condiciones autoinmunes.
Fate Therapeutics는 림프종 및 자가면역 질환을 위한 상비용 ADR 무장 CAR NK 세포 제품인 FT522의 초기 임상 데이터를 발표했습니다. 1상 림프종 연구에서 FT522는 호전된 안전성 프로파일과 완전 반응을 보였으며, 조혈모세포 이식 전처치 없이 CD19+ B 세포를 표적하고 지속할 수 있는 능력을 입증했습니다. 회사는 표준 치료를 보완하기 위해 B 세포 매개 자가면역 질환에 대한 1상 바스켓 연구를 시작하고 있습니다. 초기 데이터는 용량 제한 독성 없이 관찰되었으며, 각각의 림프종 환자에서 완전 반응과 다른 림프종 유형에서 부분 반응이 있었습니다. 이 연구는 용량 의존적인 활성을 드러내고 성공적인 B 세포 고갈을 보여, 자가면역 질환 치료에서 FT522의 잠재력을 뒷받침하고 있습니다.
Fate Therapeutics a présenté des données cliniques initiales pour FT522, son produit de cellules NK CAR armées ADR prêt à l'emploi, pour le lymphome à cellules B et les maladies auto-immunes. Dans l'étude de phase 1 sur le lymphome, FT522 a montré un profil de sécurité favorable avec des réponses complètes et a démontré sa capacité à persister et à cibler les cellules B CD19+ sans chimiothérapie de conditionnement. La société initie une étude de phase 1 sur les maladies auto-immunes médiées par les cellules B en complément des traitements standards. Les données initiales n'ont montré aucune toxicité limitante de dose, avec des réponses complètes observées chez les patients atteints de lymphomes indolents et des réponses partielles dans d'autres types de lymphomes. L'étude a révélé une activité dépendante de la dose et une déplétion réussie des cellules B, renforçant le potentiel de FT522 dans le traitement des conditions auto-immunes.
Fate Therapeutics hat erste klinische Daten zu FT522, seinem sofort einsetzbaren, ADR-ausgerüsteten CAR-NK-Zellprodukt gegen B-Zell-Lymphome und Autoimmunerkrankungen, präsentiert. In der Phase-1-Studie zu Lymphomen zeigte FT522 ein günstiges Sicherheitsprofil mit kompletten Antworten und bewies die Fähigkeit, zu persistieren und CD19+ B-Zellen ohne konditionierende Chemotherapie zu zielen. Das Unternehmen startet eine Phase-1-Korbstudie für b-zellvermittelte Autoimmunerkrankungen als Zusatz zu Standardbehandlungen. Erste Daten zeigten keine dosislimitierenden Toxizitäten, mit kompletten Antworten bei Patienten mit indolentem Lymphom und teilweisen Antworten bei anderen Lymphomtypen. Die Studie enthüllte eine dosisabhängige Aktivität und eine erfolgreiche B-Zell-Depletion, die das Potenzial von FT522 zur Behandlung von Autoimmunerkrankungen unterstützt.
- No dose-limiting toxicities or serious adverse events reported in Phase 1 trial
- Complete responses achieved in all three indolent lymphoma patients at first dose level
- Demonstrated ability to function without conditioning chemotherapy, expanding potential patient base
- Successful B-cell depletion observed with each FT522 dose
- 20-fold increase in median cumulative pharmacokinetics at higher dose level
- Two DLBCL patients did not respond to treatment at first dose level
- efficacy data available from small patient population
Insights
The initial Phase 1 data for FT522 represents significant clinical progress. The therapy shows promising efficacy with complete responses in indolent lymphoma patients and a favorable safety profile with no major adverse events. Key highlights include:
- Successful B-cell depletion without conditioning chemotherapy, a major advancement for autoimmune treatment
- Functional persistence of cells through Day 15
- Complete responses in the conditioning arm at both dose levels
- Expansion into autoimmune diseases including AAV, IMM, SSc and SLE
The preclinical data showing dose-dependent tissue infiltration and effective B-cell depletion in SLE donor samples strongly supports the therapeutic potential in autoimmune conditions. The companion FT596 data with 85% complete response rate in follicular lymphoma provides additional validation of the platform technology.
This data represents a significant commercial opportunity in both oncology and autoimmune markets. The ability to deliver effective treatment without conditioning chemotherapy could be a game-changing differentiator, potentially expanding the addressable patient population and improving the competitive position against existing cell therapies. The dual-market strategy targeting both cancer and autoimmune conditions significantly expands the commercial potential. The strong safety profile and efficacy signals position FT522 favorably for potential accelerated development pathways, particularly in autoimmune indications where treatment options are
Phase 1 Basket Study for B Cell-mediated Autoimmune Diseases to Assess FT522 as Add-on to Standard-of-care Induction and Maintenance Regimens without Conditioning Chemotherapy
Initial Phase 1 Clinical Data in Relapsed / Refractory B-cell Lymphoma Show Favorable Safety Profile, Complete Responses, and Persistence of FT522 Live Cells
Selective Targeting and Reduction of CD19+ B Cells Observed with Each FT522 Dose in Study’s First Low-dose Cohort without Conditioning Chemotherapy, Supporting Novel ADR Technology
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 Company’s Phase 1 study of FT522 in relapsed / refractory B-cell lymphoma at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. FT522 is the Company’s off-the-shelf, CD19-targeted chimeric antigen receptor (CAR) natural killer (NK) cell product candidate that incorporates multiple novel synthetic controls of cell function designed to target and deplete pathogenic immune cells, and is the Company’s first product candidate to integrate its alloimmune defense receptor (ADR) technology to enable effective treatment of patients without administration of intense conditioning chemotherapy. The Company is also initiating a Phase 1 study of FT522 across a basket of B cell-mediated autoimmune diseases as add-on to standard-of-care induction and maintenance regimens without administration of conditioning chemotherapy to patients.
“We are very excited with the initial data emerging from the low-dose cohorts of our FT522 Phase 1 study in B-cell lymphoma, where we have observed a favorable safety profile, complete responses with conditioning chemotherapy, and the potential of our ADR-armed CAR NK cell product candidate to functionally persist and selectively deplete pathogenic CD19+ B cells without administration of conditioning chemotherapy to patients,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “We believe these data provide compelling support for our highly-differentiated therapeutic strategy in autoimmunity, and we look forward to clinically assessing FT522 as an add-on to standard-of-care induction and maintenance regimens without administration of conditioning chemotherapy to patients.”
Initial FT522 Phase 1 Clinical and Translational Data in Relapsed / Refractory B-cell Lymphoma
The Company’s ongoing multi-center, Phase 1 clinical trial in relapsed / refractory B-cell lymphoma (NCT05950334) is assessing up to three doses of FT522 (Day 1, 4, and 8) in combination with a single dose of rituximab, with and without administration of conditioning chemotherapy to patients. As of a data cutoff date of November 8, 2024, there have been no dose-limiting toxicities (DLTs) and no events of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), or graft-versus-host disease (GvHD).
In the study’s conditioning arm (Regimen A), at the first dose level of 300 million cells per dose (A-DL1; n=6), all three patients with indolent lymphoma achieved a complete response (CR) and one patient with mantle cell lymphoma achieved a partial response (PR), while two patients with diffuse large B-cell lymphoma (DLBCL) did not respond to treatment (1 stable disease (SD); 1 progressive disease). At the second dose level of 900 million cells per dose (A-DL2; n=3), two of three patients with DLBCL achieved an overall response (1 CR; 1 PR; 1 SD). The potential for FT522 dose-dependent activity was supported by pharmacokinetics (PK), which showed a greater than 20-fold increase in median cumulative PK between the two dose levels (>80,000 copies*day/µgDNA for A-DL2 and <4,000 copies*day/µgDNA for A-DL1).
In addition, three patients have been treated without administration of conditioning chemotherapy in the study’s second arm (Regimen B), which is intended to provide a stringent assessment of the Company’s ADR technology designed to target 4-1BB+ immune cells and promote functional persistence without ablating a patient’s immune system. At the first dose level of 300 million cells per dose (B-DL1; n=3), live FT522 cells were detected in the patients’ peripheral blood through Day 15 (one week post-infusion of the third dose), demonstrating the ability of FT522 to persist in the presence of an unmatched, fully-intact immune system. Notably, in all three patients, each dose of FT522 on Day 1, 4, and 8 maintained functional activity as evidenced by a similar percent reduction in circulating CD19+ B cells in the patients’ peripheral blood with each infused dose. These first-of-kind translational data support the potential of live FT522 cells to functionally persist and deplete pathogenic CD19+ B cells without administration of conditioning chemotherapy to patients.
FT522 Phase 1 Basket Study in B cell-mediated Autoimmune Diseases
The Company’s Phase 1 study is designed to assess the safety, pharmacokinetics, and activity of FT522 across a basket of B cell-mediated autoimmune diseases, including anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), idiopathic inflammatory myositis (IMM), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). The Phase 1 study is intended to treat patients with up to four doses of FT522, without administration of conditioning chemotherapy, as an add-on to rituximab induction therapy (Regimen A) and as an add-on to maintenance therapy in combination with rituximab (Regimen B). Dose escalation is expected to commence at 900 million cells per dose.
In a preclinical in vivo biodistribution study, FT522 showed dose-dependent trafficking, infiltration, and residency in primary, 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). In addition, in an in vitro re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, FT522 uniquely drove rapid and deep CD19+ B cell depletion, maintained functional persistence, and eliminated alloreactive T cells, indicating that FT522 has the potential to function effectively in the presence of an unmatched host immune system.
FT596 Phase 1 Clinical Data in Relapsed / Refractory B-cell Lymphoma
The Company also presented Phase 1 clinical data from FT596, its prior-generation CD19-targeted CAR NK cell product candidate, in relapsed / refractory B-cell lymphoma (NCT04245722). The completed study enrolled 68 heavily pre-treated patients (median of 4 prior lines of therapy) with late-stage disease (
Durable responses across histologies were observed, with an overall and complete response rate of
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 safety and therapeutic potential of the Company’s iPSC-derived CAR T-cell product candidates, including FT522 and FT596, 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 FT522 and FT596, 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
FAQ
What are the initial results of FT522 Phase 1 trial for B-cell lymphoma (FATE)?
How many complete responses did FT522 (FATE) achieve in the first dose level?
What autoimmune diseases will be studied in FT522's Phase 1 basket trial (FATE)?
