FT516 / Fate Therap, University of Minnesota - LARVOL DELTA

Off-the-shelf induced pluripotent stem-cell-derived natural killer-cell therapy in relapsed or refractory B-cell lymphoma: a multicentre, open-label, phase 1 study. (PubMed, Lancet Haematol) - P1 | "Our findings suggest that cell therapy using iPSC-derived, gene-modified natural killer cells in combination with monoclonal antibody and IL-2 is safe and active in B-cell malignancies and might address limitations of currently available immune-cell therapies, including manufacturing time, heterogeneity, access, and cost."

Journal • P1 data • Acute Myelogenous Leukemia • B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • IL2

FT516-101: FT516 in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov) - P1 | N=72 | Terminated | Sponsor: Fate Therapeutics | Trial completion date: May 2039 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2024 ➔ Oct 2023; The study was terminated by the Sponsor.

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Fate Therapeutics | Trial completion date: Jan 2037 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2023 ➔ Aug 2023; This study was terminated by the Sponsor.

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Fate Therapeutics | Completed ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Jan 2037

Combination therapy • Enrollment closed • Metastases • Trial completion date • Oncology • Solid Tumor

FT516-101: FT516 in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Fate Therapeutics | Recruiting ➔ Active, not recruiting | N=234 ➔ 72

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Fate Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Aug 2037 ➔ Jan 2023 | Trial primary completion date: Aug 2022 ➔ Jan 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Phase I results of FT516, an off-the-shelf, iPSC-derived NK cell therapy expressing a high-affinity, non-cleavable CD16 (hnCD16) combined with avelumab in patients with advanced solid tumors (SITC 2022) - "A Phase I dose-escalation study of FT516 in combination with rituximab for patients with B-cell lymphomas has shown favorable safety and anti-tumor activity...Methods Patients initially received 2 treatment cycles, with the option for 2 additional cycles, each cycle consisting of 3 days of outpatient conditioning chemotherapy (cyclophosphamide 500 mg/m 2 and fludarabine 30 mg/m 2 ) followed by 3 once-weekly doses of FT516 with subcutaneous IL-2 (6 MIU)...Conclusions Up to 900 million FT516 cells administered with IL-2 in multiple doses and multiple cycles in combination with avelumab are safe and tolerable, with evidence of anti-tumor activity following failure of prior anti-PD-(L)1 therapy. These data support the development of next-generation iPSC-derived NK cells engineered with additional synthetic functional elements designed to enhance anti-tumor activity in solid tumors."

Clinical • P1 data • Breast Cancer • Cutaneous Melanoma • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL2

Phase I Study of FT516, an Off-the-Shelf iPSC-Derived NK Cell Therapy, in Combination with Rituximab in Patients with Relapsed/Refractory B-Cell Lymphoma (ASH 2021) - " Primary objectives of the study are to determine the recommended Phase II dose of FT516 in combination with rituximab (R) or obinutuzumab (G) in R/R BCL and to evaluate safety and tolerability in patients (pts) with R/R BCL...The ongoing dose-escalation stage assesses FT516 for up to 2 cycles, each consisting of 3 days of conditioning chemotherapy (cyclophosphamide [CY] 500 mg/m 2 and fludarabine [FLU] 30 mg/m 2 ), a single-dose of R (375 mg/m 2 ), and 3 weekly doses of FT516 (30-900 million cells per dose) each with IL-2 support (6 MIU)...Following dose escalation, further investigation of safety and efficacy will be conducted as follows: FT516 + R or G following FLU/CY in pts with R/R diffuse large B-cell lymphoma (DLBCL) or R/R follicular lymphoma (FL) who have not received prior CAR T-cell therapy; FT516 + R following FLU/CY in pts with R/R BCL who have previously received CAR T-cell therapy; and FT516 + R following bendamustine... As of 07 July 2021, 13 pts (2 at..."

Clinical • Combination therapy • P1 data • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • IL2

Fate Therapeutics to Present Clinical and Preclinical Data for iPSC Product Platform at the Society for Immunotherapy of Cancer 37th Annual Meeting (GlobeNewswire) - "Fate Therapeutics...announced that the Company will present clinical and preclinical data for the Company’s induced pluripotent stem cell (iPSC) product platform at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting being held in Boston, MA, and virtually, November 8-12, 2022."

P1 data • Preclinical

Long-Term Stability of iPSC-Derived CD34+ Cell Banks Supports the Sustainable Manufacture of Off-the-Shelf Immunotherapies (ASGCT 2022) - "We observed no changes in vitality, phenotype, differentiation potential or iNK and iT cell potency. Taken together, our studies show that long-term stored iCD34 cells can serve as an intermediate feedstock for rapid mass production of multiplexed engineered iNK and iT cell therapies."

IO biomarker • Hematological Disorders • Oncology • ANXA5 • CD34

Fate Therapeutics Reports First Quarter 2022 Financial Results and Highlights Operational Progress (GlobeNewswire) - "...In the second quarter of 2022, the Company plans to submit a new clinical protocol to the FT596 Investigational New Drug (IND) application to assess the safety and activity of adding FT596 to R-CHOP, the standard first-line immunochemotherapy for patients with aggressive lymphomas....FT516 Multi-disciplinary RMAT Meeting Planned for mid-2022....The Company plans to hold a multi-disciplinary meeting with the FDA in mid-2022 to discuss key CMC topics and pivotal study design in patients who have progressed or relapsed following prior treatment with FDA‑approved CD19‑directed chimeric antigen receptor (CAR) T-cell therapy....On-track for First Patient Treatment with FT536 CAR MICA/B-targeted NK Cell Product Candidate....the study’s first clinical site to initiate enrollment in the second quarter of 2022."

Enrollment status • FDA event • IND • New P3 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

FT516 and IL2 With Enoblituzumab for Ovarian Cancer (clinicaltrials.gov) - P1 | N=3 | Completed | Sponsor: Masonic Cancer Center, University of Minnesota | Recruiting ➔ Completed | N=31 ➔ 3 | Trial completion date: Jan 2027 ➔ Jan 2022 | Trial primary completion date: Jan 2027 ➔ Jan 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Study of FT516 for the Treatment of COVID-19 in Hospitalized Patients With Hypoxia (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: Masonic Cancer Center, University of Minnesota | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL6

"FT516/FT538: both candidates in the clinic to treat AML do not have a CAR." (@JRMKE3)

Acute Myelogenous Leukemia

FT516-101: FT516 in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov) - P1; N=234; Recruiting; Sponsor: Fate Therapeutics; N=72 ➔ 234; Trial completion date: May 2026 ➔ May 2039; Trial primary completion date: Jul 2021 ➔ May 2024

Clinical • Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Phase I Study of FT516, an Off-the-Shelf iPSC-Derived NK Cell Therapy, in Combination with Rituximab in Patients with Relapsed/Refractory B-Cell Lymphoma (ASH 2021) - " Primary objectives of the study are to determine the recommended Phase II dose of FT516 in combination with rituximab (R) or obinutuzumab (G) in R/R BCL and to evaluate safety and tolerability in patients (pts) with R/R BCL...The ongoing dose-escalation stage assesses FT516 for up to 2 cycles, each consisting of 3 days of conditioning chemotherapy (cyclophosphamide [CY] 500 mg/m 2 and fludarabine [FLU] 30 mg/m 2 ), a single-dose of R (375 mg/m 2 ), and 3 weekly doses of FT516 (30-900 million cells per dose) each with IL-2 support (6 MIU)...Following dose escalation, further investigation of safety and efficacy will be conducted as follows: FT516 + R or G following FLU/CY in pts with R/R diffuse large B-cell lymphoma (DLBCL) or R/R follicular lymphoma (FL) who have not received prior CAR T-cell therapy; FT516 + R following FLU/CY in pts with R/R BCL who have previously received CAR T-cell therapy; and FT516 + R following bendamustine... As of 07 July 2021, 13 pts (2 at..."

Clinical • Combination therapy • P1 data • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • IL2

ASH Poster Walk on Natural Killer Cell-Based Immunotherapy (ASH 2021) - "This poster walk would highlight both pre-clinical and clinical studies that show the progress in this field. The following abstracts will be featured in this session: iPSC-Derived Natural Killer Cells and Macrophages Synergistically Kill Acute Myeloid Leukemia Blasts , Benjamin Goldenson Phase I Study of FT516, an Off-the-Shelf iPSC-Derived NK Cell Therapy, in Combination with Rituximab in Patients with Relapsed/Refractory B-Cell Lymphoma , Krish Patel Using NK-Derived Exosomes to Treat Leukemia, Aladin Samara Cryopreserved CAR-like NK Cells Pre-Complexed with the CD30/CD16A Bispecific Innate Cell Engager (ICE®) AFM13 for the Treatment of CD30+ Malignancies , Joachim Koch FLT3 OR CD33 NOT EMCN Logic Gated CAR-NK Cell Therapy (SENTI-202) for Precise Targeting of AML , Brian Garrison"

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD33 • FCGR3A • IL15 • TNFRSF8

Fate Therapeutics Highlights Positive Durability of Response Data from FT516 Phase 1 Study for B-cell Lymphoma and Announces FDA Regenerative Medicine Advanced Therapy Designation Granted to FT516 for Relapsed / Refractory DLBCL (GlobeNewswire) - "In addition, the Company today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to FT516 for the treatment of relapsed / refractory diffuse large B-cell lymphoma (DLBCL). The RMAT program provides all of the benefits of the fast track and breakthrough therapy designation programs such as early interactions with the FDA to discuss potential pathways for accelerated approval."

FDA event • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Fate Therapeutics Highlights Positive Durability of Response Data from FT516 Phase 1 Study for B-cell Lymphoma and Announces FDA Regenerative Medicine Advanced Therapy Designation Granted to FT516 for Relapsed / Refractory DLBCL (GlobeNewswire) - P1, N=72; NCT04023071; Sponsor: Fate Therapeutics; "Fate Therapeutics, Inc...presented positive clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT516 for patients with relapsed / refractory B-cell lymphoma (BCL) at the 63rd American Society of Hematology Annual Meeting and Exposition...Of the ten patients naïve to treatment with CAR T-cell therapy, eight patients achieved an objective response (80%), including five patients that achieved a complete response (50%). Three of eight patients previously treated with CAR T-cell therapy achieved an objective response (38%), all of whom achieved a complete response...All 11 responding patients in the second, third, and fourth dose cohorts continued in ongoing response at three months following initiation of treatment (61%)."

P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Fate Therapeutics to Host Virtual Event at the 2021 ASH Annual Meeting (GlobeNewswire) - "Fate Therapeutics, Inc...announced that management will host a virtual event entitled 'B -cell Lymphoma Franchise Update' on Tuesday, December 14, 2021 at 8:00 AM ET. The event will highlight interim Phase 1 clinical data from the Company’s FT516 and FT596 programs for the treatment of relapsed / refractory B-cell lymphomas."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Fate Therapeutics; Recruiting ➔ Active, not recruiting; N=27 ➔ 12

Clinical • Combination therapy • Enrollment change • Enrollment closed • Oncology • Solid Tumor

Fate Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Operational Progress (GlobeNewswire) - "At the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), the Company plans to present IND-enabling preclinical data for FT536, its off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate that incorporates a novel CAR targeting the alpha-3 domain of the pan-tumor associated stress antigens MICA and MICB....FT596 Oral and FT516 Poster Presentations to Highlight Updated Phase 1 Data for R/R Lymphoma at ASH on Monday, December 13; Eight Abstracts Accepted for Presentation."

P1 data • Preclinical • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Fate Therapeutics Announces Eight Presentations at the 2021 ASH Annual Meeting (GlobeNewswire) - "Fate Therapeutics, Inc...announced that three oral and five poster presentations for the Company’s induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition being held from December 11-14, 2021...The oral presentations will include updated Phase 1 clinical data of FT596...The poster presentations will include updated Phase 1 clinical data of FT516...Additional presentations will include an oral presentation describing preclinical and clinical translational data of FT596; a poster presentation describing the making of the clonal engineered master iPSC line for FT819...and a poster presentation describing the preclinical activity of multiplexed-engineered, iPSC-derived T cells incorporating three distinct tumor-targeting modalities (CAR, TCR and hnCD16)."

P1 data • Preclinical • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Preliminary results of a phase I trial of FT516, an off-the-shelf natural killer (NK) cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line expressing high‑affinity, non-cleavable CD16 (hnCD16), in patients (pts) with relapsed/refractory (R/R) B-cell lymphoma (BCL). (ASCO 2021) - P1 | " This is a Phase I trial of FT516 combined with rituximab (R) in pts with R/R BCL . Treatment consists of 2 cycles, each with 3 days lympho-conditioning (fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2) and 1 dose of R followed by 3 weekly infusions of FT516 (planned doses 30-900 million/dose) with IL-2 (6 MIU after each FT516 dose)... Administration of up to 6 doses of FT516 cells, including up to 300 million cells/dose, appears to be safe and tolerable, without CRS, ICANS, or GvHD . Activity was observed, including CRs, in heavily pretreated pts . Dose escalation is ongoing ."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Fatigue • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • IL2

Fate Therapeutics Announces Positive Interim Clinical Data from its FT596 and FT516 Off-the-shelf, iPSC-derived NK Cell Programs for B-cell Lymphoma (GlobeNewswire) - P1, N=285; NCT04245722; P1, N=75; NCT04023071; Sponsor: Fate Therapeutics; "Fate Therapeutics...highlighted positive interim clinical data from the Company’s FT516 and FT596 programs for patients with relapsed / refractory B-cell lymphoma...10 of 14 Patients in FT596 Single-Dose Escalation Cohorts 2 and 3 Achieved Objective Response; 7 Patients Achieved Complete Response, including 2 of 3 Patients Treated with FT596 in Combination with Rituximab Following Autologous CD19 CAR T-cell Therapy...8 of 11 Patients in FT516 Multi-Dose Escalation Cohorts 2 and 3 Achieved Objective Response, including 6 Patients that Achieved Complete Response; 5 of 8 Responders Continue in Ongoing Response at Median Time of 5.2 Months."

P1 data • Hematological Malignancies • Lymphoma • Oncology