Fate Therapeutics Announces Encouraging Interim Phase 1 Data for iPSC-derived NK Cell Programs in Relapsed / Refractory Acute Myeloid Leukemia

4 of 9 Patients in FT516 Monotherapy Study Achieved Objective Response with Complete Leukemic Blast Clearance in the Bone Marrow

2 Patients in Second Dose Escalation Cohort of FT516 Monotherapy Study Continued in Remission without Further Therapeutic Intervention at 6-month Follow-up

1 of 3 Patients in First Dose Escalation Cohort of FT538 Monotherapy Study Achieved Objective Response with Complete Leukemic Blast Clearance in the Bone Marrow

No Observed Dose-limiting Toxicities and No Events of Any Grade of Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, or Graft-vs-Host Disease

Management to Host Virtual Event Today at 5:00 PM Eastern Time

SAN DIEGO, May 13, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today announced encouraging interim Phase 1 data from the Company’s off-the-shelf, iPSC-derived natural killer (NK) cell programs in relapsed / refractory acute myeloid leukemia (AML). The ongoing Phase 1 dose-escalation study of FT516 as monotherapy is currently enrolling patients in the third dose cohort (900 million cells per dose), with three patients treated in the first dose cohort (90 million cells per dose) and six patients treated in the second dose cohort (300 million cells per dose). The Phase 1 dose-escalation study of FT538 as monotherapy is currently ongoing, with three patients treated in the first dose cohort (100 million cells per dose).

As of the data cutoff date of April 16, 2021, five of 12 patients had achieved an objective response with complete leukemic blast clearance in the bone marrow (FT516 [n=9]: 3 complete remission with incomplete hematologic recovery [CRi], 1 morphologic leukemia-free state [MLFS]; FT538 [n=3]: 1 CRi). Of the four patients achieving a CRi, one patient successfully proceeded to allogeneic stem cell transplant and the other three patients remained on-study and in remission without further therapeutic intervention, two of whom remained in remission having been on-study for more than six months. Clinical assessments were based on the 2017 European LeukemiaNet (ELN) response criteria (Blood (2017) 129 (4): 424–447).

Importantly, no dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. Patients had received a median of three prior lines of therapy, with 11 of 12 patients refractory to their last prior therapy. At baseline prior to conditioning chemotherapy, 11 of 12 patients had significant hematopoietic impairment, with both neutrophil counts below 1,000/µL and platelet counts below 100,000/µL.

“We are highly encouraged by these Phase 1 data in patients with relapsed / refractory AML, which clearly indicate that off-the-shelf, iPSC-derived NK cells administered as monotherapy in the outpatient setting were well-tolerated, and have the potential to induce complete leukemic blast clearance in the bone marrow and confer durable remissions without further therapeutic intervention. Complete leukemic blast clearance in the bone marrow is essential as recent studies in relapsed / refractory AML have shown that this clinical outcome results in a statistically-significant improvement in patient survival,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “Additionally, we are excited that a patient receiving FT538 in the initial dose escalation cohort achieved a complete remission with incomplete hematologic recovery, and that FT538 continued to be detected in the peripheral blood at Day 8 post-infusion. This suggests that the additional engineered functionality of FT538 can augment NK cell pharmacokinetics without the need for exogenous cytokine support during patient treatment.”

FT516 Phase 1 Study
FT516 is an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal engineered master induced pluripotent stem cell (iPSC) line. The Phase 1 clinical trial in relapsed / refractory AML is assessing FT516 administered as monotherapy. Up to two cycles of treatment are administered, with each cycle consisting of three days of conditioning chemotherapy followed by three weekly doses of FT516, with IL-2 cytokine support after each FT516 dose. FT516 may be administered in the outpatient setting with no requirement for inpatient monitoring during the treatment period.

Three patients in the first dose cohort of 90 million cells per dose and six patients in the second dose cohort of 300 million cells per dose were assessed for safety and activity (see Table 1). Of the nine patients, eight had adverse molecular risk based on the 2017 ELN risk category and eight patients were refractory to their last prior therapy. Patients had received a median of three prior lines of therapy. At baseline prior to conditioning chemotherapy, all nine patients were significantly cytopenic, with eight patients having neutrophil counts below 1,000/µL and nine patients having platelet counts below 100,000/µL, and the median bone marrow leukemic blast percentage was 39%.

Safety Data
No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose treatment schedule was well-tolerated with no treatment discontinuations due to adverse events. Three patients experienced Grade 3 febrile neutropenia, and no other FT516-related Grade 3 or greater adverse events were reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Activity Data
Six of nine relapsed / refractory AML patients showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts, with four patients achieving an objective response with complete clearance of leukemic blasts in the bone marrow. Three of these four responders achieved a best overall response of CRi based on 2017 ELN response criteria, including two patients in the second dose cohort (Table 1: Subjects 1006 and 1007), each of whom had ongoing remission without further therapeutic intervention at six months’ follow-up, and one patient in the first dose cohort (Table 1: Subject 1001) who successfully proceeded to allogeneic stem cell transplant.

FT538 Phase 1 Study
FT538 is an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line engineered with three functional components designed to enhance innate immunity. The Phase 1 clinical trial in relapsed / refractory AML is assessing FT538 administered as monotherapy. Up to two cycles of treatment are administered, with each cycle consisting of three days of conditioning chemotherapy followed by three weekly doses of FT538 without IL-2 cytokine support. FT538 may be administered in the outpatient setting with no requirement for inpatient monitoring during the treatment period.

Three patients were enrolled in the first dose cohort of 100 million cells per dose, two of whom were evaluable for safety and anti-leukemic activity and one patient who discontinued from the study prior to completion of the first treatment cycle due to clinical evidence of failure to respond to therapy (see Table 2). Of the two evaluable patients, one patient had adverse molecular risk based on the 2017 ELN risk category. Both patients had received at least three prior lines of therapy, were refractory to their last prior therapy, and were significantly cytopenic with neutrophil counts below 1,000/µL and platelet counts below 100,000/µL at baseline prior to conditioning chemotherapy.

Safety Data
No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose treatment schedule was well-tolerated with no FT538-related Grade 3 or greater adverse events reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT538 in the outpatient setting without the need for patient matching.

Activity Data
Both evaluable patients showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts. One patient (Table 2: Subject 1003), who was refractory to their two most recent prior therapies (an investigational CD33-targeted tri-specific NK cell engager [TriKE], followed by glasdegib in combination with low-dose cytarabine), achieved a CRi based on 2017 ELN response criteria at the end of the first treatment cycle and remained on-study. FT538 was detected in the peripheral blood at Day 8 prior to administration of the second dose in both patients.

Table 1. Interim Data from FT516 Phase 1 Study in Relapsed / Refractory AML
Subject #	Baseline Patient Characteristics				Best Overall Response
	# Prior Lines	2017 ELN Molecular Risk	Last Line Response	% Bone Marrow Blasts	% Change in Bone Marrow Blasts		2017 ELN Response
Dose Cohort 1 – 90 million cells / dose
1001	3	Intermediate	Refractory	6%	-100%		CRi
1003	3	Adverse	Refractory	39%	-21%		SD
1005	4	Adverse	Refractory	40%	+13%		SD
Dose Cohort 2 – 300 million cells / dose
1006	1	Adverse	Relapse	26%	-100%		CRi
1007	1	Adverse	Refractory	12%	-100%		CRi
1008	6	Adverse	Refractory	95%	+3%		SD
1011	3	Adverse	Refractory	91%	-7%		PD
1012	5	Adverse	Refractory	20%	-100%		MLFS
1015	3	Adverse	Refractory	44%	+36%		PD

Table 2. Interim Data from FT538 Phase 1 Study in Relapsed / Refractory AML
Subject #	Baseline Patient Characteristics				Best Overall Response
	# Prior Lines	2017 ELN Molecular Risk	Last Line Response	% Bone Marrow Blasts	% Change in Bone Marrow Blasts	2017 ELN Response
Dose Cohort 1 – 100 million cells / dose
1001	3	Unknown	Refractory	70%	0%	SDa
1002	3	Adverse	Refractory	25%	-40%	SD
1003	4	Intermediate	Refractory	30%	-100%	CRi

CRi (Complete Remission with incomplete hematologic recovery) = Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; recovery of either neutrophils to ≥1,000/µL or platelets to ≥100,000/µL
MLFS (Morphologic Leukemia-free State) = Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; residual neutropenia (<1,000/µL) and residual thrombocytopenia (<100,000/µL)
PD = Progressive Disease
SD = Stable Disease
As of April 16, 2021 database entry. Data subject to source document verification.
^a Subject 1001 received 2 of 3 doses of FT538 in the first treatment cycle and discontinued from study due to evidence of non-response to therapy.

Today's Webcast
The Company will host a live audio webcast today, Thursday, May 13, 2021 at 5:00 p.m. ET to review the relapsed / refractory AML treatment landscape and discuss interim Phase 1 clinical data for the Company’s FT516 and FT538 off-the-shelf, iPSC-derived NK cell programs. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company's website at www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).

About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Company’s immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). 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 NK cell product candidates, including FT516 and FT538, its ongoing and planned clinical studies, and the expected clinical development plans for FT516 and FT538. 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 results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay 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, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, 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
Stern Investor Relations, Inc.
212.362.1200
christina@sternir.com