Fate Therapeutics Announces Positive Interim Clinical Data from its FT596 and FT516 Off-the-shelf, iPSC-derived NK Cell Programs for 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

FT596 and FT516 Treatment Regimens were Well-tolerated; No Dose-limiting Toxicities, and No Adverse Events of Any Grade of ICANS or GVHD, were Observed; Two Low-grade Adverse Events of CRS were Reported in FT596 Single-Dose Escalation Cohorts 1 and 2

Management to Host Virtual Event Today at 4:30 PM Eastern Time

SAN DIEGO, Aug. 19, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim clinical data from the Company’s FT516 and FT596 programs for patients with relapsed / refractory B-cell lymphoma. FT516 is the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The Company’s FT596 program incorporates both the hnCD16 Fc receptor and a chimeric antigen receptor (CAR) targeting CD19, which is designed to enable multi-antigen targeting of tumor cells, as well as an IL-15 receptor fusion (IL-15RF) to enhance NK cell activity and survival.

“We are very pleased with the interim safety, response rates, and durability of responses observed in our ongoing clinical studies of FT516 and FT596 for the treatment of patients with relapsed / refractory B-cell lymphomas. These data continue to demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates can uniquely deliver substantial therapeutic benefit and expand patient access to cell-based cancer immunotherapies,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “At this time, we are initiating multiple indication-specific, dose-expansion cohorts to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including in patients that have experienced disease progression following autologous CD19-targeted CAR T-cell therapy. In addition, early clinical data with the single-dose FT596 treatment schedule have shown robust 30-day response rates and we look forward to further assessing both single-dose and multi-dose treatment regimens to validate its potential best-in-class therapeutic profile.”

FT596 Program
The ongoing clinical trial in relapsed / refractory B-cell lymphoma is assessing a single dose of FT596 as monotherapy (Monotherapy Arm) and in combination with a single dose of rituximab (375 mg/m²) (Combination Arm) following three days of conditioning chemotherapy (500 mg/m² of cyclophosphamide and 30 mg/m² of fludarabine). As of the data cutoff date of June 25, 2021, 10 patients in the Monotherapy Arm and 10 patients in the Combination Arm were evaluable for assessment of safety and efficacy in the first, second, and third dose cohorts of 30 million cells (n=3 each), 90 million cells (n=4 each), and 300 million cells (n=3 each), respectively (see Table 1). Patients had received a median of four prior lines of therapy and a median of 2.5 prior lines containing CD20-targeted therapy. Of the 20 patients, 12 patients (60%) had aggressive B-cell lymphoma, 10 patients (50%) were refractory to most recent prior therapy, and seven patients (35%) were previously treated with autologous CD19-targeted CAR T-cell therapy.

In the second and third single-dose cohorts of the Monotherapy and Combination Arms comprising a total of 14 patients, 10 of 14 patients (71%) achieved an objective response, including seven patients (50%) that achieved a complete response (CR), as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following FT596 dosing. Eight of 10 patients (80%) that had not previously received CD19-targeted CAR T-cell therapy achieved an objective response, including five patients (50%) that achieved CR. Two of four patients (50%) that had previously received CD19-targeted CAR T-cell therapy, both of whom were treated in the Combination Arm, achieved a CR. In the first single-dose cohorts of the Monotherapy and Combination Arms comprising a total of six patients, only one patient achieved an objective response, suggesting dose-response treatment effects for FT596. The ongoing dose-escalation study of FT596 is currently enrolling patients in the fourth single-dose cohort of 900 million cells in each arm.

Table 1. FT596 Interim Phase 1 Data – 1 Dose x 1 Cycle
Dose Escalation Cohort	Monotherapy  (n=10)		Combination  (n=10)		Total  (n=20)
Single Dose, Single Cycle	OR	CR	OR	CR	OR	CR
DC1 = 30M	1/3 (33%)	0	0/3 (0%)	0	1/6 (17%)	0
DC2 = 90M	3/4 (75%)	2	2/4 (50%)	2	5/8 (63%)	4
DC3 = 300M	3/3 (100%)	1	2/3 (67%)	2	5/6 (83%)	3
≥ 90M FT596 cells	(n=7)		(n=7)		(n=14)
aCD19 CAR T Naïve	6/6 (100%)	3	2/4 (50%)	2	8/10 (80%)	5
Prior aCD19 CAR T	0/1 (0%)	0	2/3 (67%)	2	2/4 (50%)	2
Total	6/7 (86%)	3	4/7 (57%)	4	10/14 (71%)	7
aCD19 = autologous CD19-targeted CAR T-cell therapy; CR = complete response; DC = dose cohort; M = million; OR = objective response a Interim FT596 Phase 1 results are as of June 25, 2021 data cutoff date. Data subject to source document verification. b Response assessment for three patients was entered into database subsequent to data cutoff. c Objective response (OR) and complete response (CR) are based on Cycle 1 Day 29 protocol-defined response assessment per Lugano 2014 criteria

The FT596 treatment regimens were well tolerated. No dose-limiting toxicities, and no treatment-emergent adverse events (TEAEs) of any grade of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) were observed. Two low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) were reported, both of which occurred concurrently with other confounding clinical events and resolved on the same day of onset.

FT596 Patient Case Studies
The multi-antigen targeting functionality of FT596 is designed to uniquely address tumor heterogeneity and overcome antigen escape, and has the potential to drive responses in patients that might not effectively be treated with single-antigen targeted modalities, such as monoclonal antibodies, bispecific engagers and CAR T-cell therapies. The following are two case studies from the clinical trial:

• Patient 2014. In the Monotherapy Arm, a 78-year-old woman with splenic diffuse red pulp small B cell lymphoma, who had received four prior therapies including three CD20-targeted regimens, presented with CD19^High and CD20^Null tumor cells indicative of CD20 antigen escape. The patient achieved a CR after single-dose, single-cycle treatment at 90 million FT596 cells as monotherapy with resolution of all metabolically active disease including clearance of baseline bone marrow involvement, demonstrating the activity of the product candidate’s CAR receptor.
• Patient 2016. The Combination Arm included a 68-year-old male with transformed indolent lymphoma who had received six prior therapies, including three anti-CD20-containing regimens and autologous CD19-targeted CAR T-cell therapy. The patient achieved a CR after single-dose, single-cycle treatment at 300 million FT596 cells in combination with rituximab with resolution of all metabolically active disease, suggesting that the product candidate’s hnCD16 receptor can synergize with rituximab to drive complete responses in patients that have progressed following CD19-targeted CAR T-cell therapy.

Re-treatment with Second FT596 Cycle
The FT596 protocol currently allows for the re-treatment of eligible patients with a second, single-dose cycle subject to consent of the U.S. Food and Drug Administration (FDA). All requests by the Company for re-treatment were approved by the FDA. Of note, based on review of data submitted to date to the FDA, the Company is amending its FT596 clinical protocol at the FDA’s recommendation to allow for re-treatment with a second FT596 cycle without requiring the agency’s consent.

In second and third single-dose cohorts of the Monotherapy and Combination Arms as of the data cutoff date, four patients with CR at the end of the first single-dose cycle were re-treated, all of whom remained in CR following disease assessment at the end of the second cycle, and an additional four patients were re-treated and had not yet been assessed for response. The second, single-dose FT596 cycle was well tolerated, and no events of any grade of CRS, ICANS, or GVHD were observed.

FT516 Program
The clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m² of cyclophosphamide and 30 mg/m² of fludarabine), a single dose of rituximab (375 mg/m²), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting. Dose escalation is currently ongoing in the fourth multi-dose cohort of 900 million cells per dose.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting held in June, the Company highlighted positive interim clinical data for 11 patients treated in the second and third multi-dose cohorts of 90 million cells per dose (n=4) and 300 million cells per dose (n=7). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy. No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no TEAEs of any grade of CRS, ICANS, or GVHD were reported.

Ongoing Response Assessment
Of the 11 patients treated in the second and third multi-dose cohorts, eight patients (73%) achieved an objective response, including six patients (55%) who achieved CR, as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following the second FT516 treatment cycle. Notably, two of four patients (50%) previously treated with autologous CD19 CAR-T cell therapy achieved CR. At three months following first infusion, all eight responders maintained their response without further therapeutic intervention (3-Month Rate of 73% OR and 55% CR). As of the data cutoff date of July 7, 2021:

• Five patients (45%) maintained their response without further therapeutic intervention, including four patients that remained in CR (4.6-9.5 months) and one patient that remained in partial response (6.1 months);
• Two patients that had achieved CR experienced disease progression (4.2 and 5.1 months); and
• One patient that had achieved partial response was treated with additional anti-cancer therapy (4.1 months).
  

FT516 Patient Case Study
The ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months’ duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. The patient received a second FT516 treatment cycle, after which the response assessment continued to show complete response. As of the data cutoff date of July 7, 2021, the patient’s most recent assessment at 4.9 months showed MRD negativity, confirming a profound CR.

Today's Webcast
The Company will host a live audio webcast today, Thursday, August 19, 2021 at 4:30 p.m. ET to review interim clinical data for the Company’s FT516 and FT596 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 FT596
FT596 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 anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; 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; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

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 FT596, the Company’s plans and timelines for its ongoing and planned clinical studies, and the expected clinical development plans for FT516 and FT596. 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 interim results and results from earlier studies, may not be predictive of final results or results observed in ongoing or future studies involving these product candidates, the risk of a delay in the initiation of, or in the enrollment or evaluation of subjects in, any clinical studies, 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