• Phase 1 Clinical Study to Evaluate Multiple Doses of FT538 as Monotherapy for Acute Myeloid Leukemia and in Com­bi­na­tion with Anti-CD38 Monoclonal Anti­body Therapy for Multiple Myeloma
• Off-the-shelf NK Cell Product Candidate Derived from Clonal Master iPSC Line Engineered with Three Functional Components to Enhance Innate Immunity

San Diego, CA (Press Release) – Fate Thera­peutics, Inc. (NASDAQ: FATE), a clin­i­cal-stage bio­pharma­ceu­tical com­pany ded­i­cated to the de­vel­op­ment of pro­grammed cellular immuno­therapies for cancer and immune disorders, an­nounced to­day that the U.S. Food and Drug Admin­istra­tion (FDA) has cleared the Com­pany’s Inves­ti­ga­tional New Drug (IND) appli­ca­tion for FT538, the first CRISPR-edited, iPSC-derived cell ther­apy. FT538 is an off-the-shelf natural killer (NK) cell cancer immuno­therapy that is derived from a clonal master induced pluripotent stem cell (iPSC) line engi­neered with three functional components to en­hance innate immunity: a novel high-affinity, non-cleavable CD16 (hnCD16) Fc re­cep­tor; an IL-15/IL-15 re­cep­tor fusion (IL-15RF); and the elimination of CD38 ex­pres­sion. The Com­pany plans to ini­ti­ate clin­i­cal in­ves­ti­ga­tion of three once-weekly doses of FT538 as a mono­therapy in acute myeloid leukemia (AML) and in com­bi­na­tion with dara­tu­mu­mab, a CD38-directed mono­clonal anti­body ther­apy, for the treat­ment of mul­ti­ple myeloma.

“We are very pleased to ex­pand the clin­i­cal appli­ca­tion of our pro­pri­e­tary iPSC prod­uct plat­form to mul­ti­ple myeloma, where rates of relapse remain high,” said Scott Wolchko, Pres­i­dent and Chief Executive Officer of Fate Thera­peutics. “Clinical data sug­gest that deficiencies in NK cell-mediated immunity, which are evident even at the earliest stages of myeloma, con­tinue to accumulate through dis­ease pro­gres­sion. We be­lieve admin­istra­tion of FT538 to patients can restore innate immunity, and that the anti-cancer effect of cer­tain standard of care treat­ments, such as mono­clonal anti­bodies, can be more ef­fec­tive when com­bined with the engi­neered functionality of FT538.”

The three functional components of FT538 are de­signed to boost the innate immune re­sponse 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 endogenous NK cells, with the poten­tial to confer sig­nif­i­cant anti-tumor ac­­tiv­ity to patients through mul­ti­ple mech­a­nisms of action in­clud­ing:

• Expression of the hnCD16 Fc re­cep­tor, which im­proves anti­body-dependent cellular cyto­tox­icity, a potent anti-tumor mech­a­nism by which NK cells recog­nize, bind and kill anti­body-coated cancer cells;
• Expression of the IL-15RF cytokine complex, which promotes NK cell sur­vival and persistence and induces trans-activation of endogenous NK cells and CD8 T cells; and
• Elimination of CD38 ex­pres­sion, which en­hances innate effector function, in­clud­ing granzyme and perforin levels and resistance to oxidative stress, and prevents anti-CD38 anti­body-mediated NK cell death.

The first-in-human, multi-center, dose-escalation Phase 1 clin­i­cal trial of FT538 is de­signed to de­ter­mine the maximum tolerated dose (MTD) of three once-weekly doses of FT538 in up to 105 adult patients across four dose cohorts (100M cells per dose; 300M cells per dose; 900M cells per dose; and 1.5B cells per dose). The study will assess two treat­ment regi­mens: Regimen A as a mono­therapy in patients with re­lapsed / re­frac­tory AML; and Regimen B in com­bi­na­tion with dara­tu­mu­mab, an FDA-approved anti-CD38 mono­clonal anti­body, in pa­tients with re­lapsed / re­frac­tory mul­ti­ple myeloma who have failed at least two lines of ther­apy. In addi­tion, the Com­pany may ini­ti­ate a third treat­ment regi­men in com­bi­na­tion with elotuzumab, an FDA-approved anti-SLAMF7 mono­clonal anti­body, in pa­tients with re­lapsed / re­frac­tory mul­ti­ple myeloma who have failed at least two lines of ther­apy starting at one dose level below the MTD of Regimen B. For all regi­mens, mul­ti­ple in­di­ca­tion- or dose-specific dose-expansion cohorts of up to 15 patients per cohort may be en­rolled to fur­ther eval­u­ate the clin­i­cal ac­­tiv­ity of FT538.

FT538 is the fourth off-the-shelf, iPSC-derived NK cell prod­uct can­di­date from the Com­pany’s pro­pri­e­tary iPSC prod­uct plat­form cleared for clin­i­cal in­ves­ti­ga­tion by the FDA. The Com­pany has ini­ti­ated clin­i­cal manu­fac­ture of FT538 at its GMP facility in San Diego, CA.

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 cycles of 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 300 issued pat­ents and 150 pend­ing pat­ent appli­ca­tions.

About Fate Thera­peutics, Inc.

Fate Thera­peutics is a clin­i­cal-stage bio­pharma­ceu­tical com­pany ded­i­cated to the de­vel­op­ment of first-in-class cellular immuno­therapies for cancer and immune disorders. 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 prod­uct can­di­dates in­clude natural killer (NK) cell and T-cell cancer immuno­therapies, which are de­signed to synergize with well-established cancer ther­a­pies, in­clud­ing immune checkpoint in­hib­i­tors and mono­clonal anti­bodies, and to target tumor-associated an­ti­gens with chi­meric an­ti­gen re­cep­tors (CARs). The Com­pany’s immuno-regulatory prod­uct can­di­dates in­clude ProTmune™, a pharmacologically mod­u­lated, donor cell graft that is cur­rent being eval­u­ated in a Phase 2 clin­i­cal trial for the prevention of graft-versus-host dis­ease, and a myeloid-derived sup­pressor cell immuno­therapy for promoting immune tolerance in patients with immune disorders. 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 and clin­i­cal studies, the Com­pany’s progress, plans and timelines for the clin­i­cal in­ves­ti­ga­tion of its prod­uct can­di­dates, the thera­peutic poten­tial of the Com­pany’s prod­uct can­di­dates in­clud­ing FT538, and the Com­pany’s clin­i­cal de­vel­op­ment strat­e­gy for 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 of dif­fi­culties or delay in the initiation of any planned clin­i­cal studies, or in the en­roll­ment or evaluation of subjects in any on­go­ing or future clin­i­cal studies, 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 or to sup­port regu­la­tory ap­prov­al, 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), the risk that results observed in pre­clin­i­cal studies of FT538 may not be rep­li­cated in on­go­ing or future clin­i­cal trials or studies, and the risk that FT538 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.

Source: Fate Thera­peutics.