• FT516 off-the-shelf NK cell cancer immuno­therapy cleared for clin­i­cal in­ves­ti­ga­tion by FDA
• Product can­di­date derived from clonal master iPSC line engi­neered with novel CD16 Fc re­cep­tor
• Clinical trial to eval­u­ate multi-dose cycles of FT516 for treat­ment of hema­to­logic malig­nancies, in­clud­ing in combi­nation with targeted anti­body ther­apy

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 allowed its Inves­ti­ga­tional New Drug (IND) appli­ca­tion for FT516, the Com­pany’s off-the-shelf natural killer (NK) cell prod­uct can­di­date derived from a clonal master induced pluripotent stem cell (iPSC) line engi­neered to express a novel CD16 Fc re­cep­tor. FT516 is the first-ever cell ther­apy derived from a ge­net­ic­ally engi­neered pluripotent stem cell cleared for clin­i­cal testing in the world, and is the Com­pany’s sec­ond off-the-shelf, iPSC-derived NK cell prod­uct can­di­date cleared for clin­i­cal in­ves­ti­ga­tion by the FDA within the past two months. The Com­pany in­tends to ini­ti­ate clin­i­cal testing of FT516 in patients with cer­tain re­lapsed / re­frac­tory hema­to­logic malig­nan­cies, in­­clud­ing acute mye­log­e­nous leukemia (AML) as a mono­therapy, non-Hodgkin's lym­phoma (NHL) in com­bi­na­tion with ritux­i­mab­, and mul­ti­ple myeloma (MM) in com­bi­na­tion with elotuzumab.

“This allowance by the FDA of our FT516 IND appli­ca­tion is a watershed event in the clin­i­cal devel­op­ment of engi­neered cell ther­a­pies. Our industry-leading iPSC prod­uct plat­form enables the manu­fac­ture of engi­neered cell prod­ucts that can be extensively char­ac­ter­ized, cryopreserved and de­liv­ered ‘on demand’ to reach more patients,” said Scott Wolchko, Pres­i­dent and Chief Executive Officer of Fate Thera­peutics. “FT516 is a first-of-kind cell prod­uct in that it originates from a single ge­net­ic­ally engi­neered pluripotent stem cell, which serves as a clonal master cell line that can be repeatedly used to mass-produce large quantities of homogeneous cell prod­uct in a cost-effective manner. This inno­va­tive ap­proach uniquely sup­ports a new treat­ment paradigm with engi­neered cell ther­a­pies, where mul­ti­ple doses of cell prod­uct are readily avail­able for admin­istra­tion with the goal of driving deeper and more durable re­sponses. We look for­ward to treating patients with mul­ti­ple doses of FT516, in­­clud­ing in com­bi­na­tion with FDA-approved mono­clonal anti­body ther­apy, across mul­ti­ple treat­ment cycles in this first clin­i­cal study.”

CD16 is naturally ex­pressed on NK cells and mediates anti­body-dependent cellular cyto­tox­icity (ADCC), a potent immune mech­a­nism through which NK cells can recog­nize, bind and kill anti­body-coated cancer cells. ADCC is an under­lying mech­a­nism asso­ci­ated with the clin­i­cal ef­fi­cacy of many mono­clonal anti­bodies that are approved for the treat­ment of var­i­ous cancers, in­­clud­ing hema­to­logic malig­nan­cies and solid tumors. The ex­pres­sion of CD16 on NK cells can undergo con­siderable down-regu­la­tion in cancer patients, which sig­nif­i­cantly in­hib­its the immune sys­tem’s anti-tumor re­sponse. FT516 in­cor­po­rates a novel CD16 Fc re­cep­tor, which has been modified to prevent its down-regu­la­tion and to augment its binding to tumor-targeting anti­bodies, for en­hanced ADCC.

The initial clin­i­cal study of FT516 is in­tended to assess the safety and tolerability of three weekly doses for the treat­ment of cer­tain re­lapsed / re­frac­tory hema­to­logic malig­nan­cies. The study in­cludes three independent, dose-escalating treat­ment arms: mono­therapy for AML; com­bi­na­tion with ritux­i­mab­ for NHL; and com­bi­na­tion with elotuzumab, plus poma­lido­mide and dexa­meth­a­sone, for MM. All subjects will re­ceive low-dose con­di­tioning chemo­ther­apy con­sist­ing of cyclo­phos­pha­mide and flu­dar­abine (Cy/Flu) and cytokine sup­port with IL-2. Subjects are eli­gible to re­ceive a sec­ond treat­ment cycle fol­low­ing an initial 28-day safety assess­ment.

FT516 is the sec­ond off-the-shelf, iPSC-derived NK cell prod­uct can­di­date cleared for clin­i­cal in­ves­ti­ga­tion by the FDA from the Com­pany’s pro­pri­e­tary iPSC prod­uct plat­form. In No­vem­ber 2018, the FDA cleared the Com­pany’s IND appli­ca­tion for FT500, an off-the-shelf, iPSC-derived NK cell prod­uct can­di­date for use in com­bi­na­tion with checkpoint blockade ther­apy for the treat­ment of solid tumors.

About Fate Thera­peutics’ iPSC Product Platform

The Com­pany’s pro­pri­e­tary iPSC prod­uct plat­form enables mass pro­duc­tion of off-the-shelf, engi­neered, homogeneous cell prod­ucts that can be admin­istered in repeat doses to mediate 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 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 to treat many patients. As a result, the Com­pany’s plat­form is uniquely ca­pa­ble of addressing the lim­i­ta­tions asso­ci­ated with the pro­duc­tion of cell ther­a­pies using patient- or donor-derived cells, which is logis­tic­ally complex and expensive and is fraught with batch-to-batch and cell-to-cell variability that can affect safety and ef­fi­cacy. Fate Thera­peutics’ iPSC prod­uct plat­form is sup­ported by an in­tel­lec­tual property port­folio of over 100 issued pat­ents and 100 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 is pioneering the devel­op­ment of off-the-shelf cell prod­ucts using its pro­pri­e­tary induced pluripotent stem cell (iPSC) prod­uct plat­form. The Com­pany’s immuno-oncology pipe­line is com­prised of FATE-NK100, a donor-derived natural killer (NK) cell cancer immuno­therapy that is cur­rently being eval­u­ated in three Phase 1 clin­i­cal trials, as well as iPSC-derived NK cell and T-cell immuno­therapies, with a focus on devel­op­ing next-gener­a­tion cell prod­ucts in­tended to synergize with checkpoint in­hib­i­tor and mono­clonal anti­body ther­a­pies and to target tumor-specific an­ti­gens. The Com­pany’s immuno-regulatory pipe­line in­cludes ProTmune™, a next-gener­a­tion donor cell graft that is cur­rently 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 planned clin­i­cal studies, the thera­peutic poten­tial of the Com­pany’s NK cell prod­uct can­di­dates, in­­clud­ing FT516, the Com­pany’s regu­la­tory strat­e­gy, and the Com­pany’s plans for its in­tended clin­i­cal in­ves­ti­ga­tion of FT500 and FT516. 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 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 FT516 may not be rep­li­cated in on­go­ing or future clin­i­cal trials or studies, and the risk that FT516 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.