Fifth in­dus­try col­lab­o­ration to eval­u­ate niro­gace­stat as a BCMA po­ten­ti­ator across modalities

Stamford, CT (Press Release) – Spring­Works Thera­peutics, Inc. (Nasdaq: SWTX), a clin­i­cal-stage bio­pharma­ceu­tical com­pany focused on devel­op­ing life-changing med­i­cines for patients with severe rare dis­eases and can­cer, to­day an­nounced that the com­pany has entered into a clin­i­cal trial col­lab­o­ration agree­ment with Pfizer Inc. (NYSE: PFE) to eval­u­ate Spring­Works Thera­peutics’ inves­ti­ga­tional gamma se­cre­tase in­hib­i­tor (GSI), niro­gace­stat, in com­bi­na­tion with Pfizer’s anti-B-cell maturation an­ti­gen (BCMA) CD3 bispecific anti­body, PF‐06863135, in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma.

Gamma se­cre­tase in­hib­ition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In pre­clin­i­cal models, niro­gace­stat has been shown to in­crease the cell surface density of BCMA and re­duce levels of soluble BCMA, thereby enhancing the ac­tiv­ity of BCMA-targeted ther­a­pies, in­clud­ing CD3 bispecific anti­bodies.

“This col­lab­o­ration is another im­por­tant step in continuing to ad­vance our goal of devel­op­ing niro­gace­stat as a best-in-class BCMA po­ten­ti­ator, and we are pleased to work with Pfizer to study niro­gace­stat in com­bi­na­tion with PF‐06863135, which has recently dem­onstrated promising mono­therapy clin­i­cal data,” said Saqib Islam, Chief Exec­u­tive Of­fi­cer of Spring­Works Thera­peutics. “We now have five col­lab­o­rations with in­dus­try-leading BCMA de­vel­opers to eval­u­ate niro­gace­stat in com­bi­na­tions across modalities. We look for­ward to generating clin­i­cal data with our col­lab­o­rators to fur­ther eval­u­ate the ability of niro­gace­stat to im­prove out­comes for patients with mul­ti­ple myeloma.”

Under the terms of the agree­ment, Pfizer will sponsor and con­duct the Phase 1b/2 study to eval­u­ate the safety, tol­er­a­bil­ity and pre­lim­i­nary ef­fi­cacy of the com­bi­na­tion, and will assume all costs asso­ci­ated with the study, other than ex­penses re­lated to the manu­fac­tur­ing of niro­gace­stat and cer­tain ex­penses re­lated to in­tel­lec­tual prop­er­ty rights. Pfizer and Spring­Works Thera­peutics will also form a joint de­vel­op­ment com­mit­tee to man­age the clin­i­cal study, which is ex­pected to com­mence in the first half of 2021.

“Entering into this clin­i­cal col­lab­o­ration is a proud mile­stone in our strong rela­tion­ship with Spring­Works,” said Chris Boshoff, MD, PhD, Chief De­vel­op­ment Of­fi­cer for Pfizer Oncology at Pfizer. “We be­lieve that studying niro­gace­stat in com­bi­na­tion with PF-06863135 could hold sig­nif­i­cant thera­peutic prom­ise for patients with re­lapsed or re­frac­tory mul­ti­ple myeloma, and we look for­ward to work­ing to­geth­er to ad­vance this im­por­tant area of re­search.”

In addi­tion to its on­go­ing clin­i­cal col­lab­o­rations with BCMA-directed ther­a­pies, Spring­Works is also cur­rently con­ducting a global Phase 3, double-blind, ran­dom­ized, placebo-controlled clin­i­cal trial (the DeFi Trial) to eval­u­ate niro­gace­stat in adults with pro­gress­ing desmoid tumors.

About Niro­gace­stat

Nirogacestat is an inves­ti­ga­tional, oral, sel­ective, small mol­e­cule gamma se­cre­tase in­hib­i­tor in Phase 3 clin­i­cal de­vel­op­ment for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma se­cre­tase cleaves mul­ti­ple transmembrane pro­tein complexes, in­clud­ing Notch, which is be­lieved to play a role in activating path­ways that con­trib­ute to desmoid tumor growth.

In addi­tion, gamma se­cre­tase has been shown to directly cleave membrane-bound BCMA, re­­sult­ing in the re­lease of the BCMA extracellular domain, or ECD, from the cell surface. By in­hib­iting gamma se­cre­tase, membrane-bound BCMA can be preserved, in­creas­ing target density while reducing levels of soluble BCMA ECD, which may serve as decoy re­cep­tors for BCMA-directed ther­a­pies. Niro­gace­stat’s ability to en­hance the ac­tiv­ity of BCMA-directed ther­a­pies has been ob­served in pre­clin­i­cal models of mul­ti­ple myeloma. Spring­Works is eval­u­ating niro­gace­stat as a BCMA po­ten­ti­ator and has five col­lab­o­rations with in­dus­try-leading BCMA de­vel­opers to eval­u­ate niro­gace­stat in com­bi­na­tions across modalities, in­clud­ing with an anti­body-drug con­ju­gate, two CAR T cell ther­a­pies and two bispecific anti­bodies. In addi­tion, Spring­Works and Fred Hutchinson Cancer Re­search Center have entered into a sponsored re­search agree­ment to fur­ther char­ac­ter­ize the ability of niro­gace­stat to mod­u­late BCMA and po­ten­ti­ate BCMA directed ther­a­pies using a variety of pre­clin­i­cal and patient-derived mul­ti­ple myeloma models devel­oped by re­searchers at Fred Hutch.

Nirogacestat has re­ceived Orphan Drug Desig­na­tion from the U.S. Food and Drug Admin­istra­tion (FDA) for the treat­ment of desmoid tumors (June 2018) and from the Euro­pean Com­mis­sion for the treat­ment of soft tissue sarcoma (September 2019). The FDA also granted Fast Track and Break­through Therapy Desig­na­tions for the treat­ment of adult patients with progressive, unresectable, re­cur­rent or re­frac­tory desmoid tumors or deep fibromatosis (November 2018 and August 2019).

About PF‐06863135

PF‐06863135 is an anti-B-cell maturation an­ti­gen (BCMA) CD3 bispecific anti­body being in­ves­ti­gated in a Phase 1 clin­i­cal study to treat re­lapsed or re­frac­tory mul­ti­ple myeloma. This bispecific anti­body can be admin­istered sub­cu­tane­ously and has been op­ti­mized for binding affinity to both BCMA and CD3, enabling more potent T-cell-mediated tumor cell toxicity.

About Spring­Works Thera­peutics

Spring­Works is a clin­i­cal-stage bio­pharma­ceu­tical com­pany applying a pre­ci­sion med­i­cine ap­proach to acquiring, devel­op­ing and com­mer­cial­iz­ing life-changing med­i­cines for underserved patient pop­u­la­tions suffer­ing from dev­as­tat­ing rare dis­eases and can­cer. Spring­Works has a dif­fer­en­ti­ated port­folio of small mol­e­cule targeted on­col­ogy prod­uct can­di­dates and is ad­vanc­ing two po­ten­tially reg­is­tra­tional clin­i­cal trials in rare tumor types, as well as sev­er­al other pro­grams addressing highly prevalent, ge­net­ic­ally defined can­cers. Spring­Works’ stra­te­gic ap­proach and op­er­a­tional excellence in clin­i­cal de­vel­op­ment have enabled it to rapidly ad­vance its two lead prod­uct can­di­dates into late-stage clin­i­cal trials while simultaneously entering into mul­ti­ple shared-value part­ner­ships with in­dus­try leaders to ex­pand its port­folio. For more in­for­ma­tion, visit www.springworkstx.com and follow @Spring­WorksTx on Twitter and LinkedIn.

Spring­Works Forward-Looking State­ments

This press re­lease con­tains for­ward-looking state­ments within the meaning of the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995, as amended, in­clud­ing, without lim­i­ta­tion, state­ments re­gard­ing Spring­Works’ clin­i­cal trials and its strat­e­gy, busi­ness plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar ex­pres­sions are in­tended to identify for­ward-looking state­ments, although not all for­ward-looking state­ments con­tain these identifying words. Any for­ward-looking state­ments in this press re­lease are based on man­age­ment’s cur­rent ex­pec­ta­tions and beliefs and are subject to a num­ber of risks, un­cer­tainties and im­por­tant factors that may cause actual events or re­­sults to differ ma­teri­ally from those ex­pressed or im­plied by any for­ward-looking state­ments con­tained in this press re­lease, in­clud­ing, without lim­i­ta­tion, those re­lated to Spring­Works’ fi­nan­cial re­­sults, the timing for initiation or com­ple­tion of Spring­Works’ clin­i­cal trials of its prod­uct can­di­dates, whether and when, if at all, Spring­Works’ prod­uct can­di­dates will re­ceive ap­prov­al from the U.S. Food and Drug Admin­istra­tion, or FDA, or other foreign regu­la­tory author­i­ties, un­cer­tainties and assump­tions re­gard­ing the im­pact of the COVID-19 pan­dem­ic on Spring­Works’ busi­ness, op­er­a­tions, clin­i­cal trials, supply chain, strat­e­gy, goals and antic­i­pated timelines, com­pe­ti­tion from other bio­pharma­ceu­tical com­pa­nies, and other risks identified in the section entitled “Risk Factors” in Item 1A of Part II of Spring­Works’ Quar­ter­ly Report on Form 10-Q for the quarter ended June 30, 2020, as well as dis­cus­sions of po­ten­tial risks, un­cer­tainties and other im­por­tant factors in Spring­Works’ sub­se­quent filings with the Se­cu­ri­ties and Ex­change Com­mis­sion. Spring­Works cautions you not to place undue reliance on any for­ward-looking state­ments, which speak only as of the date they are made. Spring­Works disclaims any obli­ga­tion to pub­licly up­date or revise any such state­ments to reflect any change in ex­pec­ta­tions or in events, con­di­tions or cir­cum­stances on which any such state­ments may be based, or that may affect the like­li­hood that actual re­­sults will differ from those set forth in the for­ward-looking state­ments. Any for­ward-looking state­ments con­tained in this press re­lease rep­re­sent Spring­Works’ views only as of the date hereof and should not be relied upon as rep­re­senting its views as of any sub­se­quent date.

Source: Spring­Works Thera­peutics.