• Study met its pri­mary end­point and key sec­ond­ary end­point, demonstrating deep and durable re­sponse­s in a heavily pre-treated mul­ti­ple myeloma patient pop­u­la­tion
• Safety results are con­sis­tent with the data pre­sented in CRB-401 study

Princeton, NJ and Cambridge, MA (Press Release) – Bristol-Myers Squibb Com­pany (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) to­day an­nounced pos­i­tive top-line results from KarMMa, a pivotal, open-label, single arm, multi­center, Phase 2 study of idecabtagene vicleucel (ide-cel; bb2121). KarMMa, which eval­u­ated the ef­fi­cacy and safety of the com­pa­nies’ lead inves­ti­ga­tional BCMA-targeted chi­meric an­ti­gen re­cep­tor (CAR) T cell ther­apy can­di­date for patients with re­lapsed and re­frac­tory mul­ti­ple myeloma, met its pri­mary end­point and key sec­ond­ary end­point.

KarMMa en­rolled 140 patients, of whom 128 patients were treated with ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells. All treated patients were exposed to at least three prior ther­a­pies, in­clud­ing an immuno­modu­la­tory (IMiD) agent, a pro­te­a­some in­hib­i­tor (PI) and an anti-CD38 anti­body, and all were re­frac­tory to their last regi­men. Ninety-four per­cent of patients were re­frac­tory to an anti-CD38 anti­body and 84% per­cent were triple re­frac­tory (refractory to an IMiD agent, PI and anti-CD38 anti­body).

Results for the pri­mary end­point (overall re­sponse­ rate [ORR]) and key sec­ond­ary end­point (complete re­sponse­ rate [CR]), as well as duration of re­sponse­ (DoR) and pro­gres­sion-free sur­vival (PFS) across the target dose levels and at each of the three target doses explored in the study are pre­sented in the table below. The median follow-up duration for all subjects was 11.3 months.

Overall, the safety results were con­sis­tent with those observed in the phase 1 CRB-401 study, which eval­u­ated the pre­lim­i­nary safety and ef­fi­cacy of ide-cel. Instances of grade 3 or higher cytokine release syn­drome (CRS) oc­curred in 5.5% (7/128) of patients, in­clud­ing one fatal CRS event. In­ves­ti­ga­tor identified grade 3 or higher neurotoxicity events (iiNT) oc­curred in 3.1% (4/128) of patients and there were no Grade 4 iiNT events reported. Grade 3 or higher CRS and iiNT events were reported in <6% of subjects at each target dose. CRS of any grade oc­curred in 83.6% (107/128) of patients and iiNT of any grade oc­curred in 18% (23/128) of patients.

“For mul­ti­ple myeloma patients who have re­lapsed and be­come re­frac­tory to current treat­ment op­tions, there remains a high unmet need, as these patients typ­i­cally ex­peri­ence low re­sponse­ rates, short re­sponse­ durations and poor sur­vival,” said Kristen Hege, M.D., Senior Vice Pres­i­dent, He­ma­tol­ogy/Oncology and Cell Therapy, Early Clinical De­vel­op­ment for Bristol-Myers Squibb. “The KarMMa study provides fur­ther sup­port for ide-cel as a poten­tial thera­peutic op­tion in this heavily pre-treated patient pop­u­la­tion, and we are en­cour­aged by these data, especially the out­comes observed at the highest target dose of 450 x 106 CAR+ T cells. We are actively preparing for sub­mission of these data to Health Authorities for proposed initial reg­is­tra­tion of ide-cel as a first-in-class BCMA-targeted CAR T cell ther­apy.”

“Multiple myeloma is a relentless dis­ease and there is sig­nif­i­cant need to find new treat­ment op­tions for patients who ad­vance through the current ther­a­pies avail­able to them,” said Joanne Smith-Farrell, Ph.D., on­col­ogy fran­chise lead and chief business officer, bluebird bio. “With these data in hand, bluebird bio and Bristol-Myers Squibb remain fully focused on ad­vanc­ing ide-cel as quickly as possible for patients in late-line myeloma, while continuing to execute our broad devel­op­ment pro­gram to under­stand the poten­tial benefits of ide-cel across earlier lines of ther­apy.”

More com­pre­hen­sive data from KarMMa will be sub­mitted for pre­sen­ta­tion at a future med­i­cal meeting.

About KarMMa

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multi-center phase 2 study eval­u­ating the ef­fi­cacy and safety of ide-cel in adult patients with re­lapsed and re­frac­tory mul­ti­ple myeloma, in North America and Europe. The pri­mary end­point of the study is over­all re­sponse­ rate as assessed by an independent review com­mit­tee (IRC) according to the Inter­na­tional Myeloma Work­ing Group (IMWG) criteria. Complete re­sponse­ rate is a key sec­ond­ary end­point. Other ef­fi­cacy end­points in­clude time to re­sponse­, duration of re­sponse­, pro­gres­sion-free sur­vival, over­all sur­vival and minimal residual dis­ease eval­u­ated by Next-Generation Sequencing (NGS) assay. The study en­rolled 140 patients, of whom 128 re­ceived ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after re­ceiv­ing lym­pho­de­plet­ing chemo­ther­apy. All en­rolled patients had re­ceived at least three prior treat­ment regi­mens, in­clud­ing an IMiD agent, a PI and an anti-CD38 anti­body, and were re­frac­tory to their last regi­men, defined as pro­gres­sion during or within 60 days of their last ther­apy.

About Ide-cel

Ide-cel is a CAR T cell ther­apy targeting B-cell maturation an­ti­gen (BCMA), which is ex­pressed on the surface of nor­mal and malignant plasma cells. The ide-cel CAR con­struct in­cludes an anti-BCMA scFv-targeting domain for an­ti­gen spe­cif­icity, a transmembrane domain, a CD3-zeta activation domain, and a 4-1BB co-stimulatory domain hypothesized to in­crease T-cell activation, pro­lif­er­a­tion and persistence. Ide-cel CAR T cells are proposed to recog­nize and bind to BCMA on the surface of mul­ti­ple myeloma cells lead­ing to apop­tosis.

In No­vem­ber 2017, ide-cel was granted Break­­through Therapy Desig­na­tion (BTD) by the U.S. Food and Drug Admin­istra­tion and PRIority Medicines (PRIME) eligibility by the Euro­pean Medicines Agency based on pre­lim­i­nary clin­i­cal data from the phase 1 CRB-401 study.

Bristol-Myers Squibb and bluebird bio’s broad clin­i­cal devel­op­ment pro­gram for ide-cel in­cludes clin­i­cal stud­ies (KarMMa-2, KarMMa-3) in earlier lines of treat­ment for patients with mul­ti­ple myeloma. For more in­for­ma­tion visit: clin­i­caltrials.gov.

Ide-cel is being devel­oped as part of a Co-Development, Co-Promotion and Profit Share Agreement be­tween BMS and bluebird bio.

Ide-cel is not approved for any in­di­ca­tion in any ge­­og­ra­phy.

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer re­search is to in­crease quality, long-term sur­vival and make cure a possibility. We har­ness our deep scientific ex­peri­ence, cutting-edge tech­nolo­gies and discovery plat­forms to discover, de­vel­op and de­liver novel treat­ments for patients.

Building upon our trans­for­ma­tive work and legacy in he­ma­tol­ogy and Immuno-Oncology that has changed sur­vival ex­pec­ta­tions for many cancers, our re­searchers are ad­vanc­ing a deep and diverse pipe­line across mul­ti­ple modalities. In the field of immune cell ther­apy, this in­cludes reg­is­tra­tional chi­meric an­ti­gen re­cep­tor (CAR) T-cell agents for nu­mer­ous dis­eases, and a growing early-stage pipe­line that ex­pands cell and gene ther­apy targets, and tech­nolo­gies. We are devel­op­ing cancer treat­ments directed at key bio­logical path­ways using our pro­tein homeo­stasis plat­form, a re­search ca­pa­bil­i­ty that has been the basis of our approved ther­a­pies for mul­ti­ple myeloma and several promising com­pounds in early to mid-stage devel­op­ment. Our scientists are targeting dif­fer­en­t immune sys­tem path­ways to address inter­actions be­tween tumors, the microenvironment and the immune sys­tem to fur­ther ex­pand upon the progress we have made and help more patients respond to treat­ment. Combining these ap­proaches is key to de­livering new op­tions for the treat­ment of cancer and addressing the growing issue of re­sis­tance to immuno­therapy. We source inno­va­tion in­ternally, and in col­lab­o­ration with academia, gov­ern­ment, advocacy groups and bio­technology com­pa­nies, to help make the prom­ise of trans­formational med­i­cines a reality for patients.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global bio­pharma­ceu­tical com­pany whose mis­sion is to discover, de­vel­op and de­liver inno­va­tive med­i­cines that help patients prevail over serious dis­eases. For more in­for­ma­tion about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Face­book and Insta­gram.

About bluebird bio, Inc.

bluebird bio is pioneering gene ther­apy with pur­pose. From our Cambridge, Mass., headquarters, we’re devel­op­ing gene ther­a­pies for severe ge­netic dis­eases and cancer, with the goal that people facing poten­tially fatal con­di­tions with limited treat­ment op­tions can live their lives fully. Beyond our labs, we’re work­ing to pos­i­tively disrupt the health­care sys­tem to create access, transparency and education so that gene ther­apy can be­come avail­able to all those who can benefit.

bluebird bio is a human com­pany powered by human stories. We’re putting our care and ex­per­tise to work across a spectrum of disorders by re­search­ing cerebral adrenoleukodystrophy, sickle cell dis­ease, β-thalassemia and mul­ti­ple myeloma using three gene ther­apy tech­nolo­gies: gene addi­tion, cell ther­apy and (megaTAL-enabled) gene edit­ing.

bluebird bio has addi­tional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more in­for­ma­tion, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Insta­gram and YouTube.

bluebird bio is a trademark of bluebird bio, Inc.

Bristol-Myers Squibb Cautionary State­ment Regarding Forward-Looking State­ments

This press release con­tains “forward-looking state­ments” within the meaning of the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing, among other things, the re­search, devel­op­ment and com­mer­cial­iza­tion of pharma­ceu­tical prod­ucts. All state­ments that are not state­ments of historical facts are, or may be deemed to be, for­ward-looking state­ments. Such for­ward-looking state­ments are based on historical per­for­mance and current ex­pec­ta­tions and pro­jec­tions about our future fi­nan­cial results, goals, plans and objectives and in­volve­ in­her­ent risks, assump­tions and un­cer­tainties, in­clud­ing in­ternal or ex­ternal factors that could delay, divert or change any of them in the next several years, that are dif­fi­cult to predict, may be beyond our con­trol and could cause our future fi­nan­cial results, goals, plans and objectives to differ ma­teri­ally from those ex­pressed in, or im­plied by, the state­ments. These risks, assump­tions, un­cer­tainties and other factors in­clude, among others, the possibility of un­fa­vor­able results from addi­tional clin­i­cal trials of ide-cel or from sub­se­quent analysis of existing data from the KarMMa study or existing or new data re­ceived from addi­tional on­go­ing and future stud­ies of ide-cel, that ide-cel may not re­ceive regu­la­tory ap­­prov­al for the in­di­ca­tion described in this release in the cur­rently antic­i­pated timeline or at all and, if approved, whether such prod­uct can­di­date for such in­di­ca­tion described in this release will be com­mer­cially suc­cess­ful. No for­ward-looking state­ment can be guar­an­teed. Forward-looking state­ments in this press release should be eval­u­ated to­geth­er with the many risks and un­cer­tainties that affect Bristol-Myers Squibb’s business and mar­ket, par­tic­u­larly those identified in the cautionary state­ment and risk factors dis­cus­sion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended De­cem­ber 31, 2018, as up­dated by our sub­se­quent Quar­ter­ly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Se­cu­ri­ties and Ex­change Com­mis­sion. The for­ward-looking state­ments in­cluded in this doc­u­ment are made only as of the date of this doc­u­ment and except as other­wise re­quired by appli­cable law, Bristol-Myers Squibb under­takes no obli­ga­tion to pub­licly up­date or revise any for­ward-looking state­ment, whether as a result of new in­for­ma­tion, future events, changed cir­cum­stances or other­wise.

bluebird bio Cautionary State­ment Regarding Forward-Looking State­ments

This press release con­tains “forward-looking state­ments” within the meaning of the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing, among other things, the re­search, devel­op­ment and com­mer­cial­iza­tion of pharma­ceu­tical prod­ucts. All state­ments that are not state­ments of historical facts are, or may be deemed to be, for­ward-looking state­ments. Such for­ward-looking state­ments are based on historical per­for­mance and current ex­pec­ta­tions and pro­jec­tions about our future fi­nan­cial results, goals, plans and objectives and in­volve­ in­her­ent risks, assump­tions and un­cer­tainties, in­clud­ing in­ternal or ex­ternal factors that could delay, divert or change any of them in the next several years, that are dif­fi­cult to predict, may be beyond our con­trol and could cause our future fi­nan­cial results, goals, plans and objectives to differ ma­teri­ally from those ex­pressed in, or im­plied by, the state­ments. These risks, assump­tions, un­cer­tainties and other factors in­clude, among others, the possibility of un­fa­vor­able results from addi­tional clin­i­cal trials of ide-cel or from sub­se­quent analysis of existing data from the KarMMa study or existing or new data re­ceived from addi­tional on­go­ing and future stud­ies of ide-cel, that ide-cel may not re­ceive regu­la­tory ap­­prov­al for the in­di­ca­tion described in this release in the cur­rently antic­i­pated timeline or at all and, if approved, whether such prod­uct can­di­date for such in­di­ca­tion described in this release will be com­mer­cially suc­cess­ful, and that the col­lab­o­ration with Bristol-Myers Squibb may not con­tinue or be suc­cess­ful. No for­ward-looking state­ment can be guar­an­teed. Forward-looking state­ments in this press release should be eval­u­ated to­geth­er with the many risks and un­cer­tainties that affect bluebird bio’s business, par­tic­u­larly those identified in the risk factors dis­cus­sion in bluebird bio’s Annual Report on Form 10-K for the year ended De­cem­ber 31, 2018, as up­dated by our sub­se­quent Quar­ter­ly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Se­cu­ri­ties and Ex­change Com­mis­sion. The for­ward-looking state­ments in­cluded in this doc­u­ment are made only as of the date of this doc­u­ment and except as other­wise re­quired by appli­cable law, bluebird bio under­takes no obli­ga­tion to pub­licly up­date or revise any for­ward-looking state­ment, whether as a result of new in­for­ma­tion, future events, changed cir­cum­stances or other­wise.

Hyperlinks are provided as a con­ve­nience and for in­for­ma­tional pur­poses only. Neither Bristol-Myers Squibb nor bluebird bio bears re­spon­si­bil­ity­ for the se­cu­ri­ty or content of ex­ternal websites or websites outside of their re­spec­tive­ con­trol.

Source: Bristol-Myers Squibb and bluebird bio.