Successful manu­fac­tur­ing and re­lease of GMP vials of UCARTCS1

New York, NY (Press Release) – Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a bio­pharma­ceu­tical com­pany focused on devel­op­ing immuno­therapies based on gene-edited CAR T-cells (UCART), an­nounced to­day that the U.S. Food and Drug Admin­istra­tion (FDA) has approved the Com­pany’s Inves­ti­ga­tional New Drug (IND) appli­ca­tion to ini­ti­ate a Phase 1 clin­i­cal trial for UCARTCS1, in patients with mul­ti­ple myeloma (MM). The IND for UCARTCS1 was filed on De­cem­ber 28, 2018 and approved by the FDA within a month, on Jan­u­ary 25, 2019. Cellectis is the sponsor of the UCARTCS1 clin­i­cal study (MUNDI-01) and suc­cess­fully ensured the manu­fac­tur­ing and re­lease of UCARTCS1 GMP batches, as well as an IRB ap­prov­al.

UCARTCS1 is based on a tailored manu­fac­tur­ing process devel­oped by Cellectis, which removes both the CS1 an­ti­gen and TCR from the T-cell surface using TALEN® gene edit­ing tech­nology, before adding the CS1 CAR con­struct. This ap­proach has both clin­i­cal and op­er­a­tional ben­e­fits: the UCART is de­signed to have a lym­pho­de­plet­ing effect, and the CAR T-cell cross reac­tion is sup­pressed, allow­ing for suc­cess­ful manu­fac­tur­ing.

UCARTCS1 is the first allo­geneic CAR-T ther­apy for MM to enter clin­i­cal devel­op­ment. This mile­stone reinforces Cellectis’ leadership in the space, as it rep­re­sents the fourth TALEN® gene-edited allo­geneic CAR-T prod­uct can­di­date devel­oped by Cellectis to be approved for clin­i­cal trials fol­low­ing UCART19¹ for ALL patients, UCART123 for AML patients and UCART22 for B-ALL patients. The Phase 1 of the MUNDI-01 study is de­signed to assess the safety and tol­er­a­bil­ity at in­creas­ing dose levels of UCARTCS1 in patients living with MM.

“The last quarters have been very prod­uctive for Cellectis’ UCARTCS1 prod­uct can­di­date. We suc­cess­fully manu­fac­tured and re­leased GMP batches of UCARTCS1, filed an IND and secured ap­prov­al from the FDA to start the MUNDI-01 Phase 1 clin­i­cal study,” said Dr. André Choulika, Chairman and CEO of Cellectis. “This is the 4th time in 4 years that Cellectis dem­onstrates ex­cel­lence with an allo­geneic prod­uct can­di­date. It fur­ther dem­onstrates the strength of our inno­va­tion, our manu­fac­tur­ing process and our execution, as we are eager to bring the first allo­geneic mul­ti­ple myeloma CAR T-cell treat­ment to patients.”

We antic­i­pate the clin­i­cal re­search to be led by Dr. Krina Patel, Prin­ci­pal In­ves­ti­ga­tor, Assis­tant Pro­fessor, ­De­part­ment of Lymphoma/Myeloma, Division of Cancer Medicine at the MD Anderson Cancer Center in Houston, Texas. We plan to have two addi­tional sites en­rolling patients for this clin­i­cal study: Weill Cornell Medicine under the leadership of Dr. Ruben Niesvizky, Director of the Multiple Myeloma Center at New York Presbyterian Hospital-Cornell Medical Center and Hackensack Meridian under the supervision of Dr. Andre Goy, Chairman and Director of John Theurer Cancer Center (JTCC) at Hackensack Uni­ver­sity Medical Center.

About UCARTCS1

UCARTCS1 is an allo­geneic, off-the-shelf, gene-edited T-cell prod­uct can­di­date de­signed for the treat­ment of mul­ti­ple myeloma (MM). CS1 (SLAMF7) is highly ex­pressed on MM tumor cells and is an attractive target because there is strong evi­dence of tumor re­sponse to mono­clonal anti­body treat­ment targeting it. The lim­i­ta­tion so far has been the presence of the CS1 target on the surface of T-cells, which has hindered the access to CAR-Ts and bispecific anti­bodies. As an example, the in­tro­duc­tion of a CAR con­struct in T-cells induces cross T-cell reac­tion and leads to their self-destruction during manu­fac­tur­ing. Cellectis solved this issue by using TALEN® gene edit­ing to knock-out the CS1 gene from T-cells before introducing the CS1 CAR con­struct.

The UCARTCS1 MUNDI-01 clin­i­cal trial is a Phase 1 dose-escalation and dose-expansion study to eval­u­ate the safety, ex­pan­sion, persistence and clin­i­cal ac­­tiv­ity of UCARTCS1 (allogeneic engi­neered T-cells) in patients with MM. Dose level 1 will be admin­istered at 1x10⁶ UCARTCS1 cells per kilo­gram, and dose levels 2 and 3 will be admin­istered at 3x10⁶ and 9x10⁶, re­spec­tive­ly. The Dose Limiting Toxicity (DLT) period is 28 days in concordance with a 28-day staggering for the first 2 patients at each dose level.

MM is a cancer that forms in a type of white blood cell called a plasma cell, which helps the body to fight in­fec­tions by making anti­bodies that recog­nize and attack germs. MM causes cancer cells to accumulate in bone mar­row, where they crowd out healthy blood cells. The American Cancer Society esti­mates that 32,110 new cases of MM will be diag­nosed and 12,960 deaths are ex­pec­ted to oc­cur in the U.S. in 2019.

The manu­fac­tur­ing process of Cellectis’ allo­geneic CAR T-cell prod­uct line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, non-alloreactive engi­neered CAR T-cells. UCARTs are meant to be readily avail­able CAR T-cells for a large patient pop­u­la­tion. Their pro­duc­tion is industrialized with defined pharma­ceu­tical re­lease criteria.

Information about on­go­ing clin­i­cal trials is pub­licly avail­able on ded­i­cated websites, such as: www.clinicaltrials.gov (U.S.) and www.clinicaltrialsregister.eu (Europe).

About Cellectis

Cellectis is a clin­i­cal-stage bio­pharma­ceu­tical com­pany focused on devel­op­ing a new gen­er­a­tion of cancer immuno­therapies based on gene-edited T-cells (UCART). By capitalizing on its 19 years of ex­per­tise in gene edit­ing – built on its flagship TALEN® tech­nology and pioneering electroporation sys­tem PulseAgile – Cellectis uses the power of the im­mune sys­tem to target and eradicate cancer cells.

Using its life-science-focused, pioneering genome engi­neer­ing tech­nolo­gies, Cellectis’ goal is to create inno­va­tive prod­ucts in mul­ti­ple fields and with var­i­ous target mar­kets. Cellectis is listed on the Nasdaq (ticker: CLLS) and on Euro­next Growth (ticker: ALCLS). To find out more about us, visit our website: www.cellectis.com

Talking about gene edit­ing? We do it. TALEN® is a registered trademark owned by Cellectis.

Disclaimer

This press re­lease con­tains “forward-looking” state­ments that are based on our man­agement’s cur­rent ex­pec­ta­tions and assump­tions and on in­for­ma­tion cur­rently avail­able to man­agement. Forward-looking state­ments in­volve known and unknown risks, un­cer­tain­ties and other factors that may cause our actual re­­sults, per­for­mance or achieve­ments to be ma­teri­ally dif­fer­en­t from any future re­­sults, per­for­mance or achieve­ments ex­pressed or im­plied by the for­ward-looking state­ments. Fur­ther in­for­ma­tion on the risk factors that may affect com­pany business and fi­nan­cial per­for­mance is in­cluded in Cellectis’ Annual Report on Form 20-F and the fi­nan­cial report (including the man­agement report) for the year ended De­cem­ber 31, 2018 and sub­se­quent filings Cellectis makes with the Se­cu­ri­ties Ex­change Com­mis­sion from time to time. Except as re­quired by law, we assume no obli­ga­tion to up­date these for­ward-looking state­ments pub­licly, or to up­date the reasons why actual re­­sults could differ ma­teri­ally from those antic­i­pated in the for­ward-looking state­ments, even if new in­for­ma­tion be­comes avail­able in the future.

Note

1. Developed by Cellectis, exclusively licensed to Servier and now under a joint devel­op­ment agree­ment be­tween Servier and Allogene.

Source: Cellectis.