The field of off-the-shelf cell ther­a­peu­tics is grow­ing, with the promise of quick­er, cheap­er, and eas­i­er to man­u­fac­ture ther­a­pies than the first gen­er­a­tion of au­tol­o­gous CAR-Ts that im­pressed with their po­ten­cy but fell short on adop­tion due to man­u­fac­tur­ing wob­bles. And Pre­ci­sion Bio­Sciences — which is us­ing its gene edit­ing tech­nol­o­gy to de­vel­op cell based im­munother­a­pies de­rived from healthy donors in­stead of the pa­tient — is plan­ning ahead. On Thurs­day, the com­pa­ny un­veiled a new Durham, NC fa­cil­i­ty ded­i­cat­ed to mak­ing its off-the-shelf CAR-T prod­ucts.

No­var­tis’ pi­o­neer­ing CAR-T drug — Kym­ri­ah — was ap­proved by the FDA amidst great fan­fare in 2017, but adop­tion was ham­pered by man­u­fac­tur­ing woes. No­var­tis lat­er added ca­pac­i­ty, hav­ing bought cell and gene ther­a­py man­u­fac­tur­er Cell­for­Cure. These prod­ucts re­quire enor­mous man­u­fac­tur­ing heft — mak­ers first iso­late cells from the pa­tient, ma­nip­u­late them in the lab by adding chimeric anti­gen re­cep­tors to di­rect T cells to snuff out can­cer cells and then re-in­fuse them back in­to the pa­tient.

Durham, North Car­oli­na-based Pre­ci­sion is hard­ly the first drug de­vel­op­er that has tak­en note of these chal­lenges. Take­da, for in­stance, which plans to take its off-the-shelf CAR-Ts in­to the clin­ic in 2021, is in the fi­nal stages of com­plet­ing its in-house man­u­fac­tur­ing fa­cil­i­ty in the Boston area, which is armed with the ca­pac­i­ty to sup­ply a range of clin­i­cal tri­als.

For Pre­ci­sion $DTIL, this new plant is part of a larg­er in­vest­ment in its can­cer im­munother­a­py plat­form and fa­cil­i­ties ex­pan­sions in North Car­oli­na this year.

“(W)e’ve known from the be­gin­ning that it was crit­i­cal for us to ad­dress the need for scal­able man­u­fac­tur­ing of cell-ther­a­py prod­ucts…” not­ed co-founder and chief Matt Kane in a state­ment.

“[The plant] al­so has the po­ten­tial to be a com­mer­cial launch fa­cil­i­ty with the ca­pac­i­ty to gen­er­ate up to 10,000 dos­es of CAR T cell ther­a­pies and 4,000 dos­es of gene ther­a­pies per year,” he added.

The drug de­vel­op­er is aim­ing to have its cer­ti­fi­ca­tions in place to be­gin man­u­fac­tur­ing in the fourth quar­ter — and plans to use the fa­cil­i­ty to cre­ate drug in­gre­di­ents for Phase I/II clin­i­cal tri­als sched­uled to be­gin next year.

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.

The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.

It’s been a difficult few years for gene and cell therapy startup Abeona Therapeutics. Its newly crowned chief Carsten Thiel was forced out last year following accusations of unspecified “personal misconduct,” and this September, the FDA imposed a clinical hold on its therapy for a form of “butterfly” disease. But things are beginning to perk up. On Monday, the company said the regulator had lifted its hold and the experimental therapy is now set to be evaluated in a late-stage study.

Merck’s 2017 bet on KalVista Pharmaceuticals may have soured, after the UK/US-based biotech’s lead drug failed a mid-stage study in patients with diabetic macular edema (DME).

Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Bristol-Myers Squibb came to ASH this past weekend with a variety of messages on the new cancer drugs they had acquired in the big Celgene buyout, including liso-cel, the lead CAR-T program picked up in the $9 billion Juno acquisition. And one of the most important was that they had the pivotal efficacy and safety data needed to snag an approval from the FDA next year, with the BLA on track for a filing this month.