The num­ber of I/O can­cer drugs in the clin­ic con­tin­ues to swell at an ex­plo­sive pace -- of­fer­ing new hope, fresh con­cerns

The jug­ger­naut of im­muno-on­col­o­gy drug re­search around the world con­tin­ues to rapid­ly gain speed and mass, of­fer­ing pa­tients with vir­tu­al­ly every can­cer type the prospect of new com­bi­na­tions or monother­a­pies that may bend the course of their dis­ease, ac­cord­ing to a new study map­ping the glob­al land­scape of I/O. But it al­so rais­es fresh con­cerns about com­modi­ti­za­tion and pa­tient re­cruit­ment as the num­ber of PD-1/L1s on the mar­ket con­tin­ues to mul­ti­ply, with hun­dreds more com­ing from be­hind in the pipeline.

Vanes­sa Hub­bard-Lucey

A team at the Can­cer Re­search In­sti­tute has been study­ing the field for the past 2 years, track­ing tri­al ac­tiv­i­ty around the globe as I/O con­tin­ues to at­tract block­buster-sized in­vest­ments in pur­suit of new stan­dards of can­cer med­i­cine. And the num­bers at the end of 2018 have swelled sig­nif­i­cant­ly in most cat­e­gories.

Source: Can­cer Re­search In­sti­tute

Click on the im­age to see the full-sized ver­sion

Some of the high­lights from their re­port — which was pub­lished in Na­ture Re­views Drug Dis­cov­ery — in­clude:

— World­wide the num­ber of I/O drugs in 6 key class­es has hit 3,394 — up 67% in one year. Those drugs in­volved 417 tar­gets like CD19, at the top of the list, fol­lowed by PD-1, PD-L1 and HER2. A year ago they were track­ing 2,031 drugs in­volv­ing 273 tar­gets.

— The group count­ed 2,250 clin­i­cal tri­als un­der­way for PD-1/L1 agents, an in­crease of 748 from a year ago. And there are 1,176 com­bi­na­tion stud­ies un­der­way, with a to­tal of 240 dif­fer­ent tar­gets.

— With a hand­ful of cell ther­a­pies ap­proved, CRI tracked 448 in pre­clin­i­cal de­vel­op­ment. Nine are in Phase III and 227 are in Phase II. The spike in cell ther­a­py work has pushed it in­to the lead among all 6 cat­e­gories tracked, well ahead of can­cer vac­cines and leav­ing on­colyt­ic virus­es be­hind — though that field is still grow­ing as well.

The US eas­i­ly re­mains the leader in the ge­og­ra­phy of I/O re­search, but Chi­na has been com­ing on strong as the num­ber 2 coun­try en­gaged in new re­search in­volv­ing I/O. And a num­ber of home grown PD-1/L1 drugs are near­ing ap­proval in Chi­na, with im­pli­ca­tions for the rest of the world.

Source: Can­cer Re­search In­sti­tute

Click on the im­age to see the full-sized ver­sion

Par­tic­u­lar­ly ex­cit­ing, says Vanes­sa Hub­bard-Lucey, di­rec­tor of the CRI Clin­i­cal Ac­cel­er­a­tor, is that “al­most all can­cer types are be­ing stud­ied with PD-1/L1 ther­a­pies in clin­i­cal tri­als, in­clud­ing many rare can­cers.”

But while all the num­bers con­tin­ue to steam ahead, there has been a sig­nif­i­cant de­cline in one key cat­e­go­ry: pa­tient re­cruit­ment has slowed 70% in 4 years, they say. And that un­der­scores a dra­mat­ic need to ex­pand the num­ber of pa­tients who can be re­cruit­ed for cur­rent and up­com­ing drug tri­als.

One of the rea­sons why I/O is so pop­u­lar is due to the mega-block­buster check­point suc­cess­es at Mer­ck and Bris­tol-My­ers Squibb. But while the lead­ers con­tin­ue to do well, every­one else look­ing to score gains of their own in a field like PD-1/L1 will be fac­ing a myr­i­ad of ri­vals be­ing ad­vanced for every con­ceiv­able tar­get. And a crush of com­peti­tors could well end up com­modi­tiz­ing the field, which is one rea­son why you’re see­ing so many com­bo stud­ies un­der­way. 

The lead­ers want to main­tain their lead, and the bio­phar­mas com­ing from be­hind want to find a way to break in with some­thing new.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

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.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

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Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

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.

FDA lifts hold on Abeon­a's but­ter­fly dis­ease ther­a­py, paving way for piv­otal study

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.

Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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Roche faces an­oth­er de­lay in strug­gle to nav­i­gate Spark deal past reg­u­la­tors — but this one is very short

Roche today issued the latest in a long string of delays of its $4.3 billion buyout of Philadelphia-based Spark Therapeutics. The delay comes as little surprise — it is their 10th in as many months — as their most recent delay was scheduled to expire before a key regulatory deadline.

But it is notable for its length: 6 days.

Previous extensions had moved the goalposts by about 3 weeks to a month, with the latest on November 22 expiring tomorrow. The new delay sets a deadline for next Monday, December 16, the same day by which the UK Competition and Markets Authority has to give its initial ruling on the deal. And they already reportedly have lined up an OK from the FTC staff – although that’s only one level of a multi-step process.

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KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

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.

UP­DAT­ED: Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

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).

Ear­ly-stage can­cer biotech nails $85M C round; Flem­ming Orn­skov's Gal­der­ma scores 'break­through' sta­tus

→ Zentalis Pharmaceuticals just nabbed an $85 million round from a syndicate that includes Matrix Capital, Viking Global Investors, Redmile Group, Farallon Capital, Perceptive Advisors, Surveyor Capital and Eventide Asset Management. Their lead drug is ZN-c5, which is currently in Phase I/II trials. The biotech describes that drug as a “potential best-in-class oral Selective Estrogen Receptor Degrader for estrogen receptor-positive, HER2-negative (ER+/ HER2-) breast cancer.”