AACR: Lit­tle Apex­i­gen steals the show with their CD40/Op­di­vo cock­tail as AACR gets un­der­way

Now that the pi­o­neer PD-1 check­points have hit the mar­ket and start­ed earn­ing their bil­lions, re­searchers in on­col­o­gy are fo­cused on the next big thing in can­cer R&D: us­ing new com­bi­na­tions to reach tu­mors that re­main stub­born­ly re­sis­tant to ap­proved ther­a­pies.

To that end, you can count Apex­i­gen as the ear­ly win­ner in the AACR meet­ing in At­lanta.

Joyson Karakun­nel

A group of in­ves­ti­ga­tors or­ga­nized by The Park­er In­sti­tute for Can­cer Im­munother­a­py in part­ner­ship with the Can­cer Re­search In­sti­tute con­duct­ed an ear­ly-stage clin­i­cal tri­al that com­bined a pair of chemother­a­pies with Apex­i­gen’s CD40 drug APX005M, with or with­out Bris­tol-My­ers Squibb’s Op­di­vo. In the first part of the Phase I tri­al for ad­vanced pan­cre­at­ic can­cer, they want­ed to see how CD40 — de­signed to spur an im­mune at­tack — worked with a PD-1, which is de­signed to take the brakes off an im­mune sys­tem at­tack.

This is the first tri­al where the in­sti­tute held the IND as the prin­ci­pal spon­sor, says Joyson Karakun­nel, med­ical di­rec­tor for The Park­er In­sti­tute and vice pres­i­dent-clin­i­cal de­vel­op­ment at Ar­cus Bio­sciences, who took some time on Sun­day to ex­plain the work. And they’re par­tic­u­lar­ly hap­py that Park­er was able to or­ga­nize and ex­e­cute an aca­d­e­m­ic study like this in just 18 months, of­fer­ing a new and more ef­fi­cient ap­proach to drug de­vel­op­ment that Sean Park­er had hoped for when he found­ed the in­sti­tute.

Of the 24 pa­tients who were evalu­able by AACR, 20 ex­pe­ri­enced a re­sponse with tu­mor shrink­age. And a few of those pa­tients have re­spons­es that en­dured for more than 12 months. That’s par­tic­u­lar­ly pos­i­tive for pan­cre­at­ic can­cer, which has been re­sis­tant to PD-1 and where dis­ease pro­gres­sion typ­i­cal­ly starts in about 5 months.

“To quote (first au­thor) Mark O’Hara, you do not see those kind of wa­ter­fall plots, so it is ex­treme­ly en­cour­ag­ing,” says Karakun­nel.

Tox­i­c­i­ty, how­ev­er, is a key con­cern. Thir­teen pa­tients — 54% — dis­con­tin­ued the reg­i­men due to an ad­verse event from the cock­tail. Ten of the ad­verse events were se­ri­ous. In­ves­ti­ga­tors fol­lowed up with me to note that 9 of the 13 con­tin­ued on at least one of the drugs and 4 stopped al­to­geth­er.

So why use Apex­i­gen’s drug? There are oth­er CD40s out there.  

Karakun­nel ex­plains that se­nior au­thor Bob Von­der­hei­de was fa­mil­iar with the Apex­i­gen pro­gram and thought it would be a good choice. Odd­ly, though, while the biotech had no trou­ble dis­cussing its $73 mil­lion raise from a group of Chi­nese in­vestors last sum­mer and put out their own re­lease Sun­day, the com­pa­ny turned down an in­ter­view re­quest.

The tri­al is now push­ing ahead to the Phase II por­tion of the tri­al with the high, 0.3 mg dose of Apex­i­gen’s drug. And the pri­vate, ven­ture-backed Apex­i­gen re­searchers plan to roll out more da­ta on APX005M in com­bi­na­tion ther­a­py for pa­tients with metasta­t­ic or un­re­sectable melanoma who have pro­gressed on an­ti-PD-1/PD-L1 ther­a­py. 

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.

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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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.

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.

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.

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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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).

Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

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.

J&J team shows off 'break­through' BC­MA CAR-T da­ta, and that could cause a big headache at blue­bird and Bris­tol-My­ers

Just hours after J&J’s oncology team bragged about scoring a breakthrough therapy designation for their BCMA CAR-T drug, they pulled the wraps off of the multiple myeloma data for JNJ-4528 that impressed the FDA. And it’s easy to see why they may well be on a short path to a landmark approval — which may well be making the rival team at bluebird/Bristol-Myers more than a little nervous.

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