Pearl Huang. Cygnal

'We're ripe': Cyg­nal draws the cur­tain on Flag­ship's lat­est bet on ex­oneur­al bi­ol­o­gy — and $65M in cash

No mat­ter how many times one’s heard Flag­ship Pi­o­neer­ing’s ideation process de­scribed, there al­ways seems to be an el­e­ment of evo­lu­tion­ary won­der: bold, new con­cepts that are “sev­er­al stan­dard de­vi­a­tions away from what is known,” put through a rig­or­ous vet­ting process first aimed at try­ing to kill the idea, and on­ly the fittest sur­vive.

Noubar Afeyan

That’s per­haps why Pearl Huang found its lat­est cre­ation, Cyg­nal Ther­a­peu­tics, and its fo­cus on the pe­riph­er­al ner­vous sys­tem “ir­re­sistibly at­trac­tive.” While Huang’s ap­point­ment as CEO back in Jan­u­ary was well-pub­li­cized, Cyg­nal is just spelling out the de­tails on its plat­form to­day, with $65 mil­lion — most­ly from Flag­ship — to boast.

Be­fore she de­cid­ed to jump from Roche to take on the role, Huang did her home­work on the field that Flag­ship is call­ing ex­oneur­al bi­ol­o­gy.

“When you look back through the lit­er­a­ture, for ex­am­ple, in can­cer bi­ol­o­gy, the pe­riph­er­al nerves were de­scribed to be a part of tu­mors in the late 1800s,” she said. “So the knowl­edge was al­ready out there.”

Avak Kah­jelian

But the gen­er­al pre­oc­cu­pa­tion with the cen­tral ner­vous sys­tem and the brain, as well as a lack of meth­ods to il­lu­mi­nate the roles at pe­riph­er­al nerves play in dis­eases, rel­e­gat­ed the PNS to a wiring di­a­gram in charge of ex­e­cut­ing or­ders in many sci­en­tists minds. It wasn’t un­til bet­ter imag­ing tech­niques came around in re­cent years that they could see just how ex­ten­sive that sys­tem is in the body and in mul­ti­ple dis­ease states. And it’s al­so what at­tract­ed Flag­ship’s Noubar Afeyan, Avak Kahve­jian and Jor­di Ma­ta Fink to launch the ven­ture.

“We see that the pe­riph­er­al ner­vous sys­tem it branch­es and goes as deeply in­to tis­sue as your vas­cu­lar sys­tem,” she said. And through Cyg­nal’s work, “we can see that non-neur­al cells and tis­sues in the dis­ease state are ac­tu­al­ly coopt­ing the lan­guage of the neu­rons. They are now ex­press­ing neur­al genes and ac­ti­vat­ing neur­al path­ways but they are non-neur­al in ori­gin them­selves.”

There are six com­po­nents in Cyg­nal’s ef­fort to de­code the role the PNS plays in dis­eases and how drug hunters can use it to their ad­van­tage:

  1. Neu­roimag­ing
  2. Cul­ture tech­nolo­gies to test re­duc­tion­ist neu­ro­bi­ol­o­gy ideas where “we grow dis­ease tis­sue / cell types in the pres­ence of pri­ma­ry neu­rons to dis­sect the sig­nal­ing”
  3. Chem­i­cal ge­net­ics
  4. Iden­ti­fy causal­i­ty for a group of 2,000 ge­net­ic tar­gets dubbed the “neu­rome,” via CRISPR-Cas9
  5. Bioin­for­mat­ics plat­form fo­cused on neur­al sig­nals and neur­al path­ways
  6. A neu­rophar­ma­copia with 1,000 mol­e­cules de­signed to treat CNS dis­or­ders
Jor­di Ma­ta Fink

“Right now in this place in time, we’re the on­ly peo­ple — the on­ly com­mer­cial or­ga­ni­za­tion on the plan­et that can take those six tech­nolo­gies, put them to­geth­er, throw one ques­tion in­to that plat­form, get six dif­fer­ent an­swers and then con­nect the dots be­tween those an­swers to get nov­el in­sights in­to bi­ol­o­gy,” Huang said.

That will, in turn, lead to the dis­cov­ery of new small and large mol­e­cules — ad­mit­ted­ly tra­di­tion­al modal­i­ties that Cyg­nal be­lieves will do the job. With 41 staffers on hand (and a plan to ex­pand the of­fice to ac­com­mo­date 80), the goal is to nom­i­nate two pro­grams for de­vel­op­ment this year, most like­ly for can­cer and in­flam­ma­tion. But down the line, Huang can see plug­ging in any dis­ease from fi­bro­sis and en­dometrio­sis to wound heal­ing and obe­si­ty in­to their plat­form and yield­ing new drugs.

So why come out of stealth mode now?

“It’s kind of over­due, don’t you think?” Huang said. “It’s just time. We’re ripe.”

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

Mer­ck bags Ar­Qule's next-gen BTK can­cer drug with $2.7B buy­out deal — pay­ing more than dou­ble last close

Just 6 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 with Merck.

The pharma giant says it is scooping up the drug in an M&A deal for $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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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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Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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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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J&J's Mathai Mammen at an Endpoints News event in Boston, June 2018 (Photo: Rob Tannenbaum for Endpoints News)

J&J fronts $750M cash to grab a failed can­cer drug that’s been re­pur­posed as a pow­er­ful an­ti-in­flam­ma­to­ry

J&J has stepped up with one of its blockbuster drug buys, agreeing to pay Austin-based XBiotech $XBIT $750 million in cash and up to $600 million more in milestones for their late stage-ready anti-inflammatory drug bermekimab — which some longtime biotech observers may recognize as a failed cancer therapy with a disaster-prone past.

The drug targets the IL-1a pathway. J&J $JNJ R&D chief Mathai Mammen is cutting a check for a drug that has produced positive mid-stage data in patients suffering from a skin condition called hidradenitis suppurativa with another mid-stage program underway for atopic dermatitis.

That puts J&J in charge of a drug on the threshold of pivotal — though pricey — R&D work for a broad patient group with other related fields to explore. And it’s a very busy development arena.

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Sangamo CEO Sandy Macrae

Pa­tient #9 has been a con­cern, but Sang­amo and Pfiz­er are bull­ish about win­ning the marathon he­mo­phil­ia A gene ther­a­py race

Patient number 9 has given Sangamo and its partners at Pfizer some heart palpitations in their high profile hemophilia A gene therapy program.

After watching his Factor VIII level rise following treatment like the rest, the crucial efficacy gauge they track saw a sudden and significant plunge. At week 13, the FVIII level had dropped below normal. Then it began to rise again.

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