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.”

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.