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.”

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Per­cep­tive's fourth — yes, fourth — SPAC jumps to Nas­daq as the blank check tree con­tin­ues to ripen

The biotech SPAC boom has gone almost hand-in-hand with the industry’s IPO gold rush, and this week saw more blank check companies hop aboard the train.

Leading the way is Perceptive Advisors’ fourth SPAC, appropriately named Arya Sciences Acquisition IV, which priced Friday morning after raising $130 million. And on top of that, new Ziopharm executive chair James Huang is launching his own SPAC with MSD Partners and Panacea Venture, filing S-1 paperwork Thursday with plans to raise $200 million.

CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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