Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cel­lar­i­ty start­ed with a sim­ple — but far from easy — idea that Avak Kahve­jian and his team were float­ing around at Flag­ship Pi­o­neer­ing: to dig­i­tal­ly en­code a cell.

As he and his se­nior as­so­ciate Nick Plugis dug deep­er in­to the con­cept, they found that most of the mod­els oth­ers have de­vel­oped take a bot­tom-up ap­proach, where they as­sem­ble the mol­e­cules in­side cells and the con­nec­tions be­tween them from scratch. What if they opt for a top-down ap­proach, aid­ed by sin­gle-cell tran­scrip­tomics and ma­chine learn­ing, to gauge the be­hav­ior of the en­tire cel­lu­lar net­work?

“If you look at cell be­hav­ior from the per­spec­tive of a mol­e­c­u­lar net­work un­der­ly­ing it, then you free your­self from the tra­di­tion­al ap­proach of one-di­men­sion­al, two-di­men­sion­al, three-di­men­sion­al tar­get-based or phe­no­typ­ic-based drug dis­cov­ery ap­proach­es,” Kahve­jian, who took on the CEO role, told End­points News. “What it al­lows you to do is to use the net­work changes as your read­out.”

Flag­ship ded­i­cat­ed $50 mil­lion to get the biotech start­ed, which is how Cel­lar­i­ty has been fund­ing the build­out of its plat­form and an­i­mal ex­per­i­ments to ver­i­fy their ini­tial hy­pothe­ses in the past two years.

By in­ter­twin­ing wet labs and a dig­i­tal twin dubbed the Cel­lar­i­um, Kahve­jian be­lieves his biotech hasn’t just “re-ar­chi­tect­ed” ther­a­peu­tic dis­cov­ery, but al­so the or­ga­ni­za­tion of an AI up­start. Chad Nus­baum, founder of the Broad Tech­nol­o­gy Labs, leads the tech­ni­cal unit churn­ing out da­ta; while Milind Kamkolkar has joined as chief dig­i­tal & da­ta of­fi­cer af­ter pi­o­neer­ing the role at Sanofi.

“I want­ed to build stuff. I didn’t want to just keep sourc­ing stuff,” Kamkolkar said of his de­ci­sion to leave the phar­ma gi­ant, where ex­ter­nal part­ner­ship was the pro­to­col for gain­ing dig­i­tal com­pe­ten­cy.

It’s the com­plete op­po­site at Cel­lar­i­ty, as they are build­ing a new en­gine that can be bro­ken down in­to three lay­ers. He calls the first “da­ta in­ges­tion” — chan­nel­ing all the in­for­ma­tion gen­er­at­ed by Nus­baum’s team with mul­ti­ple method­olo­gies and species in­to a data­base where sci­en­tists can plot and cu­rate knowl­edge. Then they en­ter the ex­plo­ration lay­er, in­ter­ro­gat­ing the cell be­hav­iors while an­a­lyz­ing how well ex­ist­ing and new com­pounds can per­turb the cells. On the last lay­er, they vi­su­al­ize the find­ings by cre­at­ing a satel­lite im­age of sorts.

Right now Cel­lar­i­ty has about 250 of these dig­i­tal guides on dif­fer­ent dis­eases, which they call Cel­lar­i­ty Maps. And they can en­com­pass every step of the tra­di­tion­al drug dis­cov­ery process.

“The ma­chines are in­cred­i­bly ca­pa­ble of par­al­leliz­ing and col­laps­ing what typ­i­cal­ly used to be a lin­ear process to try to un­der­stand whether the im­pact of that drug ac­tu­al­ly does have tox­i­c­i­ty or side ef­fects,” Kamkolkar added.

With 40 staffers on board, Cel­lar­i­ty has gone broad with its tech plat­form, prob­ing any­thing from ep­ithe­lial bar­ri­er dis­or­ders and on­col­o­gy to hema­to­log­i­cal dis­or­ders and neu­rol­o­gy. The plat­form can ac­com­mo­date mul­ti­ple ther­a­peu­tic modal­i­ties, Kahve­jian said, and they’ve test­ed both small and large mol­e­cules. He isn’t dis­clos­ing a time­line for when they might steer their lead can­di­dates in­to the clin­ic, but he’s not shy about the am­bi­tion to tack­le “dozens of pro­grams” at a time, and part­ner­ing as he sees fit.

As of Sep­tem­ber, Cristi­na Rondi­none, the for­mer head of car­dio­vas­cu­lar, re­nal and meta­bol­ic dis­eases at As­traZeneca, has al­so joined as pres­i­dent to help grow the com­pa­ny and push it to the next stage, en­abling down­stream clin­i­cal de­vel­op­ment of leads.

The new hires will find them­selves in a hor­i­zon­tal or­ga­ni­za­tion where no one do­main su­per­sedes the oth­er, Kahve­jian said, and where bi­ol­o­gists, tech­nol­o­gists, and the com­pu­ta­tion­al folks work to­geth­er in an in­te­grat­ed and mul­ti­lin­gual en­vi­ron­ment where in­sights are gen­er­at­ed more quick­ly and are “ac­tion­able the minute they are gen­er­at­ed.”

Kamkolkar re­called the sur­prise of a ma­chine learn­ing sci­en­tist when he found out that he was to spend time in labs and see how the da­ta are gen­er­at­ed.

“Yeah, you’re gonna have to go in labs,” Kamkolkar ba­si­cal­ly said. “It’s quite unique.”

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Peter Greenleaf, Aurinia CEO

Af­ter pass­ing on Ac­celeron, Bris­tol My­ers eyes bolt-on ac­qui­si­tion of au­toim­mune spe­cial­ist — re­port

Bristol Myers Squibb is looking to beef up its autoimmune portfolio by scooping up Aurinia Pharmaceuticals, Bloomberg reported.

The recent overtures to Aurinia, relayed by anonymous insiders, came just as Bristol Myers turned down buyout talks with partners at Acceleron — which Merck ultimately struck a deal to acquire for $11.5 billion. Bristol Myers has reportedly decided to cash out on its minority stake, likely bagging $1.3 billion in the process, while keeping the royalty deals on two of Acceleron’s blood disorder drugs.

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So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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