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.”

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Bio­gen has a shaky end to H1 with a $542M write-off adding to its woes — but an­a­lysts see big rev­enue ahead for Aduhelm

All eyes at Biogen’s Q2 earnings call Thursday were on Aduhelm, but investors also got a glimpse of what Biogen would have faced had the FDA not opted to approve their controversial Alzheimer’s drug.

That glimpse, revealing a combination of declining sales, growing competition and failed medicines, underscores the stakes of the big biotech’s Aduhelm efforts, as execs punch back at the criticism they’ve engendered in the political and medical world and vigorously pushes its sales staff to roll out the drug as fast as possible.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.

Mod­er­na es­tab­lish­es pub­lic health-fo­cused char­i­ty; FDA ap­proves As­traZeneca di­a­betes drug for pe­di­atric use

To help promote public health and healthcare in underserved areas of the world, Moderna will establish a charity with a $50 million endowment.

The Cambridge, MA-based company announced the board of directors’ approval Thursday. The foundation will focus on “charitable, scientific and educational endeavors” with an emphasis on promoting public health and the access to healthcare, the press release said. The foundation will start operations once its status as a 501(c)(3) is approved.