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.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

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Janet Woodcock (AP Images)

Ad­vo­ca­cy groups don't want Janet Wood­cock to head the FDA, blast­ing ‘reg­u­la­to­ry fail­ures’ in opi­oid cri­sis

It turns out the controversies around Janet Woodcock’s regulatory legacy weren’t limited to Sarepta’s eteplirsen.

A coalition of advocacy groups dedicated to the opioid crisis urged Norris Cochran and Xavier Becerra — the acting and designated HHS secretary, respectively — to keep her reign as interim FDA chief a “very short transition.” During her lengthy tenure as CDER, they add, Woodcock presided over “one of the worst regulatory agency failures in U.S. history.”

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Dean Li kicks off Mer­ck­'s post-Roger Perl­mut­ter era by team­ing with Arti­va and its off-the-shelf CAR-NK tech

Even though Dean Li has now officially taken over for Roger Perlmutter as R&D chief, Merck’s appetite for dealmaking continues to be ravenous.

Li struck his first big deal at the helm Thursday morning, hammering out a collaboration with Artiva Biotherapeutics that could earn the biotech nearly $1.9 billion when all is said and done. It’s a quick rise and validation for Artiva, which just last June launched with a $78 million Series A.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Covid-19 roundup: Con­tro­ver­sy around colchicine per­co­lates af­ter study fail­ure; As­traZeneca's meet­ing with EU was 'con­struc­tive,' but did­n't solve much

A group of researchers at the Montreal Heart Institute has spelled out what they had called positive results suggesting that colchicine, an inexpensive oral anti-inflammatory drug commonly used to treat gout, could prevent Covid-19 complications in newly diagnosed patients.

The study failed its primary endpoint. But the latest scientific debate around treatments for the coronavirus is just beginning to brew.

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'Bank of BAR­DA': In­ves­ti­ga­tion finds HHS raid­ed pan­dem­ic pre­pared­ness funds for decade be­fore Covid-19

Before 2020, few Americans had ever heard of the Biomedical Advanced Research and Development Authority, BARDA, or its far-flung mission to stave off future pandemics and bio-threats. Allegedly, that made it a pretty good target for others in HHS who needed to scavenge some extra cash.

Over the last decade, other HHS officials raided BARDA’s coffers and misappropriated millions of dollars that Congress had earmarked to fund vaccine research and prepare for public health emergencies like Covid-19, according to a new report from the US Office of Special Counsel, which investigated a whistleblower report.