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.”

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III VOYAGER before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.