Out to ‘re­think the drug de­sign process,’ AI star Daphne Koller is cre­at­ing a new ma­chine learn­ing ven­ture at in­sitro with some heavy­weight back­ers

Daphne Koller has been busy.

Just two months since the high pro­file AI ex­pert ex­it­ed Google’s an­ti-ag­ing biotech Cal­i­co Labs, where she was chief com­put­ing of­fi­cer, Koller has gath­ered a group of mar­quee in­vestors to back a tech up­start — in­sitro — with plans to de­vel­op a ma­chine learn­ing plat­form equipped with cus­tom-built datasets to cre­ate a new and far more ef­fi­cient ap­proach to drug dis­cov­ery and de­vel­op­ment.

AI cir­cles have been buzzing with spec­u­la­tion and queries about what the for­mer Stan­ford pro­fes­sor planned to do af­ter ex­it­ing Cal­i­co, where she had been de­vel­op­ing com­pu­ta­tion­al meth­ods for an­a­lyz­ing bi­o­log­i­cal da­ta sets. She an­swered at least some of those ques­tions with a blog post late Tues­day that spelled out her com­mit­ment to “in­vest heav­i­ly” in cre­at­ing new datasets that can ac­cel­er­ate the use of ma­chine learn­ing in bio­phar­ma.

Koller has some high rollers back­ing the start­up, in­clud­ing some ven­ture groups well known for block­buster fundrais­ing and a yen for trans­for­ma­tion­al ven­tures. They are: Arch Ven­ture Part­ners, Fore­site Cap­i­tal, a16z, GV (for­mer­ly Google Ven­tures) and Third Rock.

In­sitro, she says, will “col­lect and use a range of very large da­ta sets to train ML mod­els that will help ad­dress key prob­lems in the drug dis­cov­ery and de­vel­op­ment process. To en­able the ma­chine learn­ing, we will use high-qual­i­ty da­ta that has al­ready been col­lect­ed, but we will al­so in­vest heav­i­ly in the cre­ation of our own datasets us­ing high through­put ex­per­i­men­tal ap­proach­es, datasets that are de­signed ex­plic­it­ly with ma­chine learn­ing in mind from the very start. The ML mod­els that are de­vel­oped will then help guide sub­se­quent ex­per­i­ments, pro­vid­ing a tight, closed loop in­te­gra­tion of in sil­i­co and in vit­ro meth­ods (an in­sitro par­a­digm).”

Ac­cord­ing to Koller, the low hang­ing fruit in drug dis­cov­ery has been picked. Reach­ing high­er, go­ing for much bet­ter drugs, will re­quire “a dif­fer­ent ap­proach to drug de­vel­op­ment.” Spend­ing bil­lions to de­vel­op new drugs — and then pass­ing the cost to pa­tients — is not sus­tain­able.

In launch­ing in­sitro with a group of hy­per con­nect­ed back­ers, Koller is in­stant­ly mak­ing her­self a top play­er in a field that has Big Phar­ma’s rapt at­ten­tion. Stream­lin­ing R&D and im­prov­ing the odds of suc­cess find­ing high im­pact ther­a­pies are con­sid­ered keys to longterm prof­itabil­i­ty. But now the fo­cus is on which out­fits can ac­tu­al­ly de­liv­er.

There will be plen­ty of peo­ple watch­ing to see if Koller and the team she’s now re­cruit­ing can per­form. And she knows it won’t be easy. She writes:

There is a lot of hype to­day around ma­chine learn­ing, with hy­per­bol­ic promis­es that it will mag­i­cal­ly solve all of hu­mankind’s prob­lems (and dire warn­ings that it will lead to the de­struc­tion of hu­mankind). We at in­sitro don’t ex­pect ML to be the so­lu­tion to all of the prob­lems in drug de­vel­op­ment, nor to be the mag­ic bul­let that helps find a treat­ment for every dis­ease. How­ev­er, we do be­lieve that the time is right to re­think the drug de­sign process us­ing a dif­fer­ent and more mod­ern toolk­it, in the hope that a new par­a­digm may help us cure more peo­ple, soon­er, and at a much low­er cost.

I’d queried Koller re­cent­ly af­ter hear­ing word about in­sitro. For now, she tells me in a mes­sage, her blog post goes about as deep in­to this as she wants to go right now. But more is com­ing.


Im­age: Daphne Koller. STAN­FORD

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

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Ahead of strate­gic up­date, new Sanofi CEO mulls op­tions for con­sumer health­care arm — re­ports

Big pharma has made moves to sharpen its focus on developing new medicines, while slow-growing consumer health divisions fall by the wayside. Looks like another large drugmaker is considering a similar move. On Thursday, reports citing sources indicated that Sanofi is reportedly mulling a joint venture, sale, or a public listing of its consumer health arm.

The French group is in discussions for options that could value the division at $30 billion, Bloomberg and Reuters reported, citing sources familiar with the matter.

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The triple crown in biotech: An all-or-noth­ing bet on an FDA ap­proval of 3 drugs over 16 months starts to­day

Bristol-Myers Squibb’s $74 billion Celgene deal closed as expected Wednesday evening. And now a new clock has begun to tick down for Celgene shareholders who came away from the deal with CVRs — contingent value rights — worth $9 or nothing. Those CVRs start trading today as $BMYRT.

The new deadline they have is the end of March 2021, a little more than 16 months from now, when Bristol-Myers will need to gain approvals on 3 late-stage drugs it’s picking up in the buyout: Ozanimod and liso-cel (JCAR017) are due up at the end of 2020, with bb2121 deadlined at the end of Q1 in 2021.

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Genap­sys fi­nal­ly un­veils vaunt­ed se­quencer, but can it dent Il­lu­mi­na?

Hesaam Esfandyarpour holds what looks like a mini-cooler up to the computer screen in his California office.

Esfandyarpour is in his late-30s, with crows feet creeping up against a youthful face. He wears a gray polo and the device in his hand — with its hard plastic-looking shell, blue-and-white pattern, and a white plastic paddle resembling a handle jutting out the front — might contain diced strawberries and peanut-butter sandwiches to meet mom and the kids at a SoCal park. Instead, Esfandyarpour tells me it’s going to change medicine and biopharma research.

Brii Bio backs in­fec­tious dis­ease start­up while ink­ing deal for its lead TB drug, dou­bling down on an­tibi­otics

Almost two years after leaving GSK to launch Brii Bio with a whopping $260 million in funding, Zhi Hong is seeing the trans-Pacific infectious disease specialist he set out to build take shape.

“Our pipeline is coming together,” he told Endpoints News, with 12 partnered assets plus some internal programs.

As its latest partner, AN2 Therapeutics, comes into the limelight for the first time with a $12 million seed round, so is Brii’s plans in the antibiotics space. Brii has obtained China rights to AN2’s antibacterial targeting mycobacterium tuberculosis for multi-drug resistant TB, which it says is in the clinical stage.

UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

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David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

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No­var­tis, Bay­er, Long­wood back ge­nomics start­up to speed search for im­munother­a­py tar­gets

Nearly a century passed between the first proto-immunotherapy attempts in cancer — crude and obscure but nonetheless with some scientific basis — and Jim Allison’s first T cell paper. Thirty-plus years flipped between the discovery of CTLA-4 as an off-switch and the approval of Yervoy. Twenty-two rolled between PD-1’s isolation and Opdiva and Keytruda. 

Longwood co-founder Lea Hachigian is betting she can hasten that. It’s a bet on newly established single-cell genomic analysis tech and the ability to crunch endless troves of data at a rate few others can, and investors including Leaps by Bayer and Novartis Venture Fund just put $39 million behind it. They call it Immunitas.