Alex Zhavoronkov, Insilico

AI study led by In­sil­i­co's Alex Zha­voronkov bol­sters case for faster, cheap­er drug dis­cov­ery

Drug de­vel­op­ment is an ar­du­ous and ex­pen­sive busi­ness. The promise of ar­ti­fi­cial in­tel­li­gence is that ma­chines can wean man­u­fac­tur­ers away from the breadth of re­sources it takes to dis­cov­er a po­ten­tial­ly po­tent com­pound, and lever­age the med­ical con­di­tions it could be used to treat. Alex Zha­voronkov, whose Hong Kong-based AI-shop In­sil­i­co Med­i­cine has en­trenched it­self in the ten­ta­cles of bio­phar­ma R&D, now has some da­ta to bol­ster the fer­vor and in­vest­ment that AI has drummed up.

On Mon­day, Zha­voronkov and his fel­low AI scouts from Wuxi and sci­en­tists from the Uni­ver­si­ty of Toron­to, pub­lished a pa­per in Na­ture Biotech­nol­o­gy that sup­port­ed the fea­si­bil­i­ty of em­ploy­ing a ma­chine learn­ing ap­proach — gen­er­a­tive ad­ver­sar­i­al net­works (GANs) and re­in­force­ment learn­ing — for de no­vo drug de­sign. The re­searchers found that they were able to iden­ti­fy a myr­i­ad of com­pounds tar­get­ing a pro­tein called Dis­coidin do­main re­cep­tor 1 (DDR1) — which is ex­pressed in ep­ithe­lial cells and in­volved in fi­bro­sis — in a swift 21 days.

Af­ter that, six mol­e­cules were then se­lect­ed for syn­the­sis in the lab — those tests re­vealed four with po­ten­tial. Fur­ther test­ing whit­tled it down to one com­pound, which was test­ed in mice. That da­ta sug­gest­ed the mol­e­cule con­ferred a po­tent ef­fect against the pro­tein — al­though much like any oth­er com­pound, its safe­ty and ef­fi­ca­cy must be val­i­dat­ed in hu­man tri­als.

This study, which was con­duct­ed in re­sponse to a chal­lenge set by a part­ner com­pa­ny, is a taste of things to come, Zha­voronkov not­ed in an in­ter­view with End­points News. The plan was to take an al­go­rithm de­vel­oped a few years ago — an al­go­rithm that is open­ly avail­able, and use it as a proof-of-con­cept to demon­strate the po­ten­tial for AI in drug dis­cov­ery, he as­sert­ed.

“Imag­ine…Pfiz­er putting out all of their pre­clin­i­cal stuff for free for every­body to use, right? They won’t do it. Or J&J putting out all of their da­ta, even the old stuff? They just don’t do it. We de­cid­ed to kind of do a de­mo. So the skep­tics are… a lit­tle bit less skep­ti­cal.”

Re­cent es­ti­mates by the Tufts Cen­ter for the Study of Drug de­vel­op­ment main­tain that tak­ing a drug all the way from dis­cov­ery to ap­proval costs rough­ly $2.6 bil­lion (in 2013 dol­lars). Steven Paul, cur­rent Karuna chief,  pub­lished a study in 2010 in which he high­light­ed the mag­ni­tude of re­sources it cost his for­mer em­ploy­er Eli Lil­ly $LLY to dis­cov­er new com­pounds: the out-of-pock­et cost for lead op­ti­miza­tion came to a hefty $146 mil­lion.

“In this work, we de­signed, syn­the­sized, and ex­per­i­men­tal­ly val­i­dat­ed mol­e­cules tar­get­ing DDR1 ki­nase in less than 2 months and for a frac­tion of the cost as­so­ci­at­ed with a tra­di­tion­al drug dis­cov­ery ap­proach. This il­lus­trates the util­i­ty of our deep gen­er­a­tive mod­el for the suc­cess­ful, rapid de­sign of com­pounds that are syn­thet­i­cal­ly fea­si­ble, ac­tive against a tar­get of in­ter­est, and po­ten­tial­ly in­no­v­a­tive with re­spect to ex­ist­ing in­tel­lec­tu­al prop­er­ties,” Zha­voronkov et al wrote in their pa­per.

Zha­voronkov com­pared the study to Al­pha­Go — the first com­put­er pro­gram de­vel­oped by Al­pha­bet’s AI com­pa­ny Deep­Mind and im­mor­tal­ized in a Net­flix doc­u­men­tary — to de­feat a pro­fes­sion­al hu­man Go play­er. Go, which orig­i­nat­ed in Chi­na over 3,000 years ago, is a de­cep­tive­ly sim­ple strate­gic think­ing board game that has an in­cred­i­ble 10 to the pow­er of 170 pos­si­ble board con­fig­u­ra­tions (which is more than the num­ber of atoms in the known uni­verse.)

“We kind of thought about this pa­per as a kind of mi­ni Al­pha­Go,” Zha­voronkov said. “I hope that the big ex­ec­u­tives will al­so kind of hear this and un­der­stand that…we ac­tu­al­ly put the en­tire dis­cov­ery process on dis­play.”

“Every sec­ond stu­dent in Chi­na wants to be an AI sci­en­tist…this (Al­pha­Go) mir­a­cle might not have im­pact­ed their lives sig­nif­i­cant­ly, but it re­al­ly changed the men­tal­i­ty for every­body,” he added. “So that is what we need in phar­ma. Peo­ple should fo­cus less on geopol­i­tics or…war­fare. This is the stuff to watch right on TV. This is the cool thing.”

A pla­toon of bio­phar­mas have linked up with the emerg­ing crop of AI spe­cial­ists itch­ing to cap­i­tal­ize on how large datasets can be har­nessed to dri­ve new ther­a­pies in­to the clin­ic. Zha­voronkov is well con­nect­ed — last year he raised funds at the be­hest of Shang­hai high-fly­er WuXi AppTec, Sin­ga­pore’s Temasek, Pe­ter Dia­man­dis and Ju­ve­nes­cence.

Iso­lat­ing com­pounds for de­vel­op­ment is one as­pect of the bal­loon­ing AI in­dus­tri­al com­plex — it al­so has ap­peal in an­oth­er is­sue drug de­vel­op­ers reg­u­lar­ly con­tend with — the low odds of suc­cess, even with com­pounds that show great po­ten­tial in ear­ly test­ing. Then there’s the gold­en ques­tion — even if AI can help make the process of drug de­vel­op­ment bet­ter, faster and cheap­er — will that trans­late to less ex­pen­sive treat­ments?

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).

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.

Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,500+ biopharma pros reading Endpoints daily — and it's free.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.