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?

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

→ The C-suite has shuffled considerably at liver disease-focused Terns Pharmaceuticals out of Foster City, CA. Senthil Sundaram now assumes the CEO post, replacing Weidong Zhong, who was at the helm since Terns was founded and is now moving into two new roles: CSO and chairman of the board. Sundaram makes his way to Terns after 2 years as CFO of Nightstar Therapeutics, which would later be acquired by Biogen. He was also VP and head of business development at NASH player Intercept after 13 years in investment banking.

Martin Shkreli (Shutterstock)

Mar­tin Shkre­li con­tin­ued to or­ches­trate an­ti-com­pet­i­tive schemes for Dara­prim be­hind bars — FTC

Martin Shkreli didn’t just blog, read up on drug development news and run his biotech business with a contraband cell phone in prison. According to the FTC, he was also coordinating the anticompetitive scheme to shield Daraprim — the drug at the center of a price-gouging controversy that earned him the “Pharma Bro” nickname — from generic rivals.

Back in January the FTC, together with New York’s attorney general, launched a federal lawsuit against Shkreli, who’s now serving a 7-year sentence for defrauding investors in his hedge fund, alleging that he effectively created a drug monopoly. While Shkreli’s notorious move to raise the per tablet price of Daraprim from $17.50 to $750 was perfectly legal, the tactics he allegedly deployed to box out competitors weren’t.

NIH director Francis Collins at a Senate Appropriations subcommittee hearing for Operation Warp Speed (Graeme Jennings/Pool via AP Images)

Covid-19 roundup: 'No­vem­ber or De­cem­ber' Collins' best bet on a vac­cine OK; First plas­ma tri­al sug­gests mor­tal­i­ty re­duc­tion

Count NIH director Francis Collins out for any wager that the FDA would authorize a Covid-19 vaccine in October.

The discussion came up during a call with reporters because some states and local governments have been told by the CDC to have vaccination plans ready to go by Oct. 1. Pharma execs, most notably from Pfizer and BioNTech, have raised hopes about a licensure during that month; President Donald Trump last week sounded an optimistic note about having a vaccine on the market “right around” Election Day on Nov. 3 — or possibly before.

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Charlie Silver (Mission Bio)

'We want to be every­where.' Mis­sion Bio rais­es $70M be­hind re­sis­tance-hunt­ing se­quenc­ing plat­form

Charlie Silver wants to look really, really closely at a lot of your cells. And he just got a lot of money to do so.

Silver’s startup, Mission Bio, raised $70 million in a Series C round Thursday led by Novo Holdings. The money, which brings Mission Bio to $120 million raised since its 2012 founding, will be used to advance the single-cell sequencing platform they built to detect early response or resistance to new cancer therapies.

Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

Qi­a­gen in­vestors spurn Ther­mo Fish­er’s takeover of­fer, de­rail­ing a $12B+ deal

Thermo Fisher Scientific had announced an $11.5 billion takeover of Dutch diagnostics company Qiagen back in March, but the deal apparently did not sit well with Qiagen investors.

After getting hammered by critics who contended that Qiagen $QGEN was worth a lot more than what Thermo Fisher wanted to spend, investors turned thumbs down on the offer — derailing the buyout even after Thermo Fisher increased its offer to $12.6 billion in July. Qiagen’s share price has been boosted considerably by Covid-19 as demand for its testing kits surged.

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