Alex Zhavoronkov, Insilico CEO

With a new $255M megaround in hand, Alex Zha­voronkov has big plans for In­sil­i­co. Are they fea­si­ble?

If you take Alex Zha­voronkov at his word, it won’t be long un­til he rules over biotech’s AI drug dis­cov­ery are­na from atop his perch as In­sil­i­co CEO.

On the heels of a megaround an­nounced Tues­day morn­ing, the me­dia-savvy ex­ec out­lined a vi­sion of the not-so-dis­tant fu­ture where AI-fo­cused com­pa­nies crash and burn akin to the dot-com bub­ble in the ear­ly 2000s. Zha­voronkov likened the cur­rent en­vi­ron­ment to 1998, when there was a glut of biotechs that soaked up cap­i­tal but proved un­able to de­liv­er on their promis­es, he opined to End­points News.

Once that hap­pens, he claims, In­sil­i­co will be primed to emerge as the field’s Ama­zon or Google.

Zha­voronkov has made blus­tery claims be­fore, though, gen­er­at­ing con­tro­ver­sy back in 2019 with a pa­per claim­ing he “dis­cov­ered” a drug in just 21 days. And he’s far from alone in seek­ing to emerge as the win­ner of the first era of ma­chine learn­ing life sci­ence star­tups: Blue-chip biotech in­vestors such as GV, ARCH and Cas­din Cap­i­tal have thrown hun­dreds of mil­lions of dol­lars be­hind In­sitro and Re­cur­sion. Soft­Bank alone re­cent­ly wrote Ex­sci­en­tia a check for up to $300 mil­lion.

First, the nit­ty grit­ty of the raise: Zha­voronkov pulled in a huge $255 mil­lion Se­ries C for In­sil­i­co on Tues­day, by far the biotech’s biggest raise and more than 300% over­sub­scribed, he said. The funds will be used to push for­ward In­sil­i­co’s slate of 16 pre­clin­i­cal pro­grams, in­clud­ing its lead com­pound for id­io­path­ic pul­monary fi­bro­sis, which they will try to put in the clin­ic by the end of 2021.

As he has in the past, Zha­voronkov kept much of the prod­uct can­di­date in­for­ma­tion — things like drug tar­gets and in­di­ca­tions — close to the vest. In ad­di­tion to the fi­bro­sis lead, he said on­ly that “more than half” of the 16 pro­grams will be in on­col­o­gy, with In­sil­i­co al­so fo­cus­ing on meta­bol­ic dis­eases, im­munol­o­gy, CNS and Covid-19.

He de­clined fur­ther com­ment on whether the raise rep­re­sents a pre­cur­sor to an IPO, though he not­ed giv­en the size and in­vestors in­volved (Tues­day’s lead is War­burg Pin­cus, with no­table par­tic­i­pa­tion from Lil­ly Asia Ven­tures, Or­biMed and Deer­field) it would be “log­i­cal to as­sume” In­sil­i­co has plans for a po­ten­tial fu­ture ex­it.

But most of the ex­cite­ment dri­ving the mas­sive raise, Zha­voronkov says, has been the way In­sil­i­co has built out its oth­er ser­vices. Where­as bio­phar­mas tra­di­tion­al­ly pre­fer to keep their pre­clin­i­cal bi­ol­o­gy and chem­istry work in-house, In­sil­i­co has con­tract­ed out most of these ef­forts to about 80 CROs, the chief told End­points. It’s al­lowed for a “fric­tion­less” busi­ness mod­el where the biotechs can do many things all at once that big­ger com­pa­nies usu­al­ly per­form se­quen­tial­ly.

“It’s saved a lot of time, a lot of cost, and in­creased the prob­a­bil­i­ty of suc­cess,” he told End­points. “We don’t have to wait for one ex­per­i­ment to con­clude and we can do some in par­al­lel, and if it fails we’ll learn.”

On top of that, In­sil­i­co has start­ed sell­ing its soft­ware to oth­er phar­ma com­pa­nies and open­ing its dis­cov­ery plat­form up for an­nu­al sub­scrip­tions. Zha­voronkov says he prefers when oth­ers can uti­lize In­sil­i­co’s IP be­cause it helps bring more at­ten­tion to the AI space as a whole while de­moc­ra­tiz­ing R&D ca­pa­bil­i­ties.

If one were to in­dulge Zha­voronkov in his grandeur, he’d de­scribe how “dozens” of com­pa­nies are al­ready try­ing to copy how In­sil­i­co op­er­ates. There have been sev­er­al in­stances, he claims, of peo­ple at­tend­ing the biotech’s pre­sen­ta­tions sole­ly to take pic­tures of their slide decks. Rather than fret over los­ing com­pa­ny se­crets, Zha­voronkov says this is “a won­der­ful thing.”

There’s a reck­on­ing com­ing for the AI space, how­ev­er, that will like­ly re­sult in sig­nif­i­cant con­sol­i­da­tion, he says. As in­vestor ap­petite for the area has heat­ed up, it’s sud­den­ly be­come much eas­i­er to launch a com­pa­ny and raise lots of mon­ey, com­pared to where In­sil­i­co was sev­en years ago when Zha­voronkov got start­ed.

Where­as In­sil­i­co strug­gled to ini­tial­ly drum up cash, nowa­days there are peo­ple who have “just quit an in­ter­net firm and sud­den­ly get $100 mil­lion,” he says. It’s on­ly a mat­ter of time be­fore the bub­ble bursts, he added.

“Some com­pa­nies just start, get a huge amount of mon­ey, and what they start do­ing is they start hir­ing, they start in­flat­ing the salaries,” Zha­voronkov said. “And that’s a bad thing. At some point in time, it needs to cor­rect. The ques­tion here is when, and the ques­tion here is when will the less so­phis­ti­cat­ed in­vestors stop fund­ing this sec­tor.”

When­ev­er this hap­pens — Zha­voronkov es­ti­mates signs will start to ap­pear with­in the next 12 to 24 months — In­sil­i­co is prepar­ing to jump at some of the tal­ents that will end up on oth­er com­pa­nies’ chop­ping blocks. If Zha­voronkov has his way, the ten­drils he’s laid out will con­tin­ue to evolve and push in­to new sec­tors past just soft­ware of­fer­ings. In this way, he likens In­sil­i­co to Ama­zon, a com­pa­ny that has its hands in every­thing.

Whether or not this fu­ture comes true re­mains to be seen. It’s im­pos­si­ble to pre­dict how the mar­ket might move or re­act to any giv­en phe­nom­e­non. And de­spite the com­pa­ny’s promi­nence in the space, In­sil­i­co is still wait­ing on that first clin­i­cal tri­al.

But Zha­voronkov be­lieves he’s in po­si­tion to take ad­van­tage of what­ev­er might hap­pen.

“If the in­vestors want­ed us to just be­come a phar­ma com­pa­ny, I imag­ine I would not still be at the helm of the com­pa­ny,” Zha­voronkov said. “We want to have our AWS, and not just be a book­store. We’ll have our Prime and Prime En­ter­tain­ment, we need to branch out and be­come even big­ger to dom­i­nate. It can­not just end at the book­store.”

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

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Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

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Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

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Mi­rati’s drug sitra­va­tinib flops PhI­II in com­bo with Op­di­vo for cer­tain lung can­cer

Mirati Therapeutics’ path to a second drug approval will likely have to wait. The San Diego biotech company said Wednesday that its investigational lung cancer drug failed a Phase III trial testing it in combination with Bristol Myers Squibb’s Opdivo.

The drug, sitravatinib, and Opdivo weren’t better than the chemo drug docetaxel at keeping patients alive, Mirati said in a press release. The spectrum-selective kinase inhibitor missed the primary goal of overall survival in patients with second- or third-line advanced non-squamous, non-small cell lung cancer.

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The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

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Athena Countouriotis, Avenzo Therapeutics CEO (website via Nasdaq)

Ex-Turn­ing Point ex­ecs plan to have their next bet, Aven­zo, on the Nas­daq next sum­mer

The crew at Turning Point Therapeutics is back together for a new biotech that wants to acquire early-stage oncology small molecules, including antibody drug conjugates, and potentially form partnerships with China-based drug developers for ex-China rights as it eyes a speedy leap onto the Nasdaq around this time next year, CEO Athena Countouriotis told Endpoints News.

After selling Turning Point to Bristol Myers Squibb, announced at the onset of last year’s ASCO confab, she and colleague Mohammad Hirmand founded Avenzo Therapeutics. The CEO and CMO already have approximately $200 million in seed and Series A financing from five big-name investors to evaluate which drugs to bring into its pipeline. That includes SR One, OrbiMed, Foresite Capital, Citadel’s Surveyor Capital and Lilly Asia Ventures. Bidding wars for assets have led Avenzo to miss out on some deals in recent months, but the biotech has three active term sheets and hopes to bring in its first asset in the third quarter, Countouriotis said in a Friday morning interview.

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FDA ap­proves Lex­i­con’s heart-fail­ure drug af­ter de­feat in di­a­betes

The FDA on Friday approved Lexicon’s heart failure drug sotagliflozin following a string of setbacks for the pharma company, including an FDA rejection in diabetes and the loss of a development deal with Sanofi.

The dual SGLT1 and SGLT2 inhibitor will be marketed as Inpefa and is a once-daily tablet. It’s been approved to reduce the risk of cardiovascular death and heart failure-related hospitalization or urgent visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The label spans the range of left ventricular ejection fraction, including preserved ejection fraction and reduced ejection fraction, as well as patients with or without diabetes, Lexicon said Friday.

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Eu­ro­pean Com­mis­sion to re­ceive few­er Pfiz­er-BioN­Tech vac­cine dos­es un­der amend­ed con­tract

The European Commission has made a few changes to its vaccine contract with Pfizer and BioNTech, reducing the dose volume while extending the delivery timeline to cope with “evolving public health needs.”

The Commission previously struck a contract in May 2021 for 900 million doses, with the option to purchase another 900 million. Of those, 450 million were expected to be delivered in 2023, though an amendment now calls for fewer doses. While neither the Commission nor Pfizer and BioNTech have revealed an exact amount, an unnamed source told Reuters that the amendment reduces the remaining expected doses by about a third.

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