Alex Zhavoronkov (Insilico)

In­sil­i­co preps first can­di­date for IND stud­ies, hop­ing to launch tri­al in IPF by end of 2021

Over the last sev­er­al years, Alex Zha­voronkov has turned In­sil­i­co in­to one of the most well-con­nect­ed AI biotechs out there. Now, the Hong Kong-based com­pa­ny is one step clos­er to reach­ing the clin­ic.

In­sil­i­co is bring­ing its first can­di­date in­to IND-en­abling stud­ies, Zha­voronkov an­nounced Wednes­day, with the goal of launch­ing an in-hu­man tri­al at some point lat­er this year. The move marks what he says is a first in AI drug dis­cov­ery, as both the tar­get and small-mol­e­cule in­hibitor in­volved in the pro­gram are com­plete­ly new and AI-gen­er­at­ed.

Zha­voronkov, who told End­points News he builds self-dri­ving ro­bots in his spare time, isn’t ready just yet to say what the tar­get or ex­per­i­men­tal drug are, but he not­ed that the fo­cus will be id­io­path­ic pul­monary fi­bro­sis. The tar­get it­self plays a key role in fi­brot­ic and in­flam­ma­to­ry path­ways, sit­ting on the in­ter­sec­tion of profi­brot­ic path­ways, he said.

More im­por­tant to In­sil­i­co is the process by which they dis­cov­ered the com­pound — de­spite us­ing more than 60 dif­fer­ent ap­proach­es, the main method was through its pro­pri­etary AI plat­form’s neur­al net­works. In­sil­i­co re­searchers start­ed by look­ing at how dif­fer­ent tis­sues sus­cep­ti­ble to fi­bro­sis can change over the course of pa­tients’ lives, but that op­er­a­tion is too dif­fi­cult for hu­mans to do on their own, as the req­ui­site datasets are mas­sive.

“We train on age, af­ter that we re-train on fi­bro­sis, get the first list of pri­or­i­tized like­ly tar­gets, and then we put them in­to bi­o­log­i­cal path­ways,” Zha­voronkov told End­points.

Af­ter that, In­sil­i­co ap­plied a sep­a­rate neur­al net­work to comb through data­bas­es over where gov­ern­ments were is­su­ing grant re­search and com­pa­nies were tak­ing clin­i­cal tri­als. That helped Zha­voronkov de­ter­mine whether the tar­get is ac­tu­al­ly new or if oth­er com­pa­nies had al­ready tried to make some­thing work with it.

Last­ly, Zha­voronkov want­ed to be able to trust the an­swers his neur­al net­works were spit­ting out. So he es­sen­tial­ly asked his AI to find po­ten­tial hid­den links be­tween the da­ta to in­crease their con­fi­dence that a drug would work, while al­so look­ing at how cer­tain key opin­ion lead­ers viewed the bi­ol­o­gy they were try­ing to crack.

In­sil­i­co de­vel­oped its plat­form in col­lab­o­ra­tion with Big Phar­mas to in­cor­po­rate how the “best of the best” hu­man re­searchers think about tar­get se­lec­tion, Zha­voronkov said, adding that in lots of cas­es, how­ev­er, tar­gets are cho­sen for busi­ness rea­sons rather than sci­ence. He wants to try to change that with his plat­form and Wednes­day’s an­nounce­ment.

“We need to find this ul­ti­mate bal­ance be­cause you re­al­ize that more than one tar­get can be im­pli­cat­ed in this dis­ease,” Zha­voronkov said. “So it is pos­si­ble there is not just one mag­ic bul­let, there could be sev­er­al bul­lets.”

When this new pro­gram ul­ti­mate­ly reach­es the clin­ic, by the end of this year at the ear­li­est, it will be a typ­i­cal Phase I study. But Zha­voronkov said he has the “lux­u­ry” of ex­per­i­ment­ing with every step of the tri­al giv­en oth­er phar­ma com­pa­nies haven’t yet en­tered this space in this fash­ion.

The im­me­di­ate next steps are to con­tin­ue push­ing out the plat­form to oth­er play­ers. In­sil­i­co has made the core of its AI open source in the hopes of bring­ing down drug dis­cov­ery costs across the in­dus­try. Zha­voronkov said val­i­dat­ing this tar­get in IPF cost In­sil­i­co on­ly $1.8 mil­lion.

“If I do not in­vent, I do not live,” Zha­voronkov said. “We will nev­er stop and we al­so have a huge pipeline of projects in AI.”

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,300+ biopharma pros reading Endpoints daily — and it's free.

BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,300+ biopharma pros reading Endpoints daily — and it's free.

No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,300+ biopharma pros reading Endpoints daily — and it's free.

FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,300+ biopharma pros reading Endpoints daily — and it's free.