Brendan Frey, Deep Genomics

SpaceX in­vestor backs Toron­to AI up­start's jour­ney in­to the 'dark re­gion' of ge­net­ic dis­eases

Bren­dan Frey set out, when he be­gan the project to pick out a lead pro­gram for Deep Ge­nomics, to prove that the ar­ti­fi­cial in­tel­li­gence sys­tems his lab has de­signed can iden­ti­fy new drug tar­gets and find a win­ning can­di­date much faster than tra­di­tion­al meth­ods. Now that they have ze­roed in on an an­ti­sense oligonu­cleotide ex­on-skip­ping ther­a­py for a sub­type of Wil­son dis­ease — se­lect­ed out of 2,400 ail­ments and 120,000 un­der­ly­ing ge­net­ic mu­ta­tions — as their face case, the Toron­to-based biotech is ready to delve in­to new fron­tiers with their AI tech.

Deep Ge­nomics plans to spend rough­ly half of its new $40 mil­lion on clin­i­cal de­vel­op­ment of DG12P1, whose first-in-hu­man tri­al is slat­ed for 2021; and the oth­er half on strength­en­ing var­i­ous com­po­nents of its ma­chine learn­ing sys­tems, from ro­bot­ics to as­says. Fu­ture Ven­tures, an in­vestor in Tes­la and SpaceX, led the Se­ries B round while Am­pli­tude Ven­tures, Mag­net­ic Ven­tures, Khosla Ven­tures and True Ven­tures joined.

While they took a splice mod­u­lat­ing ap­proach for their first AI-dis­cov­ered com­pound akin to what Bio­gen has with Spin­raza, Deep Ge­nomics is next fo­cused on hap­loin­suf­fi­cien­cies — dis­or­ders where in­creased ex­pres­sion lev­els of one func­tion­al gene would be valu­able. In oth­er words, where­as the pre­vi­ous chal­lenge lied in find­ing the right mu­ta­tion to tin­ker, the new puz­zle is how best to boost a known tar­get.

It’s a rel­a­tive­ly new ap­pli­ca­tion of oligonu­cleotides with no ap­proved drugs, which is al­so be­ing ex­plored at Stoke Ther­a­peu­tics.

“There are many dif­fer­ent mech­a­nisms that could be rel­e­vant, and so when you look at all these dif­fer­ent mech­a­nisms and all these dif­fer­ent re­gions of the gene that you could de­sign the oli­go for, there are tens of thou­sands, or even hun­dreds of thou­sands of pos­si­ble com­pounds,” says Frey, a star re­searcher that in­sil­i­co’s Alex Zha­voronkov con­sid­ers “with­out doubt in top 10 sci­en­tists in this field in the world.”

Frey elab­o­rates:

That could be in the 5’ UTR, it could be in the in­tron, it could be in an ex­on, in­tron­ic se­quences are very large, could be in a 3’ UTR, dif­fer­ent kinds of mech­a­nisms may be in­volved. It could be a mat­ter of al­ter­ing the up­stream open read­ing frame, or it could be a mat­ter of an in­tron or ten­sion bot­tle neck, it could be a mat­ter of chang­ing the polyadeny­la­tion site, it could be a com­pound that al­ters sec­ondary struc­tures.

New tools will be re­quired to test all these paths they can po­ten­tial­ly trav­el down, and Deep Ge­nomics’ team of 40-plus is al­ready per­fect­ing one mod­el de­signed to pre­dict polyadeny­la­tion pat­terns.

“Mul­ti­lin­gual­ism is an im­por­tant core val­ue for us,” he pre­vi­ous­ly said. “Every­one at the com­pa­ny has had AI train­ing, and every­one at the com­pa­ny has done wet lab work. In fact I ac­tu­al­ly se­quenced the ge­nom­ic DNA for the Wil­son tar­get to val­i­date it once we edit­ed the cell line to put the pa­tient mu­ta­tion in­to the cells.”

In ad­di­tion to deep­en­ing the clin­i­cal bench, Frey is al­so re­cruit­ing for the busi­ness de­vel­op­ment unit.

“Our pipeline is over­flow­ing, and so we’re fo­cused on sign­ing some busi­ness deals,” he tells End­points News in the lead­up to the an­nu­al JP Mor­gan con­fab in San Fran­cis­co.

That in­cludes two ad­di­tion­al pro­grams for Wil­son’s dis­ease that, to­geth­er with the lead pro­gram, would ad­dress up to a quar­ter of the 230,000 pa­tients world­wide. There’s one oth­er undis­closed meta­bol­ic can­di­date for which Frey plans to sub­mit an IND this year, some com­pounds for retinopa­thy, and a dozen hap­loin­suf­fi­cient projects in de­vel­op­ment, he says.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Or­biMed, bio­phar­ma's biggest in­vestor, clos­es $3.5B in three new pri­vate funds

One of the world’s leading biopharma investors has pulled in its next rounds of cash, with the funds planned to go to dozens of companies around the world.

OrbiMed raised $3.5 billion across three private investment funds, it announced Monday, as it continues building on its long track record in healthcare and biopharma. All in all, the firm expects to invest in at least 60 companies across the US, Asia and Europe.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

In­tro­duc­ing End­pointsF­DA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.