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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; 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.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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