Quin Wills (L) and Jack O’Meara

A UK biotech looks to up­set the pre­clin­i­cal mod­el for liv­er drug de­vel­op­ment, and now it's gear­ing up for the clin­ic

Liv­er dis­ease is one of the hard­est ther­a­peu­tic ar­eas to hit, and some re­searchers have point­ed to a dearth of mean­ing­ful pre­clin­i­cal mod­els dur­ing drug de­vel­op­ment. Now, a UK biotech has fig­ured out a workaround for its own siR­NA liv­er drugs, and it all starts with dis­card­ed hu­man or­gans.

Ochre Bio an­nounced the clos­ing of a $9.6 mil­lion seed fi­nanc­ing round, led by Khosla Ven­tures. Backed VC, Apol­lo Health Ven­tures, Selvedge, Ho­ton and Her­mes Epitek al­so par­tic­i­pat­ed in the fundrais­ing.

Ochre, which is led by co-founders Quin Wills and Jack O’Meara, us­es a strat­e­gy called “deep phe­nomics” to scan do­nat­ed liv­ers and dig­i­tize that in­fo in­to a crunch­able da­ta set. So far, the group says it has iden­ti­fied 200 new tar­gets for liv­er dis­ease.

In­stead of work­ing with an­i­mal mod­els, the com­pa­ny goes straight to hu­man liv­ers that have been do­nat­ed and deemed un­fit for use in trans­plants. The group tests its siR­NA ther­a­pies di­rect­ly on those “ex­plant­ed” liv­ers main­tained out­side the body. But the com­pa­ny has more planned: By 2022, the biotech says, it will have de­vel­oped a com­plete­ly in sil­i­co liv­er that can be used to dig­i­tal­ly per­turb a range of genes to iden­ti­fy new tar­gets at an even high­er scale.

While Wills was work­ing as the head of cel­lu­lar and sys­tems ge­nomics for No­vo Nordisk, he was pitch­ing a pared-down ver­sion of the work Ochre is do­ing, and he in­creas­ing­ly re­al­ized that dis­cov­ery in the space was go­ing the same way as a lot of car­diometa­bol­ic dis­eases.

“You can find a new tar­get if you want, but where do you go with this? Be­cause there are very poor in vit­ro mod­els, ter­ri­ble an­i­mal mod­els of un­clear rel­e­vance, the clin­i­cal tri­als have un­clear end­points, lack of bio­mark­ers,” he said in an in­ter­view with End­points News. “It’s just a messy messy space, and I don’t want to do tar­get dis­cov­ery for the next 10 years and not see it go any­where.”

The com­pa­ny is aim­ing to head to clin­i­cal tri­als by 2023. This fund­ing will help on­board five trans­plant cen­ter part­ners on dis­card­ed donor liv­ers. The com­pa­ny will go through an­oth­er round of fund­ing be­fore it heads to clin­i­cal tri­als, O’Meara said in an in­ter­view.

In a state­ment, Alex Mor­gan, part­ner of Khosla Ven­tures, said:

I have been im­pressed with the progress this very tal­ent­ed team has made to ac­cel­er­ate de­vel­op­ment of their deep phe­no­typ­ing plat­form. The liv­er is a ma­jor con­ver­gence point in hu­man me­tab­o­lism and many as­pects of health through­out the body, and the com­pa­ny’s ap­proach of de­vel­op­ing treat­ments that can im­prove the trans­plant suc­cess of liv­ers and then us­ing those in­sights to cre­ate ther­a­pies for the larg­er mar­ket of gen­er­al dis­eases as­so­ci­at­ed with the liv­er is a cre­ative and unique ap­proach.

Alex Mor­gan

The com­pa­ny, which re­lies on RNA, has been able to ride the suc­cess that has come with the tech­nol­o­gy’s jour­ney in­to be­com­ing a house­hold name, Wills said, thanks in part to Mod­er­na and Pfiz­er’s Covid-19 vac­cines.

“It’s def­i­nite­ly helped in terms of per­cep­tion, that’s very im­por­tant for us in terms of the fund­ing we’ve had, and it’s im­por­tant in terms of peo­ple who’ve want­ed to work with us,” Wills said. “If I had said even a year ago, peo­ple would have been far less re­cep­tive.”

The com­pa­ny al­so re­cent­ly opened up a Tai­wanese lab to study liv­er dis­ease in Asia, in ad­di­tion to its glob­al net­work of trans­plant part­ners that it has es­tab­lished in Eu­rope and North Amer­i­ca.

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

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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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