Stu­art Schreiber’s bid to tack­le huge class of cru­cial pro­teins nabs an­oth­er $50M

Four years af­ter launch­ing with pres­ti­gious co-founders and am­bi­tions to go af­ter a fam­i­ly of an­cient and cru­cial pro­teins, it’s still not clear how far Jnana Ther­a­peu­tics has ad­vanced. But it’s pushed far enough that in­vestors are will­ing to in­fuse more cash.

Jnana an­nounced a $50 mil­lion Se­ries B on Wednes­day led by RA Cap­i­tal. Al­though light com­pared to the megarounds that have be­come in­creas­ing­ly rou­tine for biotechs, it con­tains the same melange of A-list in­vestors that backed the com­pa­ny’s sci­en­tists from the be­gin­ning, in­clud­ing Po­laris, Ver­sant, Ab­b­Vie and Pfiz­er.

Stu­art Schreiber

Found­ed by Ver­tex co-founder Stu­art Schreiber, a cou­ple of his col­leagues at the Broad In­sti­tute, and Bris­tol My­ers vet Joel Bar­rish, Jnana’s big idea was to go af­ter SLCs, a fam­i­ly of about 450 pro­teins that traf­fic metabo­lites in­to and out of cells. Al­though drug de­vel­op­ers had tar­get­ed these re­cep­tors in­di­vid­u­al­ly — SGLT2 in­hibitors, a high­ly ef­fec­tive class of di­a­betes drugs, for ex­am­ple —no one had ever tried to go af­ter them com­pre­hen­sive­ly.

“What’s made them re­al­ly hard to go af­ter from a drug­ging per­spec­tive is they’re in­cred­i­bly di­verse, one from the oth­er,” CEO and co-founder Joanne Kotz told End­points News. “They’re di­verse in terms of their struc­ture, a wide va­ri­ety of struc­tures with­in the fam­i­ly. They’re di­verse in terms of their sub­strate; huge va­ri­ety of metabo­lites, all the way from cho­les­terol to iron.”

There was al­so the prob­lem that the pro­teins are bound to a mem­brane, so they couldn’t be eas­i­ly iso­lat­ed to study in a dish. Jnana came up with a cou­ple tech­no­log­i­cal so­lu­tions: It tried to study di­rect­ly in live cells, in­stead of iso­lat­ing them. And, rather than im­me­di­ate­ly look for small mol­e­cules that in­hib­it a giv­en pro­tein, its sci­en­tists first come up with “binders” that latch on any­where.

“The ad­van­tage this gives us is that we can de­vel­op a com­mon ap­proach to look­ing at bind­ing that you can move from one to the next,” Kotz said.

So far the fruits of those ef­forts re­main un­clear. The team has won high-pro­file part­ners, snar­ing a col­lab­o­ra­tion with Neu­ro­crine to go af­ter SLCs in the cen­tral ner­vous sys­tem, and a $40 mil­lion up­front, $1 bil­lion mile­stone deal with Roche to go af­ter re­cep­tors rel­e­vant for neu­rol­o­gy and im­munol­o­gy.

All of the com­pa­ny’s pro­grams, though, re­main pre­clin­i­cal and ex­ec­u­tives have yet to say pre­cise­ly how pre­clin­i­cal they are. With the fi­nanc­ing on Thurs­day, Jnana dis­closed that its lead pro­gram would be in PKU, a rare ge­net­ic dis­ease caused by an over­abun­dance of a mol­e­cule called pheny­lala­nine (Phe) in the blood; Jnana will look to block a re­cep­tor in kid­ney cells that re­ab­sorbs Phe, there­by al­low­ing more of the metabo­lite to fil­ter out in­to the kid­ney.

Kotz, though, de­clined to say how far along the pro­gram was or if they yet had a lead mol­e­cule.

“What I can say is that our Se­ries B fund­ing is suf­fi­cient to get the PKU pro­gram in­to the clin­ic,” she said.

Mean­while, the com­pa­ny is now look­ing to go be­yond SLCs and in­to oth­er class­es. Kotz claimed they had de­vel­oped a plat­form suf­fi­cient­ly that they can quick­ly build small mol­e­cule binders to vir­tu­al­ly any pro­teins, and then ei­ther try to in­hib­it or de­grade those pro­teins. She sees it as part of a wave of re­newed in­ter­est from phar­ma in new small mol­e­cule tech­nolo­gies, point­ing to Bay­er’s re­cent $2 bil­lion buy­out of Vi­vid­ion.

“We joke in­ter­nal­ly that SLCs as a tar­get class are so di­verse, so chal­leng­ing, that in or­der to build a plat­form to drug any SLC, we had to build what we laugh­ing­ly re­fer to as a Fer­rari en­gine,” she said. “A plat­form that re­al­ly has the ca­pa­bil­i­ty to drug any pro­tein.”

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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