CEO David Main (Notch)

'In­dus­tri­al­iz­ing the pro­duc­tion of cell­s': An­oth­er iP­SC play­er joins the quest for off-the-shelf cell ther­a­pies

Sci­en­tists have been af­ter the “Holy Grail” of cell ther­a­py — an off-the-shelf prod­uct — for years. Notch Ther­a­peu­tics is now join­ing the quest with a tech plat­form it says can in­dus­tri­al­ize the pro­duc­tion of cells. And on Wednes­day, it un­veiled a $85 mil­lion Se­ries A to get go­ing.

Notch was found­ed in 2018 by Juan Car­los Zúñi­ga-Pflück­er and Pe­ter Zand­stra, but “re­al­ly kicked off” in late 2019 when it signed a deal with Al­lo­gene to re­search al­lo­gene­ic cell ther­a­py can­di­dates, CEO David Main said. The nascent biotech got $10 mil­lion up­front, and stands to earn up to an­oth­er $294.2 mil­lion in mile­stones.

Main, who came on board in 2020, plans on us­ing Notch’s Se­ries A funds to grow two things: the staff and the pipeline. Over the next two years, Main ex­pects the 35-per­son com­pa­ny to ex­pand to about 100 em­ploy­ees, and file its first IND.

What sets Notch apart from oth­ers work­ing on al­lo­gene­ic cell ther­a­pies is what it calls its “En­gi­neered Thymic Niche” plat­form, Main said. Rather than take blood and ex­tract the im­mune cells you want to give to a pa­tient, Notch cre­ates the im­mune cells from pluripo­tent stem cells. Pluripo­tent es­sen­tial­ly means the cell can be dif­fer­en­ti­at­ed in­to any cell you want, Main said.

To do so, they’ve cre­at­ed an ar­ti­fi­cial thy­mus, which is a small or­gan near the ster­num where T cells ma­ture. A cell go­ing through the thy­mus is ex­posed to a num­ber of sig­nals that turn it in­to an im­mune cell, Main ex­plained.

The idea of us­ing in­duced pluripo­tent stem cells, or iP­SCs, to grow cells in a lab in­stead of ex­tract­ing them from donors isn’t new. John­son & John­son inked an up to $3.1 bil­lion deal with Fate Ther­a­peu­tics back in April to work on iP­SC-de­rived CAR-T and CAR-NK can­di­dates. And Ver­sant Ven­tures’ Cen­tu­ry Ther­a­peu­tics nabbed a meaty $250 mil­lion round in 2019 to ad­vance iP­SC prod­ucts for can­cer.

“Peo­ple have known in sci­ence for many, many decades, how to dif­fer­en­ti­ate stem cells and T cells, but they haven’t been able to do it out­side of the test tube in a re­search li­brary. Or if they tried to com­mer­cial­ize it that way they’re hav­ing to have thou­sands of petri dish­es to make enough cells for ther­a­py,” Main said.

With the so-called En­gi­neered Thymic Niche plat­form, Notch says it can dif­fer­en­ti­ate stem cells in a “high­ly con­trolled fash­ion,” us­ing large scale batch re­ac­tors like the ones used to grow up an­ti­bod­ies or oth­er pro­teins.

“We can be mak­ing, you know, bil­lions of cells at a time,” Main said. “So re­al­ly in­dus­tri­al­iz­ing the pro­duc­tion of cells,” he added lat­er.

Notch — named af­ter the sig­nal that must be trig­gered to dif­fer­en­ti­ate a stem cell in­to a T cell — is on the verge of hit­ting the first pre­clin­i­cal mile­stone in the Al­lo­gene deal, ac­cord­ing to Main, though he de­clined to pro­vide more de­tail on that pro­gram.

It’s al­so work­ing on es­tab­lish­ing it­self in Seat­tle, in ad­di­tion to its cur­rent Toron­to and Van­cou­ver bases. The pur­pose? To build a de­vel­op­ment team around new­ly hired se­nior vice pres­i­dent of pre­clin­i­cal trans­la­tion­al sci­ences Chris Bond, who Notch poached from Kite.

Al­lo­gene chipped in­to the Se­ries A, in ad­di­tion to Lu­mi­ra Ven­tures, and CCRM En­ter­pris­es Hold­ings, EcoR1 Cap­i­tal, Cas­din Cap­i­tal, Sam­sara Cap­i­tal, Am­pli­tude Ven­tures and an undis­closed in­vest­ment firm. An­oth­er undis­closed fund led the round.

Main called al­lo­gene­ic cell ther­a­pies the “Holy Grail” of the field. By the time a pa­tient and their doc­tor de­cide a cell ther­a­py is the best ap­proach, it of­ten takes weeks, or some­times months, to get the cells, pu­ri­fy them, grow them up, stim­u­late them and get them back to the pa­tients, Main said. Dur­ing that time, a pa­tient’s dis­ease can progress. Not to men­tion that it’s cost­ly and la­bor in­ten­sive.

“What we think we’re go­ing to be at is, we’ll be able to make the cells, have them cry­op­re­served sit­ting in a cen­tral dis­pen­sary some­where, and as soon as they’re or­dered, with­in hours they can be de­liv­ered and ad­min­is­tered to the pa­tient,” Main said.

He added lat­er, “We think we bring that fi­nal piece … to re­al­ly un­lock the po­ten­tial of cell ther­a­py to be­ing broad­ly ap­plic­a­ble and be­ing more drug-like.”

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

‘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.

Endpoints Premium

Premium subscription required

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