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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Maureen Hillenmeyer, Hexagon Bio CEO

Hexa­gon Bio rais­es $61M to con­tin­ue ef­forts to turn fun­gi in­to drugs

A year after raising a $47 million launch round, the fungi-loving drug hunters at Hexagon Bio have more than doubled their coffers.

Hexagon announced today that it raised another $61 million for its efforts to design cancer and infectious disease drugs based on insights mined from the DNA in millions of species of fungi. The new financing brings Hexagon’s committed funding to over $108 million.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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Blue­bird sends blood dis­or­der drug to FDA for ap­proval; CG On­col­o­gy en­ters col­lab­o­ra­tion with Roche for Tecen­triq

Bluebird bio announced it completed the rolling submission of its BLA to the FDA for betibeglogene autotemcel gene therapy.

The therapy, designed for patients with beta-thalassemia who require regular red blood cell transfusions, was previously granted breakthrough therapy designation for treating transfusion-dependent beta-thalassemia (TDT). If approved, beti-cel will be the first hematopoietic stem cell ex-vivo gene therapy for patients in the US.