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.”

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Michael Rome (Foresite)

In search of 'house­hold health­care brands of the fu­ture,' Fore­site Cap­i­tal rais­es $969M to sa­ti­ate a tech-heavy ap­petite

Back in April 2018, just before Foresite Capital unveiled its $668 million Fund IV and a strategy to focus on tech-driven life science bets, one of its portfolio companies quietly made an announcement.

Fount Therapeutics, a drug discovery outfit backed by Foresite and Eshelman Ventures, had raised $22 million in Series A cash to hatch several fledgling spinouts. “The first ‘NewCo,’ Kinnate, will be focused on developing precision oncology treatments,” read a press release.

Masayoshi Son, SoftBank CEO (glen photo/Shutterstock)

Japan's Soft­Bank plots bil­lions in biotech in­vest­ments in move that could keep the val­u­a­tion flood ris­ing — re­port

The valuation crazy train in biotech continues to roll into the new year with more than a dozen companies taking a chance on Nasdaq and money flowing in from all sides. Now, a Japanese institutional investor is reportedly weighing an entry into the market in a big way — will it keep the bitcoin-esque flood rising?

Already a part-time investor in biotech, SoftBank could drop billions of dollars into the industry as part of helmsman Masayoshi Son’s plan to spend around $80 billion of the firm’s own assets, according to a report from Bloomberg citing people familiar with the plan.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.