A T-cell play­er with back­ing from Roche takes next big step for BiTE drugs with 'on-of­f' switch to avoid tox­i­c­i­ty

The bis­pe­cif­ic T cell en­gager field is ab­solute­ly packed with big-name play­ers who have crowd­ed in de­spite some high-pro­file fail­ures in the class. Now, a Bay Area biotech thinks it may have the key to tack­ling BiTE tox­i­c­i­ty, us­ing an old “on-off switch” idea to give doc­tors more con­trol of the drugs’ ef­fect on pa­tients.

Kris­tine Ball

San Fran­cis­co-based So­te­ria Bio­ther­a­peu­tics un­cloaked Mon­day with a $42 mil­lion Se­ries A co-led by Roche Ven­ture Fund and 5AM Ven­tures with par­tic­i­pa­tion from the No­var­tis Ven­ture Fund to ad­vance its bis­pe­cif­ic T cell en­gagers with an “on-off” switch the founders think can avoid some of the dire safe­ty flags en­dem­ic to the class.

The biotech’s tech, dubbed T-LITE, works by us­ing an oral small mol­e­cule drug to bind and ac­ti­vate the two com­po­nents of the BiTE drug in vi­vo, giv­ing physi­cians the abil­i­ty to de­cide when and for how long to en­gage the drug in pa­tients. It’s a process known as chem­i­cal­ly in­duced dimer­iza­tion, and So­te­ria thinks it can give their drugs that sought-af­ter “switch” that oth­er BiTE drugs don’t have, CEO Kris­tine Ball told End­points News.

Zach Hill

So dimer­iza­tion is the “on” func­tion, but how about “off?” Ac­cord­ing to CSO and co-founder Zach Hill, whose re­search along­side co­founder Alex Mar­tinko — now the se­nior di­rec­tor of pro­tein sci­ence — and Jim Wells of UCSF un­der­girds So­te­ria’s tech, physi­cians can sim­ply stop dos­ing the oral small mol­e­cule. With­out the con­stant pres­ence of that chem­i­cal lig­and, the tu­mor cell anti­gen and T cell en­gag­ing com­po­nents of the BiTE drug re­vert back to their dor­mant forms with­out last­ing ef­fect.

Us­ing chem­i­cal­ly in­duced dimer­iza­tion in ther­a­peu­tic ap­pli­ca­tions isn’t a new con­cept, Hill says, but us­ing that process to bind and di­rect an­ti­bod­ies in a cell ther­a­py ap­pli­ca­tion is a big ad­vance and could give So­te­ria a big leg up over its myr­i­ad com­peti­tors in the space.

“We re­al­ly had this idea that Jim pre­sent­ed to us of say­ing look, is there a way to make a new gen­er­a­tion of chem­i­cal­ly in­duced dimer­iza­tion do­mains that uti­lize bet­ter small mol­e­cules and have pro­teins that have bet­ter prop­er­ties,” Hill said. “So he re­al­ly tasked us with this grand chal­lenge and even­tu­al­ly Alex and I were able to come up with the idea of mak­ing these around an­ti­bod­ies.”

With that break­through in hand, the Hill-front­ed brain trust set up So­te­ria in 2018 with the help of a small seed fund has been “es­sen­tial­ly in­cu­bat­ing” ever since, Hill said. Ball, who came to the team with decades in the field, in­clud­ing for a stint on the board of di­rec­tors at Forty Sev­en be­fore its ac­qui­si­tion by Gilead in March 2020, joined the team late last year to help take the wraps off its launch plans.

“Our tech­nol­o­gy is unique be­cause the T-LITEs can mod­u­late the T cell ac­tiv­i­ty by con­trol­ling the tim­ing, du­ra­tion and lev­el of bis­pe­cif­ic com­plex for­ma­tion … which should al­low us to widen that ther­a­peu­tic win­dow, push dose and have more ef­fi­ca­cious treat­ments,” Ball said.

Bring­ing Roche’s ven­ture arm on­board to the con­cept was a lucky one for Ball as she was point­ed to a con­tact through a life sci­ences pok­er group, of all things, and cold-pitched the fund on So­te­ria’s tech. The ex­cite­ment over the pos­si­bil­i­ty of tamp­ing down safe­ty risks was enough to earn their in­ter­est, and the rest is his­to­ry.

So­te­ria kicked off its lead pro­gram late last year and hopes to se­lect a can­di­date for that pro­gram some­time this year. The com­pa­ny ex­pects to use the pro­ceeds from the round to nar­row that search and move the pro­gram in­to IND en­abling stud­ies. Mean­while, So­te­ria will look to flesh out its ear­ly pipeline, and that process will be made in­fi­nite­ly eas­i­er by So­te­ria’s plug-and-play de­sign pro­gram. Cre­at­ing a new drug is as sim­ple as switch­ing out the tu­mor anti­gen com­po­nent of the T-LITE, Ball said, giv­ing the com­pa­ny plen­ty of syn­er­gy in its de­vel­op­ment process.

“Once we get our first T-LITE where we like it, there’s plen­ty of ef­fi­cien­cies from pro­gram to pro­gram,” she said.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, 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.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

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What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

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Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

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David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

The IPO 4-1-1: Four fil­ings, a pric­ing and a with­draw­al head­line this week's Nas­daq ac­tion as raise ap­proach­es $7.5B

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

Another week, another horde of biotechs is doing the Nasdaq dance.

This week saw four companies file their SEC paperwork ahead of expected debuts, another hit Nasdaq on Friday and a sixth formally withdrew its bid to go public. Aerovate Therapeutics, Ocean Biomedical and Acumen Pharmaceuticals all penciled in initial raises of $100 million, while Dermata Therapeutics is estimating a modest $18 million raise.

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Keiichi Fukuda, Heartseed CEO

Fresh off $598M deal with No­vo Nordisk, a Japan­ese stem cell com­pa­ny is on its way to the clin­ic with a dif­fer­ent ap­proach to treat­ing heart fail­ure

A common approach to treating heart failure with induced pluripotent stem cells involves grafting sheets of cells onto the surface of the heart to improve vascularization and blood flow. It’s the easiest method of transplantation — but you run the risk of not making an electrical connection with the heart and the cells not synchronizing with the patient’s heart muscle.

So what if you could inject spherical clusters of heart cells directly into the heart muscle wall? For Heartseed, that’s now the $37 million question.

Aaron Kantoff (Medicxi)

A Medicxi-backed start­up looks to tack­le treat­ment-re­sis­tant blood can­cers, and it's go­ing af­ter AML first

In the hardest-to-treat blood cancers, resistance to therapy is an existential problem for drug developers looking to permanently stave off tumors. A small biotech is chasing an emerging pathway to stop tumors’ ability to resist treatment, and its work has caught the eye of a couple of big-name investors.

Kurome Therapeutics snared a $15 million Series A round it will use to identify and develop a lead program from its platform looking at dual inhibitors of the IRAK1/4 signaling pathway and FLT3 protein receptors on heme blasts to crack treatment-resistant tumors, the biotech said Thursday.

Stuart Schreiber (Maria Nemchuk, Broad Institute)

Po­laris, Ab­b­Vie, Bay­er back Stu­art Schreiber's hunt to turn can­cer treat­ments in­to cures

What happens to cancer cells that don’t die after powerful treatment? Scientists have long known that in all but a handful of cases, they don’t vanish even if the patients appear cancer-free — instead lurking somewhere, unreachable and undetectable and preparing, like a vanquished movie villain at the start of a sequel, for a return.

Research over the last decade began to suggest there was something different about these survivor cells. It wasn’t just that they might mutate. They reprogrammed themselves, like an operating system sealing itself off after too many incorrect passwords, and entered a protective state that other cells in the body have been known to enter when threatened.

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