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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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George Church (courtesy EnPlusOne BioSciences)

George Church, Wyss sci­en­tists and North­pond chal­lenge con­ven­tion­al RNA man­u­fac­tur­ing with new biotech

RNA medicine has been at the forefront for the past few years, with the first RNA silencing therapy approved in 2018, and mRNA Covid vaccines following after. But flying under the radar has been the process of actually making RNA for these treatments.

That’s what Daniel Wiegand and Jonathan Rittichier have been working on in George Church’s lab for the past six years.

Friday morning, they unveiled EnPlusOne Biosciences, a biotech built on their RNA synthesis platform. Wiegand will serve as the Watertown, MA-based biotech’s CEO, and Rittichier will be CSO. And no different from his other startups, Church will be acting as scientific advisor. Its fourth co-founder, Dan Ahlstedt, joined through a Harvard Business School program, and will be COO.

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Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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