Clarissa Desjardins, Congruence CEO

New Or­biMed-backed biotech aims to repli­cate Ver­tex's wild­ly suc­cess­ful cys­tic fi­bro­sis pills in oth­er dis­eases

A new biotech aim­ing to tack­le pro­tein mis­fold­ing has land­ed a sub­stan­tial Se­ries A from some blue-chip in­vestors.

Con­gru­ence Ther­a­peu­tics burst on­to the scene Tues­day with a $50 mil­lion round, in­clud­ing funds from Or­biMed. The biotech will use the mon­ey to ad­vance its plat­form and move some of its pro­grams for­ward, CEO Claris­sa Des­jardins told End­points News.

Tues­day’s round was led by Am­pli­tude Ven­tures and Fonds de sol­i­dar­ité FTQ, a pub­lic de­vel­op­ment fund in Que­bec, Cana­da.

There are few oth­er de­tails about the com­pa­ny so far. Though Con­gru­ence says its plat­form uti­lizes ma­chine learn­ing and oth­er math­e­mat­i­cal and physics-based mod­el­ing sys­tems to char­ac­ter­ize pro­tein mis­fold­ing dis­or­ders, the biotech is not yet nam­ing the dis­eases it in­tends to re­search.

But the ap­proach ap­pears to re­sem­ble Ver­tex’s cys­tic fi­bro­sis treat­ments, in which the com­pa­ny uti­lized small mol­e­cule drugs to tar­get cer­tain sites on the af­fect­ed pro­tein to re­store sodi­um trans­port. Ver­tex’s drug was huge­ly suc­cess­ful, mak­ing the dead­ly ge­net­ic dis­ease treat­able for 90% of pa­tients, and proved it was pos­si­ble to treat ge­net­ic dis­eases with dif­fer­ent mu­ta­tions with a pill.

No one has been able to repli­cate the re­sults in oth­er dis­eases, how­ev­er, though sev­er­al groups are now try­ing. No­tably, Ab­b­Vie is at­tempt­ing this ap­proach in cys­tic fi­bro­sis as well, and the new At­las-backed start­up Rec­ti­fy Phar­ma­ceu­ti­cals launched last Oc­to­ber with Ver­tex vets.

Des­jardins did say that Con­gru­ence is al­so build­ing out a li­brary of the bio­phys­i­cal prop­er­ties of var­i­ous mu­tant pro­teins in hopes that a deep­er analy­sis will point to ways of cor­rect­ing them. The biotech is al­so keep­ing its dis­ease re­search ar­eas close to the vest for now.

Af­ter re­searchers iden­ti­fy what they be­lieve could be the mis­fold­ed pro­teins, they can screen po­ten­tial drug can­di­dates to see which “can re­vert the mu­tant and make it con­gru­ent with the wild type, so that we can func­tion­al­ly res­cue that pro­tein,” she said.

Des­jardins found­ed Con­gru­ence af­ter serv­ing as CEO of Clemen­tia Phar­ma­ceu­ti­cals, ac­quired in a $1.3 bil­lion deal with Ipsen in 2019. She told End­points that af­ter Clemen­tia, she want­ed to con­tin­ue re­search­ing rare dis­eases but was look­ing for the right op­por­tu­ni­ty to make an im­pact.

“In rare dis­eases, many of these sin­gle amino acid par­tial loss of func­tion mu­tants were what you call tem­per­a­ture sen­si­tive, that means that they could be cor­rect­ed in vit­ro sim­ply by low­er­ing the tem­per­a­ture,” Des­jardins said. “If you low­er the tem­per­a­ture, you ac­tu­al­ly cor­rect the mis­fold­ing and re­store cel­lu­lar func­tion. So that was fas­ci­nat­ing to me.”

Though this has been a well-known phe­nom­e­non, she added, no one re­al­ly knows why it oc­curs. The foun­da­tion­al goal of Con­gru­ence is to treat such pro­teins as poly­mers, mak­ing it pos­si­ble to map every­thing out and then use the ma­chine learn­ing plat­form to ad­dress ques­tions that nor­mal­ly wouldn’t be pos­si­ble in a wet lab.

Go­ing for­ward, Des­jardins said what sets Con­gru­ence apart from the pack is it’s go­ing af­ter tar­gets that are al­ready val­i­dat­ed, rather than try­ing to find com­plete­ly new ones. The com­pa­ny’s plat­form al­so al­lows it to re­verse en­gi­neer dis­eases in the hopes of ad­vanc­ing pro­grams more ef­fi­cient­ly, she said.

In ad­di­tion to the lead in­vestors and Or­biMed, Con­gru­ence al­so re­ceived fund­ing from Lu­mi­ra Ven­tures, In­vestisse­ment Que­bec, Driehaus Cap­i­tal Man­age­ment and oth­er un­named back­ers.

Pi­o­neer­ing Click Chem­istry in Hu­mans

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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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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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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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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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