The newest, $86M Third Rock start­up chas­es the tiny bi­o­log­i­cal ma­chines in­side of you

It took 23 years from the iso­la­tion of the gene for cys­tic fi­bro­sis to the ap­proval of the first drug to tar­get it, and an­oth­er 7 for a drug that could treat the vast ma­jor­i­ty of CF pa­tients. Third Rock Ven­ture’s lat­est start­up thinks they can build sim­i­lar drugs a whole lot faster.

MO­MA Ther­a­peu­tics has raised $86 mil­lion to in­ves­ti­gate and drug a class of en­zymes known as mol­e­c­u­lar ma­chines. These pro­teins in­clude every­thing from en­zymes in­volved in DNA re­pair to the trans­port pro­teins that go awry in cys­tic fi­bro­sis — over 400 dif­fer­ent types, by MO­MA’s count. And yet, MO­MA con­tends, they have been over­looked to date, with re­searchers both fail­ing to un­der­stand them as a co­he­sive group and fail­ing to em­ploy sys­tem­at­ic ways of find­ing and drug­ging them.

Ver­tex’s CF drugs and pro­ton-pump in­hibitors, both of which go af­ter ma­chines, are red her­rings, MO­MA wrote in a blog post ac­com­pa­ny­ing the launch: Their suc­cess is a sign of both the field’s po­ten­tial and bio­phar­ma’s over­all fail­ure.

“Not on­ly do these med­i­cines fur­ther un­der­score the ther­a­peu­tic po­ten­tial of these en­zymes,” MO­MA wrote, “they al­so il­lus­trate bio­phar­ma’s rudi­men­ta­ry ap­proach­es to pros­e­cut­ing them — near­ly all were dis­cov­ered from nat­ur­al prod­ucts, through serendip­i­ty or with­out a sys­tem­at­ic ap­proach to in­ter­ro­gat­ing the bio­chem­istry of the pro­teins them­selves.”

Reid Hu­ber

Al­though the young biotech has yet to an­nounce any tar­gets, the blog post points em­pha­sizes the role of these mol­e­c­u­lar ma­chines in can­cer and rare dis­eases. Like most Third Rock star­tups, it will be led by a firm part­ner: in this case, Reid Hu­ber, who most re­cent­ly served as CSO of In­cyte. And the com­pa­ny’s R&D ef­forts will be led by Blue­print vet­er­ans Christoph Lengauer and Tim Guzi, who step in as CSO and SVP of drug de­vel­op­ment, re­spec­tive­ly.

The com­pa­ny’s ap­proach comes large­ly out of the Howard Hugh­es Med­ical In­sti­tute, where Dorothee Kern, Eva No­gales and Jo­hannes Wal­ter col­lab­o­rat­ed. A fourth founder, Third Rock en­tre­peneur-in-res­i­dence Timur Yusufzai, will head up pro­tein sci­ences at the biotech.

Dorothee Kern

Mol­e­c­u­lar ma­chines are, as the New York Times once put it, the world’s small­est me­chan­i­cal de­vices. Sci­en­tists have just be­gun syn­the­siz­ing ar­ti­fi­cial ones, but hun­dreds of dif­fer­ent types of these puny mo­tors are run­ning in the body at every minute, break­ing down and build­ing DNA, fer­ry­ing salt and wa­ter in­to and out of cells, forc­ing mus­cles to re­lax and con­tract.

Nor­mal­ly, these mo­tors func­tion by shift­ing be­tween iso­forms — dif­fer­ent struc­tures with the same chem­i­cal make­up. But a sin­gle mu­ta­tion, such as those seen on the CFTR mol­e­c­u­lar ma­chine in cys­tic fi­bro­sis, can act like a faulty valve, caus­ing var­i­ous de­grees of mal­func­tion. Tu­mors, mean­while, can some­times de­pend heav­i­ly on one of these mo­tors to grow.

Their struc­tur­al changes are their weak­ness, Hu­ber told End­points News. Al­though all pro­teins change shape, mol­e­c­u­lar ma­chines do so at an un­par­al­leled scale. MO­MA will search for those ma­chines with ge­nom­ic da­ta and try to use small mol­e­cules to in­ter­vene, po­ten­tial­ly cor­rect­ing mal­func­tion in rare dis­eases and crip­pling tu­mors.

Think of it like the dif­fer­ence be­tween walk­ing to the mail­box at the end of the dri­ve­way vs. get­ting in a car and dri­ving to Ohio — mol­e­c­u­lar ma­chines are the lat­ter. They open, they close, they twist, they slide, they un­wind on a mas­sive scale — all in or­der to pro­duce work,” Hu­ber wrote in an email. “This unique de­pen­dence on such large changes in shape pro­vides the key op­por­tu­ni­ty for MO­MA Tx — if we can dis­rupt those changes with small mol­e­cules, we may be able to dis­cov­er nov­el med­i­cines and do it in a sys­tem­at­ic way across the en­tire class.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Ap­peals court puts the fi­nal nail in the cof­fin for Tec­fidera patent, adding to Bio­gen's bur­geon­ing set­backs

In another setback for Biogen, the big biotech lost its appeal to revive a patent for the once-blockbuster drug Tecfidera, marking a likely conclusion to the case.

The US Court of Appeals for the Federal Circuit issued the ruling Tuesday morning, saying Biogen failed to satisfy the “written description” requirement for patent law. As a result, Mylan-turned-Viatris will be able to sell its multiple sclerosis generic without fear of infringement and Biogen will have to find a new revenue driver elsewhere.

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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