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.”

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Covid-19 roundup: Eu­rope pur­chas­es 80M dos­es of Mod­er­na's vac­cine; CO­V­AXX se­cures $2.8B in emerg­ing mar­ket pre-or­ders

With the announcement of its vaccine efficacy data last week, Moderna is starting to line up customers for its Covid-19 mRNA jabs.

The Massachusetts-based biotech announced Wednesday it has agreed to sell an initial round of 80 million doses to the European Commission, with the option to double the amount to 160 million. Once the member states rubber stamp the approval, the deal will be finalized.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Feng Tian, Ambrx CEO (Ambrx)

Af­ter 5 qui­et years, a for­mer Scripps spin­out rais­es $200M and an­nounces plans to try again at an IPO

The first time San Diego biotech Ambrx tried to go public in 2014, they failed and the company’s board switched to a radically different strategy: They sold themselves for an undisclosed amount to a syndicate of Chinese investors and pharma companies.

Now, after 5 quiet years, that syndicate has raised a mountain of cash and indicated they’ll soon make another bid to go public.

Earlier this month, Ambrx raised $200 million in what they billed as a crossover round financed by Fidelity, BlackRock, Cormorant Asset Management, HBM Healthcare Investments, Invus, Adage Capital Partners and Suvretta Capital Management. It’s the largest amount they’ve ever raised and, according to Crunchbase figures, more than doubles the total amount of VC capital collected since their launch 17 years ago.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Michelle Longmire, Medable CEO (Jeff Rumans)

Med­able gets $91M for vir­tu­al clin­i­cal tri­als, bring­ing to­tal raise to $136M

As biotechs look to get clinical studies back on track amid the pandemic, Medable returned to the venture well for the second time this year, bagging a $91 million Series C to build out its virtual trial platform.

The software provider recently launched three new apps for decentralizing clinical trials, and saw a 500% revenue spike this year. And it isn’t alone. Back in August, Science 37 secured a $40 million round for its virtual trial tech, with support from Novartis, Sanofi Ventures and Amgen. Patients and researchers are taking a liking to the online approach, suggesting regulators could allow it to become a new normal even after the pandemic is over.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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