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.”

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

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Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Saurabh Saha at Endpoints News' #BIO19

On the heels of $250M launch, Centes­sa barges ahead with an IPO to fu­el its 10-in-1 Medicxi pipeline

Francesco De Rubertis made no secret of IPO plans for Centessa, his 10-in-1 legacy play. Barely two months later, the S-1 is in.

The hot-off-the-press filing depicts the same grand vision that the longtime VC touted when he did the rounds in February: Take the asset-centric mindset that he’s been preaching at Medicxi over the years, and roll up a bunch of biotech upstarts, with unrelated risk profiles, into 1 pharma company that can carry on the development at scale.

Steffen Schuster, ITM CEO

Ra­dio­phar­ma re­mains hot as Ger­many's ITM rais­es $109M to ad­vance neu­roen­docrine can­cer pro­gram

The world of radiopharmaceuticals has been heating up over the last few years, and Thursday saw another company focused on the field pull in a new nine-figure raise.

Germany’s ITM, or Isotopen Technologien München, scored a $109 million round of loan financing to push forward its precision oncology pipeline and fund late-stage development for its lead program. As part of the agreement, the loan will convert to shares in the event of future financial or corporate transactions, ITM said.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.