MOMA Therapeutics

A clinic, finally.

Somewhere in a clinical trial site, a patient is receiving a small molecule that did not exist five years ago. It was designed to jam a specific cellular engine - one of the spinning, shape-shifting enzymes that cancer leans on to survive. That molecule traces back to a lab building at 20 Acorn Park Drive in Cambridge, Massachusetts, where about 45 people work for a company called MOMA Therapeutics.

MOMA is a clinical-stage precision medicine company. That sentence took four years and roughly $236 million to earn. The company spent most of that time on a problem most of the industry preferred to walk past: a whole class of proteins that refuse to hold still long enough to be drugged the easy way.

Some proteins won't sit for the portrait.

Here is the inconvenient truth at the center of modern drug discovery. To design a small molecule that binds a protein, it helps enormously to know that protein's shape. So the field got very good at freezing proteins into a single pose and photographing them. The trouble is that the most consequential proteins in human disease - ATPases, GTPases, helicases, the cell's molecular machines - are defined by motion. They burn chemical energy to transport cargo, unwind DNA, degrade other proteins, and switch processes on and off. A snapshot of one is like a photo of a hummingbird mid-flap: technically accurate, mostly useless.

For decades, the workaround was to call these targets "undruggable" and move on to friendlier proteins. It was a tidy solution. It also meant some of the best targets in oncology stayed off-limits, not because they didn't matter, but because they wouldn't pose.

MOMA's founders looked at that pile of abandoned targets and saw the opposite of a dead end. They saw an inventory. By one company count, more than 400 molecular machines sit waiting - a backlog of biology that had been skipped for being too hard, not too unimportant.

Four academics walk into a venture firm.

In 2020, Third Rock Ventures incubated MOMA and handed it $86 million to start. The scientific founders were not newcomers hoping motion could be tamed - they were the people who spent their careers studying it. Dorothee Kern, of Brandeis and the Howard Hughes Medical Institute, built her reputation on protein motion and biophysics. Eva Nogales, of UC Berkeley and HHMI, is a pioneer of cryo-electron microscopy, the technique that earned a Nobel Prize for letting scientists see proteins closer to their natural, jittery state. Johannes Walter, of Harvard Medical School and HHMI, studies the molecular machines that maintain the genome. Timur Yusufzai, a former Harvard faculty member, came in from Third Rock itself.

Three HHMI investigators and an entrepreneur-in-residence is an unusual founding team. It is also a tell. You do not recruit that bench to make incremental tweaks to easy targets. You recruit it because you intend to make motion itself the thing you exploit.

KNOMATIC, explained without the jargon.

The platform is named KNOMATIC, and the marketing temptation is to call it magic. It is not. It is three unglamorous disciplines wired together so tightly that each one feeds the others.

First, structure: deep structural insight into how a dynamic protein actually moves, not just how it looks frozen. Second, hit-finding: industrial-scale ways to test millions of molecular fragments against that target, including high-throughput fragment screening and DNA-encoded library screening. Third, computation: machine learning and computational chemistry that take the screening results and the structural movies and predict which compounds to make next. CRISPR-based functional genomics rounds it out by confirming which targets a cancer truly depends on.

The point of fusing them is speed and conviction. Every program feeds a growing knowledge base, which makes the next program faster and the odds easier to read. It is less a microscope than an assembly line - one designed specifically for targets that move.

The market tends to be skeptical. It paid up anyway.

Platforms are cheap to claim and expensive to validate. MOMA has two kinds of validation worth more than a pitch deck. The first is its own pipeline reaching Phase 1 - the moment a thesis about enzyme motion becomes an actual molecule in actual patients. The second is that two of the most discerning buyers in pharma signed up.

Roche came first, as a discovery partner. Then in October 2024, Bayer struck an option and exclusive license deal for a small-molecule oncology program discovered on KNOMATIC. Bayer takes the preclinical, development, and commercial work from there; MOMA collects an upfront payment, a collaboration fee, milestones, and tiered royalties. Big pharma does not write those checks for press releases. It writes them when the underlying science survives its own due diligence.

Adapt the discovery, not the target.

Most companies pick targets that fit their tools. MOMA's organizing principle inverts that: build tools that fit the best targets, even when the best targets are inconveniently alive and moving. The name itself nods to molecular machines, the tiny motors that keep every cell running and, when hijacked, keep tumors running too.

It is a slightly contrarian way to run a biotech, which in a field that prizes following the herd counts as a personality. The wager is that the backlog of "undruggable" dynamic proteins is not a wall but a queue - and that whoever learns to drug motion systematically inherits a very long list of opportunities.

If motion is druggable, the map redraws.

Return to that clinical trial site. The patient getting MOMA's molecule is the proof of a narrow claim: this one program works well enough to test. The broader claim is harder and more interesting. If a platform can reliably turn motion into a liability for disease, then a whole shelf of abandoned targets reopens for business - in oncology first, and plausibly beyond it.

MOMA has not won that argument yet. Phase 1 is the start of a long road, and most drugs that enter it never reach a pharmacy. But the company has done the hard, early thing: it took a target class the industry wrote off, built machinery specifically to handle it, and convinced both the capital markets and two pharma giants to come along. The hummingbird, it turns out, can be photographed in flight. MOMA is now finding out whether you can also make it land.