Moma Therapeutics aims at molecular machines with $86M raise

Interlocking gears
“Molecular machines are a very rich target class that really function to move things around the cell," said Tim Guzi, Ph.D., Moma Therapeutics' drug discovery chief. (Getty/Chalabala)

Moma Therapeutics wants to crack a new type of drug target wide open. The company snagged $86 million from the likes of Third Rock Ventures to systematically go after molecular machines, a family of more than 400 enzymes that others have only stumbled upon by chance.

“Molecular machines are a very rich target class that really function to move things around the cell, utilizing the energy that comes from the hydrolysis of ATP,” said Tim Guzi, Ph.D., Moma’s drug discovery chief, in a video. They range from DNA helicases and chromatin remodelers, which govern genetic expression, to transporters, which shuttle materials inside cells and across membranes.

Others have drugged molecular machines before, including Vertex Pharmaceuticals, which has developed multiple drugs that target a transporter that causes cystic fibrosis due to mutations in the gene that encodes it. Approved drugs like Kalydeco (ivacaftor) as well as gastroesophageal reflux disease (GERD) med omeprazole and chemo drug etoposide showcase the promise of Moma’s approach, the company wrote in a blog post. But the biopharma industry has typically found their targets “through serendipity,” missing the chance to target molecular machines as a family.

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The financing, from Third Rock Ventures, Nextech Invest, Cormorant Asset Management, Creacion Ventures, Casdin Capital and Rock Springs Capital, will bankroll the development of a drug discovery platform for molecular machines. Moma aims to exploit “a key vulnerability inherent to all enzymes in the class,” the company said, meaning the series of steps in which the enzymes change their protein structure to do their jobs.

Using cryo-EM—electron microscopy at low temperatures—the company will look at all the different shapes a molecular machine can take to find small molecules that bind to them. The goal is to pinpoint compounds that can disrupt the cycle of shape-changing steps and change what the enzyme does.

But with 400-plus targets, more than half of which can contribute to human disease, where is Moma going to start?

“Moma picks its targets by looking at some really key features. We look for a fundamental role in the disease and the evidence we use for that or look for is either genetic or functional genomic and we align this with a patient selection strategy so that we can continually test the hypothesis throughout the drug discovery process,” said Andy Garner, Ph.D., Moma’s vice president of target biology, in the video.

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