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Start-ups

Dyne Therapeutics launches with $50 million for oligonucleotide muscle delivery

The startup, founded by Atlas Venture, is developing antibody-oligonucleotide conjugates for genetic muscle diseases

by Ryan Cross
April 3, 2019 | A version of this story appeared in Volume 97, Issue 14

 

An illustration of an antibody with two antisense oligonucleotides attached.
Credit: Dyne Therapeutics
An illustration of two antisense oligonucleotides (yellow) attached to antibody (red) via their linker regions (blue).

The hundreds of individual muscles in the human body have long vexed drug developers trying to devise therapies that restore strength to people with genetic muscle diseases.

Oligonucleotides designed to patch or block the broken genes that characterize these conditions don’t do a very good job of navigating to muscles on their own. That’s led drug companies to douse patients with high concentrations of oligonucleotide therapies, hoping that enough of the molecules will make their way into muscle. The results have been marginally effective at best, and occasionally toxic.

To solve that problem, a startup called Dyne Therapeutics has raised $50 million in series A financing to develop antibody-oligo conjugates that shuttle oligo therapies into muscle cells. The idea takes a play from the antibody-drug conjugate field, where toxic anticancer drugs are attached to tumor-homing antibodies to ensure that the drugs exert their potent effects solely on cancer cells, while leaving healthy cells alone.

“When you deliver a naked oligo, very little gets to the muscle,” explains Dyne CEO Romesh Subramanian. By attaching oligos to antibodies designed to bind receptors on the surface of muscle cells, Dyne is boosting the number of oligos that get into muscle cells, which engulf the antibody-oligo complexes whole. The approach could lead to more effective, and safer, therapies for genetic muscle diseases, Subramanian says.

Another firm, Sarepta Therapeutics, is well known for Exondys 51, an oligo therapy designed to treat Duchenne muscular dystrophy. That drug was controversially approved in 2016 with little evidence that it was effective. Oligo experts point to the lack of muscle-specific delivery as the drug’s biggest holdup for success.

Subramanian, an entrepreneur-in-residence at the biotech-focused venture capital firm Atlas Venture, and Jason Rhodes, a partner at Atlas, spotted the muscle-delivery delivery problem and decided to form Dyne to tackle it.

That move is part of a growing trend for venture firms to brainstorm ideas for a startup in-house, and then go look for scientists and businesspeople with the right expertise to back it up. Dyne doesn’t have any scientific founders—the company’s skeleton staff has been working with contract research organizations to test its antibody-oligo concept in preclinical studies. But the startup has recruited former Sarepta executives to help kick-start its oligo knowhow.

Although Dyne won’t disclose any timeline specifics, its first program will focus on using antibody-oligo conjugates to block the repetitive DNA mutations that cause the disease myotonic dystrophy type 1. Another company, Avidity Biosciences, is also developing antibody-oligo conjugates for the same disease.

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