Third Harmonic Bio launches with $155 million to develop pill for chronic hives

The Cambridge startup hopes that its experimental therapy can treat multiple conditions caused by severe allergies and inflammation.

Third Harmonic Bio has launched from stealth mode with $155 million to develop a single therapy that the Cambridge startup hopes can treat multiple diseases caused by severe allergies and inflammation.

The experimental drug, which is in early clinical studies to test its safety, came from a set of molecules that the company licensed from pharmaceutical giant Novartis.

If the drug passes its safety trial, Third Harmonic plans to test it in people with cold-inducible urticaria, a condition where exposure to cold causes a person’s skin to break out in hives. That trial could begin this summer. If the drug works for those people, it could also help control flare-ups of hives in other forms of chronic urticaria.

“It can be disfiguring, extremely painful, it disrupts sleep, and it impacts quality of life,” said chief executive Natalie Holles. “And in its most severe forms, it is torturous, because these people just don’t know when they will have a flare-up.”

Antihistamines are a standard treatment for the condition, but they don’t work for everyone. An injected drug called Xolair, sold by Genentech and Novartis, controls some forms of chronic hives, but Holles said that most people with the condition do not take Xolair and would prefer taking a pill if one was available.

Third Harmonic’s strategy for treating chronic hives is to dampen an out-of-control immune response caused by mast cells, a type of white blood cell that evolved to primarily fight parasites but is also responsible for allergic reactions and implicated in many inflammatory diseases.

“They are part of the immune system, which these days, in modern life, causes more harm than good,” Holles said.

To tamp down on misbehaving mast cells, Third Harmonic is using a drug that targets and inhibits a protein called KIT, which is found on the surface of mast cells. When KIT is active, it keeps mast cells revved up. Blocking the protein tells the mast cells to stand down and eventually causes them to die, Holles said.

Drug developers have been interested in targeting KIT for some time, but it has been hard for chemists to find drugs that only inhibit that protein and not its closely related cousins — which could cause unwanted side effects. “It is exceedingly difficult to hit only KIT,” Holles said.

Michael Gladstone, a partner at the life science-focused Atlas Venture, conceived of the idea for a startup focused on targeting KIT. Atlas founded Third Harmonic in 2019 with the premise that controlling misbehaving mast cells by inhibiting KIT could lead to a single therapy that could be used for multiple diseases.

Holles said that her company is looking at applying the drug to misbehaving mast cells in the airways and gut as well, although she is not naming specifics at this time. “We call it a pipeline in a product,” she said. “We see the potential to address a number of allergic and inflammatory conditions with a single molecule.”