Third Harmonic Bio, a biotech startup founded in 2019 by Atlas Venture, officially launched on Wednesday with $105 million in new funding to advance development of an inflammatory disease drug formerly owned by Novartis.
The company, which previously raised $50 million from Atlas and two other venture investors, is led by Natalie Holles, the former CEO of Audentes Therapeutics who left last spring in the wake of that company's acquisition by Japan's Astellas Pharma.
Holles joined Third Harmonic last August, just as the company had begun an early-stage study of its drug and contemplated raising additional funds.
"Since all of that was kind of mid-flight when I came in, we made the decision to wait until we got the financing done and do the launch of the company on the back of the Series B, which closed in December," Holles said in an interview.
Third Harmonic is now planning to begin a Phase 1b "proof-of-concept" trial of its drug in a form of chronic skin hives, one of several allergic and inflammatory diseases that the company believes could be effectively targeted by the therapy.
Dubbed THB001, the drug is designed to block a cellular receptor called KIT that regulates immune cells known as mast cells. When activated, mast cells trigger immune responses that are often features of inflammatory disorders of the skin, gut and airways.
According to Holles, the problem is that KIT has a lot of "close kissing cousins." Targeting KIT ends up hitting those related proteins as well, complicating drug development.
"The challenge today has been targeting KIT with sufficient selectivity that you have a drug profile which is viable for the treatment of allergy and inflammatory disease," Holles said.
Chronic hives, or urticaria, triggered by cold temperatures is the first indication Third Harmonic will pursue with its drug. Another biotech, Celldex Therapeutics, also is targeting cold-inducible urticaria with a drug that's designed to deplete mast cells.
Urticaria can be caused by other triggers like heat, scratching or sunlight. In other cases, the reason for its onset is unknown and the condition is considered spontaneous or "idiopathic" in origin. Oral antihistamines currently are the first treatment of choice but is only effective in about half of people with chronic urticaria, per Third Harmonic. A biologic drug called Xolair also can be used afterwards, but that doesn't work for all patients either.
While Third Harmonic has some clinical data in hand from healthy volunteers, the Phase 1b study it's planning to launch later this year will be the first real test of its therapy. Initial results are expected toward the middle of 2023, Holles said.
In the meantime, Third Harmonic plans to roughly double its headcount, from 14 employees currently to about 30 by the end of 2022. Among those planned hires will be a CFO, a chief scientific officer and a chief people officer to join the company's executive team, now made up of Holles, a chief medical officer and a chief operating officer.
Until last April, Holles was the CEO of Audentes, a gene therapy developer that Astellas bought for $3 billion in late 2019. While Astellas had originally said it would run Audentes as an independent subsidiary, the pharma later opted to fold the biotech fully into its organization as a gene therapy-focused research unit.
Holles' departure was announced as part of that shift, which saw most Audentes employees join the newly branded Astellas Gene Therapies unit.
According to Holles, "it was always a plan that the founding management from Audentes would move on" as Astellas integrated the company.
But the transition also took place at the same time as Audentes and Astellas were working through a tragic setback in clinical testing of Audentes' most advanced gene therapy for a rare neuromuscular disease. The summer before, three children given the treatment died in a study run by Audentes, leading the FDA to halt testing.
Audentes and Astellas later were allowed to resume the trial in February 2021, a few months before the integration took place and Holles left.
However, last September Astellas announced a fourth child had died after developing abnormal liver function following treatment, and the FDA suspended further study again. In all, two dozen boys with the disease, known as XLMTM, were treated with the therapy.