Advancing the next wave of medicine for allergy and inflammation

Third Harmonic Bio is a clinical-stage company developing a novel oral approach to the treatment of severe allergy and inflammation.

The Opportunity

Mast cells are an immune cell class which is concentrated at the body’s interfaces with the external environment and which has evolved to serve as the first line of defense against parasitic infections.  However, mast cells are also a well-characterized pathophysiologic mediator of allergic disease.

Once activated, mast cells “degranulate,” or release a number of vasoactive and pro-inflammatory mediators, including histamine, proteases, and proteoglycans which propagate the allergic response. Given the multimodal nature of both upstream activation and downstream degranulation, the optimal therapeutic approach to allergy is broad inhibition of the mast cell itself.

The KIT (CD117) receptor acts as the master regulator of all aspects of mast cell proliferation, differentiation, and survival. Preclinical and clinical studies demonstrate that inhibiting KIT signaling results in potent inactivation and depletion of mast cells and dramatically improves symptoms of severe allergic disease.1,2

KIT inhibition represents a unique opportunity to address a broad range of allergic diseases. The ideal therapeutic profile would combine the target selectivity and potency of a biologic with the ease of administration that an oral small-molecule affords.

Eechoute K, et al. Suppressing effects of sunitinib on allergic rhinitis: previously undefined side effects with therapeutic potential. J Clin Pharmacol. 2011 Nov;51(11):1592-5.

Cahill KN, et al. KIT inhibition by imatinib in patients with severe refractory asthma. N Engl J Med. 2017 May 18;376(20):1911-1920.

Our Approach: THB001

Our product candidate, THB001, is a first-in-class, highly selective, oral small-molecule KIT inhibitor in early clinical development for the treatment of severe allergic and mast cell-driven inflammatory diseases. Extensive preclinical studies demonstrate THB001 to have promising drug-like properties, excellent kinome selectivity, and potent mast cell depletion activity in all relevant tissue types. In early clinical studies, THB001 demonstrated robust pharmacodynamic effects as measured by serum tryptase, an established marker of mast cell activity and survival.

THB001 is initially in development for the treatment of chronic urticaria, a dermatologic disease driven by mast cell activation that results in red, itchy, painful welts or hives.

Up to one percent of the U.S. population is believed to be affected by urticaria at some point in their lives. It is estimated that up to 90% of urticaria patients who have failed antihistamine therapy either fail or forego biologic therapy, leaving tremendous unmet need in a disease with known severe impacts on mental well-being and quality of life.

Beyond chronic urticaria, we plan to pursue development of THB001 in additional skin, airway and gastrointestinal tract indications in which mast cells play a known role in the pathophysiology and symptomatology of the disease.

Pipeline and Product Potential

We’re advancing THB001 against multiple mast cell-driven inflammatory

conditions that share similar pathophysiology.


Target Indications


Phase 1a

Phase 1b


(KIT Inhibitor)

Target Indications


Chronic Inducible Urticaria

Phase 1a

Chronic Spontaneous

Phase 1a
Target Indications



Target Indications




Our Leadership

Founded by Atlas Venture in 2019, Third Harmonic Bio is led by a proven executive team with a successful track record of delivering breakthrough therapeutic approaches for patients. With a high caliber investor syndicate, necessary capital, and promising evidence supporting the potential of THB001, Third Harmonic Bio is uniquely positioned to become a leader in advancing the next wave of medicine for allergy and inflammation.


Natalie Holles

Chief Executive Officer

Edward R. Conner, M.D.

Chief Medical Officer

Robert Ho

Chief Financial Officer

Gregg Keaney, Ph.D.

Senior Vice President, Product Development

Julie Person

Chief Administrative Officer

Adrian S. Ray

Chief Scientific Officer

Steve Sweeney

Senior Vice President, Development Operations
Board of Directors

David Bonita, M.D.

General Partner, Orbimed

Michael Gladstone

Partner, Atlas Venture

Natalie Holles

Chief Executive Officer

Mark Iwicki (Chairman)

CEO, Kala Therapeutics

Shao-Lee Lin, M.D., Ph.D.

CEO, Acelyrin, Inc.

Rob Perez

Operating Partner, General Atlantic

Jason Rhodes

Partner, Atlas Venture

Martin Seidel, Ph.D.

CEO, IFM Therapeutics


The Latest News

Julie Person Joins Third Harmonic Bio as Chief Administrative Officer
Third Harmonic Bio Appoints Edward R. Conner, M.D., as Chief Medical Officer 
Third Harmonic Bio Strengthens Management Team with Addition of Adrian S. Ray, Ph.D., as Chief Scientific Officer 
Third Harmonic Bio Appoints Robert Ho as Chief Financial Officer
Third Harmonic Bio Launches to Advance the Next Wave of Medicine for Allergy and Inflammation