The inflamed, red skin characteristic of atopic dermatitis develops and worsens in a vicious cycle. Itching leads to scratching, which leads to more itching. The immune response to all of the scratching drives more inflammation. Atopic dermatitis can be treated with antibodies that block inflammation-driving pathways in the body. The lead drug candidate of Triveni Bio is also an antibody, but it takes a different approach to the chronic, autoimmune disorder.

In atopic dermatitis, the outer layer of skin becomes dysregulated, making it permeable to allergens, Triveni Chief Scientific Officer Jennifer Dovey said. Passing through this barrier, allergens stimulate inflammation that cause flare-ups of atopic dermatitis. Triveni aims to interrupt the vicious cycle of the disease.

“We’re going upstream of where other therapies are going, directly targeting what the source of the disease is in atopic dermatitis, which is this barrier permeability,” Dovey said.

Triveni has been quietly developing its novel antibody therapies, including its lead atopic dermatitis program, which is on path to reach the clinic. The Waltham, Massachusetts-based startup recently emerged from stealth with $92 million in financing to support its research.

To understand Triveni’s approach to atopic dermatitis, it helps to start with a different skin disease called netherton syndrome. The red, scaly skin that develops from netherton is caused by dysregulation of two enzymes, kallikreins 5 and 7. In a healthy person, both are counterbalanced by a protein in the body that acts as a natural inhibitor. In netherton, a genetic mutation leads to the loss of function of this inhibitor, resulting in the completely unchecked kallikrein activity that causes the skin problems characteristic of the rare disease.

Understanding the genetic drivers of netherton enabled Triveni to think about other indications with shared traits, said Vishal Patel, CEO of Triveni and an entrepreneur in residence at venture capital firm Atlas Venture. That led the startup to severe atopic dermatitis, which has similar clinical features. Problems regulating kallikreins 5 and 7 leads to the dysfunction of the skin barrier, which is the initial step in the development of atopic dermatitis.

The first line of atopic dermatitis treatment is typically topical steroids. The top biologic drug option is the Sanofi and Regeneron Pharmaceuticals blockbuster Dupixent, an antibody drug that blocks two cytokines: IL-4 and IL-13. LEO Pharma’s Adbry is an antibody that blocks IL-13. Inflammation-driving JAK proteins are the targets of small molecule drugs from Incyte, Pfizer, and AbbVie. Meanwhile, contenders aiming to enter the atopic dermatitis field include those developing antibodies that address the same targets as Dupixent but with a dosing edge, and others that are pursuing different inflammation targets entirely.

Dovey said Triveni’s approach is based on the understanding that enzymes can be selectively targeted with an antibody that mimics a physiological process. Triveni’s lead drug candidate, TRIV-509, stands in for the protease inhibitor that keeps kallikreins 5 and 7 in check. The drug is a dual antibody designed to address both enzymes. This approach also has potential applications in asthma, which is characterized by dysfunction of the airway’s epithelial barrier. Eosinophilic esophagitis is another disease with a barrier component that could be addressed by Triveni’s lead drug, Dovey said.

Triveni formed at the end of last year from the combination of two startups, Amagma Therapeutics and Modify Therapeutics. Polaris Partners-backed Amagma was co-founded by Tillman Gerngross, the serial entrepreneur behind several antibody companies. It kept a low profile, describing its science as the discovery and development of antibody therapeutics for inflammatory disease, with a particular focus on gastrointestinal disorders. Modify, seeded by Atlas, developed a data platform that analyzed genetics. Patel said the formation of Triveni was serendipity as people from both Boston-area companies had conversations.

“This is a better together platform,” he said.

Triveni’s technology enables it to identify targets for its drugs and define the patient population best suited for these therapies, said Dovey, who was Amagma’s chief scientific officer. It also allows the startup to identify opportunities for expansion to other indications, including those affecting broader populations.

Triveni’s Series A financing was co-led by Atlas and Cormorant Asset Management. Other disclosed investors in the round are OrbiMed, the private equity business of Viking Global Investors, Invus, Polaris, and Alexandria Venture Investments.

Patel said the new financing will support the advancement of lead program TRIV-509 from preclinical development through Phase 2a testing in atopic dermatitis. He expects this program will start human testing in early 2025. The capital will also support development of the startup’s immunology and inflammation drug pipeline, with the goal of nominating two additional development candidates next year. Patel said Triveni has enough cash to last into 2027.

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