A New Direction in Autoimmune Treatment
Zag Bio, a Cambridge, Massachusetts-based biotechnology company, has emerged from stealth with an $80 million Series A financing round to advance a new class of thymus-targeted therapies for autoimmune diseases. The financing was led by the T1D Fund and Polaris Partners, which founded and incubated the company, with participation from AbbVie, Regeneron, and Sanofi, among others.
The startup is focusing on developing regulatory T-cell (Treg) therapies through a proprietary thymus-targeting platform. Zag Bio’s approach seeks to deliver antigens directly to the thymus to restore immune tolerance, distinguishing it from other Treg-based efforts in the autoimmune field. CEO Jason Cole said, “The name Zag Bio shows that we are intentionally moving in a new direction to treat autoimmunity by targeting the natural mechanisms in the thymus.”
Overcoming Therapeutic Challenges
Cole, formerly CEO of SalioGen Therapeutics and a senior executive at Bluebird bio, explained that the thymus has long been a challenging organ to reach therapeutically. He said, “Despite its integral role in central immune tolerance, the thymus has been inaccessible to drugs of all types.” The company’s platform aims to change that by using bifunctional antibody drugs capable of delivering antigens to the thymus, thereby engaging the body’s natural tolerance mechanisms.
Lead Program and Future Applications
Zag Bio’s lead program, ZAG-101, targets Type 1 diabetes. The treatment is designed to carry pancreatic beta cell antigens to the thymus, teaching the immune system to recognize them as non-threatening and restore glycemic control. The company intends to begin early-stage human testing by the end of 2026. Beyond diabetes, Zag Bio is also exploring therapies for other autoimmune diseases, though specific programs have not yet been disclosed.
Scientific Origins and Innovation
The company’s approach was inspired by discoveries from the research lab of Harvard immunology professor and Zag co-founder Diane Mathis, Ph.D. Other co-founders include Chief Scientific Officer John Kulman, Ph.D., and biotech entrepreneur Jo Viney, Ph.D. According to Kulman, the idea for Zag Bio originated from scientific findings on how the thymus directs immune cells to prevent self-attack. While on vacation in Maine, Kulman reviewed related research and shared it with Viney and Polaris Partners’ Alan Crane, sparking the company’s creation.
Kulman noted that the ability to deliver a systemic agent to the thymus had not been achieved before. He said that Zag’s approach represents a breakthrough in accessing the organ to induce immune tolerance.
Vision and Investment
Alan Crane, a partner at Polaris and chairman of Zag Bio, described the company’s goal as establishing a new therapeutic pathway for thymus-targeted medicines, positioning it as an innovator in autoimmune disease treatment.
The Series A round also included funding from Mission BioCapital, Lightspeed Ventures, KdT Ventures, Boxer Capital, and Pear VC. Zag Bio’s formation coincides with renewed attention on Treg research, following the 2025 Nobel Prize in Physiology or Medicine awarded to three scientists, including Shimon Sakaguchi, M.D., Ph.D., for discovering Tregs in 1995.
While more than 200 clinical trials are currently underway exploring Treg therapies, none have yet reached the market.
The implications of this thymus-targeting strategy could be wide-reaching. For patients living with autoimmune disorders—conditions that current therapies often manage but do not cure—the possibility of resetting immune tolerance at its source is compelling. The thymus platform may allow therapies to be developed that prevent disease onset, rather than just suppress symptoms.
Moreover, the success of Zag Bio’s approach may shift how drug developers view immune therapies: rather than simply modulating immune responses at the periphery, they may increasingly focus on central immune organs like the thymus. This could lead to a new wave of treatments for lupus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.
