ai3Bio Raises $48M and Debuts a Precision Immune‑Reset Therapy That Preserves Protective Memory

Immune reset is emerging as a focal point of immunology research and development, with companies pursuing therapies that eliminate pathogenic immune cells to give the immune system a fresh start free from self‑attacking memory. While the field is still evolving, many strategies reprogram one immune cell type to target and eradicate another that drives autoimmune disease.

ai3Bio, a Watertown, Massachusetts‑based startup, pursues a simpler strategy that leverages an intrinsic cellular pathway to trigger self‑destruction of pathogenic cells. The company has emerged from stealth mode, unveiling its science and securing $48 million in Series A financing to advance a pipeline that could enter human trials as early as next year.

An immune reset essentially offers a clean slate, providing the body with new cells that lack memory of attacking healthy tissue. However, such a broad reset also erases long‑term protective antibodies—from childhood vaccinations to seasonal flu immunity. ai3Bio seeks a more precise method that spares a patient’s existing immune memory and protections.

“This strategy does not eliminate your pre‑existing memory T cells that would be specific for [cytomegalovirus], flu, and all the other things that you want to maintain defense against,” said Jonathan Kagan, ai3Bio’s scientific co‑founder. “We’d like to position ourselves as a very nice example of something that folks often champion but rarely achieve, and that is precision therapies.”

ai3Bio’s inaugural target is Th17 cells, a subset of helper T cells essential for defending against infections but whose overactivity underlies several autoimmune conditions. Existing drugs such as Novartis’s Cosentyx, Eli Lilly’s Taltz and UCB’s Bimzelx inhibit the IL‑17 signaling protein secreted by Th17 cells, yet these monoclonal antibodies do not halt production of the protein itself, necessitating lifelong treatment. By contrast, ai3Bio’s platform could extinguish IL‑17 at its source, according to CEO Steven Altschuler.

The therapeutic candidate is a lipid nanoparticle (LNP) delivering messenger RNA that instructs cells to undergo programmed death. The LNP is directed to pathogenic Th17 cells via a CD161‑targeting antibody, which binds to a protein over‑expressed on those cells. Once internalized, the mRNA engages the cGAS‑STING pathway—an immunological cascade that has been studied for two decades yet remains without an FDA‑approved modulator.

The name ai3Bio reflects its focus on three pillars: advanced immunology, autoimmunity, and artificial intelligence. The entity was formed by merging Corner Therapeutics and Novasenta. Jonathan Kagan, who holds appointments at Harvard Medical School and Boston Children’s Hospital, co‑founded Corner, which was pursuing immunotherapies for cancer and infectious diseases. Novasenta was a drug‑discovery venture launched by UPMC in 2021.

Corner contributed its lipid‑nanoparticle expertise, while further investigation revealed that activating the STING pathway within T cells could induce cell death. Novasenta supplied an AI‑driven platform for discovering druggable targets, which was instrumental in creating the CD161‑targeting antibody now employed by ai3Bio to engage Th17 cells.

“We’re not delivering a grenade into the cell,” Kagan said. “We are effectively delivering instructions to the cell to kill itself or self‑destruct.”

The platform also promises a safety advantage over alternative immune‑reset tactics. Competitors such as Cabaletta Bio and Kyverna Therapeutics are advancing CAR T‑cell approaches that require ex vivo engineering of a patient’s own T cells to treat autoimmune disease. Major pharmaceutical firms are entering the field through partnerships; Johnson & Johnson recently allied with Sail Biomedicines on an in‑vivo T‑cell reprogramming candidate that redirects cells to eliminate pathogenic B cells. Additional big‑pharma collaborations for in‑vivo cell therapies include AbbVie, Bristol Myers Squibb, Gilead Sciences, and Eli Lilly.

A common hurdle for both ex vivo and in‑vivo cell therapies is cytokine release syndrome (CRS), an excessive immune response triggered when disease‑driving cells are lysed and their intracellular contents spill into the bloodstream, activating broader immune pathways.

Kagan notes that ai3Bio’s strategy is inherently immunosuppressive, removing pathogenic cells without provoking the CRS that can accompany other modalities. The approach also simplifies manufacturing and logistics: unlike ex vivo engineered cell therapies, which require multi‑step production from a patient’s own immune cells and a pre‑conditioning regimen that erases immune memory, ai3Bio’s LNP formulation can be administered in a single infusion, prompting self‑destruction of the targeted cells without any pre‑treatment.

Removing pathogenic T cells from tissue often triggers rapid repopulation. Preclinical studies reported by Kagan show that ai3Bio’s therapy achieves depletion of inflammatory T cells and also initiates pathways that block differentiation of naïve helper T cells into Th17 cells, thereby reinforcing the reset objective. Moreover, primate data demonstrate that the effect extends beyond the circulation to include deep tissue reservoirs such as the spleen and lymph nodes—sites that are typically hard to target immunologically, according to Kagan.

The ultimate goal of immune reset is a durable, potentially one‑time therapeutic benefit. Kagan cautions that durability in humans remains to be validated. Altschuler indicates that ai3Bio will advance clinical trials initially in liver‑directed autoimmune diseases, where Th17 cell infiltration underlies conditions such as primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune chronic active hepatitis—areas with few effective treatment options.

The Series A round, led by Ziff Capital Partners (an existing Corner investor) and UPMC Enterprises (the investor behind Novasenta), raised a total of $48 million for ai3Bio. Additional participants in the financing include Cockrell Interests and Tanis Ventures.

Altschuler expects ai3Bio to advance several programs into the clinic within the next two years following its emergence from stealth. He projects the current cash runway to extend through Q2 2027, after which additional financing will be required. While the immunology landscape is becoming increasingly competitive, with most recent deals centering on B‑cell–targeted strategies, Altschuler emphasizes that ai3Bio’s technology could be adaptable to B cells, though the immediate focus remains on differentiating the company through its T‑cell reset platform.

Altschuler observed, “While numerous approaches exist to manage autoimmune disease, we aim to be among the few platforms actually resetting the T‑cell repertoire.”

Image by Flickr user NIAID via a Creative Commons license

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