Cardion GmbH

Tolerance Bio has launched with an oversubscribed $17.2 million seed round and a goal to develop therapies for immune-mediated diseases, from cancer to transplant rejection, using the thymus. The Philadelphia-based company plans to develop an allogeneic thymus-induced pluripotent stem cell (iPSC)-based cell therapy platform as well as thymus therapies in an effort to target immune diseases at their core. Columbus Venture Partners led the funding round. Other investors include Criteria Bio Ventures, Sessa Capital, BioAdvance and Ben Franklin Technology Partners. Tolerance is focusing on the thymus, an organ that plays an important role in training and maturing the body’s T cells to defend against immune issues like infections and cancers while also preventing autoimmunity. The T cells in the human body are developed in the first two years of life, but the thymus declines with age, leading to a higher risk for immune diseases. Tolerance hopes to delay and prevent the decline of the thymus, as well as restore the organ if it stops functioning. Tolerance CEO Francisco Leon, who co-founded Provention Bio, which was acquired by Sanofi for $2.9 billion in 2023, said that the startup plans to focus on a rare disease before turning to other indications. Tolerance’s first approach will be focused on restoring thymic function with an adult stem cell-derived thymic epithelial cell implant. “We can generate thymic cells in the lab from stem cells. And we can implant them into an animal, and they develop into a mini-thymus in the body of the animal. Then they train new T cells, and this is already done and published,” Leon told Endpoints News . As a preclinical proof-of-principle of the technology’s potential, Tolerance implanted these stem cells into mice that have no thymus, a well-known animal model of immune deficiency that has the same mutation as babies born without the thymus, a condition called DiGeorge syndrome. “By transplanting our thymic epithelial progenitors, we can generate a lot of T cells simply by implanting the thymic epithelial progenitors,” Leon added. “This is our first preclinical proof of concept.” At the same time, Tolerance is going to use these thymic cells combined with antigens for autoimmune diseases and cancer in order to explore whether they can induce tolerance in autoimmune diseases as well as tumor immunity in cancer. “This is not published yet, but we have a paper under review that shows we can educate the T cells to attack melanoma,” Leon said. “This is going to come out in a few months, probably after the review process.” A third aspect of a six-year plan is drug repositioning, where Tolerance will give people a drug to delay or prevent the involution of the thymus for those who still have a thymus. The target is still undisclosed, but it’s something the company will do in the coming months.