Key Highlights
- Tolerance Bio licenses clinical-stage anti-IL-33 antibody TLB-33 from Tanabe Pharma
- Second clinical-stage in-license in under six weeks
- Pipeline now spans two clinical-stage biologics and regenerative medicine platforms
- Broadest thymus-focused pipeline, per the company
- Team’s in-license-and-reposition playbook previously delivered Tzield and a $2.9B Sanofi exit
- Phase 2 planned for 2027; financing round expected
Every person’s thymus, the organ that trains the immune system, shrinks with age, and as it fades the body becomes more vulnerable to infection, cancer and autoimmune disease. Tolerance Bio has now secured what it calls the broadest pipeline aimed at slowing, stopping and reversing that loss. The Philadelphia biotech has licensed TLB-33, a clinical-stage antibody that blocks the inflammatory signaling protein IL-33, from Japan’s Tanabe Pharma, its second clinical-stage licensing deal in less than six weeks.
The deal includes up to approximately $560 million in potential milestone payments to Tanabe, plus equity and tiered royalties on sales. Tolerance Bio gains exclusive worldwide rights to develop and manufacture it for any indication and to sell it everywhere except Japan, where Tanabe keeps commercial rights.
In August, Tolerance Bio licensed efineptakin alfa, a long-acting form of the immune-boosting cytokine IL-7, from Rockville, Md.-based NeoImmuneTech in a deal worth up to $260 million, a move that made Tolerance Bio a clinical-stage company.
Tolerance Bio plans to begin Phase 2 development of TLB-33 in 2027 to test whether blocking IL-33 can protect the thymus and strengthen the immune system. The company has not said which patient groups it will study first.
The thymus is where the body trains its T cells, the immune cells that learn to attack threats while leaving healthy tissue alone. The organ shrinks steadily with age and can also break down quickly during severe inflammation. Research suggests IL-33, which the body releases when tissue is stressed or damaged, plays a role in that decline.
“We all lose the thymus at different speeds. When we lose it, that’s when we are at increased risk of developing immune diseases,” shared Francisco Leon, MD, PhD, Co-founder and CEO of Tolerance Bio. “So the questions we’re addressing are how do we prevent the loss of the thymus and how do we also boost remaining thymic function.”
A Broader Multimodal Portfolio
The new deal fills out a clinical pipeline designed to address the thymus from several directions. TLB-33, an antibody that blocks IL-33, is meant to preserve it, and efineptakin alfa to restore it. “This agreement represents another important milestone for Tolerance Bio as we continue to build a clinical-stage pipeline around complementary approaches to thymic biology,” said Leon.
Tolerance Bio expects to first test efineptakin alfa in people living with HIV whose immune systems fail to recover despite treatment. Behind those two clinical programs are the earlier-stage regenerative medicine platforms the company was founded on: replacement thymus cells grown from stem cells, and a thymus-targeted mRNA program developed through a collaboration with ZipCode Bio, the RNA company co-founded by Nobel laureate Drew Weissman.
“Now with our clinical-stage assets, Tolerance has the broadest and most advanced pipeline specifically focused on the thymus,” Phil Ball, Tolerance Bio’s chief business officer, told BioBuzz.
In the company’s announcement, Leon, called TLB-33 “a well-characterized clinical-stage antibody with substantial human safety and pharmacologic data.” He added, “Together with our recently licensed long-acting IL-7 program, TLB-33 gives us complementary approaches to preserving and restoring thymic function.”
Tanabe Pharma originally developed the antibody as MT-2990 and has tested it in more than 150 people across five clinical studies, including a Phase 2 study in endometriosis-related pain and an exploratory study in ANCA-associated vasculitis. Tolerance Bio said the safety and other data gathered so far support moving it into new uses tied to thymus health.
IL-33 has become one of the more closely watched targets in immunology this year. AstraZeneca, which anchors its U.S. R&D in Gaithersburg, Md., reported positive Phase 3 results this month for its anti-IL-33 antibody tozorakimab in chronic obstructive pulmonary disease (COPD), and the FDA has accepted its application for Priority Review. Tolerance Bio is taking the target in a different direction. “We have had a very strong interest in anti-IL-33 for some time,” Ball said.
A Proven Playbook
Licensing existing drugs and pointing them at new diseases is familiar ground for Tolerance Bio’s leadership. In 2015, Leon, then CEO of Celimmune, which had operations in Bethesda, Md., and New Jersey, licensed Amgen’s antibody AMG 714, originally developed for rheumatoid arthritis, and redirected it toward celiac disease. Amgen later acquired Celimmune.
Leon then co-founded Provention Bio, serving as chief scientific officer. The company took teplizumab, acquired from Rockville-based MacroGenics, to FDA approval as Tzield, the first therapy to delay the onset of Stage 3 type 1 diabetes. Sanofi acquired Provention for approximately $2.9 billion in 2023. Tolerance Bio’s team pairs those veterans with former members of Semma Therapeutics, the stem cell-based cell therapy company acquired by Vertex.
“The history at Provention, and at Celimmune beforehand, was in-licensing assets and repositioning them into areas where there’s higher need and great potential value,” Ball said. “It’s a playbook we’ve applied before successfully.”
Tolerance Bio said it expects to announce a new financing round to carry TLB-33 and efineptakin alfa through planned clinical trials. The company launched with a $20.2 million seed round led by Columbus Venture Partners and raised another ~$15 million this summer, which included the conversion of a ~$10M note, with participation from Beyond Celiac Investments. Its investor syndicate also includes Criteria Bio Ventures, Pacific 8 Ventures and BioAdvance Capital, the Philadelphia-based life sciences investor. Leon said the two clinical programs are now the company’s lead assets and will receive most of its future funding.
“We’re balancing the tremendous potential of the preclinical platforms with the near-term approvable indications of the clinical-stage assets,” Leon said. “The plan is to get these two assets into multiple clinical trials over the coming couple of years.”
