Merck & Co. plans to acquire Tilos Therapeutics for up to $773 million, in a deal designed to expand the buyer’s cancer, fibrosis, and autoimmune disease pipelines with therapies targeting the latent TGFβ complex.
Headquartered in Lexington, MA, Tilos focuses on developing antibodies designed to target the latency-associated peptide (LAP) of transforming growth factor-beta (TGFβ), a potent cytokine believed to play an important role in the development of cancer and fibrotic diseases.
LAP is a protein “cage” that holds TGFβ in a latent state. Anti-LAP antibodies have been shown to stabilize the LAP-TGFβ complex and prevent release of the active cytokine. According to Tilos, anti-LAP antibodies have effectively reduced tumor growth in mouse cancer models by blocking the release of TGFβ from the TGFβ-LAP complex, since reducing TGFβ levels has led to broad effects on tumor growth, reducing metastasis, immunosuppression, epithelial-to-mesenchymal transition, and angiogenesis.
As a result, Tilos reasons, anti-LAP antibodies have the potential to be a powerful new class of therapeutics in the treatment of cancer, as well as fibrosis and autoimmunity.
Tilos says its pipeline includes anti-LAP antibodies that in addition to depleting immuno-suppressive cells, can inhibit TGFβ release from inhibitory cells while leaving LAP-TGFβ in the extracellular matrix (ECM) untouched. This is anticipated to specifically inhibit pathological and immuno-regulatory processes, while avoiding interfering with the normal tissue homeostasis processes mediated by TGFβ.
Tilos also has anti-LAP antibodies that are designed to inhibit TGFβ release from the ECM, which according to the company may be most effective in the treatment of desmoplastic tumors.
Other anti-LAP antibodies can preferentially bind to LAP+ myeloid-derived suppressor cells (MDSC) relative to LAP+ regulatory T cells (Tregs), leading to preferential depletion of that inhibitory cell population. These antibodies are expected to have increased anti-tumor activity in MDSC-dominated tumors, with an additional benefit of a more favorable side effect profile, Tilos said.
In addition, Tilos has antibodies intended to destabilize the LAP-TGFβ complex and enhance release of the mature cytokine, which the company asserts will drive local induction of Tregs and be useful for the treatment of autoimmune disease.
“Compelling portfolio”
“Tilos has developed a compelling portfolio of candidates that employ a novel approach to modulating the potent signaling molecule TGFβ by binding to latency-associated peptide, with potential applications across a range of disease indications,” Dean Li, MD, PhD, senior vice president, discovery and translational medicine, Merck Research Laboratories, said in a statement. “At Merck we continue to enhance our robust pipeline through active execution of our business development strategy.”
Through a subsidiary, Merck agreed to acquire all outstanding shares of Tilos for up to $773 million, consisting of an upfront payment and payments tied to achieving milestones, both of which were unspecified in the companies’ announcement, issued Monday by Merck.
Privately-held Tilos was founded in 2016 with funding from by Boehringer Ingelheim Venture Fund, Partners Innovation Fund, and ShangPharma Innovation Fund. The company was formed to commercialize discoveries by the laboratory of Howard L. Weiner, MD, at Brigham and Women’s Hospital and Harvard Medical School, where he is director of the Partners Multiple Sclerosis Center, and co-director of the Center for Neurologic Diseases.
“We are proud that the Tilos team has advanced the discoveries of our scientific founders by developing a portfolio of anti-LAP antibodies designed to realize the full potential of TGFβ-modulating therapeutics,” Tilos CEO Barbara S. Fox, PhD, said in a statement. “This agreement with Merck, an industry leader in biopharmaceutical research and development, provides meaningful validation for our therapeutic approach and best positions our pipeline for broad clinical and commercial success.”
