Tilos has a rich pipeline of anti-LAP antibodies with attributes suited to a broad range of distinct clinical indications. The over-riding philosophy is that by targeting the primary pathological process for a particular indication, one can significantly improve the therapeutic outcome for patients. The following examples serve to illustrate the power and value of this diverse portfolio.
The extracellular matrix is believed to store the majority of latent TGFβ in the body. Tilos has anti-LAP antibodies that in addition to depleting immuno-suppressive cells, can inhibit TGFβ release from inhibitory cells while leaving LAP-TGFβ in the 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.
The depot of latent TGFβ in the extracellular matrix is thought to be critical in driving fibrotic processes associated with cancers. Tilos has anti-LAP antibodies that can inhibit TGFβ release from the ECM, which may be most effective in the treatment of desmoplastic tumors.
Different cancers have distinct tumor microenvironments dominated by different cellular infiltrates. Tilos has anti-LAP antibodies that can preferentially bind to LAP+ MDSC relative to LAP+ Treg, leading to preferential depletion of this 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.
TGFβ release drives the development of Tregs. Tilos has antibodies that destabilize the LAP-TGFβ complex and enhance release of the mature cytokine, which we believe will drive local induction of Tregs and be useful for the treatment of autoimmune disease.