Preclinical Drug Candidates

ABOUT TG-1601 (BET inhibitor)

TG-1601 is a bromodomain and extra-terminal, BET, inhibitor. It is a novel small molecule that binds with high affinity and selectivity to the epigenetic BET family of bromodomain-containing proteins and inhibits their binding to chromatin. BET proteins function as molecular adaptors, or scaffolds, to recruit the machinery necessary for activating gene transcription, e.g. the transcription of two critical oncogenes such as MYC and BCL-2. MYC over-expression appears to be particularly important for the viability of hematologic malignancies. By resetting the genome in tumor cells and reducing MYC levels, TG-1601 may increase the sensitivity of tumors to chemotherapy or specific standard of care, including Immuno-therapies like PD-L1 or CD-20 antibodies. TG-1601 is currently in pre-clinical development and is being tested in various IND-enabling studies.


Glucocorticoid-induced tumor necrosis factor receptor related protein (GITR) is regularly expressed on the surface of regulatory T-cells (Tregs) and is expressed on the surface of effector T-cells after their activation. Modulation of GITR with agonistic antibodies has been shown to amplify the antitumor immune responses in animal models via multiple mechanisms. Anti-GITR antibodies are designed to activate the GITR receptor thereby increasing the proliferation and function of effector T cells. At the same time, ligation of GITR on surface of Tregs could abrogate suppressive function of these cells on tumor specific effector T-cells thus further augmenting T-cell immune response. The GITR program is currently in preclinical development.


Interleukin-1 Receptor Associated Kinase 4, referred to as IRAK4, is a key signaling kinase that becomes inappropriately activated in tumors that carry certain oncogenic mutations of MYD88, which can be found in most patients with Waldenström's Macroglobulinemia, a rare B-cell cancer, as well as in a sub-set of patients with Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia. Additionally, IRAK4 is a key component of signaling pathways which regulate immune and inflammatory processes suggesting that inhibition of IRAK4 may also be useful in the treatment of autoimmune related disorders. The IRAK4 program is currently in preclinical development.