Simultaneous inhibition of multiple pathways is strongly recommended to treat certain heterogeneous diseases such as TNBC, considering very limited clinical benefit from single target therapy in the clinical trials. TT-00420 is a spectrum selective multi-target kinase inhibitor. It selectively blocks three signal pathways including cell cycles, JAK/STAT, and receptor tyrosine kinases. In-house MOA studies demonstrate the requirement of the above three-pathway inhibition to show synergistic activity towards majority of TNBC cell lines. TT-00420 also demonstrates the ability to modulate tumor-microenvironment, possessing a dual mechanistic property of both targeted therapy and immuno-oncology aspect. TT-00420 has demonstrated excellent efficacy and good safety profile. It is under clinical studies in both the US and China.TT-00920
PDE9, so-called the “missing culprit” in heart failure, regulates natriuretic peptide-stimulated cGMP pathway in the heart. PDE9 is highly elevated in human failing hearts, which impedes a natural protective pathway and makes the heart more vulnerable to fail. Genetic inhibition of PDE9 reversed existing heart failure in preclinical animal model. TT-00920 is a potent, selective and low brain-penetrant small molecule inhibitor of PDE9. It is expected to enter clinical trials in late 2019.