Intra-Cellular Therapies Presents Data on Antitumor Effects of Phosphodiesterase I Inhibition in a Preclinical Colorectal Cancer Model at the 2021 American Association for Cancer Research (AACR) Annual Meeting - Seite 2

At AACR we are reporting on pre-clinical studies demonstrating that lenrispodun alone decreased the numbers of infiltrating macrophages and increased the numbers of natural killer cells in the TME. These effects serve to prevent tumors from evading the host immune system and thereby potentiate the tumor killing activity of checkpoint inhibitors. When lenrispodun and an anti-PD-1 antibody were combined, tumor volumes were significantly reduced and tumor-free survival was significantly increased in a mouse model of colon carcinoma. Importantly, the effect of combining an anti-PD-1 immune checkpoint inhibitor and lenrispodun treatment produced a complete response in about 50% (7/15) of treated mice as compared to 10% (1/10) in anti-PD-1 alone treated mice, 20% (1/5) in the lenrispodun alone group and 0% (0/9) in the control group. This translated into a statistically significant effect on survival for the combination treatment group as compared to control (p=0.001).

Tumor associated macrophages can promote tumor growth in certain cancers. Our experiments indicate PDE1 inhibition prevents the migration and accumulation of monocytes and macrophages in the tumor microenvironment and could represent a novel and broadly applicable approach to the treatment of immune responsive cancers. We are currently evaluating our PDE1 inhibitors in other cancer models and are developing potential biomarkers that may assist in the translation of these data to the treatment of human cancers.

Phosphodiesterase type 1 (PDE1) inhibitor Portfolio

Our PDE1 inhibitor program is focused on diseases in which the PDE1 enzyme is over-expressed and/or abnormal immune cell function contributes to disease pathology providing opportunities to pursue innovative treatments for multiple diseases including Parkinson’s disease, heart failure and other diseases.

Lenrispodun is a potent and selective PDE1 Inhibitor and is the lead compound in the Company’s PDE1 portfolio. Lenrispodun is in development for the treatment of symptoms associated with Parkinson's disease and for the treatment of heart failure. Lenrispodun has been generally well tolerated with a favorable safety profile in six Phase 1 clinical trials. Lenrispodun works by blocking the breakdown of cyclic nucleotides (cAMP, cGMP), thus allowing these molecules to build up in the cells and to exert important functions.