evexomostat (SDX-7320)

Mechanistically, SDX-7320-mediated tumor growth inhibition likely results from both direct anti-tumor effects (given the observed intratumoral changes in the expression of cell cycle and immune response genes), and indirect effects on the host including weight loss, decreased adipose mass, improved insulin sensitivity and normalization of plasma leptin and adiponectin levels. The fact that SDX-7320 caused greater tumor growth inhibition than tirzepatide, yet caused less weight loss, suggests that direct anti-tumor effects significantly contribute to the anti-tumor activity of SDX-7320.

Evexomostat (SDX-7320) was well-tolerated with prolonged stable disease and metastatic control in an open-label, Phase I safety study. Improvements were observed in angiogenic and metabolic biomarkers.

P1/2, N=52, Recruiting, SynDevRx, Inc. | Phase classification: P1b/2 --> P1/2

P1b/2, N=52, Recruiting, SynDevRx, Inc. | Not yet recruiting --> Recruiting

P2, N=55, Recruiting, Memorial Sloan Kettering Cancer Center

In addition SDX-7320 synergized with the PI3Kα inhibitor alpelisib (Piqray®) to block the growth of ER+/Her2- MCF-7 xenografts. Intracellular pathways and proteins linked to emergence of resistance to palbociclib include cell cycle (cyclin E1), growth factor and hormone signaling (Akt, ERα) and autophagy (LC3B). The protein changes observed (representative of these pathways) suggest that combining SDX-7320 with palbociclib (Ibrance®) may extend the period of progression-free survival in patients with ER+/Her2- breast cancer relative to treatment with palbociclib (Ibrance®) alone.