CEL-031, Celek’s lead oncology product, is a clinical-stage, small molecule drug in development for the treatment of bladder cancer and acute myeloid leukemia. CEL-031 selectively induces apoptosis, or programmed cell death, selectively in tumor cells by inhibiting cGMP phosphodiesterases (PDE), primarily the PDE5 and PDE2 isoforms that are overexpressed in many tumors. Inhibition of activity of these PDEs causes an increase in intracellular cGMP levels, which activates the cGMP-dependent enzyme protein kinase G. This leads to the degradation of β-catenin, a transcription factor that is overproduced in transformed cells and that promotes cancer cell growth. β-catenin degradation, in turn, trigger pathways that lead to apoptosis.
Schematic of CEL-031 Mechanism of Action
CEL-031 was previously administered as an oral drug to more than 250 people in multiple Phase I and Phase II clinical trials. The compound had a very good safety profile, with evidence of efficacy observed in several major cancers.
Celek is developing CEL-031 for two distinct indications that exploit the compound’s targeted anticancer activity and favorable safety profile:
- For the treatment of early stage, non-muscle invasive bladder cancer, via transurethral or intravesical administration
- For the treatment of acute myeloid leukemia, via intravenous administration