IpY.20

The drug resistance seen in the presence of CDK4/6 inhibitors, such as palbociclib, can be attributed to compensatory activation of tumor cell proliferation by CDK2. In vivo, IpY.20 reduces tumor volume and increases OS in cell line-derived xenografts (CDX).IpY.20 has several important differentiating features when compared to CDK4/6 or CDK2 inhibitors: targeting p27 is more selective with fewer off-target effects than the ATP-competitive small molecule CDK4/6i currently in use; IpY.20 induces tumor cell death as opposed to cytostasis; the specific form of tumor cell death that is induced upon IpY.20 treatment, i.e., necroptosis, stimulates the innate and adaptive immune system.As the bulk of drug resistance seen with CDK or RAS/MAPK pathway targeting drugs is a result of compensatory CDK2 activity, IpY.20 will be a valuable member of the clinical arsenal for patients with drug resistant tumors. Currently, a robust clinical manufacturing process has been completed for IpY.20 formulation; along with a comprehensive characterization of nonclinical pharmacology, PK/PD, and tolerability, in preparation for the initiation of an IND-enabling program.