Leveraging new insights into the structure and function of PARP1, Tilikum is developing a novel class of PARP1 inhibitor that overcomes a range of resistance mechanisms to arrest DNA replication and repair in treatment-failed tumors.

Conventional PARP inhibitors kill tumors by a mechanism called synthetic lethality — in tumors with pre-existing DNA repair defects, inhibiting PARP1 leads to severe DNA damage, triggering cancer cell death. Tilikum’s novel “PARP-locking” compounds act through a different mechanism and are active in tumors that do not have genetic defects in DNA-repair machinery.

Commercially approved PARP1 inhibitors are currently used in a small number of patients with defined subtypes of ovarian, breast, prostate and pancreatic cancers marked by genetic defects in DNA repair machinery. Tilikum’s PARP-locking compounds will be active in patients with these diseases who are not eligible for current PARP1 inhibitors because they either lack the genetic defect or have developed drug resistance.

Tilikum’s orally-administered or ADC-delivered small molecule drugs have the potential to transform cancer care for treatment-resistant disease.