PARP inhibitors have shown its potential cancer treatments and may be used to block one of the key defence mechanisms of cancer cells against standard chemotherapy, resulting in increased tumour susceptibility or the reversal of tumour resistance.
Poly (ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme that mediates the repair of DNA single strand breaks through the activation and recruitment of DNA repair enzymes.
In addition, PARP inhibitors may be used as a stand-alone agent, targeting certain familial and sporadic cancers that are genetically deficient in DNA repair.
PARP inhibitors have also shown promise in a variety of inflammatory and ischemia/reperfusion diseases, including those related to acute cardiovascular conditions.
INO-1001 represents Inotek's lead compound in a series of PARP inhibitors discovered by Inotek.
The drug is currently in Phase Ib testing for malignant melanoma in combination with temozolomide.
Under the terms of the agreement, Genentech will make an upfront payment of $20m (€15.8m) to Inotek, with the potential for up to $405m in additional milestone payments based upon the successful completion of various clinical development and regulatory events across multiple cancer indications in multiple areas of the world.
Genentech will pay Inotek royalties based on the net amount of any sales of Inotek's lead PARP Inhibitor, INO-1001, or other next-generation PARP inhibitors in the field of cancer.
Genentech will also provide funding to utilise Inotek's small molecule chemistry expertise as part of a multi-year collaborative research program and will pay for all future clinical development costs of INO-1001 and subsequent PARP inhibitors in cancer.
"PARP inhibition represents an exciting field of biology and we are intrigued by the potential of this novel mechanism to address unmet medical needs in oncology and acute cardiovascular conditions," said Hal Barron, senior vice president, Development and chief medical officer for Genentech.
"We are looking forward to working together with Inotek, a leader in the field of PARP inhibition, to pursue products that may make an impact in the treatment of patients with serious diseases including cancer."
Additional terms of the agreement will see Genentech retain an option to develop and commercialise Inotek's PARP inhibitors to prevent cell death and complications associated with various acute cardiovascular conditions and procedures.
The option is associated with an additional fee as well as development and other milestone payments.
In total, the option, if exercised by Genentech, could be worth as much as $200m in additional payments to Inotek if development, regulatory and net sales milestones are attained in multiple acute cardiovascular indications in various parts of the world.
Inotek has retained an option to co-promote PARP inhibitors in the acute cardiovascular field in the US with Genentech.