Pipeline: Stenoparib (2X-121)
Stenoparib — A Dual PARP and Tankyrase Inhibitor
Stenoparib is Allarity’s lead program, and is an orally-available, small molecule dual-targeted inhibitor of PARP1/2 and telomerase maintenance enzymes (Tankyrase 1 and 2). At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of multiple cancers, potentially giving stenoparib a unique, dual tumor inhibitory action. Stenoparib was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121. Allarity has the exclusive, global rights for the development and commercialization of stenoparib.
The Stenoparib DRP® is validated for ovarian cancer. It is currently being evaluated for the treatment of advanced ovarian cancer using the Stenoparib DRP® companion diagnostic to guide patient enrollment and improve therapeutic outcome. Allarity is also studying the therapeutic potential of stenoparib in combination with dovitinib (a pan-targeted kinase inhibitor) in an ongoing Phase 1b trial.
Early Initial Data from Phase 2 Monotherapy Trial
Following the implementation of a protocol change in 2023 to optimize the drug exposure, taking into account the half-life of stenoparib in patients, DRP® selected patients received stenoparib in a twice daily (BID) dosing regimen (200 mg morning, 400 mg evening). After this change, the following data has been published in press releases on December 5, 2023, and March 27, 2024, on the first patients enrolled in the trial:
- Clinical benefit has now exceeded 20 weeks for each of the five patients initially mentioned in the December 5 press release
- One patient experienced a complete response (CR) by scan and by decreased levels of CA125 (a biomarker of AOC). This patient’s CR has been confirmed through multiple additional scans over time, and this patient remains on therapy, now exceeding ten months of treatment, showcasing durable and sustained therapeutic efficacy.
- The first patient remains on therapy with stable disease now more than 10 months
- The clinical benefit extends across a variety of patient profiles, including those with platinum-sensitive or resistant disease, those with BRCA wt or mutant status and those with homologous repair proficient or deficient tumors.
- All five patients had previously been treated with another PARP inhibitor, highlighting the potential differentiated mechanism of therapeutic action for stenoparib.
Myelotoxicity
Some approved PARP inhibitors have recently been shown to be associated with less favorable survival outcomes than initially established. Allarity’s Phase 2 trial data for stenoparib to date shows that the drug has much less myelotoxicity than the FDA approved PARP inhibitors. Specifically, in 42 evaluable women in Phase 2 studies with stenoparib, anemia (21%), neutropenia (2%) and thrombocytopenia (0%) was lower than the approved PARP inhibitor niraparib with anemia 51%, neutropenia in 20% and thrombocytopenia oberved in in 52% of 463 patients. Allarity anticipates that this lower myelotoxicity may make stenoparib a better candidate for combination with other drugs.
IDE
The U.S. FDA has approved an Investigational Device Exemption (IDE) for use of the Stenoparib DRP® as a companion diagnostic in the clinical trial.
