Rhizen Pharmaceuticals has initiated dosing in the Phase I/Ib clinical trial of its new poly (ADP-ribose) polymerase (PARP) inhibitor (RP12146) in advanced solid tumour patients in Europe.

RP12146 is part of Rhizen’s larger DNA Damage Response (DDR) platform that includes a polymerase theta (Polθ) inhibitor programme in the preclinical stage.

The DDR platform is expected to allow proprietary in-house combinations of its PARP and Polθ assets.

The two-part, multi-centre study will initially assess the maximum tolerated dose (MTD), tolerability, safety, and/or recommended Phase II dose (RP2D) of the PARP inhibitor.

Later, the trial will evaluate the anti-tumour activity of RP12146 in expansion cohorts with ovarian, HRR mutation-enriched ES-SCLC, and breast cancer patients.

Compared to the approved PARP inhibitor Olaparib, RP12146 showed preclinical activity, efficacy and improved safety as observed in the preclinical IND-enabling toxicology trials.

Rhizen Pharmaceuticals founder and CEO Swaroop Vakkalanka said: “PARP inhibitors are a great success story in the DNA damage response area, but they are not without safety concerns that have limited realisation of their full potential.

“Although our novel PARP inhibitor is competing in a crowded space, we expect its superior preclinical safety to translate into the clinic, which will differentiate our program and allow us to extend its application beyond the current landscape of approved indications and combinations.

“Our PARP programme is foundational for our DDR platform efforts and will be the backbone for several novel proprietary combinations that we hope to bring into development going forward.”

In September 2021, the company dosed the first patient in a Phase II clinical trial of RP7214 in mild and symptomatic Covid-19 patients with an underlying risk factor.