IMPACT announced PARP inhibitor Senaparib in combination with temozolomide IND clearance by US FDA
Impact Therapeutics recently announced that the U.S. FDA approved the Investigational New Drug (IND) application of PARP inhibitor senaparib (IMP4297) in combination with temozolomide (TMZ) for clinical study in U.S. This study is a Phase I, open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficiency of senaparib in combination with temozolomide in patients with advanced solid tumors and small cell lung cancer. US sites will join the study that has already initiated in Australia, Korea and Taiwan China. The first patient was dosed in August 2020.
Senaparib is a novel agent targeting PARP (poly-ADP ribose polymerase) developed by Impact. The company has completed two Phase I studies of senaparib in China and Australia, respectively. The latest Phase I data readout was presented in ESMO 2020, showing that senaparib had the potential to be the best-in-class PARP inhibitor with better safety profile and wider therapeutic window. These enable senaparib more suitable for long-term therapies and combination therapies. Impact and Junshi Biosciences established a 50:50 joint venture that focuses on the development and commercialization of senaparib in China., The JV is currently conducting a Phase II pivotal study of senaparib monotherapy in treating advanced ovarian cancer patients with BRCA mutation who have received at least 2 prior lines of standard treatment, and a Phase III study of senaparib as the first-line maintenance treatment in platinum-sensitive advanced ovarian cancer patients.
Temozolomide (TMZ) is an orally available alkylating agent with broad range of anti-tumor activity and the ability to penetrate blood-brain barrier that makes it the treatment of choice in certain types of brain tumors. The combination of TMZ with senaparib is supported by synthetic lethality mechanism of action. Due to its PARP inhibiting and trapping activity, senaparib could prevent tumor cells from repairing DNA damages caused by TMZ, producing synthetic lethality. In preclinical animal models, combination of senaparib and TMZ demonstrated highly significant synergistic anti-tumor activity, without additive toxicity.
Dr. Chih-Yi Hsieh, Senior Vice President and Chief Medical Officer said, “This is the first US IND approval of senaparib, as well as the second US IND approval achieved by Impact recently, This marks important steps that Impact is taking in order to take our product development to the global stage. Although there are four PARP inhibitors marketed, based on our unique clinical development strategy and differentiated molecular structure, we are highly confident to leverage characteristics of senaparib to indication neither has not been addressed nor will able to be addressed by other PARP inhibitors. Despite the addition of immunotherapy, small cell lung cancer is a malignancy with very poor prognosis which will progress quickly, hence huge unmet clinical needs still exist. Based on synthetic lethality mechanism of action, we expect to validate senaparib in combination with TMZ clinically and bringing benefit to more patients of various cancer types.”
Impact Therapeutics is a privately held, clinical-stage biopharmaceutical company and dedicates to the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality. Impact has assembled the most comprehensive global DNA damage response (DDR) pipeline of novel drug candidates generated by in-house discovery efforts, and is expanding to other novel synthetic lethality targets to broaden its pipeline. Impact has been funded by recognized venture capital firms such as Lilly Asia Ventures.