Karyopharm Commences First Stage Clinical Study with KPT-9274

Karyopharm Therapeutics Inc.

revealed the dosing of the first patient in a first stage clinical study evaluating KPT-9274, an oral, first-in-class, dual-acting p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase inhibitor, in patients with advanced solid malignancies (including sarcoma, colon and lung cancer) or non-Hodgkin's lymphoma whose disease has relapsed after standard therapy(s) (NCT02702492). Karyopharm said that this first-in-human, multi-center, open-label, dose-escalation study was expected to enroll maximum of 175 patients. According to the company, the primary endpoints of this trial were to assess the recommended Phase 2 dose (RP2D) and the maximum tolerated dose (MTD) of KPT-9274 administered alone and with extended release niacin, and to evaluate safety and tolerability. The company also indicated that the key secondary endpoint was to assess anti-tumor activity in patients expected to be more sensitive to PAK4/NAMPT inhibition. That included those with NAPRT-deficient tumors and tumors harboring IDH1 mutations. Karyopharm President and CEO, Sharon Shacham, commented, "Our first-in-class, oral, small molecule PAK4 and NAMPT modulator, KPT-9274, has synergistic anti-tumor effects through several mechanisms including immune cell activation by inhibiting ß-catenin, reduction of NAD levels which tumor cells use as a key energy source, blockade of DNA damage repair mechanisms, and induction of tumor cell apoptosis". He continued to add that "We are encouraged by the preclinical profile of KPT-9274, highlighted at the 2015 American Society of Hematology and 2016 American Association of Cancer Research annual meetings, which support the novel mechanism and demonstrated encouraging preclinical anti-tumor activity. To our knowledge, we are the only company with a compound in clinical development that directly targets both PAK4 and NAMPT. This important Phase 1 study will continue to build upon the body of scientific evidence supporting KPT-9274's safety and efficacy, and we look forward to reporting top-line data next year." On Wednesday, the stock shed 1.7 percent.