Novel small molecule drugs developer Nyrada Inc (ASX: NYR) has identified two additional, more potent candidates with improved drug-like characteristics under its cholesterol-lowering development programme.
Building on a previous in vivopreclinical study that showed that the company’s NYX-PCSK9i drug reduced total cholesterol by 57% without adverse side effects, Nyrada has now commenced a new in vivoefficacy study in the same specialised transgenic mouse model (APOE3-Leiden.CETP) to evaluate NYX-PCSK9i in combination with a statin (high cholesterol mouse study). This study aims to determine if NYX-PCSK9i enhances the efficacy of a statin drug when co-administered.
In addition, Nyrada has reported that recent medicinal chemistry work has revealed two promising drug candidates (NYX-PCSK9i-211 and NYX-PCSK9i-212) with in vitrotesting confirming they have improved potency and bioavailability (absorption) compared to NYX-PCSK9i. These new candidates may be less prone to interactions with drugs prescribed to patients with high cholesterol.
CEO, James Bonnar, said that consequently, the new in vivo high cholesterol mouse study has been expanded to evaluate the efficacy of these new drug candidates. Results from this study are expected to be reported in mid- June and will enable Nyrada to select the optimum drug candidate to take forward into preclinical safety and toxicology testing, which is expected to start shortly after completion of the in vivohigh cholesterol mouse study.
Nyrada has also selected a preferred, internationally recognised Contract Research Organisation (CRO) to oversee the preclinical safety and toxicology studies that are necessary before human clinical trials can commence. These studies aim to confirm cardiac, central nervous system, and respiratory safety and measure toxicological effects in two animal species, a requirement before starting clinical trials in humans. The design and structure of the studies have been agreed with the CRO.
Commencement of the preclinical safety and toxicology studies is dependent on having sufficient amounts of the clinical candidate available. Nyrada is optimising the route of synthesis for these compounds as it scales up from gram to kilogram quantities, which are required for these studies. The Company will provide an update on the expected commencement and duration of the Phase I clinical trial once the high cholesterol mouse study and scale-up manufacturing are complete.
Nyrada has built a strong portfolio of novel compounds that strengthen our intellectual property and create licensing opportunities for the Programme,” Mr Bonnar said.
“We are confident that scale-up manufacturing combined with the improved potency and drug-likeness of the new compounds, compared to the positive results of NYX-PCSK9i, ensures we will enter Phase I clinical trials with the optimal drug candidate.”