Phase I Study of Progerinin in Healthy Volunteers

PRG Science \& Technology Co., Ltd. (PRG S\&T) is developing Progerinin (SLC-D011) for the treatment of the rare aging diseases Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS). Progerin, an abnormal splice variant of the inner nuclear membrane protein lamin A is implicated in the pathology of HGPS and WS. It is believed that the extremely strong binding between lamin A and progerin is responsible for the nuclear abnormality phenotype observed in HGPS. WS is caused by functional defect of WRN, RecQ4L DNA helicase and rapid accumulation of progerin in WRN deficient condition is thought to be the cause of premature aging in WS. PRG S\&T has shown that Progerinin binds specifically to progerin reduces its expression in both HGPS and WS cells, Progerinin further prevents progerin-lamin A in HGPS cells. In a progeria mouse model (LmnaG609G/G609G), treatment with Progerinin via intraperitoneal (i.p) injection (20 mg/kg, twice per week) could increase the body weight and extend the life span of LmnaG609G/G609G mice up to 21 weeks. In the LmnaG609G/+ mouse model, improved morphology such as status of coat hair and body size, increased body weight and extended life span for about 16 weeks was noted following Progerinin treatment. In addition, Progerinin can suppress muscle weakness including the heart muscle. Safety pharmacology studies did not indicate any Progerinin-related effects on vital organs and systems including respiratory, cardiovascular and central nervous system. Prior to studies in the disease states, this study PRG-PRO-001, an initial first-in-human study, will be conducted in healthy volunteers to assess the safety, tolerability and pharmacokinetics of Progerinin. PRG-PRO-001 is a Phase I, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose (SAD) Study including a food interaction study, followed by a Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Profile of Progerinin in Healthy Volunteers. This is a first-in-human study. The study aims to determine the safety and tolerability of Progerinin after single and multiple doses in healthy volunteers and to evaluate the pharmacokinetics (PK) of Progerinin after single and multiple dose administrations in healthy volunteers. The estimated enrollment is around 56 healthy volunteers, with 40 subjects estimated for the SAD phase and 16 subjects for the MAD Phase at one site in the USA. Expanded Access Program is available. For more details, please use the link in the References Section below to access our company's main webpage on Expanded Access Program.