Early on November 24, pioneering pharmaceutical WeChat public number, said its independent research and development of new targeted androgen receptor (AR) protein degradation chimera (PROTAC) compound GT20029 treatment of androgen alopecia (AGA) and acne China phase I clinical trial positive results, shows that its in healthy subjects has good safety, tolerability and pharmacokinetic characteristics. GT20029 is the first topical PROTAC compound worldwide to complete a phase I clinical trial.
Preclinical studies have shown that GT20029 effectively blocks the miniaturization of hair follicle atrophy caused by the activation of AR proteins by inhibiting the AR signaling pathway, suppresses hair thinning, softening and shedding, and can effectively inhibit sebaceous gland development and sebum secretion. GT20029 produces efficacy only locally, thereby reducing systemic drug exposure by limiting skin penetration. Repeated results of the pharmacodynamic studies of dihydrotestosterone (DHT) -induced mouse model showed that GT20029 significantly reduced hair loss with statistical differences. In addition, the results of the pharmacodynamic study of testosterone propionate (TP) -induced sebaceous gland spot acne model showed that GT20029 can significantly inhibit the enlargement of sebaceous gland spots with statistical differences.
The phase I clinical trial in China is a randomized, double-blind, placebo-controlled study to assess the safety and pharmacokinetics of the topical topical drug administration of GT20029 (gel and tincture). Single and multiple doses of GT20029 (gel and tincture) were administered in healthy subjects.
The phase I clinical data showed that 92 subjects received at least one dose of the trial medication, with 68 subjects receiving the gel and 24 subjects receiving the tincture.
GT20029 is safe and well tolerated in healthy subjects with low levels of exposure to human drug concentrations. After a single dose, all subjects had no in vivo drug exposure, and all samples in all dose groups were below the lower limit of quantification (LLOQ,0.001ng/mL). After 14 consecutive days of administration, the mean maximum blood concentration in each dose group was below 0.05 ng/mL. Adverse events related to the study drug (TRAE) occurring during the trial were all occurring at grade 1, and no TRAE occurring at or above grade 1 occurred.
Dr. Tong Youzhi, Founder, Chairman and CEO of Pioneer Pharmaceutical, said, " As the world's first topical PROTAC compound to complete clinical phase I, GT20029 showed good safety and tolerability in clinical phase I in nearly 100 healthy subjects. This human trial provides two key data: 1) the pharmacokinetic results prove that external PROTAC compounds can be soaked into the body, and the body exposure is much lower than foritane (small molecule antagonist), indicating controllable external safety; 2) repeated high dose (2%) administration of external PROTAC compounds observed no skin surface damage, proving the local safety of AR targeted protein, laying the foundation for future clinical phase II drug effectiveness observation. Based on the clinical results, the company will determine the clinical phase II dose as soon as possible, start the corresponding clinical trials, and maintain the leading position in the development of topical innovative drugs using PROTAC technology worldwide.”
