Kintor Pharmaceutical Limited announced the positive top-line results from the U.S. Phase I clinical trial of GT20029, a Kintor Pharma in-house developed and fully owned proteolysis targeting chimera (PROTAC) compound. The data showed GT20029 was safe, well tolerated and had good pharmacokinetic characteristics in healthy subjects as well as subjects with androgenetic alopecia (AGA) or acne. GT20029 is the first topical PROTAC compound in the world which has completed Phase I clinical trial in both China and the U.S. This is a randomized, double-blind, placebo-controlled, parallel group, dose escalation Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of GT20029 following topical single ascending dose administration (SAD) in healthy subjects and multiple ascending dose administration (MAD) in subjects with AGA or acne. The results showed that GT20029 was safe and well tolerated at all dose levels in all cohorts.

No treatment-emergent adverse events (TEAEs) related to GT20029 in the SAD stage were reported. The most common TEAEs in the MAD stage were mild, including dryness, itching, burning and pain at application site. No serious adverse events (SAEs) were reported.

No severe (Grade =3) TEAEs and no subject withdrawal or death caused by TEAEs were reported. In the SAD stage, subjects had no systemic exposure at all dose levels, and all sample concentrations were below the lower limit of quantification (LLOQ, 0.003ng/mL). In the MAD stage, after 14 days of continuous administration in subjects with AGA or acne, the systemic exposure was very limited and the mean maximum observed concentration (Cmax) of all dose levels fluctuated near the LLOQ, with the highest not exceeding 0.015 ng/mL.

In preclinical studies, by degrading androgen receptor (AR) protein, GT20029 could block the shrinkage and miniaturization of hair follicles which was caused by the activation of AR signaling pathway. As the result, it prevented the hair from thinning, softening and falling out. GT20029 could also effectively inhibit sebaceous gland development and sebum secretion.

With limited skin penetration, GT20029 could avoid high systemic exposure and achieve a better safety profile. The repeated pharmacodynamics studies in dihydrotestosterone (DHT)-induced mouse model showed that GT20029 significantly promoted hair growth, with statistical difference. The study of testosterone propionate (TP)-induced skin hamster flank organ acne model showed that GT20029 significantly inhibited enlargement of flank organ, with statistical difference.