ASCLETIS-B (01672) announced that ASC30 once-daily oral tablets have achieved positive top-line pharmacokinetic (PK) data in a randomized, double-blind, placebo-controlled US Phase Ib multiple ascending dose (MAD) study (NCT06680440) conducted in obese subjects with body mass index (BMI) of 30-40 kg/m².

In Cohort 1 (20 mg) and Cohort 2 (40 mg) of the Phase Ib MAD study, ASC30 drug exposure (AUC0-24h) at steady state reached 3,560 ng.h/mL and 5,060 ng.h/mL, respectively. These drug exposure levels were consistent with placebo-adjusted mean weight loss from baseline: after 28 days of treatment, Cohort 1 (20 mg) achieved 4.5% weight reduction, while Cohort 2 (40 mg) achieved 6.5% weight reduction, indicating that higher drug exposure produces more significant weight loss effects.

Cross-trial comparisons show that drug exposure for 20 mg and 40 mg ASC30 once-daily oral tablets was approximately 2.3-fold and 3.3-fold higher, respectively, compared to orforglipron once-daily oral capsules (24 mg cohort, AUC0-24h 1,520 ng.h/mL). After 28 days of treatment, orforglipron (24 mg cohort, AUC0-24h 1,520 ng.h/mL) produced only 3.6% placebo-adjusted mean weight loss from baseline.

Despite higher ASC30 drug exposure in Cohort 1 (20 mg, AUC0-24h 3,560 ng.h/mL), no vomiting occurred in this cohort, while the orforglipron 24 mg cohort (AUC0-24h 1,520 ng.h/mL) had an 18% vomiting incidence rate, suggesting that Ascletis' lead compound and formulation optimization strategy played a role in improving tolerability.

In the Phase Ib MAD study, ASC30 once-daily oral tablets demonstrated good safety and tolerability, with no serious adverse events (SAEs) reported and no Grade 3 or higher adverse events (AEs) observed, including gastrointestinal (GI)-related AEs. No elevation in liver enzymes (including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL)) occurred during treatment. Laboratory tests, vital signs, ECGs (electrocardiograms, including heart rate-corrected QT interval (QTc)), and physical examinations showed no abnormalities.

"Based on currently available clinical data, we believe that for small molecule GLP-1 receptor (GLP-1R) agonists, including orforglipron, higher drug exposure produces more significant weight loss effects," said Dr. Jinzi Wu, Founder, Chairman and CEO of Ascletis. "In head-to-head studies in non-human primates, ASC30 drug exposure was higher than orforglipron, and this data has further translated to human clinical studies. Cross-trial comparisons show that ASC30's drug exposure in humans is approximately 2.3-fold to 3.3-fold higher than orforglipron, which we find very exciting. Given that ASC30's higher drug exposure produced more significant weight loss effects in obese subjects, we believe that compared to orforglipron, ASC30 once-daily oral tablets have competitive and differentiated potential for treating obesity."