Ascletis Presents Full Analysis of Phase Ib Study of ASC30 Oral Tablet, Phase Ib Study of ASC30 Injection, and Preclinical Study of Combination of ASC31 and ASC47 at ObesityWeek® 2025
-Positive data from Phase Ib study of ASC30 oral tablet demonstrated up to 6.5% placebo-adjusted mean body weight reduction; safe and well tolerated with only mild-to-moderate gastrointestinal (GI) adverse events (AEs) across all multiple ascending dose (MAD) cohorts.
-Phase Ib study data of ASC30 subcutaneous (SQ) injection showed that observed half-life reached 46 days for the treatment formulation (Injection A) and 75 days for the maintenance formulation (Injection B).
-Combination of ASC47 and ASC31, a novel peptide agonist targeting both GLP-1R and GIPR, significantly outperformed both tirzepatide and ASC31 monotherapy in promoting weight loss, body fat loss, and muscle preservation in diet-induced obesity (DIO) mouse studies.
-Presentations further highlight the promising efficacy and safety profiles of
Abstract Title: A full analysis of 28-Day MAD Study of Oral GLP-1R Biased Small Molecule Agonist ASC30 for obesity
Results:
Efficacy: Body weight changes from baseline were 6.3% reduction (multiple ascending dose (MAD) 2, n=8, 40 mg), 4.3% reduction (MAD 1, n=7, 20 mg), and 0.2% increase (placebo, n=6). No plateau was observed at Day 29. Body weight change from baseline was 4.8% reduction for MAD 3 (n=7, 60 mg), with the maximum body weight change being 9.3% reduction in this cohort. Excluding two outliers, the mean body weight change from baseline was 5.9% reduction for MAD 3.
GI Tolerability: In the MAD study, MAD 1 (20 mg cohort) showed no vomiting, while MAD 2 (40 mg cohort) had events. Titrating from 2 mg to 5 mg did not cause vomiting in MAD 1, but titrating from 2 mg to 10 mg did result in vomiting in MAD 2. Compared with MAD 2, MAD 3 showed no increasing trend in severity or incidence of gastrointestinal (GI) adverse events (AEs), despite two discontinuations due to principal investigator's decisions, and one discontinuation due to subject withdrawal.
Safety: No serious adverse events (SAEs) or Grade ≥ 3 AEs, including GI events, were observed. Labs, vitals, ECGs (QTc), and physical exams were normal. No hepatic safety signals were detected across all MAD cohorts.
Conclusion: ASC30 once-daily oral tablet demonstrated up to 6.5% placebo-adjusted mean body weight reduction from baseline after 28-day treatment. The highest dose level (MAD 3, 60 mg) exhibited up to 9.3% body weight reduction, showed no increasing trend in severity or incidence in GI AEs. ASC30 was safe and well tolerated with only mild-to-moderate GI AEs across all MAD cohorts. The safety profile of ASC30 tablets was consistent with or better than that of the GLP-1R agonist class.
Abstract Title: ASC30, a Once-Monthly SQ Injected Small Molecule GLP-1RA in Participants with Obesity: A Ph Ib Study
Results: The observed half-life (time for ASC30 concentrations to reduce to fifty percent (50%) of ASC30's Cmax) reached 46 days and 75 days, for ASC30 subcutaneous (SQ) treatment formulation (Injection A) and ASC30 SQ maintenance formulation (Injection B), respectively. Cmax-to-Cday29 ratio of 1.5:1, supports ASC30 SQ treatment formulation monthly dosing, while Cmax-to-Cday85 ratio of 2.5:1, supports ASC30 SQ maintenance formulation quarterly dosing.
No SAEs or Grade ≥ 3 AEs were observed. GI-related AEs were mild to moderate. Labs, vitals, ECGs (QTc), and physical exams were normal. No hepatic safety signals were detected across all cohorts.
Conclusion: ASC30 ultra-long-acting, slow-release SQ depot formulations demonstrated 46-day observed half-life (treatment formulation) and 75-day observed half-life (maintenance formulation), supporting both once-monthly treatment and once-quarterly maintenance therapies.
ASC30 SQ formulations were well tolerated, with only mild-to-moderate treatment-emergent adverse events (TEAEs), comparable or superior to those observed with GLP-1R agonists. Developed with
Abstract Title: GLP-1R/GIPR Peptide Agonist ASC31 + ASC47 Shows 119.6% More Weight Loss than Tirzepatide in DIO Mice
Results: The combination of ASC47 plus ASC31 resulted in a 44.8% reduction in weight compared to a 19.1% reduction for ASC31 monotherapy. This was a 134% greater reduction than ASC31 alone. The combination of ASC47 plus tirzepatide resulted in a 38.1% reduction in weight compared to a 20.4% reduction for tirzepatide alone. This was an 87% greater reduction in weight compared to tirzepatide alone. The mean greater reduction in weight of ASC31 in combination with ASC47 compared to ASC31 alone (134%) is statistically significantly higher than that of tirzepatide plus ASC47 compared to tirzepatide alone (87%).
Conclusion: The combination of ASC47 and ASC31 significantly outperformed both tirzepatide and ASC31 monotherapy in promoting weight loss, body fat loss, and muscle preservation. The combination of ASC47 with either ASC31 or tirzepatide restored the body composition of obese mice to the level of healthy non-obese mice. ASC31 is a dual GLP-1R and GIPR peptide agonist. ASC47 is a small molecule thyroid hormone receptor beta (THRβ)-selective agonist and was designed with unique and differentiated properties to enable targeted delivery to adipose tissue.
Detailed data presented at ObesityWeek® 2025 can be found at
"These presentations highlight the exciting efficacy and safety profiles of our diverse obesity pipeline of both small molecules and peptides and validate our proprietary AISBDD and ULAP technologies," said
About ASC30
ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both oral tablet and subcutaneous injection administrations. ASC30 is a new chemical entity (NCE), with
About ASC31
ASC31 is an in-house discovered and developed novel peptide agonist targeting both GLP-1R and GIPR, which demonstrated a favorable pharmacokinetic profile in non-human primates as well as promising in vitro activities and in vivo efficacy in the diet-induced obese (DIO) mice. ASC31 is part of
About ASC47
ASC47 is an adipose-targeted, once-monthly SQ injected THRβ-selective small molecule agonist, discovered and developed in-house at
About
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Peter.vozzo@icrhealthcare.com
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