Ascletis’ ASC37 Shows Strong Weight Loss Results in Preclinical Study

Next-generation triple peptide agonist outperformed tirzepatide in obese mice

Ascletis Pharma Inc. has announced encouraging preclinical results for ASC37, a next-generation GLP-1R/GIPR/GCGR triple peptide agonist being developed for the treatment of severe obesity and chronic weight management.

In a diet-induced obese (DIO) mouse model, ASC37 demonstrated greater weight loss than tirzepatide, a widely known medicine used for weight management and other metabolic conditions.

After 11 days of treatment, mice receiving ASC37 showed an 88% greater relative reduction in body weight compared with mice receiving tirzepatide at the same dose of 1 nmol/kg.

ASC37 also produced dose-dependent weight loss of up to 41.5% in the DIO mice.

The results are from preclinical studies, so they do not yet show whether the same level of weight loss will be achieved in humans.

ASC37 targets three metabolic pathways

ASC37 is designed to activate three receptors involved in metabolism and body weight regulation.

These include:

• GLP-1 receptor (GLP-1R)
• GIP receptor (GIPR)
• Glucagon receptor (GCGR)

This triple agonist approach is designed to act on multiple biological pathways at the same time.

GLP-1 and GIP pathways are already well known for their role in glucose control, appetite regulation and weight management.

The glucagon pathway is also being studied for its potential role in energy expenditure and metabolic regulation.

By combining activity across all three pathways, Ascletis is developing ASC37 as a potential next-generation treatment for people living with severe obesity.

ASC37 delivered up to 41.5% weight loss in mice

The company reported that ASC37 produced weight loss in a dose-dependent manner in the DIO mouse model.

At higher doses, the treatment achieved weight loss of up to 41.5%.

The company also compared ASC37 directly with tirzepatide.

When both treatments were administered at 1 nmol/kg for 11 days, ASC37 produced an 88% greater relative body weight reduction compared with tirzepatide.

The difference was statistically significant in the study.

However, these findings come from an animal model. Clinical trials will be needed to determine how ASC37 performs in humans and whether its safety and effectiveness can be confirmed.

The company is developing monthly injectable and oral versions

Ascletis is working on two formulations of ASC37.

The first is a once-monthly subcutaneous injection.

The second is an oral formulation.

The company plans to submit Investigational New Drug (IND) applications for both formulations to the US Food and Drug Administration (FDA) in the third quarter of 2026.

If clinical development is successful, Ascletis plans to submit Biologics License Applications (BLAs) for both formulations following completion of Phase 3 clinical trials.

This means the company is developing ASC37 under the biologics regulatory pathway rather than as a traditional small-molecule drug.

ASC37 has 41 alpha amino acids

Ascletis said ASC37 was engineered with 41 alpha amino acids, which qualifies the candidate as a biologic.

The company believes this classification could provide regulatory and commercial advantages.

Ascletis is also developing ASC35, a next-generation GLP-1R/GIPR dual peptide agonist that also contains 41 alpha amino acids.

ASC35 is also planned to be submitted through the BLA regulatory pathway.

ASC37 could support once-monthly dosing

One of the key features Ascletis is highlighting is the long duration of ASC37.

In non-human primate (NHP) studies, the company's Self Assembly Lipid Depot (SALD) formulation of ASC37 had an average observed half-life of approximately 17 days.

The company compared this with retatrutide, another triple peptide agonist, which showed an average half-life of approximately 2.5 days in the referenced studies.

Based on these results, ASC37 demonstrated an approximately seven-fold longer observed half-life than retatrutide.

Ascletis believes the longer half-life supports the potential for once-monthly or less frequent dosing.

For patients, less frequent dosing could make long-term weight management easier compared with treatments that require more frequent administration.

The actual dosing schedule and performance of ASC37 will need to be established through human clinical trials.

Ascletis sees potential for a first-in-class monthly triple agonist

Jinzi Jason Wu, Ph.D., founder, chairman and CEO of Ascletis, said the company believes the preclinical results support ASC37's potential as a first-in-class once-monthly subcutaneous triple peptide agonist.

He also highlighted the potential advantages of developing ASC37 as a biologic.

According to Wu, the biologics pathway could provide longer statutory exclusivity and extended protection from government price negotiations compared with small-molecule drugs.

The company is now preparing to move ASC37 toward clinical development.

Biologic status could affect future market protection

Ascletis is also highlighting the potential commercial impact of ASC37's biologic classification.

Under the Inflation Reduction Act, certain biologics have a 13-year period following FDA approval before becoming subject to government price negotiations, compared with nine years for small molecules, according to the company's announcement.

Ascletis also noted that biologics do not have the same regulatory pathway for pharmacy compounding that applies to certain small-molecule medicines.

The company believes this could reduce the possibility of third-party compounding pharmacies offering compounded versions of ASC37 and ASC35.

These factors could become relevant if the medicines eventually reach the market, although ASC37 is still at the preclinical stage and has not yet been approved for use in humans.

ASC37 is part of Ascletis’ broader obesity pipeline

ASC37 is one of several metabolic drug candidates being developed by Ascletis.

The company's pipeline includes treatments designed to target different pathways involved in weight management and metabolic health.

Its lead programme, ASC30, is a small-molecule GLP-1 receptor agonist being developed in oral and injectable formulations.

The company is also developing ASC36, an amylin receptor peptide agonist, and ASC35, a once-monthly subcutaneous GLP-1R/GIPR dual peptide agonist.

Other programmes include ASC39, an oral small-molecule amylin receptor agonist, along with fixed-dose combinations that pair different metabolic targets.

These programmes are intended to provide potential treatment options for chronic weight management and metabolic diseases.

Ascletis is using multiple technology platforms

Ascletis says its drug discovery and development programmes are supported by proprietary technologies.

These include Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD), the Ultra-Long-Acting Platform (ULAP) and Peptide Oral Transport ENhancement Technology (POTENT).

The company is using these platforms to develop both small-molecule and peptide drug candidates.

For ASC37, the focus is on combining triple receptor activity with a long-acting formulation that could potentially allow patients to receive treatment once a month or less frequently.

The company plans to submit IND applications for the once-monthly subcutaneous and oral versions of ASC37 in the third quarter of 2026. Further development will depend on regulatory review and the results of future clinical studies.