Ascletis Submits FDA IND for ASC39 to Combat Obesity with Selective Amylin Agonist

Ascletis Submits FDA IND for ASC39

Ascletis Pharma Inc. has made a significant move in the fight against obesity by submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for its new drug candidate, ASC39. This is an oral small molecule selective amylin receptor agonist, which has shown promising results in preclinical studies.

In preclinical trials, ASC39 demonstrated a selective affinity for the human amylin 1 receptor (hAMY1R) that is comparable to eloralintide, a known amylin peptide analog. The drug was found to be approximately 40 times more selective for the hAMY1R compared to the human calcitonin receptor (hCTR), indicating a potentially better efficacy and tolerability profile which could set ASC39 apart in the obesity treatment landscape.

Mechanism and Preclinical Data

ASC39 was developed using Ascletis' proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. This innovative approach not only led to the identification of ASC39's unique chemical scaffold but also highlighted its potential in activating the hAMY1R effectively. In an activated assay that compared ASC39 to eloralintide, the effective concentration (EC50) for ASC39 was 21.4 pM, which was very close to eloralintide's 21.2 pM.

Despite its performance on the hAMY1R, ASC39 showed significantly lower activity on the hCTR with an EC50 of 846.1 pM compared to eloralintide's 1,350.8 pM, reaffirming its selective nature. The findings from these assays have been vital in supporting the drug's advancement into clinical trials.

In an essential study on diet-induced obesity (DIO) rats, a 5 mg/kg dose of ASC39, administered once daily for six consecutive days, resulted in a noteworthy 6.6% weight loss compared to placebo-treated rats. This indicates ASC39's effectiveness in driving weight loss, an essential factor given the rising global obesity epidemic. Additionally, the pharmacokinetic profiles of ASC39 in non-human primates suggest that it can be dosed once daily in humans as well.

Strategic Implications

As one of the few selective amylin receptor agonists in development, ASC39 is uniquely positioned within Ascletis' expansive metabolic disease portfolio. Jinzi Jason Wu, the Founder and CEO of Ascletis, stated, "ASC39 is the only oral small molecule amylin receptor agonist in development designed to be selective for the amylin receptor over the calcitonin receptor, replicating the pharmacology of eloralintide rather than that of non-selective dual agonists."

This strategic differentiation may be crucial as the drug approaches Phase I trials, anticipated to start in the fourth quarter of 2026. With the successful IND submission, Ascletis not only expands its pipeline but also enhances its credibility in the biopharmaceutical sector focused on tackling metabolic disorders.

Besides ASC39, the company is actively advancing ASC30, its Phase III drug candidate, and a series of other programs targeting the chronic weight management and diabetes markets. The development of ASC39 allows Ascletis to cover a broader range of therapeutic options for patients suffering from obesity.

Conclusion

The regulatory approval of ASC39 is a milestone for Ascletis as it seeks to establish itself as a leader in obesity therapeutics. This development underscores a strong commitment to innovating treatment solutions for metabolic diseases through a blend of intelligent design and rigorous scientific validation. The gate is now open for potential groundbreaking advancements in obesity management as the clinical trials of ASC39 unfold in the near future.

For additional information on Ascletis Pharma and its product pipeline, visit the company’s official website at www.ascletis.com.