[Edaily Reporter KIM SAE-MI ] Peptron, Inc.(087010)In response to E-Daily’s report on the patent for its long-acting glucagon-like peptide-1 (GLP-1) formulation, Peptron, Inc. refuted the claim, stating that the anti-obesity efficacy observed in mice at two-week intervals does not indicate the drug’s maximum duration of action. Related article☞ [Exclusive] Peptron, Inc., which touted “once a month, up to 3 months”… Efficacy tests in the patent were conducted at intervals of up to two weeks

However, the crux of the previous report is that the longest dosing interval for which anti-obesity efficacy was directly verified in the patent specification was two weeks. Notably, competitors have also presented data from animal studies confirming a longer half-life. Critics point out that the difference in half-life between animals and humans, as emphasized by Peptron, Inc., is insufficient on its own to prove the anti-obesity efficacy and safety in humans for once-monthly or every 2–3-month dosing.

“Half-life is longer in humans than in mice”… Separate verification needed for efficacy in humans with once-monthly dosing

In a notice posted on its website on the 16th, Peptron, Inc. stated, “The data from the anti-obesity efficacy trial at two-week intervals does not mean that the drug’s maximum duration of action is two weeks,” adding, “This result indicates that ‘efficacy was confirmed when administered at two-week intervals,’ not that ‘the drug’s effect does not persist beyond two weeks.’”

However, the fact that anti-obesity efficacy was confirmed at two-week intervals and the fact that sufficient efficacy is maintained even at longer dosing intervals are separate issues.

Citing data from the European Medicines Agency (EMA), Peptron, Inc. noted that the half-life of semaglutide differs between mice (approximately 8 hours) and humans (approximately 148 hours). The company argues that because the rate of drug elimination differs between animals and humans, the dosing interval from the mouse efficacy trials should not be directly applied to humans.

However, these figures represent data on the species-specific pharmacokinetic characteristics of semaglutide itself. They do not constitute direct results verifying how long the drug is released or how long the actual weight-loss effect is maintained when “PT403”—Peptron, Inc.’s biodegradable polymer (PLGA) microsphere formulation—is administered to humans.

A distinction must be made between the drug’s half-life, the drug release period of the sustained-release formulation, and the duration during which actual anti-obesity efficacy is maintained. For long-acting formulations, it is difficult to determine the appropriate dosing interval based solely on the half-life of the existing semaglutide, as the rate at which the drug is released from the polymer microspheres interacts with the body’s absorption and elimination processes.

A preclinical expert in the biotech industry stated, “Generally, there is a tendency for initial release to decrease and the half-life to increase as one moves from small animals to large animals and then to humans,” but added, “It is difficult to apply a uniform rule regarding exactly how many times the half-life increases.”

He continued, “These interspecies differences can manifest differently between small-molecule compounds and biologics, and biologics tend to be more challenging to apply,” pointing out that “to apply specific half-life values to long-acting formulations, the underlying evidence and calculation methods must be clearly verified.”

In fact, “Wegovy,” an existing semaglutide injection, has a half-life of about one week in humans but is administered once weekly. This means that the mere fact that the drug is eliminated slowly from the body does not guarantee that sufficient drug concentrations and efficacy for treatment will be maintained throughout a specific dosing interval.

ADA Presents Animal Studies with 3-Week Dosage Intervals… Efficacy for Human Weight Loss Unverified

Last June, Peptron, Inc. presented the results of preclinical studies and preliminary human trials for its once-monthly semaglutide candidate, PT403, at the American Diabetes Association (ADA 2026) conference.

According to the official abstract, PT403 was administered at 2-week or 3-week intervals to diet-induced obese (DIO) mice, resulting in approximately 30% weight loss by week 4 of the study. However, the animal study with a 3-week dosing interval does not directly prove efficacy in humans for once-monthly or 2–3-month dosing regimens.

The preliminary human trial, announced alongside the animal study, was conducted on 16 healthy adults. It compared the safety and tolerability of a single 4 mg dose of PT403 in 8 participants with four weekly doses of 0.5 mg semaglutide in the other 8.

Although no nausea or vomiting was observed in the PT403 group, this study was not designed to demonstrate weight loss efficacy. The published abstract also did not provide specific human pharmacokinetic (PK) data. While securing initial human safety and tolerability data for PT403 is significant, it is difficult to interpret this as evidence that the weight loss efficacy of once-monthly dosing has been verified.

Emphasis on

70-Day PK in Mini-Pigs… Separate from Proving Anti-Obesity Efficacy in Humans

Peptron, Inc. also emphasized that it observed blood drug concentrations up to 35 days post-administration in rats and up to 70 days in mini-pigs.

The company explained, “The possibility of 1- to 3-month dosing described in the patent specification is not based solely on the dosing interval from a specific mouse efficacy study, but is described after comprehensively considering the formulation design, release characteristics, and nonclinical pharmacokinetic data.”

However, the fact that drug concentrations in the blood were observed over a long period and the fact that concentrations sufficient for treatment were maintained during that period, resulting in actual weight loss, are two separate issues. To determine the appropriate dosing interval in humans, it is necessary to comprehensively evaluate drug exposure, weight loss efficacy, and safety following repeated administration.

Nonclinical data showing prolonged drug release have also been confirmed by competitors. According to the patent for semaglutide sustained-release microparticles (KR10-2375262) registered by G2GBIO, Inc. in 2022, drug release was observed for up to 63 days in certain formulations administered to rats. This is longer than the 35-day observation period for the rat pharmacokinetic study described in Peptron, Inc.’s patent specification. G2GBIO, Inc. subsequently disclosed rat pharmacokinetic data for a 3-month sustained-release semaglutide formulation.

Regarding the additional research data, Peptron, Inc. clarified, “The mere fact that additional data has not been disclosed does not mean that such data does not exist or that the results are negative.” However, E-Daily did not assert that the additional data does not exist. It reported that the company had not disclosed whether it possessed the relevant data or its specific details.

Despite Peptron, Inc.’s rebuttal, a key issue that remains unresolved is whether sufficient anti-obesity efficacy and safety are maintained in actual human subjects when administered once a month or at intervals of two to three months. Although the company presented data on differences in half-lives between animals and humans, as well as preclinical pharmacokinetic data, these serve only as evidence supporting the feasibility of developing a long-acting formulation; they do not directly prove the efficacy and safety of the specified dosing regimen in humans.

Peptron, Inc. stated, “We are continuing to conduct research and development on SmartDepot-based long-acting GLP-1 formulations and to strengthen our intellectual property rights,” adding, “We will provide updates on related R&D achievements and business progress as and when they can be disclosed.”