CureGene Doses First Subject in Phase I Trial of Oral Liver-Targeted Therapy CG-0416

Phase I study begins in Australia

CureGene Pharmaceutical has announced that the first subject has been dosed in the Phase I clinical trial of CG-0416, its investigational oral liver-targeting THR-β agonist.

The first-in-human study is being conducted in Australia, and subject enrollment is progressing as planned. The trial is designed to provide the first clinical data on the safety, tolerability, pharmacokinetics and pharmacodynamics of CG-0416 in humans.

The company is developing CG-0416 for chronic metabolic diseases, including obesity and metabolic dysfunction-associated steatohepatitis (MASH).

What is CG-0416?

CG-0416 is an oral small-molecule therapy developed using CureGene's proprietary prodrug technology.

The drug is designed to release its active component mainly in the liver. The idea is fairly simple: if more of the active drug reaches the liver and less reaches other tissues, the company hopes to improve the treatment's activity while reducing unwanted effects outside the liver.

CG-0416 is being studied as a potential treatment for metabolic conditions where excess liver fat, abnormal lipid metabolism and impaired glucose control play an important role.

Liver targeting is a key part of the design

One of the main features of CG-0416 is its liver-targeting mechanism.

According to CureGene, the prodrug is designed to achieve high levels of active drug release inside the liver while keeping systemic exposure relatively low. This could help limit off-target activity in tissues outside the liver.

The company believes this approach could be useful for long-term treatment of metabolic diseases that require chronic daily therapy.

Potential effects on liver fat and metabolic health

Preclinical studies showed that CG-0416 can activate lipid metabolism in the liver.

In animal studies, the treatment reduced the accumulation of liver fat and was associated with improvements in inflammation and fibrosis. The company also reported favorable changes in lipid profiles and glucose tolerance.

These findings are particularly relevant to MASH, where excess liver fat can contribute to inflammation and progressive liver damage.

However, these results are from preclinical research. The ongoing clinical trial will help determine how the drug performs in humans.

Weight loss with a focus on muscle preservation

CureGene is also studying CG-0416 for obesity and related metabolic complications.

In preclinical studies, the company reported that CG-0416 produced weight loss comparable to commonly used GLP-1 receptor agonists such as semaglutide when used as a monotherapy.

The company also reported less muscle loss with CG-0416 compared with what is typically associated with weight reduction.

CG-0416 is also being evaluated as a potential combination treatment with GLP-1 receptor agonists. In preclinical research, the combination produced additional weight reduction and maintained a favorable muscle-preservation profile.

These findings will need to be tested in clinical studies before the potential benefits in people can be understood.

The drug uses a different activation pathway

Another feature of CG-0416 is its proposed non-CYP metabolism pathway.

The drug is activated through hydrolysis rather than relying mainly on CYP450 oxidative metabolism. CureGene believes this could reduce the potential for drug-drug interactions and decrease differences in drug exposure between individuals.

The company has also reported oral bioavailability of up to 92% in preclinical development.

If these characteristics are confirmed clinically, they could be useful for a medicine intended for long-term daily use.

Phase I study will focus on safety and drug behavior

The Phase I study in Australia is a randomized, double-blind, placebo-controlled trial involving healthy participants.

Participants will receive single and multiple ascending doses of CG-0416. Researchers will monitor how well the treatment is tolerated and how the drug behaves inside the body.

The main areas being evaluated include:

• Safety
• Tolerability
• Pharmacokinetics (PK)
• Pharmacodynamics (PD)

The single-ascending-dose and multiple-ascending-dose portions are expected to provide important information about appropriate dose levels for later clinical studies.

The study is also intended to generate data that can support the company's broader global development plans.

Why Australia was selected for the first-in-human study

CureGene is conducting the Phase I trial in Australia because of the country's established clinical research infrastructure for early-stage studies.

For a first-in-human program, companies need to carefully evaluate safety and drug exposure before moving into larger patient studies. The Australian trial is expected to provide these early clinical data for CG-0416.

The results could help guide the next stages of development and potential expansion into additional indications.

CG-0416 is being developed for MASH and obesity

CureGene is positioning CG-0416 as a potential therapy for several chronic metabolic conditions.

MASH is one of the key areas of interest because the disease is closely linked to liver fat accumulation, inflammation and fibrosis.

Obesity is another major focus. The company is exploring whether CG-0416 can provide meaningful weight reduction while helping preserve muscle mass.

The potential combination with GLP-1 receptor agonists could also become an important part of the development strategy if clinical studies confirm the preclinical findings.

CureGene CEO comments on the clinical milestone

Dr. Gongxin He, Founder and Chief Executive Officer of CureGene, said that dosing the first participant represents another step in the company's expansion into cardiovascular and metabolic diseases.

He also highlighted the company's focus on using its prodrug technology to develop therapies that could offer improved safety, clinical value and convenience.

The Phase I study will now provide the first opportunity to evaluate whether the characteristics seen during preclinical development translate into humans.

About CG-0416

CG-0416 is an investigational liver-targeted THR-β prodrug being developed for MASH and obesity-related complications.

Its proposed tissue-selective activation is intended to address several metabolic processes in the liver, including lipid accumulation, inflammation and fibrosis.

CureGene has also positioned CG-0416 as a potential oral treatment that could be used alongside GLP-1 receptor agonists.

Preclinical comparisons reported by the company showed favorable metabolic activity compared with compounds such as resmetirom and VK-2809. These comparisons remain preclinical and will require clinical validation.

About CureGene Pharmaceutical

CureGene Pharmaceutical was founded in 2018 and develops innovative medicines using its proprietary technology platforms.

The company focuses on areas including cardiovascular and cerebrovascular diseases, antiviral therapies and metabolic diseases.

CureGene has built a pipeline of drug candidates that are being advanced through different stages of development, with the company targeting therapies that it believes could have first-in-class or best-in-class potential.

The company's development strategy also includes global clinical development and the use of its internal technology platforms to move drug candidates from research toward clinical testing.

What comes next for CG-0416

The immediate focus for CG-0416 is the ongoing Phase I study in Australia.

The safety, tolerability, PK and PD results from the trial will be important in determining how the program moves into later-stage development.

If the clinical data support continued development, CureGene could advance CG-0416 into patient studies for conditions such as MASH and obesity and further evaluate its potential use alongside GLP-1 receptor agonists.