[Edaily Reporter KIM SUNG-JIN ] While glucagon-like peptide-1 (GLP-1) drugs—treatments for obesity and metabolic disorders—have become the dominant trend as the biggest issue in the global pharmaceutical and biotech industries, the development of therapies targeting 11β-HSD1, which regulates cortisol production, is drawing attention.

11β-HSD1 refers to the enzyme that converts cortisone into the active form, cortisol. While cortisol is a crucial hormone that influences the body’s metabolism and stress regulation, excessive production can lead to elevated blood sugar levels and increased insulin resistance, which may cause the accumulation of abdominal fat.

It is expected that inhibiting cortisol production via 11β-HSD1 will help avoid side effects such as appetite suppression and muscle mass loss compared to existing GLP-1-based treatments for metabolic dysfunction-associated steatohepatitis (MASH) and weight-loss drugs. However, since major global pharmaceutical companies have conducted extensive research targeting 11β-HSD1 in the past without achieving significant results, the key challenge lies in how to overcome these technical hurdles.

The Limits of 11β-HSD1 That Even AstraZeneca and Roche Could Not Overcome

According to industry sources on the 21st, J2H Biotech has completed a domestic Phase 2a clinical trial for its 11β-HSD1-targeted MASH treatment and is currently preparing for a Phase 2b trial. J2H Biotech is a new drug development company led by CEO Kim Jae-seon, who previously served as head of the new drug team at SKCHEMICALS(285130). In June, the company entered into a strategic partnership with SKCHEMICALS for the domestic and international development and commercialization of the MASH therapeutic candidate “J2H-1702.”

11β-HSD1, which J2H Biotech is researching, is not a new target. It is a target that global pharmaceutical companies have long focused on, investing substantial capital and conducting numerous clinical trials.

Roche is cited as a leading company that has shown interest in 11β-HSD1. Since the late 2000s, Roche has conducted extensive research targeting 11β-HSD1 for conditions such as diabetes, fatty liver disease, and ophthalmic disorders. In particular, according to the clinical trial information search website ClinicalTrials.gov, Roche advanced a candidate compound (RO5093151) to Phase 1b clinical trials for the treatment of non-alcoholic fatty liver disease (NAFLD).

The company conducted clinical trials based on the hypothesis that inhibiting cortisol production in the liver could improve fatty liver disease. While the trial results showed a reduction in liver fat content in clinical patients, adverse neurological side effects emerged, preventing the drug from progressing to the commercialization stage.

AstraZeneca also has a history of developing “AZD4017,” a therapeutic candidate targeting 11β-HSD1. Starting in the 2010s, the company identified 11β-HSD1 as a potential target for treating obesity and metabolic syndrome and conducted a Phase 1 clinical trial in patients with abdominal obesity. It also expanded its scope to include clinical trials aimed at securing other indications, such as type 2 diabetes and diabetic wound healing. However, since the company was unable to demonstrate a statistically significant difference across the entire patient population, further development did not proceed.

Focusing on the Liver to Maximize Efficacy… J2H’s Differentiation Strategy

As major global pharmaceutical and biotech companies have set their sights on 11β-HSD1 but failed to produce clear results, attention is now turning to J2H Biotech’s strategy and plans.

J2H Biotech completed a Phase 2a clinical trial in the first half of this year, involving 87 patients at risk for MASH across 11 medical institutions in South Korea. The trial divided participants into treatment groups receiving 50 mg, 100 mg, and 200 mg, and the company explained that the degree of improvement increased with higher doses.

Unlike Roche and AstraZeneca, J2H Biotech employed a method to maximize drug efficacy by concentrating the drug in the target organ—the liver. Kim Jae-seon, CEO of J2H Biotech, stated, “Previous failures in inhibiting 11β-HSD1 were not due to issues with the target itself, but rather the inability to utilize the drug efficiently,” adding, “J2H Biotech employed an approach that specifically lowers cortisol levels in liver tissue, rather than reducing cortisol in the bloodstream.”

J2H Biotech explained that when using J2H-1702, drug exposure in liver tissue is approximately 6 to 7 times higher than in the bloodstream. CEO Kim said, “While companies like Roche and AstraZeneca use a daily dose of 800 mg, our clinical results show that we can achieve sufficient efficacy with a 200 mg dose by targeting the liver.”

J2H Biotech is currently preparing for a Phase 2b clinical trial, targeting a start in the second half of next year. Judging that it would be difficult for J2H Biotech to conduct the Phase 2b trial independently, the company is currently seeking a global partner.

Will Oral Administration and Muscle Preservation Secure Competitive Edge in Commercialization

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J2H Biotech’s 11β-HSD1 inhibitor is currently being developed as an oral formulation, offering the advantage of a simpler administration method compared to existing treatments that primarily rely on injections. Furthermore, the company explains that it enables the maintenance of muscle mass and avoids side effects associated with appetite suppression.

However, since GLP-1-based MASH treatments are already being launched in oral form, and other treatments designed to reduce fat while preserving muscle mass are also in development, the key question is whether the company will be able to secure competitiveness after commercialization. In fact, Novo Nordisk launched the oral version of Wegovy in the U.S. market this past January, and Lilly introduced the oral version of Foundeo in April.

Development of treatments that preserve muscle mass is also gaining momentum. A prime example is HanmiPharm’s technology export on the 24th of its obesity treatment candidate “HM17321” to Genentech, a wholly-owned subsidiary of Roche. The total contract value is $2.305 billion (approximately 3.2 trillion won), marking the largest-ever contract in the domestic industry for a single compound, with the upfront payment alone totaling $190 million (approximately 260 billion won). Unlike GLP-1 agonists, “HM17321” is a non-incretin-based therapy that targets CRF2.

An industry official stated, “Since MASH and the obesity treatment market have emerged as the largest markets in the global industry, various candidate compounds are being developed, and research into simplifying administration methods and minimizing side effects is actively underway,” adding, “Ultimately, the key will be how well companies can control pricing during the commercialization phase to secure a leading position in the market.”