[Edaily Reporter YU JIN-HEE ] Ensol Biosciences has discovered the key to solving the “yo-yo effect” in obesity treatments—a problem long considered a major challenge in the global pharmaceutical and biotech industries. Having recently elucidated the precise mechanism of action following confirmation of its efficacy, the company is expected to see a surge in technology exports.

Oral Obesity Treatment H1K: Technology Transfer Discussions Underway with Global Companies

According to industry sources on the 8th, Ensol Bio has been confirmed to be engaged in concrete technology transfer (L/O) negotiations with leading global pharmaceutical and biotech companies regarding “H1K,” an innovative oral obesity treatment candidate.

These negotiations are a follow-up to the disclosure last year of data on combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1RA, hereinafter GLP-1). At that time, the global big pharma company noted the drug’s outstanding weight loss and yo-yo effect prevention efficacy but presented a technical challenge: to elucidate the precise molecular biological mechanism of action. After Ensol Bio successfully elucidated the mechanism of action following approximately 10 months of research, the negotiations—which had stalled—are now gaining momentum.

The key competitive advantage of H1K, as revealed by NGeneBio Co., Ltd.’s research team, is its ability to perform “dual-target regulation” in response to acidity (pH). H1K is a short peptide consisting of nine amino acids. Research findings showed that H1K exhibits a unique characteristic: it autonomously detects changes in the acidity of its surrounding environment and adjusts its binding targets and activity accordingly. In highly acidic environments, such as the gastrointestinal tract (pH 2–5), it bound as an agonist to the insulin-like growth factor receptor (IGF-1R)—a metabolic regulatory pathway—and induced its activity.

In contrast, in neutral environments such as blood and liver tissue (pH approximately 7.4), its binding affinity for IGF-1R decreased sharply. Instead, it bound to cell differentiation cluster 28 (CD28), which is involved in obesity-induced inflammation and immune responses, and acted as a partial antagonist. In effect, it functions as a molecular switch that changes its function depending on its route of transport within the body. Results from actual protein binding assays (MST) and cellular assays showed that while it did not stimulate the IGF-1R in a normal neutral environment, it selectively activated the receptor in an acidic environment with a pH of 3.5, similar to that inside the stomach.

At the same time, it resolved the issue of digestive stability, which has long been a chronic limitation of oral protein formulations. H1K retained more than 98% of its original structure even after 30 minutes in strongly acidic conditions at a pH of 3. It also demonstrated stability by remaining intact even after a stress test involving three hours of treatment with pepsin, a potent proteolytic enzyme. This fully validated its potential as an oral formulation capable of safely passing through the gastrointestinal tract and being absorbed.

The fundamental reason global pharmaceutical companies are showing such strong interest in H1K is that it can address the critical limitations of existing GLP-1 drugs. Products currently dominating the market, such as Novo Nordisk’s “Wegovy” and Eli Lilly’s “Zepbound,” boast excellent weight-loss effects. However, they are criticized for frequent gastrointestinal side effects—such as nausea and vomiting—and a critical weakness: a rapid weight rebound, where most of the weight lost is regained within a year after discontinuing the medication.

In animal efficacy trials conducted by Ensol Bio, the GLP-1 monotherapy group experienced a 17% weight loss at the 4-week mark, while the GLP-1 combined with H1K group achieved a 26% reduction, demonstrating superior synergy. Magnetic resonance imaging (MRI) results showed that most of the weight loss was attributable to a reduction in visceral abdominal fat.

The decisive difference became apparent after treatment was discontinued. Three weeks after discontinuing the medication, the GLP-1 monotherapy group maintained only a 2% weight loss, with most of the weight returning to its original level. In contrast, the H1K combination therapy group maintained a 13% weight loss, demonstrating strong yo-yo effect suppression.

Furthermore, in a mouse model fed a high-fat diet, H1K prevented fat accumulation in liver tissue and significantly lowered blood cholesterol levels. This indicates the potential to expand the treatment scope to include metabolic and fatty liver disease (MASLD), a condition commonly associated with obesity.

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Industry observers predict that this elucidation of the mechanism of action will serve as a key catalyst for a major technology export deal worth trillions of won. The global obesity treatment market is a massive market projected to exceed $100 billion (approximately 134 trillion won) by 2030, recording an average annual growth rate in the double digits.

Ensol Bio already has a proven track record in technology transfers. “P2K (SB-01),” a treatment for degenerative lumbar disc disease that was exported via Yuhan to U.S.-based Spine Biopharma, is currently undergoing procedures to resume Phase 3 clinical trials in the U.S. in the second half of the year. “E1K,” a treatment for knee osteoarthritis, is also progressing smoothly, having secured a 100 billion won contract for domestic rights and completed the enrollment of the first patient in its Phase 3 clinical trial.

In addition, the company plans to achieve significant overseas success in the metabolic disease sector—an area with high unmet medical needs—led by ‘H1K.’ If a technology export deal worth trillions of won with a major global pharmaceutical company is finalized, the company will be able to completely break free from its long-standing pattern of chronic losses.

This is also expected to serve as a decisive positive factor in the technology evaluation required for the company’s transfer listing from KONEX to KOSDAQ. Alteogen Inc.(196170) The fact that Hyung In-woo, CEO of Smart & Growth and the company’s largest shareholder—who played a key role in its early success—recently participated in a third-party private placement worth 5 billion won, providing a total of 65 billion won in funding, serves as a solid foundation that enhances the company’s negotiating power.

Kim Hae-jin, CEO of Ensol Bio, stated, “Following our confirmation of the drug’s efficacy in suppressing the yo-yo effect that occurs after discontinuing GLP-1 treatment, we have now, for the first time in the world, fully verified the pH-dependent dual-target regulation mechanism of H1K.” He added, “Based on this scientific data, we will rapidly advance technology transfer negotiations with global partners to prove our worth to the market.”