Sunho Biologics has registered a first-in-human Phase I clinical trial for ISH0688, a recombinant human IgG1 Fc-FGF21 fusion protein targeting hypertriglyceridemia and metabolic-associated steatotic liver disease. The trial, registered in April 2026 and set to begin enrolment at a site in Luoyang, China, marks the clinical debut of a molecule that appears to have been developed internally by Sunho Biologics (HKEx: 2898.HK) using the company's Armed ImmunoCytokine (AIC) Fc-fusion protein platform. While Sunho's pipeline has historically concentrated on oncology and autoimmune disease, ISH0688 represents an expansion into cardiometabolic medicine, entering the long-acting FGF21 agonist class.
The Phase I study is randomized, double-blind, and placebo-controlled, enrolling up to 104 participants across two sequential parts. Part 1 administers single-ascending doses to healthy volunteers aged 18–65 with normal fasting triglycerides, while Part 2 moves to multiple-ascending doses in adults aged 18–75 with confirmed hypertriglyceridemia, defined by fasting triglycerides at or above 2.3 mmol/L (200 mg/dL). ISH0688 is administered subcutaneously at dose levels of 75, 150, 300, and 600 mg on a Q4W schedule. Primary endpoints cover safety and tolerability, with primary completion expected by Q1 2027.
The FGF21 development rationale
The biological case for FGF21 as a metabolic target rests on its role as an endocrine regulator of lipid and glucose homeostasis. Endogenous FGF21 acts through the FGFR1c/β-Klotho receptor complex expressed on hepatocytes, adipocytes, and hypothalamic neurons. Signalling through this complex activates RAS-MAPK and PI3K-AKT cascades, suppressing hepatic de novo lipogenesis via SREBP-1c downregulation, reducing VLDL-triglyceride secretion, promoting fatty acid oxidation through PGC-1α, and upregulating adiponectin in adipose tissue. The net effect is a coordinated reduction in circulating triglycerides, liver fat, and insulin resistance — a profile directly relevant to both severe hypertriglyceridemia and MASLD.
Native FGF21 has a plasma half-life of roughly one to two hours, making it unsuitable for therapeutic use without structural modification. Fusing the FGF21 moiety to an IgG1 Fc domain substantially extends half-life and enables subcutaneous delivery on a monthly schedule, which is the engineering logic underlying ISH0688 and its closest structural analogue, efruxifermin (Akero Therapeutics). The foundational Fc-FGF21 engineering work was published by Amgen researchers in 2012 and subsequently developed into efruxifermin through Akero's exclusive licence. Sunho's ISH0688 appears to represent an independently engineered proprietary variant of this class, built on the same published pharmacological and structural principles but developed within Sunho's own platform without any disclosed third-party licence.