Ecnoglutide (XW003)
Ecnoglutide (XW003) is a long-acting Fc-fusion GLP-1 receptor agonist developed by Sciwind Biosciences and Gan & Lee Pharmaceuticals for obesity and type 2 diabetes, administered as a once-weekly subcutaneous injection.
Ecnoglutide (XW003) is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist developed by Sciwind Biosciences in collaboration with Gan & Lee Pharmaceuticals. It is an Fc-fusion protein in which a modified GLP-1 analogue peptide is fused to a human immunoglobulin Fc domain, conferring an extended half-life suitable for once-weekly subcutaneous dosing.
Overview
Ecnoglutide represents a growing class of Fc-fusion GLP-1 receptor agonists designed to provide potent, sustained GLP-1 receptor activation with convenient weekly dosing. The Fc-fusion approach extends the peptide's circulating half-life through FcRn-mediated recycling, increased molecular size that reduces renal clearance, and protection from proteolytic degradation. Unlike small-molecule GLP-1 analogues such as semaglutide (which achieves long half-life through fatty acid acylation and albumin binding), ecnoglutide's duration of action derives from its Fc domain.
Clinical development has been focused primarily in China, where the obesity and type 2 diabetes burden is rapidly growing. Phase 2 trial results demonstrated approximately 16% body weight loss at 24 weeks, placing ecnoglutide's efficacy in a competitive range with established GLP-1 agonists. The compound entered Phase 3 trials in China for both obesity and type 2 diabetes indications.
Sciwind Biosciences, the originating company, is a biopharmaceutical company specializing in metabolic diseases. Gan & Lee Pharmaceuticals, a major Chinese insulin manufacturer, holds co-development and commercialization rights in China and select markets.
Mechanism of Action
Ecnoglutide functions as a potent GLP-1 receptor agonist through the following interconnected pathways:
GLP-1 Receptor Activation: The GLP-1 analogue portion binds to and activates GLP-1 receptors with high affinity. The peptide sequence incorporates modifications that enhance receptor binding potency and confer resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage, the primary degradation pathway for native GLP-1.
Glucose-Dependent Insulin Secretion: Upon binding GLP-1 receptors on pancreatic beta cells, ecnoglutide stimulates cyclic AMP (cAMP) production and protein kinase A (PKA) activation, potentiating glucose-dependent insulin exocytosis. This glucose-dependent mechanism minimizes the risk of hypoglycemia.
Glucagon Suppression: Ecnoglutide suppresses glucagon secretion from pancreatic alpha cells in a glucose-dependent manner, reducing hepatic glucose output and contributing to improved glycemic control.
Central Appetite Regulation: GLP-1 receptor activation in the hypothalamus (particularly the arcuate nucleus and paraventricular nucleus) and brainstem (nucleus tractus solitarius, area postrema) reduces appetite and food intake. Ecnoglutide promotes satiety signaling, reduces meal size, and decreases food reward-seeking behavior.
Gastric Emptying Delay: Like other GLP-1 agonists, ecnoglutide slows gastric emptying, contributing to postprandial glucose stabilization and enhanced satiety. This effect is mediated through vagal afferent signaling and direct GLP-1R activation on gastric smooth muscle.
Fc-Mediated Half-Life Extension: The human IgG Fc domain engages the neonatal Fc receptor (FcRn) in endothelial cells, enabling pH-dependent binding, endosomal recycling, and release back into circulation. This recycling mechanism, combined with the increased molecular size that reduces glomerular filtration, extends the circulating half-life to approximately 5-7 days.
Reconstitution Calculator
Reconstitution Calculator
Calculate your peptide dosing
Set up a clean workspace with all supplies ready.
7x / week for weeks
Research
Phase 1 Clinical Studies
Initial Phase 1 studies of ecnoglutide evaluated safety, tolerability, and pharmacokinetics in healthy Chinese adults and patients with type 2 diabetes. Single ascending dose and multiple ascending dose cohorts demonstrated dose-proportional pharmacokinetics, a half-life consistent with once-weekly dosing, and a safety profile dominated by mild-to-moderate gastrointestinal adverse events. The Phase 1 data established the dose range for subsequent efficacy trials and confirmed the expected pharmacokinetic profile of an Fc-fusion GLP-1 agonist.
Phase 2 Type 2 Diabetes Trial
Ecnoglutide was also evaluated in a Phase 2 trial in patients with type 2 diabetes inadequately controlled on metformin. Results demonstrated significant reductions in HbA1c (up to 1.5-2.0 percentage points from baseline) and fasting plasma glucose, with concurrent weight loss. The glycemic improvements were consistent with the known effects of GLP-1 receptor agonism on insulin secretion, glucagon suppression, and hepatic glucose output.
Comparison with Established GLP-1 Agonists
The approximately 16% weight loss at 24 weeks positions ecnoglutide's efficacy favorably relative to other once-weekly GLP-1 agonists. For context, semaglutide 2.4 mg achieved approximately 14.9% weight loss at 68 weeks in the STEP 1 trial, and tirzepatide achieved up to 22.5% at 72 weeks in the SURMOUNT-1 trial. Direct comparisons require caution due to differences in trial populations, duration, and BMI entry criteria, but ecnoglutide's 24-week results suggest strong efficacy that could increase with longer treatment duration.
Fc-Fusion GLP-1 Agonist Class
Ecnoglutide is part of a broader class of Fc-fusion GLP-1 agonists under development globally. Dulaglutide (Trulicity), an approved GLP-1 agonist, also uses an Fc-fusion approach but with lower GLP-1R agonist potency. Ecnoglutide's modified GLP-1 sequence is designed for enhanced receptor affinity compared to dulaglutide, potentially explaining the superior weight loss observed in clinical trials.
Phase 2 Obesity Trial
The Phase 2 randomized, double-blind, placebo-controlled trial evaluated multiple doses of ecnoglutide in adults with obesity (BMI >=28 kg/m2 by Chinese criteria, or >=24 kg/m2 with at least one weight-related comorbidity) over 24 weeks. Results showed dose-dependent weight loss, with the highest dose group achieving approximately 16% mean body weight reduction at 24 weeks compared to approximately 2% in the placebo group. The magnitude of weight loss was considered clinically meaningful and competitive with other GLP-1 agonists in the same treatment duration. Weight loss was progressive throughout the treatment period, with no plateau observed at 24 weeks, suggesting further weight reduction with continued treatment. Wang, L. et al. (2024) — Lancet Diabetes Endocrinol.
Safety Profile
Ecnoglutide's safety profile is consistent with the GLP-1 receptor agonist class. In Phase 2 trials, the most commonly reported adverse events were gastrointestinal: nausea (20-30%), diarrhea (10-15%), vomiting (8-12%), and decreased appetite (10-20%). These events were predominantly mild to moderate in severity, dose-related, and most frequent during the initial weeks of treatment or during dose escalation. The incidence of GI adverse events generally decreased over time as patients adapted to treatment.
No cases of pancreatitis were reported in Phase 2 trials, though the sample sizes were limited. No thyroid neoplasms were observed. Injection site reactions were uncommon and mild. Hypoglycemia was rare in patients not receiving concurrent insulin or sulfonylureas. Immunogenicity assessments revealed low rates of anti-drug antibody (ADA) formation, with no neutralizing antibodies detected that impacted efficacy or safety. The Fc-fusion design may confer advantages in immunogenicity profile compared to PEGylated or acylated peptide approaches.
Longer-term safety data from Phase 3 trials will be essential for characterizing the full safety profile, including rare events such as gallbladder disease, pancreatitis, and potential thyroid effects.
Clinical Research Protocols
- Dosing (obesity): Dose escalation from lower doses (e.g., 0.6 mg) up to target doses of 3.0-4.5 mg subcutaneously once weekly, with escalation steps every 4 weeks to improve gastrointestinal tolerability.
- Dosing (type 2 diabetes): 0.3-3.0 mg subcutaneously once weekly, with dose titration based on glycemic response and tolerability.
- Key trials: Phase 2 obesity (NCT05294822), Phase 2 T2D, Phase 3 trials initiated in China (2024).
- Duration: Phase 2 obesity trial: 24 weeks treatment. Phase 3 trials: 52-72 weeks planned.
- Routes: Subcutaneous injection only. Pre-filled syringe or autoinjector formulations under development.
Subpopulation Research
- Chinese obesity population: Primary development population. Chinese BMI criteria (overweight >=24, obesity >=28 kg/m2) differ from Western criteria. Phase 2 demonstrated ~16% weight loss at 24 weeks.
- Type 2 diabetes on metformin: Phase 2 demonstrated significant HbA1c reductions (1.5-2.0 percentage points) with concurrent weight loss.
- Non-Chinese populations: Global clinical development has been discussed but trials outside China are at earlier stages.
- Elderly/renal impairment: Dedicated studies in special populations are anticipated as the program advances.
Pharmacokinetic Profile
Ecnoglutide (XW003) — Pharmacokinetic Curve
Subcutaneous injection (once weekly)Ongoing & Future Research
- Phase 3 obesity trials (China): Pivotal trials in Chinese adults with obesity, targeting regulatory approval by NMPA (China's National Medical Products Administration).
- Phase 3 diabetes trials: Pivotal T2D trials with active comparators (likely semaglutide or dulaglutide).
- Global expansion: Potential clinical development outside China in partnership with additional pharmaceutical companies.
- Long-term weight maintenance: Evaluation of sustained weight loss and metabolic benefits beyond 52 weeks.
- Cardiovascular outcomes: A cardiovascular outcome trial (CVOT) will likely be required for regulatory approval in certain indications and markets.
- Combination therapies: Potential evaluation with SGLT2 inhibitors, insulin, or other metabolic agents.
- Head-to-head studies: Comparisons with semaglutide, tirzepatide, or other GLP-1 agonists to establish relative positioning.
- NASH/MASH: Given the established benefits of GLP-1 agonists in fatty liver disease, evaluation in NASH/MASH populations is a natural extension.
Quick Start
- Route
- Subcutaneous injection (once weekly)
Molecular Structure
- Formula
- Proprietary (Fc-fusion protein)
- CAS
- 2566535-08-2
Research Protocols
subcutaneous Injection
It is an Fc-fusion protein in which a modified GLP-1 analogue peptide is fused to a human immunoglobulin Fc domain, conferring an extended half-life suitable for once-weekly subcutaneous dosing. Clinical Research Protocols - Dosing (obesity): Dose escalation from lower doses (e.g., 0.6 mg) up to tar
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Dosing (obesity) | 0.6 mg, 3.0-4.5 mg | Once weekly | 4 weeks(Route: Subcutaneous Injection) |
| Dosing (type 2 diabetes) | 0.3-3.0 mg | Once weekly | —(Route: Subcutaneous Injection) |
| NASH/MASH | See literature | Once weekly | — |
Interactions
Peptide Interactions
The approximately 16% weight loss at 24 weeks positions ecnoglutide's efficacy favorably relative to other once-weekly GLP-1 agonists. For context, semaglutide 2.4 mg achieved approximately 14.9% weight loss at 68 weeks in the STEP 1 trial, and tirzepatide achieved up to 22.5% at 72 weeks in the ...
What to Expect
What to Expect
Levels begin building after first administration; half-life of ~5-7 days (estimated from once-weekly dosing) means steady state reached over week 4-6
Dosing (obesity): Dose escalation from lower doses (e.g., 0.6 mg) up to target doses of 3.0-4.
Results showed dose-dependent weight loss, with the highest dose group achieving approximately 16% mean body weight reduction at 24 weeks compared to...
Phase 3 trials: 52-72 weeks planned.
Continued use as directed
Quality Indicators
What to look for
- Phase 3 clinical trial data available
Caution
- Short half-life may require frequent dosing
- Injection site reactions reported
Frequently Asked Questions
References (3)
- [2]Zhang, Y. L. et al Efficacy, safety and immunogenicity of ecnoglutide in adults with type 2 diabetes Diabetes Obes. Metab. (2023)
- [1]Wang, L. et al Efficacy and safety of ecnoglutide (XW003) for weight management in adults with obesity Lancet Diabetes Endocrinol. (2024)
- [3]Gao, F. et al XW003 (ecnoglutide), a novel long-acting GLP-1 receptor agonist: Phase 1 trial Diabetes Obes. Metab. (2023)
Dynorphin A
Dynorphin A is a 17-amino acid endogenous opioid peptide derived from prodynorphin that acts primarily as a kappa-opioid receptor (KOR) agonist, with research applications in pain modulation, stress responses, addiction neurobiology, and mood disorders.
EGF (Epidermal Growth Factor)
EGF is a 53-amino acid polypeptide that binds the EGF receptor to stimulate cell proliferation, differentiation, and survival, with applications in wound healing and anti-aging skincare.