Ecnoglutide (XW003)

Ecnoglutide’s core differentiation comes from bias toward the cAMP signaling pathway. Conventional GLP-1 receptor agonists trigger two downstream pathways simultaneously after activating the receptor: the Gαs/cAMP pathway (mediating therapeutic effects) and the β-arrestin pathway (causing receptor internalization and signal termination). Through molecular design, ecnoglutide selectively enhances cAMP signaling and weakens β-arrestin recruitment, keeping the receptor on the cell surface longer.

Clinical significance: reducing gastrointestinal adverse reactions at equivalent glucose-lowering and weight-loss potency. In the SLIMMER trial the discontinuation rate due to AEs was only 2.0%, far below the 4.3%–7.0% of the STEP series. Notably, tirzepatide also shows cAMP bias at the GLP-1 receptor, which is thought to be one of the mechanisms behind its efficacy advantage over semaglutide.

SLIMMER (NCT05813795) is the pivotal registration Phase 3, led by Professor Ji Linong at 36 centers in China with 664 patients randomized, published in Lancet Diabetes Endocrinol 2025;13(9):777-789. Eligibility: non-T2D adults with BMI ≥28, or ≥24 with comorbidities; mean baseline weight 91.3 kg, BMI 32.5.

SLIMMER 48-week body weight change data:

3.1 EECOH-1: placebo-controlled Phase 3

32 centers, 211 T2DM patients, 24 weeks. HbA1c reduction in the 1.2 mg arm was -2.43% (placebo -0.87%), with 76.1% reaching HbA1c ≤6.5% and discontinuation due to AEs of only 1.4%. Published in Nat Commun 2026;17:1420.

3.2 EECOH-2: head-to-head Phase 3 against dulaglutide

52 centers, 621 patients in the FAS, 52 weeks, open-label. This is the most valuable head-to-head comparison:

EECOH-2 HbA1c reduction at Week 32:

On weight, reductions in the ecnoglutide arms were -5.2% to -5.7%, about twice that of the dulaglutide arm (-2.8%). Published in Lancet Diabetes Endocrinol 2025;13(10):863-873.

4.1 Core deal terms

4.2 Pfizer’s strategic logic

4.3 Sciwind’s urgency

As of the end of June 2025, book cash was only RMB 780 million, with ordinary share redemption liabilities of RMB 2.923 billion. No in-house sales team, relying entirely on Pfizer to execute commercialization. It has filed twice for a Hong Kong IPO (Morgan Stanley + CICC as joint sponsors), refiling its prospectus on March 24, 2026.

5.1 Six-way competitive matrix

5.2 The price war breaks out in full

5.3 Ecnoglutide’s three pillars of differentiation

First, the tolerability advantage from the biased mechanism — a discontinuation rate due to AEs of 2.0% vs 7.0% for semaglutide, appealing to GI-sensitive patient groups; second, Pfizer China’s commercial execution — a medical promotion network built up over the long term in core endocrinology/metabolism departments; third, room for differentiated pricing as a Class 1 innovative drug. But the absolute weight loss of -15.4% at 48 weeks is weaker than tirzepatide’s -22.5% (72 weeks), and the latter is already on the NRDL.

Preliminary results from the Australian Phase 1 of the oral formulation XW004: 30 mg daily for 6 weeks reduced body weight by 6.8%. The China oral Phase Ib/IIa trial (NCT07243171) had not yet started recruiting as of April 2026, and launch is still 5–7+ years away.

Full R&D pipeline

Commercialized: XW003 injectable (T2D + weight management); Phase 1: XW004 oral peptide · XW014 oral small molecule; IND: XW015 injectable amylin · XW016 oral amylin; Preclinical: XW019 once-monthly injection · XW020 next generation without muscle loss.