Zhongsheng Pharma’s RAY1225 Achieves 22.2% Weight Loss in Phase III REBUILDING‑2 Trial – Biweekly GLP‑1/GIP Dual Agonist Outperforms Tirzepatide Response Rates on Key Thresholds

Guangdong Zhongsheng Pharmaceutical Co., Ltd. (SHE: 002317) announced positive topline results from its Phase III REBUILDING‑2 clinical trial evaluating RAY1225 Injection (Bilpatide Injection), a first‑in‑class dual GLP‑1/GIP receptor agonist with every‑two‑weeks (Q2W) dosing, in 641 overweight or obese Chinese adults – with the 9 mg dose group achieving 22.24% body weight reduction at 52 weeks, 99.3% of participants achieving ≥5% weight loss, and 82.1% achieving ≥15% weight loss, numerically surpassing corresponding response rates reported by tirzepatide in the SURMOUNT‑CN trial.

Regulatory Milestone

Item	Detail
Product	RAY1225 Injection (Bilpatide Injection / 倍尔泊肽注射液)
Drug Class	Category 1 innovative peptide drug; dual GLP‑1/GIP receptor agonist
Trial	REBUILDING‑2 – Phase III, multicenter (50 sites), randomized, double‑blind, placebo‑controlled
Enrollment	641 participants (overweight/obese Chinese adults)
Dosing	3 mg, 6 mg, 9 mg or placebo; every two weeks (Q2W) for 52 weeks
Primary Endpoints	(1) % body weight change from baseline at Week 52; (2) proportion achieving ≥5% weight loss at Week 52
Result	Both primary endpoints met – statistically significant across all dose groups (P<0.0001)
Weight Loss Plateau	Not reached at Week 52 – continued decline observed
Intellectual Property	Global IP rights held by Zhongsheng Ruichuang (subsidiary)
Diabetes Indication	Phase III for type 2 diabetes actively ongoing
Next Steps	Regulatory communication with NMPA; NDA filing planned at earliest opportunity

Drug Profile & Mechanism of Action

• Molecule: RAY1225 (Bilpatide) – a novel‑structure innovative peptide with global independent intellectual property rights, developed by Guangdong Zhongsheng Ruichuang Biotechnology Co., Ltd. (“Zhongsheng Ruichuang”), a majority‑owned subsidiary of Zhongsheng Pharma
• Dual Target: GLP‑1 receptor and GIP receptor – co‑agonism of both incretin pathways, leveraging synergistic effects on appetite suppression, gastric emptying, insulin secretion, and energy expenditure
• Dosing Innovation: Thanks to superior pharmacokinetic properties, RAY1225 demonstrates ultra‑long‑acting potential with every‑two‑weeks (Q2W) subcutaneous injection – offering a meaningful convenience advantage over currently marketed GLP‑1/GIP therapies that require weekly (semaglutide, tirzepatide) or daily (liraglutide) dosing
• Competitive Differentiation: Among all GLP‑1/GIP dual agonists in clinical development globally, RAY1225 is one of the few designed for biweekly dosing, potentially reducing annual injection burden from 52 (weekly) to 26 (biweekly) – a significant patient adherence and quality‑of‑life advantage

Clinical Evidence – Phase III REBUILDING‑2 Trial

Study Design

• Centers: 50 clinical trial sites across China
• Population: 641 overweight or obese Chinese adults
• Randomization: RAY1225 3 mg, 6 mg, 9 mg, or placebo; Q2W dosing for 52 weeks
• Primary Analysis: Treatment‑policy strategy (intention‑to‑treat)
• Supplementary Analysis: Hypothetical strategy

Primary Efficacy Results – Body Weight Change at Week 52

Endpoint	RAY1225 3 mg	RAY1225 6 mg	RAY1225 9 mg	Placebo
Weight Reduction from Baseline	Not disclosed	Not disclosed	22.24 %	~1.8 % (implied)
Placebo‑Adjusted Weight Reduction	11.23 %	17.42 %	20.46 %	–
P‑value (vs. placebo)	P<0.0001	P<0.0001	P<0.0001	–

Supplementary Analysis (Hypothetical Strategy) – 9 mg Group
Weight Reduction from Baseline	22.30 %
Placebo‑Adjusted Weight Reduction	20.50 %
P‑value	P<0.0001

Weight Loss Response Rates – 9 mg Group vs. Tirzepatide SURMOUNT‑CN

Response Threshold	RAY1225 9 mg (Q2W, 52 wk)	Tirzepatide 15 mg (QW, 52 wk, SURMOUNT‑CN)
≥5 % weight loss	99.3 %	85.8 %
≥15 % weight loss	82.1 %	61.4 %
≥20 % weight loss	53.8 %	Not disclosed

Note: Cross‑trial comparisons should be interpreted with caution due to differences in study design, population characteristics, and analytical methods. The company presented these numerical comparisons for informational context.

Key Secondary Endpoints – Cardiometabolic Improvements

RAY1225 demonstrated dose‑dependent, statistically significant improvements (P<0.0001 vs. placebo) across multiple cardiovascular and metabolic risk factors:

Parameter	Result
Waist Circumference	Dose‑dependent reduction; significant vs. placebo (P<0.0001)
Blood Pressure	Dose‑dependent reduction; significant vs. placebo
Triglycerides	Dose‑dependent reduction; significant vs. placebo
LDL Cholesterol	Dose‑dependent reduction; significant vs. placebo
Serum Uric Acid	Dose‑dependent reduction; significant vs. placebo
Liver Fat Content	Dose‑dependent reduction; significant vs. placebo
Visceral Fat Content	Dose‑dependent reduction; significant vs. placebo

Safety Profile

Safety Parameter	Result
Overall Safety	Good safety and tolerability; consistent with prior RAY1225 trials and GLP‑1 class profile
Hypoglycemia Risk	Low
New Safety Signals	None identified
Most Common AEs	Gastrointestinal (GI)‑related adverse events
GI AE Severity	Mostly mild
GI AE Rates vs. Tirzepatide	Diarrhea, nausea, vomiting, and constipation rates numerically lower than or comparable to tirzepatide SURMOUNT‑CN reported values

Clinical Context – Obesity Therapeutics Landscape

Drug	Mechanism	Dosing Frequency	Phase III Weight Loss (China Population)
Semaglutide 2.4 mg (Wegovy)	GLP‑1 RA	Weekly (QW)	~15–17 % (STEP trials)
Tirzepatide 15 mg (Zepbound)	GLP‑1/GIP dual agonist	Weekly (QW)	~19–20 % (SURMOUNT‑CN)
RAY1225 9 mg (Bilpatide)	GLP‑1/GIP dual agonist	Biweekly (Q2W)	22.24 % (REBUILDING‑2)
Survodutide	GLP‑1/glucagon dual agonist	Weekly (QW)	Phase III ongoing

The GLP‑1/GIP dual agonist class has emerged as the most efficacious pharmacological approach to obesity, with tirzepatide setting the current efficacy benchmark. RAY1225’s Phase III data suggest that biweekly dosing does not compromise efficacy – and may in fact deliver numerically superior weight loss and response rates – while offering a 50% reduction in injection frequency compared to weekly alternatives.

Market Impact & Outlook

• China Obesity Market: China has the world’s largest overweight and obese population by absolute numbers, with an estimated 500+ million adults classified as overweight or obese. The obesity pharmacotherapy market is in its early commercialization phase, with GLP‑1‑based therapies just beginning to penetrate the Chinese market at scale.
• Biweekly Dosing Advantage: RAY1225’s Q2W dosing represents a first‑in‑class convenience advantage among GLP‑1/GIP dual agonists. In a market where injection burden is a key barrier to patient adoption and long‑term adherence, reducing annual injections from 52 to 26 could drive meaningful patient preference, adherence, and persistence advantages.
• Efficacy Benchmark: The 22.24% body weight reduction at 52 weeks (9 mg group) and the 99.3% ≥5% response rate position RAY1225 among the most efficacious GLP‑1/GIP therapies reported in Chinese Phase III populations, providing a strong competitive narrative against imported alternatives.
• Cardiometabolic Pleiotropic Benefits: The broad improvements in blood pressure, lipids, uric acid, liver fat, and visceral fat extend RAY1225’s value proposition beyond cosmetic weight loss into comprehensive cardiometabolic risk reduction – a positioning that aligns with evolving regulatory expectations for obesity drugs to demonstrate cardiovascular outcome benefits.
• Diabetes Indication Pipeline: A Phase III trial for type 2 diabetes is actively ongoing, providing a potential dual‑indication (obesity + T2D) commercial platform that mirrors the franchise model of semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound).
• NDA Filing Timeline: Zhongsheng Pharma stated it will actively engage with regulatory authorities to pursue early NDA submission. Complete efficacy and safety results will be finalized in the clinical study report (CSR); topline data represent preliminary statistical analysis.
• Financial Impact: The company stated that the topline results will not have a material impact on near‑term financial performance, consistent with the pre‑commercial development stage.

Forward‑Looking Statements
This brief contains forward‑looking statements regarding the clinical outcomes, regulatory trajectory, and commercial potential of RAY1225 Injection in obesity and type 2 diabetes. Topline Phase III results represent preliminary analysis and may differ from final clinical study report findings. Actual outcomes may differ due to risks including regulatory review results, NDA filing and approval timelines, competitive dynamics, pricing and reimbursement decisions, and the inherent uncertainties of pharmaceutical commercialization.-Fineline Info & Tech