A Best-in-Class Oral Small-Molecule GLP-1 Receptor Agonist with Superior Weight Loss and Appetite Suppression Efficacy | PharmaTimes BD Opportunity

On August 7, 2025, Eli Lilly reported its second-quarter financial results, which exceeded expectations, and raised its full-year guidance. Its flagship product, tirzepatide, is poised to become the world’s top-selling drug this year. However, the market response was unexpected: Lilly’s stock plummeted 14% that day, erasing approximately $100 billion in market value. This counterintuitive divergence—strong financials coupled with a sharp stock decline—was primarily driven by underwhelming Phase III clinical data for orforglipron, its investigational oral small-molecule GLP-1 receptor agonist, which appears to lag behind semaglutide in efficacy. Although no head-to-head data are available, the perceived efficacy gap has triggered investor concerns, highlighting the immense market expectations for oral GLP-1-based weight management therapies.

Oral GLP-1 receptor agonists offer compelling commercial advantages due to their convenient administration, lower manufacturing costs, and potential for broader patient adoption. They are well-positioned to penetrate markets inaccessible to injectable formulations and are expected to become the next-generation standard of care in metabolic disease management.

In this context, numerous Chinese biopharmaceutical innovators are actively advancing their pipelines in the oral small-molecule GLP-1 space, achieving several high-profile licensing deals:

• In November 2023, Chengyi Bio licensed its oral small-molecule GLP-1 receptor agonist, ECC5004, to AstraZeneca with a potential deal value of up to $2.01 billion. Optimized from Eli Lilly’s orforglipron scaffold, ECC5004 demonstrates significantly improved oral bioavailability and is being developed for obesity, type 2 diabetes (T2D), and related comorbidities.
• Hansoh Pharma has also made rapid progress. Its internally developed oral GLP-1 receptor agonist, HS10535, was licensed to Merck & Co. in late 2024, securing an upfront payment of $112millionandpotentialmilestonepaymentsofupto$1.9 billion—underscoring global recognition of China’s growing innovation capacity in drug discovery.

Recent developments highlight significant momentum in China’s oral GLP-1 pipeline:

• On July 15, 2025, Hengrui Medicine announced successful Phase III trial results for HRS9531, a dual GLP-1/GIP receptor agonist. The company has submitted a New Drug Application (NDA), marking the transition toward commercialization. Concurrently, Hengrui is advancing its oral small-molecule GLP-1 program, HRS-7535, which has successfully mitigated the hepatotoxicity risks previously observed with Pfizer’s danuglipron, and is accelerating its global development strategy for weight management.
• On July 22, 2025, Huadong Medicine’s wholly-owned subsidiary, Sinopharm Huadong, announced that its self-developed oral small-molecule GLP-1 receptor full agonist, HDM1002, received FDA clearance for clinical trials in the U.S., intended for weight management in individuals with overweight or obesity. Data from China-based Phase I and II trials in over 800 subjects showed that the 100 mg and higher dose cohorts achieved mean weight reductions of 4.9% to 6.8% over 28 days, with favorable safety and tolerability profiles.
• Shortly thereafter, on August 5, 2025, Innovent Biologics announced FDA IND clearance for IBI3032, its novel oral small-molecule GLP-1 receptor agonist. The compound exerts its effects through potent and selective activation of the GLP-1 receptor, triggering downstream signaling cascades that delay gastric emptying, suppress appetite, and enhance glucose-dependent insulin secretion—making it a promising candidate for the treatment of obesity and type 2 diabetes.

Additionally, companies such as Rigor Medicines, DerE Digital Therapeutics, Haisco Pharmaceutical, Xinyi Pharmaceutical, and GlobeImmune are actively advancing their programs, with candidates at various stages of clinical development.

As the global prevalence of obesity and type 2 diabetes continues to rise, GLP-1 receptor agonists are undergoing a paradigm shift—from injectable to oral formulations. The convergence of enhanced convenience and robust efficacy is driving this therapeutic class toward even broader clinical and commercial potential. The Chinese market, in particular, represents a high-growth opportunity with vast unmet medical needs.

Currently, the PharmaTimes Business Development (BD) team is seeking strategic partners for a best-in-class oral small-molecule GLP-1 receptor agonist with superior weight loss and appetite suppression effects.

Project Overview

• Project Code: DT-20250717-078
• Project Title: An Oral Small-Molecule GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes and Obesity
• Indications: Type 2 Diabetes (T2D), Obesity
• Drug Class: Small Molecule
• Target: Glucagon-Like Peptide-1 Receptor (GLP-1R)
• Development Stage: Preclinical Candidate (PCC)

Key Advantages:

1. Exceptional oral pharmacokinetic (PK) profile with high bioavailability and sustained exposure.
2. Best-in-class efficacy in body weight reduction and appetite suppression in preclinical models.
3. Potent glucose-lowering effects at ultra-low doses, enabling low-dose regimens.
4. Favorable safety and tolerability profile with a wide therapeutic index.
5. Low risk of CYP450 inhibition, hepatotoxicity, and no evidence of genotoxicity in standard preclinical assays.

Partnership Opportunity: License-out, global or regional collaboration, co-development.

For further information or to initiate discussions, please contact the PharmaTimes BD team.

Contact us:

For any questions, please contact DrugTimes BD Team at BD@drugtimes.cn, please include Project ID in the subject. Many thanks!