New GLP-1 Players Emerge + AI Drug Discovery Accelerates—How Custom Synthesis Meets the Dual Surge in Demand
I. GLP-1 Landscape: From a Single Player to a Crowded Field
July 2026 has brought a dense wave of milestones for oral small-molecule GLP-1 receptor agonists.
On July 7, Hengrui Medicine announced positive topline results from its Phase III HARBOR-1 trial of HRS-7535, an oral small-molecule GLP-1 receptor agonist, in Chinese adults with obesity or overweight. The HARBOR-1 trial enrolled 556 obese adults with a mean baseline weight of 94.1 kg. At week 44, the 180 mg dose group achieved a mean weight reduction of 10.9% from baseline, with continued improvement to 11.1% at week 50. Based on the efficacy estimand, the 120 mg and 180 mg dose groups achieved weight reductions of 9.5% and 10.9% at week 44, respectively, compared with 2.5% in the placebo group. Additionally, 58.6% (120 mg group) and 68.2% (180 mg group) of participants achieved ≥5% weight loss. Based on these results, Hengrui plans to submit a new drug application for HRS-7535 for weight management in China this year.
On July 16, Ascletis Pharma announced that the U.S. FDA has cleared its IND application for ASC30, an oral small-molecule GLP-1 receptor agonist, to initiate a Phase III clinical trial in the U.S., with expected completion by July 2028. This marks the second oral small-molecule GLP-1 weight-loss drug to enter the clinical冲刺 phase, following Eli Lilly's orforglipron (brand name Foundayo), which was approved in April this year. Model predictions indicate that ASC30 could achieve 15% weight loss at week 72, outperforming orforglipron's 11.5%. Top-line results from the Phase II study showed that at week 13, the 20 mg, 40 mg, and 60 mg maintenance doses achieved placebo-adjusted weight reductions of 5.4%, 7.0%, and 7.7%, respectively, with a favorable safety profile.
Additionally, on July 15, Ascletis announced the selection of a fixed-dose combination of ASC48, an oral small-molecule GIPR agonist, and ASC30 (ASC30_48 FDC) for clinical development, targeting a "once-daily, one-pill" oral obesity therapy. ASC48 was discovered using structure-based AI-assisted drug discovery technology and demonstrated superior agonistic activity compared to tirzepatide in head-to-head human GIPR cAMP activation assays (EC50 = 1 pM for ASC48 vs 3 pM for tirzepatide). In head-to-head non-human primate studies, the fixed-dose combination achieved 10.5% weight loss over 8 days of continuous dosing, representing approximately 52% greater efficacy compared to ASC30 monotherapy. The ASC30_48 FDC is expected to file an IND with the FDA in Q4 2026.
Meanwhile, Eli Lilly's Phase III ACHIEVE program for orforglipron continues to generate data. The ACHIEVE-2 trial demonstrated that orforglipron achieved superior A1C reduction compared to the SGLT2 inhibitor dapagliflozin. The ACHIEVE-5 trial showed that orforglipron added to basal insulin significantly reduced A1C with clinically meaningful weight loss. The ACHIEVE-4 trial confirmed orforglipron's long-term cardiovascular safety: compared with insulin glargine, orforglipron demonstrated a 16% reduction in major adverse cardiovascular events (HR = 0.84), with A1C reductions of -1.6% vs -1.0% and weight loss of -8.8%.
II. AI Drug Discovery: From Concept Validation to Phase III
On July 7–8, Insilico Medicine announced the initiation of a Phase III clinical trial for Rentosertib (ISM001-055). This is the first drug candidate whose target was discovered and molecule designed by AI to reach Phase III, for the treatment of idiopathic pulmonary fibrosis. The Phase III trial is a randomized, double-blind, placebo-controlled study expected to enroll 320 patients across 47 centers in China. In the Phase IIa study, the 60 mg once-daily arm demonstrated a mean forced vital capacity improvement of 98.4 mL at 12 weeks.
Industry observers have recognized 2026 as the most data-dense year for AI pharma, with over a dozen AI-discovered or AI-optimized drugs advancing into Phase III trials simultaneously. Since 2021, Insilico has nominated 31 preclinical candidates, with 13 having achieved IND clearance.
III. The Convergence of Two Trends: The Strategic Value of Custom Synthesis Is Growing
Intensified competition in the GLP-1 space means more companies are entering clinical stages, driving sustained demand for high-purity fluorinated heterocyclic intermediates and chiral building blocks. Meanwhile, the acceleration of AI-discovered drugs into Phase III means that demand for custom synthesis services for target validation and candidate optimization is shifting from "nice-to-have" to "mission-critical."
AI can generate 100 new targets in a week, but each target's functional validation and SAR studies require high-quality tool compounds and structural analogs—compounds that are often unavailable from commercial catalogs and must be addressed through custom synthesis.
IV. Beixinke Chem—Your Custom Synthesis Partner for the Dual Surge
Beixinke Chem is a custom synthesis service provider specializing in inhibitor small molecules, heterocyclic intermediates, and chiral building blocks, serving pharmaceutical R&D labs worldwide.
Our core capabilities:
●Retrosynthetic analysis: Designing accessible, cost-effective, and efficient synthetic routes
●Chiral construction: Chiral resolution, chiral catalysis, asymmetric synthesis
●Heterocyclic assembly: Construction of complex heterocyclic scaffolds including piperidines, pyrrolidines, azetidines
●Process scale-up: From milligrams to kilograms, maintaining purity and reproducibility
Analytical support: Full HPLC, LC-MS, NMR data
For GLP-1 drug development and AI-driven target validation, we offer:
●GLP-1 intermediates: Fluorinated heterocyclic building blocks; stereoselective construction of chiral piperidine/pyrrolidine scaffolds
●Target validation tool compounds: Design and synthesis of structural analog series around target of interest
●AI-predicted compound validation: Rapid feasibility assessment and process development for AI-generated molecules
Why Beixinke Chem?
●R&D flexibility: 50 mg–500 g, covering all stages from screening to validation
●Rapid response: Typically deliver feasibility assessments within 24 hours
●Data transparency: Every batch comes with HPLC, LC-MS, and NMR full spectra
●IP protection: Strict confidentiality agreements