Case Study: Accelerating Next-Generation Oral Cyclic Peptide from Lead Optimization to GMP Readiness

Background: non-GLP-1 pathway

The rise of GLP-1 receptor agonists as breakthrough treatments for diabetes and obesity has sparked a wave of innovation across the industry. When a clinical-stage biotech company with a bold vision, set out to develop a differentiated, orally available peptide drug targeting a non-GLP-1 pathway for weight control, they turned to WuXi TIDES.

From 1,000+ peptides to 10 hits and finally 1 preclinical candidate

While cyclic peptides offer enhanced pharmacological properties – such as improved stability and bioavailability – their synthesis can be challenging, depending on the complexity of the cyclization process. During the library synthesis stage, the WuXi TIDES Discovery Chemistry team supported client’s search through diverse side-chain mutations and various cyclization types, including Ring-closing metathesis (RCM) and Nobel Prize-winning “Click Chemistry”[1] (a set of efficient selective chemical reactions ideal for drug development). They successfully delivered multiple rounds of different libraries totaling more than 1,700 cyclic peptides with greater than 95% purity, each at a scale of 1-5 mg.

From this initial library screening campaign, 10 hits exhibited strong and selective activity. These hits were rapidly resynthesized and scaled for validation and detailed pharmacological profiling. Our Discovery Chemistry and Testing teams worked hand-i

n-hand to refine molecular properties, advancing three optimized leads with favorable in vitro and in vivo profiles. Within one year, a preclinical candidate was selected based on its potency, stability, and developability. WuXi TIDES’ Discovery Chemistry team successfully delivered eight consecutive ~50g scale batches of this candidate with an expedited lead time of 2-3 weeks per batch to support the client’s evolving testing needs as it moved forward.

From discovery to development phase

Impressed by the speed and scientific rigor of the program, the client chose to continue with WuXi TIDES into the development phase. Often, transitioning from discovery to development can involve delays, revalidation, and fragmented coordination that slow progress and increase risk. However, due to our fully integrated CRDMO platform, the tech and material transfer from the Discovery Chemistry team to our API Development and Analytical teams was conducted seamlessly, taking just one business day – eliminating bottlenecks and accelerating timelines.

During the process development, to meet the client’s urgent delivery requirements, all teams from WuXi TIDES worked closely together. The Development team managed to scale up from a 50 g demo scale batch to a 1 kg demo batch and a 6 kg GLP batch within six months to support the client’s preliminary toxicological study. The peptide development team scouted four routes and screened eight sets of conditions to greatly enhance the scalability and robustness of the process, increasing the crude purity and final yield by more than 70% and 140%, respectively.

WuXi TIDES CRDMO platform

Today, the client’s lead candidate is advancing through API process development, paving the way for IND-enabling studies. The client expressed strong satisfaction with the collaboration – highlighting our scientific excellence, operational efficiency, and speed as key to the success of their pipeline advancement.

This collaboration is a testament to how WuXi TIDES’ integrated CRDMO platform empowers biotech innovators to move faster, smarter, and with greater confidence. In the race to bring next-generation therapies to patients, we’re not just a service provider – we’re a true partner, offering scientific precision, and accelerated progress.

At WuXi TIDES, we move fast so our clients can move forward.

Find out how we develop oral peptide drugs>>