How Peptide Conjugate Developability Is Shaped Before a Candidate Is Nominated

• Of the 106 peptide and nanobody drug conjugates in active development, roughly 63% are still preclinical, which places many of the decisions that shape manufacturability in the design phase.
• Cyclization, lipidation, chelator installation and payload conjugation each add process and analytical requirements that are best addressed while the molecule can still be changed
• WuXi AppTec carries those design decisions through building-block supply, analytical development and manufacturing within one global quality system.

San Diego, CA, Oct. 23, 2026 (GLOBE NEWSWIRE) -- There are about 106 peptide and nanobody drug conjugates in active development, and around 63% of them are still preclinical, according to a 2026 Citeline analysis of Pharmaprojects data.¹ For most of those programs, including the peptide conjugates among them, the structural choices that decide whether the molecule can be made at scale are not yet locked, which makes design the stage that shapes much of peptide conjugate development. Each added element, whether a lipid, a chelator or a payload, brings its own chemistry, impurities and analytical demands. After nomination, a change to the sequence, the modification site or the conjugation strategy can send the program back through characterization and biological testing. 

WuXi AppTec, a contract research, development and manufacturing organization (CRDMO), works as a trusted partner to biotech and pharmaceutical innovators across more than 30 countries. For peptide conjugate programs, five decisions made before nomination shape whether the molecule can be manufactured at scale.

Map Each Structural Modification to Its CMC Consequence

The first decision is to write down what each modification adds to the chemistry, manufacturing and controls (CMC) package, because the consequences are specific and, for the most part, foreseeable.

Modification	What it adds to the process	What it adds to the analytics
Macrocyclization	Ring-closing chemistry; residual-catalyst control when metal-catalyzed	Resolution of ring-size and linkage variants
Lipidation	Greater hydrophobicity; altered solubility and aggregation; different purification behavior	Methods that track self-association and aggregation
Chelator installation	Sensitivity to trace metals from solvents, reagents and containers; a metal budget	Separation of species that differ only in the metal occupying the chelate
Payload conjugation	Containment for potent payloads; linker-stability control	Assignment of conjugation products and free-payload impurities

Secure Specialized Building-Block Routes Before the Candidate Depends on Them

Conjugates draw on nonstandard components, including unnatural amino acids, linkers and chelators, that are often available only in research quantities or from one supplier. For each of them, the decision before nomination is whether a scalable, reproducible route exists or has to be built alongside the peptide. A component found to be single-source after nomination leaves two options: either a long wait or a redesign that reopens biology.

Develop Analytical Methods That Resolve Closely Related Species

Conjugation produces species that resemble the product, including sequence variants and under-reacted and over-reacted conjugation products. Where a chelator is present, the process can also form complexes with adventitious metals that co-elute with the product and resist assignment by mass alone. Methods are ready only when they can separate and assign every species the construct is expected to generate. Running method development alongside route development surfaces any co-eluting species the method cannot resolve while the team can still adjust the chemistry.

Set the Control Strategy Around the Individual Construct

A control strategy written for a linear peptide will not carry over unchanged to its lipidated, cyclized or chelator-bearing analog. For chelator-containing molecules in particular, the choice of solvents, the sequence of process steps and the materials that touch the product are all fixed against a limit on allowable trace metals, decided at the start of process development rather than discovered at release.

Carry Design Decisions Through One Global Quality System to Clinical Supply

The value of making these decisions early depends on keeping them intact as the program advances. WuXi TIDES, the peptide and oligonucleotide platform of WuXi AppTec, connects discovery synthesis, unnatural amino acid and linker supply, conjugation chemistry, analytical development and manufacturing within one CRDMO platform and one global quality system, so the metal budget, the method and the supply route chosen during optimization are designed to carry through to development and commercial supply.

“By connecting chemistry development, manufacturing, and supply within a unified system, teams can operate in parallel, anticipate challenges, and maintain consistent quality across regions,” said Yu Lu, Senior Vice President of WuXi TIDES, part of WuXi AppTec.

In a published case study, WuXi AppTec reported supporting a cyclic peptide-based radionuclide conjugate program by developing an in-house route for a critical unnatural amino acid and coordinating discovery, testing, process development and impurity control. Analytical and purification teams developed methods to distinguish metal-containing species, while process and formulation teams evaluated solvents, operating conditions and contact materials to limit metal contamination. Overall yield rose from 29% to 44%, and a telescoped synthesis process reduced the synthesis cycle and material use by approximately 30% each. Outcomes depend on the individual program.

Frequently Asked Questions

Question: What are peptide conjugates, and why are they used?

Answer: Peptide conjugates attach another component to a peptide to add a function. A drug payload can enable targeted delivery, a fatty-acid moiety can prolong circulation through albumin binding, and a chelator can carry a radionuclide for imaging or therapy, as lutetium-177 dotatate does for somatostatin receptor-positive neuroendocrine tumors. Peptide-drug conjugates face a particular constraint: peptides clear quickly, so the construct has to reach its target and release its payload within a short window.

Question: What makes peptide conjugates harder to develop than linear peptides?

Answer: Each added element brings chemistry beyond standard chain assembly, along with its own impurities and analytical requirements. A linker, a lipid, a chelator or a payload changes how the molecule behaves in purification, how it aggregates, which species the analytical method must separate and, for potent payloads, how the process must be contained. None of these is unmanageable, but each has to be designed for, which is why conjugate programs benefit from process and analytical input during optimization rather than after nomination.

Question: Why do trace metals matter in chelator-containing peptide conjugates?

Answer: A chelator such as DOTA, built to hold a therapeutic radionuclide, will also pick up metals that leach from solvents, reagents and container surfaces. Those metals occupy chelation sites and can reduce the efficiency of later radiolabeling. The resulting complexes look like the product on the column and can be hard to assign by mass alone, so they are easy to miss and hard to remove. Controlling them means setting a trace-metal limit at the start of process development, choosing solvents, step order and contact materials against that limit, and using an analytical method that can tell apart species that differ only in the metal held in the chelate.

Question: How do potent payloads change peptide conjugate manufacturing?

Answer: They add containment and impurity-control requirements that a plain peptide process does not carry. A highly potent payload has to be handled in facilities and equipment designed to protect operators and prevent cross-contamination, and the analytical package has to track free payload and payload-related impurities alongside the peptide species. Linker stability becomes a process parameter as well as a pharmacology one, because premature release during synthesis, purification or storage shows up as an impurity. Those requirements are easier to meet when the payload and linker are chosen with the manufacturing route in view.

Question: How does lipidation affect peptide purification and formulation?

Answer: A fatty-acid chain added to extend half-life makes the molecule more hydrophobic and more prone to self-association. In purification that can shift retention, lower recovery and complicate separation from related species. In formulation it can limit achievable concentration, affect stability and narrow the choice of dosage form. Evaluating those effects when the lipidation site and linker are chosen lets the team select the variant that extends exposure without creating a purification or formulation problem later.

Source: 

¹ Citeline, "Peptide and nanobody drug conjugates pipeline takes shape," June 2026, based on Pharmaprojects data current to January 2026.

About WuXi AppTec

WuXi AppTec is a trusted partner and contributor to the pharmaceutical and life sciences industries, providing R&D and manufacturing services that help advance healthcare innovation. With operations across Asia, Europe, and North America, we offer integrated, end-to-end services through our unique CRDMO (Contract Research, Development, and Manufacturing Organization) platform. We are privileged to work alongside partners across 30+ countries, supporting their efforts to bring breakthrough treatments to patients. Guided by our vision that every drug can be made, and every disease can be treated, we are committed to advancing breakthroughs for patients—one collaboration at a time. Learn more at https://www.wuxiapptec.com.