Main Conference - Day 3 (May 14)Thursday, 14 May 2026

Traditional solid phase peptide synthesis often involves the use of large volumes of a number of challenging solvents and reagents, including polar aprotic solvents, chlorinated solvents, and TFA. Efforts to remove these types of solvents and reagents has led to concerted efforts to investigate alternative platform strategies that both eliminate these chemicals, and also drive down synthesis cost and PMI. Additionally, the synthesis of peptides using purely liquid phase chemistries offers an option to designate more advanced sub-fragments of the peptide with favorable physical properties as potential registered starting materials.

Disulfide bond formation is a key step in the manufacture of cysteine‑containing peptides, yet established oxidation methods frequently rely on hazardous reagents such as iodine or hydrogen peroxide. These approaches can introduce safety concerns, material compatibility issues, limited scalability, and undesired side reactions including over‑oxidation and oligomer formation. We describe a new oxidation platform based on dehydroascorbic acid (DHA), the oxidized form of vitamin C, as a mild, selective, and sustainable reagent for disulfide bond formation. The method supports efficient oxidation under aqueous conditions and is compatible with both high‑concentration in‑solution processing and an integrated on‑column implementation during preparative HPLC purification. DHA‑mediated oxidation shows a consistently favorable impurity profile and avoids common side reactions observed with conventional oxidants, even for peptides with limited solubility or high aggregation propensity. The DHA‑based platform simplifies process design by enabling higher working concentrations, reducing unit operations, and allowing oxidation to be integrated into existing purification workflows. The use of a non‑hazardous, vitamin‑derived reagent improves operational safety and equipment compatibility while significantly lowering process mass intensity and solvent consumption. Together, these features support robust scale‑up and align peptide manufacturing with modern sustainability expectations, making the technology well suited for both late‑stage development and commercial production.

Enlicitide decanoate (MK-0616) is an orally bioavailable inhibitor of PCSK9 which has demonstrated clinically meaningful reductions in LDL cholesterol. The convergent manufacturing route of this macrocyclic peptide relies on several biocatalytic steps. One key step in this process is a cascade in which five engineered enzymes work synergistically to generate the penultimate intermediate within a single reaction vessel. The challenges and discoveries that enabled implementation of this enzymatic transformation will be discussed.

The GLP-1 boom in obesity and metabolic disease has triggered a capacity crunch, hitting emerging biotechs hardest. This talk explores two pressure points in GLP-1 API manufacturing: (1) defining defensible starting materials for complex dual agonists under regulatory scrutiny, and (2) securing scarce development and GMP capacity at CDMOs dominated by big pharma. We share pragmatic tactics to keep small sponsors competitive without sacrificing quality or speed.v

PolyPeptide introduces advanced laboratory process‑optimization tools alongside its modular manufacturing design to accelerate development and industrial deployment. These innovations enhance throughput, flexibility, and sustainability while enabling rapid scale adjustments. By aligning next‑generation lab technologies with intensified process design, PolyPeptide addresses the fast‑evolving challenges of a market driven by the metabolic wave, ensuring faster time‑to‑market and robust manufacturing adaptability.

Over the past decade, the pharmaceutical industry has transitioned from traditional small molecules toward complex new modalities, including peptides, antibody-drug conjugates (ADCs), and oligonucleotides. The structural complexity and similarities inherent in these modalities pose significant characterization challenges, requiring analytical scientists to extend the boundaries of modern techniques. While Size Exclusion Chromatography (SEC) and Reversed-Phase Liquid Chromatography (RPLC) are essential for assessing physical stability and chemical purity, one-dimensional chromatography is often insufficient for full characterization. To address this, we have developed an array of multidimensional techniques coupling orthogonal retention mechanisms, such as RPLC-RPLC, RPLC-SEC, SEC-RPLC, and RPLC-HILIC. A primary challenge in these systems is mobile phase incompatibility between dimensions; we address this through a novel interface utilizing In-Line Mixing Modulation (ILMM) for sample homogenization. Furthermore, non-denaturing SEC methods are critical for peptides to preserve native conformation and higher-order structures (HOS), which are essential for biological activity and quality control. Developing these methods is often difficult due to secondary interactions that limits the use of physiological aqueous buffers requiring reasonable amounts of organics. We present strategies to suppress these interactions, enabling separations based on pure hydrodynamic volume. This presentation will highlight the current analytical challenges and the advanced strategies to achieve comprehensive peptide characterization.