This talk explores how biologic CMC (Chemistry, Manufacturing, and Controls) principles can be effectively applied to peptide production across the discovery-to-development continuum. By leveraging established frameworks from biologics, we demonstrate strategies to enhance peptide quality and regulatory readiness. Key topics include process development, analytical characterization, and quality control, emphasizing a streamlined approach to accelerate peptide therapeutics toward clinical success.

This presentation outlines a science- and risk-based framework for building robust analytical control strategies for therapeutic peptide APIs. It highlights how manufacturing choices, starting materials, critical quality attributes, impurity risks, and orthogonal analytical methods shape product quality throughout the lifecycle. Emphasis is placed on impurity characterization, regulatory expectations, lifecycle management, and the role of standards and reference materials in supporting consistent manufacturing, patient safety, and successful regulatory approval.

The global therapeutic peptide market is projected to reach $164 billion in 2026, driven by sustained GLP-1 adoption. However, immunogenicity risks from manufacturing-related impurities in peptide drugs remain poorly understood, and regulatory guidance has been limited, with implications for patient safety and the development of generic peptides. This presentation highlights new FDA draft product-specific guidances on impurity thresholds and immunogenicity assessment that provide a clearer path for generic peptide products.

Currently, there is no dedicated guidance for assessing immunogenicity risk in novel peptide therapeutics. The FDA clinical pharmacology guidance on therapeutic peptide development does not provide specific recommendations for evaluating peptide immunogenicity and instead refers to the 2014 guidance for therapeutic proteins. This presentation will highlight immunogenicity information from approved peptide therapeutics and explore how these data can inform the evaluation of peptide immunogenicity.

Today’s peptide therapeutics increasingly rely on chemistries beyond the 20 canonical amino acids to achieve exceptional pharmacological functions. Their manufacture relies on chemical methods, generating on average 13,000 kg of waste per kg of peptide, of which >50% is organic solvents. This talk will demonstrate how genetic code expansion enables the scalable biomanufacture of peptides and proteins that incorporate multiple non-canonical amino acids, in a reprogrammed E. coli host.

This talk describes the development of the manufacturing process of Zolucatetide, a helicon peptide which is a first-in-class direct inhibitor of the b-catenin/TCF protein-protein interaction, a key driver in many cancers. A systematic optimization of the route and key reaction steps will be presented, highlighting control of deleterious olefin migration during ring-closing metathesis. Implementation of the manufacturing strategy is demonstrated in a kilogram-scale synthesis of Zolucatetide.

Unnatural or non-canonical amino acids expand the therapeutic potential of peptides but are often laborious to prepare in protected, coupling-ready form. We present a concise two-step synthesis from readily available terminal alkynes that combines mild gold(I) catalysis with inexpensive chiral tert-butylsulfinamide to deliver diverse, bench-stable building blocks—including N-methyl variants—with excellent enantiomeric excess. Preequipped with a removable N-sulfenyl protecting group and a mildly activated carboxyl, these amino acids couple directly without additional activation, proceeding with negligible to no epimerization even for challenging residues such as phenylglycine. The method integrates seamlessly into both solution- and solid-phase synthesis of peptides.

This presentation will highlight Immunethep’s strategy to advance a peptide-based vaccine concept targeting bacterial GAPDH (bGAPDH) to help prevent E. coli infection. We will review the target rationale and antigen design, including a tandem peptide construct built from selected bGAPDH-derived regions to target a conserved virulence factor while avoiding cross-reactivity with human GAPDH. We will summarize the development path, early learnings, and next steps toward a scalable, vaccine-ready profile.

Enzymatic macrocyclization offers a route to structurally complex peptides that are difficult to access through conventional methods. This presentation will describe recombinant production strategies that pair peptide expression with PapB-mediated thioether formation to generate conformationally constrained macrocycles and polymacrocycles. Key considerations include construct design, enzyme compatibility, reaction efficiency, product recovery, and analytical validation, with emphasis on enabling diverse peptide architectures for discovery and therapeutic development.

Inflammasomes are promising therapeutic targets, yet current approaches fail to selectively modulate individual signaling components or specific immune cell populations. We identified Mycobacterium tuberculosis-derived peptides that independently regulate NLRP3 and ASC and incorporated these discoveries into macrophage subtype-specific peptide-drug conjugates (PDCs). This strategy enables precise inflammasome reprogramming, restores beneficial gut microbiota, enhances anti-tumor immunity, and suppresses both inflammation-associated and chemoresistant colorectal cancer.

Peptides occupy the therapeutic space between small molecules and antibodies, yet most remain injectable and confined to nature's 20 amino acids. Aizen's DaX is an interaction-centric foundation model that learns the physics of molecular binding rather than sequence patterns—enabling de novo design of non-canonical peptides beyond the reach of conventional discovery. This talk presents the approach and what it takes to advance such molecules from design toward the clinic.

Parkinson’s disease still lacks therapies that neutralize pathogenic a-synuclein assemblies. HELICURE is a proprietary intranasal helical peptide platform designed to selectively engage toxic a-synuclein oligomers and fibrils while sparing the physiological monomer. In a mouse model of Parkinson’s disease with established synucleinopathy, our lead peptide reached dopaminergic neurons, reduced aggregated and phosphorylated a-synuclein across key disease-relevant brain regions, preserved nigrostriatal integrity, normalized neuroinflammation, and restored motor performance to near-normal levels.

The global market for peptide therapeutics is expanding rapidly, yet development is complicated by the inherent physicochemical instability and rapid clearance. This presentation discusses strategies to enable both oral and parenteral delivery of GLP-1 peptides through rigorous biophysical and molecular investigations. Using advanced techniques like NMR and SRS, three case studies from the drug substance, drug product, and delivery perspectives are explored. These studies elucidate the molecular mechanisms of liraglutide oligomerization, its aggregation from interfacial stress, and the role of SNAC as an oral permeation enhancer, providing critical insights into overcoming key peptide stability and delivery obstacles.