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Here’s What Happened
TIDES 2026, held in Boston in May, remains the premier conference for the oligonucleotide and peptide therapeutics community. Among hundreds of presentations, five stood out for their implications on the direction of the peptide field: the first public data on oral GLP-1/GIP dual agonists, a manufacturing breakthrough in macrocycle scale-up, new regulatory guidance signals from FDA, AI-driven peptide discovery crossing into IND territory, and the emergence of India as a GMP peptide CDMO competitor.
1. Oral GLP-1/GIP Dual Agonists: The Next Frontier
Eli Lilly presented preclinical data on an oral GLP-1/GIP dual agonist — an oral formulation of tirzepatide, essentially — using a novel permeation enhancer technology distinct from the SNAC system used in Rybelsus. The key data point: 4.8 percent oral bioavailability in non-human primates, a roughly 4× improvement over oral semaglutide’s 0.8–1.2 percent in humans. If these numbers translate to the clinic, an oral tirzepatide could deliver efficacy comparable to the injectable formulation without the massive overformulation that makes Rybelsus economically challenging. Lilly indicated a Phase I start in Q4 2026.
2. Macrocycle Scale-Up: Enzymatic Cyclization at Kilogram Scale
A joint presentation from Bachem and the University of Zurich described the first kilogram-scale synthesis of a 14-residue macrocycle using enzymatic cyclization. The traditional bottleneck in macrocycle manufacturing is the cyclization step — performed at high dilution (1–5 mM) to favor intramolecular over intermolecular reactions, requiring thousands of liters of solvent per kilogram of product. The enzymatic approach, using an engineered subtiligase variant, achieved cyclization at an unprecedented 50 mM concentration — a 10–50× improvement that reduces solvent consumption and reactor volume proportionally. Bachem indicated plans to deploy this at commercial scale by 2028.
3. FDA Signals: ICH M7 for Peptide Impurities
Dr. Sarah Kim, a CMC reviewer in the FDA’s Office of Pharmaceutical Quality, presented an overview of the agency’s evolving thinking on peptide-related impurity control. Two notable signals: the FDA is considering aligning peptide impurity thresholds more closely with ICH M7 guidelines for DNA-reactive (mutagenic) impurities, which would require additional Ames testing for certain peptide synthesis byproducts; and the agency is exploring aplatform-based quality assessment for well-characterized peptide classes (GLP-1 analogs, somatostatin analogs) that could reduce the CMC data burden for follow-on products. Both signals suggest a more structured but potentially more streamlined regulatory framework for peptides by 2028.
4. AI-Discovered Peptides Enter the Clinic
Insilico Medicine presented the structure of ISM-001, an AI-designed macrocyclic peptide targeting the pro-fibrotic target integrin alpha-V/beta-1, which entered Phase I in Q1 2026. This is believed to be the first wholly AI-designed peptide to reach clinical development. The molecule was identified from a computational screen of 10⁸ virtual macrocycles, synthesized as a 120-member focused library, and optimized to picomolar affinity in three design-make-test cycles over 11 months — roughly one-third the timeline of a traditional med-chem campaign.
5. India’s GMP Peptide Manufacturing Emergence
Three Indian CDMOs — Biocon, Laurus Labs, and Sai Life Sciences — presented their newly qualified GMP peptide manufacturing capabilities. Combined, they represent approximately 0.6 metric tons of annual capacity, with plans to double by 2028. India’s peptide manufacturing value proposition mirrors its success in small-molecule generics: costs 50–seventy percent below Western CDMOs, a large pool of skilled organic chemists, and deep experience with US FDA and EU GMP regulatory filings. The Indian entrants could erode both Western and Chinese CDMO pricing power for generic peptide APIs.
Expert Insight: What Wasn’t Presented
Conspicuously absent from TIDES 2026: any presentation on sustainable peptide manufacturing. SPPS is an environmentally intensive process, generating 5,000–15,000 liters of organic solvent waste per kilogram of peptide API. At current GLP-1 production volumes, that translates to 30–100 million liters of acetonitrile and DMF waste annually. No major CDMO or pharma company presented a comprehensive sustainability strategy. The first company to solve green SPPS — through solvent recycling, aqueous coupling chemistry, or enzymatic synthesis — will have a significant competitive and reputational advantage. The silence at TIDES suggests no one is close.
Further Reading
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Last reviewed: June 2026. Peptide Proof Editorial Team.
