The Rise and Rise of Peptides

INTRODUCTION

Dear Community,

Welcome to Issue 2 of Synthesis: The Rise and Rise of Peptides.

In recent years, increased investment in peptide manufacture has been a notable trend. We’ve rapidly moved from a time when very few people were talking about peptide manufacture to a point where it feels almost mandatory to have a foot in the peptide world. This growing interest from both innovators and CDMOs has led to a significant shift in gear in a relatively short time span.

Peptides are hot property. But are we ready for them?

In addition to the surge of demand for peptide-based Type II Diabetes and obesity drugs, which infamously led to shortages, we’re also seeing a shift from injectable to oral dosing. This latest trend adds further pressure to manufacturing capacity; after all, oral dosing requires around 10 times more active ingredient.

Meanwhile, the success of GLP-1 receptor agonists has ignited the peptide discovery engine in other big therapeutic areas, including oncology, which points to even more demand in the future.

I’d argue that any company with peptide-based drugs in development should be considering how they will manufacture at the metric ton scale. Capacity based on traditional solid phase peptide synthesis cannot keep up with demand in a cost-conscious environment.

I firmly believe that liquid phase peptide synthesis is the answer – and I’m proud to say that Cambrex is leading the way. But where do you see the peptide field heading? Do you, like me, foresee an explosion in demand? Or will peptides be replaced by the next “big thing?” I’d love to hear your thoughts.

Until next time,
Matt Bio

THE LEAD REACTION

Turning the tide for LPPS

When a huge team of chemists in China successfully synthesized insulin 60 years ago, they likely couldn’t imagine the AI-powered age of 2026 – nor the existence of a conference dedicated to oligonucleotide and peptide therapeutics.

Last year in Boston, Eric Fang (General Manager at Snapdragon Chemistry, a Cambrex company) looked back to that insulin example of liquid phase peptide synthesis (LPPS) at TIDES USA. Eric was there – “60 years late,” he quipped – to emphasise the potential of LPPS in tackling the twin issues of cost and sustainability in peptide scale-up.

He echoed other speakers by noting that high-volume peptides – namely, GLP-1 agonists – had necessitated the development of hybrid approaches that combine solid phase peptide synthesis (SPPS; for fragment formation) followed by LPPS coupling.

The move to a fully liquid phase process – made possible by flow chemistry – could be considered a final evolution towards solution phase that brings several advantages; for example, the ability to use standard reactors, higher reaction concentrations, reduced excess reagents, reduced solvents and simplified analysis.

Eric admitted that LPPS is relatively new, meaning that space remains for exciting breakthroughs. First, he highlighted an example of algorithmic reaction optimization that discovered a process 60 times more efficient than starting conditions. Second, he demonstrated the highly favorable process mass intensity (PMI) of Snapdragon LPPS – especially when compared with Phase 1 SPPS. Third, Eric unveiled AI-assisted LPPS automation (complete with timelapse video of a 24/7 development tool in action).

Watch Eric’s TIDES 2025 presentation here.

Hungry for more? Adrian Gabriel Amador, Erik Feldmann, and Hannah McLachlan cover LPPS technology, peptide crystallization, and analytical considerations in this insightful webinar.

THE METHOD

Crystal clear rewards

Few chemists would argue that peptide crystallization is easy. But how many would argue it is worth it? Likely all those who value full structural determination, simplified processing and a higher purity product. And once you’ve jumped the “how to” hurdle, you can add a significant cost advantage over column chromatography to the list.

In this peptide crystallization case study, Cambrex experts share three strategic milestones for success, quoting a specific example.

Milestone 1. The team evaluates peptide solubility in great detail, which aids in the discovery of optimal conditions for later crystallization. Next, high throughput screening ascertains experimental conditions that allow for crystallization of the free peptide (or its salt form) while avoiding gelation, aggregation, amorphous solids and liquid crystals.

Milestone 2. Experts seek out scalable elements of the process, assessing the critical process parameters at the 100mL to 1L scale using next-generation technology, such as the Blaze Metrics 3-in-1 PAT tool. The main aim is to find conditions that deliver the highest yield, the highest purity and best efficiency in filtration – all in the minimal reaction volume.

Milestone 3. Our tech transfer gurus ensure consistent results in the client’s plant, using data and analysis from hands-on experiments as well as state-of-the-art modeling software.

In short, peptide crystallization scale-up requires careful strategy and next-gen technology. But there’s no substitute for expertise!

Read the full case study.

ANALYZE THIS

Where do peptides belong?

In a recent presentation, Adrian Gabriel Amador, Director of Chemistry, and David Wang, Senior Director, Analytical Science, both at Snapdragon Chemistry, explored the opportunities and challenges of LPPS from regulatory, analytical and quality control perspectives.

Considering the current regulatory framework, David raised the seemingly innocuous question, “Where do peptides belong?”

The key takeaways:
i) Regulatory expectations for peptides are closer to biologics than small molecules.
ii) Peptide stability testing must go beyond small-molecule HPLC-UV; in fact, LC-MS with sequence integrity is essential.

In short, the complexity and unique degradation chemistry of peptides require tailored analytics and an expanded analytical armamentarium, with LC-HRMS being a primary tool.

David’s expert analytical insight generated some great questions from the audience, with regulatory expectations high on the agenda.

Watch the webinar to see if your peptide analysis questions were answered; if not, feel free to reach out to the team by replying to this email.

THE CATALYST

What we are reading 

Nature-Inspired Continuous N-C Chain Elongation Enables Sustainable Peptide Synthesis (January 29, 2026). This recent preprint on ChemRxiv outlines a protection-free strategy for solution-phase peptide elongation using unprotected amino acids. The authors demonstrate high per-step coupling efficiency while reducing intermediate isolations and material intensity compared with conventional protecting-group workflows. Compatibility with non-canonical residues and application to pharmaceutically relevant sequences highlight the potential of streamlined solution-phase approaches to improve scalability, cost profile, and sustainability in therapeutic peptide manufacturing.

A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis (January 30, 2026). A recent publication in Nature Communications reports an innovative polymer-targeting platform designed to selectively deliver a therapeutic payload to diseased tissue. The study combines synthetic polymer chemistry with biological targeting validation to demonstrate controlled localization and functional activity in vivo, underscoring the growing role of engineered macromolecular systems in precision drug delivery. The work highlights how advances in macromolecular design continue to expand the toolbox for improving selectivity, exposure, and therapeutic index across emerging modalities.

THE SIDEBAR

By using great analytical techniques at a very small scale, we can get more useful crystallization results with less material – results that can be scaled up for manufacture, saving more money. Peptide material is expensive, so if we can get more with less, it's a fantastic thing.