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Guide: Merck has described macrocyclic peptides as "the next wave of drug discovery".

On January 23, Merck signed a $220 million Biobucks agreement with UnnaturalProducts (UNP for short) to further expand its footprint in the macrocyclic peptide sector.UNP was founded in 2017 and focuses on macrocyclic compounds, a class of molecules capable of addressing complex targets that are intractable to traditional small molecules and biologics.

Small molecules can penetrate cells and be delivered orally, yet they struggle to bind to complex targets. Biologics only act on extracellular targets and are generally administered via injection.

Naturally occurring macrocycles have evolved to transcend the boundaries of cell permeability and oral bioavailability, engaging complex targets with high specificity.

UNP’s AI-empowered discovery platform enables the engineering and synthesis of synthetic macrocycles that mimic natural macrocyclic compounds. The company has established technologies for the intelligent design, rapid synthesis and screening of cyclic peptide macrocycles.

Merck has described macrocyclic peptides as “the next wave of drug discovery”.

Now, Merck will leverage UNP’s technology to develop macrocyclic drug candidates against an undisclosed challenging oncology target.

MK-0616, an investigational therapy from Merck & Co., is a macrocyclic peptide that binds to PCSK9 and is currently in Phase 3 trials for its ability to lower low-density lipoprotein cholesterol.

The press release did not disclose any financial details, only revealing that UNP will receive an undisclosed upfront payment plus potential development and commercial milestone payments of up to $220 million.

Rob Garbaccio, Head of Discovery Chemistry at Merck Research Laboratories, stated in the press release: “Merck continues to harness our strong medicinal chemistry capabilities to advance our oncology pipeline. We look forward to collaborating with the Unnatural Products team to develop candidate drugs aimed at this challenging oncology target.”

Macrocyclic drugs have a long history of clinical use, with examples including the immunosuppressant cyclosporine and the antibiotic erythromycin. However, systematic efforts to develop macrocyclic compounds have faced a series of challenges related to pharmacokinetics, cell permeability and oral bioavailability.

Notably, UNP closed a $32 million Series A financing round last December.

The financing was led by the Merck Global Health Innovation Fund (MGHIF) and TechBio-focused venture capital firm ARTIS Ventures. New institutional investors also included First Spark Ventures, The Venture Collective, Humain Ventures, Longe VC and Not Boring Capital, alongside participation from existing investors.