Novartis, Unnatural Products Sign $1.8B Cardiovascular Macrocyclic Peptide Deal

California-based Unnatural Products has signed a research collaboration and licensing agreement with Novartis to develop macrocyclic peptide therapeutics for an undisclosed cardiovascular program. The deal was announced Wednesday and is worth up to $1.8 billion.

Under the agreement, Unnatural Products will receive up to $100 million in upfront and pre-investigational new drug milestone payments. In addition, the company may receive up to $1.7 billion in development, regulatory and commercial milestones. Unnatural Products will also be eligible for tiered royalties ranging from the mid-single digits to the low double digits on annual net sales.

The collaboration pairs Unnatural Products' AI-enhanced macrocycle discovery engine with Novartis' global development and commercialization capabilities. Unnatural Products will focus on early research activities, while Novartis will assume responsibility for investigational new drug-enabling studies and all subsequent clinical development, manufacturing, and global commercialization of products emerging from the collaboration.

Macrocyclic peptides are ring-shaped molecules that bridge the gap between small molecules and biologics. Their cyclic structure makes them more resistant to digestion, increasing their potential for oral delivery. They are considered promising candidates that combine the precision and potency of antibodies with properties compatible with pill-based medicines.

The agreement underscores growing industry interest in macrocyclic peptides. Long explored in academia and niche biotech circles, macrocycles are now gaining momentum. Recent late-stage successes in inflammation and cardiovascular disease have drawn big pharma into the field, while a new wave of biotechs are developing next-generation platforms to improve oral bioavailability and scalability.

The Global Head of Global Discovery Chemistry, Biomedical Research at Novartis stated that advances in macrocyclic chemistry are opening entirely new avenues in drug discovery, allowing engagement with targets at a dose and with a pharmacological versatility not possible with many other approaches.

The CEO and co-founder of Unnatural Products stated that the collaboration validates the strength of the company's program and highlights the ability of the platform to deliver differentiated macrocyclic therapeutics for high-value biological targets for chronic diseases with high unmet need. The CEO also noted that Novartis has built a highly respected engine in cardiovascular innovation.

This agreement follows another major partnership for Unnatural Products. In summer 2025, the company signed a $1.5 billion collaboration with argenx to discover and develop synthetic oral macrocyclic peptide drugs against multiple immunology targets considered "undruggable." Together, the deals position Unnatural Products as a rising player in the fast-evolving macrocycle space.

For Novartis, the agreement adds a next-generation modality to its cardiovascular pipeline. The companies did not disclose the exact nature of the cardiovascular program or specify which disease targets they are pursuing.