Novartis expands cardiovascular pipeline with $1.8bn macrocycle agreement with Unnatural Products

The collaboration pairs UNP’s AI-enhanced discovery platform, with the company focusing on early research activities, and Novartis’ global development and commercialization capabilities, with the Swiss drugmaker leading the program from Investigational New Drug (IND)-enabling studies through clinical development, manufacturing and worldwide commercialization.

Targeting the “undruggable”

The agreement between UNP and Novartis underscores growing industry interest in macrocyclic peptides. Those 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 therefore considered promising candidates that combine the precision and potency of antibodies with properties compatible with pill-based medicines. UNP has built an integrated discovery engine for macrocyclic peptides that combines AI-guided molecular design, large-scale parallel synthesis and rapid biological screening.

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 (for instance Orbis Medicines, Vilya and Circle Pharma) are developing next-generation platforms to improve oral bioavailability and scalability.

“Advances in macrocyclic chemistry are opening entirely new avenues in drug discovery, allowing us to engage targets at a dose and with a pharmacological versatility not possible with many other approaches,” said Muneto Mogi, Global Head of Global Discovery Chemistry, Biomedical Research at Novartis in a press release.

Financial terms and milestones

Under the deal, UNP is eligible to receive up to $100 million (€84 million) in upfront and pre-IND milestone payments. The company could earn up to $1.7 billion (€1.4 billion) more in development, regulatory and commercial milestones. In addition, UNP qualifies for tiered royalties ranging from the mid-single digits to the low double digits on annual net sales. For Novartis, the agreement adds a next-generation modality to its cardiovascular pipeline.

This agreement follows another major partnership for UNP. In summer 2025, the company signed a $1.5 billion (€1.2 billion) collaboration with argenx to discover and develop synthetic oral macrocyclic peptide drugs against multiple immunology targets considered “undruggable.” Together, the deals position UNP as a rising player in the fast-evolving macrocycle space.

“This collaboration validates the strength of our program and highlights the ability of UNP’s platform to deliver differentiated macrocyclic therapeutics for high-value biological targets for chronic diseases with high unmet need,” said Cameron Pye, Ph.D., CEO and co-founder of UNP, in a statement.