Company aims to drug the ‘undruggable’ with macrocyclic peptide approach that has potential in multiple age-related diseases.
Curiously-named US biotech Unnatural Products (UNP) has signed a research collaboration and licensing agreement with pharma giant Novartis aimed at developing new therapeutics with applications in cardiovascular disease. The deal puts UNP in line to receive up to $100 million in upfront and pre-IND milestone payments, and up to $1.7 billion tied to development, regulatory and commercial milestones.
Based in Santa Cruz, CA, UNP has developed a platform for designing and optimizing macrocyclic peptides – its “unnatural products” – to reach biological targets that have historically been considered undruggable. Beyond cardiovascular disease, the company believes it approach has potential to drive in a wide range of chronic and age-related conditions.
“This collaboration reflects the broader potential of our macrocyclic peptide platform beyond any single program,” UNP CEO Dr Cameron Pye, told us. “Many of the most important chronic diseases, from cardiovascular, obesity, and metabolic disorders to neurodegeneration and fibrosis are driven by protein interactions that have historically been difficult to target with conventional small molecules or biologics.”
Dr Cameron Pye is the CEO of Unnatural Products
Macrocyclic peptides sit in a middle ground between small molecules and biologics – large enough to achieve the kind of selectivity and binding strength associated with biologic drugs, while still offering chemical flexibility that can support drug-like properties, including the potential for oral dosing. UNP claims these qualities make them particularly suitable for targets where small molecules struggle to bind effectively and antibodies face challenges related to delivery, tissue penetration, or the need for injections.
“By combining AI-enhanced design with rapid synthesis and screening, we can create orally deliverable macrocycles capable of modulating these challenging targets,” Pye told us. “Our goal is to open new therapeutic avenues across a wide range of chronic diseases associated, where patients urgently need more precise and durable treatment options.”
For the Novartis collaboration, UNP will contribute its discovery engine and platform expertise, while Novartis will take responsibility for IND-enabling studies and then carry products forward through clinical development, manufacturing and global commercialization. The emphasis on cardiovascular disease indicates where the companies expect the approach could fit, whether by enabling new mechanisms, improving selectivity against complex targets, or offering dosing formats that are more practical for chronic use.
“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 Novartis’ head of discovery Muneto Mogi.
UNP has already leaned extensively into pharma collaborations as a route to scale its platform and validate its work. In July of last year, the company announced a potential $1.5 billion research collaboration with argenx focused on discovering and developing oral macrocyclic peptide drugs against traditionally difficult targets. In 2023, the company raised a $32 million Series A financing led by Merck Global Health Innovation Fund and ARTIS Ventures.
Main Photograph: EllaSD/Shutterstock; photograph of Dr Cameron Pye courtesy of UNP.