Novartis AG announced a licensing agreement with Unnatural Products, Inc. that grants Novartis the rights to develop macrocyclic peptide‑based therapies for cardiovascular indications. Under the deal, Novartis will conduct IND‑enabling studies, clinical development, manufacturing, and global commercialization of any resulting products.
The agreement provides Unnatural Products with up to $100 million in upfront and pre‑IND milestone payments and up to $1.7 billion in development, regulatory, and commercial milestones, bringing the total potential value to $1.8 billion. Tiered royalties ranging from mid‑single digits to low double digits on annual net sales are also included.
The collaboration combines Unnatural Products’ AI‑enhanced macrocycle platform with Novartis’s global development and commercialization capabilities. Macrocyclic peptides offer the selectivity of biologics while retaining the drug‑like properties of small molecules, potentially enabling the targeting of previously “undruggable” cardiovascular disease mechanisms.
The deal is part of Novartis’s broader cardiovascular strategy, which includes the $1.4 billion acquisition of Tourmaline Bio in September 2025 and a focus on expanding its cardiovascular pipeline after the 2025 patent expiration of its blockbuster heart‑failure drug Entresto, which generated $7.7 billion in sales in 2025.
Unnatural Products has previously partnered with Merck & Co. on oncology programs and with BridgeBio Pharma, underscoring the validation of its platform. The new partnership will allow Novartis to accelerate the development of macrocyclic therapeutics across a range of cardiovascular diseases, though specific indications remain undisclosed.
"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. Novartis has built a highly respected engine in cardiovascular innovation, and we are excited to collaborate with them to unlock the full therapeutic potential of this asset. Together, we have the opportunity to advance medicines that could meaningfully improve patient lives across various diseases," said Cameron Pye, CEO and Co‑Founder of Unnatural Products.
"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. We believe this collaboration positions both organizations to accelerate the development of new therapies with strong scientific and clinical potential. We look forward to working together to bring innovative medicines to patients," said Muneto Mogi, Global Head of Global Discovery Chemistry, Biomedical Research, Novartis.
The licensing deal represents a significant strategic investment for Novartis, providing a new modality to diversify its cardiovascular portfolio and mitigate the revenue impact of Entresto’s patent cliff. By leveraging Unnatural Products’ AI‑driven design capabilities, Novartis aims to bring novel macrocyclic therapies to market faster, potentially capturing new revenue streams in a highly competitive cardiovascular landscape.
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