Novartis Signs Up to $1.8B Licensing Deal with UNP for Cardiovascular Peptide Therapeutics

Novartis has signed a research partnership and licensing agreement with Unnatural Products (UNP) valued at up to $1.8 billion to develop macrocyclic peptide therapeutics targeting cardiovascular diseases. The partnership combines UNP's AI-driven macrocycle platform with the worldwide development and commercialisation expertise of Novartis, aiming to produce next-generation treatments for previously undruggable targets.

Under this agreement, Novartis will lead investigational new drug (IND)-enabling studies and oversee all subsequent clinical development, manufacturing, and global commercialisation of any resulting therapeutic products. The focus lies on harnessing macrocyclic peptides, which merge the selectivity and potency of biologics with the drug-like properties of small molecules.

UNP is eligible for up to $100 million in upfront and pre-IND milestone payments, as well as additional development, regulatory, and commercial milestone payments that could total up to $1.7 billion. The company will also be entitled to tiered royalties on annual net sales, ranging from the mid-single digits to low double digits.

UNP reasons that macrocyclic peptides offer an effective new class of therapeutics that combine the selectivity and potency of biologics with the flexibility and drug-like properties of small molecules. UNP says its platform is an integrated discovery engine that rapidly generates highly potent and selective oral and injectable macrocycles by joining AI-guided molecular design, "massively" parallel synthesis, and direct-to-biology screening.

UNP's process starts by screening candidate molecules against a protein target using technologies and established approaches for testing macrocyclics like phage display or messenger RNA (mRNA) display. The hits are then fed into the company's computational drug platform, where they are modified and optimized.

The CEO and co-founder stated: "This collaboration validates the strength of our programme 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."

The global head of discovery chemistry at Novartis said: "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."

The Novartis collaboration comes seven months after UNP inked an up-to-$1.5 billion-plus collaboration with argenx to discover and develop synthetic oral macrocyclic peptide drugs targeting multiple "undruggable" immunology targets. In 2024, Merck & Co. agreed to partner with UNP on designing and developing macrocyclic candidates against an oncology therapeutic target. Merck agreed to pay UNP an undisclosed upfront payment, plus up to approximately $220 million in payments tied to achieving milestones toward developing and commercializing a candidate product.

Three years earlier, UNP and BridgeBio Pharma agreed to partner on generating drug-like macrocycles for intracellular targets associated with potential oncology applications as well as rare fibrotic diseases. BridgeBio later exercised its option to license UNP-developed macrocyclic therapeutics for development in both therapeutic indications. As a result, UNP received undisclosed milestone payments for the progress of the research and the option, and is set to receive further development and sales milestone payments, also undisclosed, as the program progresses, plus tiered royalties upon commercialization.