Novartis will apply Unnatural Products (UNP)’s artificial intelligence (AI)-guided macrocyclic peptide platform to develop next-generation cardiovascular disease therapeutics, through a collaboration that could generate more than $1.8 billion for the Santa Cruz, CA-based biotech.
UNP has signed a research collaboration and licensing agreement with Novartis launching the partnership, beginning with an undisclosed program. The collaboration is intended to enable access to previously undruggable targets by marrying UNP’s platform with the pharma giant’s global development and commercialization capabilities.
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. There is no black box algorithm in the process, Pye told GEN last July. “What the platform’s about is being able to take smart shots on goal” in order to “find a successful hypothesis to weave your way through that chemical landscape to a development candidate.”
“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,” Muneto Mogi, Novartis’ global head of discovery chemistry based at the company’s Biomedical Research unit (formerly Novartis Institutes for BioMedical Research), said in a statement. “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.”
In a Q&A article posted on Live.Magazine, Novartis’ official global in-house publication, Mogi said Novartis was using machine learning in drug design as well as synthesis design: “By doing this, not only can we increase the speed with which we pursue our projects—more importantly, I’m very, very confident that this will increase our probability of success.”
Novartis has agreed to oversee investigational new drug (IND)-enabling studies and all subsequent clinical development, manufacturing, and global commercialization of products emerging from the collaboration.
$100M upfront
In return, Novartis agreed to pay UNP up to $100 million in upfront and pre-IND milestone payments, and up to $1.7 billion in development, regulatory, and commercial milestones. UNP is also eligible to receive tiered royalties from Novartis on annual net sales ranging from the mid-single up to low double-digits.
“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,” stated Cameron Pye, PhD, UNP’s CEO and co-founder. “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 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.
And 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.
The Merck collaboration was not UNP’s first to be focused in cancer. In 2021, 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.
Three years later, BridgeBio 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.
