Novartis Commits $100M to Startup With Tech That Brings Peptides to Undruggable Targets Leave a comment
Novartis is looking to build up its cardiovascular drug pipeline and it’s now partnering with Unnatural Products to support the effort. The pharmaceutical company is committing up to $100 million to begin a licensing and research collaboration leveraging the startup’s technology for developing peptide drugs for elusive targets long considered undruggable.
Santa Cruz, California-based Unnatural Products, or UNP, develops macrocyclic peptide drugs. While peptides can bind to targets that are challenging for small molecules, peptides can’t be easily made into oral formulations. In a macrocyclic peptide, the amino acid chains of the peptide are formed in a ring-like shape. This structure gives the peptide more versatility in binding to targets, including targets that have eluded small molecules.
UNP develops its macrocycles with a proprietary technology platform that combines parallel experimentation and machine learning in a continuous optimization loop that it says makes a macrocycle more drug-like with each cycle. These potential drugs may be developed for both oral and injectable formulations.
The category of cardiovascular, renal and metabolic disease is one of four core therapeutics areas of Novartis. The other three are immunology, neuroscience, and oncology. The heart failure medication Entresto is Novartis’s top cardio drug and top seller overall with more than $7.7 billion in revenue in 2025. But that figure is a 1% decline from the prior year, reflecting competition that has started from generic versions of the twice-daily pill, the company said in its annual report. That means Novartis needs new cardio meds to make up for the coming revenue decline from Entresto.
Entresto pairs two mechanisms of action, inhibiting neprilysin and blocking the angiotensin receptor. The target and cardiovascular indication of the Novartis program partnered with UNP remain undisclosed. According to terms of the agreement announced Wednesday, Novartis will be responsible for the investigational new drug application (IND)-enabling studies for candidates that stem from the collaboration. The pharma company will also handle clinical development, manufacturing, and commercialization of partnered 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,” Muneto Mogi, global head of global discovery chemistry, biomedical research, at Novartis, said in a prepared statement. “We believe this collaboration positions both organizations to accelerate the development of new therapies with strong scientific and clinical potential.”
Novartis already has familiarity with peptide drugs formed into rings. The pharma company is partnered with Bicycle Therapeutics, which forms its short peptides into two loops that stabilize its structure and facilitate binding to targets. This alliance, which started in 2023, is still in the preclinical stage pursuing cancer targets that remain undisclosed. Other startups have entered macrocyclic peptide R&D. Orbis Medicines is developing macrocyclic drugs for undisclosed targets. When preclinical Orbis closed its €90 million (about $93.4 million) Series A financing a little more than a year ago, it said it was focusing on targets that have already been validated by injectable biologic drugs.
UNP emerged in 2019 backed by $6 million in seed financing. In 2023, Merck Global Health Innovation Fund and ARTIS Ventures led the startup’s $32 million Series A round.
Novartis is the latest biopharmaceutical industry partnerships for UNP. In 2024, BridgeBio Pharma exercised its option to license macrocyclic peptide candidates developed by UNP for undisclosed rare diseases and cancer. A partnership with Merck is focused on developing macrocyclic drug candidates for an undisclosed cancer target. Last year, UNP began a multi-target collaboration to develop oral macrocyclic peptide drugs for targets selected by Argenx.
The $100 million that Novartis is committing to UNP is a combination of upfront and pre-IND milestone payments. Achieving development, regulatory, and commercial milestones could bring the startup up to $1.7 billion more. UNP would also receive royalties from sales of a commercialized product.
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