Unnatural Products and Novartis Enter Licensing Agreement for Macrocyclic Peptide Therapeutics in Cardiovascular Disease
Unnatural Products, Inc. (UNP), a privately held biotechnology company headquartered in Santa Cruz, California, announced a research collaboration and licensing agreement with Novartis (Basel, Switzerland) to develop macrocyclic peptide therapeutics against an undisclosed target in cardiovascular disease. Under the Novartis licensing agreement, UNP serves as the technology originator and licensor, contributing its AI-enhanced macrocyclic peptide platform to generate drug candidates, while Novartis assumes responsibility for IND-enabling studies, clinical development, manufacturing, and global commercialization of any products emerging from the collaboration. The deal appears to grant Novartis worldwide rights, consistent with the press release language referencing "global commercialization," though specific territorial terms were not detailed. Financial specifics of the deal were partially disclosed.
UNP will receive up to USD 100 million in combined upfront and pre-IND milestone payments, though the split between cash at signing and contingent pre-IND milestones was not broken out separately. The company is also eligible for up to USD 1.7 billion in development, regulatory, and commercial milestone payments, bringing the total potential deal value to approximately USD 1.8 billion in biobucks. UNP will additionally receive tiered royalties ranging from mid-single digits up to low double digits on annual net sales of any commercialized products. No option structure was disclosed, suggesting Novartis has committed rights from the outset rather than an opt-in arrangement. No equity investment by Novartis in UNP was referenced in the announcement, distinguishing this deal from UNP's July 2025 collaboration with argenx, which did include an equity component.
Deal Context
Macrocyclic peptides occupy a modality space between conventional small molecules and large biologics. These constrained cyclic structures can engage protein surfaces — including protein-protein interactions and other binding interfaces historically resistant to small-molecule intervention — with selectivity and potency closer to that of antibodies, while retaining physicochemical properties more amenable to oral delivery. UNP's peptide drug discovery platform integrates AI-guided molecular design, massively parallel synthesis, and direct-to-biology screening to identify and optimize macrocyclic candidates. The company has emphasized oral bioavailability as a core capability of its macrocyclic peptide platform, a property that remains technically challenging for peptide-class molecules and that would represent a differentiating feature relative to injectable biologics in chronic cardiovascular indications.
The specific biological target and indication within cardiovascular disease were not disclosed. The press release characterizes the program as addressing a "previously undruggable" target, language consistent with protein-protein interactions or intracellular targets where conventional modalities have had limited success. No clinical trial registrations associated with UNP or with a Novartis-sponsored macrocyclic peptide cardiovascular program were identified on ClinicalTrials.gov at the time of announcement, consistent with a preclinical or discovery-stage program. The deal structure — in which Novartis takes over from IND-enabling studies onward — further supports an early-stage characterization.
For Novartis, the Unnatural Products licensing deal adds a modality not previously represented in the company's disclosed cardiovascular portfolio. Novartis's existing cardiovascular pipeline includes inclisiran (Leqvio), an siRNA targeting PCSK9 licensed from Alnylam Pharmaceuticals; pelacarsen, an antisense oligonucleotide targeting lipoprotein(a) licensed from Ionis Pharmaceuticals and currently in Phase 3 (NCT04023552); and abelacimab, an anti-Factor XI monoclonal antibody developed through Novartis-backed Anthos Therapeutics. These assets span nucleic acid therapeutics and antibodies but do not include macrocyclic peptides. The addition of UNP's platform-derived candidates gives Novartis access to a modality that could address target classes outside the reach of its current approaches, particularly if oral delivery proves feasible for the selected cardiovascular target. Novartis has prior experience with macrocyclic peptide partnerships through its existing relationship with PeptiDream (Tokyo, Japan), which has supplied macrocyclic peptide hits across multiple therapeutic areas, though those collaborations have not been publicly linked to cardiovascular programs.