Argenx and Unnatural Products Sign $1.5 Billion Deal to Develop Macrocyclic Peptide Therapies

Argenx has entered into an agreement with California-based Unnatural Products (UNP) to explore the development of macrocyclic peptides for challenging biological targets. The arrangement includes up to $1.5 billion in potential payments to UNP, covering research, development, regulatory, and commercial milestones, as well as option fees.

The collaboration centers around the use of UNP’s proprietary discovery platform. This platform is designed to produce macrocyclic peptides that are “potent, selective, and orally available,” according to the release. The specific disease targets selected for the program were not disclosed, but they will be determined by Argenx.
As part of the agreement, UNP will be responsible for the early stages of research and development. This will include work leading up to studies necessary for progressing a therapeutic candidate toward clinical trials. Argenx retains the right to advance any selected candidates through human testing and commercial launch if it chooses to exercise that option.
Although the exact figures for the upfront payment and R&D funding have not been revealed, UNP confirmed that the deal includes near-term and research funding components. In addition to the milestone-related financial terms, UNP is also eligible to receive royalties on future product sales if any therapies reach the market.
The partnership also involves a strategic equity investment by Argenx in UNP. Argenx, headquartered in Amsterdam, is known for its autoimmune treatment Vyvgart, and its subcutaneous variant Vyvgart Hytrulo.
UNP has promoted its drug discovery platform as “the first scalable platform to engineer synthetic macrocycles using AI-guided design, parallel synthesis, and direct-to-biology screening.” This technology aims to address long-standing issues in macrocyclic drug development, such as challenges with pharmacokinetics, cell permeability, and oral bioavailability.

Macrocyclic compounds, including cyclosporine and erythromycin, have been used in medicine for decades. However, efforts to systematically develop this drug class have been limited due to technical hurdles. The field has gained renewed attention in recent years, with pharmaceutical companies considering macrocyclic peptides as a potential new therapeutic category.
Merck & Co., which has previously invested in UNP and entered into its own collaboration with the biotech, had described macrocyclic peptides in 2023 as the “next wave of drug discovery.”