Biopharma company Argenx has announced a strategic partnership with startup Unnatural Products to develop oral macrocyclic peptides, marking a significant shift toward more convenient drug delivery methods for inflammatory and immunological diseases. The collaboration, valued at up to $1.5 billion, represents one of the largest deals in the macrocyclic peptide space and highlights the growing interest in this emerging drug class.
Partnership Structure and Financial Terms
The comprehensive agreement includes an undisclosed upfront payment in the double-digit millions, milestone payments, research and development funding, and an equity investment in Unnatural Products. According to Cameron Pye, CEO of Unnatural Products, the timing of this partnership is particularly strategic given the challenging biotechnology investment climate over the past half-decade.
"We've always found [collaborations] to be great opportunities, not just to bring dollars in the door when the equity markets can be a little bit challenging—as they have been for, say, the last half-decade—but also to bring some additional learnings and strategy to the table," Pye explained.
The partnership emerged organically when Argenx's business development group approached Unnatural Products approximately 6-9 months ago, just as the startup was planning to reach out to the company about potential collaboration opportunities.
Addressing Current Treatment Limitations
Argenx currently focuses on immunology and markets antibody drugs for myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. The company's lead product, Vyvgart (efgartigimod), recently received FDA approvals and helped Argenx achieve profitability for the first time last year.
However, like other antibodies, Vyvgart must be delivered by infusion or injection, as does Argenx's second investigational drug, empasiprubart. This delivery limitation represents a significant treatment burden for patients, despite the therapeutic advances these medications provide.
"Patients now suddenly have options that they never had before," Pye noted. "They can treat and manage their diseases in a way that was really unmanageable even 5 or 10 years ago, but they come with a lot of asterisks. What we're looking to do is remove those asterisks and provide a shelf-stable, once-daily, oral pill solution for these things."
Macrocyclic Peptide Advantages
Macrocyclic peptides are small chains of amino acids that form loops, a structural feature that provides several therapeutic advantages over traditional antibodies. The looped shape offers more surface area for disrupting protein-protein interactions and helps the drug remain intact inside the body, unlike traditional antibodies which are vulnerable to breakdown by proteases.
This stability translates to practical benefits including shelf stability without the cold storage requirements of traditional antibodies and the potential for oral administration as simple pills. These characteristics could significantly improve patient convenience and treatment adherence while reducing healthcare system costs associated with infusion centers and specialized storage.
Development Strategy and Timeline
While Pye declined to specify exact targets, diseases, or clinical development timelines beyond "as fast as possible," the partnership encompasses multiple targets of interest identified by Argenx across multiple indications. The collaboration allows Unnatural Products to leverage Argenx's expertise in immunology while providing validation for the startup's technology platform.
"Backing from Argenx also helps Unnatural Products claw our way up the validation ladder as a small company," Pye acknowledged.
Broader Pipeline and Future Plans
Unnatural Products, which employs a 40-person team, maintains existing collaborations with BridgeBio Pharma and Merck & Co. for rare diseases and cancer applications. The company continues advancing its internal pipeline alongside the partnered assets and is currently in the process of raising a Series B financing round.
The partnership represents a significant validation of macrocyclic peptides as a viable drug class and could accelerate development timelines for oral alternatives to injectable immunology treatments. As the biotechnology industry continues to face funding challenges, strategic partnerships like this one may become increasingly important for advancing innovative therapeutic platforms.
