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Sentynl gains US rights to Mereo's Phase III alvelestat for alpha-1 lung disease

Sentynl gains US rights to Mereo's Phase III alvelestat for alpha-1 lung disease

Mereo BioPharma (Nasdaq: MREO) and Solana Beach, California-based Sentynl Therapeutics have entered an option and license agreement granting Sentynl exclusive US commercial rights and global manufacturing rights to alvelestat, a Phase III-ready oral neutrophil elastase inhibitor for alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). Mereo retains global development leadership and all ex-US commercial rights.

The deal centers on a two-stage payment structure. Mereo receives an undisclosed non-refundable option fee at signing; on exercise, it becomes eligible for up to USD 40 million in upfront and research and development payments through new drug application filing, plus double-digit tiered royalties on US net sales. The companies will use a short option period to refine the global Phase III design, with trial initiation targeted for early 2027.

Alvelestat, described by the company as designed to inhibit neutrophil elastase — a serine protease involved in lung tissue destruction — has been evaluated in over 1,000 patients across multiple respiratory indications, including AATD-LD, according to Mereo. It holds FDA Orphan Drug Designation, FDA Fast Track designation, and European Commission Orphan Drug Designation for AATD-LD. The company said two Phase II studies generated positive efficacy data supporting the Phase III design. If approved, Mereo asserts it would be the first oral treatment for the condition, which affects an estimated 50,000–80,000 people in the US.

Sentynl has expanded its rare disease portfolio through a series of acquisitions and licensing deals, including Zokinvy (lonafarnib) for Hutchinson-Gilford Progeria Syndrome and progerinin (SLC-D011), another progeria program. The company also received US FDA approval for ZYCUBO (copper histidinate) for Menkes disease in January 2026.

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AATD-LD is also attracting competing development approaches. Sanofi is advancing efdoralprin alfa, a recombinant AAT-Fc fusion protein acquired through its approximately USD 2.2 billion Inhibrx transaction, following positive Phase II data reported in 2025. Alvelestat instead directly inhibits neutrophil elastase and could offer an oral alternative to protein replacement and intravenous augmentation approaches if its Phase II findings translate into the planned Phase III program.


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