Sentynl Secures Option for U.S. Rights to Mereo’s Alpha-1 Lung Disease Drug

Rare Daily Staff

Sentynl Therapeutics has entered into an option and license agreement with Mereo BioPharma for U.S. commercialization rights to alvelestat, an investigational oral therapy for alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD).

Under the agreement, Sentynl, Zydus Lifesciences’ U.S.-based rare-disease subsidiary, has an exclusive option to license alvelestat for commercialization in the United States. Mereo will retain commercial rights outside the U.S. and lead the global Phase 3 study and regulatory interactions through study completion. Upon exercise of the option, Sentynl would also receive global manufacturing rights for alvelestat.

Mereo will receive an undisclosed, non-refundable option fee. If Sentynl exercises the option, Mereo could receive up to $40 million in upfront and research-and-development payments through new drug application filing, as well as double-digit tiered royalties on U.S. net sales. The deal also includes up to $435 million in potential regulatory and commercial milestone payments.

The companies will use the short option period to advance manufacturing plans and refine the design of the planned global Phase 3 trial. If Sentynl exercises the option, it would fund the Phase 3 development program, which could begin in early 2027.

For Sentynl, the deal expands its rare-disease commercial portfolio with a late-stage respiratory asset. For Mereo, it provides a potential source of U.S. development funding and commercialization support while preserving the program’s value outside the United States. The transaction remains contingent on Sentynl exercising its option.

People with severe alpha-1 antitrypsin deficiency lack sufficient alpha-1 antitrypsin protein, which normally helps protect the lungs from enzyme-mediated damage during inflammation. The resulting lung disease can lead to emphysema, worsening shortness of breath, chronic cough, sputum production and acute exacerbations.

Alvelestat is an oral small-molecule inhibitor of neutrophil elastase, an enzyme implicated in inflammation and lung-tissue destruction. Mereo is developing the candidate for AATD-LD, the pulmonary manifestation of inherited alpha-1 antitrypsin deficiency.

If approved, alvelestat could become the first oral treatment specifically for AATD-LD. Current care can include nonspecific respiratory therapies and, for some patients, regular intravenous augmentation therapy—an important clinical, commercial and patient-access rationale for the partnership.

Mereo said alvelestat is supported by positive efficacy findings from two Phase 2 studies and has been evaluated for safety and tolerability in more than 1,000 patients across respiratory-disease studies. The drug has received orphan drug designation from the FDA and European Commission for AATD-LD, as well as FDA Fast Track designation.

“This partnership marks a pivotal moment for Sentynl’s rare disease strategy.  Mereo’s alvelestat is a highly promising, differentiated candidate that meaningfully expands our portfolio and has the potential to address an area of significant unmet need,” said Sharvil Patel, managing director, Zydus Lifesciences. “AATD-LD has a profound impact on patients’ lives. If approved, alvelestat has the potential to be a meaningful new option that could help their quality of life.”

Photo: Sharvil Patel, managing director, Zydus Lifesciences.