Sentynl Therapeutics secured a U.S. option for Mereo BioPharma’s alvelestat, an oral neutrophil elastase inhibitor advancing toward Phase 3 in AATD-LD.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Sentynl Therapeutics, the U.S.-based biopharmaceutical subsidiary of Zydus Lifesciences, has entered an option and license agreement with Mereo BioPharma for alvelestat, an oral neutrophil elastase inhibitor in development for alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). If Sentynl exercises the option, it will commercialize alvelestat in the United States, while Mereo will retain rights in the rest of the world and lead global development.
Partnership Advances Alvelestat Toward Phase 3
The agreement covers U.S. commercial rights and global manufacturing rights for alvelestat. Mereo will receive a non-refundable option fee and, if Sentynl exercises the option, up to $40 million in upfront and research and development payments through the filing of a New Drug Application (NDA). Mereo will also receive double-digit tiered royalties on U.S. net sales.
The companies will use the option period to refine the design of a global Phase 3 program and advance manufacturing activities. The Phase 3 study could begin in early 2027, with Mereo leading the trial and regulatory interactions until study completion.
Targeting a Key Driver of Lung Damage
AATD is a genetic disorder characterized by deficient levels of alpha-1 antitrypsin, a protein that protects lung tissue from enzymes released during inflammation. Severe deficiency can lead to pulmonary emphysema, causing progressive shortness of breath, chronic cough, sputum production and susceptibility to acute exacerbations.
Patients can also develop asthma and bronchiectasis. The companies estimate that approximately 50,000 to 80,000 people in the U.S. have the Pi*ZZ form of AATD associated with lung disease.
Current management can involve generalized respiratory therapies and, for some patients, frequent intravenous treatment. The development of an oral therapy could therefore address an important treatment burden if clinical efficacy and safety are confirmed.
Phase 2 Data Support Further Development
Alvelestat is an oral small molecule that inhibits neutrophil elastase (NE), an enzyme involved in inflammation and lung tissue destruction. According to the companies, its small-molecule properties allow it to reach both cell-bound and soluble elastase and penetrate lung tissue.
Mereo has reported positive efficacy findings from two Phase 2 studies and is preparing the candidate for Phase 3. However, the announcement does not disclose the numerical efficacy results, endpoint data or statistical analyses from those studies.
The safety and tolerability profile has been evaluated in more than 1,000 patients across respiratory disease programs, including AATD-LD, COPD, bronchiectasis, cystic fibrosis, COVID-19 and bronchiolitis obliterans syndrome following allogeneic stem cell transplantation.
Executive Perspective
Dr. Sharvil P. Patel, Zydus Lifesciences highlighted alvelestat’s potential to address a significant unmet need in AATD-LD by providing a new treatment option for patients.
Denise Scots-Knight, Mereo BioPharma emphasized that positive Phase 2 efficacy data have positioned alvelestat for global Phase 3 development, with the partners now refining the trial design.
Regulatory Designations and Next Steps
Alvelestat has received Orphan Drug Designation from both the FDA and European Commission for AATD-LD, as well as FDA Fast Track designation.
The partnership now shifts the program toward Phase 3 preparation. If Sentynl exercises its option, it will fund the Phase 3 development program and commercialize alvelestat in the U.S., while Mereo continues global development and retains commercial rights elsewhere.
For AATD-LD, the key development question is whether the Phase 3 program can translate the Phase 2 efficacy signal into clinically meaningful outcomes and establish alvelestat as an effective oral treatment option for this progressive genetic lung disease.
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About the Writer
Samiksha Vikram Jadhav (LinkedIn) is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.