Sentynl, Mereo Partner to Advance Oral AATD Lung Disease Therapy

Sentynl Therapeutics, a U.S.-based biopharmaceutical company and wholly owned subsidiary of Zydus Lifesciences, has entered into an option and license agreement with clinical-stage rare disease company Mereo BioPharma to advance alvelestat, an investigational oral therapy for alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD).

Under the agreement, Sentynl will receive an exclusive option to acquire U.S. commercial rights to alvelestat for AATD-LD, while Mereo will retain commercial rights in markets outside the United States. Sentynl will also receive global manufacturing rights for the therapy. If Sentynl exercises the option, the agreement provides funding for the next stage of alvelestat’s development, including a planned global Phase 3 program that could begin in early 2027.

Mereo will receive a non-refundable option fee from Sentynl. If the option is exercised, Mereo could receive up to $40 million in upfront and research and development payments through the filing of a New Drug Application (NDA). The company would also be eligible for double-digit tiered royalties based on U.S. net sales of alvelestat.

Mereo will continue to lead the global Phase 3 study and regulatory interactions through completion of the study. During the option period, the two companies will work together on manufacturing activities and further refine the design of the planned Phase 3 program.

Alvelestat is an oral small-molecule inhibitor of neutrophil elastase (NE), an enzyme involved in inflammation and the destruction of lung tissue. By inhibiting NE, the therapy is designed to reduce inflammatory damage and potentially slow disease progression in patients with AATD-LD.

Alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder in which patients have insufficient levels of alpha-1 antitrypsin, a protein that protects lung tissue from enzymes released during inflammatory responses. Severe deficiency can lead to progressive emphysema and other respiratory complications.

Patients with AATD-LD may experience severe shortness of breath, chronic coughing and sputum production, as well as an increased susceptibility to acute exacerbations. Some patients may also develop asthma or bronchiectasis. Mereo estimates that approximately 50,000 to 80,000 people in the United States have AATD-LD associated with the Pi*ZZ genetic variant.

If approved, alvelestat could become the first oral treatment specifically targeting this rare genetic lung disease, potentially offering an alternative to current treatment approaches that can involve frequent intravenous administration.

The drug’s development is supported by clinical experience across more than 1,000 patients with various respiratory conditions, including AATD-LD, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, COVID-19 and bronchiolitis obliterans syndrome following allogeneic stem cell transplantation. Mereo said alvelestat has demonstrated an established safety and tolerability profile in clinical trials.

The candidate has also received regulatory designations intended to support its development. Alvelestat has received Orphan Drug Designation from both the U.S. Food and Drug Administration and the European Commission for AATD-LD. The FDA has additionally granted the program Fast Track designation.

Mereo has been preparing alvelestat for global Phase 3 development following positive efficacy findings from two Phase 2 studies. The company expects its collaboration with Sentynl to help further optimize the Phase 3 study design and strengthen manufacturing readiness ahead of the planned trial.

Sharvil P. Patel, Managing Director of Zydus Lifesciences, said the agreement represents an important development for Sentynl’s rare disease strategy. He highlighted alvelestat’s potential to provide a new treatment option for patients with AATD-LD, a condition associated with significant disease burden.

Matt Heck, CEO of Sentynl Therapeutics, said the partnership expands the company’s focus from ultra-rare conditions to a larger population within the rare disease community. He also pointed to the potential benefits of an oral treatment compared with existing approaches that may require frequent intravenous treatments.

Mereo CEO Denise Scots-Knight said the company believes Sentynl’s rare disease expertise and commercial infrastructure make it a strong partner for alvelestat. The companies will now collaborate during the option period while preparing for the next phase of development.

The agreement adds another late-stage opportunity to Mereo’s rare disease portfolio, which also includes programs targeting osteogenesis imperfecta and autosomal dominant osteopetrosis type 2. For Sentynl and parent company Zydus, the deal provides an opportunity to expand their presence in rare respiratory diseases and potentially bring a differentiated oral therapy to patients with AATD-LD.