Alvelestat

iStock, piyaphat50 Mereo BioPharma’s asset, dubbed alvelestat, is set to enter Phase 3 development for AATD-LD in 2027. Sentynl Therapeutics now has the chance to take charge of the future U.S. commercialization for Mereo BioPharma’s investigational therapy for alpha-1 antitrypsin deficiency-associated lung disease, a rare and genetic respiratory disorder. Under a Tuesday agreement , Sentynl paid an undisclosed fee for the exclusive option to market Mereo’s drug, called alvelestat, in the U.S. If Sentynl exercises that option, it will pay $40 million to Mereo, covering the deal’s upfront and R&D payments until the submission of a new drug application for the asset. Sentynl, a subsidiary of Indian multi-national Zydus Lifesciences, has also offered up to $435 million in potential milestones to Mereo, plus double-digit tiered royalties on net U.S. sales of alvelestat. Sentynl is headquartered in California. ezstandalone.cmd.push(function () { ezstandalone.showAds(129); }); Alvelestat is a small molecule blocker of the neutrophil elastase enzyme, which plays a key role in inflammation and has been implicated in the destruction of lung tissue, according to Mereo’s announcement. The oral drug is being developed for alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD), which arises from lack of the AATD protein that under healthy conditions protects the lungs against damaging enzymes like neutrophil elastase. Symptoms include shortness of breath and chronic coughs, progressing to asthma and bronchiectasis. Around 50,000 to 80,000 patients in the U.S. have AATD-LD. Phase 2 data for the asset, released in May 2023 , showed an 83.5% reduction in neutrophil elastase activity for the lower dose of alvelestat, ramping up to a 93.3% suppression in the higher dose group. Both effects were significantly superior to placebo, Mereo said at the time. The biotech subsequently aligned with the FDA on a Phase 3 design for alvelestat but in January 2024 said that it was looking for potential development partners to take the asset forward. The Sentynl deal on Tuesday will help Mereo initiate its late-stage program, which could be launched early next year, according to the release.

Sentynl Therapeutics and Mereo BioPharma have announced that they have entered into an option and license agreement for the US commercial and global manufacturing rights to alvelestat for AATD-LD. Alvelestat is a neutrophil elastase inhibitor being readied for phase 3 and, if approved, would be the first oral treatment for this rare, progressive genetic lung disease affecting an estimated 50,000-80,000 individuals in the US. The option and license agreement grants Sentynl the exclusive right to acquire a license to commercialise alvelestat for AATD-LD in the US, with Mereo retaining commercial rights in the rest of the world. The agreement also grants Sentynl global rights to manufacture alvelestat for AATD-LD and on option exercise, it provides funding for the alvelestat phase 3 development program, which could be initiated in early 2027. Dr. Sharvil P Patel, Managing Director (MD), Zydus Lifesciences, said, "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. 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." Mereo will receive a non-refundable option fee from Sentynl and, on exercise of the option, the company would also receive up to USD 40 million in upfront and R&D payments until NDA filing. Under these terms, Mereo would also be eligible to receive double-digit tiered royalties on US net sales of alvelestat. Mereo will lead the global phase 3 study and regulatory interactions until the study is completed. However, during the option period, the companies will collaborate to advance manufacturing and streamline the phase 3 study design. Matt Heck, CEO, Sentynl Therapeutics, said, "We take great pride in having built a sustainable approach for developing therapies for ultra-rare conditions, and this partnership allows us to expand that strategic focus to a larger population within the rare disease community, enabling us to help more people. For patients with AATD-LD, the current standard of care is demanding, often relying on generalised therapies or frequent intravenous treatments. We see a clear opportunity to improve upon that with alvelestat. Mereo has built a strong foundation for this asset, making them an ideal partner as we collaborate during the option period to prepare for the next phase of development."