Nivalis Therapeutics

Nivalis Therapeutics, founded in 2007 and formerly known as N30 Pharmaceuticals, was a clinical-stage pharmaceutical company headquartered in Boulder, Colorado. The company focused on developing small-molecule therapeutics for patients with cystic fibrosis (CF). Nivalis' core strategy revolved around the inhibition of S-nitrosoglutathione reductase (GSNOR), an enzyme linked to depleted levels of S-nitrosoglutathione (GSNO) which is associated with cystic fibrosis.

The company's lead product candidate was cavosonstat (N91115), an orally bioavailable GSNOR inhibitor designed to work as a CFTR modulator. Cavosonstat's mechanism aimed to stabilize the cystic fibrosis transmembrane conductance regulator (CFTR) protein, complementing existing corrector and potentiator therapies. Nivalis advanced cavosonstat through several clinical trials, including Phase 1 studies and multiple Phase 2 trials to evaluate its safety and efficacy as an add-on therapy for patients with specific CFTR mutations. In 2016, the U.S. FDA granted cavosonstat both Fast Track and Orphan Drug designations.

Despite initial promise, a pivotal Phase 2 trial in late 2016 failed to meet its primary endpoint of demonstrating a benefit in lung function. Following these disappointing results, Nivalis announced in early 2017 that it would discontinue the development of cavosonstat for CF, wind down its research and development activities, and explore strategic alternatives. This led to a significant restructuring, including laying off the majority of its staff. After evaluating numerous proposals, Nivalis entered into a definitive merger agreement with Alpine Immune Sciences in April 2017. The all-stock transaction was structured as a reverse merger, which provided Alpine with Nivalis' Nasdaq listing and remaining capital, creating a combined entity focused on developing protein-based immunotherapies for inflammation and immuno-oncology. The merger was completed in the third quarter of 2017, and the combined company continued under the Alpine Immune Sciences name.

Keywords: Nivalis Therapeutics, cystic fibrosis, cavosonstat, N91115, GSNOR inhibitor, CFTR modulator, small molecule therapeutics, clinical trial, reverse merger, Alpine Immune Sciences, pharmaceutical, biotechnology, F508del mutation, N30 Pharma, lung function, orphan drug, rare disease, respiratory therapeutics, drug development, biopharmaceutical