Quote:sorry to attempt to leverage your scientific expertise, but what do you think about Insmed's brensocatib relative to our drug
First I took a look at the mechanism of action. It inhibits DPP1 and it's activation of neutrophil serine proteases. My first thought was that could be a recipe for badness. I've outlined before that complete or almost complete blockade of individual proteins could cause serious adverse events because it doesn't allow normal levels of functionality. Also that leronlimab allows normal levels of functionality through the use of other receptors. Brensocatib by shutting down NSPs could throw the immune system into quite an imbalance.
So then I looked for adverse events in a trial. In their non-cystic fibrosis bronchiectasis trial the level of overall treatment-emergent adverse events (TEAEs) was nearly the same level as placebo. In serious and severe TEAEs there was a slight improvement although one would expect much better given the statistical significance in the trial results. The large increase vs. placebo in hyperkeratosis might be alarming. They don't specify what kind of hyperkeratosis it is. If it's bronchial or lung hyperkeratosis that's extremely rare and could cause major problems. The cause of that might be lack of neutrophil activation and response of macrophages to clear dead or dying tissue.
https://investor.insmed.com/2024-05-28-Insmed...chiectasis
Non-cystic fibrosis bronchiectasis is caused by chronic inflammation. Cystic fibrosis is on the disease list and anti-inflammatory in combo with CFTR modulators is listed as the usage. So non-cystic fibrosis bronchiectasis is in our wheelhouse.
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