Apnimed has raised $25 million to develop a pharmacological treatment for obstructive sleep apnea (OSA). The series B financing will enable Apnimed to deliver data from phase 2 trials of its oral drug candidate in the second quarter and push on into late-stage development.
In OSA patients, muscles that normally keep the upper airway open collapse repeatedly during sleep, causing intermittent low oxygen levels and leading to long-term morbidity and mortality. Continuous positive air pressure is effective in OSA, but poor adherence to the treatment, which entails wearing a mask during sleep, is suboptimal. Neurostimulation implants are also effective, but some patients are ineligible for the devices and other people are reluctant to undergo the surgical procedure.
Apnimed is betting that there is a market for a pharmacological alternative. Morningside Ventures has bought into the idea, backing Apnimed in an earlier financing before returning to lead the series B with assists from new investors Seligman Investments and Tao Capital Partners.
The money will support development of AD109, an oral therapy that contains atomoxetine and the new chemical entity aroxybutynin. Atomoxetine is a selective norepinephrine reuptake inhibitor used in the treatment of attention deficit hyperactivity disorder. Brigham and Women’s Hospital scientists identified atomoxetine as a molecule that can counter the withdrawal of endogenous noradrenergic drive that is thought to lead to OSA during non-REM sleep.
Aroxybutynin, a selective antimuscarinic molecule, is used in combination with atomoxetine because there is also evidence that active muscarinic inhibition contributes to OSA in REM sleep. Originally, Apnimed used a different antimuscarinic molecule, oxybutynin, in combination with atomoxetine, but it advanced AD109 after completing a 140-subject phase 2 trial of the older drug cocktail.
Apnimed began two phase 2 clinical trials of AD109, one which is focused on mild-to-moderate OSA patients and another which is also accepting patients with severe disease, in late 2020, early 2021. With top-line data from the studies due in the second quarter, Apnimed is now making plans for its move into phase 3. The series B will support the initiation of the phase 3 program.
The clinical trial program is part of a multidecade effort to develop a pharmacological OSA therapy. That effort has failed to deliver an effective therapy, but multiple groups are still trying. Bayer is running a phase 2 trial of a drug designed to block protein channels in the upper airways, while other groups are exploring molecules such as acetazolamide, eszopiclone and venlafaxine alone and in combination.