Alto raises $120m for resistant depression programme
Amit Etkin, Alto's founder, president, and CEO.
NYSE-listed Alto Neuroscience has raised $120 million in a private placement that will be used to advance its recently acquired candidate for treatment-resistant depression (TRD) into a pivotal trials programme.
Led by Commodore Capital, the financing shores up the Mountain View, California biotech's cash reserves as it prepares to start a phase 2b study of ALTO-207 (formerly CTC-501), a fixed-dose combination of dopamine D3/D2 agonist pramipexole and 5-HT3 receptor antagonist ondansetron originally developed by Chase Therapeutics, in the first half of this year.
Alto – which is developing a pipeline of drugs based on what it calls 'precision psychology' – said the proceeds will allow it to advance ALTO-207 through a planned phase 3 programme due to start in early 2027 and toward potential marketing applications. The company ended last year with cash reserves of $177 million, enough to fund operations into 2028.
Pramipexole is known primarily as a treatment for Parkinson's disease, but is also used off-label as an adjunctive treatment for TRD as well as treatment-resistant bipolar depression.
It is plagued by side effects like nausea, however, and ALT-207 seeks to overcome that limitation with the addition of ondansetron, a drug that has been used for decades to prevent nausea and vomiting; for example, in people receiving chemotherapy or radiotherapy.
Alto's founder and chief executive, Amit Etkin, said the drug is a potential game-changer in TRD, which affects millions of people around the world, pointing to the recent PAX-D study published in The Lancet Psychiatry, in which pramipexole was used to augment standard antidepressant treatment, improving symptoms over 12 weeks, but also increasing the side effect burden for patients.
Etkin said the study "provides robust, independent validation of our approach, and we are moving ALTO-207 into a potentially pivotal phase 2b trial with high conviction."
Depression that doesn't respond to standard serotonin- and norepinephrine-acting antidepressants has been a major unmet medical need for many years, although, new therapeutic options have started to emerge, including Johnson & Johnson's glutamate-acting nasal spray Spravato (esketamine), approved in 2019, and various psychedelic therapies in clinical testing.
According to Alto, the PAX-D results showed a significantly larger effect size than current standard-of-care treatments for TRD. Its phase 2b trial will enrol a target of 178 patients with TRD in the US and UK, and will compare ALT-207 to placebo given on top of their baseline antidepressant medication.
The company is anticipating four key data readouts across its precision psychiatry pipeline in the next couple of years, including phase 2 results with PDE4 inhibitor ALT-101 for cognitive impairments associated with schizophrenia, and phase 2b data with melatonergic agonist and serotonergic antagonist ALTO-300 in major depressive disorder and neural plasticity enhancer ALTO-100 in bipolar depression.
