Autifony Therapeutics is gearing up to test its schizophrenia candidate AUT00206 in a pair of Phase Ib studies. The advance of the asset, which comes one year after Pfizer Venture Investments and others bankrolled Autifony’s expansion into schizophrenia, is underpinned by safety data from a 60-person Phase I trial.
London, U.K.-based Autifony spun out of GlaxoSmithKline ($GSK) in 2011 to develop an age-related hearing loss program, before branching out into schizophrenia in response to evidence that Kv3 voltage-gated potassium channels play a role in the disease. Pfizer’s ($PFE) VC wing, SV Life Sciences and other investors handed Autifony £8 million ($10.5 million) to explore this idea last year, giving the company the financial means to push AUT00206 through the Phase I trial.
The single-site, double-blind, randomized, placebo-controlled study featured two parts. In the first stage, participants, who were either fasting or fed, received up to 5 single doses of AUT00206 or a placebo. The second stage was a multiple ascending dose study.
Autifony has exited the Phase I trial with data it thinks show AUT00206 is safe, well tolerated and has pharmacokinetics capable of supporting clinically effective concentrations of the drug. Armed with the data, Autifony is pushing ahead with a pair of Phase Ib trials designed to give it a clearer picture of whether the effects it has seen in preclinical translate into the clinic.
One of the studies will be overseen by Bill Deakin, a professor at the University of Manchester who has spent more than a decade researching schizophrenia. Autifony has described the trial as a “ketamine challenge study.” In challenge studies, researchers induce diseaselike states in subjects. Johnson & Johnson ($JNJ) is among the companies that have used ketamine for this purpose. The Big Pharma gave low doses of the party drug to induce psychotic symptoms in healthy volunteers, enabling it to gauge the effectiveness of its candidate JNJ-40411813.
The second Phase Ib planned by Autifony will enroll patients with schizophrenia. Autifony is looking to this trial to generate data on clinical biomarkers of efficacy.
The belief that AUT00206 can have an effect on patients with schizophrenia is underpinned by knowledge of the role Kv3 channels play in the control of parvalbumin-positive interneurons. These interneurons are thought to malfunction in schizophrenia, leading to suggestions that modulation of the Kv3 channels could improve outcomes in patients.
Autifony is exploring this idea in parallel to its work on hearing disorders. Both aspects of the pipeline are built upon understanding of Kv3 channels, which, as well as being linked to schizophrenia, are involved in the neural circuits that handle the processing of sound. AUT00063, Autifony’s lead drug, is currently being tested as a way to improve speech recognition in users of cochlear implants.
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