Stevenage, UK and Orlando, Fla., US – 11 April 2019 – Autifony Therapeutics Limited (“Autifony”), a clinical stage company developing new drugs to treat serious disorders of the nervous system, today announced the positive results of AUT00206 in a Phase Ib “ketamine challenge” study in healthy volunteers. AUT00206 demonstrated a significant central nervous system effect, consistent with modulation of Kv3.1/Kv3.2 ion channels, which is a first for this mechanism of action in human subjects.
The data from this clinical trial were reported today by Professor Bill Deakin of University of Manchester at the 2019 Congress of the Schizophrenia International Research Society in Orlando, Florida, USA, who was the Principal Investigator for the study.
A ketamine challenge study involves acute infusion of ketamine to healthy volunteers, which temporarily disrupts the balance of neural network activity before this is quickly restored to normal. This effect is measured by a transient increase in the blood oxygen level dependent (BOLD) signal in the brain. The acute changes in brain activity induced by ketamine are thought to model aspects of the neural dysfunction observed in patients with psychosis.
Previous studies in rodents showed that AUT00206 could inhibit the ketamine-induced increase in BOLD signal. In humans, ketamine also markedly increased the BOLD signal in two target brain areas, the dorsal anterior cingulate and thalamus, when measured using magnetic resonance imaging (MRI). AUT00206 significantly reduced the ketamine-induced increase in both areas in a dose-dependent manner. Thus, the results of this trial are highly supportive of the potential for AUT00206 to treat psychiatric disorders such as schizophrenia.
The trial design was a single-centre, double blind, placebo-controlled crossover study for 16 healthy participants. 23 healthy volunteers were randomised and 15 completed all 4 scanning sessions. AUT00206, at two dose levels or placebo, was administered prior to intravenous infusion of ketamine or saline during MR BOLD imaging. Both doses of AUT00206 were well tolerated.
John Hutchison, Autifony’s Chief Medical Officer, said: “These exciting results provide clear evidence of target engagement by AUT00206 with an entirely novel Kv3.1/3.2 mechanism in a human model relevant to psychiatric disorders such as schizophrenia. These data will inform the further development of AUT00206.”
AUT00206 is also currently under evaluation in a Phase Ib clinical trial in patients with schizophrenia, which is expected to report in H2 2019. Further molecules are showing significant promise, both in schizophrenia and other indications. Kv3.1/3.2 modulators also have the potential to treat other CNS disorders in areas of unmet medical need, such as Fragile X syndrome and certain hearing disorders.
Boehringer Ingelheim acquired an exclusive option to purchase Autifony’s Kv3.1/3.2 positive modulator platform in December 2017.
About Autifony Therapeutics Ltd
Autifony Therapeutics is an independent UK based biotechnology company formed in 2011 as a spin-out from GSK, which retains equity in the company. The Company is focused on the development of high value, novel medicines to treat serious diseases of the central nervous system. It is funded by SV Health Investors, Touchstone Innovations plc (now part of IP Group), Pfizer Venture Investments, International Biotechnology Trust PLC, and UCL Business plc.
For more information see www.autifony.com.
About Boehringer Ingelheim
Innovative medicines for people and animals have for more than 130 years been what the research-driven pharmaceutical company Boehringer Ingelheim stands for. Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies and to this day remains family-owned. Day by day, some 50,000 employees create value through innovation for the three business areas human pharmaceuticals, animal health and biopharmaceutical contract manufacturing. In 2016, Boehringer Ingelheim achieved net sales of around 15.9 billion euros. With more than three billion euros, R&D expenditure corresponds to 19.6 per cent of net sales.
Social responsibility comes naturally to Boehringer Ingelheim. That is why the company is involved in social projects such as the “Making More Health” initiative. Boehringer Ingelheim also actively promotes workforce diversity and benefits from its employees’ different experiences and skills. Furthermore, the focus is on environmental protection and sustainability in everything the company does. More information about Boehringer Ingelheim can be found on http://www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.
Schizophrenia remains a major healthcare challenge throughout the world. Patients with the condition have a poor quality of life and prognosis. Antipsychotics are the main treatment but in up to a third of people with schizophrenia, the illness shows a poor response to these drugs. Particularly debilitating are cognitive symptoms of schizophrenia, such as poor decision making, attention and memory, and negative symptoms, such as social withdrawal and anhedonia, which make work and relationships difficult to sustain. Side effects of the currently approved antipsychotic drugs are also problematic, including weight gain, diabetes, heart disease, movement disorders and sexual dysfunction. There is a clear need for more effective drugs with fewer side effects.
See ‘The Abandoned Illness’, a report by the Schizophrenia Commission, November 2012.
Issued for and on behalf of Autifony Therapeutics by Instinctif Partners.
For more information please contact: Autifony@instinctif.com