With an aim to develop ADX63365, an orally available drug candidate for the potential treatment of schizophrenia and other undisclosed indications, allosteric modulation company Addex Pharmaceuticals has signed an exclusive worldwide license agreement with Merck & Co., Inc. The deal also includes mGluR5 PAM backup compounds discovered by Addex, revealed the company source.
ADX63365, currently in preclinical development, is a positive allosteric modulator (PAM) that targets the metabotropic glutamate receptor 5 (mGluR5), which is believed to be important as a target for the treatment of schizophrenia and other conditions. Allosteric modulators are an emerging new class of therapeutic agents.
Under the terms of the agreement, Addex will receive $22 million upfront fee and up to $455 million in research, development, regulatory and sales milestones for the first product developed for two indications. Also the company is eligible to receive up to $225 million in additional development, regulatory and sales milestones for a second product developed in two indications.
Addex said it would also receive royalties on sales of any products resulting from this collaboration. In addition, the company has an option to co-promote in certain European Union countries and will participate in the joint oversight committee for further development that will be led by Merck.
"We are thrilled to establish a second deal with Merck to develop this groundbreaking new approach for patients suffering from schizophrenia and other important diseases," said, Vincent Mutel, CEO, Addex. "This deal confirms that Addex can successfully leverage its technology to produce drug candidates that can have broad benefit for human health."
"Merck scientists were the first to identify the potential for targeting mGluR5 to treat schizophrenia," said, Darryle D. Schoepp, senior vice president and franchise head, neuroscience, Merck Research Laboratories. "Through this second collaboration with Addex, we have now gained access to a promising drug candidate targeting this receptor that potentially allows us to address an area of high medical importance where current therapies are clearly inadequate."
Earlier, on December 3, 2007, Addex announced a separate collaboration with an affiliate of Merck, Merck Sharp & Dohme Research Ltd, to discover and develop PAMs targeting mGluR4 for the treatment of parkinson's disease and other undisclosed indications.
"We now expect 2008 full year cash burn to be in the range of CHF 25-30 million," said, Tim Dyer, CFO of Addex.
mGluR5 in Schizophrenia
Preclinical research shows that activation of mGluR5 using positive allosteric modulators can act as an antipsychotic and reverse cognitive dysfunction of schizophrenia. As a result, a product like ADX63365 could become first-line anti-psychotic therapy that also improves cognitive dysfunction, thereby offering substantial advantages over other therapies on the market or in development. In schizophrenia cognitive impairment is regarded as a core deficit and was recently recognized by FDA as a separate indication within schizophrenia for which a drug could win approval.
Schizophrenia is a chronic, severe, and disabling brain disease. About 1.1 per cent of the US population over 18 years of age are suffering from the illness in any given year, according to the US National Institute of Mental Health (NIMH). Although schizophrenia affects men and women with equal frequency, the disorder often appears earlier in men, usually in the late teens or early twenties, than in women, who are generally affected in the twenties to early thirties.