collaborations
Johnson & Johnson
Our partnership with Ortho-McNeil-Janssen has demonstrated the strength and success of our platform. The project started in 2005 as a platformbased discovery collaboration around metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAM).
Activation of mGluR2 is an approach that was validated in Phase II clinical trials (data were published in 2007 in Nature Medicine), which showed improved symptoms of schizophrenia with efficacy similar to leading marketed drugs. At the same time, the mGluR2 agonist was differentiated compared to marketed drugs because it did not cause weight gain, extrapyramidal symptoms or lactation, all side effects that can be associated with currently marketed schizophrenia drugs. ADX71149 is well differentiated compared to other mGluR2 activators in development because of its allosteric mechanism.
From 2005 to 2007 Addex and J&J scientists collaborated on optimizing the leads that Addex brought to the partnership. Addex utilized its platform and J&J contributed medicinal chemistry and preclinical testing.
From 2007 to mid-2009 J&J advanced ADX71149 and backup molecules through preclinical development. In June 2009, an important milestone was reached when J&J began clinical testing of ADX71149. The event was ground-breaking because it was the first PAM of any mGluR subtype to enter clinical trials. ADX71149 has potential to treat schizophrenia, anxiety and other disorders.
J&J will fund and perform future development and commercialization of ADX71149, which is nearing the end of Phase I clinical testing. Under the terms, Addex has received €3 million up front, €4.3 million in research funding and a €1 million milestone payment when ADX71149 entered Phase I testing in June 2009. Addex is eligible for undisclosed additional milestone payments plus royalties.
Merck & Co., Inc.
Addex has two separate partnerships with Merck. The first, started in late 2007, is focused on discovering and developing mGluR4 PAM as drugs for Parkinson’s disease; the second, initiated in early 2008, is focused on developing mGluR5 PAM for schizophrenia.
mGluR5 PAM
Our positive allosteric modulator (PAM) of mGluR5, ADX63365, is being developed by partner Merck. This drug candidate, along with additional mGluR5 PAMs from the same chemical series, already have demonstrated efficacy in preclinical models of schizophrenia and are undergoing the final stages of testing prior to entering clinical development.
Although existing drugs have been shown to be effective at controlling psychosis, patients often experience cognitive impairment, which means they are unable to learn skills or support themselves. As such, cognitive impairment in schizophrenia is recognized by the U.S. FDA and other regulatory authorities as an unmet medical need.
In schizophrenia, the function of N-methyl-D-aspartate (NMDA) receptors is compromised. These receptors are a major subtype of glutamate receptors, whose function is considered critical for complex behaviors, such as associative learning, working memory, behavioral flexibility, and attention, many of which are impaired in schizophrenia. The mGluR5 are able to change the way NMDA receptors respond to glutamate.
Researchers from Merck published data showing that treatment with mGluR5 PAM reversed signs of both psychosis and cognitive dysfunction in a preclinical schizophrenia model. On this basis Addex believes that mGluR5 PAM, such as the ones partnered with Merck, may one day offer schizophrenia patients the most important therapeutic advance in decades – improved cognition.
The deal shows that Addex was able to discover and independently complete medicinal chemistry that is up to the standards of an organization like Merck, which has a reputation for excellent chemistry.
Under our agreement, Merck is responsible for funding and performing all future development of mGluR5 PAM for schizophrenia and other undisclosed indications. Under the terms, Addex received USD22 million up front and is eligible for milestone payments of up to USD680 million, plus royalties on sales. Addex has an option to co-promote mGluR5 PAM.
mGluR4 PAM
In November 2009, Merck and Addex extended the mGluR4 PAM research agreement for an additional year, with Merck agreeing to cover USD1.8 million in research costs at Addex in addition to the original terms of the deal. The decision followed the achievement of the first two preclinical milestones – showing that the collaboration had yielded orally available mGluR4 PAM with efficacy in an animal model of Parkinson’s disease.
The agreement, signed in December 2007, is focused on developing mGluR4 PAM for the treatment of Parkinson’s disease and other undisclosed indications. To date, Addex has received USD3 million up front, preclinical milestone payments of USD750,000, technology access fees of USD500,000 and research funding of USD600,000.
Under the terms, Addex is eligible to receive up to USD106.5 million in research, development and regulatory milestones for the first product developed for multiple indications. Additional milestones of up to USD61 million would be payable if a second and third product are developed. Addex is eligible to receive undisclosed royalties on sales of any products resulting from this collaboration. Merck is responsible for clinical development. Addex has an option to co-promote mGluR4 PAM.