Addex Therapeutics Ltd. (fka ADDXF)

[tykundegex]

Article from Sep 5:
https://www.addexpharma.com/fileadmin/user_upload/Media_Exposure/T_11.09.05_Scrip_-_mGluR4_Returns.pdf

Addex Pharmaceuticals, the Swiss biotech, has found itself once again a potential innocent bystander in the integration of Merck & Co and Schering-Plough. On 2 September, just after the markets had closed, Addex announced that Merck had opted not to continue developing orally available positive allosteric modulators (PAM) targeting the metabotropic glutamate receptor 4 (mGluR4) as potential treatments for Parkinson’s disease and other undisclosed indications.

It appears that Addex is the victim of internal R&D debate at Merck. “The decision to discontinue the research collaboration was based on the continuing prioritisation of our pipeline,” Merck spokeswoman Caroline Lappetito told Scrip.

Merck will instead focus its Parkinson’s disease research on its Phase III candidate preladenant, a novel selective adenosine 2A (A2A) receptor antagonist.”It is a proven clinical target for Parkinson’s disease and one where we have developed deep knowledge around the clinical profile of the target. mGluR4 remains an attractive preclinical hypothesis with a potentially useful candidate but is still in early discovery and much remains to be learned about it,” added Ms Lappetito.

mGluR4 activators are thought to work via two distinct mechanisms to alleviate Parkinson’s disease and possibly slow disease progression. First, mGluR4 activation triggers a compensatory mechanism that may spare or potentiate the use of dopamine receptor activators. Second, mGluR4 activation may have a neuroprotective effect that helps to preserve the brain’s dopaminergic neurons.

Despite retreating from its deal with Addex, Merck confirmed to Scrip that it believes mGluR4 remains an attractive preclinical hypothesis with a potentially useful candidate profile. “We are committed to studying this and other hypotheses for developing potential treatments for Parkinson’s disease,” added Ms Lappetito.

Addex first attracted Merck as a partner for the mGluR4 programme in 2007, soon after it had identified and validated hits and started lead optimisation. The signing on fee was $3 million with the promise of additional potential milestones up to $167 million. Two preclinical milestones were received by Addex in 2008 and 2009, securing an additional $3.3 million in funding. In 2009, Merck extended the research collaboration beyond the scope of the original 2007 accord.

The collaborative phase of theagreement came to an end late 2010 and Merck had been expected to advance leads into late preclinical development, towards clinical testing.

While acknowledging that the programme is still preclinical, Addex’s management is convinced that the mGluR4 approach has much promise and that its efforts are more advanced than those of others. “A lot of companies are looking at this target. We hit two important preclinical milestones and have not seen anyone else achieve that yet. We will now get all the know-how, compounds, assays, data and assets back and will re-evaluate the package and then look for new partners,”Dr Bharatt Chowrira, Addex’s newly installed CEO, told Scrip.

“The financial market attributed no value to the programme as it was still preclinical. Now that it is unpartnered it is potentially more valuable as we will be able to monetise the assets,” Addex Chief Financial Officer, Mr Tim Dyer told Scrip. Mr Dyer estimates that the programme has attracted approximately $20 million of investment based on the full time equivalents contribution of both partners for the duration of the collaboration.

Addex has yet to decide what it will do with the mGluR4 programme. “We could look for another partner now or continue to develop it ourselves, which could help accelerate the pace of the programme. What we do know is that these assets will not end up sitting on a shelf. We will move them forward,” Dr Chowrira told Scrip.

This is the second programme that Merck has halted with Addex. At its first half year results on 27 July, Addex revealed that Merck had handed back all intellectual property associated with ADX63365 and other mGluR5-targeted PAM candidates, as well as back-ups, as potential treatments of schizophrenia. The deal was originally signed in January 2008 with an upfront fee of some $22 million and the potential for an additional $680 million in milestones.

Addex has two programmes currently in Phase IIa testing: dipraglurant (ADX48621), a mGluR5 negative allosteric modulator to treat Parkinson’s disease levodopainduced dyskinesia; and ADX71149, an mGluR2 PAM, being developed by partner Janssen Pharmaceuticals, to treat schizophrenia.