Servier has decided to exercise the option under its deal with Cortex Pharmaceuticals for Alzheimer drug candidate CX1632/S47445 and will pay $2 million. With this option Servier takes over all remaining rights to this jointly discovered compound. In connection with the option exercise, Cortex will earn certain royalties and milestone payments.
Cortex discovered CX1632 using its Ampakine technology under a research agreement with Servier, which was signed in October 2000. In November 2010, Servier selected the compound for further development. In June of this year Servier paid Cortex $1 million for the exclusive, worldwide option.
Servier reports that since then it has completed a Phase I study with the compound. “High-impact Ampakine molecules such as CX1632/S47445 may well represent a disease-modifying approach to treating memory and cognitive impairments in patients with Alzheimer disease and other disorders, given the demonstrated ability of the compounds to stimulate protective growth factors within the brain,” notes Mark Varney, Ph.D., Cortex’ president and CEO.
Emmanuel Canet, M.D., Ph.D., head of Servier R&D, adds, “S47445 is now in clinical development as a potential first-in-class compound. Such development exemplifies our commitment to finding innovative treatments for patients suffering from Alzheimer disease and our belief that AMPA modulation is a promising way to improve cognitive disorders in such patients.”
Cortex' Ampakine platform generates compounds that increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer disease.
Ampakine compounds are designated as either low impact or high impact. Both types of compounds positively modulate the AMPA receptor function. Low-impact compounds increase the amplitude of the neuronal action potential, while the high-impact compounds generally increase both the amplitude and the half-width of the neuronal action potential.
Additionally, the high impact compounds activate the expression of certain genes in the neuron, including neurotrophins such as brain-derived neurotrophic factor (BDNF). BDNF mediates the differentiation and survival of neurons by providing the necessary trophic support and modulates synaptic transmission and plasticity. Although low-impact Ampakine compounds do not significantly enhance neurotrophic factors, they are able to improve the strength of the synaptic connections through their potentiation of the AMPA receptors.
Besides the Servier-partnered CX1632/S47445, Cortex’ clinical pipeline includes CX717 for drug-induced respiratory depression (Phase II), CX1739 for sleep apnea (Phase II), and CX1739 for ADHD (Phase I). All three candidates are high-impact ampakines. Preclinical development includes candidates for treating Alzheimer and Parkinson diseases and are low-impact ampakines.