**The following is a news release published October 25 by Amarantus BioSciences discussing positive behavioural efficacy data for MANF, the company’s powerful therapeutic protein with neuron-protective properties. Data from a neurorestoration 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease shows superiority of MANF over GDNF, a neurotrophic factor currently in a Phase 2 clinical trial as a disease-modifying treatment for Parkinson’s disease. MANF is currently pre-clinical development for the treatment of several apoptosis-related disorders, including Parkinson’s disease. MANF has the potential to serve as a first-in-class treatment and through the potential to save neurons from cell death may stop and/or reverse debilitating effects. There is a short position failure to deliver for Amarantus BioSciences, according to NASDAQ.**
Amarantus BioSciences Announces MANF Demonstrates Superiority over GDNF in Neurorestoration Behavioural Animal Model of Parkinson’s Disease
SUNNYVALE, Calif., Oct. 25, 2012 /PRNewswire/ — Amarantus BioSciences, Inc. (AMBS), a biotechnology company developing new disease-modifying treatments and diagnostics for Parkinson’s disease and Traumatic Brain Injury centred on its proprietary anti-apoptosis therapeutic protein MANF, today announced that the Company has received positive behavioural efficacy data for MANF in a neurorestoration 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease. The data shows superiority of MANF over GDNF, a neurotrophic factor currently in a Phase 2 clinical trial as a disease-modifying treatment for Parkinson’s disease, by demonstrating that when MANF is delivered directly to the primary brain region associated with Parkinson’s called the substantia nigra, MANF significantly reduced behavioural deficits in the model, whereas GDNF did not.
In Parkinson’s disease, the nigro-striatal network (substantia nigra – striatum) is compromised due to the degeneration of dopaminergic neurons in the substantia nigra, which results in dopaminergic nerve terminal retraction from the striatum towards the substantia nigra. This leaves the striatum with inadequate dopamine levels, which in turn causes motor function deficits and other symptoms. Currently approved drugs that relieve symptoms focus on replacing the dopamine lost in the striatum; however, the symptom relief is temporary and the drugs typically lose their ability to abate symptoms roughly 7-10 years after the initiation of drug therapy. There are no approved therapies that focus on re-innervating the striatum by protecting dopaminergic neuron cell bodies in the substantia nigra while restoring dopaminergic innervation in the striatum.
In rat studies conducted by an independent academic laboratory contracted by Amarantus, 6-OHDA was injected directly into the striatum on one side of each rat’s brain, causing their dopaminergic terminals to retract from the striatum towards the substantia nigra, and creating Parkinson’s-like behavioural symptoms that were quantified by counting the number of times the rats turned in a circle in the same direction (behavioural deficits) in a given 120 minute period of time. MANF and GDNF were delivered directly into the substantia nigra of separate groups of rats 2 weeks following the administration of the 6-OHDA, in order to mimic as closely as possible in rats the treatment setting in humans where treatment would be administered after an extended timeframe following the initiation of dopaminergic nerve terminal retraction, each at the optimal dosing level of 10 micrograms. Four weeks following MANF treatment into the substantia nigra, behavioural deficits were reduced by ~43%, and six weeks following MANF treatment, behavioural deficits were reduced by ~53%; four weeks following GDNF treatment into the substantia nigra, behavioural deficits were reduced by ~16%, and six weeks following GDNF treatment, behavioural deficits actually increased by ~20%.
“The data obtained in this study provide clear evidence that MANF had a strong positive and restorative effect on the behaviour of animals in this pre-clinical Parkinson’s disease study when delivered to the substantia nigra, whereas GDNF had no such effect,” said John W. Commissiong PhD, Chief Scientist at Amarantus and former Head of the Neurotrophic Factors Group at the National Institutes of Health. “The localization of the drug treatment in this study is critical because, as Parkinson’s disease progresses, dopaminergic nerve terminals typically retract from the striatum towards their cell bodies in the substantia nigra, resulting in the disruption of the basal ganglia network that is responsible for proper motor function. Translated, the longer you have Parkinson’s disease, the less likely a neurotrophic factor will work when delivered to the striatum because there are fewer dopaminergic nerve terminals remaining to act on, and so neurotrophic factor drugs for later-stage patients will likely work best when delivered to the substantia nigra. No neurotrophic factor other than MANF has demonstrated efficacy in the neurorestoration behavioural 6-OHDA model of Parkinson’s disease when delivered to the substantia nigra, so this makes today’s result very significant. We are currently working to complete the analysis of histology data to confirm that it is in fact dopaminergic re-innervation of the striatum that is responsible for the results reported today. We expect to release the final results, including histology, to the public when the final data package is assembled in the next few months, and we will submit the final study report and manuscript for publication to a peer-reviewed scientific journal jointly with our academic collaborators and study sponsors at the same time. If the histology data confirm the mechanism underlying the behavioural results reported today, the biology causing today’s result would represent a major scientific achievement that could lead to a medical breakthrough in treating Parkinson’s disease.”
Neurotrophic factors have been promising drug candidates for Parkinson’s disease for over two decades because they have special biological properties that allow them to selectively protect certain neurons. Large biotechnology companies and leading academic investigators have conducted a number of clinical trials on GDNF in Parkinson’s disease first initiated in 1996, at an estimated total cost of over $400M, where GDNF has shown promise as a disease-modifying treatment. However, technological limitations of delivering neurotrophic factors to the brain, limitations that Amarantus believes have been resolved by researchers in academia and industry, have delayed the translation of the underlying biology of neurotrophic factors into approved medicines. A unique drug such as MANF that potentially acts by re-innervating the striatum when delivered to the substantia nigra, combined with newly improved delivery technologies capable of getting MANF to the substantia nigra, could complement or replace drugs in development that may get to market ahead of MANF, especially in later-stage patients.
“Today’s announcement is transformational for Amarantus from a scientific data standpoint,” said Gerald E. Commissiong, President & CEO of Amarantus. “Despite the many clear scientific advantages we believe MANF possesses over GDNF, most notably impacting protein folding and modulating toxic calcium levels, the Company had previously been unable to point to a definitive behavioural animal model data to show improved benefit of MANF over GDNF in the Parkinson’s disease indication. The data we now have validates the approach we have been taking over the last several years, and we believe that it will allow us to attract the interest of investment firms and potential partners who will be able to now characterize the substantial opportunity our technology represents. We believe that we are well positioned to leverage the MANF opportunity for Amarantus shareholders and Parkinson’s patients because of the expansive intellectual property (IP) portfolio the Company owns, including composition of matter patents in the US and Europe, use patents worldwide and provisional delivery dosing patents that have been filed based on today’s data, extending marketing exclusivity for MANF through 2031. This IP position may make MANF more attractive to a potential partner than other neurotrophic factors in development that do not have the same patent runway.”
About Amarantus BioSciences, Inc.
Amarantus BioSciences, Inc. is a development-stage biotechnology company founded in January 2008. The Company has a focus on developing certain biologics surrounding the intellectual property and proprietary technologies it owns to treat and/or diagnose Parkinson’s disease, Traumatic Brain Injury and other human diseases. The Company owns the intellectual property rights to a therapeutic protein known as Mesencephalic-Astrocyte-derived Neurotrophic Factor (“MANF”) and is developing MANF-based products as treatments for brain disorders. The Company also is a Founding Member of the Coalition for Concussion Treatment (#C4CT), a movement initiated in collaboration with Brewer Sports International seeking to raise awareness of new treatments in development for concussions and nervous-system disorders. For further information please visit www.Amarantus.com.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about the possible benefits of MANF therapeutic applications and/or advantages presented by Amarantus’ PhenoGuard technology, as well as statements about expectations, plans and prospects of the development of Amarantus’ new product candidates. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including the risks that the anticipated benefits of the therapeutic drug candidates or discovery platforms, as well as the risks, uncertainties and assumptions relating to the development of Amarantus’ new product candidates, including those identified under “Risk Factors” in Amarantus’ most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q and in other filings Amarantus periodically makes with the SEC. Actual results may differ materially from those contemplated by these forward-looking statements Amarantus does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this presentation.
MEDIA CONTACTS Amarantus BioSciences, Inc.
Gerald E. Commissiong