|By Marketwired .||
|January 7, 2013 01:13 AM EST||
GENEVA -- (Marketwire) -- 01/07/13 -- Addex Therapeutics / Addex Announces Positive Data with ADX71441 in a Pre-Clinical Transgenic Model of Charcot-Marie-Tooth 1A Disease . Processed and transmitted by Thomson Reuters ONE. The issuer is solely responsible for the content of this announcement.
ADX71441, a novel oral small molecule positive allosteric modulator, on track for Phase 1 clinical testing in the first half of 2013
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today achievement of a positive Proof of Concept for its lead GABA-B receptor (GABA-BR) positive allosteric modulator (PAM) compound, ADX71441, in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A). CMT1A is a rare (1:5,000) hereditary motor and sensory demyelinating peripheral neuropathy (also known as Hereditary Motor and Sensory Neuropathy, HMSN) which is caused by an intrachromosomal duplication and consecutive toxic overexpression of the PMP22 gene on chromosome 17. CMT1A is one of the most common inherited peripheral nerve-related disorders which is passed down through families in an autosomal dominant fashion. CMT1A disease becomes evident in young adulthood and slowly progresses with distally pronounced muscle weakness and numbness. Pain can range from mild to severe. The disease can be highly debilitating with wheel chair-boundness and is often accompanied by severe cases of neurological pain. There is no known cure for this incapacitating disease.
"We are very excited about the promising results obtained with the Addex GABA-BR PAM candidate" said Professor Michael Sereda, of the Max-Planck Institute of Experimental Medicine, Göttingen, Germany, in whose laboratories the study was performed. "Current CMT1A therapies are primarily symptomatic such as physiotherapy and only focus on the manifestations of the disease, while the data obtained with the Addex compound seem to suggest that positive modulation of GABA-B receptor could lower toxic PMP22 overexpression and potentially delay the progression of the disease and offer a unique therapeutic opportunity for CMT1A patients".
ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Addex GABA-BR PAM was studied in the transgenic CMT rat model which has 1.6-fold PMP22 overexpression (mRNA level) and exhibits clinical abnormalities, such as reduced nerve conduction velocity and lower grip strength that mimic findings in CMT1A patients. Nine week oral therapy of ADX71441 in CMT rats (5 weeks every other day at 10 mg/kg followed by 4 weeks at 5 mg/kg every day) down regulated PMP22 mRNA, reduced the amount of hypo-myelinated axons and increased compound muscle action potentials in peripheral nerves when compared to vehicle treated CMT rats. It also prevented grip strength loss in CMT rats compared to wild type rats.
"These data confirm previous observations obtained using a GABA-BR agonist and the GABAB1-/- mice (knock-out mice), which identified the importance of GABA-BR in the inhibition of the proliferation and in the reduction of the synthesis of specific myelin proteins, in particular PMP22" noted Sonia Poli, VP Non Clinical Development at Addex. "These and other data further reinforce the central role of GABA-BR in a broad range of important diseases and conditions, including spasticity, Fragile X, autism, pain, anxiety, obsessive-compulsive disorder, overactive bladder and alcohol binge drinking".
"We are rapidly advancing ADX71441 into clinical development. Phase 1 clinical testing with this compound is planned for the first half of this year, initially for the treatment of spasticity associated with multiple sclerosis (MS)" said Graham Dixon, CSO at Addex. "These data are very encouraging as they indicate that the compound may also have a therapeutic benefit in treatment of patients with this debilitating rare disease."
CMT1A is a rare hereditary motor and sensory neuropathy (HMSN) which causes demyelination of the peripheral nerves with a consequence of severely and uniformly reduced nerve conduction velocities and consecutive axonal loss. The disease leads to damage or destruction to the myelin sheath covering around nerve fibers. Nerves that stimulate movement, the motor nerves, are most severely affected. The nerves in the legs are affected first and most severely. Similar symptoms may appear in the arms and hands, which may include a claw-like hand. The disease is highly invalidating with cases of accompanying neurological pain and muscle loss. A combination of lower motor neuron-type motor deficits and sensory symptoms are observed: paresis and muscle atrophy develops, with areflexia. The chronic nature of the motor neuropathy will result in foot deformity, hammertoes, very high-arched feet, loss of lower leg muscle, which leads to skinny calves, numbness in the foot or leg, "steppage" gait (feet hit the floor hard when walking), foot drop (inability to hold foot horizontal) and weakness of the hips, legs, or feet. Involvement of the hands may follow as the disease progresses. Signs of sensory system dysfunction are common (70%) and include loss of vibration and joint position sense followed by decreased pain and temperature sensation. Onset of the disease is between age 5 and 25 years, with a prevalence of 1 in 5,000. Charcot-Marie-Tooth is one of the most common inherited nerve-related disorders passed down through families in an autosomal dominant fashion. Charcot-Marie-Tooth disease slowly gets worse. Some parts of the body may become numb, and pain can range from mild to severe. Eventually the disease may cause disability. There are no known cures for this debilitating condition. Duplication of a chromosome 17 fragment harbouring PMP22 (= CMT1A) represents 43% of the total CMT cases, whereas the yield of duplication detection rises to 70% in CMT1. PMP22 is an essential component of myelin expressed in all myelinated fibers in the PNS and is produced by Schwann cells. While PMP22 represents only 2-5% of the amount of peripheral myelin protein in rodents and humans, it is necessary for stabilizing compact myelin. However, PMP22 is not only an essential constituent of myelin, but too much or too little of the protein causes neuropathy, possibly by disturbing Schwann cell growth and differentiation.
Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically & commercially validated. Generic GABA-B receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for OAB, but is not commonly used due to severe side effects of the drug and rapid clearance. Orthosteric GABA-B receptor agonists have also shown clinical validation in gastroesophageal reflux disease (GERD). Addex' GABA-B receptor PAMs have shown efficacy in multiple preclinical models including: CMT1A, OAB, pain, osteoarthritis pain and anxiety.
Addex Therapeutics (www.addextherapeutics.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (ADX48621, an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients suffering from major depressive disorder. Addex also is advancing several preclinical programs including: GABA-BR PAM for spasticity in MS, OAB and other disorders; mGlu4 PAM for Parkinson's, MS, anxiety and other diseases. In addition, Addex is applying its proprietary discovery platform to identify highly selective and potent allosteric modulators of a number of both GPCR and non-GPCR targets that are implicated in diseases of significant unmet medical need.
Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.
This announcement is distributed by Thomson Reuters on behalf of Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and other applicable laws; and
(ii) they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Addex Therapeutics via Thomson Reuters ONE
Chief Financial Officer
+41 22 884 15 61
An IoT product’s log files speak volumes about what’s happening with your products in the field, pinpointing current and potential issues, and enabling you to predict failures and save millions of dollars in inventory. But until recently, no one knew how to listen. In his session at @ThingsExpo, Dan Gettens, Chief Research Officer at OnProcess, discussed recent research by Massachusetts Institute of Technology and OnProcess Technology, where MIT created a new, breakthrough analytics model for ...
Dec. 7, 2016 08:00 AM EST Reads: 413
DevOps is being widely accepted (if not fully adopted) as essential in enterprise IT. But as Enterprise DevOps gains maturity, expands scope, and increases velocity, the need for data-driven decisions across teams becomes more acute. DevOps teams in any modern business must wrangle the ‘digital exhaust’ from the delivery toolchain, "pervasive" and "cognitive" computing, APIs and services, mobile devices and applications, the Internet of Things, and now even blockchain. In this power panel at @...
Dec. 7, 2016 07:45 AM EST Reads: 795
More and more brands have jumped on the IoT bandwagon. We have an excess of wearables – activity trackers, smartwatches, smart glasses and sneakers, and more that track seemingly endless datapoints. However, most consumers have no idea what “IoT” means. Creating more wearables that track data shouldn't be the aim of brands; delivering meaningful, tangible relevance to their users should be. We're in a period in which the IoT pendulum is still swinging. Initially, it swung toward "smart for smar...
Dec. 7, 2016 07:30 AM EST Reads: 816
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place June 6-8, 2017, at the Javits Center in New York City, New York, is co-located with 20th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry p...
Dec. 7, 2016 06:45 AM EST Reads: 1,994
@DevOpsSummit at Cloud taking place June 6-8, 2017, at Javits Center, New York City, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long developm...
Dec. 7, 2016 06:30 AM EST Reads: 1,803
Kubernetes is a new and revolutionary open-sourced system for managing containers across multiple hosts in a cluster. Ansible is a simple IT automation tool for just about any requirement for reproducible environments. In his session at @DevOpsSummit at 18th Cloud Expo, Patrick Galbraith, a principal engineer at HPE, discussed how to build a fully functional Kubernetes cluster on a number of virtual machines or bare-metal hosts. Also included will be a brief demonstration of running a Galera MyS...
Dec. 7, 2016 06:15 AM EST Reads: 5,326
"We build IoT infrastructure products - when you have to integrate different devices, different systems and cloud you have to build an application to do that but we eliminate the need to build an application. Our products can integrate any device, any system, any cloud regardless of protocol," explained Peter Jung, Chief Product Officer at Pulzze Systems, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 7, 2016 05:15 AM EST Reads: 1,055
"We are an all-flash array storage provider but our focus has been on VM-aware storage specifically for virtualized applications," stated Dhiraj Sehgal of Tintri in this SYS-CON.tv interview at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 7, 2016 04:00 AM EST Reads: 868
Internet of @ThingsExpo has announced today that Chris Matthieu has been named tech chair of Internet of @ThingsExpo 2017 New York The 7th Internet of @ThingsExpo will take place on June 6-8, 2017, at the Javits Center in New York City, New York. Chris Matthieu is the co-founder and CTO of Octoblu, a revolutionary real-time IoT platform recently acquired by Citrix. Octoblu connects things, systems, people and clouds to a global mesh network allowing users to automate and control design flo...
Dec. 7, 2016 02:00 AM EST Reads: 629
In addition to all the benefits, IoT is also bringing new kind of customer experience challenges - cars that unlock themselves, thermostats turning houses into saunas and baby video monitors broadcasting over the internet. This list can only increase because while IoT services should be intuitive and simple to use, the delivery ecosystem is a myriad of potential problems as IoT explodes complexity. So finding a performance issue is like finding the proverbial needle in the haystack.
Dec. 7, 2016 01:45 AM EST Reads: 6,164
Between 2005 and 2020, data volumes will grow by a factor of 300 – enough data to stack CDs from the earth to the moon 162 times. This has come to be known as the ‘big data’ phenomenon. Unfortunately, traditional approaches to handling, storing and analyzing data aren’t adequate at this scale: they’re too costly, slow and physically cumbersome to keep up. Fortunately, in response a new breed of technology has emerged that is cheaper, faster and more scalable. Yet, in meeting these new needs they...
Dec. 7, 2016 01:15 AM EST Reads: 1,879
Data is the fuel that drives the machine learning algorithmic engines and ultimately provides the business value. In his session at 20th Cloud Expo, Ed Featherston, director/senior enterprise architect at Collaborative Consulting, will discuss the key considerations around quality, volume, timeliness, and pedigree that must be dealt with in order to properly fuel that engine.
Dec. 7, 2016 01:00 AM EST Reads: 1,618
When it comes to cloud computing, the ability to turn massive amounts of compute cores on and off on demand sounds attractive to IT staff, who need to manage peaks and valleys in user activity. With cloud bursting, the majority of the data can stay on premises while tapping into compute from public cloud providers, reducing risk and minimizing need to move large files. In his session at 18th Cloud Expo, Scott Jeschonek, Director of Product Management at Avere Systems, discussed the IT and busin...
Dec. 7, 2016 12:45 AM EST Reads: 3,938
According to Forrester Research, every business will become either a digital predator or digital prey by 2020. To avoid demise, organizations must rapidly create new sources of value in their end-to-end customer experiences. True digital predators also must break down information and process silos and extend digital transformation initiatives to empower employees with the digital resources needed to win, serve, and retain customers.
Dec. 7, 2016 12:45 AM EST Reads: 1,245
The WebRTC Summit New York, to be held June 6-8, 2017, at the Javits Center in New York City, NY, announces that its Call for Papers is now open. Topics include all aspects of improving IT delivery by eliminating waste through automated business models leveraging cloud technologies. WebRTC Summit is co-located with 20th International Cloud Expo and @ThingsExpo. WebRTC is the future of browser-to-browser communications, and continues to make inroads into the traditional, difficult, plug-in web co...
Dec. 7, 2016 12:15 AM EST Reads: 1,377