· ADX71441 produced dose-dependent changes on growth hormone (GH) plasma concentrations in a preclinical model
· The data confirms the role of gamma-aminobutyric acid (GABA) in modulating GH plasma concentrations previously reported in humans and animals
· GH plasma concentrations occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction
· ADX71441 on track to initiate Phase 1 testing in H1 2013
LAN-LES-OUATES GENEVA, Switzerland I May 21, 2013 I Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today that its gamma-aminobutyric acid B (GABA-B) receptor positive allosteric modulator, ADX71441, caused dose dependent changes in growth hormone (GH) plasma concentrations compared to vehicle control in a rodent preclinical model.
These data are consistent with published scientific literature demonstrating that GABA, the endogenous neurotransmitter for GABA-B receptors, plays both a stimulatory and inhibitory role in modulating the neuro-endocrine regulation of GH secretion in both animals and humans. GH plasma concentration changes occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction. “The data obtained with ADX71441 demonstrate that growth hormone can be used as a potential biomarker for an efficacy signal and fully supports its inclusion in our first-in-man program,” stated Graham Dixon, Ph.D., CSO at Addex. “The use of growth hormone as a biomarker in the Phase 1 will allow us to obtain early information about target engagement, guide dose selection for further clinical development and possibly provide us an understanding of the therapeutic potential of ADX71441.”
The study was performed on samples from single oral treatment studies where ADX71441 was given at doses of 5, 20 and 80 mg/kg. Assessment of GH and ADX71441 plasma concentrations were performed at 4 and 24 hours post-treatment. The results demonstrate a direct relationship between plasma concentrations of ADX71441 and effect on GH levels. GH changes occur at doses (
About ADX71441 and GABAB Activation
ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically and commercially validated. Generic GABA-B receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for overactive bladder (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.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a development stage company focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform. The Company’s two lead products are being investigated in Phase 2 clinical testing: dipraglurant (dipraglurant, an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson’s disease levodopa-induced dyskinesia (PD-LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. to treat both schizophrenia and anxiety as seen in patients suffering from major depressive disorder. Addex is also advancing several preclinical programs including: GABA-BR positive allosteric modulator (PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for MS, Parkinson’s disease, anxiety and other diseases. Allosteric modulators are an emerging class of small molecule drugs 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 target receptors and other proteins that are recognized as essential for the therapeutic modulation of important diseases with unmet medical needs.
SOURCE: Addex Pharmaceuticals
Post Views: 185
· ADX71441 produced dose-dependent changes on growth hormone (GH) plasma concentrations in a preclinical model
· The data confirms the role of gamma-aminobutyric acid (GABA) in modulating GH plasma concentrations previously reported in humans and animals
· GH plasma concentrations occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction
· ADX71441 on track to initiate Phase 1 testing in H1 2013
LAN-LES-OUATES GENEVA, Switzerland I May 21, 2013 I Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today that its gamma-aminobutyric acid B (GABA-B) receptor positive allosteric modulator, ADX71441, caused dose dependent changes in growth hormone (GH) plasma concentrations compared to vehicle control in a rodent preclinical model.
These data are consistent with published scientific literature demonstrating that GABA, the endogenous neurotransmitter for GABA-B receptors, plays both a stimulatory and inhibitory role in modulating the neuro-endocrine regulation of GH secretion in both animals and humans. GH plasma concentration changes occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction. “The data obtained with ADX71441 demonstrate that growth hormone can be used as a potential biomarker for an efficacy signal and fully supports its inclusion in our first-in-man program,” stated Graham Dixon, Ph.D., CSO at Addex. “The use of growth hormone as a biomarker in the Phase 1 will allow us to obtain early information about target engagement, guide dose selection for further clinical development and possibly provide us an understanding of the therapeutic potential of ADX71441.”
The study was performed on samples from single oral treatment studies where ADX71441 was given at doses of 5, 20 and 80 mg/kg. Assessment of GH and ADX71441 plasma concentrations were performed at 4 and 24 hours post-treatment. The results demonstrate a direct relationship between plasma concentrations of ADX71441 and effect on GH levels. GH changes occur at doses (
About ADX71441 and GABAB Activation
ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically and commercially validated. Generic GABA-B receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for overactive bladder (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.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a development stage company focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform. The Company’s two lead products are being investigated in Phase 2 clinical testing: dipraglurant (dipraglurant, an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson’s disease levodopa-induced dyskinesia (PD-LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. to treat both schizophrenia and anxiety as seen in patients suffering from major depressive disorder. Addex is also advancing several preclinical programs including: GABA-BR positive allosteric modulator (PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for MS, Parkinson’s disease, anxiety and other diseases. Allosteric modulators are an emerging class of small molecule drugs 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 target receptors and other proteins that are recognized as essential for the therapeutic modulation of important diseases with unmet medical needs.
SOURCE: Addex Pharmaceuticals
Post Views: 185
