RespireRx (formerly known as Cortex Pharmaceuticals, Inc.) Pharmaceuticals Inc., focused on the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, and ResolutionRx Ltd, an unlisted public Australian company, and a subsidiary of RespireRx, jointly announce that on October 9, 2023, ResolutionRx entered into a Master Services Agreement (“MSA”) with Ab Initio Pharma Pty Ltd, (Ab Initio) an Australian company under which Ab Initio will manufacture, formulate, test and supply ResolutionRx with therapeutic drugs based on lipid nanoparticle technology licensed from RespireRx.
The initial services relate to ResolutionRx’s repurposing of dronabinol and its development programme for obstructive sleep apnea pursuant to which Ab Initio will, among other things, manufacture and test our new dronabinol lipid nanoparticle formulation for pharmacokinetic, pharmacodynamic, and pivotal clinical trials, as well as ultimately for commercialization. The initial term of the MSA is two years and automatically renews for one-year periods unless ResolutionRx provides written notice to Ab Initio of its intent not to renew at least ninety days prior to the end of the initial term or any renewal term.
“The importance of this partnership cannot be overstated,” said Arnold Lippa, co-CEO and CSO of ResolutionRx and CEO and CSO of RespireRx. “With its formulation expertise and GMP manufacturing facilities, Ab Initio will complete our original laboratory experiments to determine a final, optimum dronabinol formulation, scale up and manufacture the chosen formulation for clinical use. The lipid nanoparticle technology not only represents a major step forward in the development of dronabinol, but the potential for more widespread use for insoluble or poorly soluble drugs.”
The RespireRx Group is developing a pipeline of new and repurposed drug products based on our broad patent portfolios for two drug platforms: pharmaceutical cannabinoids, which include dronabinol, a synthetic form of ?9-tetrahydrocannabinol (“?9- THC”) that acts upon the nervous system’s endogenous cannabinoid receptors and neuromodulators, which include AMPAkines and GABAkines, proprietary chemical entities that positively modulate (positive allosteric modulators or “PAMs”) AMPA-type glutamate receptors and GABAA receptors, respectively.
The RespireRx Group holds exclusive licenses and owns patents and patent applications or rights thereto for certain families of chemical compounds that claim the chemical structures and their uses in the treatment of a variety of disorders, as well as claims for novel uses of known drugs.
RespireRx has contributed by sublicense and license with ResolutionRx, its sleep apnea drug development program subject to certain liabilities. ResolutionRx will now engage in the research and development (“R&D”) associated with that program, initially for the development of a new formulation of dronabinol for use in a Phase 3 clinical trial and the filing of regulatory approval for the treatment of obstructive sleep apnea (“OSA”). The current total budget for that program over the next several years is approximately US$16.5 million, most, but not all of which is expected to be eligible for the Australian R&D Tax Incentive (“RDTI”). Dronabinol, an endocannabinoid receptor agonist, has already demonstrated significant improvement in the symptoms of OSA in two Phase 2 clinical trials. OSA is a serious respiratory disorder that impacts an estimated 90 million people in the United States, Australia, Germany and the United Kingdom and that has been linked to increased risk for hypertension, heart failure, depression, and diabetes. There are no approved drug treatments for OSA.
Because dronabinol is already US FDA approved for the treatment of AIDS related anorexia and chemotherapy induced nausea and vomiting, RespireRx and ResolutionRx further believe that its repurposing strategy would only require, in the United States, approval by the FDA of a 505(b)(2) new drug application (“NDA”), an efficient regulatory pathway that allows the use of publicly available data.
Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. (UWMRF) and on behalf of its EndeavourRx business unit, RespireRx has licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific, subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. EndeavourRx currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.
KRM-II-81 has displayed a high degree of anti-convulsant activity in a broad range of preclinical studies, including in treatment resistant and pharmaco-resistant models. Not only was KRM-II-81 highly effective in these models, but pharmaco-resistance or tolerance did not develop to its anti-convulsant properties. These latter results are particularly important because pharmaco-resistance occurs when medications that once controlled seizures lose efficacy as a result of chronic use and it is a principal reason some epileptic patients require brain surgery to control their seizures. In support of its potential clinical efficacy, translational studies have demonstrated the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ to brain slices excised from treatment-resistant epileptic patients undergoing surgery.
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