RespireRx Pharmaceuticals Inc. (OTC Markets: RSPI) (“RespireRx” or the “Company”), a leader in the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is pleased to announce the publication of four articles describing the pharmacological activity of novel structural analogs of KRM-II-81, the Company’s lead GABAkine.
Glen Rock, N.J., April 03, 2023 (GLOBE NEWSWIRE) -- RespireRx (Formerly Known As Cortex Pharmaceuticals, Inc.) Inc. (OTC Markets: RSPI) (“RespireRx” or the “Company”), a leader in the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is pleased to announce the publication of four articles describing the pharmacological activity of novel structural analogs of KRM-II-81, the Company’s lead GABAkine. Like KRM-II-81, these analogs enhance GABAergic neurotransmission and function as orally-bioavailable anti-seizure agents in the absence of the sedation typically associated with GABA augmentation. KRM-II-81, itself, has been shown to be effective across a broad array of anti-seizure models including those predicting efficacy in patients that are pharmaco-resistant and in brain tissue from epilepsy patients who are no longer treatable with drugs. In addition KRM-II-81 is active in relieving acute, chronic, and neuropathic pain in a number of models without developing tolerance or producing sedation.
The articles (Kosmowska et al. Biomolecules. 2023, 13:197; Ping et al., Drug Dev Res. Epub ahead of print, doi: 10.1002/ddr.22042; Pandey et al., J Pharmacol Exp Ther. 385:50-61 document the preclinical effects and tolerability of structural analogs of KRM-II-81. In established rat models predicting efficacy in essential tremor and in tremor associated with Parkinson’s Disease, MP-III-024 was an effective anti-tremor compound. Also described are three novel structural analogs with sufficient blood and brain levels after oral administration to produce a pharmacological response and a deuterated derivative of KRM-II-81 that produced long-lived anticonvulsant activity after oral administration. An earlier article (Mian et al., ACS Omega. 2022, 7(31):27550-9) described the synthesis of a water souble, hydrochloride salt of KRM-II-81, another important analog in this series with the added potential of intravenous delivery. The compounds described in these articles were efficacious as anticonvulsants and the most characterized of these, KPP-III-34, displayed robust activity in more advanced anti-seizure models. All compounds were effective without producing sedative effects.
Distinguished Professor, James M. Cook, head of the medicinal chemistry group, said that “the viability of the imidazodiazepine structural platform to generate drug-like molecules with broad predicted therapeutic efficacy and good tolerability has enabled the creation of compounds that can serve as backups for KRM-II-81 as it proceeds in development.” Dr. Lippa added, “We are very excited about developing KRM-II-81 and expanding the IND enabling studies so as to begin human studies. Pending clinical validation, we believe that KRM-II-81 has the potential to represent a breakthrough treatment for pain, epilepsy, and certain neuropsychiatric disorders.” Jeff Margolis, CFO, noted that “the recent business arrangements of its subsidiary company, ResolutionRx, will enable RespireRx, the parent company, to now focus more on this exciting new opportunity with the development of KRM-II-81.”
The RespireRx team is led by Drs. Arnold Lippa, RespireRx Executive Chairman and Chief Scientific Officer, James M. Cook, Jeffrey M. Witkin and Rok Cerne, all of whom are RespireRx Research Fellows in addition to their academic affiliations at The University of Wisconsin-Milwaukee, Ascension St. Vincent Hospital and Indiana University/Purdue University, respectively. The team has extensive expertise in drug discovery and development, including the development of novel analgesic, anxiolytic and antidepressant drugs and an extensive publication record with a combined total of over 1,000 scientific publications.
About RespireRx Pharmaceuticals Inc.
RespireRx Pharmaceuticals Inc. is a leader in the discovery and development of medicines for the treatment of psychiatric and neurological disorders, with a focus on treatments that address conditions affecting millions of people, but for which there are few or poor treatment options, including obstructive sleep apnea (“OSA”), attention deficit hyperactivity disorder (“ADHD”), epilepsy, pain, recovery from spinal cord injury (“SCI”), and certain neurological orphan diseases. RespireRx is developing a pipeline of new and re- purposed drug products based on our broad patent portfolios for two drug platforms: (i) pharmaceutical cannabinoids, which include dronabinol, a synthetic form of ∆-9-tetrahydrocannabinol (“Δ-9-THC”) that acts upon the nervous system’s endogenous cannabinoid receptors and (ii) 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 Company 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.
EndeavourRx: Neuromodulators
GABAkines. 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. The Company 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.
In addition, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In intact animal models of pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.
AMPAkines. Through an extensive translational research effort from the cellular level through Phase 2 clinical trials, the Company has developed a family of novel, low impact AMPAkines, including CX717, CX1739 and CX1942 that may have clinical application in the treatment of CNS-driven neurobehavioral and cognitive disorders, spinal cord injury, neurological diseases, and certain orphan indications. Our lead clinical compounds, CX717 and CX1739, have successfully completed multiple Phase 1 safety trials. Both compounds have also completed Phase 2 proof of concept trials demonstrating target engagement, by antagonizing the ability of opioids to induce respiratory depression.
AMPAkines have demonstrated positive activity in animal models of ADHD, results that have been extended translationally into statistically significant improvement of symptoms observed in a Phase 2 human clinical trial of CX717 in adult patients with ADHD. Statistically significant therapeutic effects were observed within one week. We believe AMPAkines may represent a novel, non-stimulant treatment for ADHD with a more rapid onset of action than alternative non stimulants, such as Straterra® (atomoxetine), and without the drawbacks of amphetamine-type stimulants.
In a series of important studies funded by grants from the National Institutes of Health and published in a number of peer reviewed articles, Dr. David Fuller (University of Florida), a long-time RespireRx collaborator, has demonstrated the ability of CX1739 and CX717, the Company’s lead AMPAkines, to improve motor nerve activity and muscle function in a number of animal models of spinal cord injury (SCI).
ResolutionRx: Pharmaceutical Cannabinoids.
ResolutionRx Ltd (Australian Company Number a/k/a ACN 664 925 651) was formed in Australia on January 11, 2023 by RespireRx as an unlisted public company. RespireRx intends to contribute, sub-license, assign or otherwise make available to ResolutionRx, its cannabinoid drug development program subject to certain liabilities. ResolutionRx would then 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 refund. Dronabinol, a synthetic version of ∆-9-THC, a naturally occurring substance in the cannabis plant, 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 to be between 29.4 and 54.1 million people in the United States (American Association of Sleep Medicine and Lancet Respiratory Medicine, respectively) and 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 FDA approved for the treatment of AIDS related anorexia and chemotherapy induced nausea and vomiting, the Company further believes that its re-purposing strategy would only require 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.
Additional information about RespireRx and the matters discussed herein can be obtained on the Company’s web-site at www.respirerx.com or in the Company’s filings with the Securities and Exchange Commission at www.sec.gov.
Not a Securities Offering or Solicitation
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Cautionary Note Regarding Forward-Looking Statements
This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”) and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the Company intends that such forward-looking statements be subject to the safe harbor created thereby. These might include statements regarding the Company’s future plans, targets, estimates, assumptions, financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about research and development efforts, including, but not limited to, preclinical and clinical research design, execution, timing, costs and results, future product demand, supply, manufacturing, costs, marketing and pricing factors.
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We caution investors, as well as potential collaborators and other potential stakeholders, not to place undue reliance on any forward-looking statement that speaks only as of the date made and to recognize that forward-looking statements are predictions of future results, which may not occur as anticipated. Actual results could differ materially from those anticipated in the forward-looking statements and from historical results, due to the risks and uncertainties described in the 2021 Form 10-K and in this press release, as well as others that we may consider immaterial or do not anticipate at this time. These forward-looking statements are based on assumptions regarding the Company’s business and technology, which involve judgments with respect to, among other things, future scientific, economic, regulatory and competitive conditions, collaborations with third parties, and future business decisions, all of which are difficult or impossible to predict accurately and many of which are beyond the Company’s control. Although we believe that the expectations reflected in our forward-looking statements are reasonable, we do not know whether our expectations will prove correct. Our expectations reflected in our forward-looking statements can be affected by inaccurate assumptions that we might make or by known or unknown risks and uncertainties, including those described in the 2021 Form 10-K and in this press release. These risks and uncertainties are not exclusive and further information concerning us and our business, including factors that potentially could materially affect our financial results or condition, may emerge from time to time.
For more information about the risks and uncertainties the Company faces, see “Item 1A. Risk Factors” in our 2021 Form 10-K. Forward-looking statements speak only as of the date they are made. The Company does not undertake and specifically declines any obligation to update any forward-looking statements or to publicly announce the results of any revisions to any statements to reflect new information or future events or developments. We advise investors, as well as potential collaborators and other potential stakeholders, to consult any further disclosures we may make on related subjects in our annual reports on Form 10-K and other reports that we file with or furnish to the SEC.
Company Contact:
Jeff Margolis
Senior Vice President, Chief Financial Officer, Treasurer and Secretary
Telephone: 917-834-7206
Email: jmargolis@respirerx.com
RespireRx Pharmaceuticals Inc.
126 Valley Road, Suite C
Glen Rock, NJ 07452
www.respirerx.com
