LTListener
8 hours ago
Based on the wording in the last PR, it seems as though further development of their AMPA program is on hold pending funding. As you suggest it appears tricky to get these compounds to work at lowest dosage and no side effects. Guessing additional funding to support OSA program is a higher priority for various reasons.
This leaves the GABA program and KRM-II-81. How long do these tier 3 preclinicals take to look at more defined pain models and direct abuse liability? CEO said not quick, more intermediate type work. 4 months? 6+ months? Assuming they started to process in Q1, feels like they could be nearing some early indication results, although just a gut thought there, no idea how long the process could take...
Given the high profile nature of the opioid crisis, there is no way an under resourced OTC is gonna lead into human trials. Their filings essentially indicate that. Logically, it would make sense to bring the preclinical effort for KRM-II-81 to maturity, partner/JV going forward and use that value creation to further the OSA program in Australia. Until we begin to hear again from the company however, everything is pure speculation. Good luck to all.
NeutrinoKid
1 day ago
“AMPA-glutamate receptors (AMPARs) are expressed throughout the CNS and mediate the majority of fast excitatory synaptic transmission. Ampakines are orally available small molecules that bind allosterically to AMPARs and enhance excitatory currents elicited by the endogenous agonist glutamate.
In preclinical studies, ampakines are effective in ameliorating symptoms in a battery of neurodegenerative and neuropsychiatric diseases in which excitatory transmission is compromised. However, the development of ampakines as medicines was slowed by the emergence of neurotoxicity and seizures in rodents due to some ampakines. Here, we describe the preclinical pharmacology of a novel ampakine, CX1739, that does not induce seizures in animals or humans at efficacious doses.
CX1739 dose-dependently enhanced long-term potentiation in vivo in rats, a process thought to be a molecular substrate of learning and memory. Correspondingly, CX1739 dose-dependently enhanced performance in assays that probed multiple aspects of cognition—the novel object recognition test, the winshift radial arm maze, and the five-choice serial reaction time task in rats. CX1739 also abrogated amphetamine-induced locomotor activity, demonstrating that it may be given in conjunction with stimulants for pro-cognitive gains while mitigating the side effects of stimulant-based ADHD medications. CX1739 also rapidly reversed opioid-induced respiratory depression. While efficacy in these tests occurred at doses of 0.03–18 mg/kg, there were no adverse events detected in safety studies in rats up to 2000 mg/kg.
These preclinical findings suggest that CX1739 can be translated safely into the clinical setting to potentially treat dementia, neuropsychiatric disorders, and the life-threatening complication of opiate-induced suppression of endogenous inspiratory breathing rhythms.”
NeutrinoKid
1 day ago
The specific competence that the Australian subsidiary brings to RespireRx is access to the manufacturing and testing of the lipid nanoparticule in situ drug delivery formulation. This is done in collaboration with a third party located also in Australia, Ab Initio.
Dronabinol is, if you want, incidental. The purpose is to harness the nanoparticles, which can be used with other compounds. Note that the particular challenge that the Ampakines drugs faced was effective delivery, since high potency versions had unacceptable side effects, while the gentler low potency drugs tended to not get to the target tissue in adequate amounts or timing. Such that the nanoparticles can rehabilitate the Ampakine pipeline. And the same holds for the GABAkines, i.e. KRM-II-81, and analogs.
“ the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ.”
https://ab-initio-pharma.com/news/2023/10/13/ab-initio-signs-master-service-agreement-with-resolution-rx
oldstocks
1 day ago
RespireRx Pharmaceuticals Inc. (RSPI) has been involved in several key activities and updates in 2024:
Cannabinoid Confusion: There has been ongoing debate and confusion in the U.S. regarding cannabinoids. Despite this, RSPI’s Australian deal is considered financially sensible, although there has been no recent update on this matter.
Preclinical Progress: It is assumed that preclinical work with new formulations is in progress, but there has been no update on any FDA discussions or additional funding for their development path.
Drug Platforms: RSPI’s filings have suggested that all their drug programs should be partnered, joint-ventured, or sold. The status of one of the three main platforms could significantly impact the other two.
OSA Drug Development: For the OSA drug, RSPI is awaiting the manufacture of new formulations. With roughly half of the funding in place and intent to list on the ASX, they are a few steps away from clinical trials with the new formulations.
Clinical Trials for Other Candidates: The recent PR suggests that trials for the spinal and ADHD candidate might occur later this year, pending funding. The epilepsy/pain candidate drug is in tier 3 of NIH, and the CEO has indicated a short-term goal of securing funds to support it.
Stock Performance: There has been mention of dilution, but shares are considered tight as investors are believed to be absorbing available shares in numbers.
These updates reflect RSPI’s ongoing efforts in drug development and its strategic moves in the pharmaceutical industry. The company seems to be progressing towards clinical trials for its new formulations and seeking partnerships to advance its drug candidates.
oldstocks
1 day ago
KRM-II-81 is a novel compound that has been making significant strides in medical research, particularly in the treatment of epilepsy and pain management. Here are some key points from the latest research in 2024:
Epilepsy Treatment: A case report published in Heliyon journal detailed the effects of KRM-II-81 on epileptiform activity in brain tissue surgically removed from a 19-year-old patient with pharmaco-resistant epilepsy. The compound, a GABA A receptor potentiator, successfully suppressed epileptiform bursting in the excised brain tissue. This finding supports the potential of KRM-II-81 to reduce seizure burden in patients resistant to standard anti-epileptic treatments.
Pain Management: KRM-II-81 has also been reported to show promise in preclinical pain relief studies. It has advanced to the next level of evaluation within the NIH HEAL Initiative® Preclinical Screening Platform for Pain (PSPP) program. The compound demonstrated the ability to block pain-like behaviors in rats without significant side effects, which is a crucial step towards developing non-opioid pain therapeutics.
Future Prospects: Although KRM-II-81 has shown efficacy comparable to diazepam in various animal models of epilepsy and pain, it has not yet undergone trials in humans. The ongoing research and development suggest that KRM-II-81 could potentially be a breakthrough medication for epilepsy, pain, and other neuropsychiatric disorders pending clinical validation.
These developments indicate a promising future for KRM-II-81 as a potential treatment option for conditions that currently have limited effective therapies.
oldstocks
1 day ago
Is research going on with KRM-II-81 in Australia?
Yes, there is ongoing research involving KRM-II-81 in Australia.
RespireRx Pharmaceuticals Inc. has reported that as part of an ongoing collaboration, translational studies have demonstrated the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ.
This suggests active preclinical research efforts are being conducted to further understand and develop KRM-II-81’s therapeutic potential.
For more detailed information on the specific nature of these studies or any collaborative efforts in Australia, it would be best to refer to the latest publications or announcements from RespireRx Pharmaceuticals Inc. or their research partners.
KRM-II-81 is a novel compound that acts as a positive allosteric modulator of the GABAA receptor.
It is particularly selective for the alpha2 and alpha3 subunits of this receptor.
The mechanism of action for KRM-II-81 involves enhancing the inhibitory effects of the neurotransmitter GABA (gamma-aminobutyric acid) at the GABAA receptors.
This modulation results in anxiolytic, antidepressant, and anticonvulsant effects.
Notably, KRM-II-81 has been shown to have fewer adverse effects compared to some other GABAA positive allosteric modulators (PAMs). It is associated with low to no sedation and does not lead to tolerance development, which are significant advantages over other similar compounds.
Additionally, KRM-II-81 has demonstrated effectiveness in treating seizures better than diazepam, a commonly used anticonvulsant, and has shown promise in pharmaco-resistant models of epilepsy. This makes it a potentially valuable addition to the treatment options for conditions that involve neuronal hyperexcitability, such as certain types of epilepsy.
As of the latest available information, KRM-II-81 has advanced to the next level of evaluation within the NIH HEAL Initiative®Preclinical Screening Platform for Pain (PSPP) program.
This program evaluates non-opioid assets in a battery of established preclinical pain models. The emerging data showed that KRM-II-81 blocked pain-like behaviors in rats with minimal or no detectable side effects.
While KRM-II-81 has shown promise in preclinical studies, including effectiveness in relieving acute, chronic, and neuropathic pain without tolerance development or sedation, it appears that it has not yet entered human clinical trials.
The RespireRx team is expanding the IND (Investigational New Drug) enabling studies to begin human studies.
Pending clinical validation, KRM-II-81 is believed to have the potential to be a breakthrough medication for pain, epilepsy, and other neuropsychiatric disorders.
oldstocks
1 day ago
RespireRx Pharmaceuticals Inc. is actively developing a diverse drug pipeline with a focus on disorders caused by the disruption of neuronal signaling.
Their pipeline includes:
Cannabinoid Platform:
Pharmaceutical Cannabinoids:
They are working on treatments for conditions like Obstructive Sleep Apnea, with Dronabinol being a key compound in development for this purpose.
Neuromodulators:
AMPAkines: This platform includes compounds like CX1739, which has shown promise in preclinical research for improving bladder function after spinal cord injury.
GABAkines: This platform is focused on developing non-opioid treatments for conditions such as epilepsy and pain.
Just seeing what I can find out there. Nothing new yet. 10Q needs filing
The last thing we know is the 8K filed on 4-16-2024 The exercise price is $0.0015 per share
tem 1.01 Entry into a Material Definitive Agreement.
Demand Promissory Note and Warrant Agreement
General
On April 10, 2024, the RespireRx Pharmaceuticals Inc. (“RespireRx” or the “Company”) entered into a Demand Promissory Note and Warrant Agreement (“Purchase Agreement”) and issued a demand promissory note (“Demand Promissory Note”) and a warrant (“Warrant”) associated with the Purchase Agreement. Pursuant to the Purchase Agreement, both RespireRx and the investor (“Investor”) made representations to one another including, but not limited to representations by RespireRx as to its the good standing, subject to any Delaware Franchise Tax that may remain due and payable as of the date of the Purchase Agreement, the authority and enforceability of the Purchase Agreement, non-contravention, litigation, title, intellectual property, and debt for borrowed money and representations by the Investor including, but not limited to the nature of the arrangement being a binding obligation, that the Investor had been advised that the securities have not been registered under the Securities Act of 1933, as amended (the “Securities Act”) or any state laws, that the Investor understands that there are restrictions on transfer, that the Investor has sufficient knowledge of financial and business matters and that the Investor is an accredited investor as defined in Rule 501 of Regulation D under the Securities Act. The forms of the Demand Promissory Note and the Warrant are Exhibits A and Exhibits B to the Purchase Agreement.
The Demand Promissory Note accrues interest at the rate of 10% per annum based on a 365/366 day year, as applicable. Principal and interest are payable on demand of the lender (“Lender”). Accrued unpaid interest is added to principal at the end of the year that principal is unpaid. Payments are applied first to interest and then principal. To secure its obligations under the Note and to induce the Lender to extend the loan (“Loan”) to RespireRx (“Borrower”), the Borrower granted, a security interest in and to, all of such Borrower’s right, title and interest in and to all of the property identified in the Note, provided, that to the extent that any of the Collateral is subject, prior to the date of the Borrower’s Note to a security interest in favor of a third party and the agreement with such third party expressly prohibits any grant of a security interest therein, the Borrower will not be deemed to have a security interest in such Collateral only for so long as such prohibition continues. The terms of the Purchase Agreement and the Warrant are governed by the laws of the State of New York, without giving effect to any choice or conflict of law provision or rule. The terms of the Note are governed by the laws of the State of Delaware, excluding rules related to conflicts of laws.
The Warrant is exercisable in whole or in part at any time from the issuance date (April 10, 2024) to the expiration date which is five years from the initial exercise date. The exercise price is $0.0015 per share of RespireRx’s common stock, par value $0.001 (“Common Stock”). The Warrant may be exercised by cashless exercise in accordance with a formula described in the Warrant. The number of shares of Common Stock into which the Warrant may exercise and the exercise price may be adjusted for capital reorganizations or reclassifications such as stock splits, reverse stock splits, stock dividends and similar capital reorganizations or reclassifications. The Warrant and the shares of Common Stock into which the Warrant may be exercised are subject to transfer restrictions. Certain representations were made by the Warrant holder.
Dariusz Nasiek and Sara Nasiek, JTTEN
The Purchase Agreement is with the Dariusz Nasiek and Sara Nasiek, JTTEN and identified a $100,000.00 loan in the form of a Demand Promissory Note and a Warrant exercisable into 33,333,333 shares of RespireRx Common Stock. Dariusz Nasiek is a member of the Board of Directors of the Company.
The above is a summary of what the Company believes are key the provisions of the Purchase Agreement, the Demand Promissory Note and the Warrant. A copy of the entirety of each is filed as Exhibits 10.1-10.3 to this Current Report on Form 8-K. The above summary is qualified in its entirety by this Current Report on Form 8-K including the copy of the Purchase Agreement, the Demand Promissory Note and the Warrant between Dariusz Nasiek and Sara Nasiek, JTTEN and RespireRx Pharmaceuticals Inc. dated April 10, 2024 filed as Exhibits 10.1-10.3 to such report.
LTListener
3 days ago
I agree. They look to historically struggle getting any funding for their programs. I think the point out of the NIH trials, is that if the final preclincals continue to point to human trials, then the NIH will be funding some of that via grants and I think the investment thesis is "purse strings" will open from BP to take the baton and run with it. Given the current published success with KRM-II-81 in preclinicals for a wide array of pain indications and epilepsy, the thought or maybe the "gamble" is there are various paths of development and partnerships possibly under consideration to move the ball forward. I would speculate all other drug development programs would be on hold until they have direction with this.
One has to admit the silence and lack of 10-k, and a BOD loan... considering the extremely positive progress with the NIH is a change in the status quo, ho hum OTC penny stock life. Could also be desperation. But in OTC world, there is a fine line and sudden switch possible between desperation and a 100 bagger... lol
Trade like a pro: Leverage real-time discussions and market-moving ideas to outperform.
hondobud
5 hours ago
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