meixatech
1 day ago
Arnold S. Lippa
Executive Chairman, President & CEO, RespireRx Pharmaceuticals, Inc.
Arnold S. Lippa is an entrepreneur and businessperson who founded 6 companies, which include: DOV Pharmaceutical, Inc., Patch International, Inc. and Atypical BioVentures Fund, LLC and who has been the head of 5 different companies. Presently, Arnold S. Lippa is Executive Chairman, President & CEO at RespireRx Pharmaceuticals, Inc., Executive Chairman for Xintria Pharmaceutical Corp. (which he founded in 2006), Manager at Atypical BioVentures Fund, LLC (which he founded in 2004) and Senior Managing Director at T. Morgen Capital LLC (which he founded in 2005). Dr. Lippa is also President of Aurora Capital LLC and Manager at Atypical BioCapital Management LLC (he founded the company in 2004).
In the past Dr. Lippa held the position of Director at DOV Pharmaceutical, Inc. (he founded the company in 1995), President & Chief Operating Officer for Patch International, Inc. (he founded the company in 1984), Director-Molecular Neurobiology at Wyeth Holdings LLC, Professor at City University of New York and Professor at New York University School of Medicine.
LTListener
3 days ago
Just another example of a possible utilization of the ampakine platform adding tremendous value.
However, this potential goes unnoticed and ignored by potential investors as it is not even listed on their outdated website, pipeline nor any follow-up. Back in 2010 they sold the ampakine platform to Biovail for 10 million plus milestones. Biovail gave it back essentially due to their restructuring. Today with a DOD funded phase 2 for SCI which is probably a lead in to decide how to approach ADHD trials coupled with potential for orphan indications, I think these low impact ampakines are better positioned and much more valuable today then in 2010. Yet we hear nothing and the company wallows on the EM with a puny 1 million valuation.
With all the publication efforts related to ampakines, it does suggest they are prepping the platform for higher levels of interest. I think it would be logical that they spin out the platform coupled with investment monies to develop a pipeline for SCI, ADHD, orphan indications.
meixatech
3 days ago
Pattern sensitivity of ampakine-hypoxia interactions for evoking phrenic motor facilitation in anesthetized rat
Prajwal P. Thakre and David D. Fuller*
Journal of Neurophysiology - preprint
20 DEC 2023 https://doi.org/10.1152/jn.00315.2023
Repeated hypoxic episodes can produce a sustained (>60 min) increase in neural drive to the diaphragm. The requirement of repeated hypoxic episodes (vs. a single episode) to produce phrenic motor facilitation (pMF) can be removed by allosteric modulation of a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors using ampakines. We hypothesized that the ampakine-hypoxia interaction resulting in pMF requires that ampakine dosing precedes the onset of hypoxia. Phrenic nerve recordings were made from urethane-anesthetized, mechanically ventilated, and vagotomized adult male Sprague-Dawley rats during isocapnic conditions. Ampakine CX717 (15 mg/kg iv) was given immediately before (n = 8), during (n = 8), or immediately after (n = 8) a 5-min hypoxic episode (arterial oxygen partial pressure 40โ45 mmHg). Ampakine before hypoxia (Aprior) resulted in a sustained increase in inspiratory phrenic burst amplitude (i.e., pMF) reaching +70?ยฑ?21% above baseline (BL) after 60 min. This was considerably greater than corresponding values in the groups receiving ampakine during hypoxia (+28?ยฑ?47% above BL, P = 0.005 vs. Aprior) or after hypoxia (+23?ยฑ?40% above BL, P = 0.005 vs. Aprior). Phrenic inspiratory burst rate, heart rate, and systolic, diastolic, and mean arterial pressure (mmHg) were similar across the three treatment groups (all P > 0.3, treatment effect). We conclude that the presentation order of ampakine and hypoxia impacts the magnitude of pMF, with ampakine pretreatment evoking the strongest response. Ampakine pretreatment may have value in the context of hypoxia-based neurorehabilitation strategies
LTListener
3 days ago
Yeah everyone is thirsty for information and to see them hit the GO button here.
Seems like they have been straddling that button for quite awhile with the (will they or wont they file) saga after the BOD member loaned 100k when the filings were due and of course supposed commentary about shareholder letters and updating websites, etc, etc but they just "can't put a timeframe on it"... In any case on the EM now with minimal volume as most can't trade it and longs with due diligence completed are looking for pennies, nickels and dimes.
Meanwhile. The SCI phase 2 with DOD funding is supposedly coming at some point. The NIH is likely to grant money for the epilepsy candidate trials, probably in Q1 2025 and the OSA program has been held up for some unknown reason, but just look at funds competitors are raising for this eliminate CPAP solution and RSPI's new dronabinol formulation may be best candidate of all.
This plane has gotta take off sooner than later or stakeholders are going to get agitated and tired of scratching their scalp.
LTListener
4 days ago
Yeah I believe several of the publications and commentary related to ampakines essentially say that high-impact ampkines can be powerful but also come with a propensity for very serious side effects rendering them too risky for pharma development.
I think in the research realm, they are still studied because maybe someday there is delivery technology and other actions that can mitigate side effects while harnessing the utilization of high impact ampakines.
In any case, related to RSPI, their low impact ampakines, the gabakine and OSA program all have significant potential and the science team in my opinion has done a good job in studying and preparing these platforms to head onto the best possible clinical path for success. Unfortunately, to date, the communication, presentation and financing ends of the company are severely lacking. Hopefully they will emerge from the shadows with a significant partner and leadership so these assets can have the opporuntity to achieve greatness and not remain stagnant perpetually which does nobody any good.
meixatech
4 days ago
A patent that is inactive is no longer active, and is either lapsed, abandoned, or withdrawn. Once a patent is inactive, it can't be enforced or monetized, and the owner is no longer entitled to exclusive use of it. The patent then enters the public domain, and anyone can use it.
Here are some reasons why a patent application may be inactive:
Abandoned
The application is no longer live and can't mature into a registration. This can happen for many reasons, such as missing the filing deadline to respond to an office action.
Withdrawn
The applicant voluntarily decides to withdraw the patent application and not pursue protection
This implies that on November 21 2024 RSPI inactivated their patent for CX-929. I don't get it ???
meixatech
4 days ago
AMPAkines have site-specific analgesic effects in the cortex
Elaine Zhu, et al..
https://doi.org/10.1177/17448069231214677
Abstract
Different brain areas have distinct roles in the processing and regulation of pain and thus may form specific pharmacological targets. Prior research has shown that AMPAkines, a class of drugs that increase glutamate signaling, can enhance descending inhibition from the prefrontal cortex (PFC) and nucleus accumbens. On the other hand, activation of neurons in the anterior cingulate cortex (ACC) is known to produce the aversive component of pain. The impact of AMPAkines on ACC, however, is not known. We found that direct delivery of CX516, a well-known AMPAkine, into the ACC had no effect on the aversive response to pain in rats. Furthermore, AMPAkines did not modulate the nociceptive response of ACC neurons. In contrast, AMPAkine delivery into the prelimbic region of the prefrontal cortex (PL) reduced pain aversion. These results indicate that the analgesic effects of AMPAkines in the cortex are likely mediated by the PFC but not the ACC.
meixatech
4 days ago
Organophotoredox-Catalyzed Decarboxylative Carbon-Heteroatom Bond Formation: Access to Ampakine APIs and Quinazolinone Alkaloids
Organic Chemistry 29 November 2024, Version 1
Sameer R. Sonavane , Tushar B. Kale , Gaurang J. Bhatt , Santosh B. Mhaske
Show author details
This content is a preprint and has not undergone peer review at the time of posting.
Abstract
The study describes a novel and general protocol for metal-free intramolecular decarboxylative construction of carbon-heteroatom (oxygen, nitrogen, and sulfur) bond, enabling direct access to the bioactive ampakine and quinazolinone class of molecules. The cross-coupling of natural or unnatural amino acid based electrophiles with phenols, amides, and thiophenols via organophotoredox catalysis represents an innovative approach towards the synthesis of bioactive heterocycles. The present approach utilizes photochemical decarboxylative single electron oxidation to generate carbon-centered radical intermediate directly from amino acids under mild conditions, eliminating the need for preactivation. The designated protocol offers a convenient method to synthesize ampakine drug molecules CX-614 and CX-554, which have promising potential for treating Alzheimerโs and Parkinsonโs diseases. Interestingly, with nitrogen nucleophile, quinazolinone class of natural products deoxyvasicinone and mackinazolinone could be synthesized, whereas sulfur nucleophile furnished dihydro-thiazenone scaffolds. The reported protocol exhibits high functional group tolerance and scalability. A plausible mechanism has been proposed based on fluorescence quenching experiments and cyclic voltammetry analysis
LTListener
4 days ago
meixatech,
Thanks for continuing to provide info about ampakines here. I think there is plenty of information in past filings and notes from RSPI's history as to why they have only focused on developing low-impact ampakines CX-1739, CX-717 targeting SCI and ADHD. I think the question is can something like the lipid nanoparticle techniology revive the high-impact amapkines into a "new" patentable candidate drug that can be powerful but with mitigated side effect profiles? If so, it obvioulsy would open up a new realm to revist these past molecules. I think you would need to go directly to the science team here to get a true answer.
If it is possible, would RSPI with "apparently" ZERO resources, think about pursuing a revival as such? Clearly they have amped up their efforts on the publication front for ampakines the past few years. Whether the purpose is a prelude to spinning out the ampakine portfolio to a newco or possibly there is a BP ready to license the portfolio for development is a good question. Remember they have continually stated ALL their assets should be licensed, JV or sold. One would think too a successful SCI phase 2 trial beginning ???? would accelerate both valuation and efforts related to ampakines. Some updates and color would be nice on this front!