[LTListener]

Bread crumbs generally are small

[LTListener]

Oh yeah I guess you just need to be granted professional or sophisticated status to trade bread crumbs…

[DTGoody]

Lack of funds is my belief.

[NeutrinoKid]

On the expert market it seems transaction only happen in small lots.

[loanranger]

How many accredited investors do you think it might take to execute less than $2,000 in trading? Woohooo?

[lakers17]

Still bizarre to me they haven't filed with all the potential and what they are doing. Is there a valid reason why they haven't filed?

[LTListener]

Maybe some accredited are accumulating? Hopefully we get some updates and strategery soon leading into activity with the platforms in Q1 2025.

Could be exciting next quarter and year or more as multiple clinicals get underway.

[hondobud]

RSPI- Looking better today. GLTA HB

[LTListener]

Isn't that the nature of investing in the pharma industry and developing safe and effective therapeutics? Many times you fail!

In my opinion, the past is the past. The current science team has boiled down the AMPA platform to pathways that are most investible with the highest potential for success. Low-Impact ampakines for the SCI, ADHD and orphan indications. Could it be valuable to explore the past failures of various high impact and other ampakines, maybe, but certainly not for an under resourced company. And certainly not one that has 2 other promising platforms dealing with OSA and epilepsy/pain that is most logical patented approach (OSA) and superior to status quo in preclinicals (KRM-ll-81)...

This story will be written upon how these assets move forward unencumbered by the past. And that truth lies within all successful pharmas.

[LTListener]

Hard to say what kind of negotiations have been going on in the background. Really the only explanation is there is a larger move in play. They have hinted at spinning out the AMPA and GABA division and lamented about the OTC issues in raising capital. I just dont think you go radio silent and fail your stakeholders on the communication and presentation front with this embarrasing choice of EM market without a viable path to stardom. They have significant equity positions at stake as well. So who knows when and how they emerge from this stagnation which is a limiting approach.

One thing to think of though, imagine what these assets and their development now progressing into clinicals would be worth IF... there was a reputiable website with clarity and up-to-date information... a flow of communication to highlight projected timelines, milestones, strategies... and trading on an exchange like the NASDAQ with some institutional support and a little bit of cash in hand to manage 3 extremely promising platforms...

Seeing many pharmas trade 50-100 million in valuation with much much less of a pipeline potential... But it is a good time of year to remind oneself of those holiday stories where fortunes can and will turn on a dime. GLTA.

[NeutrinoKid]

A lack of critical understanding was not the problem per se because no one understood how to modulate on AMPA receptors anyway. The problem was that some deep pockets were led into believing that someone was going to figure it out quick, and pull a marketable product out of a bag for them. And modulating on AMPAr turned out to not lend itself to short-termism. Boo.

[meixatech]

I agree. The last 5 years have been incredible in the understanding of neurological processes. I noted before that Cortex just lacked this critical understanding which led to its demise., but it was on the right track which RSPI is building on. IMO critical was making available to groups worldwide of RSPI compounds and then reaping results in these preclinical studies.

[DTGoody]

All of it is meaningless unless they bring us current though. I found that interview to show the incredible potential as long as this company just follows through.

[LTListener]

Good article for prospective investors and highlights differences in approach with dronabinol and why the new formulation is so important. The improved solubility should help mitigate the inconsistency in absorption from person to person while controlled release should help utilize a lower dosage for extended duration of effect. On the surface that approach is most logical.

And look at the money competitors have raised to tackle OSA. Incannex recently has access to over 50 million in capital. RSPI brought in a VP dealmaking guy a year ago. Then radio silence. Supposedly this platform is valued 20 million and possibly multiples of. Not sure the hold up on the pk studies with new formulation, or maybe those are in progress? Quite possibly too, maybe there is a partner in the wings now that company is spun out in Australia and has chunks of money committed. Curiously, the predecessor to Incannex was in discussions with RSPI I think back in 2019 or something, but then both went separate ways apparently.

What are the immediate plans and strategy for this platform? Twiddle thumbs as time erodes value in patents and brings in competitive pressures? Take the assets to shark tank so real action on creating value can begin?

[LTListener]

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.

[Menace212]

[Menace212]

Insightful article below released in 2022

''Incannex met recently with the US Food and Drug Administration (FDA) to discuss the drug candidate IHL-42X, the name for its fixed-dose combination of dronabinol and acetazolamide, and is now using the feedback from the FDA meeting to refine and finalize the drug candidate formulation.

Overall, Bleackley says, “The FDA was really positive in the feedback that they provided us with.”

https://sleepreviewmag.com/sleep-disorders/breathing-disorders/obstructive-sleep-apnea/dronabinol-synthetic-thc-strong-contender-for-first-sleep-apnea-pill/

[DTGoody]

RespireRx collaborating with University College London to study treatment options for GRIA disorders:

[meixatech]

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 40–45 mmHg). Ampakine before hypoxia (Aprior) resulted in a sustained increase in inspiratory phrenic burst amplitude (i.e., pMF) reaching +70?±?21% above baseline (BL) after 60 min. This was considerably greater than corresponding values in the groups receiving ampakine during hypoxia (+28?±?47% above BL, P = 0.005 vs. Aprior) or after hypoxia (+23?±?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]

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.

[Menace212]

What's bid and ask now?

[Catpole]

I am in full agreement! We could see this blow up quickly! Just requires patience with it being in EM.

[StocktonCA]

Signs of life!!! just because it does not have a lot of activity going on stock wise does not mean activity is going on behind the scenes. when this emerges from EM, i believe those who held and believed will be smartly rewarded!!! GLTA

[Gladiator 83]

0,0015$ 💥🤑🚀

[LTListener]

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]

Yeah. I was intrigued by the extraordinary preclinical results of CX-929. But its patent HAS expired. Perhaps it can be reconstituted as a use patent? Oral administration appears to make this ampakine unique?

[LTListener]

I am fairly certain that in an old cortex filing that specific molecule had a patent expiration in 2022. IMO there needs to be clarity as to what is high-impact versus low-impact ampakines. There is enough confusion around this company and their choices to begin with. I think it is clear that along the ampakines route they are focused on CX-1739 and this SCI phase 2 trial that may be a lead in to utilizing this compound for ADHD a much bigger market. Outside of that, they have no bandwidth to pursue a revival of past compounds.

Now maybe if they had better communication and presentation and was attractive to sustainable investment resources a deeper pursuit could be undertaken, but I don't see that anywhere in their future. They have potentially a superior OSA formulation/solution and a superior preclinical gabakine for epilepsy/pain that needs to launch and get off the ground rolling. These should be primary focus.

But I am just a lowly retail investor, hobbying up discussions on a message forum.

[meixatech]

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]

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]

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 Alzheimer’s and Parkinson’s 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

[loanranger]

1. "ResolutionRx and the OSA program is already spun out"
2. "I am curious whether that company eventually is listed for trading and RSPI distributes shares to current shareholders."

1 is technically not true unless and until 2 occurs. ("Or will RSPI be more like a holding company?").

[LTListener]

Thoughts on possible spin out of assets scenarios.

The company has continued to reference this possibility making it both forefront and logical considering how broad their pipeline is. ResolutionRx and the OSA program is already spun out. Logical and program looks ripe for a partner to jump in. I am curious whether that company eventually is listed for trading and RSPI distributes shares to current shareholders. Or will RSPI be more like a holding company? Either way, it is curious that they hired a VP to focus on business side of ResolutionRx almost a year ago and there has been silence ever since. Partner and plans in place to get the balling rolling after the holidays hopefully? Would like to understand why the apparent delay with majority of funding committed and no update on pk studies, if started.

The ampakine and gabakine platforms could possibly be spun out or definitely partnered separately in my opinion. Reason is the ampakine program has a history and different pathways for different indications and questions regarding possibly reviving older molecules with newer delivery technology would be present.

KRM-ll-81 has had so much preclinical success and now presumably awaiting grant funding likely in early 2025 makes one wonder if that won't go an entirely different route.

I guess they have talked so much about JV, license or selling all their assets and really imply that the current OTC lack of liquidity is not a place to raise funding for drug development, I am just wondering as an investor do they see making RSPI a holding company or is there plans to take the entire company off the OTC somehow.

[All City Baby]

Does anyone know the bid/ask?

[LTListener]

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!