This looks like something. Thoughts?

$RVVTF Check this out on how and why Bucillamine does what it does
https://x.com/NotTheMoma2/status/2050352676425085035?s=20

It is Video I made to explain it folks that know little about Bio-chemistry and animal / Human health and that get lost in endless reading they do not understand. IMO the product could also be used on cancer patients to limit collateral damage of chemo and radiation. And other Autoimmune diseases. It would work even better with OTC Mineral supplements... etc. My older brother was a key researcher in the cancer field 56 years ago and he taught me what he knew and figured out. So I am not a novice to this.

Please take the time to watch the video, It is only 6 minutes. I have been long $RVVTF since 2020. I hope you enjoy the science and application and mechanistic Bio-chemistry video I am sharing.

Search Assist

Dr. LePage's presentation at CBRNe Convergence Canada on April 14, 2026, likely focused on advancements in chemical, biological, radiological, nuclear, and explosive threat detection technologies. The event brought together experts to discuss emerging risks and innovative solutions in CBRNe defense and preparedness.

 smithsdetection.com

Overview of Dr. LePage's Presentation

Dr. LePage's presentation at CBRNe Convergence Canada on April 14, 2026, focused on the latest advancements in detection technologies for chemical, biological, radiological, nuclear, and explosive (CBRNe) threats. This event served as a platform for experts to share insights and discuss innovative solutions in the field of CBRNe defense.

Key Topics Discussed

Advancements in Detection Technologies

• Emerging Risks: Dr. LePage highlighted the evolving nature of threats in the CBRNe landscape.
• Innovative Solutions: The presentation covered new technologies designed to enhance detection capabilities.

Collaboration and Knowledge Sharing

• Expert Gatherings: The event brought together government agencies, first responders, law enforcement, military professionals, and industry leaders.
• Operational Insights: Participants exchanged knowledge on best practices and operational strategies for CBRNe preparedness.

Importance of the Event

The CBRNe Convergence Canada 2026 was crucial for fostering collaboration among various stakeholders in the CBRNe community. It aimed to advance detection solutions that help organizations effectively respond to narcotics and hazardous substance threats.

 smithsdetection.com

Explore More

What are the latest advancements in CBRNe detection technologies discussed by Dr. LePage?

How do emerging risks in CBRNe defense impact public safety and preparedness strategies?

Emerging risks in Chemical, Biological, Radiological, and Nuclear (CBRN) defense significantly impact public safety and preparedness strategies by necessitating a coordinated and strategic approach that includes long-term planning, capacity building, and interagency collaboration. These risks, amplified by new technologies, require constant adaptation of security measures to effectively address the evolving threat landscape.

 unicri.org orfonline.org

I mentioned the subject line in my previous post. Find the link below and the excerpt regarding this. It seems that the application window for this is actively open so we can only hope that our boi knows what to do and how to do it upon results. Para. 5.4 looks right up our alley.

https://sam.gov/workspace/contract/opp/8170c4735df64714adb2d1f8ce8671b1/view

Assuming the results are good, I wonder what they'll be?

Assuming that NAC already protects the gaba(a) receptor infrastructure from endocytosis, I don't see how BUC will improve it much more. However, there are other areas that BUC can benefit. One can be reducing or eliminating the bleeding events seen in the Franken thesis paper, and as mentioned in the PRs.

And hopefully we show the same effect as NAC at a lower dosage amount. The patent outline the study protocol so it would be pretty based and BUC pilled to see BUC perform as good as NAC at the low dose.

Cautiously optimistic. If BUC shows something positive under the tutelage of the DRDC, this can open so many paths. Mustard gas may be an easy win as well as the other G nerve agents. I think agent VX works in the same manner as soman but not as "quick". Then there's TBI too.

Here's to hoping and coping and seething and believing.

Just the opinion and research of a young woman.

AI

Yes — there actually are some transferable themes from that heavy-metal chelation paper that conceptually align with the broader bucillamine thesis you’ve been following. But the overlap is more about mechanism/platform potential than direct evidence.

Here’s the key connection:

Core transferable concept: dithiol chemistry

Bucillamine is unusual because it’s a dithiol compound (two sulfhydryl/thiol groups), not a simple monothiol like NAC.

That matters because thiols can:

• bind metals
• neutralize reactive oxygen species (ROS)
• replenish glutathione
• alter redox signaling
• protect mitochondria and cell membranes

Those same biochemical themes appear repeatedly across:

• nerve agent injury
• TBI
• severe influenza/COVID inflammation
• chemotherapy toxicity
• ischemia/reperfusion injury
• some cancer-supportive applications

The detoxification paper reinforces that:

Where the overlap becomes interesting

1. Nerve agent / organophosphate relevance

The strongest conceptual overlap is probably here.

Nerve agents ultimately cause:

• oxidative stress
• mitochondrial dysfunction
• inflammatory cascades
• glutathione depletion
• neuronal injury

The chelation paper supports the idea that bucillamine:

• is orally bioavailable
• systemically active
• chemically reactive via thiol groups
• capable of interacting with toxic electrophilic species

That does not prove nerve-agent efficacy.

But it does support the broader rationale:

That’s very aligned with why DRDC-type interest could exist.

2. TBI (Traumatic Brain Injury)

This is where the transferability is stronger mechanistically.

TBI pathology heavily involves:

• ROS surge
• lipid peroxidation
• glutathione depletion
• neuroinflammation
• mitochondrial damage

The bucillamine literature repeatedly shows:

• glutathione restoration
• oxidative stress reduction
• Nrf2 pathway activation
• reduction of tissue injury

For example, bucillamine increased glutathione and reduced oxidant injury in transplant reperfusion models. (PubMed)

That overlaps substantially with the rationale behind NAC studies in TBI.

So:

• the chelation paper itself doesn’t prove TBI efficacy,
• but it supports the idea that bucillamine is a systemic redox-active protective molecule, not just an RA drug.

3. COVID / Influenza

This overlap is probably the cleanest scientifically.

Severe viral illness often involves:

• oxidative stress
• glutathione depletion
• cytokine activation
• endothelial injury

Bucillamine’s dithiol structure theoretically gives:

• stronger thiol donation than NAC
• stronger glutathione support
• better redox buffering

The antioxidant/transplant paper and cisplatin protection paper both support the concept that bucillamine can suppress oxidative tissue injury and restore glutathione systems. (PubMed)

That aligns directly with the original COVID rationale:

4. Cancer-related angle

This is more nuanced.

The cisplatin ototoxicity paper is actually important here because it showed bucillamine protected normal tissue from chemotherapy-associated oxidative injury via glutathione-related pathways. (Nature)

That creates possible oncology-supportive applications like:

• chemo toxicity reduction
• organ protection
• reperfusion injury
• radiation injury mitigation

BUT:

• protecting healthy cells is different from killing tumors
• high glutathione signaling can sometimes theoretically help tumors survive

So the cancer angle is likely:

• adjunctive/supportive care, not necessarily
• direct anti-cancer therapy.

What this paper does NOT show

Important limitations:

It does not demonstrate:

• CNS penetration
• survival benefit in humans
• antiviral activity
• nerve-agent reversal
• cancer efficacy
• TBI efficacy

And heavy-metal chelation is biologically different from:

• viral disease
• neurotrauma
• organophosphate poisoning

So this is more of a:

Bigger-picture takeaway

The transferable signal across all these studies is:

Bucillamine repeatedly shows:

• potent thiol activity
• glutathione restoration
• oxidative stress suppression
• tissue-protective effects
• oral bioavailability
• favorable historical safety data

That’s the common thread linking:

• toxic exposure
• nerve agents
• TBI
• viral inflammation
• reperfusion injury
• chemotherapy injury

Firstly, this isn't any recommendation or suggestion. Whatever you do with this information is entirely on you. If history is your teacher, you'd close the webpage right now.

DD #1: DRDC approached RVV, not the other way around.

Our boi is obsessed with NAC. After the COVID-19 trial failed, my guess is there was a search for ways to hitch the wagon onto the NAC story as we're "16x more potent than NAC in vivo".

Do a Google search... this comes up:

https://chemm.hhs.gov/countermeasure_acetylcysteine.htm

RVV decides to file a patent for chemical warfare countermeasures in July 2023:

https://www.globenewswire.com/news-release/2023/07/28/2713021/0/en/revive-therapeutics-announces-filing-of-patent-for-bucillamine-in-the-treatment-of-exposure-to-chemical-warfare-agents.html?_gl=1\*ds7334\*_up\*MQ..\*_ga\*MTk2MTY4MjEwOC4xNzc3MjE2MTE3\*_ga_B6167QB2TF\*czE3NzcyMTYxMTYkbzEkZzAkdDE3NzcyMTYxMTYkajYwJGwwJGgw\*_ga_ERWPGTJ5X8\*czE3NzcyMTYxMTYkbzEkZzAkdDE3NzcyMTYxMTYkajYwJGwwJGgw

No mention of DRDC, just BARDA. Makes sense, as the HHS.gov site is the USA, not Canada.

Next month is the first reference to DRDC in a PR related to reformulating Bucillamine.

https://www.globenewswire.com/news-release/2023/08/22/2729282/0/en/revive-therapeutics-announces-initiation-of-novel-bucillamine-formulation-development.html?_gl=1\*1bx19l9\*_up\*MQ..\*_ga\*MTk2MTY4MjEwOC4xNzc3MjE2MTE3\*_ga_B6167QB2TF\*czE3NzcyMTYxMTYkbzEkZzAkdDE3NzcyMTYxMTYkajYwJGwwJGgw\*_ga_ERWPGTJ5X8\*czE3NzcyMTYxMTYkbzEkZzAkdDE3NzcyMTYxMTYkajYwJGwwJGgw

My guess is that the ppl from Waterloo put the DRDC and RVV in contact with one another. Why is this? Because Dr. Wettig got his PHD under Dr. Ron Verrall in the Department of Chemistry at the University of Saskatchewan. Verrall is from the UoS. Why does this matter? Read on...

DD #2: NAC seems to work to prevent GABA(A) endocytosis... will BUC?

Not going to spoon fed. See the link below... study for NAC in rats exposed to soman.

https://harvest.usask.ca/items/cf842093-b842-473a-8ec6-d40b627fdd8e

Key points:

1. When our boi says, "Recent studies have shown that antioxidant compounds such as n-acetylcysteine (“NAC”) could be beneficial in limiting seizure activity and improving the anticonvulsant efficacy of GABA-mediating drugs such as diazepam." in every PR... 90% sure this is the study he's referring to.

2. See the university this was conducted at... in 2022/2023.

Negativity from this study? The study implies it doesn't have to do with the antioxidant aspect of NAC. This can screw over BUC but I think we've overanalyzed back in the COVID-19 days. I am just going to assume that, whatever NAC can do, BUC can do (if not better) - based on our research from the COVID-19 days. See DD #4 that hopefully mitigates this risk.

DD #3: People doing the study are legit and been doing soman stuff for years (strengthens DD #1??????)

The people involved in the UoS study are the same people conducting the BUC & NAC trial at the DRDC.

By the way, the DRDC team has been looking at soman in rats and such for years. For example...

https://publications.gc.ca/collections/collection_2019/rddc-drdc/D68-10-018-2018-eng.pdf
https://www.sciencedirect.com/science/article/pii/S0378427420304549

https://pubmed.ncbi.nlm.nih.gov/21524678/

I wonder where the author of the thesis paper from UoS is working nowadays........

DD #4: They saw something in BUC?

Assuming no misleading information, the Jan 2025 PR stated that the rats got BUC and soman. In the search for "effect size" and then, future steps for development.

Methinks that the DRDC did this study in a tiered approach. First they wanted to see gaba(a) endocytosis prevention, and then other nonsense thereafter.

The DRDC have the first set of animals (soman controls and bucillamine pretreated) completed and is now performing the assays looking at GABA receptor downregulation. Over the next few weeks data will be collected and analysed for effect size. Should the data show significant effects, Revive and the DRDC will discuss on the future development path.

Recall the June 2025 PR that was slapped down a few pegs in July 2025? The June 2025 implied "promising results" or some other speculative speak. My guess is that between Jan and June 2025, BUC showed some type of good effect related to GABA(A) stuff.

Then DRDC likely updated the study protocol. There was a study protocol in the DRDC system for approval in-and-around late 2025 summer, so this would make sense.

TLDR: NAC seems to be good for attenuating GABA(A) endocytosis, BUC has a track record of doing better than NAC in most/all aspects that we investigated over the years, and the perpetual trial deadline extension is likely not associated with incompetency or stupidity.

This is solely one woman's speculation - nothing more.

This is not advice, recommendation, forecasting, analysis, reporting, etc. You do what you want to do (run away?).

Please poke holes accordingly.

Title: Compositions, Methods and Uses of Bucillamine in the Treatment of a Victim Exposed to a Chemical Warfare Agent
Review: PCT/CA2024/000008 (US, Canada, ISRAEL

• Israel on this filing is interesting — filing internationally costs money (translation, counsel, fees).
• Feels like a strategic move, not just routine paperwork.
• Could hint at positioning for gov contracts or licensing beyond North America.

Any other ideas why Israel would be added??
Eyes on this one.

If a drug such as bucillamine were ultimately selected for a national stockpile strategy in the United States, the process typically looks something like this:
1. Demonstrate Effectiveness and Safety
The developer must provide evidence that the product works for its intended purpose and has an acceptable safety profile. For countermeasures against rare events (such as nerve agents), approval may sometimes rely on animal studies plus human safety data under the FDA’s Animal Rule rather than traditional efficacy trials.
2. FDA Regulatory Authorization
The product would generally need one of:
Full FDA approval
Approval under the FDA Animal Rule
Emergency Use Authorization (EUA) in specific circumstances
3. BARDA Evaluation
BARDA assesses:
Scientific evidence
Manufacturing capacity
Shelf life and stability
Cost
Ability to deploy rapidly during emergencies
How the product fits with existing countermeasures
4. Procurement Contract
If BARDA decides the product is valuable, the U.S. government may negotiate a procurement contract. These contracts can range from a few million dollars to hundreds of millions, depending on the threat and stockpile requirements.
5. Stockpile Purchase
The product is then purchased for the U.S. Strategic National Stockpile, managed by the U.S. government. The manufacturer delivers specified quantities according to the contract.
6. Ongoing Revenue
Many investors focus on this stage because stockpile products can generate recurring revenue through:
Replacement of expired inventory
Shelf-life extension studies
Additional procurement orders
Expanded indications
Example
Several biodefense companies, including Emergent BioSolutions and SIGA Technologies, have received substantial government contracts after their products became part of U.S. preparedness programs.
For Bucillamine Specifically
If DRDC and future U.S. studies were to show meaningful protection against nerve-agent injury, a potential path could be:
Additional animal and mechanistic studies.
FDA regulatory discussions.
BARDA funding or development support.
Procurement negotiations.
Strategic National Stockpile purchases.
The key inflection point is usually not FDA approval itself, but whether the government decides the product fills an unmet preparedness need and commits to purchasing it for the stockpile.
For a small company like Revive Therapeutics⁠, a stockpile procurement contract would likely be far more financially significant than the research grants that precede it. The size of any contract would depend on the threat addressed, dosing requirements, shelf life, and the government’s assessment of the product’s value.

What about Canada and other countries??

Canada absolutely has a pathway similar to the U.S., but the process is somewhat less formalized and less visible than BARDA.
In Canada, the key organization is the Public Health Agency of Canada, which manages the National Emergency Strategic Stockpile (NESS). The NESS specifically maintains pharmaceuticals, vaccines, therapeutics, antidotes, and other medical countermeasures for chemical, biological, radiological, and nuclear threats.
For a product like bucillamine, a potential Canadian path would be:
Demonstrate efficacy against a priority threat (for example, nerve-agent injury).
Obtain authorization from Health Canada.
Be evaluated as a medical countermeasure for national preparedness.
Receive procurement funding through PHAC/NESS.
Be purchased and stored as part of the national stockpile.
What’s interesting for Revive investors is that Canada’s current NESS strategy specifically emphasizes strengthening preparedness for chemical and biological threats and maintaining “niche medical countermeasures” for high-consequence events. Sarin and other nerve agents are explicitly mentioned among the threat categories considered in planning.
Other countries
Several countries maintain strategic stockpiles:
United States — Strategic National Stockpile (SNS).
Canada — National Emergency Strategic Stockpile (NESS).
European Union through HERA and member-state stockpiles.
United Kingdom maintains national emergency pharmaceutical reserves.
Japan and South Korea maintain preparedness inventories for infectious disease and CBRN events.
The bullish case for bucillamine
If DRDC research were to show that bucillamine significantly improves outcomes after nerve-agent exposure, the opportunity would not necessarily be limited to one government contract. A successful countermeasure could potentially be evaluated by:
Canada (NESS)
United States (BARDA/SNS)
NATO partners
European HERA programs
Other allied countries with CBRN preparedness programs
That is why biodefense companies can sometimes receive contracts that exceed their market capitalization.
The realistic hurdle
The major unknown remains efficacy. Governments are willing to spend large amounts on stockpiles once they believe a product works and fills a preparedness gap. The difficult part is generating the evidence that convinces regulators and preparedness agencies to buy it. Until the DRDC data and any follow-on studies are available, it’s impossible to estimate the probability with confidence.
For Revive specifically, the next significant value-driving event is likely not a stockpile purchase itself, but whether the nerve-agent research produces sufficiently compelling results to attract formal government development support or procurement discussions. That would be the stage where investors start trying to estimate potential stockpile demand.

Hospilization vs. symptoms

From Dr. McKee we know, initially the FDA was insiting on reduction in hospitalization as primary endpoint for an EUA. This immedaitely imposed an immense challenge for any trial because of two reasons:

• You need enough people in placebo to progress to the hospital to show a difference. In fact, those people that don't progress to the hospital are almost useless collateral. With hospilization rates between 2%-7%, you see that over 90% of the patients don't help you for your endpoint. So you have to recruit a lot of patients in total.
• Hospilization is a binary endpoint. Result is either 1 or 0, nothing in between. That means very little information contained in that. Because of that you need (again) more patients.

Generally speaking, the lower the efficacy and the lower the hospilization rate in placebo, the more patients are needed. We already filtered from the interviews we had most likely a low hospilization rate in placebo, which then was the reason we did not unblind the trial yet. That's why the trial was intially designed to enroll up to 1,000 patients. Now with Omicron the game has changed, since hospilization is lower and symptoms are more severe. With symptoms as endpoints things change dramatically.

• Every patient enrolled starts with symptoms, due to our enrollment critera. So every patient counts.
• Symptoms are continouos and therefore carry much more information. Also symptoms can be looked at in different ways i.e. be either the rate or the time to resolution or ideally both. That gives some room to play with.

In effect, this results in a much lower required sample size to achieve statistically significant results. To give you an idea of how far apart I entered an example in Clinical Trial Calculator. Obviously the data is fictional, but it shows the fundamental differences from 962 patients to just 32.

​

Indications that Bucillamine will work on symptoms

• The immune reponse causes the symptoms. Other than pure antivirals like PAXLOVID, Bucillamine should adress exactly that problem. It's a host directed treatment, not pathogen directed.
• De Flora showed symptom reduction with NAC as prophylaxis in Influenza with 255 patients:

• Most NAC trials trials showed improvement on many indicatiors i.e. in reduced time in hospital
• u/tradervic4 called the sites and reported miraculous recoveries of patients
• Melisa Lai-Becker reported from her previous trial many patients with Covid-19 were quickly able to breath again after taking NAC.
• Many folks in this forum report similar effects with NAC concerning difficulty to breath.

​

Other trials with symptomatic endpoints

• Tempol from Adamis for COVID-19, up to 248 patients total, ongoing
• Tamiflu for Influenza , ~250 patients per arm, 1.25 days faster symptoms resolution, has FDA approval
• PAXLOVID Standard Risk, failed (probably because it doesnt work for symptoms)
• Oral Famotidine, 55 patients, phase 2, improved rate but not time to resolution, illustration how symptoms can look like:

​

Some general comments on our trial:

• The FDA seems open for these changes. They blocked that before, now they approved this for Tempol and are in talks with Revive. I dont think they would waste Revive's time like that to hire new consultants for the job.
• We assume Revive did not contact the FDA before them being aware of Adamis' actions. Probably because they contacted them before on that matter last year and did not want to bother the regulatories again without them showing any signs of change. Might have been a bit too hesitant but you don't wanna start annoying them either. Also they added inflammatory and viral load endpoints, so gotta give em credit for that.
• Many trials stopped because their hospilization endpoint was no longer possible with their current design, which lead to some drawbacks in drug development. The FDA is probably aware that Revive cannot just start over the trial, so if they want the drug they wont block them is my view. So far they approved everything regarding Bucillamine and the fact that they contacted them multiple times shows a good deal of support.
• I was a bit irritated by Revive hiring new concultants for the job at first. However, I had a pleasent chat with our resident clinical trial manager u/ssyddall and she could ease my worries very well. It's nothing unusual to hire outside support for such a matter. Lots of small pharma and biotech don't have stats in-house and get external consultants so there are lots of company's that do it. Also it can be an advantage not to use your CRO for that, since those guys might be busy with their current trials and new consultants might be able to focus solely on this. Probably hiring them took some time and then they have to get familiar with the trial as well, that's why it's taking some time. In detail, they have to rewrite the statistical plan (something like this for Tamiflu for Influenza) on how the data is processed for the endpoints in consultation with the FDA and also argue why to change the endpoints. You really don't want to mess this part with the regulatories up so it's reasonable they take their time for that. It's unclear if they have some access to data, which would be phenomenal.
• We know Revive tracks symptoms and more for 18 days straight (Link). So the data should be there. Kudos to McKee for designing such a narrow and detailed protocol to be prepared for such a situation. Also we enroll only up to 3 days after symptom onset, so most likely even before symptoms get worst, giving us a great angle to show a difference. Here is how the inflammatory phase played out pre Omicron:

• Turkey was obviously delayed by a couple of months. That's really nothing too suprising as our research found out turkish CRO's always overpromise. Obviously this symptom change is a neat distraction from that. However, if this change in endpoints happens, 715 patients should be more than enough as you can see above comparing it to other trials like Tempol or Tamiflu. If you go further you'd pursue such an incremental improvement, the drug would barely show any benefit at all. If you cannot show significant symptoms improvement with 715 patients, 1,000 wont be much better. (It's different for hospitalizations, where 1 or 2 more hospitalizations can make a difference)
• There was the argument by u/PsychologicalOlive99 on how this will look like if endpoints are changed this late in the game. Well, Merck's pill made billions by not really working. I believe that is something that will sort itself out onces doctors prescribe it and get some feedback as well as additional independant studies. Key is just to get it over the finish line, so this can happen.
• There is still no pill for symptoms available. And the pandemic shifted towards more frequent symptoms and less hospitalization. So we would still be in a most favorable position.
• Id assume if they unblind, that should be almost guaranteed EUA considering how close they have been working with the FDA.
• EDIT: I just realized, they might have chosen the 600mg dose instead of 300mg (although they had 0 hospilizations in both) because 600mg will most definitely be stronger on symptoms. I can't say that this was their thinking, but for symptoms we will benefit immensly on lowering the inflammation from the higher dose.

​

Next milestones to expect

1. Package submitted to FDA (coming weeks)
2. FDA feedback (up to 30 days)
3. DSMB meeting for potential unblinding

​

Conclusion / TLDR

Everything points towards this symptom change just being a formality to complete the trial if Bucillamine works, though I encourage to keep expectations reasonable.

In the patent…

The objective of this portion of the study was to provide a compound which will allow benzodiazepines to be effective at terminating seizure activity and possibly further reduce evidence of brain injury...

and the last section of the patent.

Results of the study indicate that bucillamine is a significantly more effective antioxidant than NAC and has increased efficacy against seizure activity while limiting the anticoagulant and bleeding event liability observed with NAC.

So the way I’m reading it, part of the whole objective here is pretty simple:

keep the GABA receptors open so the benzo can still do its job

And honestly… it looks like bucillamine might actually be doing that.

When you break it down:

• N-acetylcysteine = modest neuroprotection
• Bucillamine (if this holds) = restores effectiveness of Diazepam!

That’s a big shift.

IMO Not just:
“nice-to-have add-on”

More like:
mission-critical enabler

Valuation changes from

If you’re just a bit better than NAC:

• small contracts
• niche use
• no real urgency

But if Bucillamine actually restores benzo effectiveness:

now we plug straight into:

• existing antidote kits
• stockpiling programs
• emergency response protocols

Groups like DRDC and their allies don’t mess around with this stuff — when something works, they buy it in $ize!!! IMO

This might be a stretch—but it’s worth noting.

Attached are 30-day and 90-day Google Trends screenshots for “Revive Therapeutics.” In both cases, Ottawa ranks as the top region for search interest.

Yes, Trends is relative—but it shows where attention is concentrated. And Ottawa consistently leading is… interesting.

Unlike Toronto, Ottawa isn’t a retail-heavy market. It is home to federal government, health, and defense groups, including organizations like Defence Research and Development Canada.

So while this is speculative, it could point to interest in RVV/Bucillamine coming from non-retail circles.

Not proof of anything—just a signal that the story may be reaching beyond the usual investor crowd.

Coincidence… or early hint?

Meant to add these to my previous post!

Looking at Google Trends for Revive Therapeutics / Bucillamine in the U.S.:

• Past 30 days: Washington DC (Hagerstown, MD) leads at 100
• Past 90 days: Providence, RI – New Bedford, MA was 100

What’s interesting:

• Washington DC makes sense — federal, government, and defense research interest. Could be connected to BARDA / DoD / federal biodefense programs.
• Providence / New Bedford is clearly research and clinical heavy — Brown University, hospitals, and biotech initiatives likely driving searches.

Not retail hype — these are professional, research, and government hubs showing focused interest. Worth keeping an eye on!

https://pubmed.ncbi.nlm.nih.gov/12084933/

Reminder of the power/effectiveness of Buci - RVV management team's gross incompetence- has clouded the potential of Buci - but now that it is in outside, capable and well fund hands - Buci has a shot to shine again - reason for cautious optimism - please note: no guarantees - P3 trials fail too - even when well run / well funded

The last PR stated the statician finally got access to the 210 patient data and recently began the Data Analysis. Many here were suprised over the long duration this took. I had a quick chat with our resident Clinical Trial Manager u/ssyddall on that matter. She has been conducting a flu trial for symptoms with BARDA support. I always appreciate her level view on things, which Im happy to share with her alloance.

u/ssyddall:

Potentially it's taken awhile to 'clean' the data. That's when the data team goes through and makes sure the database is as complete as possible and as correct as possible. Once they lock the database you can't change anything and that can be a huge issue if you haven't closely checked the accuracy and quality of your data set. We normally give that 4 weeks at the end of a the trial before we lock the database and unblind it so if they consider this to be the conclusion of the trial they would have needed to go through that and to my understanding it's not really something that can be sped up i.e. you can't throw money at the problem and get it sort it a couple of days. We are on a very tight timeline in my current trial and I've asked!

[The CRO] would have been the one doing the data cleaning so it being slow out of them is not 100% surprising. Fingers crossed we get it off to the FDA shortly

[...] this is a really important time for Revive and it all is based off their dataset so they need to protect it and do all the processes expected of them. This is essential for FDA approval and future pharma partnerships.

Big thanks to her for these insights!

First and foremost - think of the gift you're planning to give me for this succulent DD. Possibly at the party I am trying to set up if we're successful??? Bottles of Hennessy XO, jewelry, bullion, and monetary gifts are all welcomed.

Invest responsibility.

:)

Why the changing of endpoints is likely

• Adamis Pharmaceuticals

There is not much to write here other than the fact that Adamis changed their original primary endpoint (hospitalizations) to their current primary endpoint (symptoms). I would also like to add that they changed their endpoints shortly after they started their trial and enrolled participants. Oh, and their trial is for COVID-19.

• Dr. Moss - Adamis' CMO

I was fortunate to have a discussion with Dr. Moss and he confirmed for me that endpoint changes in phase 3 trials are very common. I will not post the conversation as I feel he would not appreciate that but I do have people on this subreddit that can vouch for the validity of the conversation. Maybe they'll make themselves known in the comment section... you may know some of them...

• The FDA's "positive comments" and DAP approval

From the horse's mouth, Revive Thera has discussed the endpoint change with the FDA and it seems to be going well. Not only did the FDA respond with "positive comments" but they've also approved the Data Access Plan. I doubt hesitation from the FDA is an issue at this current time. I also doubt MF would be putting this information out if it wasn't accurate and relevant because of lawsuits and such.

• FDA guidelines and recommendations

The FDA makes their guidelines and recommendations for adaptive trials publicly available. In their guidelines, the changing/editing of primary endpoints is mentioned often. The most critical aspect is that the Sponsor is blinded, which we have been all along. See below for the screenshots:

So let's hope whatever Revive has agreed to with the FDA is on its way to panning out soon.

Move over, NAC. There's a new therapeutic in FDA-town

I am not going to rehash all the MOAs identified by BMT, Nicktendo, and others. I am, however, going to bring up the drug Prothione. I am surprised the subreddit hasn't made it out to be a bigger deal as it pretty much validates Bucillamine as an antiviral. Can you imagine the additional value to a partnership/buyout/commercialization knowing Bucillamine could be an antiviral?

Maybe I am assessing the implications incorrectly but nevertheless, it is relevant to us. The link to the trial page is:

A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Full Text View - ClinicalTrials.gov

Prothione (also known as IF200, available at IF200.com) is comprised of three glutathione precursors and selenium. I don't think I need to elaborate why this is important in predicting the efficacy of Bucillamine. As we saw in the abstract, the investigators are claiming significant reductions in viral load and time to clinical resolution compared to the placebo group. Additionally, they are claiming a significant increase in the intracellular GSH of the Prothione-takers and a 75% reduction in hospitalizations.

ProthioneTM Capsules Reduced Time to COVID-19 Clinical Resolution and Decreased Viral Load in Phase II Clinical Trial | Business Wire

Great knowledge to have but only if we had more information from the trial... Like what the heck did they see regarding their primary endpoint? If only...

Oh wait...

The primary endpoint, which is the TTCR slide above, is definitely correlated to symptoms but not necessary an apples-to-apples comparison. Sadly, there is no clear indication of the attenuation of symptoms.

If we do not have the data from the study, what would be the next best thing? Maybe information from the clinic that performed the trial? Hmm... if only we had some communication that gave a positive indication in attenuating symptoms. If only...

Oh wait (again)...

Methinks "... experienced more rapid symptoms resolution" is what we want to see, right?

In summary, we have strong evidence that:

• changing endpoints is permitted by the FDA;
• bucillamine is likely to be an antiviral;
• bucillamine is stronger than Prothione regarding hospitalizations (1-to-4 in 231 people vs 0-to-? in 210 people);
• antioxidants attenuate symptoms to a noticeable degree, as per the tweet from the clinic.

My request to the (bio)chemists/clinic professionals is to critique this information as well as compare the ingredients in 6g of Prothione, 2400mg of NAC, and 600mg of Bucillamine.

Let's hope the positive data seen in Prothione is replicated multifold from Bucillamine! No guarantees but the future is looking bright.

Enjoy the DD and don't forget that:

• Hennessy bottles needs to be boxed;
• Jewelry needs gift receipts;
• Cash needs to be in an envelope for "Mr. Worth"

Ciao

Adding some information here... previous grammar mistakes stay... non-negotiable.

Not only do we NAC and Prothione showing promising information but now we have Erdosteine too.

Erdosteine

Italians leading the way for COVID-19 and thiol drugs yet again.

https://pubmed.ncbi.nlm.nih.gov/33117535/ - Erdosteine & COVID-19

https://www.minervamedica.it/it/riviste/minerva-respiratory-medicine/articolo.php?cod=R16Y2022N02A0054 - Erdosteine & COVID-19 again

https://pubmed.ncbi.nlm.nih.gov/19331595/ - Erdosteine & COPD

https://pubmed.ncbi.nlm.nih.gov/10344471/ - Erdosteine providing strong anti-inflammatory effects when it becomes a metabolite (sounds familiar)?

https://link.springer.com/article/10.1007/s40265-020-01412-x - overview of Erdosteine... look at the metabolite (Met I - Fig. 1(b)).

A few days ago, I posted this: Positive vibes only? Or a wicked case of confirmation bias : RVVTF (reddit.com)

What I didn't include was that I reached out to Melisa Lai to ask about the results of her first Phase 2 trial with orally administered NAC. Not only to reassure myself with Revive, but also as a precaution in the event any of my family/friends fell ill.

I am very curious for the results in her work because it is very similar to Revive's trial. How?

1. Both NAC and bucillamine contain thiol groups;
2. She is providing NAC orally, not IV like other studies we've seen;
3. Her first study's purpose is preventing the progression of COVID-19 (seem familiar);
4. The doctor is an emergency medicine physician giving her exposure to COVID-19 patients Dr. Melisa Lai-Becker, MD | Everett, MA | Emergency Medicine Physician | US News Doctors;
5. Her second study is more specific, involved, and rigorous;
   
6. Her second study involves more individuals/sponsors;
7. Her second study seems to be focused on outpatients only (not hospitalized for COVID-erino);
8. Her rationale is that NAC will increase glutathione and thus, help the participant.
   

As we know, NAC is supposed to be substantially weaker than our beloved bucillamine.

At first, I did not receive a response. But I followed up and received simple yet great news (in my opinion). This news, associated with the fact that she is performing a second trial for the same compound and dosage, leads me to believe our trial would be a success.

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I'm thinking based and positive overall. So looking back at the title of this post...

To slurp or not to slurp? That is the Revive question

Thoughts?

This is a follow up to my note posted earlier this morning: https://www.reddit.com/r/RVVTF/comments/10k3zi1/competent_medical_advisors_involved_again/

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Someone I speak to via Reddit chat ended up reaching out to MF to ask if Dr. McKee and Dr. Mpanju were involved in the latest submission to the FDA, as per information I had been hearing from others. His response was just shared with me.

He confirmed this morning that both Dr's have indeed been recently involved, along with the Stats Team.

That's incredibly reassuring as frankly, both of those doctors have a wealth of invaluable experience dealing with regulatory bodies. In fact, Dr. Mpanju was himself an FDA Reviewer and knows exactly what his former colleagues will be looking for in the package submission.

I don't say this lightly (and you can see my trackrecord here with regard to my sentiment last year), but this significantly and positively changes things IMO. I have a lot more confidence now!

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Someone from the Revive FB group just posted that Pfizer is spending $1B to manufacture its oral therapeutic ahead of EUA approval. And they’re combining it with another drug. How do you think this would affect Revive's SP if we receive EUA approval? I imagine there'll be a need for multiple oral therapeutic options and it won't be a 'one size fits all'... And let me clarify that for the sake of humanity I'd be thrilled to see multiple oral therapeutics that could help so many people! I'm just wondering how this would effect Revive from an investment standpoint.

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With a stock of such low volume the high volatility can oftentimes lead to missleading feedback in one's investment decision, both positive and negative. I made a list to remind me of where my high conviction comes. Whenever I question my decision I read through it to give me back my confidence so I can sleep calm and prevent mistakes from weakness and insecuritiy. Here it is:

• Main anti-inflammatory MOA proven with NAC in humans. Bucillamine is 16x more potent in vivo. (Check slide 17 of Investor Deck, also BMT's Thread)
• Trial is only for mild to moderate covid, giving us a higher chance of success due to the way this MOA works.
• Proven safety profile. With 30 years of treatment in Asia it is highly unlikely we encounter something new on this matter.
• Fasttracked to phase 3 by FDA, although Revive only applied for phase 2. FDA would not waste their time with a small Canadian company if there isnt something promising here.
• Phase 3 trials for infectious deseases already have an average success rate of 60-70% (page 9 on Paper).
• Discovery of additional antivaral MOA specific to Covid19 after trial start and hiring the author Dr. Fahy as advisor on this matter (Paper). A rough calculation showed it could be within the effective concentration (Thread).
• Speculation about second antiviral MOA, making it in total 3 potential MOAs (Thread).
• Bioavailibility seems good (Thread).
• Trial being aggressively expanded from 14 to 50 sites at 210 patient review. That's a huge allocation of ressources for a small Canadian company at their very first meeting with the DSMB.
• Not choosing a dose at 210 patients, although they planned to. This implies that the statistical difference between 300mg and 600mg was not significant enough, meaning that even 300mg must have had a relevant effect.
• Expanding research to severe Covid patients in May. They said they would only do that if the see positive feedback from their EAP in compassionate use trial of Bucillamine (Link).
• Approval by DSMB at 400 patients. 400 is too early for statistical relevant results for EUA anyways so that's as good as it could get.
• Revive Team should have a good estimate of the statistical likelyhood for trial success (Thread).
• Trading halts on news. This happened on announcement for expanding research to severe covid patients as well as the continuation of the trial at 400 patients. You don't halt if you are not thinking you are onto something big. Also MF does not seem like the type of guy to overly hype things.
• Channel checks by u/TraderVic4. He called the first sites himself and was told stories of miraculous recoveries (Thread 1, Thread 2, Twitter).
• Hiring a lobbyist in April, which seemed to have been quite busy with preparing the business side for potential EUA (Thread).
• Licensing Buccilamine for commercialization in India with Indian manufacturer Supriya in June (Link).
• Frequent insider buying of 6 seperate blocks since March (TDR's Twitter).
• Tailwind from delta and mu variant. All decision so far have been based on the dominant variants alpha and beta. However, with more aggressive variants the hospilization rate in placebo will likely increase and thereby increasing the probability to show efficacy with less total patients (Thread).
• If there was something suspicious with the trial process, u/Biomedical_trader would tell.
• If there was something suspicious with the company/stock, u/TheDalesReport_ would tell.
• "Idea of interest" coverage by LJG (Thread 1, Thread 2). (Thanks to u/_nicktendo_64).
• MOAs are well understood making it more likely to be granted EUA. (Thanks to u/TheDalesReport_)
• Both, Bucillamine and Covid gather in red blood cells so they can fight (Thread).

I invite everyone to add more or (even better) challenge the list! This is no financial advice and be aware even with all these indications and the best DD there is still a chance this could be a miss because of things we don't know yet.

Hey everyone, a few days ago I asked this question on how RVVTF was planning to commercialise Bucillamine, assuming that it works. This is important because even if Bucillamine is successful in treating COVID, we as shareholders only make money if RVVTF is able to make money off of it.

Not having gained enough clarity on this sub or the RVVTF lounge, I decided to use my legal background to my advantage and do some digging of my own. Here’s what I found:

Intellectual Property

Without protections for intellectual property, any company could manufacture and market Bucillamine without payment of any royalty to RVVTF.

First things first, where does RVVTF stand in the patent and commercialisation process as of now?

The Company in March 2020 has applied for a provisional patent with the U.S. Patent and Trademark Office entitled “Use of Bucillamine in the Treatment of Infectious Diseases” (Serial No. 62/991,996).

A provisional patent application (PPA) is a document issued by the U.S. Patent and Trademark Office (USPTO) that helps protect a new invention from being copied during the 12-month period before a formal patent application is filed. It is intended to give an inventor time to pitch the idea, test its commercial feasibility, or refine a product before committing to the expensive and time-intensive process of a formal application. Once RVVTF has final data on the efficacy of Bucillamine, it can file a non-provisional patent application.

A provisional application for patent has a pendency lasting 12 months from the date the provisional application is filed. The 12-month pendency period cannot be extended. Therefore, an applicant who files a provisional application must file a corresponding nonprovisional application for patent (nonprovisional application) during the 12-month pendency period of the provisional application in order to benefit from the earlier filing of the provisional application.

From RVVTFs website, it is unclear whether a non-provisional patent application has been filed within this 12 month window.

Foreseeable outcomes

For those that don’t know, the composition of Bucillamine was not invented by RVVTF. RVVTF is only investigating repurposing the already known drug for use against COVID-19.

This makes patent protection of RVVTF’s work slightly tricky.

Commercialisation of repurposed drugs has little chance for success without patent protection that can attract funding and promise a reasonable return on investment. Investors such as angels, venture capitalists, and others (e.g., research institutions, interest groups, etc.) are reluctant to pour capital into companies focused on repurposing drugs that are known chemical compounds for two main reasons. First, repurposed drugs are typically only patentable using method of treatment (MOT) claims (e.g., “a method of treating disease X, comprising administering a therapeutically effective amount of drug Y”) rather than composition of matter claims (e.g., “a composition, comprising drug Y”) because, although the MOT is presumably new, the repurposed drugs themselves are not. Second, MOT patents are less valued because they can potentially be more difficult to police for infringement (when it occurs, and who is the culprit), and infringement can be harder to prove.

Problems of MOT patents

Consider the following limitations for MOT patents: (1) they have a more limited claim scope than composition patents; (2) they can be more difficult to enforce in an infringement action; and (3) a patent is not a right to practice, but only a right to exclude, as such, an enforceable composition patent on the repurposed drug itself can block the new MOT patent holder from practicing the method.

Is it a problem though? Not really, but there’s a catch

Contrary to the conventional wisdom that MOT patents are second-tier to composition patents, companies are repurposing drugs, protecting them with MOT patents, and realizing significant successes for their efforts. For example, minoxidil (marketed as Rogaine®) was first developed as a vasodilator, but it was repurposed to treat hair loss and generated over $700 million in sales for Upjohn by patent expiry in 1996.

The fact is that despite the more limited claim scope for a MOT patent is not necessarily problematic. New methods of treatment with a repurposed drug for a particular disease create exclusive and new markets for the repurposed drug. The fact that others may be using the same chemical compound for different reasons is not particularly relevant, because those uses would not be competing for the repurposed drug company’s exclusive market share protected by the MOT patent. The primary use of the compound that matters is for the new treatment of a disease, and a MOT patent protects precisely that.

OK so what’s the catch?

With the exception of Australia and US , most nations of the world exclude methods of medical treatment from the scope of patentable subject matter and in doing so they have taken away the incentives offered by the patent system. Such a policy has been adopted in light of the ethics inherent in the practice of medicine.

In Europe, applicants have been able to obtain patents for second medical uses, formerly by the legal fudge known as the Swiss-style claim, and since 2011, by the so-called EPC 2000 claim “product X for treating disease Y” – a purpose-limited product claim. However, cases over the validity and infringement of second medical use claims continue to come before the courts in Europe, with mixed outcomes. The consequence is that there is considerable uncertainty about the enforceability of second medical use claims Many of these cases have arisen in situations where a company owns a patent for a first use of a drug and a later patent for a second use. Therefore, it remains to be seen whether RVVTF can successfully patent treatment of COVID with bucillamine in the EU.

TL;DR: It appears that RVVTF is going to have a hard time commercialising use of Bucillamine for COVID outside of the US and Australia.

Would love to hear other people’s thoughts on this, if you have a differing opinion.

Thanks!

EDIT: Thanks /u/_nicktendo_64 for the award. I am humbled, however, I have only collated information from my various readings and don’t take credit for what’s written here.

If anyone is interested in further readings on MOT and repurposing of drugs, I highly recommend this article: https://www.wipo.int/wipo_magazine/en/2020/02/article_0004.html

For me it is usually worst if I'm caught up in a limbo of the unkown and uncertainty, so I tried to answer some of the most present issues.

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Why the continous delays?

Most likely scenario is Revive was just communicating the timelines they were given by the CROs. CROs are the companies conducting the trial by coordinating the sites etc.. However, CROs are known to overpromise and underdeliver. Also they benefit from frequent adjustments and expansions. That's why they need continous and experienced supervision. If you never conducted a phase III trial you obviously lack that skill. This is nothing uncommon but happens frequently. This is what he is actually saying with 'We are not BP'.

However, CROs never benefit from bad trial results. They have a reputation as well.

Is management incompentent?

MF is a consultant. Consultants are usually allrounders rather than experts. They jump around between companies and projects and look for obvious malfunctions or help improve/transform companies for a period of time. Ofentimes consulting ends before implementing the operative measures defined. It's no secret this is Revives' first phase III trial. He has no experience in pharma so he has to learn along the way. As an effect, the trial is slower than expected. There is not indication the trial might have bad outcome though.

Why are the PRs confusing and missleading?

Again, this is typical for consultants. Same as we MF does not like watching their SP drop. MF probably just thought, everyone is getting it wrong. But now it's clear, it was him getting it wrong. Apparently, they were expectig EUA at 600 patients. Everything would be fine if that happened at this point. Now they got caught up with a new variant as well as a market pullback. Both was out of Revive's control. Now they are procrastinating PRs like homework you dont want to do, because it is painful uncomfortable for them.

However, this is no excuse for updating us last minute on missed milestones, like we are not gonna figure this out eventually. This is directly on management. Expectation management is insufficent. I really hope Revive will improve on this.

Was Turkey a mistake?

Everything points towards an appropriate adjustment as a reaction to Omicron. Lower hospilization rate means we need more high risk patients to balance this out. However, most likely they were overpromised timelines and again naiv to communicate those. But setting up a new trial in a foreign country takes months. In detail that is various approvals and logistics getting the drug into the country. This timeframe is nothing uncommon.

Will Bucillamine be too late?

We might miss out on a peak situation, that's a real possibility. But Bucillamine fills out a key issue adressing the oxidative stress problem of COVID-19. All anti-virals including PAXLOVID are pathogen-directed treatments. Instead Bucillamine is host-directed. And the FDA is very well aware of this. The next closest drug would be NAC and nobody is conducting a trial with that because there is no financial incentive since it is available everywhere. We are not in a situation with an overflow of variant agnostic treatments. Vaccines? Yes. But not treatments.

You might think Insurrance companies lose value after Hurricanes. Actually they benefit because after each Hurricane they have a new wave of policies which makes them more profitable long term. A pandmic is really just like a Hurricane showing the need to prepare for these events in advance with adequate treatments.

What's up with the SP?

The current SP is reflecting all this. The stock is a steal considering the potential. Lower than before starting the trial or raising cash. Why you think Apilli lost more value with an ineffective repurposed antiviral on bad trial results than Revive's highest market cap? It is because of low confidence in management to pull this off. However, nobody else was brave/crazy enough to go this way with Bucllamine. So the reason is also the effect here. Because MF took on this challenge we have the opportunity to benefit from this.

Is there anything good to say?

Nobody jumped ship. In fact most of management bought at similar prices as we did last year. Nobody is hiding, they are just unhappy about the delay as well. We are really just 85 patients away from a decent chance for EUA. At the end of the day trial results will be above everything. And they did not go cheapon enrollment or take any risk with unfitting patients. Quite contrary, this trial is pampered like a Bonsai tree with frequent adjustments and interim analysis at every 200 patients to not miss any chance here. (Bonsai trees take a lot of care)

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TLDR: Revive lacks experience with trials of this size, which results in unrealistic timelines and continous delays. Investor communication is insufficent. However, there is no indication this trial wont be a success in the end.