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I did admit I was wrong, on that number and yes, but you basically repeated what I said.
No, I realized later that I understated… meant to say millions. Millions of shares would be normal at that stage. 10, 20, 50, 60.
Yes, you basically affirmed my main point, you just needed to pretend it was all your point. I get it.
Everything else basically you repeated.
My point was that the number is adjusted, no one payed the price stated for those shares. It was not my major point as to how many shares they had outstanding, and yeah, not the focus, the focus was basically that that number is a calculated one and that companies that have long-development periods for expensive regulated areas like drugs, tend to require investors who understand what that entails. Shorts use that information to imply things that while “true” technically, can also be used to deceive, as larger context is basically always required in these circumstances, context they conveniently leave out to sell an simplified story, for their own purposes.
You basically just repeated what I said. The multi-thousand dollar share price is a reverse calculation. No one bought those shares for the price indicated. It basically undies adjustments to shares and dilution.
But anyone and their mother knows that companies that have huge regulatory hurdle, and no commercial business until that is completed, will need to dilute like mad. That is this sector. Understanding it before you invest is a necessary part of investing.
The 2018 ASCO Expert theater presentation allowed patients to discuss their experiences, and there was at least one non-gbm patient there. Unfortunately, the company seems to have removed many of those old videos. But the CEO, I believe, has also previously discussed that they have a wide range of compassionate use data. I expect you know where to actually find it if you want to do so.
It seems nuts to me but it’s all about transhumanism. I think people are going to run the risk of damaging themselves and their brains, long-term. But maybe people don’t want to live long anymore either. Or they actually believe if you download their memories into a computer they are actually “immortal”.
Fascinating sci-fi, but I suspect that people will eventually be disillusioned. In the meantime, it lets some entrepreneurs capture imaginations and use that attention to keep funding their other ventures.
Yeah, it’s a whole scam for shorts to play the role of “disgruntled longs”, “seeking transparency” , “shareholder advocates”… They do it because legally it protects them in their manipulative activities, it’s a legally acceptable role, but we all know some of those “advocates” are completely insincere and their aims are more about price manipulation or worse. And they understand that these companies must dilute to survive, and if they suppress the price, they ensure much more dilution, so it’s an easy and profitable run, doesn’t even really matter the company. I won’t speak to any one person.
It was never $1300 per share, that is a “calculated” price based on the fact that it probably only had tens of thousands of shares issued at the beginning. Many small start-up bios with long development periods for a new kind of platform like this, have similar stats, for the very same reason. Anyone investing in those early years typically figured out they have to manage for the long development period. It does not define the potential for profit in the future and in fact I have bought in recent years and been up by as much as 10 times my investment and more and still am up a good amount as they prepare for commercial launch by seeking approvals.
I think Musk has his reasons for making his arguments. While Chinese batteries are supposedly advanced, you have all kinds of disasters with exploding cars there way worse than here. And my understanding is the government is buying massive fleets of cars that no one wants, because they are not good, and so those many thousands of course are graveyarded in China. This subsidizes their ability to go into other markets, with inferior products, claiming they are better. But everyone knows in truth that their manufactured products are not of quality. Chinese people in China, that are not CPC who need to, for their safety, always say otherwise, know that to be the case.
The reasons are likely not clear rather than a failing of the study. My understanding is there are various other studies that have found that 30-40% of nGBM patients receiving the standard of care convert from unmethylated to methylated MGMT status. But it's still an area being studied. Meaning we don't absolutely know what happens to patients receiving the standard of care, but the nature of their tumor tissue may change.
We know that methylated MGMT patients with DCVax-L have a much higher rate of survival than the same patients in the external control arm, the mOS being just over 30 months, rather than 21 months for the placebo arm, an increase of 142% for the median patients receiving DCVax-L so categorized. That is very possibly going to extend survival for a good chunk of those patients with DCVax-L substantially, but it's not an absolutely known factor, something that is being studied and upon which this study was not focused.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847
Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P?=?.03). . . In patients with nGBM with methylated MGMT, mOS was 30.2 (95% CI, 23.7-33.9) months from randomization (33.0 months from surgery) in 90 patients receiving DCVax-L vs 21.3 (95% CI, 18.3-25.1) months in the 199 patients in the ECP (HR, 0.74; 95% CI, 0.55-1.00, P?=?.03)."
dCas9/CRISPR-based methylation of O-6-methylguanine-DNA methyltransferase enhances chemosensitivity to temozolomide in malignant glioma
Research
Open access
Published: 15 January 2024
Volume 166, pages 129–142, (2024)
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Journal of Neuro-Oncology
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Serendipity Zapanta Rinonos, Tie Li, Sean Thomas Pianka, Terry J. Prins, Blaine S. C. Eldred, Bryan M. Kevan, Linda M. Liau, Phioanh Leia Nghiemphu, Timothy F. Cloughesy & Albert Lai
Background
Malignant glioma carries a poor prognosis despite current therapeutic modalities. Standard of care therapy consists of surgical resection, fractionated radiotherapy concurrently administered with temozolomide (TMZ), a DNA-alkylating chemotherapeutic agent, followed by adjuvant TMZ. O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylated lesions from tumor DNA, thereby promoting chemoresistance. MGMT promoter methylation status predicts responsiveness to TMZ; patients harboring unmethylated MGMT (~60% of glioblastoma) have a poorer prognosis with limited treatment benefits from TMZ.
Methods
Via lentiviral-mediated delivery into LN18 glioma cells, we employed deactivated Cas9-CRISPR technology to target the MGMT promoter and enhancer regions for methylation, as mediated by the catalytic domain of the methylation enzyme DNMT3A. Methylation patterns were examined at a clonal level in regions containing Differentially Methylation Regions (DMR1, DMR2) and the Methylation Specific PCR (MSP) region used for clinical assessment of MGMT methylation status. Correlative studies of genomic and transcriptomic effects of dCas9/CRISPR-based methylation were performed via Illumina 850K methylation array platform and bulk RNA-Seq analysis.
Results
We used the dCas9/DNMT3A catalytic domain to achieve targeted MGMT methylation at specific CpG clusters in the vicinity of promoter, enhancer, DMRs and MSP regions. Consequently, we observed MGMT downregulation and enhanced glioma chemosensitivity in survival assays in vitro, with minimal off-target effects.
Conclusion
dCas9/CRISPR is a viable method of epigenetic editing, using the DNMT3A catalytic domain. This study provides initial proof-of-principle for CRISPR technology applications in malignant glioma, laying groundwork for subsequent translational studies, with implications for future epigenetic editing-based clinical applications.
I did not say they were a national exchange. Your desire to argue this point and pretend to be an expert on these matters, when you’re not, is noted.
I did not say they were a national exchange. In fact I said the other exchanges are SRO’s.
I’ve already explained what triggered the massive issuance of shares, it was not some “scam” by NWBO, it was basically a scam by shorts, but shorts are allowed to rob companies and their shareholders, this is part of the problem currently with the regulation of our exchanges, yes, even the NASDAQ… criminals in charge. Bernie Maddoff was the CHAIRMAN of the NASDAQ.
Shareholder authorization was not the issue with those shares issued. And no, if you have shares available you can issue them to raise funds. Every issuance does not require shareholder authorization because they are authorized when you create the shares for management to run the company and continue to finance it. No shares were issued without shareholder authorization, just just put a big lie in your post.
The shares that led to the delisting were required by previously authorized contract. There was never an issue if that contract was authorized. The issue was that the NASDAQ counted those topping up shares issued over a period of time in the same period and the company needed to issue more shares for their current requirements, that it debt. They chose to delist because they did not want to take on more debt and they did not want to do so AND do a reverse split to save their listing. It made no sense to do all of that and undermine the confidence of their supportive shareholders through it all. It would have been extremely risky and exactly NOT the circumstances in which you would want to do a r/s.
Shorts were trying to back them into a corner and constantly try to get regulators to take punitive actions against them intentionally to create the very narrative you are laying out. It’s part of a game for shorts. And there is likely always also someone standing with open arms to be the black hatted “white knight” to take advantage of them on the other side as well. Shorts rip these companies off and the shareholders and then project the blame onto the companies and the shareholders that defend them.
It’s all indirect, using markets, legally attacking them, undermining them through third-parties, so the opportunity to stay behind the reach of the law and make easy money, is just too tempting for some spoiled brats in our society.
No, you're incorrect. I was correct. I said the same SEC rules apply and they do. There is no special distinction for OTCQB.
What you are describing are SRO rules, and those rules I did not reference. SRO, self-regulatory organizations, including the national exchanges, have their own additional rules.
However, the bulk of rules and the most important ones that involve disclosure, are SEC rules. SRO rules are very nice to have, but they are NOT a pink sheet company which is one of the wrong things shorts repeat.
No, the reason the NWBO dropped off of the NASDAW was about shorts destroying their financing for years back by attacking their past financings but not saying so. I've explained this many times. That triggered contractual clauses that yes, by their nature and the fact that they were years worth of financing at very favorable terms, had to be refinanced at very unfavorable terms because of the short destruction of the share price. The end result was the re-issuance of shares that had been used for payment at favorable prices of many more shares at unfavorable prices to pay their supplier who was obligated not to sell those shares, for cash payment. Obviously when you have spent money as a supplier, and agree to hold shares used as payment, they have to be topped up if the share price crashes. This is a common attack by shorts and yes, it required that they either, delist, or go into massive debt. They chose not to go into such massive debt, but rather to honor the contract and issue the share in payment. The shorts understood that either option was terrible, but issuing the shares would basically ensure that their short positions were profitable. This is why they attack those clauses, called most favored nations clauses (meaning the holder of the previously issued shares in payment, get the benefit of the pricing for future issuances).
They had to pay their bills. The reality is, the exchanges are best for established companies, not development stage biotechs. They really do not have rules that accommodate companies that are more like private equity than public equity. Many of the things you point out, are not uncommon for these tiny companies, but also do not necessarily mean what shorts suggest when they create the cascade of circumstances that allow them to destroy and then gobble up these companies and their assets.
What can you do. The style of shorts is to choke out forums with immense amounts of noise. Apparently this is what Inquirig is here to do.
I don’t pump, but yes, Advent is the responsible party in UK, for a drug that is not licensed and sold under the Specials program. But misstating whose drug it is, who is responsible for it and whose business ultimately it is, is yours and Inquirg’s lie, not NWBO’s.
You are incoherent.
Already have many times including to you. You don’t care about conclusive proof, you make up your own reality to perpetuate your fud and lies. What is your purpose here if not to do that?
Sorry, it’s established directly by UCLA officially and its personnel as DCVax-L. Your efforts to sow confusion are sad, but expected.
You’re misinformed and putting out false information. But nothing new for you.
They are not on pink sheets. They are on OTC. The same SEC regulations apply here as elsewhere. You really need to keep better informed.
I refer to her as “Bride of HyGro”.
You’re about to go on ignore because you play it both ways pretending you’re just kidding, but harassing. I would suggest you get lost.
No one here is likely paid but shorts.
I am definitely not paid and have no interest or desire to be paid.
It must really upset you that your lack of sophistication is so obvious. You keep posting at me, but I don’t really care.
Well, ordinary investors chatting about their stocks is a reality. Watch Dumb Money.
The unfortunate thing for shorts is we’re all on to you now, and we do our own thing to counter.
If you don’t like it, that’s your problem.
The older personas were not very credible anymore, so, they launder with new ones or ones they’ve used for other drugs and forums. My guess is some have maybe switched sides, still critical but more the “disgruntled and disillusioned” than the full on basher, undermining with concern posts and similar critiques. I think they are starting to think the handwriting is on the wall in terms of likely approval, and now they need to keep the market from too much positivity. Squeezing shares from and discouraging longs tends to be a tactic at this stage also, I believe.
Hi Chiugray, and maybe think about them as range of potential market size as well as potential market cap, not necessarily actual. Obviously much depends on assumptions, execution, ability to deliver DCVax-L and various other factors. But in terms of the opportunity ahead, many want us to presume that based only on brain tumors and the UK, you can’t expect much, and I think just looking at the basic potential says otherwise.
They will try to distract with other arguments as well, no doubt. But the basics are all there for massive growth and opportunity, not even looking beyond to a general cancer vaccine and other opportunities which I think will also come more rapidly than some want to suggest. Not immediately, and clearly the company wants to meet the most obvious and clear demand first, and some doctors will be forward thinking and have patients who want off-label options.
This has major potential and there are people saying it’s a tiny puddle. The market may believe a range of narratives. I just wanted to rationally discuss what I think is potentially reasonable. Some of the numbers may ultimately come in smaller. They might not get as broad a label everywhere for brain tumors maybe? But I suspect the new data, and past decisions by regulators suggest they are likely willing to give the broadest label.
Right now, the way shorts seem to want to keep it down is by not being so uncredible as their old arguments would be at this time, and trying to downplay the opportunity, even if they get approved.
Honestly, agreed on all points Gary. Thought you sounded a little less excited in that previous post but I think I misunderstood. Thanks for the clarification.
Given the potential after the UK approval, I agree that a 30 multiple would be justifiable given the larger markets them just likely ahead.
I wrote this on my phone and kind of quickly and corrected my self as I went along, but let’s not say actual market cap but potential addressable market after all the discounting. I do think the later numbers are reasonable estimates for a potential market cap as well, ultimately and assuming a credible commercial company exists, which likely means deep pockets backing. And it is not a share price estimate as that depends on dilution as well, ultimately.
Surprisingly negative post Gary.
I do not generally put up numbers but I don’t intend to sell for $3 per share either.
So, I am breaking my general rules to put up some numbers that I do not think are unrealistic, to bat about. These are not trillions nor every cancer under the sun. In fact, I think they miss huge categories like recurrent patients and patients from markets beyond the big 4 we have already potentially just ahead.
Let’s consider first the UK.
Market size of the UK, of course I do not necessarily presume all patients could be operated on or be patients getting DCVax-L, though I do think there will be a lot of off-label patients with other cancers who may want to get DCVax-L, if they can, once it is approved.
However, here is what ChatGPT said about the size of the brain tumor market broadly defined as in the new application, in the UK, but it has a hard time coming up with a recurrent patient set of numbers, mainly newly diagnosed:
“Yes, that appears to be the correct interpretation. The figure of around 3,200 annual cases specifically pertains to newly diagnosed Glioblastoma (GBM) in the UK. In contrast, the larger number of around 12,300 includes a broader range of brain, CNS, and intracranial tumors, encompassing both malignant and non-malignant types, not just GBM. This broader category results in a higher total number of cases due to its inclusivity of various types of brain-related tumors.”
“The specific percentage of brain tumor patients in the UK who undergo surgery, including those for GBM, isn’t explicitly detailed in the sources I found. However, general statistics on cancer treatment in England from 2013 to 2016 indicate that 45% of cancer patients were treated with surgery. This figure includes various types of cancer, and the proportion specifically for brain tumor patients might differ.
Additionally, The Brain Tumour Charity notes that over 12,000 people are diagnosed annually with a primary brain tumor in the UK, including 500 children and young people. This figure aligns with the estimate of around 12,300 new cases of brain, other CNS, and intracranial tumors mentioned by Cancer Research UK.
It’s important to note that these statistics cover a broad category of brain tumors and might not provide a direct answer to your question about the specific surgical treatment percentage for GBM or other specific types of malignant gliomas. The treatment approach can vary based on several factors, including the type and stage of the tumor, patient’s overall health, and specific medical circumstances.
For more detailed information, consulting specialized medical databases or direct inquiries with health institutions or cancer registries in the UK might provide more specific insights into the surgical treatment percentages for GBM and other malignant gliomas….”
“The incidence of glioblastoma and other malignant gliomas varies across different regions. In the United States, the annual incidence of malignant gliomas is approximately 5 cases per 100,000 people, with over 14,000 new cases diagnosed each year. This includes glioblastomas, which are the most common primary malignant brain tumors, with an annual incidence of around 5.26 per 100,000 population or 17,000 new diagnoses per year.”
“ 1. Corrected UK Incidence Rate: Approximately 4.71 cases per 100,000 population.
2. Corrected Average Incidence Rate: Approximately 4.98 cases per 100,000 population (average of the US and UK rates).
3. European Union (EU):
• With an estimated population of 447 million, the EU would have approximately 22,274 new cases of glioblastoma and other malignant gliomas annually.
4. Canada:
• With an estimated population of 38 million, Canada would have approximately 1,894 new cases annually.
These corrected calculations provide a more realistic estimate of the number of cases in the EU and Canada, considering the average incidence rates from the US and UK.”
I’m not one who puts out future market caps. I do believe the reforms will get DCVax-L treating other cancers far faster than the old dogs around here looking to old rules.
However, has anyone noticed that shorts saying it won’t be approved have been replaced by new ID’s trying to convince people that the market cap can’t go higher than…. But they don’t specify?
I agree there are unrealistic ideas and numbers bandied about. But suddenly all the new negative posters are here mostly to beat on people who have been here for years, and suggest they don’t know anything. Which is amusing.
Seems like there has been a change in the negative sentiment mostly conceding approval, now mainly trying to keep any euphoric rise and optimism tamped down. New ID’s replace the old ones, but some sound like previous posters. And of course the old ID’s make cameos still.
Just saying, there is a whole different conversation focus now, and mostly, though there are a few reminders or minor newbie shorts, the focus is on approval and post approval market cap.
Something has changed.
Just my thoughts Eagle but my pleasure as always, to share. Have a great weekend ahead!
No, just that financial markets and coverage of them and companies in them is very carefully managed by papers and major media to avoid promoting things that may not be reliable. They'd happily promote Dr. Liau and UCLA. But honestly, it seems like Duke is perhaps better at self-promotion than UCLA. There is a lot of noise in the US as well. Many, many companies claiming that they have "The Answer". Media are terrible distinguishing them from one another. They'll tell just about any story. But say "penny stock" and that's a deal killer in terms of certain kinds of reporting. And even then, like I said, you have plenty of companies that are NOT penny stocks and the coverage focuses on the doctors, patients and trial without often mentioning the company names. Science reports are seen differently. But, often it is hard to get the attention of general media. Science media, as I said, will cover. And we saw LOTS of reports in science media about the clinical trial. But those are not general interest media, which means your dad or uncle or mom, aunt or sister is not going to likely hear about it unless they happen to read very narrow science coverage in industry related media typically.
I will note that there was surprisingly less coverage of the Phase 3 JAMA publication in the UK media than the interim results publication. So the US is not unique. I did not see it in Canada, and I'd expect that we'd have heard about German coverage if it had occurred. So the US is not unique. It's just the nature of things. Some stories are too complicated for major media to really parse what is significant and what is not and without approval and more news of patients living long with GBM, you're probably not going to see a lot of curious journalists promoting the story.
Thanks. Was not aware she was so poetic. :)
Well, as I said, some things go over people's heads because they lack the comprehension to really understand things. Is that simple enough? I did not use "big words" like connote.
Stick with Big Pharma investments. These tiny companies and new technologies are not for you. We are just investors talking amongst ourselves. No one wants you to invest or put your money here. Feel free to focus your attention on investments that you think will prosper you.
You don't understand the context of the overall contractual arrangement. You gave a narrow view. People were already aware of the basics, so providing the link to a contract and simplistically making the assumptions you made is not factual, it's a perfect demonstration of the Dunning-Kreuger effect. You think you know things you don't know. You don't appear to have the competence to know the things you don't know. And you're extremely certain that you know everything you need to know, even when you state things in your messages that clearly show you have large pieces of information missing from your understanding.
But the reality is that no one wants you to invest. We discuss our investment amongst ourselves here. This is an obscure board for investors. You've invested in Merck and are interested in MRNA vaccines. This is not the place for you. So now there is no explanation for why you are expending so much energy and time harassing NWBO investors about their investment decision. Usually there is a real motive behind such behavior. Typically, when one has shorted and is insecure about the short position, one might spend a lot of time harassing investors because that is the only way to try to make one's bet go the way one might want it to go, perhaps. And look, I'm not saying that harassment doesn't work. I think it does. But it's crooked. And in a case like this, it's disgusting, unethical and immoral. But that typically doesnt' discourage shorts. They can pretend to be moral and it seems to allow them to do immoral thins and feel OK about it because their pretensions feel very compelling to them. But as we know also, some of them have engaged in illegal activity.
Good for you. Those are already established companies and technologies. Not a hugely adventurous investment, but then you have no reason to be ghosting around here trying to harass NWBO investors now do you?
You definitely don't post factually. You post partial facts, partial stories in some very few cases. Mostly it's all opinion.
If you don't know what happened, how can you claim you post factually?
It was lifted, Bride of Hygro. Regulators have to be careful disclosing too much and spoiling a trial inadvertently, twice in a situation like this one. So, you can presume whatever you want. But that seems to me to be the most likely answer given all the details. You're not a big detail person. So it's doubtful you could get to any kind of rational determination beyond your own initial and immediate opinion.
You think "connote" is a big word? OK.
You know, it's only 7 letters...
It was not a "Halt", it was a partial halt, and not for safety. Likely for the fact that crossover was so broad, likely owing to the fact that patients saw the treatment as very successful for their peers, that there was no longer a placebo arm and enrolling new placebo patients would be unethical. That would not prevent a trial from proceeding on to approval from any regulator, and especially not when a regular wanted the crossover to address risks that turned out to be non-existent.
You know that giggles don't somehow connote that you actually know what you're talking about. More likely the opposite.
Dunning-Kreuger syndrome is a profound thing.
Yeah, it's a pretty hard and fast rule. Even if you're not one, they often won't say the name of a company related to a breakthrough drug. You'll see stories about the trial and doctors and they might slip in the name, very circuitiously somewhere in the article at best. It might not appear at all. The journalists see it all as pure science, not commerce and when it comes to tiny penny stocks, their entire mindset has been filtered by old news not contemporary news, which is why hedge funds have such an advantage in knocking companies down, putting them on the OTC and then messing with them. It's a very imperfect market.
Too much ignorant BS in your posts.