Immupharma Share Discussion Threads

[coldspring] 16/5/2018 08:37

Don't speak to him brad. If he is ignored and put on filter he will melt away and be ranting to himself.

[nobbygnome] 16/5/2018 08:35

In short .....yes! Muller and the IMM management have failed spectacularly so far. I have worked in this field for 34 years so do know what I am talking about. I may have said that before....

[nobbygnome] 16/5/2018 08:13

I see che is being a bitter troll again over on the TLY thread. He is beginning to sound desperate. It really is very sad....

Just sums up the people on this thread. I will keep on making well argued scientific based statements, whilst my troll has to ruin another thread because he is so bitter.

Ho hum

Nobby

[nobbygnome] 16/5/2018 08:09

LOL

I have been completely consistent, the drug has some parmacological activity but not at the concentrations obtained after the currently used dose!

My interest is in getting this drug to patients in the right way which IMM have spectacularly failed to do!

Consistent and persistent.

Nobby

[andyr42] 16/5/2018 07:57

nobhead on the one hand you keep persisting drug will work on correct dosage and in other posts you say it will never work ... this is an obvious contradiction. How can you say the drug does not work when data has clearly shown it does??? You are on a vengeful mission against IMM for some reason. Either you work for a competitor who have 'paid' you to go on this crusade or you hate IMM management or you are senile. In all these cases it is clouding your judgment to make objective analysis. You are paranoid, obsessive and psychotic. This is why I and others can't take you seriously. Its obvious you are on a mission. But in time your deliberate, wrongful tactics will be found out.

[brad44] 16/5/2018 07:56

you promised you wouldn't come back on this thread, yet here you are, apparently holding no shares, now if that isn't a contradiction then i don't know what is?

also at the time of the share price collapse, you claim to have been long and short, that proves to me you did not have a clue what the result was going to be, irrespective of your supposed experience.

[nobbygnome] 16/5/2018 07:45

Here is my original post from September.

S_k and I met up for a discussion last night and as a result ahead of that meeting I did some further research. During that research I unearthed some pretty shocking revelations about Lupuzor which I will explain.

Two of the 3 papers this infomation is based on were referenced in Prof Muller's talk last year and the third is cross referenced from one of those. The full references are below for you all to read if you want.

So this concerns the concentration of the P140 peptide used in the in vitro experiments and the animal models. First of all let's work out the maximum possible concentration of Lupuzor in humans after the monthly dose of 200ug. For this calculation I have assumed that 100% of the drug reaches the blood which is actually very unlikely and that the meaningful body compartment is blood. Again that is being very generous because really the drug would have to get into the tissue so the volume of distribution would be higher. However, to make the calculation easy I will use the figure the drug is diluted into as the 5 litres of blood found in an average person.

So if you punch the figures into a molarity calculator which you can find on line, using a molecular weight of 2.8kDa, the maximum possible concentration of drug in humans is 15nMolar. I got my son who is doing a biochemistry PhD. to independently verify this figure.

Now if we go to the papers I wonder what concentrations all the experiments are performed at? Well the lowest concentration used is 5 uMolar, so over 300 times higher than the maximum possible concentration in the blood. Shocking!

So what about the animal experiments? Surely they use a proportional amount of drug taking into account the size of a mouse relative to a human. Mice are roughly 1/3000 of a human so a proportionate dose in mice would be 66ng. But no, the dose actually used in the mouse experiments was 100 ug per mouse so 1500 times more than a proportionate amount. Again truly shocking.

So what this means is that all the experimental data and animal model data generated with the P150 peptide has absolutely no relevance for what is going on in humans. Essentially you can't use any of that data to justify a mode of action in humans. The really astonishing aspect to me is how on earth did they decide that 200ug once a month is the right dose taking into account the experiments they had performed. Perhaps someone can help here but I find it truly amazing.

So the bottom line is that the company has a lot of explaining to do.....

I am sorry to be the bearer of bad tidings for the zealots here but again do not shoot the messenger; I am just reporting scientific facts, which anyone with a basic scientific knowledge could have extracted from the papers.

Nobby

Refs
1. Page et al (2011) Ann. Rheum. Dis.70:837-843
2. Marci et al (2015) Autophagy 11:472-486
3. Wang and Muller (2015) Frontiers in Immunlogy Volume 6, Article 252

[nobbygnome] 16/5/2018 07:40

I don't really know why I am engaging with someone so rude but please point out my contradictory statements. The two characteristics I have which you may have noticed are persistent and consistent!

[nobbygnome] 16/5/2018 07:13

>> lerichman

In all the experiments, Muller used about a 1000 times higher concentration of peptide than can be achieved in patients. My original post from September after my meeting with S_K has the references for this data. And of course that drug level I am talking about will only be achieved on the first day of dosing and then for the other 27 days there will be no drug present because of the very short half-life.

The complete muddle over the MOA is also a big issue. Unless you know which cells you need to target and for how long it is difficult to determine what concentration you need and for how long. Don't forget Muller changed her story to say that the place of action was in the skin. For me that is just not credible.

Plus so far all the trials have essentially failed. The only positive result came from cherry picking data. False positive phase II data has been achieved frequently in Lupus because of the nature of the disease. The only way forward is with a higher dose.

Nobby

[lerichman] 16/5/2018 01:39

Nobby: By what do you base your assertion that the dose is too low and should be adjusted upward? I have seen no data to support this arguement, and in fact the data suggests greater efficacy in smaller doses. If you truly have vast experience in the world of medicine you should know hat powering up the dosage does not create a parallel increase in efficacy and often times quite the opposite It does however increase possibility of a negaative safety profile at the higher dosage.

[chalky230] 15/5/2018 22:24

Jov1

I think the point being made by using patients from mauritious was because there standard of care may not have been very good prior to trial ... so once they are given good standard of care then they feel better , even though they may be on placebo

With GSK they didnt make that mistake , hence why there placebo was lower i guess

Having said that although the company was silly to do this i wonder actually how many in Mauritius were actually on placebo

[brad44] 15/5/2018 21:28

Some good comments on lse tonight

[jovi1] 15/5/2018 19:47

The reason who I am still in and I have more share now than pre trial is that I cannot quite understand the difference in result between placebo used here and the one used testing GSK drug ( cannot remember the name)
If both where standard of care the result should have been very similar.
Is my understanding that IMM drug performed better than GSK but the placebo results were very impressive that tell me something is gone very wrong here or in the previous test
Standard of care has not really improved as far as I am aware and potentially someone must know the reason for this and maybe this will create some value here.
If I am right on this point I suspect GSK would likely to be interested if nothing else to protect in part the original investiment from competitors

[fuji99] 15/5/2018 16:31

Agree Nobby. Trials should not be carried out on desperate patients or/and where superstition (usually linked to alternative medicines) plays a major role in people's life. Desperate patients will always react positively to any new medicine they receive. Psychology is playing a big role in peoples perception of reality as they could easily believe anything they want to believe in. To me it was a fatal mistake by people I initially thought were smart. Placebo - in higher proportion - should be used in western countries.

[teddy boy1] 15/5/2018 16:09

22P is not too far away now. I fear for this share !

[mcsquared] 15/5/2018 15:10

Nobbygnome - point taken - makes any ultimate regulator decision more statistically fuzzy and, possibly in this case, largely, although not necessarily exclusively, a consequence of trial size as much as anything else.

[nobbygnome] 15/5/2018 15:03

>> mcsquared

It is just the reality of life. If you got an injection site reaction on a trial, would you think you were on drug or the placebo, which is usually saline. There is absolutely nothing you can do about that as it is an inherent flaw.

The rigour point is exactly why going to third world countries to do these trials is not a good idea. Nevertheless, that is the decision the IMM management took. I suspect it was a case of 'beggars can't be choosers' because they were struggling to recruit patients but that is just IMHO.

Nobby

[mcsquared] 15/5/2018 14:56

Nobbygnome - Your comment puts into question the rigour in adherence-to and setting-of a trials protocol that must be appreciated as vital to ensuring a well controlled trial evaluation and further puts into question the professionalism of the clinicians involved and possibly the professionalism of those that conducted the trial. In your opinion how much of an issue is this in general ? Lack of rigour puts into question the whole of the regulatory procedure irrespective of phase (e.g. II/III). After spending millions if not billions on drug development it beggars belief that such laxity should be the basis of a possible unjust outcome.

[youngharry2] 15/5/2018 14:47

It would appear to me that there is a growing consensus around the following points:

Will the drug be approved? Not a cat in hell's chance on the basis of the PIII data,

Is the drug dead or alive? Alive, due to the ds DNA anti body bio marker data but the drug is in need of intensive care, even the harshest critic has admitted there is evidence of pharmacological action

What is the scope and extent of the intensive care required? This remains a matter of debate on the BB and no doubt in IMM board meetings. On the one hand we have people suggesting a second 200 patient PIII trial with biomarker patients would be sufficient to meet the primary end point, p value less than 0.05. On the other hand we have the let's put all the furniture in the front yard approach. My prescription would be to take a cautious approach, de risk the company through a licence deal and let the partner decide on reformulation, further dosing trials and size of the PIII trial.

What's the company worth? The consensus on this is mediated during trading hours.

[nobbygnome] 15/5/2018 14:45

mcsquared

My answer from yesterday

The reason I went long and short is because no trial is ever really blind. For example if the patient gets an injection site reaction (and there are a few with Lupuzor) the patient assumes correctly they are on drug. So with a waxing and waning disease such as Lupus that would add to the placebo effect and increase the number of positives in the drug group. Plus quite often the person giving the drug will know what the patient is getting especially if they are dosing multiple patients because the placebo and drug aren't likely to be exactly the same e.g. difference in viscosity. So although that shouldn't matter in reputable centres because they won't communicate anything to the patient, nevertheless in places like Mauritius the centres are likely to be less rigorous. So the bottom line is there was always the chance of a spurious result especially with a disease like Lupus. After all there have been multiple 'falsely' positive phase II trials in Lupus.

[mcsquared] 15/5/2018 14:43

Then the puzzling thing is - why did you open a short and a long before the results were declared. I respect professional opinion and I don't wish to denigrate yours, as an expert in my own field I can fully understand that, but you must admit that there is an inconsistency in your reasoning when after the fact that the trial failed (not necessarily the drug) you come down hard on the failure side of things. Your earlier trade action doesn't support your conviction on efficacy at too low a dose.

[nobbygnome] 15/5/2018 14:40

>> bmcb

I will keep on making logical well researched points based on the science and hope that the reasonable people will at least consider them. We are wasting our time with the majority of the posters though who are not interested in the truth but just their misguided (IMHO) long position.