Immupharma Share Discussion Threads

[nobbygnome] 06/11/2018 11:23

>> colsmith

I paste below my seminal post from September last year. All the science suggests you need a much higher amount to have an effect than can possibly be achieved with the current dose. This is why the place of action of the drug is so important. Muller's original papers suggested the spleen was the place of action. Then she completely changed her tune and suggested to me in an email that it was in the skin at the place of injection. To me that is just not feasible and shows they don't have a clue about the MOA. Plus of course because of the very short half-life there will be no drug present after the first day. So for the other 27 days of the dosing period you are expecting the drug to magically carry on working. The only conclusion is higher and more frequent dosing is the only answer. The drug does have some effects but only at concentrations way higher than can be reached in vivo with the current dose. The experimental data really is very clear.


'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'

[stockriser] 06/11/2018 10:57

So it's true - there is life after death ;-)

[colsmith] 06/11/2018 10:42

Nobby - change the dose? What is the information available publicly that an increase in does will be more effective and what is the source of that?

Proper trial is in the market - there is sufficient evidence that its worth giving doctors and patient's the option to take; with apparently little or minimal side effects and for some folks in the P3 test good results. The only real trial is on the market - the MAP approach seems a step in that direction; P3 as I see it in general use seems to be precise but vague - a good indicator of efficacy but should be seen as a provisional pass subject to use on market experience.

Its interesting as to why 60 folks wanted to continue the trial - one view is that they felt better; alternately that they didn't feel worse and thought they might improve on a longer trial. Unfortunately the company hasn't given much info on this. Anyhow Q2/19 when the 60 folks results comes out will be interesting.


Have a nice day

[nobbygnome] 05/11/2018 22:09

>>gabber

Appreciate the apology; a rare thing on this board! I assure you I would be extremely happy if the board saw sense, changed the dose and did a proper trial where the drug actually has a chance of working. It is all so sad.....and predictable!

[gabberdemon] 05/11/2018 20:03

Maybe bordatoue 😂

[gabberdemon] 05/11/2018 20:02

Fine you are right..it is the FDA and I do agree and have said myself a higher dose is needed. But people must realise side effects are worse when a product is working. It's simply the disease leaving the body and organs working hard. Sorry to take my anger out on you. I just don't like all this negativity and it's awful to see that they are being knocked down again for such a potential lifesaver. Grrr. Lol.

Again,apologies for my childish behaviour. I don't hope you choke really 😂💗

[bordatoue] 05/11/2018 19:09

It is without a doubt IMM will be taken into administration, any company led by Tim always end up being liquidated in the end. Just wait for 2p target.

[nobbygnome] 05/11/2018 18:34

PS The irony is that I think it stands a reasonable chance of working if the right dose was used. However, the incompetent Board continue on their merry way wasting the shareholders' money with the current dose which the science proves has no chance of working. Therefore, the target for your ire should be them not me!

[spawny100] 05/11/2018 18:12

No bottom here as far as I can see - it is just a very long slow motion car crash...

[1he warrior] 02/11/2018 15:20

Oh yeah, just like 2p bottom on bpc too.



BigSi22 Nov '18 - 10:20 - 33649 of 33651
0 0 0
Yep- looks bottom

[nobbygnome] 02/11/2018 14:47

But Lupuzor has been proven not to be efficacious. I remind you that it has never ever met a primary end point. Yes it is safe, I will give you that one....but that is because at the dose used it is essentially a homeopathic medicine.

I see the price is now below 10p.....I think the market is speaking about the management's current approach!

[colsmith] 02/11/2018 10:49

NJ - thanks NJ interesting and well articulated opinion. However, it's really all down to use on a wider population - or I guess the market. The attached link I found interesting and the extracts below are perhaps obvious in terms of what is learnt from market use.

So the IMM product on market would be a realistic practical test of it with its as stated by the company 'exceptional safety profile' and good efficacy. The MAP approach is in line with this.

The means of drug approval is of interest to us all and goes beyond the IMM situation of course.


Have a nice day

---------------
EXTRACTS
One-Third Of New Drugs Had Safety Problems After FDA Approval

It took a median of 4.2 years after the drugs were approved for these safety concerns to come to light, the study found, and issues were more common among psychiatric drugs, biologic drugs, drugs that were granted "accelerated approval" and drugs that were approved near the regulatory deadline for approval.


"All too often, patients and clinicians mistakenly view FDA approval as [an] indication that a product is fully safe and effective," he says. "Nothing could be further from the truth. We learn tremendous amounts about a product only once it's on the market and only after use among a broad population."


on the market and only after use among a broad population."

[bigsi2] 02/11/2018 10:20

Yep- looks bottom

[stockriser] 02/11/2018 10:00

IMM oversold - well the chart says it is ;-)

[njb67] 01/11/2018 15:53

Col Smith

The primary role of the global regulatory agencies (FDA, EMA, MHRA in the UK etc.) is to protect the general public from medicines: where the potential harm outweighs the benefit or there is no benefit at all. As such these agencies require a robust level of proof before they will approve a medicine for use. This works reasonably well for most conditions.

In some areas, cancer most notably, medicines with strong phase 2 data can be granted a licence. This tends to be for cancers where patients would be unlikely to survive for long, even with the existing treatments. While Lupus is a severe long term condition, it is not immediately life threatening, hence why they need to successfully complete a phase three programme.

There is a broader debate about whether the regulatory approach could become more permissive and I think this is a reasonable ask for those diseases, like cancer, where patients may have no effective treatment option and are facing imminent death. There may also be an argument for those diseases where conducting phase three studies is problematic. However, this greater permissiveness would need to be considered against the increased risk that the public would be exposed to medicines that do them greater harm than good or would go on to be proven ineffective. No one would want to see another thalidomide type health issue.

I am not on the group chaired by Andrew Witty who will decide which medicines are given accelerated status. What I can say is that I met with the Accelerated Access Review authors (Hugh Taylor and John Bell) as part of the formal process where they were developing their thinking for the report. I have also met them on a number of occasions since they published their recommendation so have a clear view about what they are trying to achieve.

The AAR is mainly intended to help smaller UK pharma companies get their most promising medicines to market more quickly than currently happens today. It is part of a broader UK government life sciences industrial strategy to grow this part of the economy. At the moment UK pharma start ups tend to run out of money or get bought out by foreign companies before they have the chance to establish themselves in their own right. The government have stated their ambition to create four multi-billion pound UK pharma businesses as part of this strategy. The AAR is about helping smaller companies navigate the existing processes rather than changing the regulatory processes and standards per se.

AAR is also not just about medicines btw. It is looking at diagnostic approaches, digital healthcare interventions, medical technology and devices too. It is possible that the AAR programme will not select any medicines to fast track.

Hunt, who I have also met, is not a regulatory expert and although the AAR was published while he was Health Minister, he contributed publicly very little to the debate ahead of its publication.

[popples] 01/11/2018 14:56

1retirement
Brilliant. What an insight.
Any share can go to zero at any time.

[ukdannyboy] 01/11/2018 14:00

How low can this one go?