The only purpose of deregistering the unsold shares seems to be what Eso told in his " And so it begins ". I just wonder if this was done just because of a demand of a single company or if there is possible a general bidding going on, or perhaps this was done hoping that biddings are easier to compare ( if there will be any ??) in the future.
In any case to me it is clear that PBT2 is closer than any other drug in solving AD and HD problem. At the same time Big Pharmas have difficulties finding new drugs to sell. Of course this has been the case many years and no signs of any bidding so far. I do hope that Eso got it right and we will see soon the next step.
If prana would not like to delist all but only a part of unsold, they would ask to delist let us say 20.000.000 of them but not 20.864.934. This number looks to be the number of left overs and not the number after careful consideration by the board. The other perculiar thing is that the number 7.864.000 has same 864 numbers as the delisted number 20.864.934. May be just an odd case but more likely there is a reason to have these same numbers and so 7.864.000 are included. They also tell that "the 20.864.934 unsold" are delisted and not a part of them. If only a part of the left overs would be delisted, it would be even more difficult to understand why this partial delisting is happening, it would be too stupid to get this thing done, left overs of 50M and part of 7.864.000.
So I am thinking that this action is done for a purpose.
IMO seems that Eso has a good point. "And so it begins". It could only mean that the board has easier to make a proposal to big pharma when the number of unsold is 0.
IMO they deregistered also 7.864.000 ordinary shares listed only last year in August so to me it looks like that these were not expired if there is a 3y dead line.
"Recent findings have indicated that decreasing brain tau levels in APP Tg mice uncouples Aß from downstream pathogenic mechanisms and improves cognitive performance (Roberson et al., 2007
). While Robertson et al did not differentiate between solution states of brain tau, we found that PBT2 (but not CQ) decreased insoluble and soluble phosphorylated tau in the APP/PS1 mice (Figure 6) and insoluble total tau in the Tg2576 mice (although soluble total tau was also increased in the Tg2576 model [Figure S7]). Therefore, if tau reduction contributes to the cognitive improvements we observed, the mechanism may involve preventing tau (either phosphorylated or nonphosphorylated) from precipitating. The differential effect of CQ and PBT2 may be due to the increased brain penetration of PBT2, or its increased ionophoric activity and ability to impact upon tau phosphorylation, and warrants further investigation".
So the main thing was that cognition improved with PBT2.
biotech_inv, read: Adlard et al in Neuron 2008, 10 July p. 44-55, it is a free paper and there is a chapeter how PBT2 works on tau.
Read how PBT2 works on Tau from Neuron 10 July 2008, written by Adlard PA et al. "Rapid restoration of cognition...."
...... that higher F2 isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.
Drug Alcohol Depend. 2014 Jul 3. pii: S0376-8716(14)00957-0. doi: 10.1016/j.drugalcdep.2014.06.030. [Epub ahead of print]
History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress.
Durazzo TC1, Mattsson N2, Weiner MW3, Korecka M4, Trojanowski JQ4, Shaw LM4; for the Alzheimer's Disease Neuroimaging Initiative.
Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS.
Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated.
Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years.
This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isop
Safety of PBT2 is a marvellous thing when thinking any partnerships. AD is a brain disoder and a complex one. Brain controls everything. No side effects ( just some minor ones) is a almost a miracle. Think about almost any medicine, they all have side effects. Those treating brain disoders have quite a lot of them but PBT2 seems to have very little of them if any. With this kind of record ( the treated numbers are still quite low) it is not a big risk to big pharma to partner.
6y ago we were waiting a deal with a big pharma after the positive Euro-study results. There were rumors that a deal was very close but all fell apart after the world wide economic turmoil started.
Before the Imagine study results it was apparent that Prana was also looking possible partners but at this time perhaps the initial poor results have stopped the negotiations, or have they been stopped ???
Now at least when there is better understanding about the Imagine study results (that they were not so poor at all), I would think there could again be something going on.
There has been a lot of new information about PBT2 during the past 6 years and independent research about clioquinols ( S Lindquist et al) that at this time there is much more to sell than 6y ago. HD and age related memory loss are totally new possible indications for PBT2.
We all know that Prana needs a partner to do big AD and age related memory loss studies. I can not understand that " the company remains enthusiastic about the prospects of a large trial powered to demonstrate cognitive benefit" if it would not have something real in it's plans, perhaps a partner IMO.
This not very important but may still interest some of us.
Acta Neuropathol. 2014 Jun;127(6):803-10. doi: 10.1007/s00401-014-1290-2. Epub 2014 May 7.
Do current therapeutic anti-Aβ antibodies for Alzheimer's disease engage the target?
Watt AD1, Crespi GA, Down RA, Ascher DB, Gunn A, Perez KA, McLean CA, Villemagne VL, Parker MW, Barnham KJ, Miles LA
Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer's disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.
Esoteric, thank you ! IMO Data mining is very essential in research when we try to get forward in unknown territories as in AD research. All big follow-up studies as AIBL etc are all data mining studies, but very valuable when trying to find new solutions. In them lot of data is collected, even irrelevant at the moment of collecting but even irrelevant data can later become valuable.
AF`s goal is not to find an AD drug. His goal is to play with pps.
What Masters actually did was that he made a litterature review about drugs designed to lower Abeta. In that PBT2 seems to be the best and even looks like it could lower the hippocampus atrophy rate related to memory. Other drug designers have not yet found that hippocampus vol measure is much better than measuring total Abeta by PET-scan when evaluating drug efficacy. In fact it looks like most of AD researchers believed in that still in last year ( read Canadianhegemony's comment ). Only now we know that PET scan is perhaps only for diagnostics (Ong et al 2014) and that result was made by data mining AIBL data.
Seems that AF is still talking about Abeta visible by PET and not about much more relevant biomeasure hippocampus vol. The fact that the Imagine study found a clear trend in slowering hippocampus atrophy was not a finding made by data mining and it was IMO the most essential finding of the Imagine study, even still only a statistical trend. The effect of PBT2 on more relevant spinal fluid oligomers has been known for years.
He explained different pools of Abeta (unpublished data of Roberts and Ryan) and told ( I think to to Big Pharma) that PBT2 is the only of the developed drugs targetting the toxic abeta oligomers by inhibiting their formation and promoting their clearance and so in the end reducing hippocampal atrophy ( only trend) and improving cognition (Euro study)
PBT2 seems to have effect on total Abeta (as was the hypothesis in the Imagine study), best effect if Abeta in brain is on very high level. By using historical data ( published about the best drug Bapi reperted to lower Abeta) Masters demonstrates that PBT2 was better than that even in this respect. So PBT2 could have some effect also on a bigger pool of abeta and not only the oligomers (but the most important in AD). But when Bapi does not target the oligomers (only few % of the total Abeta) there is no help in cognition.
The table of the hippocampus atrophy demonstrates well how the mean atrophy rate in treated is smaller than that of placebo but that the numbers are too small for statistical significance (placebo population). It is evident that genetics has a role both in developing brain atrophy and also when trying to slow down it by a drug, but these numbers were too small for these analyses.
Now when Masters is a consultant of both Lilly and Prana, I would think that there will be some consultations about co-operation aswell.
Here is one, it is free on the net:
PLoS One. 2012;7(3):e33552. doi: 10.1371/journal.pone.0033552. Epub 2012 Mar 23.
The zinc dyshomeostasis hypothesis of Alzheimer's disease.
Craddock TJ1, Tuszynski JA, Chopra D, Casey N, Goldstein LE, Hameroff SR, Tanzi RE.
pjemmet, I think that there is a mistake in the tables. I think the triangles are the ApoE4 carriers, but in any case you are reading the tables right. I think this should be asked from Prana.
In the Masters's presentation, there was also APOE presented, but the numbers were very small. 3 ApoE4 cases in the placebo group,( 20%) and 6 in PBT2 treated group (24%). Looks like ApoE4 was not the factor in explaining placebo group amyloid measurements.
interestingtome, thank you ! The papers you have seen in Copenhagen will be published in some 2 years in various journals. You will be now at least 1y ahead of us who did not travel to the meeting. Thanks for posting !
Interestingtome, thanks again ! This is a very important paper again explaining also the role of ApoE in iron metabolism of the brain.
The biggest risk factor of AD is related to metal balance !!! ( Hot copper has all of the abstract posted by interestingto me).