We did see an improvement in executive function twice (once in AD followed by HD). I am thinking that we really don't know how to test for a specific function and how to interpret the results (at least not within a small sample size). The TMT part B is evidently a test that fits in that it is just complex enough to reveal a real change/improvement in a patients ability and along with the change in bio-markers should be interpreted as a disease modifying result. If a given test has its threshold far from the "operating point" of the individual/patient, it will likely not show a relevant result. Apparently the TMT is hitting the correct cognitive hotpoints and has a broad threshold making it sensitive to a broad group of patients with widely diverse capabilities (patients with low capability to patients with high capability). Knowing that many of the patients are home bound with little intellectual stimulation, there must be a bias toward further decline with or without drug intervention. This variable adds to the "noise" in the system and makes testing and test interpretation even more complex. For a person to learn new things/behaviors, he/she needs intellectual stimulation and incentive. I'm guessing that many of the patients lack both in their daily living. Also note that in the Lawler video, his wife described a change in behavior (a noticeable improvement). But I am not sure if any test which he has been given would pick up this or even look for it. Anyway, the FDA will have to show some understanding of the limited tools available for these trials and make a determination as to which are the relevant tests and accompanying bio-markers which reveal the true effects of a disease modifying drug.
One important aspect of puppy's hypothesis is that it fits the mice experiment. The mice recovered very quickly after being given Pbt2 and were able to improve on their water-maze test within hours after taking the drug. It was not necessary to wait for 12 weeks. The same is true of the old non-genetically-engineered mice in the Adlard experiment where they recovered their learning abilities very quickly to the level of the young adult mice. This implies that the drug is working very quickly (within hours). Thus a 12 week sampling period is too long and will show results after the brain has reached a new "normal" equilibrium as puppy says. However, note that we also know from the Adlard experiment that the drug increases dentritic spine density, promotes new neuron formation and VGLUT1 was signiﬁcantly
increased following PBT2 treatment [PBT2 (+26%), P = 0.03] (Fig. 4a of Adlard paper), and this was concomitant with a signiﬁcant net increase in glutamate levels in the PBT2-treated mice [PBT2 (+39%), P = 0.02] (Fig. 4b of Adlard paper). Google "A novel approach to rapidly prevent age-related cognitive decline" to find the link to the Adlard paper (or go to the IV board and the link to the Adlard paper is at the top of the PRAN message board page). Therefore my expectation is that if the patient continues taking the drug (Pbt2), he/she will improve over time as the patient's "new" neurons and more efficient processes (within the patient's brain) will contribute to learning "new tricks." Who says you can't teach an old dog new tricks? Evidently you can teach an old mouse new tricks. ;-)
From the Article: Prana Biotech Updates Appendix 4D; Reports Larger Investment in PBT2
They added $4 million in January to their cash when they received a tax incentive from the Australian Government.
-- Reported loss of A$7.93M (Dec 2012: A$4.33M)
-- Cash position at 31 December 2013 of A$19.3M (A$13.3M at 30 June 2013)
-- Subsequently, A$4.09M R&D tax incentive received in January
Rachelle Doody, Baylor College of Medicine, Houston, is only saying that she has not seen the data and is thus not qualified to comment on the safety of the drug. Many are reading this as a negative comment, which it is not. However, we do have a positive from the doctors on the safety committee who knew far more regarding the drug's safety within the trials and determined that it was safe enough to continue the trials and also do an extension trial on the AD.
Your second paragraph is another comment from a doctor who is un-informed which is again being interpreted/spun by the street as negative. I respect the doctor who admits to wanting to see the data and a peer review before giving out an opinion. "I was pleased to hear these results would be submitted to peer-reviewed publications,” noted Cristina Sampaio, CHDI, Princeton, New Jersey. "A proper evaluation of this trial must await full access to the data. Until that happens, undue enthusiasm can only harm the patients."
These are NOT negatives regarding PBT2. They are benign comments!
Note that the FDA has said that they would consider bio-markers as part of their evaluation for possible approval for an AD drug. So far Pbt2 has shown to be safe, effective (considering the statistically significant results in Executive Function in two consecutive phase 2 trials for AD and HD) , and PBt2 has shown improvements in bio-markers in the mice experiment where it brought the levels of these bio-markers in the old mice to the levels seen in the "young" mice. Now, if the AD results coming in March show that A-Beta Plaque levels have been reduced in patients given Pbt2, then PRAN would have all three FDA "hot-points" (in humans) for approval covered for a disease which has NO disease modifying drugs on the market.
I put up a lot of links yesterday on stocktwits and twitter including scientific papers which support PRAN's science. All responses or tweets from the short/bash side were hand-waving, non-scientific, "it doesn't work" type with no references or links. After reviewing all the papers I can't help but come to the conclusion that Pbt2 will be positive for the patient breaking up toxic oligomers, restoring metals homeostasis, promoting new neuron formation, and increasing dentritic spine density. Since Pbt2 does so much good, it should show up in the patient as a measurable benefit. In the mean time, the detractors of the technology are setting the stage (at least on Twitter) to downplay and twist a headline such as "Pbt2 meets its primary endpoint" into a negatively spun bash by setting the bar so high in the minds of traders that anything less than FDA approval on the spot should be seen as a failure. It is disgusting to see such behavior among this group that call themselves "professionals." Let's hope for good results for the patients first as well as the longs who cheer for their well-being. Think how sick these bashers must be to cheer for failure for a drug addressing such serious issues.
I disagree. The odds of good results for AD are very-very favorable based on previous phase 2a trial results and other trials on mice which show Pbt2 Increases Dentritic Density, Promotes New Neuron Formation, breaks up Amyloid-Beta Plaque, and improves other markers in the aged to the levels found in the young. What we are seeing is panic selling by the weak hands encouraged by the shorters and options players. I'm expecting very good AD results and will not be shaken out by "players" on Wall Street. Good results will lead to a deal with a Big Pharma and bring in a lot of cash up-front to PRAN. This is the likely reason that PRAN has not been raising money during the recent share price advance. My guess is that PRAN has a possible Big Pharma Partner lined up that is ready to do a deal based on AD results. Note that the Market Cap of PRAN is very low given the neuro-degenerative markets it is addressing with likely Disease Modifying drugs. Other companies in similar situations have had market caps Far Higher than PRAN's. Note ELN which rose to a market cap of over $15 Billion prior to the phase two failure of their AD drug (Bapinuzumab). Also note the $7 Billion Market Cap of ICPT currently. Now compare that with the Market Cap of PRAN at less than $300 Million. IMHO PRAN would be undervalued at $20 currently! Then, ask yourself what should PRAN's Market Cap be if AD results are Good?
mm4equity-You said: -“Humans see what they want to see.” Rick Riordan, The Lightning Thief -
If you take your Pbt2, you will also see the 20 years of research behind PRAN's Metals Homeostasis approach and the many independent experiments/papers which back the science. You should not try to justify your fear of investing in PRAN by accepting the two-minute scientist's hand-waving arguments which have no basis in fact. These unsubstantiated arguments spreading Fear-Uncertainty-Doubt might as well have been made by Bart Simpson as someone suggested in a previous post.
Their logic in their so-called "newsletters" is lacking and does not pass the "reasonability" test.
biotech_invest,-- It is obvious from your writing that you are not an educated person. You could not possibly have any knowledge of biotechnology. Since you have obviously not answered any of my relevant questions regarding PRAN's statistically significant phase 2a AD trial results in a cognitive measure, you are just here to spread Fear, Uncertainty and Doubt (FUD). In simple words that you can understand, you are a FUDster!
In the phase 2a AD trial results showed that there was a statistically significant improvement in executive function and a statistically significant dose response. They did this with 40 patients. Read the published results! You are trying to confuse people. If you had no interest in Trashing the stock you would not be here spreading your poison.
In the phase 2a AD trial results showed that there was a statistically significant improvement in executive function and a statistically significant dose response. Did you predict that? How do you explain it? Look at page 784 of the article
Could you give us your prediction on the phase 2a trial for AD? Also, have you had this discussion with Dr. Rudy Tanzi? What success have you had in convincing Dr. Tanzi that he has been pursuing the wrong path and that he really has no concept or understanding of Alzheimer's Disease?
FUDsters have no moral compass. It's best to ignore the BS and stick to the facts. The FUDsters are doing nothing more than howling at the moon (and claiming that they are responsible for making it a full moon).
I believe it involved ELN's Bapinuzumab trial and ELN and its shareholders were the victims. Does not involve PRAN.
You're right and thanks. I have just put some things together and taken advantage of other's research as well. I view the internet and the chat boards as a vehicle for us retail people to help each other do our due diligence. It helps to level the playing field for the little guy. ;-)
Parkinson's Disease is also a very big market and PRAN has Pbt434 lined up!
Here is a "copy and paste" from the road show slides:
Phase II trial reporting in early 2014 --This refers to HD
Phase II trial reporting in March 2014--This refers to AD
So, I don't see why the thumbs down on my post! I'm Long and Strong waiting for the results!!
You have mis-read PRAN's announcement! PRAN has NOT said early first quarter. They have said "Early 2014." !!!