View Full Version : Prana Biotechnology Ltd
Haven't seen much on this/couldn't see a thread, has anyone been following this?
http://pranabio.com/
PBT.ASX, PRAN.NASDAQ current mcap $295m
Prana Biotechnology is developing first-in-class therapies to treat neurodegenerative disease.
The Company's lead drug candidate – PBT2 – is being developed for the treatment of Alzheimer’s and Huntington's diseases. The Company is targeting lodgement of a New Drug Application for Huntington's disease in 2016/2017 pending positive trial results.
Prana Biotechnology also has advanced a drug candidate for Parkinson’s disease and other movement disorders (PBT434) and brain cancer (PBT519), which are in pre-clinical toxicology testing. Development of PBT434 has received funding from the Michael J. Fox Foundation and Parkinsons UK.
The Company has a library of more than 1000 Metal Protein Attenuating Compounds (MPACs) which may support new therapies for neurodegenerative disease and other highly prevalent conditions. Other potential applications for this platform technology include specific cancers.
The earliest beginnings of Prana Biotechnology began in the laboratory of Professor Rudolph Tanzi at Massachusetts General Hospital in the 1980s when he was investigating the molecular and genetic basis of neurological disease.
Prana Biotechnology was incorporated in Melbourne, Australia in 1997. The Company listed on the Australian Securities Exchange (ASX: PBT) in 2000 and listed on the NASDAQ (NASDAQ: PRAN) in 2002.
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They are currently testing their PBT2 drug which is targetting alzheimers and huntington's disease.
It has last year finished phase2a trials in the REACH2HD program, primary endpoint of this trial was to test safety in test subjects - of 109 patients 104 continued the program (95%). The secondary endpoint was efficacy which showed some improvement in executive function.
However, and it is taking some negative criticism for this, "No significant changes were seen in motor, functional, behavioural or global assesssments in either PBT2 treatment group compared to placebo over the 26 week treatment period.
The more exciting results pending are in the IMAGINEAD trial (phase 2b, primary endpoint being efficacy) with results due end of March.
Announcements regarding the HD trial results were made available yesterday and to me look pretty exciting
If anyone is interested there is a webcast at 9.30am AU time today regarding the results and I imagine there will be some talk of what effect this might have on/what it may mean for the upcoming AD results/trial.
MELBOURNE, Tuesday February 18th, 2014: Prana Biotechnology (ASX: PBT/NASDAQ:PRAN) will hold an investor conference call and webcast for professional investors on Wednesday 19th February at 9.30am Australian Eastern Daylight Savings Time (Tuesday 18th February US EST 5.30pm; US PST 2.30pm) to discuss the results of its Reach2HD Phase 2 clinical trial investigating PBT2 as a treatment for Huntington disease.
The trial results announcement is expected to be released later today.
Investors can participate in the event either by webcast or conference call.
Webcast Link
To participate in the webcast please register via the link below up to 15 minutes prior to the scheduled call commencement:
http://event.on24.com/r.htm?e=753375&s=1&k=DF6BADFC8050EA35D9AECB907FD6620E
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Link to the official released results PDF for the REACH2HD trial: http://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=01492451
Summary from first page:
Prana Announces Successful Phase 2 Results in Huntington Disease Trial
Key Points:
Primary endpoints of safety and tolerability met.
Secondary endpoint: Statistically significant improvement in a measure of executive function (cognition) in research participants administered 250mg PBT2 daily (p=0.042).
PBT2 250mg was also associated with a favourable signal in functional capacity.
Preliminary evidence suggests PBT2 250mg reduced atrophy of brain tissue in areas affected in Huntington disease, seen in a pilot imaging sub-study.
Company plans to advance PBT2 to a confirmatory Phase 3 clinical trial.
DYOR, discl currently holding. This is a company I am happy to get on board with as after reading on the way this drug works to combat the effects of AD, which is different to other current drugs available, I believe this is going to make a significant difference in the quality of life for AD sufferers. Alzheimers is the leading cause of dementia and affects about 1/9th of americans over 65, and 1/3rd over 85. Although this is a bit ironic as I don't believe humans should be working to preserve/lengthen the life of old people as long as possible, as the earth is already overcrowded, I do believe in improving the quality of life for those who still have some way to go
/edit as an aside note, PRAN are up $3.13/43% today on the NASDAQ following the results, with 21.7m shares changed hands. In the past 2 months the price has been driven from $6 up to $13, then back down to $7.25 yesterday. There has been talk that there has been a LOT of shorting this stock, so the huge volume and rising price today could be explained by shorters scrabbling to pick up shares - I read somewhere that the call date for a lot of these shorts is Feb 21 2014 (Friday US time)
Finished the day at $1.11 up 21% at 5.5m shares. May be a retrace tomorrow I am not sure. Disc regardless I will be holding until AD trial results. DYOR
Some new research released by H C WAINWRIGHT & CO (haven't heard of them, anyone know if they are reputable?)
http://pranabio.com/wp-content/uploads/2014/02/14-0218_PRAN-FT_Reach2HD.pdf
I will try and update this thread later with my thoughts on why the shareprice has suffered even after what I take as a positive HD trial results. There have been a couple of negative articles by The Street/Motley Fool, and a more positive one by a more scientific author/editor - am looking forward to reading some peer review studies for a more fact-based analysis rather than by unqualified stock commentators who may or may not have a hidden agenda (shorting, anyone?)
PBT closed Friday 86c, open 89c and currently 92.5c on ok volume (1.2m shares). RSI & stochastic looks ok to me currently. I believe we will now be in an uptrend until AD results due by end of march, could still be another pull back prior to then though. AD results will be the make or break/sink or swim moment I feel.
Disc; holding and accumulating
Something I missed on the above Wainwright coverage - they have issued a buy rating with price target $20.50 for PRAN - this equates to around $2.20 shareprice on ASX with ADR's/exchange rate. 10 shares for PRAN.NASDAQ are around 1 share for PBT.ASX http://www.streetinsider.com/Hot+New+Coverage/H.C.+Wainwright+Starts+Prana+Biotechnology+%28PRAN %29+at+Buy/9182188.html
Collection of some of the articles/research notes I have found, some positive some negative. Adam Feuerstein of The Street seems to be the one with the biggest negative agenda of the stock, whether he is right or wrong. Some interesting back and forth tweets/comments between him and Rudi Tanzi at the end of this article
http://www.thestreet.com/story/12401827/1/cheerleading-tweets-from-prana-harvard-scientist-propel-shares-higher.html
http://www.thestreet.com/story/12421308/1/independent-experts-cast-doubt-on-prana-hd-drug-efficacy-claims.html
http://www.alzforum.org/news/research-news/drug-appears-safe-huntingtons-experts-split-functional-benefit note this has some comments posted on the article by Rudi Tanzi, chief scientific officer of Prana Biotechnology
http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2011.07402.x/full
http://www.techandinnovationdaily.com/2014/02/22/prana-biotechnology/
http://seekingalpha.com/article/2039103-positive-phase-2-results-for-prana-biotechnology-in-huntingtons-disease-behind-the-smoke-and-mirrors?source=yahoo
http://www.caseyresearch.com/cm/medicines-604-billion-memory-miracle?utm_expid=5346348-27.IsOj3gO_T4WFtUxr3fLvDA.1 this one seems like a waste of time and the author is trying to sell his book/services by alluding to the company without mentioning it by name
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http://seekingalpha.com/article/2031451-prana-biotechnology-and-mannkind-corp-bad-news-obeys-its-own-special-laws
food for thought in relation to this article/author: (copy-pasted from HC)
Some excellent detective work on the YMB by Goutah3006
Does Shawn Vincent = Shawn Vincent?
.
Today's negative Seeking Alpha article about Prana has internal weaknesses aplenty, but the author isn't listed by name in the by-line. The name given is "EnhydrisPECorp". Click on that name in the by-line and it brings up more detailed info on the author, listing him as one Shawn Vincent, Ph.D, former CEO of Enhydris Private Equity, who describes himself thus:
"I have a background in A&P, genetics, cellular biology, developmental biology, clinical trials, statistical analysis, and business development. I have owned multiple businesses, taught on the collegiate level, and currently work as an independent biotech consultant."
Now google the following phrase:
"IU-Kokomo professor arrested in New Orleans for child solicitation eyewitness news"
This will take you to a bunch of news stories from July 2009. The WTHR Eyewitness News article shows a mugshot of the suspect, one Shawn Vincent, Ph.D, assistant professor of anatomy at Indiana University, Kokomo. Dr. Vincent was charged with soliciting sex from a Secret Service agent who was posing online as a 14-year-old girl.
Now google "Shawn Vincent Ph.D Philippines biotechnology linkedin" to find the LinkedIn page of Shawn Vincent, Ph.D, former CEO or Enhydris Private Equity. There's a single gap in his resume, from July 2008 to May 2009.
Next, go back to the WTHR article and note that the suspect began working at IU Kokomo in the fall of 2008. He was invited to return for the 2009/2010 school year. After the end of the 2009 school year (presumably late May 2009), the suspect returned to his hometown of New Orleans to spend the summer. That's where he was caught by the Secret Service sting operation. When interviewed, the Vice Chancellor of the university indicated that Dr. Vincent "will be the focus of an internal investigation by the university that will determine if he's allowed to return to campus".
Is the Shawn Vincent in Seeking Alpha the same Shawn Vincent busted in New Orleans in 2009?
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http://www.thestreet.com/story/12400705/1/prana-bio-huntingtons-disease-drug-fails-key-efficacy-hurdles.html
note the primary endpoint of the REACH2HD phase2 trial for PBT2 on huntington's was safety with efficacy as secondary endpoints - which again this Adam Feuerstein completely misses/chooses to ignore
http://www.thestreet.com/story/12265416/1/biotech-stock-mailbag-prana-biotech.html
http://en.hdbuzz.net/158
of course this information should not be considered a signal to buy or sell. do your own research :)
corlemar
25-02-2014, 11:16 AM
I like this company and if one is patient, think the rewards will come in time !
Appendix 4D Half Yearly Report and Accounts
http://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=01495612
Commentary on Half Year Financial Results
http://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=01495619
Note this is an old article from march 2013 and I have not been able to find any follow up announcements/news on this
http://www.nytimes.com/2013/03/14/health/fda-to-ease-alzheimers-drug-approval-rules.html?_r=0
By GINA KOLATA (http://topics.nytimes.com/top/reference/timestopics/people/k/gina_kolata/index.html) Published: March 13, 2013
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The Food and Drug Administration (http://topics.nytimes.com/top/reference/timestopics/organizations/f/food_and_drug_administration/index.html?inline=nyt-org) plans to loosen the rules for approving new treatments for Alzheimer’s disease (http://health.nytimes.com/health/guides/disease/alzheimers-disease/overview.html?inline=nyt-classifier).
Drugs in clinical trial would qualify for approval if people at very early stages of the disease subtly improved their performance on memory or reasoning tests, even before they developed any obvious impairments. Companies would not have to show that the drugs improved daily, real-world functioning.
For more than a decade, the only way to get Alzheimer’s drugs to market was with studies showing that they improved the ability of patients not only to think and remember, but also to function day to day at activities like feeding, dressing or bathing themselves.
The proposal, published online (http://www.nejm.org/doi/full/10.1056/NEJMp1302513?query=featured_home) Wednesday in The New England Journal of Medicine (http://topics.nytimes.com/top/reference/timestopics/organizations/n/new_england_journal_of_medicine/index.html?inline=nyt-org), could help millions of people at risk of developing the disease by speeding the development and approval of drugs that might slow or prevent it.
The proposed policy could also be a boon for the pharmaceutical industry and researchers. They have often felt stymied by regulations that left them uncertain of how to get drugs tested and approved for marketing to people early in the course of Alzheimer’s, when the medications are most likely to be useful.
Several studies are being planned for people at high risk of developing Alzheimer’s, and the proposed regulations should lead to even more clinical trials, said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher and professor of psychiatry at Duke University School of Medicine.
“There is more motivation now to invest in the field,” Dr. Doraiswamy said. But, he added, the proposal also comes with risks.
The F.D.A. would require companies to study the drugs after they were on the market to show they actually benefited patients. But these studies might not be randomized clinical trials and so would not be as rigorous as the studies that led to approval. Even with less rigorous studies, it might be hard to get the evidence, Dr. Doraiswamy said.
“A lot of companies drag their feet and never do a postmarketing study,” he said. Even if they do one, it may take years to find out whether a drug works. Meanwhile, millions of people may be taking it, at great expense.
The agency is trying to resolve a quandary with its new policy: How can you show a drug works if patients are so early in the course of the disease that they have no obvious deterioration in their cognitive abilities or daily functioning?
In draft guidelines to the industry last month, the agency outlined a way to resolve the problem by changing the criteria for drug approval. Those at a very early stage of the disease, with no obvious symptoms, could be studied with cognitive tests (http://health.nytimes.com/health/guides/test/mental-status-tests/overview.html?inline=nyt-classifier). Those with mild symptoms could have a combined test of function and cognition.
With the draft guidelines, the agency is soliciting comments from the public and industry and may make revisions, said a spokeswoman, Sandy Walsh. But, she added, “we are ready to move forward with the plan.”
In the paper published on Wednesday, the agency aimed to explain its perspective to a wider audience. “Our goal was to provide as much regulatory clarity as possible,” said Dr. Nicholas Kozauer, a clinical team leader in the agency’s division of neurology products. “We would encourage companies to start thinking along these lines.”
Companies and researchers were elated, saying the old regulations had hobbled the field.
“This is really a huge advance,” said Dr. Eric Siemers, senior medical director for the Alzheimer’s disease team at Eli Lilly & Company. “Kudos to the F.D.A.”
Dr. Sean Bohen, senior vice president at Genentech (http://topics.nytimes.com/top/news/business/companies/genentech_inc/index.html?inline=nyt-org) for early development, praised the policy, but said he worried about how to develop appropriate tests to identify subtle cognitive changes.
“There is a lot of uncertainty,” Dr. Bohen said. “But it is an admirable effort. We have to start somewhere.”
Even before the F.D.A. issued its proposal, several companies and the National Institutes of Health had been planning studies of people who are very early in the course of the disease.
Dr. Paul S. Aisen of the University of California, San Diego, and Dr. Reisa Sperling of Harvard are leading a federally financed study that will enlist 70-year-olds who seem perfectly normal but are accumulating amyloid plaques in their brains, a sign that Alzheimer’s could arise within about 15 years. Of 1,000 people with plaques, half will get an experimental drug made by Lilly and the rest will get a placebo. The study will also include 500 70-year-olds without plaques, for comparison.
The researchers will assess the drug by giving subjects several tests, including ones that involve remembering lists of words and paragraphs and tests of an ability to follow instructions to change symbols to letters. Large studies indicate that people who are going to get Alzheimer’s decline faster on these tests than those who will not get the disease. If the drug works, it may slow or stop that decline.
Later this year, Lilly will start a new test of a drug in people with mild symptoms. The drug was already tested in a mixed group of patients, some with mild symptoms and some with more advanced disease. It failed. But the company gave its raw data to academic researchers who discovered that if they looked only at memory tests and only at patients with mild disease, it seemed to benefit them. So the company will redo the study with just those who now seem most likely to be helped.
Genentech is planning a study of its own drug in people who have no symptoms, but have a gene mutation that virtually guarantees they will get Alzheimer’s eventually. The hope is that the drug will prevent or delay it. But if there are no symptoms, Dr. Bohen asked, what is the best way to look for subtle cognitive changes? The agency will not accept changes on brain scans alone as evidence of efficacy. Yet it could take years for symptoms to develop in those with the gene.
“It feels like we are taking a risk,” Dr. Bohen said.
The company, he added, will be sending a comment to the F.D.A.
Another big night of ADR trading on the NASDAQ - closed up 19.95% / $1.87
WC Wainwright have also increased their price target from $20.50 to $33 (http://www.americanbankingnews.com/2014/02/26/prana-biotechnology-price-target-increased-to-33-00-by-analysts-at-hc-wainwright-pran/) this is for the NASDAQ ADR's - 10 ADR's equates to 1 ASX share so increase from 2.05 to $3.30
brief chart as of last night's NASDAQ trading attached, any TA'ers want to take a look and let me know if my musings are correct?
MACD set to cross the EMA, signs of showing upward strength still?
RSI/stochastics getting up there but potentially not showing oversold levels just yet. Strong blue candle to finish today showing upward momentum still strong? and building volume again an indication of this?
Appreciate any viewpoints/advice :)
5557
Strong finish up 18.5c/17.8% on 3.3m shares, I imagine we may be likely to see some profit taking tomorrow being friday and possibly a drop in SP? We seem to follow the NASDAQ a bit overnight so will be interesting to see what they do overnight.
/edit This is still a highly speculative and high risk stock, has anyone else been following this that wants to offer some contrary views? I believe in the company and the product and trying to find more scientific data for and against what the results coming may show, it is a little hard to keep an objective mind about it. DYOR!
I got in this over a year ago at 20c but only 5000 shares. As you say high risk, spec. i liked the biological rationale of the drug as it relates to Alzheimers but it could prove ineffective in further tests. so far it seems to be shaping up as having some positive effect but have a look at Pharmaxis to show what can happen when things don't pan out. My strategy was to sell about a third to recover my original capital which leaves me with a zero cost involvement in a high risk investment. My next strategy may be to sell off another third if it gets back to 1.30 +. This is just to make sure I don't give up all profits if it tanks but I still have an interest if it goes well.
These bio stocks rely on ticking off the tests with positive results. One fail and they can fail beyond recovery.
Prana Presents at 34th Cowen Healthcare Conference
http://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=01497460
Dr Kemplar interview from Bloomberg - credit to the person on yahoo message board who posted it up, subscription only article. Dr Kemplar being chairman & CEO
March 03 2014 -- 09:28:34am
Geoffrey Kempler, executive chairman and chief executive officer of Prana Biotechnologies, said he is optimistic about the results of the Imagine trial, testing lead candidate PBT2 in Alzheimer's disease due this month. In an interview with Bloomberg's Elizabeth Krutoholow, he said the agent may be useful early stages of the disease when it can combat the prevention of memory formation. He said the company's recent Phase II results in Huntington's disease provide additional support for the drug's mechanism.
Q: Are you on track to announce top-line results from the. Imagine study this quarter?
A: We are on track for a March target.
Q: Will you pursue a Phase IIb or registrational Phase II/III adaptive trial?
A: We have started to think about it, and it is something we will discuss with the regulators. We are a small ambitious company. The trials we have conducted are small in terms of patient numbers. The question is how many times do we need lightening to strike to prove our drug works? I am optimistic for several reasons. In an earlier trial we have shown a 13 percent reduction in beta-amyloid and we improved executive function scores. These results were published in the Lancet Neurology in 2008 and 2009. The data looked good, so we invested more money in the program
Everyone has been chasing beta amyloid and after several failures, the hypothesis was questioned. Still, the genetics point to beta-amyloid, Oligomers are toxic and their formation is a metal dependent event. If the metal is removed, they won't aggregate. This is where PBT2, our metal-protein attenuating compound comes in. In addition, metals in the brain are part of memory formation, so it is useful to remove them from oligomers and plaques and redistribute to neurons for improved function and increased synaptic transmission. We can best intervene early in the disease. In the Imagine study, our primary endpoint is a decrease in beta-amyloid as measured by PET imaging. We have an enriched population since PET scans were performed as part of our entry criteria. We hope we can catch people early in the disease.
Q: What is your sense of the regulatory view of a decrease in brain amyloid beta without an improvement in executive function? Why did you choose the imaging endpoint as your primary endpoint?
A: It is not reasonable to expect functional improvements in patients with very early disease because patients may not yet have functional problems to treat. The NEJM article published last year by the FDA says it may be possible to achieve early approval for a drug by demonstrating improvements in cognitive tests, and that companies may be able to look for functional improvements afterwards. More specifically to your question, in the NEJM article the authors said that a lot more work is needed because a decrease in brain amyloid alone, without some cognitive benefits, would be enough for approval.
Q: If you obtain a disease modifying claim, what is the market opportunity?
A: The disease modifying claim versus the symptomatic treatment has been debated for a long time. It is important to look at the sustainability of the benefit. There is a large number of patients. This is the Holy Grail. With an aging population, there would be massive demand. Safety must be established first. If there is a real and meaningful benefit, there are millions of
people who could be treated.
Q: Let's talk about Reach2HD results. You saw improvements in cognitive function at the highest dose after 12 and 26 weeks. Why do you think there wasn't an effect on motor function, behavior or functional capacity?
A: This was a small Phase II study, not a Phase III trial. It was conducted to establish safety and tolerability. We met the primary endpoint, and had 95 percent of participants finish the study. We saw a statistically significant improvement in executive function as measured by the Trail Making Test Part B. We don't think this was a fluke since we saw that PBT2 also improved executive function Alzheimer's disease patients in an earlier trial. This is why we are so enthusiastic. This was a go/no-go trial and we think what we have seen in the real. Regarding other measures, it is too soon to say if PBT2 will/won't have an effect as these parameters are probably best addressed in a larger Phase III population.
Q: You spoke to the heterogenous patient population in this study. Will you look to better stratify patients in the Phase III trial?
A: We might stratify different characteristics in the next trial. In Reach2HD, we saw a very small but positive signal in the TFC scale. We enrolled patients that were TFC (Total Functional Capacity) 6-13, which captures early-stage to midstage disease. The signal was seen in the early stage group, so it might be useful to focus more on this group in the next trial.
Q: What is your capital position? When will you look to raise additional capital/pursue partnerships?
A: We have about 20 million AUD and we will have a few million additional in tax credit at the end of March. We can raise additional capital any time after we see the Imagine results. There is a possibility of working with a pharmaceutical partner. We hired Dr. Peter Smith as our VP of business development. He will make us reaction ready when it comes to any partnerships. We are open to it.
End
Couple of new articles on seeking alpha today also
Henry Su - more of a pro-prana perspective
Bipolar Prana: PBT2 For Alzheimer's Dementia, Implications Of The Upcoming IMAGINE Trial Results
http://seekingalpha.com/article/2060553-bipolar-prana-pbt2-for-alzheimers-dementia-implications-of-the-upcoming-imagine-trial-results?source=kizur_seekingalpha
Michael Sacardote
Prana: Right Drug, Wrong Dose
http://seekingalpha.com/article/2062823-prana-right-drug-wrong-dose?source=kizur_seekingalpha
The Cowen presentation/webinar is now available, approx 30mins long slideshow with Audio
http://www.wsw.com/webcast/cowen16/pran/
you will need to register, then it will show you the webinar
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Whitehead Institute
MARCH 3, 2014
TAGS: LINDQUIST LABNERVOUS SYSTEM
CAMBRIDGE, Mass. (March 3, 2014) – Using a yeast model of Alzheimer’s disease (AD), Whitehead Institute researchers have identified a drug that reduces levels of the toxic protein fragment amyloid-β (Aβ) and prevents at least some of the cellular damage caused when Ab accumulates in the brains of AD patients.
“We can use this yeast model to find small molecules that will address the underlying cellular pathologies of Alzheimer’s, an age-related disease whose burden will become even more significant as our population grows older,” says Kent Matlack, a former staff scientist in Whitehead Member Susan Lindquist’s lab. “We need a no-holds-barred approach to find effective compounds, and we need information about their mechanism of action quickly. Our work demonstrates that using a yeast model of Ab toxicity is a valid way to do this.”
The U.S. National Institute on Aging estimates that 5.1 million Americans may have AD, the most common form of dementia, which progressively robs patients of their memories, thinking, and reasoning skills. Research focused on the disease has been hampered by the affected cells’ location in the brain, where they cannot be studied until after an AD patient’s death. To explore the cellular processes compromised by AD, researchers in Lindquist’s lab created a yeast model, first described in the journal Science in 2011, that mimics in vivo the accumulation of Aβ that occurs in the human disease.
In the current research, which is described in this week’s issue of the journal Proceedings of the National Academy of Sciences (PNAS), a team of scientists in Lindquist’s lab used the yeast model to screen approximately 140,000 compounds to identify those capable of rescuing the cells from Aβ toxicity. One of the more promising classes of compounds has previously shown efficacy in animal models of AD and is about to complete a second phase II trial for AD. The mechanism by which the best-studied member of this class, clioquinol, targets Ab within the cell – where a large portion of it is produced in neurons – was unclear.
“Our work in the yeast model shows that clioquinol decreases the amount of Aβ in the cells by 90%,” says Daniel Tardiff, a scientist in Lindquist’s lab. “That’s a strong decrease, and it’s dose-dependent. I’ve tested a lot of compounds before, and I’ve never seen anything as dramatic.”
Clioquinol chelates copper, meaning that it selectively binds the metal. In many AD patients, Aβ aggregates have higher concentrations of copper and other metals than normal, healthy brain tissue. Biochemical experiments also show that copper makes Aβ more toxic.
With clioquinol’s chelation capabilities in mind, Tardiff and Matlack, co-authors of the PNAS paper, tested clioquinol’s effect on Aβ-expressing cells in the presence of copper. The drug dramatically increased the degradation of Aβ in a copper-dependent manner, and even restored the cellular protein-trafficking process known as endocytosis, which is disrupted in both the yeast model and in AD-affected neurons.
“The clioquinol probably has a slightly higher affinity for copper than Aβ does, but it is not a strong enough chelator to strip the cell’s normal metalloproteins of the copper they need,” says Matlack. “From what we’ve seen in the yeast model, we think the drug pulls the copper away from Aβ. That would alter Aβ’s structure and likely make it more susceptible to degradation, thus shortening its half-life in the cell.”
The results from clioquinol in yeast and the clinical potential of closely related compounds are promising. While these compounds are not yet ready to serve as AD drugs in the clinic, the identification of an AD-relevant compound and cellular pathology – along with the Lindquist lab’s previous identification of human AD risk alleles that reduce Ab toxicity in yeast – suggests that this discovery platform will continue to yield information and lead to more compounds with equal or greater effectiveness, some of which will hopefully make a difference in human disease.
“It is important to remember that this class of compounds was shown to work in mouse models and in a limited human trial,” says Lindqust, who is also a professor of biology at MIT and an investigator of the Howard Hughes Medical Institute. “We have validated the yeast model and shown that we can find such compounds at a speed that was inconceivable before—indeed we found some compounds that look even more effective.”
This work is supported by the Howard Hughes Medical Institute, National Institutes of Health (R03 Grant DA032472), the Ellison Foundation, National Research Service Award (NRSA F32NS061419), the JPB Foundation, and the Edward N. and Della L. Thome Memorial Foundation.
Written by Nicole Giese Rura
* * *
Susan Lindquist’s primary affiliation is with Whitehead Institute for Biomedical Research, where her laboratory is located and all her research is conducted. She is also a professor of biology at Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute.
* * *
Full Citation:
“Clioquinol promotes the degradation of metal-dependent amyloid-β (Aβ) oligomers to restore endocytosis and ameliorate Aβ toxicity”
PNAS, March 3, 2014.
Kent E.S. Matlack (1,*), Daniel F. Tardiff (1,*), Priyanka Narayan (1), Shusei Hamamichi (2), Kim A. Caldwell (2), Guy A. Caldwell (2) and Susan Lindquist (1,3,4).
1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142
2. Department of Biological Sciences, University of Alabama, Box 870344, Tuscaloosa, AL 35401
3. Department of Biology, MIT, Cambridge, MA 02142
4. Howard Hughes Medical Institute
* These authors contributed equally. Less (http://finance.yahoo.com/mbview/threadview/?&bn=d3a80d22-394e-3b69-81f5-4282c29a0628&tid=1393949478349-eb93e774-d4ab-45da-9092-8519750658ca&tls=la%2Cd%2C2%2C3#)
Sentiment: Buy
(clioquinol being PBT1, which was withdrawn due to toxicity concerns and superceded by PBT2)
picking results in week of 17-21 march... can barely contain myself :D
PBT
Addition to S&P/ASX 300 Index – March 21, 2014 After Market Close
http://www.asx.com.au/asx/statistics/displayAnnouncement.do?display=pdf&idsId=01499745
Official announcement - this was not unknown/unexpected so I think unlikely to have a great effect on the SP.
PBT are presenting at the 21st Annual Future Leaders in the Biotechnology Industry conference on the 28th of March - as we still have not seen AD results yet which according to the latest guidance are still expected in 'late March' the timing could coincide nicely
"Future Leaders connects leading portfolio managers, bankers and analysts with investor-validated, milestone-rich private and public companies in key therapeutic areas, offering new investment and partnering opportunities and the chance to find companies with tier-jumping potential.
Future Leaders provides the industry's best venue — in a single day — to identify solid investment and partnering prospects. Wall Street and pharma executives will have the opportunity to assess private and public companies with healthy financial profiles, poised to deliver on milestones that could lead to the next tier of valuations.
Last year, more than 500 delegates congregated at Future Leaders, representing top financial institutions, pharmaceutical business development executives, and high net worth investors active in the sector. Last year's Future Leaders audience controlled more than $650 billion in equity assets.
By popular demand the Future Leaders Class of 2014 expands to include a new "Next Wave" track featuring 15 early stage, privately held companies hand-picked by BioCentury. The "Next Wave" track promises to showcase platform plays and product companies advancing their assets to the clinic and proof of clinical concept. Attendees have the opportunity to hear their stories in a 9-minute 'elevator pitch' format and to meet their management teams."
Price sensitive announcement is up, can't see it yet - they have kept to their indication that results will be released in March so at this stage it's looking like may be the long awaited phase 2b results for Alzheimer's.. potentially the make or break momemt (or more likely a 2 day TH so more nailbiting hah). Although perhaps they will go into TH today, release results at close of ASX, gives time for nasdaq/ASX to digest it before trading opens (first tomorrow for ASX, then nasdaq monday open overnight tomorrow our time)
Trading halt until commencement of trading Wednesday 2nd or until the company releases the announcement.
I am thinking ASX close today or ASX close tomorrow depending on whether they want to give ASX or NASDAQ first run at trading after announcement released
That"s a pity! I had hoped they were on to something that would at least help control Alzheimers. Still, Having protected my capital early in the piece I'll just have to quit the rest and move on. It's a tricky business this bio stuff!!
Yep pretty sad - from the conference call it looks like they are now thinking they did not gear the primary/secondary endpoints properly, too late for that now. huuuuuuuge sell depth on ASX - wonder what price i'll be able to get out at. they are still hopeful to push forward PBT2 for HD to phase3/orphan status in 2016-2017 so weighing up whether I keep a few in there for that. tough decisions ahead!
baller18
01-04-2014, 12:14 PM
Was reading an article on Biotech stocks, only 1 out of 1000 make it out of a 2B or 3a trial, so sell the majority of your holding and some profit during the run up and keep the free holding shares....
Indeed a good lesson I have learnt the hard way :D end of the day no money lost that I couldn't afford to lose. Little sad, looking forward to a beer or three after work :D
I sold my remaining free holding shares today. I knew when I started with this company it was a gamble so only had 5000 shares @ .20c. More for the experience than anything else. I did what baller suggested early on but with hindsight my profit was conservative at 10% plus fees. Still, a profit is a profit and the experience pretty invaluable.
blueswan
01-04-2014, 04:23 PM
Im still long SRX ( Sirtex) less volatile and RGS ( Regeneus) more volatile.
They are still heading for phase3 trials for PBT2 in application towards huntingtons disease (targeting 2016-2017), also have PBT434 (this may be wrong, can't remember exactly, think it's something 434 - prk434?) targetting parkinsons also but not much firm news related to that. They still have 25m cash in the bank so not fully out of it yet. This is a big blow to them however no doubt
You can have mine off market mate, 40c ea a steal :D
I like you moosie, not that much :P
psychic
02-04-2014, 07:44 PM
Mr. Kempler concluded: "Whilst not meeting all of our hopes, this result does not deter us from the future development of PBT2, a safe and well tolerated drug candidate for Alzheimer's disease. Our scientists and those from other institutes have developed a strong body of evidence for the efficacy of PBT2 in Alzheimer's disease. The suggestion of beneficial effect of PBT2 on brain volumes first seen in the Reach2HD Huntington disease trial and now in this Alzheimer's disease IMAGINE trial is intriguing. We are consulting with experts in the field to further assess these results and to consider how best to progress PBT2 in Alzheimer's disease. Indeed, the IMAGINE Extension trial is continuing, and data from this trial is likely to inform the next steps for an AD program."
Read more: http://www.nasdaq.com/press-release/prana-biotechnology-announces-preliminary-results-of-phase-2-imagine-trial-of-pbt2-in-alzheimers-20140331-00213#ixzz2xhzCqZKO
What a blow, but they clearly believe PBT2 is of use, I hope they are right. Worth watching.
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