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Sometimes yes. But in this case Sinopharm wanted first crack at PV-10 after seeing some liver data. The license will be for all indications. Sinopharm has 90 days of being exclusive. The PIII protocols need to be sent over once finished. Sites for testing are already being set up. Sinopharm is the largest pharma over there with some 70% of the market. It is run by the Chinese State government and I do not think we will see delays like the ones in our government.
Network One has an expert who works closely with China and was instrumental. But I hear you.
Is everybody calm now? Once the protocols are finished and sent over there the deal should be finalized. Should be plenty of money rolling in to cover the trials. This license, once agreed, will be for every indication.
This MOU should move India to sign as well or risk their territory licensed to China for even more money.
I don't always agree with mgt
But those times I disagree I do so privately and avoid airing dirty laundry
Such public disagreements can and do affect share price in a negative way
As a shareholder that would be counter intuitive
I did not approve of those couple of years they took a higher salary than they have now
I have no problem with what they take now
If you wish to bring up class envy then let's us look at that from another point of view
Let's assume you are a motor mechanic and you fix one car a day for $30k per year
You then look at someone making $500,000 or more a year and saying not fair... Pigs
Can you fairly equate a mechanic who went to one year of trade school with doctors and PhDs who paid hundreds of thousands for school, earning zip for eight years of med school
And whose product seems to outperform every cancer drug ever invented.
What do you wish them to be paid?..... Nothing because the sp is low?
If it jumped to $40 a share tomorrow would you complain? Probably not.
And if not then your argument is not about pay but disappointment that the share price is not higher
That disappointment then leads to laying blame on causes.... Namely mgt.
The seemingly lack of progress you point out assumes they sat on their butts doing nothing
95% of what they do you cannot see or hear about
What you fail to realize is the natural delays caused by the interactions with the FDA
Let's take the time of the past four years
In 2010 they finished pII treatments. They then had to wait for one year for the very last patient for os data and pfs. Now it takes about six months to process the data and send it in to the FDA. You then wait months for the FDA to get back to you and give you an indication on how to do a pIII. But wait....this is a local drug that has systemic effects... Wth? And it's injectable locally....wtf???
Hold on there....time to scratch heads and butts. So Pvct writes up a study proposal....ummm FDA says no. But it's just like the other drug studies.....don't care. Try three times.... Finally they say do btd... And they did say that.
It is no different than big Pharma and their delays can often be longer. It's the nature of the beast.... It does suck.
I understand your anger and sometimes I get angry too.
I had hoped to be retired by now
Contrary to what some think I do not work for the company not do I receive compensation
I work for me....and by extension you
This has been a difficult year and I work to learn as much as I can to pass it on and hold all of us together until the end. Something the company is poorly positioned or not allowed to do. Those of you who have lost patience I suggest you sell at the first opportunity you are in the black. Mgt will go on in the current mode and I don't see complaining at this point will have any positive effect.
As for me I plan on holding fast to the end
Have a bit more patience.... The drug works better than you can imagine
There will be more vindication of this soon
Big Pharma runs into a pipeline crisis next year
The pIII in my opinion will end in six months after 50 patients are enrolled and not 30 months with 210 patients
See my posts about stoppage rules
I somehow thought that this would come up. Ok....let me put it another way. If you were a CEO of a company and had to choose who to hire. Do you hire four researchers who have nothing invented and hope to discover something for $200,000 each or do you hire four guys with a cancer treatment that's looks very promising for $500,000 each. What would you do? These guys came up with something the whole rest of the world and all the big pharmas and all the doctors never did.....ever. I mean ever. Never in the history of the world did someone else do this....but they did. And as a result people think they should live off of ramen noodles during this time? No, I am a bit more realistic....they deserve to be paid a lot. Where do you get $40mm in pay from? Your not doing your homework. Go back and look at their pay.
Now let me educate you on something about those delays. I was around then too. I was there each and every time thew FDA said no to their proposed study. The FDA kept changing what they wanted. It seemed to me that the FDA was stalling them for some reason. This was a whole new type of drug and I don't think the FDA knew what to do with it. So I think the decision makers kept kicking the can down the road for someone else to deal with it. PVCT finally got their SPA written when the FDA said "no....we got this BTD thing now....do that". PVCT has the document from the FDA that proves that. Before you believe in the hype, start delving into the facts.
Lifestyle company? What lifestyle? Do you even know these guys?
Half their pay goes to taxes. They are not living it up despite what people's imagination conjures up.
Now for a couple of years the took a larger salary and that got paid back....end of that argument. Go back and look at their salaries back to 2002.
Most people don't make $500,000/year....I get that. Those same people did not go through med school (eight years of 20 hrs a day living off ramen noodles and living at the hospital earning almost no money), become PhD's, invent a treatment for cancer.
In addition....they have to put up with the FDA, Wall Street, the SEC, Bashers, AF and Seeking Alpha, lawsuits......and us shareholders. Personally you couldn't pay me enough to deal with all that.
Another point. It NORMALLY takes 15-20 years to get a drug to market. It NORMALLY takes between 1.5 BILLION and 5 BILLION to get a drug to market. TOTAL Money spent by PVCT.....LESS THAN $150 million. Total time spent on the process so far?....12 years.
I really don't see a problem.
But maybe we should have paid them $100,000/year instead and let this cost $5 billion to get it to market in 20 years.
No, they did not tell me....and I am not going to ask.
There is a group in NYC that wish to finance a different deal that came up but will be back in later. No biggie. Got this info from one of them. Makes sense if another opportunity pops up right at this moment.
If that is your opinion so be it. I will disagree but I can see why you are frustrated. Most, including I, thought we would be done and done with our investment by now. Even if PVCT got the BTD there would have been a short bridging study in all likelyhood. I had thought the BTD was a shoe-in. To require PIB data when there was none to be gathered was the epitome of asinine in my opinion.
For those that question the drug need also to question the data from Moffitt and others. No....the evidence is stacking up in favor of PV-10. Dr. Weber even changed his tune and is now a lead proponent.
Everyone looks at the share price and wonders if something is wrong with the drug. We need to remember that a big short attack and AF had quite an effect and it will take time to recover. The failure of the BTD hurt the sp as well.
But it will recover.
Don't beat me up on this but I think the delay is a benefit. I will expound on my seemingly optimistic bloviation.
*The delay puts the company in a time frame where big pharma will be in a pipeline crisis.
*I have heard two big pharmas just recently completed their own mouse studies and verified the results....I have no proof other than something I have heard...treat this info for what it is....but it makes sense they do so.
*I have also heard that a murine combination study with immunotherapies has been completed and the results to be published....when? I do not know. It's hearsay until it's in print.
*It would seem that the PIII study has timeline points in it to peek at the data....something that should interest the DMC and could lead to a stoppage recommendation.
The Blog, I and others work very hard to gather info and provide others facts and our opinions based on that info. Are we always right? No.
But many times our info goes unheeded. For instance the Blog warned EVERYBODY that a bear raid was coming at least a month before it happened. Nobody listened and everyone got burned. I correctly predicted that there would be some sort of deal with Cantor based on my watching their behavior on level two. That did happen. Over time we proactive investors build more and more connections. We do so because we have a lot of money invested and we are making damn sure it is going to give us a ROI.
But alas, nobody controls the future and some things can and do change. We are but weathermen and that's all we are. As time goes on our understanding gets better and our predictions should get better as well. But even if the prediction is for a clear sky, always keep an umbrella handy.
You are correct....but they are consolidated to one case as you point out. Personally I am not concerned but others may be. I think their case is weak. I think their lawyers think PVCT will want to settle for the insurance money. Just my opinion.
Up until the last moment there seemed to be no lead plaintiff. One popped up. Sorry....it took me by surprise.
I am not worried about it....it's just an annoyance to me.
Since they will be opening many new sites I think that will help enrollment a lot. No one can know the time it will take....you do your best to maximize your chances to do it as quick as you can.
Studies are stopped at mid point and earlier. Most of the time it is for adverse side effects. Then there is the cases where they stop the study because the safety and efficacy is much higher than the comparator drug. In the case of PV-10 vs chemo and based on prior efficacy and safety, I call it a foregone conclusion that PV-10 will show such superiority to qualify for a recommended stoppage of the PIII study.
It is my opinion that the study will be stopped before midpoint by the DMC after about 50 patients (the equivalent of that short bridging study). My guess is about May 2015 if enrollment starts mid November of this year. If that happens then PVCT will go to the FDA to see what they think. If the FDA agrees then the OS data will be gleaned from a rolling PIV post marketing study. This is called a conditional approval whereby the drug goes to market and is allowed to be sold as long as the OS data continues to look good. This OS data will be tracked for ten years while the drug is on the market.
The liver trials will be run mainly overseas probably as joint ventures with china and India
They will be paying for those
Will they get a china or India deal?
I have no doubt
The main problem to consummate a deal in my opinion
Is the middle part of the deal
Up front money
Big money for hurdles
Royalty payments
The middle part of those type of deals can be worth nine figures
But they need to know what they need to replicate in their own studies
That requires pIII protocols
So to consummate the regional deal requires the pIII protocols
Buy sell hold at your own risk
This is my opinion
I've been studying the stoppage rules and the data monitoring committee process
There is the process where by at a certain point the DMC determines that a drug works so well and is safe against the comparator that they recommend stopping the study and moving the comparator group to the new drug
Plenty of examples
When I studied those examples I determined the Pv-10 exceeds those requirements for stoppage by a long shot as long as the data is repeatable from prior studies
It is my opinion that about 50 patients in and about six months into the study that stoppage will happen
If so the DMC will recommend a stop and proceed to the nda
Pvct then will go to the FDA to see what they think
If the FDA agrees with the stoppage....and they usually go along with the DMC recommendation
Then the secondary endpoint of os will be rolled into the phase 4 post marketing
If so we are looking at about 3-4mm spent
Time line
Give another six weeks to complete the pIII protocols
It's going to be over 2000 pages just like the spa
Then give it 30 days more to be approved by the FDA
This puts us at mid October
It should only take 30 more days to start enrollment
Mid November
By May we should reach the point where a stoppage should occur
If it happens that will be the equivalent of a mid point interim analysis
Now let us back track to time of protocols being finished
I would expect mid October to send those protocols to India and china to consummate the regional deals
By then more sites will be open and ready
More money flows in to take the company to the end of pIII if need be
So if my viewpoint is correct
We are just one year delay for big Pharma
But wait
Timing is everything
That puts the company right smack in the middle of a pipeline crisis of big Pharma
The leverage will go to us
And some members of the boa are smaller than others
It puts us in a position of a dark horse riding in
Us being all of us shareholders and company
Big Pharma is fucked
We will be in the cat birds seat
Now there are those in NYC who are worn out and tired
They want to sell
Fine
If they do we trade them for new shareholders who will not have to wait that long
The early bird gets the worm
But the second mouse gets the cheese!
This has been the Vorlon Report
Buy sell hold at your own risk
Initial treatment as an outpatient...maybe
But remember all of these patients had to fail at least one other treatment to qualify
And this is a drug under study
They will be checking for progression externally and internally
They will be checking toxicity even if they think it's not
They will run tests on all organs
Let's not forget the PIB data
And hell yes the hospital will want all of this done to their benefit
Crazy expensive even if the drug is pennies to make
Ok
Patient enters study....you pay docs for weeding out those that can and cannot
Pay the hospital and docs for all the testing to determine that
Now get treated
Pay the doc and nurse
Pay the hospital
You have follow up visits to follow any progression
Get scans to make sure cancer not progressed internally
Lab work...x-rays... MRI .... Cat scans...pet scans.... Blood work...check functions of all organs to make sure all is well.... Piss that's in the cup
Pay all the docs and staff to do this
Pay the hospital
Pay the labs
Repeat several times up to at least a year or more
Pay the data monitoring committee, who are doctors, several thousand per patient to labor over all the data and organize it...analyze it... group it all with the others.... analyze the group....write the reports
Just to name some of the expenses....it adds up quick
Look back at my posts about the DMC and stoppage rules. If ever there was a drug that deserves to stop early because of efficacy and safety it's this one. That being said, it is my opinion that only $3-$4mm will be spent by the time the study will be shut down. That is why I am not concerned.
They still retain the authority to sell shelf stock through Cantor....up to 50mm shares which right now would bring in $43mm.
That is a NON issue. They would rather not go that route as that would cause dilution.
Questions I want you to ask on today's CC.
Are the protocols done for the PIII?....if not then how much longer?
(realize that this is over 2000 pages to write)
What is the status on the foreign license deals?
(realize that it will take the finished protocols to consummate)
How many new sites are you opening up for liver and melanoma, here and overseas?
(have them name them...there should be quite a few)
In this study they will be allowed to treat those patients who do not qualify for other PV-10 trials....that makes it more open. The cup program's data is closed from publication. By doing this study, not under the FDA's restrictions, they will be able publish a broader spectrum of cases....and to be sure they will be publishing.
How to get around the FDA restrictions that hamper seeing more things about PV-10:
http://utm-ext01a.mdacc.tmc.edu/dept/prot/clinicaltrialswp.nsf/Index/2014-0065
More open than the CUP program. Wow!
And the data will be reportable unlike the CUP program.....Double WOW!
I think they ended up with one that had enough shares to be a lead plaintiff.
Because the PVCT shareholders are not ready yet from what I hear.
I would rather stay out of the stock buying/holding/selling advice business. I would prefer just to provide my insight on the drug itself. I think tom123 is much more suited for such consultations.
What we have to look forward to.....
Monday is the latest date to be a lead plaintiff in those lawsuits....there are none so far and I would imagine only a few piddly shareholders even signed on. From my point of view it looks like they will all go away.
We should be expecting a conference call the second week in August. I am expecting to hear about the PIII progress and I am hoping to hear about licensing deals that have been in the works for some time.
I am also hoping to hear about new enrollments in the liver study and since Moffitt had suggested that PV-10 might be a good candidate for a combo study of anti-pd-1 drugs then I imagine they are probably doing one now since they also do work for Merck. Maybe they are doing the preliminary combo work for Merck to see if it is advisable for Merck to proceed with the combo study and associated costs.....I give a 90% chance that this is going on....common sense.
http://en.m.wikipedia.org/wiki/Haybittle–Peto_boundary
Here we see the rules for stoppage when the difference in efficacy is significant or not
Stoppage rules apply when the drug shows no significant difference or a large difference after a certain number of patients. Anything in between will dictate the study be run to the end.
http://m.jme.bmj.com/content/31/7/410.full
I tried to show both sides of the stoppage rule
I hope I have explained it in detail
It's called a stoppage rule.
The DMC will determine the threshold for such a recommended stoppage.
Many in the industry argue that early stoppage may skew the results of a study.
But in some cases where safety is assured and efficacy is supreme then such stoppage is considered ethical in oncology cases and moving the comparator group to the investigational drug advisable.
It's in the FDA rule book.
The articles I posted do not show up well on phones
I just checked
Review on your computer please
There is an established process where the data monitoring committee reviews the progress of the study
It is FDA standard procedure to not run a pIII to the end if the data shows real improvement over the comparator ... It is considered unethical in oncology cases
The only reasons to run it to the end is if the data is just so so and you need the numbers to see the significance
The links I provided explains in detail those rules
By my post I am assuming such significance will be shown
Again I apologize for the confusion
http://mobile.bloomberg.com/news/2014-03-31/novartis-says-final-phase-study-on-heart-drug-was-successful.html
No no no
That's not what I meant but I can see how you took that wrong
Sorry for not being more clear
I meant that if the data management committee, who will be monitoring the pIII trial does what they are suppose to do, i.e. A rolling data analysis... Shows that Pv-10 is superior after 4-6 months.... Around 50 patients...they will recommend the study to be shut down and that the comparator group be switched to Pv-10
I am assuming that Pv-10 will show superiority
If that is the case then the difference in the time line would be about the same
And only about 3-4mm will have been spent
I posted links to the FDA sites on the rules on that
I did not mean to suggest a short bridging study equals a full blown pIII
The pIII are run until a significant difference is shown then enrollment is shut down per FDA
Full pIII is run when the data is so so
Read the links to the FDA I posted which explains that
I will not, in good conscience, purposely mislead anybody
Why people worry.....expectations did not match reality, bashers instilling doubt and fear, not being comfortable with understanding the process, the drug, and the influences.....and all of this is reflected in the share price.
Why I am not worrying....I understand what happened and why....I dismiss the bashers because their overt agenda (though from time to time they made valid points worth investigating), I have spent enough time to earn a PhD in understanding the drug and the drug approval process. I am not always right but when I am wrong I try to understand why. So far I have seen the past and understand the path forward. There were detours and obstacles unforeseen but now I see an open meadow and a straight path forward.
Confidence is derived from educating yourself and developing an understanding of the big picture.
Areas to familiarize yourself in:
How pv-10 works
The other drugs and how they work
The response rates associated with the all the drugs
The approval process....AA, BTD, and the standard PIII
The endpoints in each process
The DMC....data monitoring committee and it's responsibilities
The route to the NDA
Reading all the data and reports from all the independent doctors and hospitals involved....seeing Dr. Weber change his opinion to being one of the biggest proponents of PV-10 is a big eye opener.
Understanding why it took years to get to the BTD application
Understanding what the FDA was doing to them on PIII/SPA endpoints during that time
Why the FDA rejected the BTD and why it does not matter because the way forward now will take about the same amount of time to get to the NDA as the BTD would have....IMO.
With educating yourself you either become more confident or less.
I for one have become more.....but confidence does not mean certainty and we yet may see the path twist and turn some more.
The Big Picture
I am the guy who said he was not worried...lol. Does that make me an idiot?...maybe. But I understand how the drug works on all levels, I also understand how the industry works to some degree.
When the drug makes it through PIII the total amount spent getting there will be about $150mm or less compared with the industry average of $1.3 to 5 billion.
http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/
http://www.forbes.com/sites/matthewherper/2013/08/11/how-the-staggering-cost-of-inventing-new-drugs-is-shaping-the-future-of-medicine/
Does this make management inept?....I don't think so. Has the process gone smooth as it was hoped for?....obviously not...but all in all things are not that bad. Many jumped in hoping for a quick payday and that did not happen....welcome to biotech. The FDA turned down the BTD on a technicality (no PIB data.....but even if they tried to acquire it there would still be no PIB data to measure). Why did they try then for the BTD?...because the FDA suggested they go that route. Is that contradictory?....yes. One must realize that there are many groups in the FDA....ones that guide a company and ones that give approvals....those groups ended up not agreeing.
What about those bashers who ridicule PV-10 being derived from a dye? The whole modern drug business came right out of the commercial dye industry....the first antibiotic was a dye.
http://www.cbmh.ca/index.php/cbmh/article/view/40/39
So what is ahead?
Enrolling PIII, Running PIII and getting it to the midpoint of the study where big pharma sees that the data should be the same as the second half of PIII.....the point they usually step in. Big pharma will know at that point that the data will be enough for a NDA once the FDA gets a NDA application.
Historically after a drug has had 30-50 patients reach the 4-6 month point the independent DMC takes a peak at the progress compared to the comparator.
http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm127073.pdf
If the investigational drug is fairly safe and is statistically more effective than the comparator then they usually ask the FDA to shut the study down early, switch the comparator group to the new drug, and recommend proceeding to NDA.
Recruitment is stopped in a PIII when you show you have the better drug:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014474/
Everyone would have been happy with a BTD with a bridging study...in all likelihood the bridging study and the PIII would have been about the same amount of time.
Everyone feel better now?
Let me give a shot at answering this.....and please think about my answers.
In talking to big pharma.....and I have to a small degree....my uncle was one of the founders of Amgen.....they like to purchase small biotechs at the right moment. When a pharma becomes a very big pharma they get in the way of their own progress....too much red tape. So they go around and find smaller biotechs to acquire but usually when the small biotechs finish most of their work.
That's why most small pharmas get bought up in the middle of PIII....the work is just about done by then. One reason they would make an offer earlier is if another big pharma made a move. Nobody moves until somebody moves then everybody moves.
Another reason they would move earlier is if the small biotech has a promising product but no money and they need to step in and partner to get it done. Do not expect this with PV-10 as they have the money for now.
Big pharma is waiting for PVCT to get all the work done on the drug. Stepping in at this moment would load it all down with red tape and corporate bureaucracy. Everything is proceeding now just like most small biotechs should. I find myself more calm now that the everything is following the formulated path.
Who said I left?....lol
When I have something to say I will say it....:D
I still have all my shares and I have no concerns whatsoever at this point.
But if you would like me to say something I will.
28th of this month is the deadline to be a lead plaintiff in the lawsuits....there are no lead plaintiffs to my knowledge and it looks like they will all go away. No real money will have been spent for defense.
I imagine they are busier now than they have ever been.
Likely things they are working on:
*Getting PIII enrollment process started
*Getting regional deals wrapped up
*Getting ready to set up testing sites in other countries
*Getting ready to do a combo study (likely with an anti-PD-1 agent)
*Lining up the CRO's to run the studies and CRO's to watch the progress
Busy busy busy
We should get an update in a few weeks.
I am also looking forward to any new news coming out of Moffitt...didn't they suggest combo treatments?....hmmmmmm
I agree
Maybe a three direction approach to get to the 100%
But the problem is cost
The two other treatments you suggest in combination with each other brings the treatment cost to over $200,000
They need to get the cost down on their drugs to allow a three prong approach to be affordable.
Bystander effect only 50% of cases
Not all cells in a tumor are alike. Those cells on the outside see more oxygen and food than the ones in the center. The ones in the the center evolve to live in the harsher nutrient poor conditions. They change. So when the whole tumor is destroyed by Pv-10 it may be the case that the center cells breakdown before the immune system gets a chance to see them. If that's the case the immune system will not set up a defense against those changed cells.
Breaking tolerance
Why does the immune system sometimes doesn't see the cancer.... Part of that is tolerance. When a person is allergic to something a doctor will give the patient low dose shots of the antigen to put the immune system to sleep. It becomes tolerant to the allergens. The immune system keeps seeing the antigens and no longer sees them as threats. Cancer is a cell of the body which in many cases looks enough like a normal cell to put the immune system to sleep. The difference of the surface antigens might not be high enough for the immune system to react. How do you awaken the immune system.... You break the tolerance with a massive dose to get the immune systems attention. You increase the odds that the immune system sees a difference. In the bystander effect it is thought that massive exposure to cancer antigens in context breaks the immune system tolerance. The more tumors you treat at the same time increases the odds of breaking tolerance.... i.e...more of a chance for dc and apc cells to see intact dead cancer cells.
Another problem with single antigen targeting is that cancers can evolve. What you may be targeting today may be good today but sometimes some of the cells have changed to not have that marker your targeting. So you get shrinkage of the tumor initially but you allow those changed cells to now flourish and the cancer comes back.
Pv-10 injection causes the whole tumor to go necrotic by brute force. The bystander effect kicks in about 50% of the time.... Probably due to the fact that only in about 50% of the treatments the immune system has a chance to read the antigens in context before the cells are completely destroyed.
Something I have noticed in the results of the treatments.... So far the results have a type of negafibonacci pattern.