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A BRIEF REVIEW OF THE LAST WEEK…
So…Some time over the last weekend I awoke…
I looked around…
OMG…
I was covered in puke…
And other bodily excretions…
Where am I…???
What just happened…???
Right now…
Not a clue…
OK…
Let’s gather our wits…
Hmmm…
I’m beginning to remember…
Oh…Yeah…
There was a news release.
And what did it say…???
“Results of the analysis demonstrated that the bavituximab plus docetaxel group did not show a sufficient improvement in overall survival as compared to the docetaxel group to warrant continuation of the study. The interim analysis showed that the bavituximab combination group is performing as expected according to the original trial assumptions in terms of overall survival, while the docetaxel group is dramatically outperforming overall survival expectations based on the original trial assumptions and as compared to recently published studies”
So the “Docetaxel group dramatically outperformed…”
I staggered over to my wine rack, pulled out a Cab. and then went to my computer. I pulled up my SUNRISE projection and looked for the possibilities. Well I’ll be damned there it is…In black and white…At a projected MOS of 13 the number of events the number of event around the end of January is between 72 & 78 events per arm. I bracket the group to include an MOS of 12 to 14…See below:
So…What’s the bottom line…???
Both arms were trending towards an MOS of about 13 with a range of +/- 1
AND SO WHAT…???
On a personal level I feel good that I created a projection that ultimately reflected reality. And I am disappointed that the reality is, the control group exceeded my (In my view) overly optimistic projection of exceeding its historical highest number by 20% (My upper limit for the control arm…12 months) by ~30%. FWIW that’s a 100% increase over the mean for all of the historical data.
Epitaph and Elegy:
I will print a copy of the spreadsheet and crumple it into a ball…
Light some candles and incense then ceremonially light the spreadsheet.
Mutter some words like…
A brilliant piece of work…Ultimately useless…But brilliant none the less…
Now back to the real world.
What to make of the “dramatically outperforming control group”?
More sabotage…?
Better post progression treatment (Including Opdivo)…?
At the end of the day, it doesn’t really matter. Here’s the big picture.
PPHM is in a dog fight…We are the Chihuahua and we are facing a pack of Pit Bulls.
A few weeks ago mojojojo asked me to look at the checkmate 057 trial (Opdivo). I tried to con him into buying a case of Brunello but he was having none of that. But I did do some analysis.
Here’s the significant part:
OPDIVO TRIAL:
Estimated Enrollment: 574
Study Start Date: October 2012
Estimated Study Completion Date: May 2016
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Number of trial sites: 117
SUNRISE TRIAL:
Estimated Enrollment: 582
Study Start Date: December 2013
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Number of trial sites: 161
They started checkmate 057 a month after PPHM reported results of our PII NSCLC trial and the subsequent discovery of sabotage.
They were able to recruit (enroll) all of the 582 patients in 13 months from start of enrollment to enrollment complete.
They were able to recruit the same number of patients with 44 less sites (161 – 117 = 44) in almost half the time…!!!
This speaks volumes about the power of BP…And tells you what the Chihuahua is up against.
I’ve read some very insightful posts over the last week coming from some of the posters that I have a high regard for. My ignore list is over 20 now.
Here’s a brief summary of some of the points and issues.
The importance of halting the trial now. This will give management access to all of the data generated to date. This trial was designed to include translational data, data that will provide some clarity WRT the immune systems response. It may provide additional support for the theory of adoptive immunity provided by Bavituximab.
Filing a BLA for the combo of Bavituximab & Docetaxel. I guess there’s some possibility…but I don’t see it as a worth while pursuit. PPHM cannot submit a BLA with data from the sabotaged PII trial alone. If they could have…They would have. Supporting data from the SUNRISE trial would have to be included in any BLA. That data needs to mature and won’t be available until the end of this year at the earliest. Money will need to be spent to continue this data collection.
As has been stated by several posters…The oncology landscape has changed radically over the time period that SUNRISE was planned and executed. I/O’s are NOW on the market and many combinations are already in clinical trials. Bavituximab has got to be in the mix NOW.
I’m hoping that the CC this coming Wednesday will shine some light on the plan going forward. However I am taking a new tack with this investment…Like many here I’m now significantly underwater. At nearly 69 years old my focus has changed. It’s about living life to the fullest and enjoying every day as if it’s my last. So I will be playing golf this Wednesday morning as I have for a long time. I will come home mid-afternoon and sit at my computer and read the several hundred posts that will be posted, listen to the re-play of the CC as I sip my wine…and reflect.
Here’s what I HOPE will happen over the next few months
Management will make every effort to negotiate a decent partnership, one that includes a significant amount of up front money and milestone payments
The poison pill will be allowed to expire. An interested party will offer an unsolicited buy-out offer. Other interested BP’s will counter that offer…Management can pick and choose…
Che sera, sera…
Regards
golfho
Good morning CP…
It looks like we are completely in agreement…Again…!!!
Oh…And by the way, Tradero responded to a post from jg1234 last Saturday when jg1234 posed the same question…Why did he raise the same question again about drop-outs…???
Tradero post #253034
MY RESPONSE:
Because I’ve expended a significant amount of time creating an enrollment projection…
Because my PRIMARY goal when I started to post on this board in 2009 was to calculate the RISK/REWARD proposition of this investment...
I take calculating probability VERY…VERY…Seriously…
I understand that these two posts (Your #253842 & exwannaby’s #253321) address calculations presented to this board by CP & tradero…
I also note that you responded to one of my earlier projections…(#253029) which I did not respond to.
I propose that we both try to understand what the other person is saying so that at the end of this process a better…global understanding can be achieved.
I’ll start with your two comments from different posts:
Hi Danny…
CP...
Just catching up on all of the posts…
From a previous post:
Truth be told...
It was 49 degrees in Sarasota this morning...Too cold for these old bones to play golf...
Bad news is that I had more time to read this board...
I have 14 people on my ignore list...
That's not enough...!!!
I'm getting frustrated with all of the negativity. PPHM is in the best shape that its ever been.
Just the share price is behind.
I'm going to go out and take a long walk...
Ohmmm... Ohmmmm...
Regards
golfho
I wrote this response to a post that I read a few minutes ago…
It’s still worth a read.
I realize that this is an exercise in futility…But I’ll try none the less.
From this:
http://finance.zacks.com/nasdaq-delisting-rules-7450.html
We get this:
(NOTE: There are many other sources)
Deficiency Notice Triggers
Failure of a company to meet a minimum closing bid price of at least $1 for 30 consecutive trading days can trigger delisting. When this happens Nasdaq issues a deficiency notice to the company. Another action that brings a deficiency notice is a company's failure to file periodic reports by dates specified by the Securities and Exchange Commission.
Receipt of Deficiency Notice
Any Nasdaq company receiving a deficiency notice has four business days to file an 8-K form with the SEC or to issue a press release to announce the notice. However, reporting failures require a company-issued press release. The company must provide the deficiency notice’s receipt date, unmet listing requirements, and action plan. The company must send a copy to Nasdaq before issuing the press release.
Return to Compliance
After receiving a deficiency notice, a company has 180 calendar days to return to compliance. A company warned about its shares' minimum bid price must achieve a closing price of $1 or more for 10 consecutive trading days during this period. Report-filing offenders must file the required reports, and then must file subsequent reports by the due dates.
Additional Grace Period
If a company with a minimum market value of $1 million in shares held by non-affiliates satisfies the other listing requirements, it may receive a second "cure period" of 180 calendar days. To receive this, the company must notify Nasdaq of its intent to correct the deficiency. Nasdaq may exercise its discretion in determining whether it believes the company can cure the deficiency.
Delisting Letter
If a company fails to comply with the minimum requirements during the first grace period or any second grace period, Nasdaq will issue a delisting letter to the company. As with the deficiency notice, the company must notify the investing public of the delisting letter within four business days, by filing an 8-K with the SEC. The company then can appeal its delisting to the hearings panel.
Hearing Process
Once a company receives a Nasdaq delisting letter, it has seven days to formally request a hearing. This request effectively halts the delisting process until the panel renders a decision. At the hearing, the company must present a detailed plan to regain and maintain listing compliance. The panel may consider the company’s financial strength, general market overview and historical pricing.
Delisting and Appeals
After the seven days, Nasdaq delists a company. First it suspends trading of its security, then it finalizes the delisting. If a company appeals but the panel rules in favor of delisting, Nasdaq gives the company 15 more days to further appeal to Nasdaq or in federal court, but it begins final delisting procedures.
OK…
GOT IT…???
1- 30 consecutive trading days can trigger delisting. When this happens Nasdaq issues a deficiency notice to the company. The last date that PPHM closed above $1.00 was 1-28-16. That’s only 6 trading days to date. 30 consecutive trading days brings us to 3-10-16…Got it? Now ANY day during that period between now and 3-10-16 the PPS closes above $1.00 the clock is reset…Got it…???
2- IF the share price remains below $1.00 for 30 consecutive trading days a deficiency notice is sent to the company and the company must report that to the public.
3- The company then has 180 calendar days to return to compliance. A company warned about its shares' minimum bid price must achieve a closing price of $1 or more for 10 consecutive trading days during this period. That bring us to 9-7-16…Got it…???
4- If a company with a minimum market value of $1 million in shares held by non-affiliates satisfies the other listing requirements, it may receive a second "cure period" of 180 calendar days. To receive this, the company must notify Nasdaq of its intent to correct the deficiency. That bring us to 3-4-17…Got it…???
My question to you is…
DO YOU REALLY THINK THAT PPHM WILL REMAIN BELOW $1.00 AND NOT RISE ABOVE IT FOR LESS THAT 10 DAYS FROM NOW TO 3-4-17…???
If you do sell NOW
Regards
golfho
Thanks...
It is the published report for this IST:
https://clinicaltrials.gov/ct2/show/NCT01264705?term=bavituximab&rank=10
Slowly but surely...
Regards
golfho
FWIW...
They added a new site for the breast cancer trial...
California
https://clinicaltrials.gov/ct2/show/NCT02651610?term=bavituximab&rank=3
Regards
golfho
How I got there…
This in response to exwannabe’s & tradero’s posts of a few days ago.
Ex, there are several questions that you raised in your post that I would like to discuss further however, I’m not sure that I fully understand the details of your questions.
Gentlemen...
I just returned from a round of golf and had an opportunity to catch up on reading this board. Unfortunately I need to move along...Dinner with wife & friends...
I will try to address questions later this week (Golf on Mon. & Wed)...They don't call me golfho for nothing...!!!
Regards
golfho
Some interesting factoids...
As of December 9, 2015, there were 229,701,808 shares of common stock.
39,622,557 shares of common stock reserved for issuance under outstanding option grants and available for issuance under our stock incentive plans;
2,090,892 shares of common stock reserved for and available for issuance under our ESPP
273,280 shares of common stock issuable upon exercise of outstanding warrants; and
45,745,760 shares of common stock issuable upon conversion of our outstanding Series E Preferred Stock
321,299,554 shares are outstanding or reserved for issuance at a later date.
So now we know why the request for an increase in authorized shares from 325M to 500M was needed in October.
Subsequent to October 31, 2015 and through December 10, 2015, we sold 1,939,413 shares of common stock for aggregate gross proceeds of $2,261,000.
Subsequent to October 31, 2015 and through December 10, 2015, we sold 1,925,844 shares of common stock for aggregate gross proceeds of $2,371,000.
Average price per share for the 2 ATM sales were ~$1.20
Total cost & expenses 2013: $50,035,000
Total cost & expenses 2014: $58,107,000
Total cost & expenses 2015: $77,280,000
Total cost & expenses ½ year 2016: $46,772,000
I choose to be conservative and assume that the rate of expenditures will remain about the same for the second half of the FY that will end on 4-30-16
~$46M
From which we can subtract money already raised through the ATM from 10-31-15 to 12-9-15 = ~ $4.6M
Additionally we can subtract AVID I projected revenue per management guidance. (~ $30M to $35M less ~ $18.9M realized in the first half = ~ $11M to $16M) = ~ $25.4M to 30.4M by end of FY.
Other factors are:
1- Additional revenue from AVID II
2- reduction of cash on hand.
What is implied…???
Baring any significant positive news or cash infusion we end the 2016 FY with ~255M to 260M shares outstanding. (I assume ~$1.00 per share)
On to SUNRISE…
Historical data for Docetaxel suggests that a MOS number for a similar health level of patients is about 10 months. I arbitrarily select a margin of error of +/- 20%...That yields an 8 to 12 month range. It’s a little bit more difficult to establish a range for Bavituximab + Docetaxel so I will select what I consider a reasonable number…Like 13 months and select a larger margin of error (+/- 25%). I then started to review the rules for Permutation and Combination…Whoa…!!! Cowboy…That yields a very big number…!!! In an attempt to save my sanity, I chose to use only whole number and used a manual binary search. I know…I know…Some of you are saying…The old boy has finally lost it…Tsk…tsk…
What am I saying…??? There are many potential outcomes that are, or becoming, virtually mathematically impossible. They would be the projected low MOS numbers i.e. 10:8, 11:8, etc.
What else…???
A picture is worth a thousand words:
1- The first look-in will most likely occur within the next few weeks. (2 to 4)
2- We will most likely complete enrollment within the next two weeks.
As Couch says often…The rest is noise.
Regards
golfho
FOCUS ON 2016…
OK I can stop saying that now…Because we are here…!!!
And…???
What can we reasonably expect over the next 12 months?
END OF SUNRISE ENROLLMENT
While I am just slightly disappointed that we didn’t complete enrollment by 12-31-15 we should acknowledge the fact that we have over 90% of the expected enrollment complete, and currently have sufficient patient enrollment based on the assumptions of the study to allow the trial’s planned interim evaluations and final readout based on the primary endpoint of overall survival.
So we know that we have enrolled (582 X .9 = 523.8 ) 524 patients as of 12-10-15.
OMG…
I look at my SUNRISE ENROLLMENT PROJECTION SPREADSHEET and for the scenario of an average of one patient every 4.5 to 4.75 months (137.6 to 144.6 days) enrollment will complete around the end of January to the beginning of February. In that scenario my projections calculate that the number of patients enrolled at the 2nd week in December mark was…526 patients…!!! At this point I feel more confident in my projection and when “Enrollment complete” is announced, I believe within the next 4 to 5 weeks, I will update my projections.
START OF BREAST PII/PIII
I would have enjoyed the morale boost this announcement would have provided for the holiday season. After reading several of the recent posts by MH & eb0783 concerning the pressure on recruiting patients for clinical trials…I had to search for my old bottle of Prozac…!!! And I was doing so well…!!!
Yervoy+Bavi
This IST, as were most others, cheap but slow to produce results. I’m almost certain that they never enrolled the total number needed. Having said that, I would hope that the sponsor will produce a report on those patients that have completed treatment. A while back I thought that this might be worthy of a NYAS or ARCO presentation…But now…Not so much.
Durvalumab+Bavi
NSCLC: I agree with CP. I don’t think that they would initiate this trial until SUNRISE is complete. So a February or March start is reasonable.
Multiple solid tumors: This could start in the January or February timeframe.
PPHM will be running these two trials…To me that speaks volumes about the confidence that AZ has in its newest partner/collaborator. Not only is AZ supplying Durvalumab for free but I suspect that they will use there substantial heft to encourage recruitment of patients and doctors. Both of these trials could recruit patients rather quickly.
Financing
With the commencement of several new clinical trials and continuing data collection for SUNRISE I suspect that there will be a need for more money this year. How much…??? For now I’ll WAG it at about $60M for the year. This might be an interesting exercise for those inclined. At this point I’m not inclined…!!!
Good Luck and Happy New Year.
Regards
golfho
Hi MH...
PPHM has used K & L Gates in the past. How would you compare them to GS. Do you think that they (K & L Gates)are still involved is some way? They still do M & A deals...No? When I ask about "compare" I would like you to consider integrity as well as other criteria such as size, power & loyalty.
Thanks in advance for any insight.
I would also like to wish you and everyone else in this extended dysfunctional family known as the Ihub posters a very happy, healthy and prosperous new year...Especially to you Krak.
Regards
golfho
GREAT WORK…
NO…
REALLY GREAT WORK…!!!
I was waiting for the enrollment complete announcement before I updated my projections again but when I read your post this morning I reviewed my data and…
Well first, to your question of…
“Now, I am unclear on how many events will be needed for the 1st Lookin. I for one would appreciate some clear insight on this matter from any knowledgeable poster.
So I drew two possible cases:
a.166 events for 1st Lookin
b.200 events for 1st Lookin”
Nobody knows the number for “the predetermined number of events” for the look-ins. A while back there was a discussion on this board about that subject. One thing for sure is that it will not be a percentage of total enrollment (582) but most likely a percentage of total enrollment i.e. 80% or some fixed number like 500. For the sake of simplicity and totally arbitrarily I chose those numbers. 80% X 582 = 465.6 = 466 and 500.
I as well, modeled different cases of projected MOS numbers. You selected:
CASE1: BAVI 13 Months MOS. Placebo 9.9 MOS (13:9.9)
CASE2: BAVI 15 Months MOS. Placebo 9.9 MOS (15:9.9)
CASE3: BAVI 17 Months MOS. Placebo 9.9 MOS (17:9.9)
One of my cases; as it turns out is:
CUMULATED NUMBER OF EVENTS TOTAL (15:10)
Hmmmm…
So now we have two different people with two different approaches and a single comparison point…
What do we get?
Using the numbers above of 154 and 165 for numbers of events for first look-in and comparing them in your chart for case #2, it appears that the intercept points are, respectively…
Your projections:
466 EVENTS 33% = 154 early to mid February
500 EVENTS 33% = 165 early March
My projection:
466 EVENTS 33% = 154 late January
500 EVENTS 33% = 165 early to mid February
Our projections differ by only a few weeks and not having the right side boundary of enrollment set yet; I think that that is very confirming.
It also falls in line with SK’s comments in the last C.C. of early 2016 for first look-in vs. first half of 2016 in the previous C.C.
NOTE TO ALL READERS…
The above should NOT be used as investment advice…In previous posts I have labeled my projections as an exercise in mental_masturbation and written for my own amusement.
Moving on…
The bavituximab/Yervoy trial status. Prior to the C.C. I had hoped for a presentation at either NYAS or ASCO in 2016. I don’t think that that is going to happen. Recruitment was painfully slow and it appears that we did not achieve full enrollment. It addition, during the past two years since this trial started the SOC has changed. I hope, at the minimum they can garner enough information to demonstrate that Bavituximab can improve the performance of Yervoy and not add to the toxicity.
To me the most important event was the arrival of a much more pro-active and supportive collaborator AZ. In my view it allows SK to say to BMY…We don’t see the need for us to continue testing Yervoy at this time. The PD-1 and PD-L1 products that are entering the market are presenting to us a far greater opportunity for future growth.
Sniff…Sniff…
I smell something cooking…
Regards and thank you again tradero
golfho
Freudian slip...
I agree with your conclusion...
FOCUS ON 2016 (FINAL)
My first few posts this year started with the header:
FOCUS ON 2016
FOCUS ON 2016 Part 2
FOCUS ON 2016 Part 3
Well we are nearly there…
It’s been a long and frustrating 3+ years since 9/2012 but I believe that we are now in sight of the finish line.
The recently announced planned trials with AZ will commence soon. Sunrise will finish enrolling. The melanoma trial is fully enrolled and I hope that we will be able to present some data on this trial at the next NYAS meeting in February…though at this moment we are not presenting. Perhaps ASCO...?
http://www.nyas.org/Events/Default.aspx
Monday, February 29, 2016 | 9:00 AM - 5:00 PM
Emerging Approaches to Cancer Immunotherapy
Keynote Speakers: Renier Brentjens (Memorial Sloan Kettering Cancer Center), Jedd Wolchok (Memorial Sloan Kettering Cancer Center)
Speakers: Jane Gross (Emergent Biosolutions, Inc), John Hunter (Compugen Ltd), Jane S. Lebkowski (Asterias Biotherapeutics), Jens-Peter Marschner (Affimed AG), Charles Nicolette (Argos Therapeutics, Inc), Charles L. Sentman (Dartmouth Geisel School of Medicine), Roland Walter (Fred Hutchinson Cancer Research Center)
Emerging strategies for Cancer Immunotherapy are changing the face of cancer treatment. This symposium will bring together experts in immunotherapy and immunology to discuss emerging approaches, challenges, and opportunities in this evolving field
In the interim I’ve been keeping myself busy playing with numbers…It’s a pastime.
For nearly two years I’ve maintained and modified projections on the Sunrise trial. I’ve traded notes with several posters during that time. My latest version narrows down the enrollment rate to a range one patient enrolled every 4.0 to 4.75 months (121.6 to 144.6 days)
That is represented in three scenarios noted below. On of which will go away in 5 days.
I will now ramble on…
For the average of one patient every 4.0 to 4.25 months which represents 4 months and a week (121.6 days to 128.6 days) enrollment will complete around the beginning of November and that didn’t happen.
For the average of one patient every 4.25 to 4.5 months (129.6 to 136.6 days) enrollment will complete around the end of November to the beginning of December.
For the average of one patient every 4.5 to 4.75 months (137.6 to 144.6 days) enrollment will complete around the end of January to the beginning of February.
This will be the first reality check. Did we complete enrollment by the end of 2015 or not. We did not complete enrollment early (November) so the first scenario is looking poorly. If we complete enrollment on time (December) then the second scenario is in play. If we complete enrollment late (January-February) then the third scenario is in play.
We will know this within the next ~35+ days.
The next issue for me is when the two scheduled look-ins will occur.
We have been told that the look-ins will occur at the 33% & 50% point of a predetermined number of events…And we don’t know the number.
The only guidance the company provided was at the last CC when SK was repeatedly asked about the companies anticipated look-in time frame and finally deviated from his standard answer of “We are not prepared/able to provide any guidance at this time” to…Within the first half of 2016 for the first look-in and around mid year for the second.
Here are my assumptions on number of events and most recent updates.
Assumption #1 is, assume that 80% of total enrolled patients (80% X 582 = 466) 33% of 466 is 154 and 50% is 233
Assumption #2 is, assume a fixed number of patients enrolled I chose 500. 33% of 582 is 164 and 50% is 250
For MOS I chose a subset of possibilities 7, 10, 12, 15, 18 & 20 months. I then selected several combinations of the above subset that might represent some possible outcomes. i.e. (10:7) or (15:10) etc.
What has my three scenarios indicate to date?
Scenario #1 In general for some of the very low MOS numbers the event trigger would have already occurred. For some of the very long MOS numbers the event trigger for first look-in will not occur until the February to March time frame and for the second look-in around the March to May time frame.
For scenario #2 (Enrollment complete at the end of December) the very low MOS numbers the event trigger would have already occurred. For some of the very long MOS numbers the event triggers remain fundamentally the same as the first scenario.
For scenario #3 (Enrollment complete at the end of January or beginning of February) the very low MOS numbers the event trigger will occur between now and December. For some of the very long MOS numbers the event trigger for first look-in will not occur until the February to April time frame and for the second look-in around the March to end of June time frame.
So what can I conclude now with only the above information?
The pattern appears to me to indicate that the MOS numbers must be on the high side. Once we have a date for complete enrollment the average rate of enrollment will be known and the rate of events will be constrained to a narrower number of possibilities. My goal is not to predict the MOS numbers. My goal is to determine the time frame for the two most important SUNRISE milestones, first and second look-ins AND more importantly predict the outcome for these events.
From a previous post…
Now for my interpretation of certain words:
Possibility: I use this term to define things that can occur regardless of the odds.
Probability: I use this term to define things that can more likely occur and generally I try to attach a percentage of probability (Odds) of it occurring.
This is the interesting part…IF the MOS numbers are tracking towards a ratio of 15 months for the Bavituximab combo vs. 10 months for placebo combo then my predicted number of events for first look-in indicate:
Bavituximab combo = 30 to 40 events
placebo combo = 120 to 130 events
What are the odds (probability)?
28%...A little better than 1 in 4
That implies that there is, in my view a 28% probability that the trial could be stopped at the first look-in.
Not likely…But possible with a 28% probability.
SECOND LOOK-IN:
Bavituximab combo = 70 to 80 events
placebo combo = 150 to 165 events
WELL NOW…
What are the odds (probability)?
47.6%...Nearly a 50-50 proposition…!!!
Slightly less likely then likely by only 2.4%
Some other thoughts…
IF full enrollment is achieved by 12/2015 and the treatment cycle takes about 4 months then all patients will have been treated by the end of April 2016. If the first look-in occurs as management predicts in the first half of 2016 then HOW AND WHY WOULD OR COULD THE IDMC STOP THE TRIAL FOR SAFETY…??? Almost everyone would have received the full course of treatment. What are they going to do…??? Suck the treatment out of them?
Here’s another thought…
There has been some discussion on the board on the topic of the IDMC recommending stopping the trial at the first or second look-in and the impact of that stopping. Here’s my take; if the IDMC recommends that the trial be stopped in either look-in it will have ZERO impact on the results of the trial…ALL patients will have had their full course of treatment, the only thing left is continuing the data collection that would be on the sponsors nickel. Do you really think that PPHM would not spend the extra money to get the full data set? The money is in the plan already. If the IDMC recommends stopping the trial it is implied to me that that means that they think that there is enough evidence to recommend seeking marketing approval from the FDA before the complete data set is achieved. Implied is that the interim data at one of the look-ins is overwhelming. Does anyone really think that all of the patients would be lost to further follow-up?
Regards
golfho
Hi CP;
I don't have specific info on that...
But, I think that that is a reasonable interpretation.
Regards
golfho
I was thinking...
A well placed back of the hand to the face...
or...
A Greek mothers "FAPA" applied to a misbehaving child's head...
or...
An Italian mothers wooden spoon applied anywhere...
In any case I'm enjoying the moment.
To all attending the ASM...Any and all information/observations will be greatly appreciated, public or private.
Regards
golfho
The point being...??? EOM
Please understand...
This is not addressed to you specifically...
But to everyone expressing a desire for management to explain, justify, clarify the need for an additional 175M authorized shares...
Has anyone tried to contact IR and request more information?
Has anyone tried to contact the company and request clarification?
Of the nearly two dozen poster complaining about lack of explanation/justification has ANYONE contacted management to request more details?
OT...Analogy...
People have gathered at the railroad station...Why?...Because the train has been arriving late for years...They all start to complain about the shoddy service, lack of management responsibility to the ridership...Yet...Nobody...I mean nobody...Has taken the issue to management.
Nope...
Lets just sit around the train station and complain amongst ourselves.
How about asking for more color...???
Regards
golfho
I would like to respond to this statement and your response to it. First I agree that with only the publically available information any projection is a WAG (Wild_Ass_Guess). As a retired engineer I like to refer to my WAG as a SWAG (Scientific_Wild_Ass_Guess)…Results are sometimes a bit different…Sometimes not…!!!
I started making enrollment projections around the end of February 2014. At that time there were only 9 sites added to the list. 1-Dec, 3-Jan and 6-Feb. I was becoming concerned that at that pace we could never achieve the goal of completing enrollment by 12/2015. March was dismal as well, then came 5 consecutive months with double digit additions with May peaking at 38 sites. The surge in new sites added between April 2014 to August 2014 (120 sites) gave me some hope that we could achieve our enrollment goal. We still (9-9-15) have management reassuring us that we are on track/target for completion by 12/2015. Note that the 5 months surge in site openings will produce periodic surges in enrollment. (Perhaps that is the source of the hockey stick statement…!!!) With only 3.5 months left in 2015 I think that it is reasonable to assume that their projections are on track/target. I would like to state that, if we roll into January I won’t have a coronary event. Simple math produces the number ~3.75 patients per site for the entire trial. A casual glance can tell you that that’s not going to fly…Why…? Because sites were added over a 17 month period. Which is why I created a slide rule projection spreadsheet. Primitive…But effective. What’s implied? IF the projections from management that we are on target to complete enrollment by 12/2015 still hold, then enrolling 582 patients by 12/2015 MUST produce an overall average, modified by the rate of site activation and its periodic surge. Mumbo…Jumbo…Bla…Bla…Bla…
I submit the following commentary…
From: mmignot
Quote:
________________________________________
Although SK estimated the 1st look in to occur during the first half of 2016, I believe he is being ultra conservative with his estimate. My belief is that both lookins will occur much sooner than stated.
________________________________________
From: exwannabe…
SK has information that none of us have. The enrollment numbers (which is more than just completion date), events-to-date and the actual trigger point (33% of what).
All true…However if one chooses to speculate…Then a reasonable number can be assigned to “Trigger points”. I think that either you or Jbain came up with a reasonable 80% of enrollment as a fair number. With that as an assumption then 33% = 165 patients and 50% = 250 patients. My calculation, based on a patient enrolled, on average every 4 months concludes that first look in will occur around October. I add the periodic enrollment wave using my slide rule spreadsheet and conclude that the first look in must occur between 10/2015 and 1/2016 otherwise:
1- Enrollment will NOT be completed before 12/2015
2- Patients are living longer…Much longer.
3- Some really funky enrollment pace is occurring.
With that data, we all could make reasonable predictions. But w/o them we are really taking wild guesses.
YES… absolutely yes…I favor my SWAG
If the second look was expected (by SK) in the first half, his statement would not be conservative, it would be a lie. Regardless of when it actually happens, he can not give a bogus estimate.
With all due respect, an estimate is just that…An estimate. Let’s assume that SK knows the exact number of patients enrolled and the exact number of events. How could anyone assume that with that data and that data alone one can reasonably predict the next patient enrollment or event? Under the circumstances a conservative estimate is the prudent thing for management to provide.
So SK does NOT expect the first look before mid '16 (unless you think he would blatantly lie, which I do not). And so it is unreasonable for any of us to expect such an early look.
My calculations allow for the possibility of a MOS comparison of 7:10 up to 7:15 and several other possibilities in between. In my view…If we are still on track for completion of enrollment by 12/2015 then one of two things must be true:
1- Both arms are doing extremely well or…
2- Bavituximab is kicking some serious butt
Regards
golfho
Fair enough
All things considered...
Why are you here...???
golfho
A very likely scenario...
Sad...Truly sad.
Regards
golfho
NEW NUMBERS…
A few weeks ago I changed some of the numbers that I have been using in my “SUNRISE ENROLLMENT PROJECTION” spreadsheet. After reading exwannabe’s post pointing to the error in assuming that first and second look-in would occur at the 33% & 50% of total enrollment I changed the number of events based on what appears to be a reasonable assumption for “preliminary reporting of clinical trials” that is ~80% of events. 80% of 582 is 465.6…So let’s go with an even 500 (86%) That would then yield at 33% 165 events and at 50% 250 events.
Again management has stated that enrollment was on track to complete by EOY 2015. All 3 scenarios that I continue to update are:
1 - First patient enrolled within 2 month and an additional patient enrolled every 4 months there after per site.
2 - One patient enrolled per site every 4 months.
3 - One patient enrolled per site every 3 months.
All 3 scenarios project enrollment completion before 1-1-16 (Sept, Nov, & July respectively) NOTE: the enrollment scenario #3 can be discounted in August as being to aggressive.
Other considerations…The MOS for each cohort.
I now modeled 4 different MOS possibilities:
7 Months
10 Months
12 Months
15 Months
For various reasons I’ve allocated 7 & 10 months as very possible MOS’s for the control and 10, 12 & 15 as very possible MOS’s for Bavituximab…
I fully understand that these assumptions are pure guesses but some of my rational goes like this. The historical MOS for Docetaxol is ~7. Two recent Docetaxol MOS numbers came in at ~10. Bavituximab never failed to achieve a result greater that 10 but I included that number for Bavi just in case…12 & 15…I think that these results are believable and obtainable numbers in a healthier patient population than the PII trial had.
Here are my revised and expanded assumptions at the first look-in using the revised event number of 165:
For Scenario 1:
MOS for the Bavituximab arm = 10 months with 51-66 evented patients
MOS for the Bavituximab arm = 12 months with 12-33 evented patients
MOS for the Bavituximab arm = 15 months with 2-5 evented patients
MOS for the placebo arm = 7 months with 103-124 evented patients
MOS for the placebo arm = 10 months with 51-66 evented patients
Data distribution was similar to the PII data and the std dev was similar.
The projected time frames for the first look-in for different MOS assumptions are:
CUMULATED NUMBER OF EVENTS TOTAL (10:7) June 2015
CUMULATED NUMBER OF EVENTS TOTAL (12:7) July 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:10) October 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:7) September 2015
I know…June has passed and some combinations are not represented but at the end of the day…between NOW and 10/2015 at the latest for this scenario, we will hear about the first look-in.
For Scenario 2
MOS for the Bavituximab arm = 10 months with 51-66 evented patients
MOS for the Bavituximab arm = 12 months with 12-33 evented patients
MOS for the Bavituximab arm = 15 months with 5-6 evented patients
MOS for the placebo arm = 7 months with 103-124 evented patients
MOS for the placebo arm = 10 months with 51-66 evented patients
Data distribution was similar to the PII data and the std dev was similar.
The projected time frames for the first look-in for different MOS assumptions are:
CUMULATED NUMBER OF EVENTS TOTAL (10:7) August, Sept. 2015
CUMULATED NUMBER OF EVENTS TOTAL (12:7) Sept., Oct. 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:10) Nov., Dec. 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:7) Oct., Nov. 2015
For Scenario 3
MOS for the Bavituximab arm = 10 months with 36-52 evented patients
MOS for the Bavituximab arm = 12 months with 7-14 evented patients
MOS for the Bavituximab arm = 15 months with 1-2 evented patients
MOS for the placebo arm = 7 months with 102-123 evented patients
MOS for the placebo arm = 10 months with 36-52 evented patients
Data distribution was similar to the PII data and the std dev was similar.
The projected time frames for the first look-in for different MOS assumptions are:
CUMULATED NUMBER OF EVENTS TOTAL (10:7) June, July 2015
CUMULATED NUMBER OF EVENTS TOTAL (12:7) July, Aug. 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:10) Oct., Nov. 2015
CUMULATED NUMBER OF EVENTS TOTAL (15:7) Aug., Sept. 2015
I wrote this in my May post:
“I have tried to understand and get additional information about Statistical Significance in clinical trials. In March I made a public request on the board for any enlightenment on this subject. Without any additional input to the contrary I will post what I consider as possible outcomes for the two look-ins.”
AND:
Now for my interpretation of certain words:
Possible: I use this term to define things that can occur regardless of the odds.
Probable: I use this term to define things that can more likely occur and generally I try to attach a percentage of probability (Odds) of it occurring.
AND:
“With the above assumption, in both cases, we could achieve Statistical Significance with the second look-in and achieving a P-value >.01”
“So…My calculations indicate that it is possible that the trial could be stopped at the first look-in and there is a good probability that the trial could be stopped at the second look-in.”
I still stand by those statements above.
As I stated in an earlier post my projection spreadsheet is more like a slide rule that a calculator. The columns are monthly dates and so are the rows. The number of sites that were opened for that month is inserted in the appropriate row for the first time and then inserted in the associated column at the rate for that assumption.
If anyone would like a copy you can e-mail me at:
akagolfho@gmail.com
I intend to go to the ASM in Oct. and hope to meet some of the interesting denizens from this board.
Regards
golfho
I thank both of you for this important observation...
I was using the same assumption as CP WRT the number of events vs. total enrollment.
Gotta go...
I'll post revised numbers later.
Regards
golfho
I think that Bungler addressed that...And Thanks
Please note responses in red below
Quote:
WHY WE ARE AT $1.50:
There are many factors that have affected our share price over the years. Why you choose to ignore the most important one I find a little surprising. In September 2012 we were well on our way to concluding a $2B deal with Abbvie. We were…Well call it what you want…Botched, Intentional miss-labeling, willful failure to follow FDA rules or Sabotage. That single one event caused us to suffer through nearly 3 years of continued dilution. Over 100M additional shares had to be sold to keep this company moving. With the number of shares then and the current market cap we would be at ~$3.00 right now. If the NSCLC PII trial was not tampered with we would have had marketing approval in 2013 and only required to perform a confirmatory PIII trial with less patients. Question to you is. With Abbvie marketing team selling Bavituximab and their research team behind development of applications and clinical trials, what do you think the PPS would be today?
1) NO DRUG CURRENTLY APPROVED.
TRUE
2) LOSES TEN OF MILLIONS EVERY YEAR.
TRUE
3) NO LATE STAGE RESULTS TO BE RELEASED ANYTIME SOON.
You need to define “Anytime soon”
4) ONLY ONE DRUG IN DEVELOPMENT AND THAT DRUG HAS NEVER HAD A SUCESSFULL BEYOND QUESTION LATE STAGE TRIAL(STAGE TWO OR GREATER).
That one drug as you call it has BROAD read VERY BROAD application. If you don’t understand that after 16 years invested in this company you need to reevaluate.
Reminder WRT “SUCCESSFUL BEYOND QUESTION LATE STAGE TRIAL”
Nobody would sabotage a placebo…Something that could seriously upset the financial order?…Much more likely.
5) NO PARTNER TO FUND PLANNED EXPANSION(YOU KNOW WHAT THAT MEANS) DILUTION HERE I COME.
NO PARTNER/COLLABORATOR YET…
QUESTION: WHAT HAS HAPPENDED IN 2015 THAT WOULD MAKE A PARTNER COME ABOARD NOW:
1) PRE-CLINICAL DATA- PLEASE NOT WHILE I AM EATING.
I don’t think that anyone is saying that. Do you…?
2) MSK COLLABORATION- NICE TO HAVE BUT WILL HARDLY CONVINCE SOMEONE TO FORK UP $100,000,000 PLUS. AGAIN, YOU NEED A SUCCESSFULL LATE STAGE TRIAL TO DO THAT.
I don’t think that anyone is saying that either. Do you…?
ANYONE NOTICE THAT THE PIPELINE ON THE WEBSITE HAS BEEN UPDATED. APPARENTLY, WE NO LONGER HAVE ANY ONGOING PHASE II TRIALS. IT IS GOING TO BE YEARS, FACE IT. I KNOW, I HAVE WAITED SIXTEEN.
Don’t know how to address this one.
Quote:
I HAVE A QUESTION AND WILL TAKE NOTE OF THE RESPONSES.
IF THE COMPANY FUNDS THE COMING TRIALS BY DILUTING THE CURRENT SHAREHOLDERS, ARE THEY DOING US A DISSERVICE?
MY ANSWER IS AN UNEQUIVOCAL YES. THE COMING TRIALS WILL NOT BRING RESULTS FOR YEARS. WHY NOT USE THE FUNDS CURRENTLY AVAILABLE TO FINISH PHASE III?
I can’t speak for management. However I can speculate…
“WHY NOT USE THE FUNDS CURRENTLY AVAILABLE TO FINISH PHASE III?”
The have sufficient funds to complete the PIII trial. They are planning additional clinical trials to broaden the application for that “One drug” They have not announced how they plan to finance this yet. I suspect that they are currently formulating a plan to finance. I have no idea what that plan will be. I only have what I think are possible avenues.
PLEASE INCLUDE A YES OR NO IN YOUR ANSWER SO IT IS CLEAR WHO STANDS WHERE. LET US SEE WHO IS WILLING TO GO ON THE RECORD.
Hope this helps…And gives you an idea of where I stand. Please reply with detailed answers that includes you investment plans going forward WRT PPHM.
Take your time and think about it.
I need to get going now. I have to start to getting ready to go out to a friend party. I’ll check in tomorrow.
Regards
golfho
Focus on 2016…Part 3
Why have I started most of my posts this year with the statement “Focus on 2016”?
Because…
The frustration level of many long posters has had a very detrimental impact on the overall psyche of this board. No matter how hard we humans try; it remains virtually impossible to detach our emotions in major decision making events. But if you want to be a successful Biotech investor you need to have a keen analytical mind. You MUST be able to separate your emotions from your thinking process and most importantly…You must have the “Patience of Job”.
“Partnership coming to fruition in the coming year” That one statement spawned a THOUSAND posts. Many of those posts were deriding the management or BoD of PPHM.
“List of upcoming catalysts” That list spawned another THOUSAND posts. Most of those posts were mocking in nature.
I could go on listing the many banalities posted on this board…But what’s the point.
If you are invested in this stock on the long side, your two main concerns are:
When will the price go up?
When will YOU exit?
If you are on the short side it’s:
When will the price go down?
When will YOU exit?
Simple…NO…???
I’m long this stock so I have no interest in the short proposition.
NOW ABOUT…FOCUS ON 2016…
I have been tracking and attempting to project into the future the SUNRISE trial milestones that need to be accomplished to achieve a successful outcome. CP has made similar calculations. Our calculations differ to some degree but are well within an acceptable margin of error.
Milestones:
Enrollment is complete
First look-in
Second Look-in
Preliminary data readout
Final data readout
Submission of BLA
FDA approval
FWIW here are my current calculations:
Enrollment can complete between ~July 2015 and Nov. 2015
First look in can occur between ~July 2015 and Sept. 2015
Second look in can occur between ~Oct. 2015 and Dec. 2015
Note that for the above three milestones CP’s calculations produce a slightly earlier date for each but again, they are well within an acceptable margin of error. I will stick with mine as any optimistic projects are always met with…Well you know.
Now for my interpretation of certain words:
Possible: I use this term to define things that can occur regardless of the odds.
Probable: I use this term to define things that can more likely occur and generally I try to attach a percentage of probability (Odds) of it occurring.
What can be gleaned from ClinicalTrials.gov
Preliminary data readout: Not defined on website but it could be after last enrolled patient is treated. 12/2015 plus ~4 months = 4/2016
Final data readout: = 12/2016
Submission of BLA: Technically this would occur some time after final data collection. In that PPHM has Fast Track designation that allows for rolling submissions the BLA could be submitted within 30-60 days of final data collection = 1/2017 or 2/2017
FDA approval: Up to 4/2017
So what am I saying…???
I’ll tell ya’
IF the SUNRISE TRIAL is the most important event AND frustration is your primary emotional state then set your eyes on the end of 2016 and step away from reading and writing on this board and clearly…don’t read the following.
I have tried to understand and get additional information about Statistical Significance in clinical trials. In March I made a public request on the board for any enlightenment on this subject. Without any additional input to the contrary I will post what I consider as possible outcomes for the two look-ins.
Here are my assumptions at the first look-in:
MOS for the Bavituximab arm = 10 months with 66 evented patients
MOS for the placebo arm = 7 months with 124 evented patients
Data distribution was similar to the PII data and the std dev was similar.
Here are CP’s assumptions:
MOS for the Bavituximab arm = 12 months with 67 evented patients
MOS for the placebo arm = 7 months with 127 evented patients
I add that data distribution was similar to the PII data and the std dev was similar.
With the above assumption, in both cases, we could achieve Statistical Significance with the first look-in and achieving a P-value >.01
Here are my assumptions at the second look-in:
MOS for the Bavituximab arm = 10 months with 124 evented patients
MOS for the placebo arm = 7 months with 180 evented patients
Data distribution was similar to the PII data and the std dev was similar.
Here are CP’s assumptions:
MOS for the Bavituximab arm = 12 months with 101 evented patients
MOS for the placebo arm = 7 months with 191 evented patients
I add that data distribution was similar to the PII data and the std dev was similar.
With the above assumption, in both cases, we could achieve Statistical Significance with the second look-in and achieving a P-value >.01
So…My calculations indicate that it is possible that the trial could be stopped at the first look-in and there is a good probability that the trial could be stopped at the second look-in.
What’s a “Good probability”…???
In my view…2 out of 3, 66%
Why 66%...???
Because I have to factor in the possibility that the SOB’s are not finished messing with us.
I fully understand that the first look-in is primarily for safety and futility. But IF my calculations on P-value are correct I can’t see how the DMC would NOT stop the trial and allow those patients still under treatment to receive Bavituximab instead of the placebo.
A note on partnerships/collaborations:
I agree with CP’s current assessment with regard to the agreements that management might be envisioning. I still believe that management is looking for regional agreements, possibly up to three; the US, Europe and Asia. I also believe that they want as much control of Bavituximab’s development as possible. I will admit that I am frustrated as well with the pace of progress and angry at the events of 9/2012. But, I also recognize and acknowledge that management were victims as well.
Two final notes:
OT: 1- The reason I’m posting this today is because I developed a severe sinus/bronchial infection and can’t play golf today…See what happens…!!!
2- I’ve re-arraigned my fall schedule. I fully intend to go to the ASM this October. I spoke to Chris and asked what the data for the ASM was. He stated that the date was not yet firmly set but most likely it would be on the 15th or the 22nd. I’m looking forward to meeting all of the posters that intend to go to the meeting as well. Looking at the remaining months of this year (Calendar 2015); we will have ASCO where I hope to hear news on the Yervoy combo. We will have our Annual report (Mid-July); at the CC I hope to hear, at the minimum, continued good news on enrollment (On track) and perhaps an announcement of some meaningful collaborations.
Time will tell
Regards
golfho
I need a little help…
In understanding, and more importantly, calculating how to determine the P-value or statistical significance of my projected results for the first look-in.
My goal was to determine whether there would be sufficient data points (~192 patients) to determine whether statistical significance would be achieved at the first look-in assuming that the MOS assumptions I make are achieved.
I was able to find definitions of the abstract concept and even some online calculators. All of which require more information than I have available, such as, the full data set, the calculated std dev for each data set, the null hypothesis (Not greater than 2 months…?). Are we using the statistical significance of two means formula?
Here are my assumptions:
MOS for the Bavituximab arm = 10 months with 66 evented patients
MOS for the placebo arm = 7 months with 124 evented patients
Data distribution was similar to the PII data and the std dev was similar.
Here are CP’s assumptions:
MOS for the Bavituximab arm = 12 months with 67 evented patients
MOS for the placebo arm = 7 months with 127 evented patients
Data distribution was similar to the PII data and the std dev was similar.
Calculator:
http://www.answersresearch.com/means.php
FWIW the calculator concluded that the results would be statistical significant.
exwannabe…??? Jbainseky…??? Sempre…???
Anyone with knowledge of statistics…
Thanks in advance
Regards
golfho
Focus on 2016…Part 2
Reviewing the list of 15 Docetaxel PIII clinical trials provided by FTM a while back provides the following data:
The lowest MOS was 5.7
The highest MOS was 10.4
The Mean for MOS in the 15 trials was 7.7 months with a Std. Dev. of 1.3
That indicates that the range for the most likely MOS in our PIII trial for the control arm is 6.4 to 9.0.
In our sabotaged PII trial we achieved an 11.7 MOS. There were no other trials conducted with this combination for this indication.
Some important thing to remember:
The pre-combined MOS for the control arm was 5.6…Lower that the lowest MOS from the FTM data set. I don’t think it would be prudent to assume that we would see that again. The combined control arm was calculated to be 7.3. That is at least within the range of the historic data and close to the mean.
We now know that the 2 look in are planned at ~194 and ~291 events.
I used this info to adjust my enrollment modeling tool. I use the average (9.7 rounded up to 10.0) of the MOS from historic Docetaxel data (7.7) and the PII Bavituximab data (11.7) and came up with the following:
I make four enrollment per site assumptions:
1 - First patient enrolled within 2 month and an additional patient enrolled every 4 months there after per site.
In this scenario the first look in will occur around: Sept. 2015
The second look in will occur around: Oct. 2015
Enrollment will be complete by: Sept. 2015
2 - One patient enrolled per site every 4 months.
In this scenario the first look in will occur around: Dec. 2015
The second look in will occur around: March 2016
Enrollment will be complete by: Nov. 2015
3 - One patient enrolled per site every 3 months.
In this scenario the first look in will occur around: Oct. 2015
The second look in will occur around: Dec. 2015
Enrollment will be complete by: July 2015
4 - One patient enrolled per site every 6 months.
In this scenario the first look in will occur around: Feb. 2016
The second look in will occur around: May 2016
Enrollment will be complete by: July 2016
In summary:
First look in can occur between ~Sept. 2015 and Feb. 2016
Second look in can occur between ~Oct. 2015 and May 2016
Enrollment can complete between ~July 2015 and July 2016
The only way that this trial could be stopped on the first look in for favorable reasons would be if the patients in the control arm evented at a historically high rate and simultaneously; the patients in the Bavituximab arm evented at half that rate. That would project an MOS at the very lowest range for the control arm (5.6 to 6.0) while Bavituximab comes in again at a similar or better MOS than the PII results of 11.7. I don’t see this as a realistic probability.
FOCUS ON 2016…
FOCUS ON 2016…
What else…???
I think that all of us are waiting on news about partnerships/collaborations. I am hoping that the latest shelf registration is in anticipation of starting several combo trials with other IO candidates. I’m hoping for an announcement with details that include a non dilutive source of financing. (Early Christmas List)
Regards
golfho