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tech, I think you are absolutely right that the SK comments on which I asked here for clarification were related to front line NSCLC. I appreciate you straightening me out on that, as requested. It also appears that "central reads" vs. "domestic reads" implies a difference between foreign and US test sites in that instance...an implication only. Applying the comments to pancreatic trials does not make sense. Remember, I stated up front that I needed clarification on what my notes implied, and received that clarification from you and Nuke and FTM. At this point a hypothesis that the snafu involved foreign testing sites or techniques is reassonable, but, as stated, is only a hypothesis. Appreciate the input.
NUKE, I think you are right! That's why I was reluctant to post those notes because I was not absolutely certain of the context. That's also why I asked for help and clarification. So thank you. That's also why I was not always (ever) an A student. I remember now that King was talking about BOTH first line NSCLC and Pancreatic in almost the same breath, and I must not have gotten the 1stline designation in my notes cuz things were going so fast. Yes, I agree. He must have been talking about 1st line NSCLC and not pancreatic. It DID sound like domestic (US) centers were getting better results than foreign centers in that instance though, fwiw.
roger1, interesting stuff thanks
learning curve, absolutely terrific article. This is a sad situation,and a problem well above the level of PPHM management and attorneys, all swept along in the current. Probably the only sabotage is the entity (PPHM or a competitor) that blew the whistle, or focused the light of discovery on the problem. And worse, those responsible, operating in the background, are obviously manipulating the stock price. Get to the bottom of it indeed. Enormous implications, and as you point out with the referenced article, not a new problem.
Friday Wrap: USS Peregrine becalmed in the doldrums during the dog days of summer, afloat despite a disastrous blow to its bow while under full sail, fully healed-over, all hands aboard, and all supporters ashore, exhilarated. The cause of the gaping hole in the hull? The smoking gun ashore, or the one OFF-shore? Was it a torpedo or did it originate in the hold? Would the Chinese, with their Cotara news black-out want PPHM bankrupt? Would the Swiss gnomes in Rochetal, Genentec's alpine chateau, be pleased? How about the Russians? We know the Indians would not stoop to industrial sabotage, say, inflating results or mis-staging disease. Inside job? I don't think so. Carlton Johnson, board chairman grumbled, "...until we get to the bottom of this..." And now we have an "internal investigation," a smokescreen or reality. If the FBI, Interpol, and the FDA are all over this thing, it would temporarily be classed "internal". The stuff for a novel...a costly one... fascinating. The seriousness of the situation reminds me of when PPHM almost crashed and burned before being able to move "signal seeking" Bavi trials to India where a few investigators there got a good look at it, and turned in favorable clinical results. Then Russia, and ditto. What's going on?! I held out the following ASM content because is so ...uh...sobering, and also difficult to interpret. Did anyone else get this? Here's a direct transcription from the ASM:
"PII pancreatic ca w gemcitabine
not clear how drug was tracking.
similar results in both [testing sites???]
discordant response in two groups
differences in central read [foreign centers?] vs. local hospitals… put off interpretation
MOS to be reached late this year or early next year. Too early to tell .
Pancreatic: completed enrollment June this year.
Primary endpoint MOS? “WHEN? end of this year or beginning next year
Okay crew. Any ideas? The beginning of the end of FDA-sanctioned foreign trials? Is that what SK was intimating? That there is trouble with the Bavi pancreas trial also? If corners were cut anywhere it was in going offshore for trials. But before the flak starts flying, I'll say management had no choice. The thing nobody here wants to see is that the US trial sites did not show the significant effect for Bavi that the foreign centers did. Anyone else hear this and put it together better than I did? How did I make it through med school taking notes like that?
north40k, if you'd believe that from Wildhorses you'd believe anything!
PS. Enjoyed meeting you and your lovely wife. How fortunate you are to have an MD/attorney (for a biotech co. yet!) on your side. Further...I'm not even old enough to be your little bro.
nice heartfelt post Dr.R. My instinct is that the longer we wait on results the better our chances of getting positive feedback. As said before, rotten/useless information is easy to recognize. It seems that anything positive salvaged from the PII data must of necessity be coupled with FDA reaction to it, and that is liable to take some time and negotiation. The data at this point is meaningless unless sanctified by the FDA, or unless it is smashingly good enough (original results confirmed)that PIII is a fait accompli.
pgg, dammit, good thinking. You said, "We were going [to ASM] but the cost compared to the share price made me feel like buying more [PPHM stock] if I was going to spend anything..." Yes. That's a lot of shares I cudda had. Hey, on the ASM subject, I must say one of the most satisfying parts of the trip was meeting all the young [really! young from my perspective] people who read this board and don't post. One of them said at dinner there are 5500 retail stockholders, and if age ratios are similar between attendees and stay-at-homes, we have many young, bright people involve here. One other point, it isn't that I necessarily believe SK and Garnick when they say they think Bavi works, but they really don't have to say that with lawyers lurking by their sides if they know the opposite to be the truth. Flagrant stuff happens. We hear about it every day in the news. But it is one positive byte of information imo, that's all.
bioBS nice post. welcome.
tech and gandolph: a young attendee...lots of hair...handsome...taking copious notes.
I confess. That would have been me!??!
volgoat, I didn't get the feeling the blame has changed. I got no feeling about that at all. However, one day after BlackMonday I said, "do the math", and I'll say it again. The reality is that when looking for efficacy and safety, there was obviously tumorcidal activity in Bavi, and probably acceptable side-effect profile, regardless of all the possibilities of massive/slight over/underdosing or even mixing with placebo. That is basic. This was a dosage study, though, and that is problematic...and will remain so. I've also said before that the biggest issue is whether there was staging "creep", with some less advanced cases in the study. The answer to that is, if randomized, the "creep" should affect all groups equally. Another way of saying all this is, suppose an FDA officer says to SK, "It appears Bavi has anti-cancer activity and acceptable safety. You did a PII to establish optimal dose. What did you conclude in that regard? What dose level do we use for PIII?" All the above imho only.
techwriter, well-written summary. thanks. One of the most interesting comments was master of ceremonies, Carl Johnson (attorney at law), said in relation to the PII snafu, "when we get to the bottom of this." I thought it an interesting choice of words.
Hey tek, whoah! I think you have an entirely wrong take on what happened today. There was no warm fuzzy feeling, and not even any fruit punch. If your gut tells you we're worse off than one year ago, I think you should reconsider. Where does this come from? "It sounded a 1000% worse than what we were hearing before where CSM botched the job and it would be weeks to get answers. Now it sounds like many months, more dilution, loss of a fair amount of credibility amongst the investment and scientific community." I was there an didn't remotely get those impressions.
You said, "the CEO of this company allowed the early release of news of the company's lead candidate before all was made right." I don't think he had a choice but to do exactly what he has done. I won't comment on,"This punished and even torture many dedicated and loyal longterm shareholders!"
senrex, take a deep breath. regretably, in my one-on-one discussions with Steve King I did not come away with a very gratifying feeling about Cotara. I asked him why on earth we have no data out of China for lung cancer after all this time, and he deflected the question with vague references to the poor quality of the trial designs there. I asked him specifically about the possible need for more Cotara PII and he hedged that one too, saying, when asked specifically, that what the trial number PII, PII_III) was did not matter so much as that the regulatory pathway was clearly defined. It sounded as if they would dearly love to find a home for the orphan. I told him if I were sitting on the FDA I would ask how we establish that Cotara-I131 delivered directly to tumor bulk is better than I131 alone without Cotara. He said he thought that Cotara did help get tumorcidal doses of I131 to tumor core. I muttered that the catheter might be able to do that too. I asked if a more "modern" construct of Cotara (DNA-histone seeking) MABs were in the pipeline, venturing that Cotara is kinda clunky. He said that one problem with a more streamlined missile is that its "pass through" is faster and more of a problem too.
We touched on the virtues of fully humanized vs. chimeric Bavi, and I told him that was the only area of difference I had with PThorpe, and SK backed up the inventor repeatedly by not only mentioning other chimeric MABs (Rutuxin) that seem to work "time and time again" in the same patient without causing allergic reactions. He said, "of course we wanted to construct all-human Bavi, and we did it". When asked about 2C3 he didn't have much of a response other than to say Affitec was moving forward with it in Russia. Amen
eb0, no doubt in my mind that the message was they were [sic]"very close" to a deal involving board seat, and also the use of the phrase "when we get to the bottom of all this" was telling. I've said here before that an inventor's enthusiasm for his invention must be excused as normal. SK's enthusiasm for Bavi must be from a position of great inside knowledge and also at least some wishful thinking. When an MD looks me in the eye and says I think it works, when he's seen all the information out there, I give that a least some weight in my considerations. How well does it work? I said years ago I think Bavi will eventually be approved, and that it will be a squeaker. We'll see. Here are some of my notes on PII Bavi NSCLC: "PII NSCLC randomized study
discovered inconsistencies. reevaluating study. detailed, ongoing, how long? can’t rush thorough, complex,
testing of investigational produts; testing patient samples; reviewing operations of multiple vendors, their activities. goal is to gain a thorough understanding of discrepancies.
Where we want to take this program." The last sentence is a puzzler. One would think they know where they want to take the Bavi program....
nuke, here are my notes: gawd knows what some of it meana:
PII pancreatic ca w gemcitabine
not clear how drug was tracking.
MOS to be reached late this year or early next year.
Too early to tell.
Pancreatic: completed enrollment June this year.
Primary endpoint MOS “WHEN? end of this year or beginning next year.
wook, there was tension, but all was cordial. Probably about 30-40 stockholders; Many employees. Most of management was there. I am 99% certain Garnick was there, but he didn't say anything, and I was talking with King afterward, so didn't get to introduce myself. There was security aplenty. One was ex-LAPD who I chatted with for awhile. Elegant surroundings. Great food tidbits: full-blown bagel treats, hard boiled egg bits, sour cream, onions, chives; all you could drink java; fruit; donuts, and bottled water. First-class meeting all-in-all, except content was almost totally boiler plate. I'm glad I came.
SM Snippets:King: "Bavi IMAGING will be looked at for MULTIPLE DISEASES, such as Altzheimers and arterial disease
King: "Promising PIIa lung and breast ca data"
King: "One more study to run with regard to registration pathway on Cotara"
King: results onfrontline NSCLC and pancreatic. The former MOS has not evented.
L. Johnson re. PII snafu: “we’ll get to the bottom of this”
Lyle: "potential partners still interested: they want to see PII results"
When is PPHM getting more board members involved with industry/biotech?: "we were in the process, and it was put on hold due to PII snafu. "we were “close”
private conversation with King: "I can say this, "I believe Bavi works"
aykayeh, local color from Irvine? Dinner at Buco last night with IHub PPHM stockholders was greatfun. My flight from SFO to JohnWayneAirport(!!) was 30 minutes late, and when I arrived about 8PM, all (15-20) were assembled in a private room at a long table reminiscent of DaVinci's portrayal of the last supper, with FTM (free the mice) at table center and virtually everyone present who had said here they would be...and more. Quite a diverse group, really, with a surprising and gratifying representative of very young people (almost all old enough to trade stocks though). There were no PII surviving patients present we could relate to, and no PPHM execs. Everyone had ordered by the time I arrived, and so I was told not to, that we would share what promised to be large portions of pasta, calamari, etc., and we were not disappointed on that. I had a large Peroni on tap, and was interested to see that about half those present were drinking tea/water, and the others beer and wine in moderation, auguring well for today's performance. I would rate the food "okay", but I am a foodie. The price was perfect! At one point I said to FTM, "we are paying for your dinner tonite," and he said, "I did the same thing you did. I didn't order anything." Very nice evening, all-in-all, and some great folks involved here. I suffered an unprovoked upgrade at the Wyndham to a "king-suite" which was imo entirely appropriate. The bar was still open so I had an Amstel lite. At my age I didn't even cause a blip on any of the lovely radar screens sitting about there, so retired alone about 11:30 to my king-suite where I am typing this. We are all dedicated to bringing back a scoop to the board, so stay tuned....
Hey nelgglen, welcome out. Nice post. I too was with RB board until it got "too wild" (your words). This latest twist with Bavi-imaging + Genentech has some pretty amazing implications imo.
good stuff FTM. What do you make of the Genentech connection and interest? I am getting even more enthused about the future of Bavi imaging.
holo,good idea. FTM, welcome back. Glad U2 will be there.
gandolph, I am in general agreement with your reservations about the incommunicado stance of management, but from an MD point of view I have always found it to a shame that if one expresses any kind of thoughtful response to a bad result in which one is a participant the attempt at doing what is right can cause loss of livelihood, reputation, home, and emotional stability. Attorneys have insinuated themselves at the top of the food chain, and we must abide by that at the moment. For reasons we probably do not understand now, and might never, I believe in this case the public interest and safety will be served, and that is what everyone in a position to make decisions will be considering. Not the stockholders, and not the management.
keep_trying: thanks for the excellent weekend posts, as always. You are one of the mainstays of this board. Sorry you won't be able to join all the [putative] celebrants at dinner the night before the stockholders meeting. I agree with the other posters here expressing the hope that the long period from BlackMonday to present is a favorable sign. It doesn't take nearly as long to decide if the information is unsalvageable, as exactly what to do with it. If there were only a glimpse of any other trial results with Bavi which are now in process, I'm sure the FDA and everyone else involved in the decision would like to see them...for obvious reasons. I'm adding small amounts each week so I can't kick myself too hard either way. Good luck all.
okay PPHM choir. rehearsal Wednesday nite at Buca di Backhoe.
Let's do "Is this capitulation?" to the tune of "[Is it] Fascination". Or, alternately, "It's capitulation time" to the tune of It's Howdy Doodie Time. Let's face it. Even [especially]the old-timers here are gasping and clutching their chests in pain and shortness of breath [egSOB]. No more resilience here. I'm bent. I'll take anything big pharma wants to dole out, and accept any lamebrain excuse. Gimme two bucks! But wait, I'm going to buy 50k more on Monday so I can break even at that price. Avid? A better anti-angiogenic than Avastin? Cotara? Fully humanized Bavi? Imaging? Yes...all of it out! Flush it with the 1mg or was it 3mg vials of Bavituximab. It's all so harrowing. Thanks guys for keeping the site alive while all the old-timers are taking a breather, and trying to talk the bank out of repossessing. I'm spending it all to get to Orange County. Stayin' where I can WiFi abscess my on-line brokerage account just in case sumpin' breaks loose. CJ and FTM: dinner on us at Buca...still.
holotawoopas...yours is my vote 4 post-of-the-week. And the ending: perfect: "nuf sed?" Here goes: "Sept. 10 CC Paul Lytle,,,
Another potential source of capital we are focused on pertains to our unencumbered pipeline. As you can imagine, given the bavituximab result that we shared with you on Friday, our partnering activities are continuing at a very active pace as we move closer towards the end of Phase II meeting with the FDA. Our stated goal is to have a partner on board before we start the Phase III trial and preferably, before the end of Phase II meeting with the FDA, as we would like our future partner to be a part of that important meeting."
"Unencumbered pipeline!" nobody's talking 'bout it here 'cept yoo and me holotawoopapas. Suppose he was talking about Cotara? What a freakin' headfake this whole thing has been. Who on Earth has the hootspa to pull it off and stand back, head shakin'? Surely not the Russians, Chinese, or Indian moollaahhhs. Those of you will be saved who had rudimentary statistics or win consistently at Texas hold'em.
horselover and attendees stockholder meeting: Dinner Wednesday at Buca di Beppo - Irvine 13390 Jamboree Road, Irvine, CA, 7:30 PM. The reserved room is under name PEREGRINE. I arrive 7PM OrangeCoAirport, hopefully, and will taxi there. Please start the celebrations without me if I'm late!
pphmtooloong, great post. L'dOL. What's best for the patients is actually going to be the outcome here, believe it or not. There's an enormous amount of intellectual energy focused here.
jmeyer, good question:you wrote, "Reading through Thorpe's work, it appears that exposed PS mimics [is a normal event in] apoptosis, and Bavi exploits that mechanism [no, Bavi does not exploit that mechanism. Cancer exploits that mechanism. How? because "flipping" cell membrane -PS inside out is a part of normal cellular senescence and death, so -PS on the outside of cancer cells "masks" the underlying cancer, making the body immune system think the cancer is just normal dying cells.
You asked, "when PS gets exposed and the cancer cell mimics apoptosis, it can avoid T-cell's attack (despite the tumor anti-gen), but how does it[the cancer] avoid the clean up system such as macrophage/phagocyte unlike the cell which goes through normal apoptosis?" Answer: routine macrophage garbage collectors are not equal to the task. Its a war. Too little, too late. Too much -PS, too many cancer cells. The -PS on the surface prevents lymphocyte recognition of abnormal cellular DNA. Bavi binds to the flipped -PS, thereby unmasking underlying immunogenic cancer cells to the immune police who photocopy the foreign material and develop a clone of cells that remembers it as foreign, continuing the attack.
vanessapu. you're the one. eom
dia, agreed. I seriously doubt that the "real" results of Bavi PII NSCLC trials will be materially different than those we've seen, and think all the players have a very good idea of how effective this approach is going to be to prolonging meaningful lifetime to those with the disease. If the side-effect profile is close to what we've been led to believe (and there are a few gaps there too), then the most sensible solution to this conundrum is to allow a PIII trial of Bavi in less seriously ill patients as co-therapy with SOC, including Bavi+Irradiation. Anti-PS is not going away, so it would behoove the DrWests of the world to stay tuned and keep reading about it. The science is compelling because it is so sensible. The company is so valuable because it has the experience with humans.
iandy, my impression, FWIW, is that Dr.West has only a superficial appreciation of critical factors at play with Bavi in specific, and PPHM pipeline in general. Non-scientist non-clinicians must listen to someone, that is true, but in this case Dr.West can barely be considered more than a pundit on this subject, not an expert. His overall thesis is sound, "if it seems too good to be true it probably is". I'll say it one more time: PPHM is worth much more than today's face value if you totally subtract this "iteration" of Bavi. Look over some other aspects of the company and get back to us on it.
loof, thanks, but IMO you remain the paladin of punsters here.
Spanky, are you suggestin' PPHM is, in fact, the dominatrixin in this drama, crackin' a whip at all those groveling M&A guys? And Carboat calls us delusional.
Fri.wrap. Welcome to all new PPHM passengers temporarily trapped aboard. Get used to it. At least the prose, fiction?, is occasionally compelling. We, the crew, continue efforts to fathom whether the severe jolt felt last Monday obliterating forward progress was slack water; dead air; or running aground while cutting too close to the rocks of certain offshore interests. Word on the street is someone missed a payoff, usually at the bottom of a bust. But no immediate news out of the FDA, and no countersuit from the "3rd paty" all augur well IMO. Compared to the stakes, collecting from the bagholder is chump change, so it looks like everyone is cooperating (except the bottom feeder attorneys clearly not trying to facilitate a cancer cure) to continue moving good ship PPHM toward a ecstatic greeting by waiting patients. It is telling that this bord has been co-opted primarily by market technicians and traders, with law suits walking on and off stage threateningly. The best part of that is that FTM and the science guys get a well-deserved literary pause. Interesting that PPHM fully owned subsidiary MAB manufacturer Avid gets no respect, and the frabjous PPHM pipeline is utterly ignored in this fixation on Bavi. My sense of it is that the FDA is not going to say no, and would love to drag its feet until a peek at Bavi/Pancreas trials can give them one more leg to stand on. More likely the announcement will be as early as next week that the decision has been made to allow Bavi to progress to PIII, thus leaving the window open, but prolonging the suspense of Bavi long-term efficacy. Personally, I am ready for a dose right now.
geo, agreed. I posted on D[for debacle]Day, "do the math", and if what we've told is accurate re test problems, you are right. The only factor that concerns me (and only a bit) is the possibility of incorrect staging, which can obviously make an enormous difference in results, but have been told that is not the issue.
learning curve, I've had that feeling for years. I think when the "white knight" BP emerges we will have an opportunity to look back and say, "I told you so". That phenom and suspicion has been ongoing. The only suspicion I have regarding this latest debacle is the timing of the announcement.
jakedawg, hoorah. The idea of unwarranted optimism (based on information then available) from any quarter related to PPHM is simply silly and malignamt conjecture. The past actions of all the principals involved, from UTSW, Thorpe, Garnick, Gerber, and PPHM management is not consistent with deliberately misleading anyone. I am not a finance or market guru, but it is clear that PPHM is now in a radically oversold position, and I think that would apply even if this "iteration" of Bavi is a total bust...and we know that is not true. I repeat: the original strategy was to use Bavi as a MAB missile capable of carrying a payload, then we found out on the way to marked that "naked" unloaded Bavi works curious effects on the immune system. We saw terrific synergy with Bavi and irradiation therapy, but for financial reasons were forced into trials in India using Bavi in combination with chemotherapy. Now we are unsorting data about Bavi + Chemo in far-advanced cancer. The science is intact and moving forward despite impediments popping up right and left.
Stockholders Meeting: dinner the night before at Buco di Beppa at 7:30. I arrive JohnWayneAirport 7PM and will cab there. See y'all there!
In the same line of reasoning....We know double-armed MAB missile BAVI has great specificity for hypoxia [environ of low oxygen supply-stressed cells, especially the non-mutating cancer blood vessel lining cells, the endothelial cells. Once coupled to the cancer blood vessel endothelial cells Bavi stimulates ingrowth if immune cells specialized at slowly destroying [embolizing] cancer blood vessels. Bavi has a "PPHM exclusive cancer docking site" with mindboggling potential. By binding to the "flipped" cell membrane phospholipid, MAB Bavi has also been dicovered to unmask the cancer as a foreign subastance...not body. We have wondered for decade how cancers evade the immune system. Thorpe and anti-PS investigators have discovered the cause: -PS. When that cell membrane building block flips outside edge in, that signals the body that normal cellular death is proceding. Not to worry. Flipped PS is sine quo non (defines) a normal cellular arc of senescence and death. Other immune cells are called to the area to clean up the mess made by chemo-, irradiation, and surgery, AND sample the cancer to which the cells begin to manufacture "immortal" self-cells that have developed a memory to the fact that the mass is malignant...not self, and then launch a longstanding attack on the cancer. So Bavi is an immunomodulator (it [favorably] affects the immune system, upregulating it. Repeat, Bavi only makes traditional therapy more efective at this stage. Wait until Bavi, a double-armed MAB, can carry cancer poison with it to the tumor. The doubgle-fisted MAB rocket conjugated to a cytotoxin was how this Bavi strategy has evolved against cancer. Along the road to discovery it was discovered that "naked" Bavi packs a statistically signicant wallop all by itself. .