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KT, thought provoking. you must be a fast typist! NSCLC is a tough nut. You have to see it (in your family, or in the hospital) to believe it, and to turn advanced lung cancer around or hold it at bay is ...miraculous? I am not looking for a miracle. Nothing about the NSCLC trial results would cause me to sell. And of course any improvement at all, with Bavi's safety profile, will bode well for its extensive use in less-sick patients. If Bavi succeeds in a significant way in blocking tumor vessels, and helps the host develop immunity to tumor... it will find use on every cancer treatment table. Regardless of NSCLC outcome. What do we have for certain now? A safe, and apparently specatacular labeling agent fir diagnostic and therapeutic imaging...and also a certifiable MAB mule that one day can also deliver cytotoxin to tumor. If I had to pick between Cotara nd Bavi for lung cancer, though,I would take a slimmed-down version of PPHMs anti-TNT MAB, Cotara.
thanks mojo. krakanos, the answer.eom
RRdog and/or others: what's your take on the company selling marketing rights and retaining manufacturing rights for Bavi?
Thanks
Threes (and KT), as you know, I am not one to split hairs when it comes to survival statistics, but the conumdrum you are batting around about mean and median survival is intriguing. It is especially so when you consider the advanced cancer cohort is so variable in their proximity to death, as constrasted, for instance, with clinical trials for rheumatoid arthritics, or pain medication, or obesity. IMO early deaths would not be nearly so important as prolonged survival, yet waiting for the last few in the cohort to die before calculating mean survival does not seem practical either. Interesting. I'm sure someone has a reasonable and logical explanation for how this is dealt with. After all, the FDA is a part of the government. (!?!)
north4k & wildhorses(#82850), great posts on buy-outs. thanks
KT and Volgoat, regarding virtues of murine/humanized MAB Bavituximab, the most interesting thing I've seen is Volgoat's last post about binding site specificity decreasing with more fully humanized MAb Bavi. I can imagine that murine MAbs probably have a more general immunoexcitatory phase than murine too. The whole idea is to convert cancer into a chronic disease like diabetes so that patients can live productive lives while being "carriers". If Bavi can prevent growth of metastases as anticipated and can be used periodically for maintenence, it will be a true treatment advance.
CJ & FTM, why do you think the slides were pulled?
FTM, let's keep our fingers crossed on that one. If it's true I'll take you to lunch.
I think the Nobel Prize for Medicine committee is the faculty at the Karolinska Sjukhuset ("sickhouse" or hospital) in Stockholm.
A question for the scientists here: What's your take on Thorpe's assertion that chimeric Bavi is as good as human anti-PS antibody? He must be talking about current short-term dosing regimens and not chronic administration. Also, surprised by his answer to whether Bavi works better in less severely ill patients: "They'are all pretty sick" is not much of an answer, even though true. That information is pretty important.Intriguing that Bavi helps body defences develop immunity to a cancer cell line; that Bavi seems to work well with almost all anti-cancer agents; that it is probably active against non-solid cancers, such as leukemias and lymphomas; and that after it induces tumor vascular collapse Bavi turns on the actual tumor cells. Things are really going to get interesting when we can use Bavi in treating smaller tumors rather than end-stage disease.
Thurly, you were absolutely right about the importance of listening to Thorpe presentation:
http://www.nyas.org/MediaPlayer.aspx?mid=25e51622-c908-46ef-bba1-95ca6a814eed
Friday wrap-up. I sense other medical clinicians and researchers here in addition to market gurus, bench scientists, biostatisticians, and other business specialists, all great at literary expression. We are here because PPHM platform is so reasonable in application, elegant in conception, and imminently sensible in a clinical setting. As a practicing physician who deals with head and neck cancers, I would definitely take either drug, Cotara or Bavituximan, and prescribe both. PPHM's radioactive iodine MAB shuttle rocket, Cotara is a logical approach to solid cancer, where it attacks necrotic core cancer cells, as is the entirely new and different anti-PS platform, PPHM's Bavituximab, a MAB that docks on an exclusive cellular surface site. PPHM has a virtual monopoly on anti-PS by virtue of the company's extensive safety and efficacy trials. The anti-PS antibody Bavituximab attaches to diseased cells, stimulates the body's scavenger immune cells (monocytes)to enter the disease area, and the MAB knocks out cancer blood vessels by attacking feeder artery endothelial cells. And this is the beginning. Fully humanized varieties are on the horizon. Bavituximab is almost certainly more effective when used in combination with irradiation therapy than with chemotherapy. Probably an unbelievable amount of improvement in radiation responses with Bavi. Best for PPHM, the company has its own in-house FDA-approved MAB manufacturing facility, Avid, with high output capacity. In the past two weeks PPHM company officers have been unusually sanguine in their appraisal of emerging survival data, one respected former-Genentec key scientist described it as the most compelling phase II data he has seen. However, exact numbers from PPHM cancer trials are still pending, and an investment today remains speculative. It is my opinion that PPHM professional managers, scientists, and board members of have to date comported themselves with the utmost integrity, and have never overplayed future possibilities. The board and management have made mistakes, and necessity has forced so moves up blind-alleys, but PPHM properties are "the real deal", and in my opinion will be applicable for treating enormous numbers of patients for many years. The price explodes when the money players are all lined up...especially if we stockholders continue to understand the value of the PPHM pipeline.
cloaked protector, been told lately how appreciate your input?! Your last, similar to all previous posts, was well thought-out and cogent. From the first day you appeared her to now you insight has been unique and helpful. Have a good weekend.
Noof, all this reminds me of "waiting for Godot", about how two guys divert themselves waiting expectantly (and vainly) for someone named Godot to arrive. They claim he's an acquaintance but in fact they don't really know anything about him except for what others have said, and readily admit they would not recognize him if and when they do see him. To occupy their time they eat, sleep, converse, argue, sing, play games, exercise, exchange jokes and insults, swap hats, and contemplate suicide – anything
Aw longshots,thanks. I've been hanging back to see if the leaders here ever looked over their shoulders for those oldsters they (and technology) have left behind. Still read the posts AVIDly, but have enormous professional commitments which today need me more than this board. Many of us did what we could when we felt our input was needed, and now can now hang back a bit because of the absolutely fantastic half-dozen contributors here whose dedication AND expertise is truly noteworthy...and comforting. I have, in the past few days, finally worked my way back to pre-split holdings, and am already spending my hard-gotten gains..again...and, of course, buying on the peaks instead of the dips. Because of my enslavement to the statistical method and its foibles, my position has been that the FDA is only going to move forward rapidly on a new drug that is not a "close-call" improvement in standard of care, and fulfilling events and results are shaping up in that direction with Bavi.
guys, "die vs. dye in the Rubicon"...hope it's the latter. And we all know what you meant. What's the substitution of one alphabet letter in a subject as complex as bavituximab? This note is mainly to thank U2 for the terrific dialog, and to reaffirm that several of us crossed the Rubicon a decade ago, and are getting old (and no richer) waiting for the baggage train.
mojo, what do you do in your spare time? great stuff. thank you. FDA has signaled it wants "wow" data points, efficacy even a blind, greedy politician or financier can see without graphs-- nothing subtle requiring mathmatical analyses. Another anticancer fromulary Medicare entry is huge dollars, and to date monoclonal antibody performance in the arena of solid-cancer killers remains mostly underwhelming. It IS coming though, and PPHM is moving up on the leaders in that field. At this point Peregrine, PPHM, AND MABs remain equally obscure to the public and investor eye. The goal is control.(!) Not cure. Cancer similar to diabetes. I am comfortable that PPHM is definitely a leader in that arena.
rolling with punches..12th round..ho hum..
down gazillions. a knock out will get it all back and more.
my money is still in PPHM. I do my homework and due diligence.
still think it's a winner. the greed on the street is amazing.
hey freethemice,sunstar,rrdog,mojojo, Jonson, and all you on the "biological" side of the reality equation (rather than numbers crunchers), thanks for making the board a most interesting site. Actually, I read most posts, and think all of you are good writers. Don't always thank you, but appreciate the effort. CJ especially. Targeted therapy? PPHM has it. Conjugates? Old hat at PPHM. Got MABS!!?? OMG, aplenty. PPHM has an FDA manufacturing unit, AVID, to cook them. Not easy. All this tech PPHM is good at moving forward onstage, and now in the New York Times. Why, everyone SHOULD know by now that PPHM has silos full of targeted MAB rocket winners, the next anti-cancer drugs that will move us closer to the goal of converting cancer into a chronic disease like, say diabetes, arthritis, or hypertension. Where's the bandwagon?
freethemice,thanks.glad you're still in the control group.eom
OH!freethemice, what would we do without you. right again. good thoughts. thanks
sunstar, thanks. you asked about "armed missile" Bavituximab, and the potential there. I've dampened my enthusiasm lately after Thorpe was quoted as saying that unarmed Bavi- looks as good as armed, and ditto with chimeric Bavis vs. fully human Bavi. Puzzling. However, there might be an unacceptable loss of "specificity" when one of the Bavi binding sites is loaded with cytotoxic agent. You can Google "truncated tissue factor" and see the work done on tumor vessel thrombosis caused by that agent, one studied by Thorpe in the past. There are a host of "small molecule" agents being tested for anti-cancer effects. The question is whether Bavi- or anti-PS MABs are the missiles of the future that will be used to shuttle these agents to specific docking sites on tumor...or if that will even be necessary. Star-wars is here.
stoneroad, traders hungry for pennies....
freethemice, agree completely. the problem is: if you think the potential of PPHM is astronomical; if I think it is enormous; can you imagine what the big players are thinking and what they can do about it (Have done) at this point. You and I will be proven right in the end. What is the best way to long-term holders to play it now? Wait and watch? Buy? Check into the ER for post-traumatic stress disorder?
stoneroad, if I had the cash I would definitely be a buyer big-time at this point. the downward pressure on the stock for so many years points to only one conclusion imo, and that is a buyout at a price that the buyers will be ecstatic about, new common stock buyers will be thrilled with, and old stockholders will reluctantly accept after being beat up so badly for so long. hindsight is going to be all that is left to us long-suffering longs. put another way, it seems to me that the only way I can make money in this stock, if at all, is to buy more now. realistically the book value is much greater than the price imo. interesting dilemma.
it is apparent there is sumpin' we don't know, or that the rest of the world doesn't know, about where things stand with PPHM at this point...the lack of response is astounding.
The recent trial data could very well have attained statistical significance, and it is wholly unrealistic to think Rob Garnick would endorse data that has not been adequately vetted. Simply won't happen. didn't happen. On the other hand, it is not clear why they would release data without fundamental statistical analysis included with it because it takes only minutes to accomplish. Several thoughts/explanations about that, but one is that it does tend to discredit any idea that the corporation is withholding and timing the release of important information. In the unlikely case the data is proven to be insignificant statistically, it would be ethically and investigationally unacceptable. I think we're okay here, and, in fact, bought some shares this afternoon for the first time in a long time. It seems almost inevitable that we are going to see some signicant overall survial data. Almost, I said.
bungler, short answer: yes. "p-value" is something everyone needs to know about a data set. Basic. No conclusions may be drawn without it. Sometimes not even WITH it. There are all different levels of statistics sophistication here on this board, at the FDA, and everywhere else, and those most versed in statistics know all the limitations of "p-values" and other statistical yardsticks.
Today's medical therapy makes an attempt be "evidence based", and essentially all evidence is "anecdotal" until it passes the statistical sniff test. That would be the "p-value" (and/or a dozen others). The most widely accepted bar is at at the p.=.05 level. As mentioned previously, it is like having a 100 chamber pistol with 5 bullets. The chances of these results being merely from chance and not real (if significant at the p.05 level) is the same as you firing a live shot. Most investigators shoot for far higher odds than that, ie 1 in 1000, but with limited sample size we take what we can get. Right now the data looks good, but is anecdotal. We'll see how it looks to the statisticians.
robertC, agree. this reminds me of my golf game. disappointment after disappointment followed by an incredible stroke right in the sweet spot. this data is "in your face" type information. That is, who can would bet against the huge likelihood of Bavi- having safe anti-cancer effect in humans. At this point anti-PS technology, and Bavituximab, is the kind of project any researcher would love to be involved in.
Stoneroad: short explanation for p value is this: What are the chances that the results obtained in this study, which show improvement with Bavi- over placebo, happened from chance?
Researchers begin an experiment obviously wanting it to succeed, (ie that Bavi works). However, the statistical format is called "the null hypothesis". We are going to hypothesize there is no difference between placebo and Bavi (and hopefully disprove it). Was the null hypothesis, of no difference, proven or disproven here? Probably disproven. It appears that Bavi is the real deal showing improvement, more than doubling overall response rate to medication (ORR), and improving median progression-free survival (PFS) by 50%. Everyone spins these findings differently, but nobody can deny the first impression of a definite anti-cancer effect in Bavi. However, there were only 90 patients in each of the two treatment groups, and the more patients, the greater the reliability of the results, statistically. In this case most experienced researchers with statistical backgrounds would probably say "there appears to be a real difference between Bavi and placebo." Are we sure? How sure? If the pvalue is better than or equal to .05, for instance, that means: If we run 100 tests just like this one the chances of having the same signifantly better results is >95%. So 95 times out of 100 we would be right. Russian roulette with a 100 chamber gun gives you 5 or fewer chances of getting hit. Here's Wikipedia on the subject of pvalue: "In statistical significance testing, the p-value is the probability of obtaining a test statistic at least as extreme as the one that was actually observed, assuming that the null hypothesis is true. In this context, value a is considered more "extreme" than b if a is less likely to occur under the null. One often "rejects the null hypothesis" when the p-value is less than the significance level a (Greek alpha), which is often 0.05 or 0.01. When the null hypothesis is rejected, the result is said to be statistically significant."
Note: all the above is cloaked in negatives, and therefore difficult.
geo, I respect your opinion in most posts, but do not agree that "if the NSLCL data is bad most shareholders will have a insurmountable climb back to see any money". How about this scenario: NSCLC data already factored into price? Imo PPHM stock price is underpriced today even if Cotara and Bavi were not on the table...or on the horizon. We are basically saying a whoe lot of PPHM's armementarium is worth zero, and only a corporate raider/acquiring interest could be satisfied with that appraisal.
sunstar, thank you for your valuable contributions here. Agreed Cotara is well below projected orbit. "Stall" comes to mind for a number of reasons. Pivotal to my calc.s is absence of an overwhelming "China effect". For years now the drug has been approved in that country for lung cancer, and probably off-label use. A leak of some kind seems inevitable if Cotara were a winner their, either in our stock price, rumor mill, or medical circles [publications]. Nothing. I don't understand it, based on concept elegance, but CAN connect dots when two entries into stage III trials are not pushed forward by PPHM or an intrested pharma.
Do not agree that NSCLC data will "decide things", other than reconfirm anti-PS MAB safety profile, a huge concern in light of expanding knowledge of anti-PS syndrome. And the pancreatic cancer and prostate cancer trials are at least AS important imo. It is even possible than not that Bavi will be used in a non-cancer application when all the dust has settled. Another app might be discoverered/decided when all the data from all the trials are crunched. Example: no cancers cured, but everyone noted a halt in the progression of their macular degeneration, arthritis, impotence, or depression. The FDA is interested FIRST in safety of an agent to be used in humans. The possibilities for this company and its properties remain strong imo. PPHM wholly owned MAB production facility, Avid, has been said here to be worth much more than present PPHM market cap. I can't vouch for that. It has repeatedly been said here also that PPHM stock could end up being the greatest asset in your grandchildren's next year Christmas stocking. All the above said, I report to you all that I am as disappointed (dazed) as y'all are. I have not given SERIOUS thought to selling, but it would be a lie to say I haven't thought about it numerous times. Cheers?
fTm, now you're cookin'(as usual). You're usually so "right on" that an occasional flight of fancy is to be human. Agreed there is probably a wide variation in representation of flipped -PS on tumor vasculature, and there might not only be a variation in that phenom. between mice and man, but there also might be a place for "pre-sorting" Bavi treatment "candidates" (if we can get this goose off the ground). Good thought. I believe Thorpe,et.al., have always used the modifier "most" when referencing solid tumor types. all imo
ftm,omg,wouldn't that be a kick in the os.
freethemice, this postulate is giving me a hard time, and seems to be contra- to all we know about solid tumors and -PS flipping.
saintsteven, where you been? welcome. Wish you'd say what you really think.
unpathedhaunt, nice. THE obvious application for Bavi
ftM:nice,very nice.tanx.
CJ&FTM..while the west coast slept. Amazing stuff. Thanks foryour efforts. I've posted here several times that I can't understand why PPHM had not pushed forward with a fully human Cotara instead of the clunky chimeric MAB being used, and you found that PPHM has had it since at least 2000, and licensed it to MerckeAG. Mind-boggling. So the paper at AACR deals fusing anti-neoplastic IL-12 to a tumor-binding antibody, NHS-IL12, the fully humanized Cotara-like MAB developed by PPHM, an antibody which also targets necrotic portions of tumors because of its high affinity for single- and double-stranded DNA, which are often exposed as tumors outgrow their blood supply. "NHS-IL12 may therefore be useful against a wide range of solid tumors, and mouse models can be used to study its mechanisms of action." Love it. Thanks again.
dogman1: a real eye opener. thanks