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thanks BCS Paladin. informative. eom
geocappy, good question. King's "disconnect" is probably the huge difference between MOS in pancreatic, and that in most other cancers. More specifically, he was probably alluding the difference in Bavi trials in first line lung cancer and pancreatic. He would not speak of the difference between pancreatic cancer and 2nd line cancer as a disconnect, or a huge difference in MOS. I traced this thread back to mojojo 111106. Very interesting. For those here who question why big dollars aren't pouring/pooring? into PPHM stock...I'm with you. At this point most people conversant with PPHM product would think it a great bet. The biotech speculative market must be off considerably...or is it just PPHM? Anyone?
Friday wrap: in 2 words:deferred gratitude.
Ridiculous.
Tenth year anniversary of Cotara's1st approval to move into PIII FDA trials. We stand poised...
Where are the Chinese? Come on. Cotara has been approved in China for several years for lung cancer...anyone think it curious there are no positive peer-reviewed literature out of China on TNT MAB Cotara in lung cancer. No negative articles either. None. Hey, it doesn't work?! Who knows. A black hole Cotara fell into. Cotara is stalled. Communications are seriously lacking here.
Reacquainted myself with posts on this board (and others) during that 10 years. Definitely not a stockholder dream, PPHM stock, during that decade. Still aboard Ship PPHM. I've said for years Bavi will be approved in a close call, and not by acclaimation. Reality has settles in. Still hope. Lots and lots of people still not in on the secret of Bavi's briliant and prosperous future. Bavi must pay dues like all other modalities that have fought their way onto the cancer treatment table. The cancer victims lose mostly. Retail PPHM stockholders get an orgasmic price bump when all the money interests are aligned. Getting "shelf space" in any market is ferociously competitive no matter HOW good the product. Mainly I would love to be a fly on an executive suite wall at PPHM to hear some of the proceeds. But retail stockholders don't rate even a fly's worth of info. I'll hold-em. What else can I do. Can't sell. I'm trapped PPHM ... until payday.
the key to Cotara success resides in China imo. eom
CJ, thanks! Agree, Stimuvax story fascinating. If FTM's theory of causation is correct, that Stimuvax trial failure is related to MAB production (purity/strength/biologic activity) failure, it would be interesting to know who manufactures the MAB. In house?
We can be glad PPHM has a FDA-approved MAB manufacturing facility, Avid. Most of us here can remember a large batch of PPHM MAB that was discarded due to similar issues. MAB mass production must be one of the more difficult industrial endeavors
Dew, good post. Thanks.
PGG: The BioBS post was deleted for reasons not clear. Anyone? The BioBS post was well-tailored but somewhat unorthodox...borderline heretical for PPHM stalworths. The BioBS post, in a nutshell, listed parallel expectations by expert PPHM Ih ub posters here, and by perceived experts posting for another biotech board, and the latter biotech crashed and burned despite all the positive crystal "balling" at this stage of development. BioBS's post was excellent because of the penmanship quality AND the reasoning, and seemed, skim-reading, no Ih ub rules were broken. My money is not on that side of the bet, so I can see how the five most assertively expert posters here might find comparing PPHM to a recent biotech wreckage offensive, he could conceivably be correct, and is definitely entitled to his point of view. BioBS asserted in post 110191 that he thinks Cotara will be kept "in house", and that could also be true because no fish are jumping out of the water to snap it up. The "Cotara reality" is closely tied to China. If China interests want it, they will have it. I've said here every three months, when all the big money interests are maneuvered into place for appropriately appeased greed, PPHM stock will be allowed to float free...and not until. I continue to believe that phospholipid membrane science has a place on the treatment table, as does an I131 delivery system. If diagnosed with lung cancer I would do my best to receive both Bavi AND Cotara. cheers!
bioBS, FAB. Post of the day...month...year?
bull,sounds like with etrade you must close out your margin position in unmarginable stock by the end of the trading day.
good one sunstar! eom
side-note perspective: close friend diagnosed recently with Hodgkin's lymphoma. Being treated at an excellent hematology-oncology department of an exceptional medical school by well-known and respected oncologist. When I mentioned the possibility of using Bavituximab with standard of care, and that patient was willing, he said, "I am not familiar with it". When I gave him a thumbnail sketch his non-sequiter response was, "We DO consider MABs for refractory/non-responsive cases. I repeated the Bavi spin, and the IST possibilities that (by inference) could increase his fame and cure rate...that Bavi could be added to standard of care...and...and...
Interestingly, I had similar experiences with clinical oncologists with Erbitux when that MAB was at a more advanced stae in clinical trial than Bavi. The point behind this post is that many here know much more about Bavi than most clinical oncologists. It takes time. It's monkey see/monkey do. And, "first do no harm".
until 2k, nice post, great prose. eom
nice post biopharm. very interesting. thanks eom
thanks green and lurker. FTM, any theories why Hodgkins lymphoma and not non-Hodgkins lymphoma?
anyone remember seeing anything about Bavi and lymphoma?
Most amazing is that we are just scratching the surface (no pun) an anti-phospholipid (surface)MAB-technology, and PPHM has a enviable lead in human testing. More important, PPHM has the proprietary MAB recipe(s), and the FDA approved MAB manufacturing facility for production. If trial numbers are good as we think there is no reason why PPHM cannot go it alone. Almost as important to the investment community for future biotech developments are the several roadblocks and detours encountered in the gene therapy field in the past few months. It does not look as if the MAB approach to disease is going to be supplanted by that tech in the near future. Cheers, and congratulations to PPHM Tustin,Phil Thorpe,PhD, and UTSW Dept. Pharmacology!
jbainseky and thurly, I am not certain on what statistical basis you are drawing your conclusions. Can you elaborate? These numbers have been crunched backward, forward, and upside down, and without a visible, clear-cut margin, which appears do-able and reasonable to me, it would be lunacy to front this PR. Respectfully requesting clarification. I understand the post-hoc consideration, which I am sure has been cleared (and precedented) with FDA, and agree w. jbainseky about importance of other trials, but it is clear, at least to me, that the NSCLC numbers will be usable.
kt,nicely said. Possibly the greatest biotech denouement in recent history. A statistician's bedtime story. ("We'll give them placebo AND 1mg" groups!). An informed investor's dream come true. I can imagine a few well-deserved smiles in Tustin and UTSW's pharmacology department...and here. Congrat.s to all who stayed aboard, and those new arrivals. This should be a lot more rewarding from here.
stoneroad, methinks you have it right...eom
CP, nice! You must be a fast typist...and thinker. Last week was one of the worst, psychologically, for me with Peregrine, considering the market reaction to Cotara. The worst since the week of "black Monday". I added a few shares (and not at the lows),and currently am holding my all-time high number of shares, but today's marketplace evauation of Cotara(AND Bavi AND Avid, etc) is a continued source of bafflement. The only possible answer to the "Why" of it is that 1)we are either sadly wrong; or 2) there are forces at play interested in keeping the price low, and in the process burning every small retail buyer who jumps into the pot. Of course I've been advocating the latter for years. The only explanation for the second "conspiracy" theory is that for years there has been a defacto BP owner using PPHM as a defacto low-cost, low priced research and development facility. Obviously there are holes in that theory as well, but the current relative paucity of speculators in the face of all the potentially good news is a source of wonderment.
thanks dia. another hefty brick in the wall. eom
FTM, guess I should clean up my vocab regarding monocytes and macrophages: "...when the cell is in blood it is called monocyte and when it enters tissues it becomes a macrophage. There are also some other differences in the type of proteins they express..." To most of us they are just one of the several white blood cells!
Bavi mechanism of action is now though to be, in part, that of facilitator...that of switching omnipotential and plastic monocyte function from body growth offense to body anti-growth defense. Bavi helps switch monocytes from such tasks as making new blood vessels, newlymphatic channels, and new stroma to that of performing tasks which are pro-host/anti-tumor, by discouraging growth and development of new blood vessels and lymphatic channels and thus discouraging metastases and growth of primary cancer sites. It appears that Bavi's action mirrors that described in FTM's last post re. pancreatic cancer, so perhaps we may reasonably expect significant increased months of survival in that disease, pancreatic cancer. Whether Bavi requires or allows for chronic administration remains a question, but appears to be a possibility. Bavi's role used in combination with surgery, irradiation, and/or chemotherapy seems increasingly promising at this point. It seems clear that in large, established, and aggresive tumors that ablation...whether surgically, chemically, or with irradiation will be necessary in the near-term until earlier cancer detection is possible. And Bavi could conceivably play a role in cancer imaging, moving that goal a step closer to reality. Finally, it seems likely that Bavi will help extend the boundaries of "operability" of certain already advanced tumors and metastases.
FTM, agreed. Reinforces what you've been writing here yo these many months. Terrific Bavi-positive stuff. Thank you.
MD125, I didn't read the posts you are responding to (came in late on this conversation), but aren't they talking about the principles of immunization, adaptive immune response, or immunological memory,and not "pills" for blood pressure, etc.,e.g. (as/per Wikipedia) "A case of somatic genetic memory is the immunological memory of the adaptive immune response in vertebrates. The immune system is capable of learning to recognize pathogens and keeping a memory of this learning process, which is the basis of the success of vaccinations. Antibody genes in B and T lymphocytes are assembled from separate gene segments, giving each lymphocyte a unique antibody coding sequence leading to the vast diversity of antibodies in the immune system. If stimulated by an antigen (e.g. following vaccination or an infection with a pathogen), these antibodies are further fine-tuned via hypermutation. Memory B cells capable of producing these antibodies form the basis for acquired immunological memory.[4] Each individual therefore carries a unique genetic memory of its immune system's close encounters with pathogens. As a somatic memory, this is not passed on to the next generation. One Bavi MOA is alleged to be "unblocking" of the body's ability to immunize itself against a "non-self" cancer.
Pardon me if I've misinterpreted the thrust of the discussion....
Hayward, a brief PubMed search using "membrane phospholipids (-PS)Alzheimers Disease" yielded several references that could bolster the concept of looking at anti-PS (or, better, anti-PE)therapy in that disease...and others. When I asked SK at ASHM what other diseases they were looking at for Bavi-, I don't think he pulled Alzheimer's at random from a basket of a gazillion diseases...
I haven't looked carefully at the latest in the anti-phospholipid syndrome tie-in, but hope to soon. Regards, and best wishes to all. This "quiet time" is a bit of a puzzle. It seems that at this point it would be clear from overall survival data whether the entire pooled NSCLC trial cohort (Bavi and placebo..whatever) survived longer than if they all had taken placebo...or all taken Bavi...or any combination. Simple math. I would think the company has moved on beyond incurable-staged disease at this point, but that should be reflected in the stock price. Let's face it. The MUST be a lot of people/companies who know the general efficacy picture.
Biochim Biophys Acta. 2010 Oct;1798(10):1969-76. Epub 2010 Jul 11.
Alzheimer's disease amyloid-beta peptide analogue alters the ps-dynamics of phospholipid membranes.
Buchsteiner A, Hauss T, Dante S, Dencher NA.
Aging Cell. 2012 Feb;11(1):63-72. doi: 10.1111/j.1474-9726.2011.00760.x. Epub 2011 Nov 28.
Alterations in phosphatidylethanolamine levels affect the generation of AĂź.
Nesic I, Guix FX, Vennekens K, Michaki V, Van Veldhoven PP, Feiguin F, De Strooper B, Dotti CG, Wahle T.
Curr Alzheimer Res. 2011 Mar;8(2):213-21.
Neuronal membranes are key to the pathogenesis of Alzheimer's disease: the role of both raft and non-raft membrane domains.
Williamson R, Sutherland C.
r622, interesting stuff about Alzheimer's and inflammation, and a possible Bavi role in that disease. The "TREM2" gene mutation appears to be a player in only 1-2% of sufferers, but as Dr. Stefansson said in the article, "Although researchers have long noticed that the brain is inflamed in Alzheimer’s patients, he had dismissed inflammation as a major factor in the disease [until this study]." You probably remember SK specifying Alzheimer's disease when answering my question about BAVI's possible role in diseases other than cancer. Let's hope he has some specific insight in that regard. For instance, the article you cited is an overview and does not specify the types of inflammatory cells inhibited with the TREM2 genetic mutation. The assumption, of course, is that they are monocytes/macrophages if they are cells capable of gobbling amyloid frags. I've mentioned before here that one of the most intruguing and gratifying aspects of primary research on a therapeutic agent that has been established to be satisfactorily safe in humans is the many spin offs that occur along the way. Our knowledge in this field of antiphospholipid therapeutic possibilities is expanding rapidly, and we [here] have front row seats. Never mind the cost of admission!
if tis good nuff for BerkshireHathowayB,
PPHM is good enough for me....
[couldn't resist]
wildhorses,good thinking AND writing. thanks
bimerkjaere, nice post. succinct. appreciated. deserving of "headlines" on this site. thanks.eom
dukesboy, god bless you and your family in this difficult time, and thank you for your information gathering efforts re. PPHM. Sharing the content of your discussion with an ex-PPHM employee helps fill some important gaps in the Bavi- puzzle. and...Remeber that inventors and their minions are not always wholly realistic or objective when assessing their own ideas, but it helps to know they are "all in" also. Best wishes.
k_t,wow.what an effort. mightily appreciated. thanks eom
DukesBoy, I'm dying of curiosity. What did your relative/friend say about PPHM? And how is your bro-in-law? Best regards to you and your lovely bride.
thanks north40k, interesting stuff
FTM, thanks. I'll bookmark that one.
sunstar, nice precis for Roche/Genentec needing PPHM. It seems only a mere formality. The role of the common stockholder here seems that of "laughingstock", what with paying all the bills for major upstream screwups. The Swiss are obviously skilled ruffians, and our investment is being diluted to pay for an investigation of foreign medical clinical trials corruption. Why partner/purchase now instead of when all the dust settles? Seems the reasonable option for us humble sackholders is to buy more stock...and hope. That's what I'll be doing next week.
Genentec/Roche is interested in BavImag. The Koji paper which follows, from Japan, in a clinical sense is a curiosity, almost amusing, when compared in applicability to BavImag. Wonder what MAB, if any they are using.
In Vivo Time-Course Imaging of Tumor Angiogenesis in Colorectal Liver Metastases in the Same Living Mice Using Two-Photon Laser Scanning Microscopy
Koji Tanaka,1 Yuhki Morimoto,1 Yuji Toiyama,1 Kohei Matsushita,1 Mikio Kawamura,1 Yuhki Koike,1 Yoshinaga Okugawa,1 Yasuhiro Inoue,1 Keiichi Uchida,1 Toshimitsu Araki,1 Akira Mizoguchi,2 and Masato Kusunoki1
In vivo real-time visualization of the process of angiogenesis in secondary tumors in the same living animals presents a major challenge in metastasis research. We developed a technique for intravital imaging of colorectal liver metastasis development in live mice using two-photon laser scanning microscopy (TPLSM). We also developed time-series TPLSM in which intravital TPLSM procedures were performed several times over periods of days to months. Red fluorescent protein-expressing colorectal cancer cells were inoculated into the spleens of green fluorescent protein-expressing mice. First- and second-round intravital TPLSM allowed visualization of viable cancer cells (red) in hepatic sinusoids or the space of Disse. Third-round intravital TPLSM demonstrated liver metastatic colonies consisting of viable cancer cells and surrounding stroma with tumor vessels (green). In vivo time-course imaging of tumor angiogenesis in the same living mice using time-series TPLSM could be an ideal tool for antiangiogenic drug evaluation, reducing the effects of interindividual variation.
FTM, this paper is enormous because it convincingly presents Bavi Imaging possibilities is an extremely favorable market position for clinicians, or the doctors ordering/supervising the actual injection/imaging/interpretation. The abstract you posted reminds us that phosphatidylserine (PS) is normally intracellular but becomes exposed on the luminal surface of vascular endothelial cells in tumors. What ARE vascular endothelial cells? VERY special body cells with very special properties, and found only as the inner lining of blood vessels. The Thorpe group optically imaged[take especial note of the term "optical imaged"] the flipped -PS markers on inner lining of cancer feeder-vessels with Peregrine's PGN635 MAB. NIR[important: NIR + near-infra-red] imaging was performed after injection of [dye-MAB] IRDye800CW-PGN635 into mice bearing glioma {Brain GBM?} or breast cancer. A clear tumor contrast[illuminated image] was visible 4 h later and became maximum 24 h later. Note! 24 hours later. The most fortuitous attribute of BavImage. The patient must come back to the doctor's office for a second time 24 hours later. That qualifies for medicare/insurance company criteria for enablling a second office visit charge. Voila! That helps enormously with radiologists/oncologists. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelial cells. "BavImage worked well in vivo to provide sensitive tumor detection. Cost effective? I think so, even [especially] with a second visit required for "reading". What's the best part? That the imaging agent (Bavi) will also probably be therapeutic (!)...it can monitor its own antitumor activity...or is the best thing about BavImaging that the image is gathered with NIR, near infrared spectoscopy which, according to Koji, et. al., "has an advantage of being a portable and inexpensive device for functional ...imaging comparable to electroencephalography (EEG), as opposed to fMRI, positron emission tomography (PET) and magnetoencephalography (MEG). It doesn’t require severely limiting subject motion.... It can measure ... hemodynamic signals with a temporal resolution of 100 Hz or higher, significantly greater than fMRI or PET aiding in the resolution of the onset time of brain activation and in filtering physiological interference from the brain activation signals of interest. Measurements can bridge from the human level down to microscopic invasive measurements in animals enabling efficient translation of knowledge in both directions. Finally, NIRS is compatible with fMRI, PET, MEG, EEG enabling interference free simultaneous multi-modal studies of brain activation.
[ref]http://www.scholarpedia.org/article/Near_infrared_imaging
FTM, nice thoughtful post. Your bottom line was why I asked SK for clarification about other "top priority" disease being looked at for Bavi. His answer was ASCVHD (vascular/heart disease), and Alzheimer's. I can think of many more, especially in the auto-immune category. Maybe you can help with a conceptual/mechanical problem I have with this schematic, and that is, if anti-PS Bavi binds to surface exposed "flipped" -PS, I picture a socket wrench covering a nut perfectly. Are we postulating that Bavi, in covering the -PS site is masking/eliminating a fatal "stay-away" signaling, or do you suppose it is creating a signal that actively recruits the immune cells? It's curious how this type of primary research "spins off" secondary knowledge useful in widely variable fields of endeavor. We're so fortunate to already be there in humans with this platform.
nuke,tech,FTM, through the "retrospectoscope" it would have been more reasonable (but time consuming!)for me to look at the Webcast to straighten out any questions I had about my notes, but didn't even think about it, and must say you were on it.....answering the question immediately. Thanks again. Could be the recent snafu will retard reporting of front-line data MOS too, so would not jump to any conclusions re MOS and current timeline.