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gentlemen and gentlewomen. At ease! The PR seems solid enough. Hit the 'reset' button, take a deep breath, and hold it for a week (your breath, not the reset button). All will turn out okay imho...maybe just not in our lifetime.
Chey, my take on it is this: Thorpe,et.al created the recipe and directions for cooking chimeric-Bavi, ergo, the genesis of the company, PPHM and its reactors [along with Epstein and Cotara technology, etc.etc), but (I think) the all-human formula must be orders of magnitude more difficult conceptually and operationally, and was deemed a job for an outside laboratory. It is my understanding that Affitec has a unique pass-through technology to nail the humanized formula, and PPHM apparently has the ability to slot it into production mode. "our collaboration with Affitech to generate fully human anti-PS antibodies has produced a number of antibodies with varying characteristics. We look forward to continuing to pursue both internal efforts and external collaborations to further explore the clinical potential of these promising development candidates" {SWKing}. I think PPHM agreed to give Affitec the Russian rights with some sales commissions and the production rights. But then, that could be the arrangement for 2C3, the "a better Avastin" MAB. Anyone? Additions? Corrections?!!
djohn,nice. definitely confirms thorpe is the real deal. Onward with anti-PS (phyosphatidylserine), phosphatidylethanolamine )anti-PE) and phosphatidylinosotol! I knew all those weird words would come back from organic chemistry to haunt me some day...
chey, that seems a legitimate concern...
2007:"In general, monoclonal antibody immunotherapy for cancer has fallen short of clinical expectations. This is due, at least in part, to the over-expression of membrane-bound complement inhibitors on the tumor cell surface. The authors proposed to prepare and investigate the effects of two novel recombinant proteins aimed at modulating complement to increase the immune response to breast tumors. During year two it was proposed to finish construction, expression, and purification of CR2Fc; characterize the recombinant protein in vitro; and begin in vivo studies. Construction and purification of CR2Fc has been accomplished. The purification of the protein was optimized and stocks of protein have been produced for these studies. The protein has been characterized in vitro and shown to bind C3 deposited on tumor cells. Technical difficulties were encountered in vitro when looking at increased C3 deposition and tumor cell lysis but are currently being resolved. The authors will finish in vitro studies and proceed with in vivo studies to determine the effect CR2Fc has on the immune response and whether it is protective against breast tumors.
2012Mar22Epub ahead of print [Journal]Blood:
A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer.Elvington M, Huang Y, Morgan BP, Qiao F, van Rooijen N, Atkinson C, Tomlinson S. Department of Microbiology and Immunology, Children's Research Institute, Medical University of South Carolina, Charleston, SC,
"Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired anti-tumor immune responses. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage dependent Fc?R-mediated antibody-dependent cellular cytotoxicity, and by direct complement mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an anti-tumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer.
PGN635 [aka 1N11] aka fully human Bavi...if you could convince someone it is worth .50/share, or essentially nothing, you could convince them of almost anything. who's kidding who here?!
follow the money (AFFITEC) and watch the belly button, not the eyes...if you want to know where someone's going:
DENVER & TUSTIN, April 22, 2009: Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing monoclonal antibodies for the treatment of cancer and serious virus infections, today announced that preclinical data presented during the AACR 100th Annual Meeting 2009 shows that one of itsFULLY HUMAN phosphatidylserine (PS)-targeting antibodies demonstrated encouraging signs of efficacy in a preclinical model of prostate cancer. These positive new data validate the anti-tumor potential of this human anti-PS antibody, which is similar to Peregrine's lead clinical stage antibody bavituximab and extends Peregrine's anti-PS antibody pipeline. Bavituximab is in Phase II clinical trials for the treatment of advanced breast cancer and non-small cell lung cancer.
Peregrine's PS-targeting antibodies bind to the cellular membrane component PS that is usually located inside cells, but which becomes exposed on the external surface of the cells that line the blood vessels of tumors (the tumor vascular endothelium), creating a specific target for anti-cancer treatments. By binding to PS, the antibodies are believed to help mobilize the body's immune system to destroy the tumor and the tumor blood vessels.
In today's presentation, researchers from UT Southwestern Medical Center in Dallas and Affitech A/S reported that similar to bavituximab, the human antibody PGN635 [aka 1N11] targets and binds specifically to the tumor vascular endothelium(1). Treatment with androgen deprivation therapy or docetaxel substantially increased the percentage of tumor blood vessels with PGN635 binding.
article rediscovered cruising "my documents: What is Macrophage Inflammatory Protein-1 Alpha (MIP-1A)?
Human MIP-1A is a 8.0 kDa protein belonging to a small class of cytokines called chemokines. Chemokines are a large family of small molecular weight proteins that mediate recruitment of mononuclear cells both in vivo and in vitro, an important step in inflammatory response. (Clark et al., 1998) "There are four defined chemokine subfamilies based on their primary structure, CXC, CC, C and CX3C. The best characterized are the CC and CXC chemokines. Members of the CC chemokine subfamily, such as MCP-1, RANTES, MIP-1 Beta and MIP-1 Alpha are chemotactic for monocytes, subsets of lymphocytes and natural killer cells, whereas CXC chemokines generally, but not exclusively, induce neutrophil chemotaxis."
…Tony Moody of Duke Univ. School of Medicine used anti-lipid monoclonal antibodies taken from auto-immune disease patients, and confirmed that [in a test tube] the Anti-PS MABs “neutralized” virus, or decreased viral cell entry, and the mechanism was via release of cell-synthesized chemical attractant compounds called “chemokines.” The specific chemokines, called MIP1a and MIP1b, are chemicals secreted by monocytes, the white blood cell scavengers, which dock on, or attach to, cell membrane receptors (docking sites), plugging the port-hole in the cell membrane [receptor site] through which HIV enters a cell, That docking site is called the CCRF receptor. Moody found that “neutralization” of virus infection could be reversed by antibodies directed against the MIP1a and MIP1b, concluding that the MOA of anti-lipid antibodies is that they stick to the host target cell and not the virus to prevent infection. A vaccine that induces such antibodies may not be able to directly neutralize HIV but it may reduce virus spreading
…
Tony Moody of Duke Univ. School of Medicine used anti-lipid monoclonal antibodies taken from patients with auto-immune disease, and confirmed that [in a test tube] the Anti-PS MABs “neutralized” virus, or decreased viral cell entry, and found that the probable mechanism was via release of cell-synthesized chemical attractant compounds called “chemokines.” Chemokines use chemical signals as attractants to other immune cells. The specific chemokines released by the antiPS MABs are called MIP1a and MIP1b, and are secreted by monocytes, the white blood cell scavengers. These chemoattractants dock on, or attach to, cell membrane receptors (docking sites), plugging the port-hole in the cell membrane [receptor site] through which HIV enters a cell, That docking site is called the CCRF5 receptor. Moody found that “neutralization” of virus infection could be reversed by antibodies directed against the MIP1a and MIP1b, concluding that the MOA of anti-lipid antibodies is that they stick to the host target cell and not the virus to prevent infection. A vaccine that induces such antibodies may not be able to directly neutralize HIV but it may reduce virus spreading
RA Chaurio published “Phospholipids: Key Players in Apoptosis and Immune Regulation, in which he said that “PS seems to be the major “eat me” signal and immune suppressor in the clearance process of apoptotic [normal death in] cells. He continues, “Since millions of cells die constantly in multicellular organisms and since there is a robust system for their rapid recognition and removal, this “silent clearance” of apoptotic cells is [somehow] associated with … impaired immunity and increased apoptosis. Cancer, exposure to irradiation, and some parasite and viral infections are considered to take advantage of this ubiquitous mechanism fostering disease development
dog,nice couple posts to go along with so many of your other good and thoughtful ones. A timely reminder that (at this point in our understanding of MABs and solid tumors) these agents are not going to cure advanced disease. Let's keep our fingers crossed that some patients have primary tumor in non-vital anatomical areas and Bavi helps keep metastases out of same. That would really be a warm moisty camel's nose under the tent flap, huh.
wook, thought-provoking verification of the realities of laboratory science...and the human condition. thanks
bigworld, one caveat: testing on nearly-deads is necessary in case there is a serious side-effect in a new drug that might hasten one's demise. That group is used for testing to minimize potential downside, not necessarily to maximize upside. Once you have the go-ahead for "safe-in-humans", there are all kinds of potential in this particular (anti-PS)arena. The obvious concern is the anti-PS syndrome, and NObody wants to be trying a medication for any indication when an obvious, serious possible side-effect is looming. That hurdle has been passed with Bavi, in spades, and now efficacy for some application must be established. Safety apparently remains more an issue with Cotara than efficacy...if I am guessing right.
bigworld: WOW!Best post of the year.Where have you been? You just said in a couple sentences what I've been TRYing to say for the past several months in quasi-erudite prose. Think about writing ad copy with such succinct thinking and prose....
frustrated, I share your anguish, but not your take on, "To be talking about new trials or indications when the company is at all time lows is ludicrous if you really hold any shares..." I might hold as many shares as anyone on this board, and may have lost as much money here. That said, I am not particularly surprised about the results of an immunostimulant pitted against a solid tumor of measurable size. I've been around the operating room, the clinical scene, and the research lab long enough to know that 1)not all avenues you choose turn out to be the right ones; and 2)not all successful applications of a product are those initially intended. It's research. It's cutting a new road, and it is not cruising on a freeway. Only invest what you can afford to lose, and only in something that makes a lot of sense. I'm a LONG way from writng this company off.
FtM, question. Why do you suppose, after all the glowing implications of Bavi combined with irradiation therapy, a trial is not in the offing? I thought the company grabbed at India/chemo because it was a last straw before drowning.
FtM, great posts as usual. It's more informative now here on this board than med school thanks to you and so many others. Agree anti CD47 is interesting. Deja vu all over again? My sense of it is that solid cancers and/or their metastases that are large enough to kill and not surgically resectable are not going to be materially diminished by immune-enhancing MABs, at least in the near future. Earlier detection methods, which involve cost-effective screening, and earlier treatment seems a perfect application for these agents. And what could be better than an MAB that "detects" small tumors, "tags" them for imaging and for follow-up, and "treats" them...all at once? That's Bavituximab. The other undeniable reality for those who have been in experimental medicine is this: If an agent is bioactive, anti-inflammatory or ant-neoplastic AND proven safe, it will probably have an application. Keep using it in the clinic long enough and another possibly more important secondary indication for its use will be found. The spin-offs from clinical research are often more valuable than primary targets.
FtM,megaditto thankyous. recap please basis for theory that 2nd line NSCLC results will better 1st line NSCLC. thanks again for all your efforts!
geo, it's the law of unintended consequences.
purpledawgs, OMG@!
hey abe, if this thing gets to $1.25 there will be a good reason for it, and doubt many regulars will be cashing out at that level.
jr,I'm not so sure independent imaging was not mentioned before during trial design. seems to me it was...but then...I'm too lazy to investigate it...
remember,Bavi and similar do best against mets and other small lesions, and would not be expected to make much of a dent in humungoid tumors. Let's see what the survival data shows in patients whose primary tumors aren't wrapped around the aorta with sizeable metastases in brain and bone. We know it works on the immune system, and we know it is safe...or relatively safe as these things can be.
example:HOT off peer-lit press:MABs for Immunotherapy of Solid Tumours. Mauerer R, Gruber R.
Sourcesynlab MVZ Labor München Zentrum GbR, Bayerstraße 5380335 München. rudolf.gruber@synlab.com.
"More than 80% of all cancers are caused by solid malignancies. More than 90% of these tumours are of epithelial origin. The main principles in tumour treatment are surgery, radiotherapy, chemotherapy or combinations of these. Complete surgical removal of the tumour is the most effective therapy for solid malignancies. Recent advances in early cancer detection led to a higher rate of resectable primary tumours and therefore prognosis will be determined especially by metastasis. Even in early stages some tumour cells may disseminate for example into the bone marrow. If these occult metastasis get evident they are mostly incurable by surgery and often highly resistant to chemotherapy. Developing new therapeutic agents to destroy these resting cells is a major challenge for the improvement of cancer therapy in the future. Advances to reach these goals were made in immunological therapies with monoclonal antibodies (MABs). These MABs are for example directed against tumor-associated antigens (TAAs). By binding selectively on tumor cells they can activate immunological effector mechanisms, e.g. antibody dependent cell cytotoxicity (ADCC) or complement mediated lysis. Other mechanisms are the blocking of inhibiting molecules to re-activate anergic tumor infiltrating lymphocytes (TILs). Furthermore growing tumours depend on oxygen supply, i.e. on effective neovascularisation. Antibodies against VEGF are able to inhibit neovascularisation and are therefore used successfully in tumour therapy.
geo, agreed. yet PPHM's financial straits do not seem so daunting as they were, say, five years ago. But, agreed, it would certainly ease the angst if something broke lose in China or Russia. Here's an answer to my question about MAbs. Good article: Ten Monoclonal Antibodies 2010 byKrishan Maggon
Consultant Pharmaceutical Biotechnology R&D & Advisor
Geneva, Switzerland & New York, USA
Global Market Analysis & Blockbuster mabs
"Despite economic downturn, the growth in the mAbs showed no sign of slowing down. The global monoclonal antibody market (mAbs) for therapeutic use was $48 billion as compared to $ 40 billion in 2009 and $ 37 billion in 2008. The combined sales of top 10 mab were 45 billion dollar. If $10 billion sales of mAbs for diagnosis and as reagents in research are included, then the total mAbs market was worth $ 55 billion. As in previous years, Remicade was the top selling mAbs brand followed by Avastin, Rituxan, Humira and Herceptin. The top 4 mabs had sales gain of over 1 billion last year over the sales of 2009. Cancer and Arthritis mAbs accounted for over 75% of the total mAbs market. The top 5 brands had sales of over $ 5 billion each. Introduction of newer monoclonal antibodies and uses in chronic conditions like Asthma, Osteoporosis will greatly expand the market. All the pharma majors now have mAbs projects in their R&D portfolio. Once again M&A and mAbs deals in R&D and marketing increased in 2010. Two new mab, Actemra and Prolia were approved by the FDA and EMA each in 2010. FDA had approved 4 new mAbs and EMA had approved 7 new mAbs in 2009, a new record. Sales of new mabs Actemra, Simponi, Cimzia, Stelara totaled 1 billion dollars in 2010. Belimumab the first mab to pass Phase III end points in Lupus was recommended for approval by the FDA expert panel. Ipilimumab, a new magical cure for metastatic melanoma waiting for the FDA approval in 1Q2011. The FDA ODAC recommended withdrawal of Avastin indication for use in breast cancer. Motavizumab a new mab for RSV infections in premature babies was rejected by the FDA. The mAbs driven M&A activity continued in 2010 with the mab tie up of Regeneron with Sanofi Aventis and the hostile takeover by Abbott of Facit for $450 million. There were at least 6 new mAbs under regulatory review, 25 mAbs and 5 mab fusion proteins (32 in 2008, 26 in 2009) in phase III and over 100 in Phase II clinical trials. Out of 457 Phase III mab trials, 185 were active and open for new patients. Majority of these studies were new indications for marketed mab brands. This is the first and earliest report providing 2010 monoclonal antibody market, sales and ranking and beat out the commercial reports by several months."
k_t, thanks for asking. 2-3 years ago I wrote here I agreed with one of the "negative" posters that [the current iteration] of Bavi might not be approved, and after the India trials (a couple years ago? seems like eons)I wrote here that approval was probably going to be a statistical "squeaker", and I'm still in that corner. The problem is that the FDA is not going to get excited about a squeaker, especially when Avastin indications are actively shrinking, rather than expanding. So questions about the control arm of the trial, and matching or barely exceeding Avastin, simply do not capture many people's imagination. We learned something of value from a trial on patients with very serious disease. That's it.Move forward with the program. Definitely. And...be grateful to those patients with such severe illness for their bravery in volunteering to help move closer to a cure. Does a continued presence here, or in PPHM stock, makes sense? I think so. The company's intellectual properties are remarkable, and their progress to date spectacular. There is increasing focus and interest in PPHM. Last week was definitely not a great leap forward, but not to get all bogged down in it.
What's next?!
k_t,thanks. You said, "demonstrating effective Bavi use and achieving approval for commercialization of Bavi in at least one indication seems like it is still an important intermediary step before PPHM can step forward with humanized Bavi or "armed" Bavi."
Agreed, and I think the odds are good that we might squeeze an indication out for poor-ole naked chimeric Bavi
I need clarification on the following k_t, not sure what you're saying here. You said, "I posted earlier about a study comparing two single treatment drugs with Paclitaxel and Carboplatin for a group of elderly patients with NSCLC. The control arm in that study was over six months for PFS, comparable to the recent Bavi study reported results. The most prominent other study I found with reference control arm data was the Avastin study that showed a PFS median of about 4 1/2 months, which was the PPHM study design bogey for PFS." And you wrote, "There is more to the story about investigator interpretation of results and independent reads than would apply just to the Bavi study, methinks. Yes, MOS is a statistic not subject to investigator bias. It looks like outperforming around 10.3 months MOS is the new Bavi NSCLC study bogey. Outperforming Avastin would be nice but matching performance would be adequate, it seems."
I just don't think any of that is material at this point. It's history. So is Avastin. If Avastin is a malapropos, how does tying a loser make a winner?
I do emphatically agree that it would be nice to have an income bridge while moving inexorably toward Nirvana. The MAB market in general, and Avid will probably support the company, and more than supports the current market price. Methinks the Russians buying the remainder of Affitec is a huge signal. Thanks again for that tidbit CJ.
krakonos, thanks. My grandma said, "child, you can overdo anything," when she was trying to explain my grandfather/her husband's penchant for gambling on land deals. So I suspect even immunostimulants have their dark side and can be overdone. You only have to google anti-phospholipid syndrome to see that nothing is really easy, and until that lurker is settled we will not be popping or snorting bavi ad lib. So far, however, so good regarding side-effects. Now we must home in on exactly what its best use is, if any, as a bridge until fully-human is batch/mass produced. If there is no best use that fills a need in the meanwhile, then there's always other MABs that need manufacturing at PPHM wholly owned FDA inspected and licensed MAB production arm, Avid. As long as that MAB market is expanding PPHM is not going broke. Anyone have any numbers on the rate of growth of MAB use/production? China is about to put some huge reactors on line if memory serves.
cj,thanks for Affitec info.you do follow the money trail....
chees,yours is the question of the WEEK. Folks,are we still about moving closer to the goal line? Shake it off and hit the next defensive line with dynamite. PPHM has that and more in the closet. Think data points. PPHM has human "numbers", and in spades, for its anti-PS MAB Bavituximab. Safety. Unquestionably immunostimulatory. Talk it down? Not. Bavi didn't budge metastatic lung cancer. Duh. Like asking an agile dancer to take out Godzilla. Anyone still posting here who is retail? Haloooo! Anyone posting here who isn't short? Splitting hairs... comparing naked chimeric Bavi- with dittoed Avastin is comparison with a dead duck. Anyone know where we are right now with all-human MABs being used for solid cancers, and not chimerics? Do MABs have a role in treating solid tumors? If so, then Bavi- deserves a place in the MAB mix. Tumor immunology. We have known early 70's tumor immunology of BCG vs. melanoma that these agents are nicely synergistic and sometimes even curative if used early enough in a relatively intact immune system. No surprises here. Now we have that agent. Oral Bavituximab. A nasal spray? Yes. Fantasy? No. It's all there in the peer-reviewed medical literature, nasal spray and all. Chimeric Bavi- is outdated in favor of all-human Bavi. Gird your loins. Get over it. We know how it works on the immune system. And it DOES work. And we know from increasing human trials experiments that it is amazingly safe. The all-human Bavi will not have the allergic risk for repeat dosing that part mouse-part chimeras have. That means earlier and longer dosing. A no-brainer: a safe immunostimulant with low side-effects. I think Bavi is going to be useful. Who's trying to fool whom? A fully humanized Bavi pill with radiotherapy seems almost a certainty. Increase those monocyte scavengers and immunocytokynes when it really helps the fight cancer. We've established that Bavi is not an end-of-life drug. That's about all. Knock it out of the arena? I don't think so. If that happens, I want to keep my fair share of the technology. Probably not the time to give up on this one. I've done that once too often. PPHM has a stable of winners. MAB delivery of RAI? PPHM has it. Need I repeat? It's scientists are the best. The medical pharmacology department of UTSW is simpy stellar, and the bench folks at Avid and PPHM are the pick of the crop. Massive layoffs? There are 154 employees poised to gear up, and the company is still hiring. What are we doing to help?
Shorts covering on Monday?
oops, make that, "think r84"..not r94!!!
best narrative (fiction?)I can muster. Think Affitec. Think r94 and pgn635. Two years ago I wrote the following, and nothing has altered that truth, especially not Friday morning "news". Naked Bavi isn't going to fly (especially for andvanced cancer) if efficacy statistics must be carried to two decimal points and we argue about significance. If Bavi is going to be used its efficacy must be obvious. r94 and pgn635? Now you're talking. Someone asked, what happened to India and Russia? I posted last week that only a few people in Denmark and Russia really know what is going on with r94 and pgn635. I say that Avid and the 154 Peregrine employees are continueing to ramp up production capabilities for those two agents. Naked Bavi use is interesting, and the safety-stalking work in humans done by that mAB will smooth the way for the real beef...r94, a better Avastin, and pgn635, all-human Bavi that can safely deliver a knock out punch...time and time again because it is all-human.
Post 53989 July, 2010 Here's the deal: PPHM's monoclonal antibody Bavituximab has been used now in combination with standard chemotherapy and found to "not interfere" in any way with results of chemo/cancer treatment, but probably actually improves results. PPHMs MAB Bavituximab now has an established safety profile. That is Huge! Huge, and that safety profile is for an inferior grade MAB, one made up, in part, of mouse parts which may cause increased levels of allergic reaction. So Bavi may be safely added to standard chemotherapy. "Naked" [unarmed] Bavi was NEVER NEVER intended to be a stand-alone cancer killer. NEVER! But a lagniape that we never imagined is that BAvi is probably an immunological stimulant even when "unarmed" and used in the cancer treatment mix. And that immune boost is documented in severely immunologically crippled advanced cancer cases. But we are not, repeat NOT, in this because Bavi showed some measurable improved survival even unarmed. We, like BMY, are after the biggie: fully-armed a fully humanized MAB cancer bomb. That's the cancer killer. Not chemo. Not naked Bavi. Read my lips: it is fully armed and fully humanized Bavi. BMY has their full-humanized MAB that docks on anti-EGF. PPHM's MAB has a better, more universally applicable cancer docking site, -PS. The science is a done deal. The animal trials are finished. The theory is sound. The patents are there. The strategy is to add two known quantities together to fight cancer, fully-armed and fully human MAB Bavi. It's a no-brainer, that's where we're going. Things evolve. We're at there now. The coup de grace is to move fully armed and fully human Bavi directly into PiiB human trials. That's why we're here. That's when the PPS share kickstarts.
k_t,thanks for that article. it seems clear (to me, at least) that Bavi- positive effects are going to increase linearly to geometrically as the tumor load decreases, and will probably find its highest use in 1) prophylaxis; 2) early cancers;
3)recurrence prevention. I think we all need to get a bit more realistic about stage IIIB and IV expectations. This article does imply that if some of the worst cases are
picking up the pieces....except for the stock price, this news is far from a disaster. Bavituximab was thrown into the mix for treating stage IIIB and stage IV untreatable metastatic lung cancer: Stage IIIB non-small cell lung cancer defined: cancer has spread from lung primary site to lymph nodes on the same side of the chest as the primary tumor and to (a) the heart; (b) major blood vessels that lead to or from the heart; (c) trachea; (d) esophagus; (e) sternum; and/or (f) carina; and/or (g) there may be separate tumors in different lobes of the same lung. Cancer may have spread to the backbone and/or the nerve that controls the larynx. Stage IV non-small cell lung cancerhas spread to the other lung, and/or to lymph nodes, fluid around the lungs or heart, and/or other places in the body, such as the brain, liver, adrenal glands, kidneys, or bones. Bavituximab (unarmed), a mild immunological stimulant which encourages proliferation of specialized white blood cells (monocytes), is added to a combination of two cytotoxic agents which are known to decrease body production of these very cells. It is almost certain that the patients have undergone other immunosuppressive therapy prior to this trial, and are suffering the non-treatment related immunosuppresive effects of advanced cancer. Am I disappointed? Of course. Miracles are what we pray for, but not what we can expect. Suprised? No. What happens when you kick a dead horse (the immune system, not the patient)? Are the results interesting? Yes. Bavi apparently did not cause additional side-effects. Is there hope for Bavi? Of course. Come on! We were in a race that could not be won. And actually have learned from it. Don't give up. Just get realistic. And don't let them give away the technology when all our chins (and portfolios) are dragging on the floor.
wwtmm, do you have a reference to the article on ipilimumab use with irradiation therapy? I am curious whether it is in clinical trials with irradiation therapy, or if the info. is from lower animals (as with Bavi + irrad.). The MAB, as correctly pointed out here by others, has some problems which are tolerable in light of the clinical trial indications for its use (metastatic malignant melanoma), but it "umblocks" the immune system by a pathway different than bavituximab. There is a good recent article out of Duke (Prostate, 2012 Feb;72(3):338-49.doi:10.1002/pros.2145 Emerging treatment options for patients with castration-resistant prostate cancer by George D, Moul JW)in which Bavi is not mentioned, concluding, "Various combinations of these (MABs) agents could theoretically be used to treat future patients...by targeting multiple signaling pathways as well as aspects of the tumor microenvironment". Additional research will be needed to understand how to best use these agents and individualize care to optimize...patient outcomes".
RRdog, I'm not certain paclitaxel and carboplatin, being anti-mitotic, i.e inhibitory to rapid cellular division, are necessarily "somewhat apoptotic,"as you assert, but maybe. Don't remember seeing that in the package insert anyway. It is such a shame Bavi must be used with such losers as pacli- and carbo-, and oxy and toxi, because Bavi's "uregulation of the immune system" consists, in part, of goading the body to rapidly reproduce specialized immune-system cells, monocytes (body garbage collectors). Unfortunately the anti-mitotic chemotherapeutic agents the decrease cellular production probably have a "down-regulatory" effect on Bavi mechanism of action. I think I have seen that dilemma in print, and posted it here a few weeks ago.
The end of the Bavi narrative imo is that, in some iteration, Bavi will almost certainly be used to upregulate the immune system--Bavi-in-your-tea, or a Bavi nasal spray--aimed at micro-sepsis and micro-tumors. Chimeric Bavi is already last year's flavor (compared to Affitech's all-human Bavi). And our naked and chimeric Bavi isn't even through trials yet. I repeat. What a monstrous mistake Bavi trials did not commence with Bavi + irradiation therapy, or surgery. Now THERE you've got sumpin'!
johnrocket, I suppose if I were threading a catheter into someone's brain tumor I might feel a bit less restrained, and probably a lot more trained/experienced if I were doing it in India, and not the US. One perplexing thought about the Cotara GBM scenario: if you are going to put a delivery catheter into the body of a tumor and deliver radioactive iodine, why do you need the MAB? Anyone?
rrdog,agree. freemice, yes!betabodies. I share your enthusiasm.
dog, agreed. what's your take on the virtual meeting the FDA and PPHM had re. Cotara, and what its latest iteration is at this point?
cloaked, seven poster presentations is a lot, for sure. The way I see it is there might be about 1000 in all, a guess, since there are 33 sections with 30 presentations each. Truly a tour de force, and emblematic of PPHM dedication to first rate peer-reviewed research. Quite a feat for a small company with such limited resources. It would almost make one think it was a front, or the research arm, for a larger corporation...or [potential] retail pathway for a university?
alvaroc, I was thinking earlier today I should look at Affitec events since it seems likely that the Russians are behind the latest increased activity, and that Affitec's fully humanized anti-PS, being tested in Russia, might be the first such product to the marketplace.