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James, you wrote, "Sunrise most certainly did not flop in any way, shape, or form. The Treatment Arm performed as expected - while the Control Arm blew away all expectations and historical norms going back decades..."
We need some real numbers to establish your assertions here, and I have no recollection of seeing those numbers. I don't remember the "blow away, and going back decades". Without specifics it maybe can be assumed that Bavi performed a couple months better than historical norms for Doce (which makes that part of the pr true) but it did not (apparently) perform better than placebo (which is probably also the case).
It is known that other placebo trials are now "outperforming" THEIR historic norms. That is, for some reason placebos are performing better than ever, and the more convincing the blinding of the placebo controlled study; the more "therapeutic" the treatment environment (e.g. IVs, modern medical equipment); and the more scientific the treatment environment appears to the patient, the better placebo groups seem to do. Finding a difference in the background and therapeutic milieu between Bavi-treated and Doce + placebo will not be easy, and finding Bavi in the placebo is truly a case of lightening striking twice.
If you recall, "spare-the-mice" left this board at about the time we had a healthy discussion here about the possible futility of using an immuno-stimulant such as Bavi with a cytotoxin such as Docetaxel. How can one expect activated monocytes (for instance) to reproduce when cell division is being discouraged and actively reproducing cells are being poisoned? Some stockholders have sat back and said maybe they will be right for all the wrong reasons, which often happens. It was a long shot from the beginning IMO. I'm waiting for Bavi + irradiation; and Bavi-labeled imaging agents, to mention only a couple realistic application for the science.
good stuff good&plenty. thank you. eom
James, thank you for your learned response. Yes, I think if the Bavi arm proved to have a MOS of 14 months it should be approved. I think Bavi should be approved anyway whether or not it helps patients with advanced lung cancer, but that is only a feeling, and there are those out there that want more in the way of proof than our feelings, as you well know. The point is to get approval for ANY indication so it can be used off-label for others. However, even at that, the problem in real-life is that off-label use is considered E/I (experimental/investigationali) by insurance companies, and will not be paid for until proof of efficacy, or after vetting in large placebo/well-controlled/double-blinded studies. If it is the subject of a clinical trial for a given indication the insurance companies won't pay for it either.
Life is a beach.
patiently waiting, for several hours in traffic jams through Oakland and San Francisco on St Pat's day for the parade and when the GoldenState Warriors are getting ready to play, I think about that post of mine, and came up with the same question you have. And then there is Carboat's point which is the most telling. If both treatment groups think think/hope they are getting the Bavi, and that it will help them then there are even more serious questions about Bavi, and all we can do is hope that the placebo and Bavi have once again been switched....and that is a bit much to hope for.
James, I don't see a lot of room for speculation about the outcome of the Sunrise trial. For instance, it is difficult to speculate on possible failure to randomize the trial cohorts from 160 sites. Even though the Doce + placebo outperformed historical survival times, clearly Bavituximab did not perform well enough to establish it as a valid treatment for advanced lung cancer. This will be the result regardless of Garnick's "post-mortem on the trial and its post-mortem". The biggest area of speculation that I can see for this trial is not what Bavi did or did not do because we have that answer, but whether or not in the future every patient being treated with Doce alone should also be treated with a placebo and told they are part of a clinical trial so that they too have an opportunity to outperform the historical norms of survival with Doce. We definitely did not prove Bavi is better than placebo, but instead re-established the value of placebos. We have learned that Bavi is not going to be used for large (bulky) solid tumors. We have apparently learned it is safe. Examination of postmortem tissues, including Doce alone and Doce +Bavi will provide some insight into possibly using Bavi to prevent/slow growth of micro metastases and to prevent recurrence via active immunity. I suppose the only thing missing from this trial design was a third group of Doce alone without placebo to see if that group would have also outperformed. The above is merely "first-pass thoughts" without much serious reflection. Any counter views are welcome.
cloaked, I do think Bavi can be significantly useful, but prolongation of life by 3-4 months against end-stage could be argued in some circle to not be a cost-effective end of life treatment. For instance, in that last two or three months of life simply getting into a car and going to a doctor's office for any treatment could be grueling. That aside, I think asking a agent with more of action similar to Bavi to significantly reduce large solid tumor load is a bit of a pipe dream. As said repeatedly, it will be of the utmost interest just to see what Bavi does to micro-metastases, for instance, and we will get that information. The "spin-off' knowledge gained from trials such as these can sometimes be as/more important than the stated goal or endpoint. And again as previously stated, I think you have to be a cancer surgeon to appreciate some of these concepts. The idea of an immunologic approach to cancer therapy has been around since before the early seventies when I came into contact with it while in surgical training. That was almost a half-century ago. The gains in I-O for solid tumors have been inordinately costly and relatively low-yield. It does sound good though. That is a part of what I classify a pipe dream.
my take-away from the cc: dawning realization in the executive suite that the Bavi PIII was a pipe dream from the beginning in terms of a home-run for Bavi as a giant (advanced lung cancer) killer, either alone or in chemo-combo. King's responses to most of the questions seemed muddled. A clear-cut strategy with Bavi remains to be defined. The immunohistological stains of [evented] trial patient tumors will be important to potential immunological treatment partners; and thank God for Avid. The most important question is why the Doce-chemo arm patients performed so much better than historical norms, and how these control patients compare to the Bavi-treated Doce group.
I don't think this study is the death-knell for Bavi or PPHM. We have all learned something from it, and I only wish I were on the inside picking up the pieces, because the post-mortem on the study (and the patients) will be immensely interesting.
This reminds me of the cochlear implant project in which the original implant inventor was almost certain of a home-run..that deaf implant recipients would be hearing in stereo with his home-made bipolar silastic and gold wire implant. However, the initial trials were a squeaker, with only equivocal improvement in hearing with the first implants. the debate was intense whether to go on. Implanted patients were farmed out to various institutions for testing. It was concluded that perhaps the implant was marginally helpful. The deaf could hear sound, but was it significantly meaningful? Since those days in the early 1970s when a crudely manufactured and implanted wire was electrically charged and the patients heard a tone, to the present time, the cochlear implant has become standard of care for deaf one-year-olds who are mainstreamed with normal-hearing peers in public school. I see that future for anti-PS, and for anti-phospholipid therapy, and suspect that Bavi is actually a crude prototype for "biosimilars" to follow. PPHM needs to continue its preeminence in this field.
Maybe Wednesday announcement has nothing to do with Avid or Bavi, as CJGaddy wrote in 2008 re patent portfolio: "Peregrine has exclusively licensed Dr. Philip Thorpe & Dr. Rolf Brekken’s VTA & APT (Anti-Phospholipid Therapy) discoveries thru a sponsored research collaboration with UTSW/Dallas, and has in-licensed “Anti-PS Methods” and B2GP1/Anti-Angiogenesis from M.D.Anderson/Houston (Dr. Alan Schroit). These technologies include Anti-Phospholipid Therapy agents (3G4/Bavituximab, other Anti-PS mabs, Anti-PE…) which provide a ‘unique approach to treating both cancers and viral diseases’, the Anti-Angiogenesis agent 2C3, and other VTAs (like Anti-PSMA & Anti-Fibronectin). Most recently (7-2007), Peregrine has in-licensed “certain Anti-PS antibodies” from The Univ. of California, possibly including Anti-PS mabs like ‘IS1’ & ‘CL1’ from UCLA (Dr. Pojen P. Chen). In 1994 & 2004, Peregrine licensed the TNT & VEA technology (Dr. Alan Epstein’s discoveries) from USC and Cancer Biologics, Inc. Maybe news from Russia or China? Good luck to all!
cloaked, thank you for all your hard work and contributions here, and thank you for your recent expositions on results of Bavi pII and PIII trials. However, I find it impossible to understand any of it, especially many of the premises. Please expound on what you said about "...one would really have to explain what AstraZeneca, MSK and NCCN are doing with bavituximab if they believe it doesn't work." What ARE they doing with bavituximab? I missed that. thanks again. .
jbain, amen. I wish I could have put it so succinctly. eom
swing trader, thanks. you can imagine the problems with using an immunostimulatory medication such as Bavi on previously treated cancers since most of the treatments are net:net immunosuppressive...and permanently so. But this subject has been addressed ad nauseam in the past as an objection to any trial with Bavi-chemotherapy. So the "outperforming" chemo-only control group may or may not be assumed to be the same as the Bavi+chem group..depending on your point of view....which leaves us with a trial with no definite conclusions other than that Bavi seems to improve survival somewhat, but does not deal a convincing deathblow to advanced cancer when used alone or in combination with chemotherapy. This was a very poor choice for showcasing Bavi, but at the time it was the only open door we had for a clinical trial.
hayward! and I thought I was suspicious. I am thinking it is shorts covering. If it were a significant volume it would knock our socks off, not 1/2 mil. bucks of buy/sell. we'll see.
Avid news is terrific! Thanks from stockholders to all in Tustin who made it happen. Avid has mostly performed like the world-class monoclonal antibody production facility it is. Cheers!
thealias2002, instead it looks as if this p3 was another similar p2? The trial design apparently assumed equality between groups. If there was, in fact, equality between the two patient cohorts, the control arm and the treatment arm, then Bavi apparently does not have significant effect on advanced lung cancer. But that remains to be seen because the Bavi-chemo treated cohort performed up to expectation, or appeared to be extending life beyond the average time that would be expected with chemotherapy alone. There are some things a trial design just cannot work around. If an athletic trial among two cohorts of first graders assumes equality, and most of one group are born in the first quarter of the year, and most of the other group are much younger, born in the last quarter, then that age difference would have a profound effect on athletic coordination. So you can imagine the control group will be of great interest to Garnick and others who designed this study, but when the control group differences are ferreted out it will be too late. Most end-stage cancer patients have been treated with multiple medications, and I believe one qualification for entrance into this study was that entrants have untreated advanced lung cancer. I could be wrong on that one.
the alias2002: like your reasoning, but doubt the CEO would cloak a near-term FDA approval prospect in such verbiage. The results of this trial are, in a word, underwhelming, and hardly the usual scenario for FDA approval, but as you and others here say, there is always that remote possibility. I personally am not doubling up on that chance.
PPHM VeryLong: It is not an indictment of the trial design. Such are only possible within a given realm of statistical probability, and this is a case (apparently) of the control group response lying significantly outside the "possible-probable". Someone better with stat.s than I am...especially those inside PPHM looking at all the numbers...can tell in an instant if the outperforming group could have possibly outperformed by chance alone, and knowing the competence of Garnick, et.al., I think the chances are slim to nil that the outperforms just happened to outperform. Nor am I throwing in another conspiracy theory, although that is only one of several answers. The real value of these trials are lab values, and particularly pathology slides of tumors and metastases, and read-labeling, etc. to see what the tumors treated with Bavi look like compared to the control group. This is a very interesting, although not particularly favorable, outcome and inquiry. Would love to be on the inside with this one.
bottom line: if I had advanced lung cancer I would definitely opt for (and pay extra for) adding Bavi to the treatment mix. Just think of what Bavi- might have done for that dynamite outperforming Doce-only lung cancer treatment cohort!
my takeaway: The trial design did not take into account the fact that the Doce only arm might be more heterogeneous than the Bavi group. The Doce-only arm "outperformance" is almost certainly not an accident. We have enough data on Doce alone to know that something other than chance is at play in such an outlier cohort. What happened with the Bavi + Doce arm was probably statistically significant. That is, Bavi probably increases, but barely, survival of those taking Doce alone in a "normal" test group. Did we prove anything with the trial? We found out Bavi is not a home-run alone or with Doce for advanced and/or metastatic lung cancer. But we knew that from the PII. Hardly a surprise. We found out a slug of information about Bavi side-effects. Let's face it: bulky tumors similar to those burdening the test groups still must be "debulked, for the most part, with surgery or irradiation. We know Bavi and the anti phospholipid science and technology has an enormous potential in anti-inflammation and anti-cancer therapy. We just did not hit the jackpot on the first (and impossible) trial. I don't see a buy-out at this point based on the hard evidence shared thus far with stockholders. If there's other inside information being acted upon by potential buyers I would like to see it. Will be interested in results of Bavi with irradiation treatment for various cancers. Also hope to see it tried as a preventative, and for other chronic conditions...not for impossible-to-cure bulky tumors.
A Saturday MD perspective: The phase III abruption tells us what we already knew: ; lung cancer is a bitch, and Bavi did not dent it. You only fully appreciate that when you have it in you hand as a surgeon. Lung cancer is a boulder, a mountain, or a planet compared with an ant-size construct such as bavituimab. And the same can be said for all immunological attacks on far advanced, well-established (end-of-life) lung cancers or other bulky solid cancers. If the side-effect profile from this study is satisfactory we can move forward on something sensible for bavituximab, such as prevention, or possibly its utility in combination with irradiation therapy. Bavituximab will continue to be undervalued until a use is nailed down. Thank God for Avid.
realist, good post.
mass hysteria, nice post. efforts appreciated! thanks. eom
Realist, if you consider that the vast majority of oncologists have not heard of Bavituximab, why do you think it would be on the radar of any other specialists, like OB, ophthalmology, or even family practice? Maybe a handful of oncologist might remember having seen Bavi listed in a group of"hopeful" anti-cancer agents. Almost all MDs have been burned a few time too in chasing the dream. I don't post here because nothing new has happened in 16 months, but I remain invested in PPHM, and have even set aside a bit of cash throw in... (bad $$ after worse?)
we'll see.
anyone know who the ceramist is doing the wheel throwing on the ad displayed here? he is good (from one potter to another). good luck to all you longs. I'm still holding PPHM...and still disgusted.
today looks like capitulation on this board.
And I've written that only twice in a decade
hypi, I enjoy your posts. You said, "without a partner the odds are very slim that they will make this a reality", which has been said here many times in many ways, and in the past might have been true, but at this point there is enough interest in this sector, and in the PPHM anti-PS/apoptosis niche, that positive results on Sunrise (and even on peripheral projects) will inevitably buoy the stock price...with or without a partner. The biggest risk at this point is the appearance of an H-bomb cancer killer. For years I have been of the opinion that PPHM is an arms-length de facto R&D arm of a large pharma, and the commercial arm of UTSW, and have not changed my mind. Can you think of a less expensive way to do R&D on a product such as Bavi?
atptx, OMG, amazingly ambitious and interesting program on -PS and apoptosis. Would love to have transcript. Let me know if it is available. And welcome to the board.
eyebuy, brill. well-said. the process mind-numbing...worse than trying to build a new house in CArmel, CA.
Paladin, the only good thing about owning a dirt-cheap commodities is Knowing for reasonably certain it is, in fact, dirt-cheap...and then buying more. I'm about ready again.
The 6 month chart looks good at a time when we coulda/shoulda kept heading down or stabilizing at 1.20 to 1.30. NObody would be investing now if they did not know something good.
We'll see if the info out there is yet enough to fill a sail or two on SS Peregrine.
the alias: the catylyst for continued upward momentum in stock price is the dawning awareness of inevitability...of the logical next step. Immunotherapy is a logical therapy to cure some cancer, and to act as an adjunct to other treatments such as irradiation, surgery, and cytotoxic chemotherapy. PPHM still appears to have a monopoly docking site on a very strategic locus
where the nitty-gritty of cellular life and death occurs... a cell membrane lipoprotein, -PS (phosphatidyl serine).
Hypi, "getting left at the altar" with a "battered and outdated bride" doesn't strike me as a serious problem at this point. Attempts at immunotherapy for cancer have been in the works for over a half-century, and have not been successful enough in the lab and clinic to make a dent in cancer, and therefore in the marketplace.
The criterion for "medical necessity" (read, reimbursement from medical insurance companies) of a medical service, device, or medication is whether it is at least as effective and cost-effective as an alternate (established) means of treatment. To my knowledge insurance companies have not begun to use the metric of whether a medication significantly improves the outcome of another, but this latter "loophole" is where we are aiming, and it seems a solid strategy.
Also important for PPHM, in addition to immunotherapy ,per se, is the manufacture and sales space of MABs, and with its MAB production facility at Avid, PPHM has the capability of being a significant player in that field. True, a significant fraction of short-term PPHM stock price is dependent on Bavi-,
but the company's long-term survival depends on MABs in general, and specifically on the potentially vast anti-PS space which PPHM is just opening up, in which Bavi is merely the flagship...an anti-PS Tesla if you will.
cj: you would think the share price would explode with this type of information. Great step forward. This phase is dejavu all over again. Seems similar to the pre-clinical years.
carboat, curious. Do you know the average liability carried by these clinical trials companies? About a prior lawsuit...what company hasn't had one? Do you know the details on that? The losses from the botched trials are, indeed, incalculable, but the criticism strikes me as being viewed through a retrospectascope rather than a prospectascope. PPHM was forced, by monetary considerations to at first go to India and Russia, etc. rather than conduct trials in US. In some cases we have to fit expenses to available resources. Only some thoughts. None of us have all the answers. It's just that "obvious" errors are easier to see in hindsight.
patientsdeservebest: with all due respect, you seem to be overreaching reality with this, "If you have followed PPHM you will know they put the best spin they can on the smallest amount of tortured-to-make-it-look-positive data." I am into the peer-reviewed medical literature in a big way every day, and think PPHM has bent over backward to be "ethical" in every sense of the word. No hyperbole. No PR missteps in recent history. For a company "thin on paper-pushers" PPHM does a remarkable job of staying inside the boundaries of scientific propriety.
The following in your post is simply incomprehensible to me:"You will also know they don't do their due diligence which is why they completely botched their Phase II". Good luck on your stock picks!
PPHMtoolong, stat/sig or statistical significance is everything.
Without it data is "anecdotal", or someone's impression that a set of observations is real. The following is grossly simplified: To get into the "stat/sig ballpark" usually require that, after doing some simple math on a data set, it can be establish that if the test were performed 100 times the observed data could only happen by chance in 5 or fewer test runs out of 100 identical trials. Test data with a p value of .01, is much more reliable because only once in one hundred similar test runs would the observed data set be expected to occur by chance. Obviously the lower the p value, the more certain is a real difference between test data and "chance" occurence. What about p=.08? Not good enough even though the data set may actually be valid. The number of observations (patients) is factored in.
Once you've taken courses in statistics your point of view becomes almost intolerable to more romantic/dreamer folks...
wook,in addition to PIII good results in bulky,metastasized,incurable cancers...a disease which I doubt will ever see much Bavi application, a huge stimulus to PPHM stock price will be the first "spin-off" use...and even pre-clinical data would do it...such as Bavi use with rheumatoid, Alzheimers, or other inflammatory states. Inflammatory states seem a natural application for an immunological adjunct to be used alone or in combination with other anti-inflammatory agents or antibiotics. This is an arena PPHM should consider licensing.
hypi:you're correct about PPHM having to be at Roth, and it was obvious that SK was simply going thru the motions. reminds me of reading a report in class fast as possible just to get thru it.
Listened to SK presentation. Did not notice mumbling. It definitely could have been slowed and simplified and better tailored for the audience since there was really nothing new, and did represent a "teaching"/sales opportunity. Agree with others here that it was simply an update. It made me think that SK knows that financing is assured through PIII results; that there are other applications for anti-PS than a combination with cytotoxic agents; and that the next big push is combination with immune checkpoint agents.
Some notes (again, nothing new): PPHM has amplified on the finding that -PS inversion on cell membrane is a primary player in immunotherapy. Bavituximab has a good safety profile and significant clnical trial lead over competition in the expanding -PS space. Bavituximab blocks immunosuppression and activates the immune system. Creates a positive tumor microenvironment for other immune checkpoint agents to act more efficiently....changes non-responders into responders. Consistent results in animals and humans with Bavi. 19 studies, 500 patients treated with good saefty profile. Removes the brakes on immune system.
Chemotherapy combos dominate near-term efforts with Bavituximab with current PIII lung cancer study. PIII "well underway". Fast track. Looking beyond, front line lung cancer and breast cancer which have shown initial good results. Combination with Taxanes in breast cancer increases presentation of T cells to tumor Rectal adenocarcinoma and irradiation study looks promising. Melanoma trial. Moving into immunotherapy combination space. Bavi is only "upstream" agent which can combine with any of the many downstream agents. Turning non-responders into responders is a goal, and has been seen consistently. Yervoy trial with melanoma is an example. Possible combination with vaccines.
Avid is profitable. Revenue going into R&D. Nice growth over past several years. Expanding Avid facility for outside orders, Bavi- production, and "other PPHM agents". Several abstracts for ASCO.
question: Discuss evolution of breast indication:
Why move into that crowded space? It has cleared out a bit. More data from Bavi is positive...75% response rate.
question: Lung cancer PII mix-up.
250 posts since PPHM medical/science was the subject...
"If" is no longer a legitimate question about PPHM share price rise, but "when". My annual (& perpetual) prediction:
PPHM share price goes up "when" big money interests are aligned. Our job is to be certain as stockholders we get our fair share, poof-positive that "altruistic investments" and IHUB communications pay off. Keep up the good work here folks. But more science now maybe?
"Free The Mice(!)...reincarnate or reappear. Please? Your fan-base is pleading. Another infusion of exciting,fresh, theoretical scientific optimism. The board's conjecture about trial is interesting, but a bit overwrought IMO, and a distraction from what is many times more important.
The PPHM anti-PS platform...not simply Bavituximab marketed by PPHM for incurable lung cancer... but THE entire anti-phospholipid platform is PPHM,s and well might define the idea of a "disruptive technology".
Bavituximab is only the flagship for this platform, one that exploits a unique docking site on a single cell...and not any cell, but those cells with cancer, or those affected by cancer, such as endothelial cell nourishing the cancer. But there are other inflammatory disease targets in the future. The myriad possibilities of Bavi-like drugs is intriguing, but also a diversion. Today we are focused on Bavi approval. Phase III in FDA pipeline. Patient enrollment good. Bavituximab, as a first example of PPHM technology, has passed through the most harrowing of FDA pipeline journeys, with exhaustive animal trials, and now human trials, one of which apparently sabotaged. Bavituximab is unquestionably safe. Side effect profile is apparently very good. It has significant accumulation at tumor, e.g. great "site specificity". Bavi- is an immunological adjunct. It excites the body immunocyte killers. Bavi-like fully humanized monoclonal antibodies can carry a payload to tumor. Bavituximab is an established double-tasker. A Bavi-byproduct carries x-ray dyes to tumor while it also encourages immunocytes to attack the tumor. Imagine following tumor progression or treatment response with Bavituximab. Naked Bavi-, or Bavi- used alone, is apparently weakly cytotoxic to cancers of several types, and occupies a unique and important niche in the immunologic attack on cancer. Bavi- is not a cure. It is a safe stone on the way across a rocky stream where on the other side is cancer not as a killer, but as a chronic disease. Obviously if Bavi is used early it will have greater application than for large, bulky, metastasized, incurable tumor. Bavi used early and frequenly appears to be where this can go. Bavi has, if memory serves, great penetration of the nasal mucosa. Better than Flonase. Bavi- is a no brainer. Warning: I thought the same of Erbitux and Cotara. What are we waiting for? The money guys to get it together. Let's move the ball closer to the goal. Cheers!
CP, the answer to your question about the apparent paradoxically good performance of "non-human Bavi-" was once given by Steven King, PPHM CEO, who said that non-human Bavi, being more antigenic than fully-humanized Bavi, actually stimulates the body's immune system to react and attack cancer better than fully-humanized Bavi in some cases). So apparently non-human Bavi acts as a "non-specific immunological adjunct" in addition to its anti-PS specificity.