Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
geo and CJ, Duke virologists are still doing "shake and bake" with designer viral membrane particles to "unblock" the body's inability to mount a competent immunological response to HIV. I see nothing related to anti-PS antibodies in the work, and get the impression their focus is on membrane GLYCO- rather than LIPO-protein. As an aside, I am a bit down in the mouth because I spent 2-3 hours on a Forbes article about PPHM, (on the Forbes website),and left it to Google sumpin', and could not get back to my work. Lost. Shoulda worked on it in MSWord. Then when the PPS share roared yesterday I thought maybe Forbes would SEND an investigative writer. Today? Not!
drragmop, interesting. That simple? "Rx Perforin po bid prn?
CJ & Firefox, nice. One critical link on the way to market Cotara is insurance company reimbursement, and the need for rapid-shedding of the "experimental/investigational" label insurance companies hang around new drugs for an unconscienalble duration, refusing thus to pay for treatments.
Many oncologists will be called on to help annoint Cotara the "standard of care" for GBM, and oncologists are only one "pressure group" in only one arm of the mighty cancer treatment troyka: surgery, irradiation, and/or chemotherapy.
Cash flow is critical even deep within the rural pastures of physician offices...or luxury oncology treatment spas...and if a cut of the action from Cotara is not possible...medical doctors/providers will probably want to be in the grandstands cheering for this one. It would be decidedly bad PR to oppose an agent that has survived the trials Cotara has. The numbers are simply too good. Cotara technology is established imo. A new reality. Elegant logic suggested by overwhelming numbers. How long to the treatment table? We'll see. The next problem to solve with missile Cotara is bone marrow suppression if used systemically in tumorcidal doses. In single dose IV form, given to the level of bone marrow suppression, Cotara had no effect on Colon cancer progression. Therefore for effective systemic use mouse parts must be history in a hurry, and that's easy. We know how to make fully human Cotara. That's what the Epstein lawsuit was about, in part, and even though the are proably working on it 24-7 in China, and have the human-MAB recipe, Affitec in Europe, and PPHM in US, can produce human MAB Cotara in a heartbeat. A smaller missile? Fully humanized? Got it. Lower doses over a longer time period of time. Simple if fully human. And we know the dosing parameters, the maximal allowable dose to avoid systemic toxicity. Easy to use Cotara for imaging of tumors. Problem solved.
The message is clear: radioactive isotopes (RAI) borne on Cotara, a monoclonal antibody (MAB) missile that targets necrotic core of cancer, delivered with a special catheter that's tip is inserted into cancer bulk, is significantly effective in slowing the growth of the most resistant of cancers. Why target core cancer cells? Because the center of cancers contains a miasma of DNA and "sleeper" cancer cells capable of escaping externally delivered chemo-irradiation; regrouping; and recurring. So radioactive isotopes, specifically delivered, continue to perform as efficient cancer killers with minimal side effects.
As mentioned in previous posts, naked-Bavi will probably be used with Cotara to stimulate macrophage activity, and as armed Bavi perhaps carry a payload of RAI, in conjunction with Cotara. Core and cell surface. And then PPHM r84, a better Avastin to shut down the blood supply A triple smoke-out. More likely the next payload for all double-armed MAB missiles will be tTF, that small molecule PPHM gem that fits nicely onto both missiles.
And the next sensation, r84, PPHMs answer to Avastin has barely been mentioned here. R84 is cooking right now in Affitec reactors for use in clinical trials in the USSR. Shouldn't be much longer. PPHM seems to be in good shape.
pphmtoolong, what kind of feedback have you had from the company or the folks doing the clinical trials?
chey,who would believe? Patriot paying a dividend is less likely than PPHM, at least for the next 10-15 years.
chey and gigwup,I'm interested in the "secret" PPHM filed with SEC to exclude information from filings. DeptDef you supponse?
jess, good-on-ya. You're right again as usual. A case of dejavu all over again? Or senility maybe. Anyway it is great stuff..and bears repeating!?!
thanks CJ, Never heard of Journal PLosOne, so glad to know about it.
The article is terrific. Everyone here who reads it must know that Genentec has PPHM activity under the microscope...or cleanly within the crosshairs.
north, interesting, thanks. Tough to know how to spin it.
dia, terrific. where was this r84 info presented?
Yes CJ,a million tanks. And U2 JGal. Igettakickoutayou.
dia, nice, thanks. Agreed, 1st generation Cotara and Bavi have put on quite a show. Lots more folks looking now, so don't kick yourself for not trading. Trading is one m.o., but not very relaxing...or rewarding sometimes. 1st generation Bavi and Cotara beat standard of care treatment, and Cotara by an extreme margin, one large enough to be...uh...huge. Whoever is shorting right now is almost assuredly doing it short-term to load up REALLY big next opportunity. Dollar cost average in. That's all the little guy can do. And you're right dia, once approval for 1st generation, then the deluge--improved second generation variaties.
Not sure how you figure $50-60 million. Per year? Net? Hmm. Surprising thing happened on the way to market with bavituximab. Naked Bavi was noted to be immunostimulatory all by itself, and armed Bavi apparently has target-specificity issues. Cotara is the ticket right now. In its favor for brain cancer use (for GBM) is that Cotara is "procedure intensive," a procedure...any procedure...and a new one at that...appeals to neurosurgeons and neuroradiologists. And it absolutely brill about GBM CNS use. MAB Cotara is such a huge and clunky missile it probably can't back diffuse into the body, or get out of the subarachnoid space to cause systemic side-effects, such as bone marrow suppression. Wonder what they are doing about necrotic tumor "wash out" from the cerebralspinal fluid. Might be a job for Bavi, recruiting macrophages and such to the site for cleanup. Mixing the two makes a huge amount of sense.
Other indications for Bavi, in addition to slowing most solid tumors? The law of unintended consequences dictates that Bavi will probably be used off label for, just for fun say Alzheimer's or arterial disease. Set your sails by one principle: Note who is behind PPHM. Inventor, PThorpe, and UTSWest. Look at the science talent. The in house boutique MAB manufacturing plant. The former CEO of Genentech just became chancellor of UCSanFrancisco Medical School. Duke U. is Virology U. This enterprise was floated and is captained by university guys, not by the group on stage at the SHM, although there were some science standouts there, and those directing in the background seem satisfied with management.
cheynew, $6 is a no-brainer and very do-able in a short time. I hesitate to say what I REALLY value PPHM assets at because it would probably look gonzo in light of past events. Suffice it to say, I have followed this science for a long time, and saw what happened to ImClone and Genentec, and think PPHM properties are better than those two...combined. And PS...Oh, to be right for once!
My take-away from gandolph's summary of SHM is that neither Cotara or Bavi are "home runs" in the clinical sense--that we will have to slog through PIII, or some abbreviated form of it-- but that Bavi and Cotara could provide company stockholders with at least a "4-bagger" in the future, and both will probably gain regulator approval if not knocked off first by newer technology. Nothing in the clinical information released to date contradicts that. Mojojo's appropriate and skillful summary of what management knows and we don't (ie a sense of the Republic of Georgia Bavi trial results) is important, and hopefully a positive. It has become glowingly obvious that something must be done to make trials more efficient, primarily because our ability to "tweak" designer drugs is lightyears faster than our ability to test them, and as noted in the SHM, the exact design of a drug at the beginning of clinical trials must be the same as that at the end, which may take years. Example: Cotara is chimeric, has allergenic mouse parts, and large in size for a contemporary MAB. We have a fully humanized MAB but can't use it. Similar story with Bavi. We are testing last year's flavor with the later, and last decade's model with the former. Nonsense. In the case of Cotara we need to find out how to use it systemically, repeatedly, with no bone marrow suppression; and with Bavi how to increase target specificity of the fully armed and fully humanized model. Meanwhile, back in the office cancer patients are waiting.
gandolph, thank you for the heroic typing effort. good info
mojo, another nice post. You're on a roll
jojo..thanks. interesting. what's all the hubbub about last couple days? Looks like more of same to me. Co.selling cheap stock to lucky investors, then lockin' them in. S'pose we'll have to repeat PII again? Never know about those Injun trials. Could be fudgin' results. Might give FDA a black eye if they don't send us back to "Go" again. Yeah, Genentec would get the same treament too.
Cotara clinical investigators have (repeatedly)provided "proof of principle," re. survival benefit of treatment of GBM with the agent, and given the severity of the disease and lack of viable options, I think any FDA evaluator(s)will do what is possible and necessary to move Cotara on down the regulatory pathway to approval. Additionally, it appears that PPHM has the personnel who can accomplish that goal. At this point a partnership and licensing deal should be quickly consummated, paving the way financially for further advancement of flagship Bavituximab. I have never been more positive about the company's prospects.
jess and magic. The following is one of the better summaries of what's happening in MAB I131 conjugates. Jess is right about Susan Knox at Stanford, and her look at Cotara with advanced colorectal ca, which did not reveal what everyone hoped. One problem was dose-related bone marrow suppression. As the following article explains (partially), Cotara injected via special catheter and pump into the subarachnoid space for GBM is probably restrained somewhat from back-entering the body circulation by the blood:brain barrier, so the problem of bone marrow suppression would not be so important. This report reinforced the idea that targeted I131 has a place at the treatment table because of its unique locus of activity (necrotic central tumor areas), but at this point will be only one arm of the treatment mix.
"To date, only tositumomab6 (131iodine-labeled murine anti-CD20 antibody) and ibritumomab7 (yttrium-90–labeled murine anti-CD20 antibody), and two radiolabeled antibodies for the radioimmunotherapy of human malignant B-cell non-Hodgkin's lymphoma, are approved for use in the United States. Along with 131I-chTNT, now approved for refractory advanced lung cancer in China, these reagents are important new biologics for the radioimmunotherapy of cancer that can lead the way to the identification of new methods to produce longer disease-free intervals and/or survival times for patients with these tumors. In this regard, the results of our study show that 131I-chTNT can be an effective radioimmunotherapeutic reagent when given systemically or intratumorally in patients with resistant lung cancer. Adverse reactions to this therapy are essentially limited to bone marrow suppression due to the circulatory time of the radiolabeled product (passenger effect). As expected, intratumorally administered reagent, which enters the circulation at a slower rate over an extended time frame, has a lower severity of thrombocytopenia and neutropenia than when given intravenously. The results also show that small-cell and non–small-cell tumors are both good targets for this form of therapy.
Although most prior studies with radiolabeled antibodies have been performed using systemic administration,5,9 a number of investigators are now focusing on the locoregional use of these reagents to treat identifiable lesions in solid tumor patients. Reasons for this include the low amount of uptake seen in tumors after intravenous injection, poor penetration into larger lesions, and heterogeneity of antibody uptake. Locoregional injection has been used most frequently in studies with malignant glioblastomas, which are tumors that are especially difficult to treat due to local extension of tumor tendrils into the white and gray matter of the brain. One such study by Riva et al24 using radiolabeled antitenascin antibodies found that catheter-directed administrations of 131I-antitenascin antibodies produced an increase in both the duration of remission and survival time in these difficult-to-treat patients, with little or no toxicity. In these studies, the results were dependent on the size of the tumor at the time of treatment. In addition, studies performed at multiple centers in the United States with 131I-chTNT-1 plus biotin produced dramatic results despite the dismal prognosis of these patients. In these studies, an infusion pump was used to deliver the radiolabeled antibody into the tumor over a 20-hour period via a surgically implanted catheter (unpublished observation). The use of the infusion pump to deliver the radiolabeled antibody slowly and forcefully may have improved the effectiveness of locoregional delivery by ensuring a more homogeneous distribution of reagent into the substance of the tumor. Although this may be an important consideration for glioblastoma, the method used in our study appears to have successfully infiltrated the full substance of the tumor, as shown by images taken shortly after infusion of tumor by the radiolabeled antibody (Fig 2). Because of the lower toxicity of this approach and the ability of radiolabeled antibody to infiltrate even large tumor masses effectively, locoregional or intratumoral injection may be a useful method of treating individual lesions such as those seen in glioblastoma or lung cancer, as described in this report.
Despite these hopeful findings, the number of complete responders in all the above-described studies was small, indicating that radioimmunotherapy might require additional treatment modalities to be used in combination for this form of therapy to reach its full potential. For example, it may be possible to improve the clinical efficacy of 131I-chTNT if it is used in combination with methods to increase the radiosensitivity of the tumor.25 In addition, as demonstrated by Anderson et al,26 prior treatment of tumors with ablative therapies increases the target size for TNT antibodies. In this study, it was demonstrated that prior radiofrequency ablation therapy of hepatic metastases, which generally produces a 1- to 5-cm zone of necrosis, significantly enhanced 131I-chTNT-1/biotin uptake in the tumor lesions. Anderson et al is the first patient study to take advantage of the basic property of TNT; namely, its proclivity to bind to dead and dying cells. When used in this manner, 131I-chTNT may become an adjuvant to other cytotoxic therapies. Chemotherapeutic drugs may also be used to generate larger areas of necrosis in tumors, and some of these drugs, such as doxorubicin, are also radiosensitizing because of their inhibition of DNA repair mechanisms. In addition, methods such as hormonal therapy used in prostate cancer patients can produce massive tumor destruction in a short period of time, thereby providing an excellent opportunity to test the adjuvant effects of 131I-chTNT in this setting.
With the approval of 131I-chTNT radioimmunotherapy for refractory lung cancer in China, it becomes possible for clinicians to study these more advanced concepts with 131I-chTNT radioimmunotherapy. It is hoped that ongoing studies in the United States and China with 131I-chTNT may provide new indications for its use or reveal its role as an adjuvant to current treatment approaches.
cj, thanks. I don't get it.
chey, poster sessions usually begin soon after the meeting, and the posters are up all through the meeting for strollers to peruse at their leisure. Often the poster presenter is available to elucidate and answer questions. Exhibitors are the firms who want to sell goods to attendees, and their fees for exhibiting usually help defray the cost of the meeting.
ysf, hilarious but painful
r62, thanks for the follow-through
hey r62, always appreciate your posts, but in the interest of time, can you connect the dots with your impression. If it seems too far out, maybe we can dig it all out ourselves. Meanwhile I'll trust your instincts. Thanks for your valued input
jake, bottom line is that both anti-PS and TNT technology have a future. If things play out as usual in the creative process, you have to almost give one away to finance the next one...if thing are to progress down the pipeline in time to be therapeutically relevant. Because of Avid PPHM is only in bad shape if the entire MAB therapeutic niche falls apart. More than anything else we are seeing the effects of war and budget deficits, a guns or butter phenom.
jake, sensible thoughts, thanks
mojo, my take on overall survival data yet to be revealed is that you just can't wait forever for someone to die. There IS a agreed-on cut-off time for these studies, and I suppose we're about there. One note of caution: if the survival numbers were spectacular they would stop the study and start putting Bavi- in the drinking water for everyone, so we'll see. I think we are going to see an incremental but definite improvement in survival. Again, with the advent of gamma knife (irradiation) therapy, DaVinci, etc. Bavi- should be coupled with that rather than used in chemo-combo for end-stage disease previously treated with chemotherapy which has caused immunological burn-out.
thurly, thanks, "...build the business on [Avid] commercial production"
Good concept...prospects for outside contract work looks strong, and and a two-ace kicker...PPHM's in-house "pets" Bavi and Cotara. If they shine in the marketplace the company is a rocket. If they flame Avid survives. Avid makes it not matter. No brainer. The question remains, who benefits from slowing rather than facilitating progress?
Thurly, all this emotional/stress overlay w sk makes me think there is a tipping point in our future sooner rather than later. If Bavi is really good at anti-viral applications that the DoD is interested in, then there is a whole separate track PPHM could be on re. covert financing and continued production that we will not know about. As usual, the government might want sumpin' badly, but not want to pay for it, at least in this budget cycle. The whole "dosage question" as a cover story has a few holes when it comes to "make or break" re a DTRA contract. That is, it could be basically true but not the whole story if they are trying to take this thing to classified status. I've said for years that the biggest stumbling block to Bavi would end up being politics and governmental budgetary priorities.
Skim-read transcript of cc. Didn't hear any stutters. Interesting Freudians or typos: "...encouraging objective response in MEDIUM progression-free survival data for our lead PS-targeting antibody..."
and "...turning the call over to Chris Eso for a discussion on ABBOTT market..."
"...we have begun seeing increased activity [antiviral, or more patients enrolled?] in our Phase 1 clinical trial evaluating Bavi in HCV infected patients..."
Over-all it seemed like a pretty straight forward report. This crowd does not appear to engage in hype.
jess, patent applic. was 2003, true, but this approval coverage is critical for anyone looking at the dollar value of the technology.
NuLoof, good to hear from you. Happy LaborDay. Last I heard you'd gone outdoors to use the 2-holer and the hogs got you. Glad you're okay. Enjoy your input. Now that you cashed out we can look forward to your non-vested interest objective insight....right?
jessme, a screamer! thanks.
geo and notbob, thanks. I wouldn't be here if I didn't agree with you. As indicated, some people can't give it a rest. However, it has crossed my mind (more than once) as a possible negotiating barrier...and that might not be bad either. Anyone know the terms of "the patent lease?" Good luck U2. Why am I in a buying frame of mind now? I was sitting on cash during the last crash (not the 2000 one), then bought back in too soon, and now at about 50% of usual holding in PPHM. Gawd, this has been grizzly (grissly? gristley?).
rcjonson,we all experienced ricardo on rb for years, and that's why we're here instead of there. Having said that, I must admit to wondering if that is not the key stumbling block in outside negotiations with PPHM, sumpin' similar to buying a house from someone who owns the lease. Owning a patent must somehow be better than owning a license. Have also wondered why the inventor(and UTSW) would want to work with PPHM rather than "a major" considering its front office composition. At some historic juncture perhaps PPHM was the only alternative. Might still be! However, the comforting thing is that all parties concerned want to make money.
until2000, nice post. Interesting, your Pfizer "friend" does not return your phone calls. Friend, huh. Maybe she doesn't want to lie about Pfizer interest in PPHM. Yesss!
Everyone wants a bonanza stock price for PPHM, and most want it NOW, dammit!
Please give me your take on why management and board are viewed in sucha dim light by your gazillionaire acquaintance bank board fellow, and why you think same PPHM brass are inclined to...uh, chart a death spiral when they are administrators for UTSW patents, and have university attorneys and inventors to answer to. All corporations, like individuals have strengths and weaknesses. Intellectual properties are PPHM's largest asset, followed by Avid MAB production facility. The game now is how low can the stock price be pushed before the announced buy-out.
stoneroad, PPHM "eaten up" is no longer news. Why announce a relationship when it is so obvious. PPHM is a cost-effective farm-club, a way to finance the numbers crunching required by a major drug launch. How much longer the GrandeLarceny in the market? Forever. MoneyMen must be satisfied before the bones are cast to the long suffering crowd that supported the charade. As they say in Vegas...
HeavyDuty, welcome to the board.
Paladin, indeed.
Jess, interesting, thanks. This thing won't break loose until someone at Genentec forgets where he's at...NewportBeach or SanFrancisco. Yawn. Announcement? Change the signs on the door? Is the inevitable nearing? "Stockholders do well at last!" A home run at this price. Testing...testing...$8-10 a share? Easily worth $500 if Bavi and Cotara fly. Big leagues indeed. And if PPHM is actually going it alone, we'll all know how to act when the next MrRussell comes along. PPHM and DNA? The "paper pros" (accountants, lawyers) have a lot of work to do in any corporate wedding, and this one is not easy for reasons enumerated here daily. As soon as everyone in the chain "gets theirs," these therapeutic agents will move forward. Pray for the players to get it figured out soon so patients may be treated.