""One brief correction is the new ENCHANT trial goes from one arm to two, not two to three...started as just an open label monotherapy in TN or HER2 patients.""

Acgood, thanks for the correction.

""In my opinion, that's where they should always have been focused. If you look at the preclinical reports, a consistent theme is that tumors that become resistant to some agent (no matter whatever type - radiation, chemo, targeted drugs) also become more susceptible to HSP90 inhibition.""

Peter, that was my view as well. I was a bit disturbed that SNTA was pushing forward with Ganetespib as a monotherapy. This shift towards combination therapy gave me enough confidence in SNTA that I added a bit more. I also bought some ARQL in two batches recently based on their focus on MET+ screening.

AS far as GERN and their drug Imetelstat, sometimes I just shake my head at the stupidity, or is it ignorance of management. Just why in the world would you use it as a monotherapy or with a microtubule inhibitor (Paclitaxel) or an angiogenesis inhibitor? Don't they have on the board or consult with experts in the telomere field? Studies have shown, or at least given good hints, that telomerase plays a role in the DNA damage repair distinct from its role in telomere maintenance. An intelligent path to pursue would be to use it in combination with anti-cancer drug that are DNA damaging agents. Such a combination would likely give the greatest chance for generating a synergistic anti-tumor response.

With regards to HSP90 inhibitors, SNTA finally announced they were going to focus more on combination therapies using Ganetespib rather than it using as a single agent. Along this line, SNTA is amending their ENCHANT breast cancer trial to include a Ganetespib/paclitaxel combination as a third arm where originally it had Ganetespid as monotherapy.

http://seekingalpha.com/article/1274011-synta-pharmaceuticals-management-discusses-q4-2012-results-earnings-call-transcript?part=single

""Ph3 trials must be a sleep-easy time. ""

A sleep easy phase III trial is a bit of an oxymoron.

""Let us see how the FDA treats it. Sure will not be decided with arguments pro and con here, will it?""

North, just what do you expect the FDA to decide?

porkchop, the truth is the truth. Sorry if you don't like it but you have to face it. There was no control in the Bavi phase II NSCLC trial because it was corrupted. Apparently you are unclear as to what constitutes a control in a trial. It can be 1) a comparison of your drug to a placebo, 2) comparing your drug to another drug and 3) comparing your drug + another drug to the other drug alone. The small (corrupted) phase II NSCLC trial using Bavi has none of these, hence has NO control for comparison. Those are the facts whether or not you want to acknowledge them.

PPHM outright lied in the quarterly report when they said the following

""Promising 60% improvement in median overall survival (OS) in the 3mg/kg bavituximab plus docetaxel arm compared to the control arm and that bavituximab was well-tolerated with no significant differences in adverse events between the trial arms. ""

There is NO control arm in the NSCLC trial due to the patient mix-up.

Now go back to the PPHM board where you spin conspiracy theories, and and fantasize without restriction. I will NOT respond to you again.

porkchop,

Apparently you are unclear as to what constitutes a control in a trial. It can be 1) a comparison of your drug to a placebo, 2) comparing your drug to another drug and 3) comparing your drug + another drug to the other drug alone. The small (corrupted) phase II NSCLC trial using Bavi has none of these, hence has NO control for comparison. Those are the facts whether or not you want to acknowledge them.

""Frequent words in PPHM’s 4Q12 PR are encouraging and promising: ""

PPHM outright lied in the report when they said the following

""Promising 60% improvement in median overall survival (OS) in the 3mg/kg bavituximab plus docetaxel arm compared to the control arm and that bavituximab was well-tolerated with no significant differences in adverse events between the trial arms. ""

There is NO control arm in the NSCLC trial due to the patient mix-up.

""PPHM earnings a/h tommorrow..i know we all can't wait,lol ""

Isn't the conference call going to be when PPHM announces that Bavi is going to be given a "breakthrough" drug designation by the FDA?

poorgradstudent,

Definitely big and good news for ONXX and its shareholders. The company is already over $6 billion in market cap I think the most we can hope for is a 50% rise. I did finally sell 5% of my ONXX last week at $77 to cut its very high percentage of my portfolio, but it surged afterward so is now an even higher percentage than it was. Not complaining as it is a very good "problem" to have. I have been holding ONXX for a long, long time and was talking about, okay, fantasizing about, a $100/share price. ONXX may just get there sooner rather than later. Just another example of it is better to be lucky than good.

In my experience, the worst CEOs and University Presidents are those with big mouths and grandiose plans. They often refuse to acknowledge the difficulties/risks inherent in their plans and squelch dissent along with people who have the balls to utter such dissent. Sounds like Perlmutter might fit this profile.

tekcor, Wasn't MNTA supposed to go down?

""MNTA bounced off of long-term resistance and is still in a channel that has been in place for all of 2012. There is major long-term support at $10, but I believe that MNTA will break below this long-term support level. A near term catalyst that might re-ignite the downtrend is the earnings release later this week. ""

A bit late but this article about Healthcare costs was interesting reading.

http://healthland.time.com/2013/02/20/bitter-pill-why-medical-bills-are-killing-us/

poorgradstudent, I agree with you regarding SGMO.

If BP thought Bavi was such a threat they would have bought PPHM, and could have done so at a very low price. It would be pocket change to BP. To think, or even worse, to post multiple times on a public forum that BP would risk major lawsuits by sabotaging the Bavi trial is truly absurd and delusional.

I asked a very simple question to PPHM longs about the latest PPHM attempt to salvage the corrupted NSCLC phase II trial was. What was the P value for OS for the Bavi 3 mg/Kg dose and the supposed combination "control"? I believe it was worse than P= 0.2. This is a dismal failure failure in achieving significance and it was ignored. Instead, the longs focused on a trial whose data was more than 13 yrs old for their historical control. Nobody in their right mind would cherry pick from a trial so long ago as their metric for a control.

Robert, Thanks for the recipe. I may just try it. As far as olive oil, I just looked up the conversion and there are just over 67 tablespoons in a liter so 4 Tbs of olive oil/day gets you only 40% of the way to 1 liter/week. However, the 4 tbs/day included that used in cooking so the amount consumed is far less.

masterlongevity,

Thanks for the input. The Spanish Oil study involved people and a regular dietary regimen, not a medical application for a specific disease. I agree that very few people would consume that much olive oil each week for 7 years.

linhdtu, thanks for telling me where you got the info. I am just assuming that there was some kind of miscommunication about the total amount of olive oil used vs actually consumed.

Oldberkeley, I would really appreciate it if you sent me that funny photo complete with its captions to dr.vinmantoo@yahoo.com

One really needs to remember the past and laugh at you own folly to learn. That Frankenstein/Bride of Frankenstein images helps me do both.

""The participants consume 1 liter of olive oil per week. ""

Where did you get that figure? That must be wrong as that is an insanely high amount. Maybe they use up that much oil via cooking but there is no way that much olive oil is consumed by each person each week.

Hey where did the great picture from oldberkeley go?

poorgradstudent, great post.

{{Back then, I responded to negative data the exact same way that PPHM investors appear to do. By ignoring it, pointing vaguely to authority, bending over backwards to find comparator data that satisfies my pre-conceived notion, and buying into distractions that were simply working to keep me from delving into the clinical data and regulatory landscape. I basically did everything in my power to ignore the clinical data and what it objectively said.

I'd write a book about the experience, but the irony is that the people who would most need to read it are the exact people who would never do so. I know, because back then I wouldn't have either.}}


Experience is the best teacher, and one learns the most through failure. My biggest failure was GTCB as many people, including jbog, were highly critical of the cash burn and horrid finances. I was also critical of the CEO too, but kept looking at the "potential" and dismissed those warnings as being made by people who didn't get it. Others pointed out how much more efficient cell culture was getting, which eroded GTCXB's production advantage. Finally even Dew, a long time GTCB advocate, pointed it out and bolted. rATIII was approved by the FDA, making it the first transgenically produced drug on the market, and the stock price went up just over my break even point so I had the chance to get out at a break even point or a small profit. Unfortunately there was a very minimal market for rATIII, as others pointed out, and that the horrid cash positions would sink GTCB. I was sure the potential would be realized as it was a transformational shift in protein production. Hell, I even bought more. Of course then stock price rapidly dropped as the financials weighed it down, and GTCB was bought for a song. I got a 90% loss for my stupidity.

A simpler and more reasonable explanation is that there was sabotage. PPHM rigged the participants and data collection to make it look like Bavi was working. That would explain why the placebo looked so bad as compared to historical controls, and why it still looks bad when combined with the 1mg Bavi arm.

""I admit I'm exaggerating a bit here because while T-DM1 is clearly an improvement over existing therapies it isn't a true breakthrough. But my point is still valid""

So you are saying that T-DM1 isn't a "game changer" and doesn't represent a "paradigm shift" in cancer therapies. :)

Robert,

You are cherry picking the data from a single trial 13 years ago when other more recent trials with a similar patient distribution had much better OS in their control arms than an the 5.6 mo in the control arm of the Bavi trial, which wasn't really a control arm because it contained Bavi treated patients.

Robert,

Did you look at the P value yet? Did that give you any clue yet as to why there is so much skepticism about Bavi? Did you figure out that the control arm than wasn't really a control arm had a much worse OS than the historical control despite containing patients receiving Bavi? What does that tell you? It tells me that if we assume Bavi is neutral or even slightly beneficial, either the patient selection was dramatically skewed towards sicked patients in the control arm or there was willful manipulation of the data to make the OS look better in the treatment arms. Either way the data cannot be trusted.

So what was the P value in the NSCLC data for Bavi? That might help answer your question.

It is pretty amazing to me that PPHM didn't fall more today.

""Lastly, I wouldn't listen to some of the "stooges" on this board who don't provide any value. ""

TA is non-sense.

{{Dr. Eric Topol, a professor of genomics at the Scripps Research Institute in La Jolla, Calif., and author of “The Creative Destruction of Medicine,” cautioned that appliances like Knome’s would still require personnel steeped in molecular biology and genetics to sift through and evaluate its findings.

“It’s not for your neighborhood doctor just yet,” he said, “although that time will come.” }}

It would be a disaster to have your neighborhood doctor to have the primary sequence data. As Dr. Topol says, someone trained in molecular biology and genetics, and I would add statistics, is needed. They will give an idea of the inherent risks and uncertainty in the primary genetic data. An untrained person attempting to analyze the primary genetic data could do more harm than good by needlessly worrying people.

<Galectin Therapeutics (GALT -3.4%) says it's submitted an Investigational New Drug application to the FDA to support a proposed indication of GR-MD-02 for treatment of non-alcoholic steatohepatitis with advanced fibrosis, or fatty liver disease>

Dav1234, GALT and its previous incarnations PRW & PRWP have been some of the most "impressive" BS artists I have run across. The longs on the yahoo boards were of the same low caliber.

""Why should we be excited about a pipeline of radiotherapies? I think this type of approach is generally less well-regarded, isn't it?""

Mcbio, I think what is less well regarded is the idea of implanting radioactive seeds adjacent to tumors. From the press release, the Molecular Insights approach is using a PMSA targeting system to bring radioisotopes only to cancer cells, rather than to a region near tumors. It is analogous to conjugating cyto-toxic drugs to monoclonal antibodies so should make it a more effective approach.

Bladerunner,

Yes I still own PGNX. How to figure there will be much of an effect on PGNX in the short term on this purchase without a better understanding of the radioisotope targeting drugs. The big concern with PGNX now has been cash burn, and this will increase it somewhat. I hadn't heard the conference call, but someone on the yahoo board did and said that while Molecular Insights has no debt, it doesn't add any cash. Salix has raised their estimates for Relistor peak sales so that may off-set the increased cash burn with the Molecular Insights purchase. That is why I am thinking it won't have much of an effect, rather than a negative one due to increased cash burn.

PGNX fate is still linked to the initial phase II data on the conjugated anti-PMSA antibodies, absent a hail-Mary from the FDA about Relistor in Chronic pain. The Molecular Insight drugs also use a PMSA targeting mechanism, so PGNX is obviously feeling (betting) this is a key antigen for specifically targeting Prostate cancer and other solid tumors. I guess is it possible that long-term, PGNX wants to couple the Molecular Insight radioisotope delivery system with the PGNX anti-PMSA antibodies. Even if that were possible, it seems like a long way off from trials. We would have to be able to find out what the scoop is with the Molecular Insight drugs on their own to understand the rationale behind PGNX buying it.

I am still looking for reducing my shares of PGNX, and this acquisition does nothing to change that view.

dav1234, Unless I am mistaken, telomeric G-quartets have been predicted for quite some time, and may have been demonstrated in vitro. That doesn't diminish finding evidence for it in vivo.

""Onyx Pharmaceuticals (ONXX) announces a 4.4M share secondary offering with a 30-day option to purchase up to an additional 660K shares to cover over-allotments, if any. ""

This offering seems a bit surprising to me as ONXX has about $650 million in the bank. They talked about clinical development in the press release and ramping up sales force for Kyprolis, but it smells like they are looking for another company or product to buy to me. One possibility is that they are going to speed up/broaden clinical trials for Oprozomib, their oral proteasome inhibitor as a follow-up to Kyprolis.

MNTA didn't drop today, so does this mean that the bad news about the legal decision has already been priced in?

Decisions like these are why I don't understand how the legals system works.

thanks poogradstudent for the information about GERN and their pipeline, or lack thereof and on Imtelesat.

Mcbio, with regard to GERN, I took a brief look at their finances and they look like they have enough cash on hand to last about 2-3 years based on current burn rate. Are they partnered with Imetelstat? What else do they have in their pipeline that you value. On my initial look, it seems a bit premature to invest.

john,

""Regarding your thoughts on my lack of expertise. There seems to be some attemp to discredit Bavituximab through me. I would advice you to take that up with Dr Phillip Thorpe. ""

I have never attempted to discredit Bavi in any way, but rather said I didn't know enough about to make a comment. I have mocked and discredited people who PRETEND to understand science but actually only misinform and confuse others by posting gibberish, half-truths or lies. I have also mocked PPHM's response to their recent fouled up NSCLC clinical trial. I have begun to get interested in ARQL based on comments for this board, and just made a small buy. However, their management worries me more than their lead drug Tivantinib's prospects do. The exchanges on this board have been very useful in weighing the merits, and raising concerns so I can go into it with eyes wide open. McBio raised my interest with a post about GERN. I bought a substantial amount of SNTA last year, in part based on discussions made on this board. Use the board for what it is a sounding board to ruthlessly dissect, discuss and argue the merits of companies. It can be hard when others criticize a company in which you have invested your cold hard cash, but you have to look at it dispassionately. That took me far to long to do so, and I suffered because of it.


As far as you latest comments,

""As cancer cells divide, telomeres become shortened. That's an elementary fact, and of which I've seen with my own two eyes. This process would continue until a point of no return was reached and the cancer cell would die, if not for up-regulation of telomerase enzyme, which is responsible for telomeres repair, and a process evident in metastatic cancers. ""

No. As cells divide, their telomeres will shorten by about 72 bp per division on one of the two sister chromatids if they don't have active telomerase. I could explain to you why this "elementary fact" occurs, but won't here. In the transformation process that enables normal cells to become tumorigenic, most of cancer cells do indeed reactivate telomeres. One might say they don't become cancer cells/tumorigenic until they reactivate telomerease, but simply activating telomerase won't make them tumorigenic. You can take primary cells and transfect them with telomerase and they become immortalized, but they sure as hell aren't tumorigenic. BY the way, about 10% of cancers don't have active telomerase, rather they use a recombination based method to generate what is presumed to be extremely long telomeres. The process is called ALT, for Alternative Lengthening of Telomeres.

In any event, all of this has nothing to do with BAVI. Your big problem is that you make declarative comments as if you are an expert and you act as if your comments should end discussion on some other topic, related or not. Ask questions, or ask for clarifications on something you think is right. People here with expertise will gladly try and provide answers as best they can. Biomaven gave a great bit of information about MYC in regards to what Watson just wrote about in is perspectives article. However, don't presume to lecture people on how things work, or are thought to work when you have little to no knowledge on a topic. That seems to be a very common phenotype among PPHM investors at least the ones who come here.

biomaven,

Thanks for the link. Yes Watson deserves some slack due to his age. I am fine with the hypothesis generating characterization. I briefly scanned the Watson article. I don't know much about MYC, so it might have some value, but the assertion about the importance of inhibiting the cell-cycle has been long known and is underway now as an anti-cancer strategy. As far as energy metabolism, I vaguely recall that about 20 or 30 years ago, a hot topic was drugs that inhibit mitochondrial function as anti-cancer agents. Watson has been an excellent fund raiser over the years, especially for Cold Spring Harbor. I am fine if he can get additional funding for research as the imbeciles in congress seem primed to keep NIH funding flat or even reduce it.

I recently presented a journal club on a perspectives article by Tim Mitchison. I thought it more interesting.

http://www.molbiolcell.org/content/23/1/1.full