"The HR for enzalutamide is 0.63. If EXEL beats enzalutamide with 960 patients, the study will not reach 578 events."
You are all over the map and everywhere except where you should be. The trial already reached 387 events at a time point prior to the 3/25 press release. I am 99% certain that the 578 patient trigger has been reached since then. We are just waiting on the CRO, DSMB and EXEL management to finish and announce the result of the final analysis.
"the November data probably will show a good chance of any benefit.."
The first cohort showed a statistically significant improvement in a number of NASH associated parameters as compared to baseline measurements and the 2 placebo patients. The 2nd cohort actually did worse than placebo. The dosage for the first cohort was at a drug concentration that was less than that found to be active in the animal models (mice and rats).
I look at the present circumstance and the only conclusion I can come to is that the sample size (6 treatment 2 placebo) is too small, the measured parameters too variable, and the trial duration too short to draw any meaningful conclusions regarding activity and efficacy. The euphoric rise in the pps following the first cohort was overdone. We will see what happens with the third group, but even if the parameters return to a positive trend, I would expect the market to regard any outcome with a bit more caution than the first time around.
Right now I am having trouble getting a "reply" box to open off the "Messages" tab. I can open a box by using a thread display and then selecting the message I want to reply to. Yahoo is goofy sometimes. They seem to make little software adjustments that affect the mb's in various ways.
"There are also statements from doctors who feel that the endpoint per Exelixis is strong in acceptance by the FDA."
Not sure where you're going with this. We aren't talking about CRPC. PFS determination requires measurable disease and only 20-30% of CRPC patients meet this requirement. MTC was approved on the basis of PFS and PFS is the primary endpoint for Celestial (RCC). Once other drugs show an OS advantage in an indication, that tends to become the de facto measuring stick for candidate drugs filling a similar space. That is why HCC requires an OS advantage whereas PFS is still an acceptable RCC endpoint. Left unsaid is that even when PFS is deemed acceptable, FDA still wants to see a numeric OS advantage even though it is not statsig.
"Can't post any messages in relation to Class action!?"
Sometimes Yahoo gets persnickety. Some common problems: A post in the thread was deleted, too much cut and paste, too many long posts, trying to include a link. Every now and then when I post a lot, some sort of filter kicks in limiting my activity temporarily. Try starting a new thread.
"I want to remind you, and others who read, that Dr. Scott Friedman, the World #1 expert in liver diseases obtained and endorsed GALT's results..."
Dr. Friedman is the best thing that ever happened to Galectin Therapeutics. I made that observation on this board several times in years past. He added much needed credibility to a company which had little to spare. Be careful though is reading too much into his consultation with GALT. He has extensive relationships with several different pharmas.
From his Mt. Sinai bio:
•AbbVie Inc.; Abbott Laboratories; Alnylam Pharmaceuticals; BiOrion Technologies BV; BioLineRx, Ltd.; Blueprint Medicines; Bristol-Myers Squibb; Conatus Pharmaceuticals; Deerfield Consulting; F. Hoffman-La Roche Ltd.; Genentech, Inc.; GlaxoSmithKline; Healthpoint Biotherapeutics; Isis Pharmaceuticals, Inc.; KineMed; Melior Discovery; Nimbus Discovery LLC; PharmaIN; Synageva BioPharma; Tobira Therapeutics, Inc.; sanofi-aventis
Scientific Advisory Board:
•Galectin Therapeutics; Nitto Denko Corporation; Takeda Pharmaceutical Company Limited
Other Activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership.
•Galectin Therapeutics; Tobira Therapeutics, Inc.; Vaccinex Inc.
•Chugai Pharmaceutical Co., Ltd.; F. Hoffman-La Roche Ltd.; Life Technologies Corporation; Mitsubishi Tanabe Pharma Corporation; Nitto Denko Corporation; Novartis
Equity (Stock or stock options valued at greater than 5% ownership of a publicly traded company or equity of any value in a privately held company)
•Angion Biomedica Corp; Galectin Therapeutics; Intercept Pharmaceuticals Inc.; KineMed; Tobira Therapeutics, Inc.
"In this case, you are alleging that lab techniques were tampered with!? You remember when Barry Shack attacked police Lab guy with: "What about that Mr. Fong!!!"...somehow your elaborate explanations rings the same bell."
I did not say anything of the kind. First, neither of these laboratories has any connection to GALT. The Italian study came to the conclusion that galectin 3 knock out mice are less prone to NASH and fibrosis. The Japanese study came to the conclusion that the same strain of mice is more prone to NASH and fibrosis. I did not say lab techniques were tampered with, I said the techniques used may have been inappropriate or errors may have been made---big difference.
How would you explain the diametrically opposed conclusions drawn by similar studies?
There are aspects to each of these studies that stand out. The Italian study used an atherogenic diet over a longer period to induce the NASH. The Japanese study showed a trend over time. Why the discrepancy? Perhaps it has to do with the method of inducing the pathology, both of which are IMO better models of the human version of the disease than toxic assault method used in the
GALT studies in rats and mice. Perhaps one or both studies erred or used invalid lab techniques to obtain the data. What this does show is that even at the pre-clinical stage there is some doubt as the validity of the concept that inhibiting galectin 3 may result in NASH improvement. Even if the pre-clinical work was completely consistent, silencing a gene has a whole cascade of upstream and downstream effects that are not perfectly replicated by a receptor blocking ligand.
But not so fast. In the literature is a similar, more recent study done by a Japanese academic group that came to a diametrically opposed conclusion. “Deficiency in Galectin-3 Promotes Hepatic Injury in CDAA Diet-Induced Nonalcoholic Fatty Liver Disease.” This study also looks like good work. In it NASH was induce with a choline deficient diet and mice were sacrificed and compared at 0, 2, 4, and 8 weeks. There was no normal diet control, all mice were fed the choline deficient diet. At each time point 2 groups of 4-6 mice were sacrificed. With 4 time points and 8-12 animals at each, the study looks to have had 40 data points. In this study the GAL- mice had much worse NASH and blood markers of inflammation. The most convincing aspect is the trends noted for the slide and marker analysis were very consistent at each time point..cont
"The way I see it is this: On molecular level things work, i.e. some form of pectin derivative bonds to harmful protein(s) responsible for growth of NASH, cancer etc. The molecules, of course, do not know whether they are in human or mouse liver. Bio-chemical reaction pectin-protein works in either one. Now the question is what effect that have in humans once it was established that the method is helping mouse liver."
Fair enough. Before we even jump to the clinical expectations, lets take a closer look at the pre-clinical work done. One of the pillars on which the theoretical efficacy of GR-MD-02 is based is that galectin 3 is involved in the liver disease process. This is largely based on the observation that genetically altered mice lacking galectin 3 expression do not develop NASH or fibrosis to the same extent as their normal cousins who do express galectin 3. The study on which this observation is based is an Italian university study entitled “Galectin-3 ablation protects mice from diet-induced NASH: A major scavenging role for galectin-3 in liver.” It looks like good work and the method for inducing the NASH in the subjects and controls was an an “atherogenic diet” of 8 month duration. 32 animals underwent liver analysis in a single examination at the end of the 8 month period . There were 4 groups of 8, GAL+ and negative on normal and hi-fat diets and the 8 GAL- mice did better than the 8 GAL+ mice on the hi-fat diet...cont.
"Oh well, hoser. Rules were made to be broken. If you're really unhappy...You can split! I won't stop you!"
Rules are arbitrary obligations which are imposed on one from an external source. Promises are a different matter. Breaking a rule simply shows a tendency to draw outside the lines. Breaking a promise is a bit different and is a manifestation of a flawed character, a moral imperfection.
As far as I'm concerned, you are more than welcome to stay. Obviously I don't get a vote in the matter anyways. But now there is more context within which to frame the consideration of your ramblings.
"....why you think we have to wait."
I still think it will happen any day. Why it's taking longer? Maybe the patients are doing better than we expected. EXEL might have asked for a full package evaluating all the secondary endpoints in addition to OS. That would involve getting all the radiographic results to measure the bone response rate and a lot of subgroup analyses. Maybe something else I haven't thought of. Beats me.
"LBA deadline is 11:59pm 8/20/14...effectively, one week from Monday."
One and a half hours until it's deadline time in Madrid. I think we have longer to wait.
"Your conjecture is that pectin is totally useless. So, is LJPC doomed ?"
That is the gist of my thinking. I don't trust internally generated preclinical work. GALT has the edge in this regard with Dr. Friedman picking up the lab studies and publishing them. He is a liver KOL (key opinion leader), so his name adds credibility. Back to La Jolla, I noticed that they did a secondary a week after the press release. Developmental biotechs try to time secondary offerings to take advantage of high pps, so it looks like their press release was timed to pump up the stock price as they rolled into the secondary.
For argument sake, let's assume all the preclinical NASH work done on the pectin derivatives is credible. That still leaves the question of whether efficacy in a toxin induced animal model will translate to efficacy in a human chronic disease model. I'm frankly skeptical.
"You've been busy Earnie. Lot's of negative posts on the GALT and EXEL boards. lol"
I actually own a big chunk of EXEL. Even though I own it, I'm not reluctant to consider all aspects of the story, both good and bad.
As I was saying...The FDA lists Pectsol-C as one of "187 Fake Cancer "Cures" Consumers Should Avoid."
First you bought into Frank Salvado's bogus claims about the meaning of the fast track designation and now you are posting quackery from Teheran University as supportive to GALT's cancer program. Up your game a bit.
Okay Mitch, let's talk about PectaSol-C Modified Citrus Pectin. That is the drug being evaluated in the article you posted. That article was written by Dr.Dr. Isaac Eliaz. He also happens to be the owner of EcoNugenics, the company which makes and markets PectaSol-C. They claim their product qualifies as GRAS (generally recognized as safe) and as such, it can be sold as a food supplement. In addition to treating Ovarian Cancer, other articles and claims for effectiveness in Prostate Cancer, Breast Cancer, Fibrosis, High Blood Pressure, chronic inflammation, Colds, Flu and more. Dr. ELiaz himself says "This new research is truly exciting because Modified Citrus Pectin is turning out to be much, much, more versatile than anyone imagined."
Come on Mitch, when something sounds a bit too good to be true, maybe you should be a bit skeptical. Here is what the FDA had to say about some of the more aggressive Pectasol-C claims.
Interestingly the FDA lists Pect
"Can you provide the exact CNBC quote by pointing to the article where it appeared."
It was a CNBC report that has been archived. You can access it by searching: "CNBC's Morgan Brennan reports on the FDA's four expediting pipelines."
"Then, majority of longs bought simply because they like to company prospects and never read promotion materials."
Mitch, here is an example of how investors are duped. Frank Salvato wrote the story touting GALT's NASH drug. That story contained gross inaccuracies regarding fast track status. GALT has been aware of the story from the beginning and Rod Martin posted it on his personal website. Since the first writing, Mr. Salvato again inaccurately referenced fast track.
The following posters have referred to Mr Salvato's stories apparently unaware of the inaccurate quotes, references and inferences that some how all of this was relevant to GR-MD-02.
bigskywy cobragene 1 vvvvvvrebel89130 mitchpit11 bmpr2bmpr jgatsby1911
Like it or not, all of you guys were "duped." That's how it happens.
"Notice how AF doesn't even attempt to refute any of the facts of the article..."
Adam did exactly that, it was just a bit too subtle for you to notice. Here is what he tweeted: "By the way, you have no idea what FDA Fast Track status means."
First, Mr. Salvato is misquoting CNBC. What CNBC actually said was that 100% of the 2013 "priority review" drugs had been approved. GALT's drug does have "fast track." Fast track, Breakthrough, and Priority Review are three different and distinct FDA designations. Mr. Salvato is playing very loose and fast with the facts. So who is actually misleading who?