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Roger everything in your post, David. Have you attended the AUA convention previously? I'm curious to know what proportion of urologists are women.
I've attended all the AUA meetings since 2005 (which was my favorite since it was in San Antonio, one of my top three favorite convention cities).
I'm guessing about 1/3 are women, but it is tough to tell just by conference attendance since AUA has a much stronger nurse/support care program at their annual meeting than ASCO. AUA sees a lot of OB/GYNs there too, which skews towards women.
Over the years I am seeing more urological oncologists at the meeting, which is probably closer to an even split by gender. The uro onc I would use, assuming there is a chemotherapy other than Taxotere approved one day, is a woman and I'm really lucky she's even local.
FWIW, which is probably nothing, I'd choose a guy for the prostatectomy and a woman for everything afterwards. The choice of the guy has nothing to do with gender, only that prostatectomy success is directly correlated to number of procedures completed and there are no women in the top ranks by that count. After that, women tend to be less pushy on a particular therapy and more in tune to patient quality of life. If (when) I'm fighting cancer, I don't want to be fighting my doc.
AUA has developed into a more useful meeting than ASCO over the years. My first ASCO was 2003 and my first AUA meeting was in 2005.
This is particularly true for prostate cancer, where AUA has been consistently ahead of every successful trend in PCa. If we're talking about PCa, and particularly Provenge, there is no better or more relevant scientific meeting than AUA to release it.
I've also attended every ASCO Prostate/Genitourinary sub-meeting except the one this year. I had really high hopes after the first one as it portrayed a great cross-section of research and new ideas in the treatment of PCa. They've gone steadily downhill since then.
Since Provenge will largely be a urology and not oncology drug, this is also the best meeting in terms of sales/marketing for the product.
Welcome to my bizarro world of DNDN.
I loved Herper's article and appreciated your critique of those two items because they are excellent examples of the nonsense I usually hear about Provenge by people like Oh and Brawley who know better. I've come to the point I don't bother to talk about it with most oncologists becuase the first three criticisms out of their mouth are those two and "the trial is too small" nonsense.
There are legit criticisms of Provenge, but those three and "the arms in 9901 were imbalanced in favor of Provenge" are my recurring favorites. You'd be surprised how many docs get their info from analyst reports they're handed when consulting for hedge funds.
Incidentally and as you probably know, the FDA specifically does not accept TTP or PFS as an approvable endpoint in PCa because there is no indication they are surrogate endpoints. That's why Oh's comment is so stupid.
Same goes for PSA. I have a rule to never bother with any drug where the data focuses on PSA -- regardless of ASCO's Phase II guidelines (which are a joke, BTW).
Scher is spending a fair amount of Cougar's money to determine whether CTC (circulating tumor cells) counts using the technology of the company he is a paid spokesperson for will work as a surrogate. Frankly, I hope so. It would be a faster path to seeing Provenge on the market in earlier stage disease.
And thanks also, Dew, for your earlier congratulations to DNDN longs. Classy and appreciated.
Today is a good day professionally, obviously. But today is a better day for all those guys out there with prostate cancer who finally have a treatment that prolongs their life without making a mess of it.
This one is for all of them.
Thanks for all the kind support so many have shown over the years. Now comes commercialization & sales. Not a bad problem to have after all this time.
David
ASCO says no EFR-inhibitors without test showing no KRAS mutation.
"Based on systematic reviews of the relevant literature, all patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy should have their tumor tested for KRAS mutations in a CLIA-accredited laboratory. If KRAS mutation in codon 12 or 13 is detected, then patients with metastatic colorectal carcinoma should not receive anti-EGFR antibody therapy as part of their treatment."
http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.21.9170v1
Not much of a surprise.
The screen you suggest was well known in the last downturn 2001/02, but didn't work for the early adopters.
Instead, focus on three items:
1. Cash on hand
2. Discount to cash
3. Drop dead date (current date + (cash/cash burn))
People who just applied the first two early in the cycle (2001) didn't do so well. They'd just bought into companies whose hype was more persistent than their neighbors. They ran out of cash and the financing window was still closed. That's why #3 is critical.
Instead of just comparing cash to market cap, run the screen sorting on #2 first, highest to lowest discount. Then run the screen on #3, sorting longest to shortest. See if there are common names towards the top, and look at those first. As with any financial screen in the biotech space, filter with fundamentals to sort out (to use a past example) Novacea-types who have lots of cash but nothing useful to do with it.
The two-step screen you suggest can be applied successfully late in the cycle, because a reopening of the financing window makes the drop dead date moot. But then you are relying more on when the financing window opens and not the merits of the screen.
In your example, I'd bet on Y if their cash use was $1M/month and X's cash use was $15M/month -- unless I believed the financing window would reopen by May or June.
I think FierceBiotech is keeping a running total. I didn't find it in a search of the site, but remember it from their e-mails. Next one I get I'll try and remember to look.
Well, insofar as I never met a RLT expert (outside of those working on a CTEP program at a big pharma) who thought the approach would work, I think they extended that one for other reasons than success. JTT failed in a prior CTEP trial, so it wasn't like this one was a surprise.
I took too long to edit the message, BTW, and intended to add the following...
insiders at Big Pharma have no economic incentive to push programs with a zero chance of success.
Torcetrapib?
There is an economic incentive because the people who manage the biggest programs are the ones who get the biggest promotions. Isn't that like the 1st law of the bureaucracy?
That said, I think Dew's point of a pharma being more likely to kill one of a 100 pipeline products than a small biotech killing their only product is absolutely true. There are Phase III trials out there that only exist because the CEO still wanted a paycheck.
Interestingly, when you have a biotech who is good at killing programs they are often not rewarded for it by investors. SGEN is a good example. They killed each of their three lead drugs (we predicted SGN-10 and SGN-15's demise. SGN-30 was eclipsed by SGN-35) and probably the number one non-valuation argument against the company is "they failed on their first three programs"
CRXX might be a bad example for some who don't like their approach, but they quickly kill drugs they don't think will work. We'll see if that holds with the latest P2 failure.
Dew likes to find evil in every decision or person he doesn't agree with, but I approach it differently. There are a minority of CEOs who extend programs explicitly because they want to collect a paycheck. Introgen was the best example. Most convince themselves the drug will work.
The biggest problem in biotech P2 to P3 is the lack of randomized P2 trials. If you look at P3 successes from pharma, they ran randomized P2s so they weren't guessing at the treatment magnitude. That, combined with the $$$ to overpower the trials, gets them more P3 successes.
Biotechs don't think they can run randomized P2s because they believe they'd have to size them the same as P3s to satisfy Wall Street's simplistic demand for p=0.05 results, so why bother. I sympathize, but I'd like to see a few bio CEOs take a shot at a randomzed P2 with a prespecified p=0.10 or p=0.15 threshold and see what Wall Street does with that. In the long run I think avoiding the P3 failure would be cheaper.
insiders at Big Pharma have no economic incentive to push programs with a zero chance of success.
Torcetrapib?
But beyond that, there is an economic incentive because the people who manage the biggest programs are the ones who get the biggest promotions. Isn't that like the 1st law of the bureaucracy.
Oh geeez, relax. All I'm saying is that it would unlikely be the first choice for most of the people I've spoken with. The number of successful MAbs created with MEDX tech pales compared to the mainstream tech. Also, MEDX as not the only "independent" MAb producer left after the acquisition spree because they weren't interested in selling or asking for too much money in comparison to the other technologies.
I like Pfizeth, with the short 'i' pronunciation like the pfaucet.
Pfizeth. The pfabulous pharmaceutical company with the pfunny name.
NEJM: "Gene Therapy Fulfilling Its Promise"
I caught some flack a while back for calling NEJM a rag. This is a good example of why I think the publication has gone off the rails.
GT has destroyed hundreds of millions in investor capital, untold millions in grant money, and 'wasted' thousands of scarce clinical trial patients.
The article re-treads the SCID-kids treated with GT and describes 10 more SCID kids treated with a slightly different gene. Now I suppose I would be a fan of GT if those were my kids, assuming my kid was not one of the 25% of kids in the original study who didn't end up with a leukemia-like disease. But to call it "fulfilling it's promise" is a stretch any serious medical journal should have caught.
I hope they eventually figure out the delivery problem, but let's be real and call the entire field a continual disappointment until they do...
Most lab jockeys I talk to think very little of MEDX's MAb technology, believing it is not as "human" as the company makes it out to be. I think that will dampen enthusiasm for their linker. We've covered them for some time, but I have to say I'm not a fan of the management team outside Geoff Nichols -- who's been pretty straight with us over the years.
I believe SGEN and IMGN have the best chances at winning, mostly due to the relationships with Genentech. Many people I talk to are using DNA's development decisions as a proxy for which of the two will be the winner. I know from talking to DNA program heads that its a bit more complicated than that, but I'd be naive to think the relative dollars DNA invests in each technology won't be a factor in investment decisions.
With different people in charge, the NASD is now going back through their files and requiring companies to conform to the letter of the law. This means issuing a separate press release for going concern letters.
If you do a Google search on "NASDAQ Marketplace Rule 4350(b)(1)(B)" you'll see dozens of companies have issued these press releases over the last few months as the NASD has started sending out letters changing prior guidance.
Prior NASD guidance was that issuing a press release publicizing the filings that contained the going concern language was enough. Yes this violates the letter of their on rule, but that sometimes happens as anyone with experience in dealing with regulators knows.
(which the company said they just couldn't run with the label for bovine in respnse to a question from david in fact)
The reason behind this is the protocol would have violated the black box warning. When Zymo approached some IRBs & KOLs, they weren't comfortable with it. That makes me even more surprised at the P4 that KG is running. Aren't they purposefully selecting patients that are likely to have a reaction?
I agree on the P3b design. They are trying to edge around the issue without having to run head-to-head trials. I suspect if the current pricing strategy doesn't get them more traction, they'll have to decide whether to invest in a meaningful trial, adopt some other strategy, or abandon the product. I doubt it will be the latter until after they see how the product does in Europe.
This makes me wonder if Zymo's Phase IIIb data is getting them traction with hematologists and the P&T committees. I agree this seems an awful risk for KG, though they are tilting the cards in their favor using a 48-hour assay (good catch on this.)
http://www.zymogenetics.com/ir/newsItem.php?id=1233795
[i} The Phase 3b open-label, single-group, multisite study evaluated the immunogenicity and safety of RECOTHROM among 205 subjects who were at increased risk for having anti-bovine thrombin product antibodies as a result of prior surgery with a high likelihood of bovine thrombin exposure. Topical RECOTHROM was applied during a single spinal or vascular surgical procedure. Immunogenicity was evaluated by enzyme-linked immunosorbent assay at baseline and Day 29. At baseline, 173 subjects (84%) were seronegative and 32 (16%) were seropositive for anti-bovine thrombin product antibodies.
At the end of the study, no patients had developed antibodies against RECOTHROM. The immunogenicity profile of RECOTHROM did not differ among patients who entered the study with or without pre-existing antibodies to the bovine thrombin product.
Your post reads like the kind of blurb the IR department at DNDN might have crafted.
That added a great deal to the discussion. Thanks for sharing.
The data in the post to which you replied is from Taxotere, which the FDA already approved.
In regards to Dendreon, "speculative" is a pretty good word.
They ran the stats and concluded they could advance the timeline with no important reduction in power. From talking with them about this they factored in all of the rational statistical/tail issues people have been talking about since the change, and still concluded it was safe to move it up. It wasn't done on a whim, but on their analysis of the data -- which I think is important.
However, it ill all come down to April. If they are right, they are geniuses. If they are wrong, they are morons.
Yeah, welcome to HR hell.
The data were updated at ASCO recently to a HR of 0.79 in 2007 from a HR of 0.76 in 2004. Converting that to the way DNDN (and, increasingly, everyone else) uses the HR gets us 1.266 in 2007 and 1.316 in 2004.
It is common for some people to see a HR of 0.76, subtract it from 1, and call it a decrease in % risk of death -- in this case, 24%. Using the same nomenclature, the 2007 updated TAX-327 decrease in risk of death is 21%. (At some point in 2H-2006 that was just 12%, see below)
Incidentally, in 2007 for Taxotere:
http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=46&abstractID=20276
Using the 2007 numbers from the slides, not the abstract...
3yr survival = 17.9%
Patients younger than 69 did better
Patients with PSA higher than 114 did better (pts. PSA <115 were not stat sig for survival)
Patients without pain did better
Patients with a worse performance status did better
Patients with lower (worse) FACT-P scores did better
Anyone who gets the logic of that data set, let me know...
If you go through the presentation (scroll down the page a little and click on the "slides" icon), you'll see all of these analyses.
Those with eagle eyes and lots of time on their hands could note the difference between the HRs in the 2003/4, 2006, and 2007 updates. Even the 3yr survival numbers are different. This is probably worth remembering in case anyone says that aging the database makes little difference in the HR. The 2006 and 2007 numbers were almost certainly run less than 6 months apart since the presentation was made 2/2007 and the abstract deadline was (I think) 10/2006 that year). Here, we have...
2003 original HR = 0.76 (1.32)
2006 updated HR = 0.88 (1.14)
2007 updated HR = 0.79 (1.27)
My favorite slide in the presentation was the last one, to which there was a big chuckle and lots of nodding heads (though they cut the audio off on the ASCO site before that)...
A mere 20-25% improvement in survival in this patient population is not going to get clinicians hugely excited
That same survival improvement (26%) was enough to get oncologists so hot about Taxotere that they've tried to launch literally dozens of new trials to push the drug into earlier-stage patients. Taxotere PCa sales have underwhelmed because patients refuse to take it due to side effects. Hell, even Maha Hussein said the side effect profile is so concerning that she believe it is OK to refer Taxotere-naive patients to clinical trials instead of giving them Taxotere. I've spoken with more than a few docs are uncomfortable with Taxotere's 2% kill rate. I know only a handful that will give Taxotere to an asymptomatic patient unless the patient insists. Urologists largely will not prescribe Taxotere because they don't have the facilities to handle the side effects.
Provenge has no such barriers to adoption by patients. It has no side effects that last longer than a couple of days. It doesn't submit the patients to the disruption caused by losing one of every three weeks for over seven months like Taxotere does. Urologists will prescribe Provenge in droves.
As far as the "bother", all the hassle in on Dendreon's side. Patients certainly have no more hassle than with chemo or any other IV cancer drug -- less because they get a total of six doctor visits for the drug in their lifetime. Those visits are likely boring, sure.
Docs using Provenge will have a slightly more strict scheduling requirement than they are used to, but otherwise they just tell the patient where to show up and when. The contract apheresis centers have all the logistics figured out on the outbound, Dendreon has it all figured out in Jersey, doctors just hook up the IV after the inbound, and FedEx has got it handled in between.
I acknowledge the drug SOUNDS different enough that salespeople will have to do a good job educating docs that it isn't the nightmare they've heard about with fully autologous immunotherapies. Adoption won't be instant. Those thinking that Provenge will sell a billion in the first year or even the second year are dreaming. Once docs have been through it a few times, it will seem as natural as any other oncology drug.
DNDN TTP
I do believe the .052 number is valid, just that the clerical correction post lock is something the FDA will never accept (and rightly so).
OK, thanks. I think what probably happened was that DNDN told the FDA about the clerical error and the FDA told them it as post-lock BUT if they wanted to pursue it they could bring all the scan data into the FDA and re-analyze the scans.
Since DNDN was told in the review process that the BLA would be decided on the basis of survival and not TTP, nobody on either side was interested in bothering to undertake that effort.
I think that was the right choice, not only due to FDA's guidance, but the extreme variability in determining TTP from xrays in prostate cancer. One reason why TTP and PFS by xray are not accepted surrogates in PCa is this variability of determining whether normal scan-to-scan variations in bone imaging is progression or a film shadow.
Top pick for a few years running. Under coverage since 2005 at $7-ish. (Dew can insert blind squirrel comment here if he likes.)
Hey, just out of curiosity, why don't you buy the 0.052 on the TTP?
Yeah, we screwed up on this one.
Taking no quantifiable position on a stock is easier, I agree. As to being bullish or bearish being equivalent to black and white? I know you're not that naive.
People like yourself who aren't actual readers often confuse the point of our service. We are a research service, not a stock picking service. We're but one tool an investor should use and they would be foolish to use only one -- us or anyone else, including you. We've admittedly contributed to this confusion by creating a model portfolio as part of our service. As readers will attest, we regularly remind folks of why it exists and what role it should play in people's own research efforts. I think having a trackable portfolio is important, however.
I'm not sure "smokescreen" is an appropriate word. We have the performance of our model in every issue. We don't hide from the fact we're having a terrible year this year. Some subscribers have even written me telling me they are tired of me writing about it!
Some of that is out of our control (all the major indexes are similar to worse), but we've made some bad choices I'd certainly like to have back. We're underperforming the major biotech indexes, though we've remained roughly equivalent to BioCentury's smallest cap biotech tracking sheet.
Unlike others in our little niche, we've made the decision to quantify/report specific positions, track their performance, not create new portfolios every time the old ones stink and/or conveniently "forget" to add a loser position to their end of year tally. Anyone who isn't specific, yet claims a successful porfolio return is just blowing smoke up people's arse, right?
In any case, I'm sorry I haven't spent more time here over the past few months. I miss the give and take.
Have a great holiday season and may 2009 be a friendly year to all biotech investors.
We had a sub-underweight call option position on YM going into the BOND-clone data. Does that qualify as "bought into" in your realm.
FWIW, I do think the drug will have efficacy and will do so without rash. I'm not about to invest significantly in the company, despite trading well below cash, until management proves they know how to demonstrate that in a well-designed, NA-enrolled, randomized trial.
Even if they do, the company won't be worth as much as that sort of successful trial might suggest unless biogeneric legislation provides a substantial patent extension for existing biologics since the patents on nimo are close to being up.
1/2 BS. (DNDN)
The trial has dosing (and therefore cost of goods) implications. Those who know the clinical path of Provenge very well likely remember the third dose was always something of a "toss in" with it not having any discernable difference in most men.
It is primarily a way to get access to Provenge for patients and keep the staff of 200 at Dendreon busy if the interim isn't successful. If the interim is successful, I doubt ProACT will ever finish enrollment.
The FDA doesn't care about the MOA of Provenge. All they care about is if the company can consistently characterize and quantify the difference between a "good" dose and a "bad" dose during manufacturing. That's already been settled.
Unless otherwise indicated, this is the personal viewpoint of David Miller and not necessarily that of Biotech Stock Research, LLC
Iloperidone was a big drug for them at the time they effectively shorted their company's stock from $65 to $2. If they thought the drug was worthwhile, do you think they would have created that position?
iloperidone moral #2: Never trust anything from a management team (TTP) that made money when its stock went down.
Next time you get a proxy statement from a clearinghouse voting facilitator, read the fine print. I've been told some hypothecation agreements (part of your agreement with your brokerage) also include the language.
It depends on how the true 100 shares voted. If they all voted 'no', then it is a distortion.
How can they not know this? Since it is self evident do you mean they are just failing to understand some technical detail?
You'd have to ask them. In my experience with this, maybe one in 100 has ever even contemplated it. Maybe 20% get it immediately, another 20-30% get it after about 20-30 minutes, and the rest either simply can't figure it out or refuse to believe me because they assume the SEC would have regulations against something that potentially damaging to corporate governance.
The latter percentage is much lower among regulators, with the difference going to the 20-30 minute group.
And don't get me started on trying to explain this to journalists... I'm well below the Mendoza line on that group.
Even if the FTD is not cleared up, both the original owner and the owner of the shorted shares gets to vote. The clearing house just cleans it up via proportionality.
Let's assume 100 true shares out and each is shorted 10 times. Everyone votes and nobody holds paper certs. 600 shares are voted yes, and 400 shares are voted no.
The clearinghouse just reports to the company that 60 voted yes and 40 voted no. Nobody is the wiser... well, except for those who read the fine print.
Unless you have a margin account at a larger firm, you wouldn't. I've received cash in lieu on every dividend stock owned outside of my Roth accounts while with Ameritrade. They have a policy of making me whole, since they make far more money loaning my stock.
The bigger issue is distortion of voting. Unfortunately, it is effectively impossible to prove any distortion exists because nobody with the clout to force a real accounting bothers to ask the question. Plus, it's only been in the last few years where the clearing houses could have even told you which shares were created from short sales and which are bonafide registered shares. There's also the issue of shares created via short sales that are in the hands of long-term owners with no way of knowing they were created out of thin air.
Frankly, the only vote I've wondered about is the Compaq/HP merger. Since that one occurred before SEC required tagging of share transactions, we'll never know.
If you ever want to have fun, try explaining the concept that short selling creates new shares out of thin air to a bunch of finance professors. It's a real hoot. Almost as much fun as trying to explain it to market regulators, if only because most regulators I've run across at least are aware they don't know much about technical market issues.
The biggest damage comes from the shorting of the shares in the first place. With today's highly-developed and liquid derivatives markets, there is no reason to allow shorting of individual shares. Bonafide hedging can be done other ways. OF course, America cannot unilaterally make that change else we lose one of the last (if not THE last) competitive market advantage we have as liquidity would scurry overseas very quickly.
Dividends and shareholder voting work the same way with naked shorting as they do with any other kind of shorting.
Yeah, poorly and unfairly.
"We are not moved by comments by committee members who say they want this drug approved because they say the approval will foster the development of a particular field. "
This is the Provenge-specific comment in the article. A few folks on the committee would have done patients a service to confine their comments to the drug instead of the field.
This is a big deal for pharma that is creeping into lots of places. Most regulatory pros we're talking to are telling us going to the FDA is noe completely random. You never know what rule they are going to make up or break today. This is a good example. Pazdur's made-up rule that a confirmatory trial has to be substantially under way to be eligible for accelerated approval is another. The use of non-approved drugs as required control arms is a third.
Watch cost issues to start creeping into the discussion, which will accelerate come next year.
For prostate cancer, specifically, an additional reason for low participation in clinical trials is that women don’t have prostates.
If you are implying low enrollment in PCa trials is because 51% of the population is automatically not eligible, then you're on the wrong track. Men rarely have breasts or get breast cancer, yet breast cancer trials have among the highest (if not the highest) participation rates by percentages or speed of enrollment in oncology.
If you're implying that women are generally more likely to enroll in trials, that's a tougher one. I would tend to agree with you, but it really isn't until you get into elderly leukemia trials of one flavor or the other that you start seeing consistently higher percentages of women in the trials. So, I'm not sure the data supports our impression here.
If I think about it, I'll start paying closer attention to gender breakouts when I look at posters and presentations at the next few scientific conferences I go to...