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The issue with ipi approval is not so much the data but whether BMY got FDA agreement for the second SPA edit. The SPA stated the study arm was ipi+gp100. BMY's comments at ASCO indicated they considered the study arm to be any ipi vs gp100. They'll clearly apply for approval for ipi monotherapy and not ipi+gp100.
Unless BMY got approval for this second edit, the stat geeks at the FDA are going to have issues with this shift. I'm not saying the FDA turns the BLA down, just that the stat review section should be interesting.
I've been away for two weeks on the road at AUA/ASCO. Did y'all come to any conclusion whether the ipi label would be limited to HLA-2+ patients (51% of the market) due to the fact these were the only patients allowed in the trial?
Activation is not the same as training.
Activation is getting them ready to do something.
Training is giving them instructions to kill something specific.
Semantincs, perhaps, but an important distinction.
We went round and round on the RAS thing with two different reovirus experts. One said reovirus reproduced only in ras+ cells. The other found no such lib=nk. After they were done sniping at the other's research, the answer was somewhere in the middle. Reovirus can replicate in any appropriate cell. There appears to be some preferential replication in ras+ cells, but it is by no means limited to ras+ cells. It certainly does not stop replication just because there are no ras+ cells to be found.
Reolysin has no role in educating the immune system. Increase tumor cell lysis and the resulting "cloud" of antigens separated from the normal "cloak" tumors cells often provide apparently results in additional immune response. This same phenomenon is seen in any cytotoxic drug that is not also heavily immunosuppressive.
I'm not harshing on Reolysin, there's just a conventional wisdom about all sorts of "extra" benefits to the drug that are not 100% accurate.
Fortunately, you are increasingly a minority in the field of oncology. Randomized Phase II programs are increasing through the hard work of Mark Ratain and others. Especially for survival endpoints, which is what Pazdur ultimately wants to see in most cases, there is always a post-progression standard of care that is not equivalent to watchful waiting.
Running a randomized P2 in your expected P3 population allows you greater clarity on magnitude of treatment against either an active control or this standard of care. Overestimating treatment effect is where most P3 oncology trials run off the rails. Randomized P2s also tend to happen in a wider variety of centers, which helps in the P3 design, speed of execution of P3, and ultimately for commercialization.
We continue to cover ONCY because we think the drug is not a zero. We are not pounding the table on ONCY because they didn't do a randomized P2. Since investments can be sized appropriate to risk, there is no conflict between liking the drug and not liking the lack of randomized P2 trials.
Truth, except in years where we are rebounding off major sector lows. Small biotech usually doesn't peak in May, though. More recently, the peak has been April.
As you may know, we cover ONCY. They are under the broader cataegory of immunotherapy, but I don't class them as active immunotherapy in the way Dendreon and some of the others are. They don't target a specific antigen, for instance.
They are an immunotherapy.
We've been generally positive on ONCY since we started coverage, though we cautioned investors it would take a lot longer to get to the finish line than they were expecting. We've always said ONCY would be a company for "the next decade" which is this decade. They're on track for that.
My biggest worry is the company is headed into Phase III without a randomized Phase II. We discuss this in more detail in our research.
Provenge is the only active immunotherapy proven to work. Show me an active immunotherapy that gets FDA approval using a different method to train APCs, and I'll modify the statement.
That may sound simplistic and circular, but I've looked at a **LOT** of these companies and each thinks it has a better way. In a decade of watching, none have. Are some of the later-stage candidates madly generating PRs with the Dendreon name hanging off of them going to get across the finish line? I hope so, but I rather doubt it. Frankly, however, of the "rules" I posted this is the one I expect to be broken first.
The initial Phase III trials had very poor antigen surveillance data. IMPACT was different. Of course each trial demonstrated PA2024 immune response. As I've said in the past, a bright college student can accomplish this.
People *REALLY* need to look at the AACR data presentation. In addition to T-cell and B-cell stimulation on PA2024, there was T-cell and B-cell stimulation against PAP. The latter was surprising.
Poorgrad has been saying Provenge is a general immune stimulant for a long time. Perhaps he'll be proven right in the end, but I'd remind him and other that we've used all manner of untargeted immune stimulation in the past 100 years on cancer and the results have been poor across unselected patient populations. Clearly, Provenge does something different than has been tried in the past.
As to Neuvenge, you raise a good point and one that has been a common critique of every active immunotherapy ever developed. The HER500 antigen is much different than the PA2024. It is more highly engineered (think Version 3 versus Version 1). That seems to make a difference. The data from the Phase II breast trials has not been well reported, unfortunately. Immune response against her2-neu has been seen (personal communication) but, for whatever reasons, wasn't broadly investigated. Safety in the Neuvenge Phase II trials was good, though efficacy was not. The theory is it has something to do with the more extensive lymph node removal seen in breast cancer patients. I've had lots of people tell me that theory is bunk, and again it was only personal communication, so take it or leave it.
Ipilimumab clearly takes the brakes off the immune system with significant adverse events resulting. 30 days ago, I would have told you I would have expected Neuvenge to have more side effects than Provenge because her2-neu is found on more healthy tissues and target tissues are not as removable as PAP tissues.
In talking with Tia Higano on the Seattle Times chat, however I learned something new: Guys without definitive prostate therapy were allowed in IMPACT. For whatever reason (usually age or comorbidities) they just go on hormone treatment. When they fail hormone treatment, they are eligible for Provenge. So, guys with completely intact prostates are getting Provenge with no apparent uptake in adverse events. (From the label: Thirty-five percent of patients had undergone radical prostatectomy, 54% had received local radiotherapy, and 82% had received combined androgen blockade.)
This implies Neuvenge will be able to demonstrate efficacy without demonstrating added adverse events.
And thanks for the congrats. Got a lot of crap over the years for our view and, frankly, it feels very wierd for everyone to be positive on the company. Very Alice in Wonderland...
It did, actually. Read the updated data from IMPACT. Both T-cell and B-cell stimulation against PAP.
The Neuvenge Phase II trial is not an FDA-approvable trial, just to be clear.
Fabulous, thank you.
Entertainment Alert -
-- On Wednesday, April 28, 2010, at 8:30 a.m. Eastern/2:30 p.m. Central European/5:30 a.m. Pacific, members of Cell Therapeutics, Inc.'s (CTI) (NASDAQ and MTA: CTIC) management team will host a conference call to discuss the Company's 2010 first quarter financial results.
Conference Call Numbers
Wednesday, April 28
8:30 a.m. Eastern/2:30 p.m. Central European/5:30 a.m. Pacific Time
1-866-225-8754 (US Participants)
1-480-629-9692 (International)
Call-back numbers for post-listening available at 11:30 a.m. Eastern:
1-800-406-7325 (US Participants)
1-303-590-3030 (International)
Passcode: 4288273#
NCI too often funds trials without taking into consideration whether patients will enroll in them. A perfect example of this is at least a dozen cooperative group trials in prostate cancer testing chemotherapy in early-stage disease. A $1,000 survey of men with PCa could have told them the trial wasn't going to enroll.
Also, too often the process devolves into petty bicerking among academics looking to get the next publishing feather in their hat. Group A won't enroll patients in a trial created by Group 'B' because Group A doesn't like the lead investigators in Group B. So Group A creates their own, slightly different trial that competes for enrollment. Neither get done.
I expect we'll hear more about the blame than the benefits as the quarters roll by. Most pharmas have patent expirations and other headwinds and HCR makes a convenient scapegoat.
At some point - probably not this decade and maybe not next - HCR will encompass financial review and some sort of large group negotiations on price. Then they'll have something to bitch about until they start making other countries pay their fair share so US consumers (and a couple of others) don't have to bear the majority of drug development costs.
I have only seen Matine speak once, and was fascinated by the way Wall Streeters related to her. Some wouldn't go near her, preferring to congregate around other executives. Others went straight to her, leaning in closely to hear her rather quiet voice. I know more than one hedgie who refused to invest in UTHR only because of her transgender status.
Their loss.
The more accurate description of these numbers is they represent what HCR will cost these companies in the short term. Costs for most, though perhaps not device companies, will be offset by added customers once UC kicks in.
Me too. Got a good chuckle out of that headline.
Well, I'm not sure where to start. The work on oncoviruses goes back decades. The reson we don't have one approved is none of them have worked. The basis for the Fortune comment about no research into metastatic processes ignores the fact we don't really have any idea how it works and, until very recently, no tools to figure it out. I like immunotherapy and do believe it is the future more than chemotherapy. Surgery "cures" way more people than drugs, though drugs plus surgery (neoadjuvant and/or adjuvant) is typically better. Once cancer comes back, you're pretty much not going to get cured -- though you can extend life quite a ways if you choose correctly.
Abstracts go through a scoring process by an army of reviewers that operate in different levels. In theory, abstracts scored higher get plugged into oral presentation slots and those that score lower end up in posters and those that score lower still are published abstract only.
Modifying this is whether the lead author is available for presentation. Also modifying this is the reputation of the lead author. Also modifying this is how well the leaders of the program for that year know the lead author.
To answer your question, you can read a little into this but not much. There are too many variables that can cause the poster/oral decision to be made on something other than the quality of data.
That whole conference call was so surreal I'd forgotten about the "Facebook & Twitter key to enrollment" comment.
The one that stunned me was the (paraphrasing) "just because you vote for more shares doesn't mean there will be dilution." SWhile technically correct, the company has no realistic option but to dilute the hell out of current shareholders.
Threatened. That was one among many things in that conference call that had me howling. The very idea that Bianco is concerned about his shareholders is so completely laughable.
The other one was the response to the shareholder email that voting for the authorized share expansion wouldn't result in resolution. It was classic Bianco: Technically correct, but completely misleading in the real world. He'll need every one of those added 400,000,000 shares to keep himself in paychecks.
Probably. This field is pretty well littered with off-the-wall types.
Turns out there may be brain cells in CTIC holders after all. Meeting postponed. Last time they said that it was because of a lack of quorum. CTI's removed all those releases from their website.
Anyone who went through it last time remember how many tries and how many months it took?
Well, $40M at $0.60 is close to the Italian vote requirement trigger. Anything below that and it absolutely triggers it. I guess we'll see what comes out of the ASM vote today at 1pm PDT. Who knows, maybe CTI shareholders are way dumber than I thought.
The issue is they'll need shareholder approval to either do an additional financing or convert the debt as either share amount will trigger the Italian and/or NASDAQ rules for a vote. Traditionally, they haven't been very successful at that.
Big issue #1 is they already offered these same debt holders a conversion and they refused. Why would they accept this time?
Big issue #2 is even if the debotrs agree this time, the company is still our of money by year end - even with the recent financing.
And yes, they could do a Genta and recap. They only have a handful of shares left under the current authorized max. If shareholders are dumb enough to allow more in today's vote, it will given them about 550M shares available.
Figure they need $60M/year for burn (1/3 of what they've EVER done BTW), $50M for the confirmatory trial, and about 5 years to get it done and approved that totals $350M. They have to keep several tens of millions outstanding for options and convertible debt registrations so let's call it 500M shares available if shareholders are dumb.
350/500 equals $0.70/share
Anyone here think they can raise money ABOVE the current price?
PYMX part 2... From the horse's (company's) mouth on your #2 question:
"The natural defensins don't fail. In humans they are used as a barrier and not as a systemic response. The barrier works well until bacteria get inside the body and we can't mount a systemic defense against them. Below are two papers which include more information. "
Zasloff et al, Nature, v415, pg 389-395. January 24, 2002
Tossi et al, Biopolymers, v55, pg 4-30. July 2000
Regarding PYMX...
$10 says Bianco is behind the rumor, conveniently printed today in a German publication of some sort, that NVS is interested in buying CTIC.
First, they weren't interested enough in either drug to actually do a real partnership.
Second, NVS can just wait until July 2 and buy any assets it wants out of bankruptcy court.
Interesting they are punting GVAX. I've never been a fan, but data I saw at a industry symposium prior to ASCO GU suggests they might have found a way to make it work. I'm not convinced it is commercializable, but it was science geek interesting, anyway.
I'll note this universal individual requirement for insurance was the GOP's idea.
http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=103_cong_bills&docid=f:s1770pcs.txt
http://www.wbur.org/npr/123670612
They created it response to Clinton's requirement that employers were required to provide insurance.
First, coverage that cannot be denied for pre-existing conditions is not equal to retrospective coverage. You'd be forced to pay uncovered bills for your initial visits.
Second, coverage is not immediate. Apply today, you'll wait 30 days for it to kick in. You'd be forced to pay for the uncovered bills in the meantime.
Third, the system now is much more expensive to society. If you opt out of insurance now, health care ethics force doctors to provide you basic care. You pay nothing for that care, while the cost of providing that care is >100% of the cost of providing similar care to an insured person. Under this plan, uninsured individuals have to pay into a fund, reducing the overall cost to society because they are at least paying SOMETHING.
Will people try and game ths system? Sure, just like they try to game the private system now by going to free clinics to diagnose (which have no or antagonistic relationships with insurance companies) then popping on private insurance while lying about pre-existing conditions. If you've ever been around free clinics, they "work with" any uninsured who ends up having some chronic/expensive-to-treat condition in order to figure out a way to get them insured.
Well, that was an utter waste of 20 minutes.
Only thing I can think of is transactional pressures (short sales unwinding and options stuff) supporting the price.
re: Genta... Wasn't that the second one? I thought the first one was "only" a billion.
Let's not forget there is likely to be money available. Genta did a billion-share penny offering.
I wouldn't be surprised if the same people did the same thing with CTIC. Unfortunately, uneducated individual investors bear the brunt of the losses in that kind of situation.
“After spending $1.4 billion of shareholders’ money, maybe it’s best for Cell Therapeutics to return what’s left to shareholders and call it a day,” says David Miller...
http://ow.ly/1pS5u
Insanity = CTIC at $0.60 Just saying.
The fact they have not only stopped new enrollment but patient dosing is a particularly bad sign.
One of the least surprising news items ever.
Yeah, that won't work. The most recent economic collapse proves the derivatives always blow back into the underlying. Impossible to separate them.
Shorting is bad enough because it creates dilution, but naked shorting is even worse. Don't like the company? Don't buy the stock. REALLY don't like a company? Fund a competitor angling to put them out of business.
Yup. I've heard from people he maintains his cert, but doesn't actually practice. No reason to doubt him in a direct question.