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ok thanks
They could have used the forum to provide clinicians with an update as to the actual numbers they got from the interim 9902A look. Too bad... that's what these meetings are all about. They may have even gotten some more investigators interested in Provenge following the presentation of the numbers.
sorry, how do you mean?
A placeholder is usually just a vaguely written abstract because, at the time, there are no data to fill it. I've written those. But they don't get removed.
I don't see the clerical error part of it. Was it just not supposed to be sent to ASCO at all to begin with?
actually it's a great soap opera...
If you'll endulge me, am i to understand that dndn submitted an abstract to asco, had it officially accepted, and then pulled the presentation?
OT:
fwiw, i browsed the yahoo dndn board.
Scary place!
I'm just joking around with you guys.
Relax.
What I said: "walldiver thinks it may be good news." (emphasis mine)
You reiterate: "so I basically said it's good news for Provenge if he is true to his word, but the jury is still out on the reliability of his word." (emphasis mine)
So you think it is good news if a certain requirement (Pazdur's honesty) is met. The word I used, "may", implies conditionality, which is consistent with your "if". Therefore, I didn't put words in your mouth. Especially in a 35 word post.
I think Pazdur is bad if you're looking for (or require) a little leniency in the approval process.
Companies looking for accelerated approval will need a relatively robust trial (>100 patients) that is clearly documented (somewhat applies to imclone). No short cuts or sloppiness.
With regards to DNDN, I don't think Pazdur is the type to allow pooling of data from separate trials *if* the company asks for it. He's not that much of a softie. That's just my opinion.
But I don't think he signals an end to cancer drug approval as some fear. Tarceva showed a clear survival benefit and was approved with relative bureaucratic haste. Velcade had a strong accelerated approval package and proceeded through the process without hang-ups. I'm sure he had a glance at those applications somewhere along the line.
It seems as if sponsors need to give Pazdur the impression that he's in control, without making him think that they're trying to slip one by. The one advantage I see for investors is that Pazdur won't let companies run wishy-washy trials. I expect companies to get firm guidance on trial design as well as firm guidance on what is and what isn't a clinically meaningful improvement in the endpoints.
So you say Pazdur may be bad news for DNDN, walldiver thinks it may be good news.
One of you is loco.
The Pazdur giant appears to be engulfing more and more of the FDA.
Some people have allergic reactions to pork meat and it is thought that the heparin may be a target. As angiomax is unfractionated heparin, that's probably why there is the contraindication.
I'll check to make sure.
I don't know what it is about BIOM, but they're stuck on the same damn script.
Theratope had an "impressive" phase II, then they had to reformulate / change manufacturing and had to do a bridging study for that drug as well.
Those who don't know history...
But they wouldn't be presenting at the conference if they didn't have outstanding data, right?
This might be what keeps Genvec solvent in the long run...
But we'll never know if they don't provide data.
Results From Phase I HIV Vaccine Study Reported at Keystone Symposium
Friday April 15, 8:00 am ET
GAITHERSBURG, Md., April 15 /PRNewswire-FirstCall/ -- GenVec, Inc. (Nasdaq: GNVC - News) announced that safety and immune response data were presented from the first of several ongoing Phase I clinical trials involving an HIV vaccine candidate developed jointly by GenVec and the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The data presented showed that the vaccine was well-tolerated and immunogenic at each dose level.
Barney S. Graham, M.D., Ph.D., the VRC study investigator, presented study results at the "HIV Vaccines: Current Challenges and Future Prospects" Keystone Symposium in Banff, Alberta, Canada, indicating that the vaccine was generally well-tolerated in 36 healthy adult volunteers and produced both antibody and cellular immune responses to the three different HIV antigens in the vaccine. The vaccine is the first of its kind to use an adenovector (gene carrier) to deliver genes from all three of the major subtypes, or clades, of HIV causing the global AIDS pandemic, and responses were detected to each of those subtypes. The double-blind, placebo-controlled, dose-escalation study tested three different dose levels, with ten volunteers receiving vaccine injections and two receiving placebo injections at each dose level.
The VRC is also testing the multi-clade adenovector vaccine delivered as a booster to a DNA vaccine to assess safety and help determine whether the vaccine, used as a booster, can provide a stronger immune response to HIV than DNA vaccine alone.
The multi-clade adenovector vaccine was developed using GenVec's proprietary adenovector technology and the Company's 293-ORF6 production cell line. GenVec produced the vaccine under a $40 million subcontract issued and managed by SAIC-Frederick that extends through 2008. All clinical testing is being conducted by the VRC.
GenVec is a publicly held clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies that improve patient care in the areas of cancer and cardiac disease, and to prevent vision loss. GenVec's vaccine program applies the Company's unique delivery technology and 293-ORF6 cell line to develop vaccines against a variety of diseases, including HIV, malaria, and foot and mouth disease. The vaccine candidate discussed in this release has not been approved by the Food and Drug Administration or any other regulatory agency. GenVec is not responsible for the design or conduct of the clinical trials discussed in this release. Additional information on GenVec is available at http://www.genvec.com and in the Company's various filings with the Securities and Exchange Commission.
Hellmann said that the NME was in oncology.
To more accurately reflect dew's comment (he knew what I meant), the velcade population was an end-of-life population similar to the CRC population for Erbitux. I do not doubt that approvals for these end stages of disease garner approvals with fewer patients.
Dendreon's population isn't as far gone in the prostate cancer scale as Velcade's myeloma or Erbitux's CRC patients.
Ok, sorry about my confusion with the patient numbers.
Still a tough call for me. I hope it works out great for you guys.
>As for previous approvals with small trial sizes, how about Gleevec?<
Provenge ain't no Gleevec. Isn't even close.
I agree with you re: safety profile. In my head, I was trying to line Provenge up with Erbitux which also has a very mild side effect profile as monotherapy. Erbitux required as many, if not more patients to achieve its approval in very late stage crc.
Tough call.
What I'm trying to get at is if the number of patients on Provenge, for the expected label, is in line with previous approvals for this disease setting.
So the 225 patients is really 112 or so on Provenge. If they apply for approval for all comers regardless of Gleason score, you're looking to achieve approval with 112 patients in prostate cancer. Restricting Gleason score drops the number of patients below 100.
The question is if the FDA is ready to approve a biologic for prostate cancer in a non-refractory population based on a pooled sample with, at best, ~112 patients worth of efficacy data? Those numbers are usually sufficient for end of the line refractory populations, but I've not seen many cases where it appears sufficient in earlier stage disease.
As someone without a vested interest in the outcome, it honestly seems like a long shot to expect approval based on 9901 + 9902a.
If you pooled the patients on provenge in 9901 and 9902A that would fit your hypothesized FDA label, how many would that total?
Just to clarify, the thread that I was following up on was specifically focused on the MOA of squalamine. When a drug hits the clinic, the efficacy and safety trumps anything that they documented in the culture dish. In that respect, I usually agree with Dew's occasional "never mind the MOA..." sign-off.
However, if someone wants to talk specifically about the MOA, then I'm not gonna sit there as they try to blow smoke up our collective asses.
Thanks.
I realize that most of those who share their insights on this board do so out of generosity and are generally pressed for time. I rely on the strengths of other posters such as yourself, as I'm admitted not as adept as you are in understanding the depths and implications of the scientific work that is done at these companies.
Anytime you want to share with "pions" such as myself, I'd be greatly appreciative.
>Not all bio's are able to produce clear cut, short-term efficacy, let alone be able to provide a staright forward description of MOA. That is why I love GENR's prospects!<
At the risk of boring other people here, I freely admit that I'm very interested in MOAs.
Can you describe to me why GENR's method of action is selective or specific for a certain subset of endothelial cells or a certain subset of calmodulin-expressing cells rather than being a general, ubiqutous description without specifics.
If you don't have specifics, I truly understand. But after the other days diatribe, I expected a little more specificity in your follow-up comments.
If a company is working out the method of action diligently rather than using a paucity of data to implicate its drug in molecular pathways that are popular to investors, then I'll give them credit.
Genaera's presentations and published work on squalamine don't provide indication that the mechanism of squalamine is well researched. Rather, they provide you what are supposedly key aspects of the mechanism, and then quickly draw arrows to anti-angiogenesis and apoptosis or whatever other "cool" pathway there is to draw the public.
For example, there is nothing presented to demonstrate why their noted apoptosis is selective or even specific to a subpopulation of endothelial cells rather than simply hitting all endothelial cells. Those looking at the scientific method of action (if they're so inclined) would legitimately ask this question; those that are not interested in it will simply see the apoptosis term and not question selectivity, specificity etc...
Antagonizing calmodulin signaling in endothelial cells and the adjacent smooth muscle cells would have the primary effect of inducing hypotension. Does squalamine induce significant hypotension? If not, then there are some investors who keep this in mind when assessing the company's future claims with respect to its MOA.
Focusing on selective aspects of the method of action while leaving obvious questions unanswered do not suggest that they have the method of action worked out.
>So what makes them stand out so much if, as you say, they provide "no more or less" than the rest of the companies you refer to?<
I made no comment that suggested Genaera stands out in their work, and don't see anything in Genaera's preclinical work that makes them stand out. In fact, they're pedestrian in this regard compared to other early stage companies that have been scientific powerhouses. See Tularik or Exelixis for examples.
If you want to discuss the clinical data, that's one matter. If you want to discuss the preclinical data, then that's another matter. Both should be stringently examined.
I didn't go to the website to look for additional info.
I went to pubmed.
Again, I see nothing in Genara's presentation of its MOA that is more or less explicit than other companies trying to retrofit an MOA to a previously existing compound. For example, it is initially hard to see why calmodulin is the prime target for their focus rather than the 2 or 3 more abundant signals in their affinity chromatography... until you look at pubmed and see that calmodulin provides an easy way for them to link their drug to a large collection of cell processes.
>they have provided a clear enough conceptual look into Evizon's MOA <
What they did was provide a conceptual look that has the buzzwords that they feel will attract investors. VEGF, angiogenesis, apoptosis etc.. It's not an indictment of Genaera specifically, just a reflection of the research capacities and requirements of smaller companies versus larger companies.
Honestly, just because Geneara (or any company) puts out a PDF presentation with a slide showing that VEGF, bFGF etc... signaling pathways are all antagonized by squalamine is not proof that the mechanism has been clarified.
First of all, no professional scientific presentation uses "etc..." when discussing signaling pathways
Second of all, calmodulin is one of the most abundant protein in cells, challenging the concept of specificity. Plus, some of the common assays used by Geneara (as with other companies) are really tissue culture-specific events. Stress fibres are really an in vitro phenomenon, and it is unclear what role the dissolution of stress fibres has in vivo.
Also, I can't find any data on pubmed describing the apoptotic effects of squalamine.
In short, I personally don't find this presentation to be informative scientifically. Possibly Genaera has more information in-house to support their claims. However, I don't see this presentation to be any more clear or any less clear than presentations from other companies using compounds that were not designed de novo for a known target. It is actually a difficult endeavour to find the target of a previously uncharacterized drug, so the only way to start is to begin by examining well known and often implicated pathways (VEGF or MAPK, for example) and hope that something pops up... that's why, for most drugs without prior MOA data, you'll often see that the early experiments show them implicated in VEGF signaling or MAPK signaling. That's because these pathways are almost universally implicated and are the first ones that labs "test" when trying to get a handle on the method of action.
>How do you protect yourself from this kind of result, where the PII data looks good but turns out to be a stastical fluke?<
A new approach I've adopted is to remain skeptical of compounds that only have one phase II trial result.
Your chance of fluking out in one phase II is much higher than fluking out in two independent phase II trials run at different centers.
I think the other important concept to grasp is that the proverbial train almost never leaves the station. Many investors think that they need to be in a full position leading up to phase III results. I think most of the case examples in biotech will show that a relatively modest position ahead of phase III results (with put protection if you want) is the way to go. Stocks almost always revisit their pre-phase III prices.
The additional danger of having a large position ahead of phase III results is that it becomes very difficult to objectively assess an investment. The money that is at risk inevitably requires investors to rationalize away the uncertainties... I find that dangerous.
Isn't this last paragraph really reality with respect to biotech investing?
So drug X is in phase III... it might fail. It succeeds in phase III, but will the company properly document the NDA for approval? It gets approved, but can the company effectively sell it?
This sliding scale of arguments is actually very valid. I laugh when investors think that such questions signify increasing levels of desperation by those evil hedge funds.
I always think it's funny when an analyst's incorrect forecast on drug sales is publicly announced and practically blamed on the company. I would think it rather embarassing to miss forecasts as badly as UBS did. Just once, I'd like to read an analyst report that says "Wow, we really thought this drug was going to sell. But it hasn't, and we're dumb."
Also, the comment about Tarceva's slow down in share gains versus Iressa is really not useful without some data to back it up. Anecdotally, it appeared that Tarceva had done a great job of eclipsing Iressa's market. So mathematically, share gains must slow down as you theoretically approach 100%. I'd hate for the UBS analyst to confuse his readers with useless interpretations of script data.
Luckily I stopped buying and selling on investment recommendations long ago
Admittedly, I don't know the accounting issues well at all.
However, don't ENMD's losses have an equal effect on Celgene's accounting regardless of what ENMD is working on? What I'm trying to say is that if Celgene records an impact from ENMD due to their high ownership (if i understand that correctly), that impact may as well be because ENMD is working on one of Celgene's compounds rather than something else.
One other small thing is that Celgene likely would keep a much larger share of this licensed compound if it went to ENMD rather than a non-affiliate, due to their ownership stake in ENMD.
But regardless, this is more discussion than ENMD is worth, in my opinion
I'd avoid the stock like the plague.
From interacting with him either directly or indirectly on Genta, it was clear to me that he really had lost his objectivity in explaining Genta's merits. The problem for me was not that he was on the wrong side of Genta, but more that his position revealed a lack of analysis insofar as the type of data that flies in front of the FDA.
He's probably learned his lesson, because his questions on the INGN conference call basically reflected the lessons that Genta taught him. But for 500 dollars, I can find better uses for my money.
Plus, there is a side to his service that I don't trust. They really only cover the smaller companies while avoiding relatively larger cap developmental stage biotechs. (Check out their coverage universe at https://www.biotechmonthly.com/coverage.htm).
Coverage for smaller companies brings the possibility of a symbiotic relationship wherein the biotech management relishes the coverage, and BTM in turn has a vested interest in continuing to cover the smaller company (despite failure) because such companies have larger retail followings... and retail is where BTM's subscribers mostly come from (imo), not larger investment houses.
In short, i think the service limits itself and, either knowingly or unknowingly, opens itself up to having its views biased by its need to continue coverage to appease their subscription base. That's the only way I can explain continued coverage of biotech carcasses like Genta and Aphton, for example, since they should be discountinued like Pharmos was...
Along rkrw's thoughts, I wouldn't completely discount this move by Celgene. Although it is a reasonable and safe bet that this product is a low priority molecule for CELG and possibly a bona fide dud (5% chance), Celgene's management is usually rather astute.
ENMD have proven themselves to be rather inept at R&D. This is a problem for CELG since they have a large ownership in ENMD. I think it is reasonable to believe that Celgene has sent this molecule to ENMD in order to use up, in a constructive manner, some of the resources that ENMD is holding. Otherwise, ENMD is going to blow their money on low- or no-yield projects (Panzem) while Celgene watches their investment in ENMD simply waste away. Basically, Celgene could be farming this out to ENMD so that they can transfer the work and costs elsewhere for the time being. Clearly this isn't a high priority molecule for Celgene, but I doubt it is an absolute dud; it would be counterproductive to send a dud out to a company that you own a large part of.
One other supporting element for the above scenario is that ENMD has really fanned out with regard to their preclinical R&D. They have too much on their plate (JNK, various ligases, various kinases, SERMS, etc...), and have now realized (imo) that they can not pursue each of these leads effectively. Why not give one of the molecules to ENMD for the time being so that they can get some of the laborious IND and phase I work out of the way before they go insolvent?
>a complex series of "if this, then that" has to happen"
Let me guess...
If pigs fly, then that will mean Advexin will be approved.
I had a hearty chuckle hearing Miller from Biotech Monthly on that conference call. How fitting for INGN because Miller is basically the kiss of death...
Our school takes a 54% overhead out of mine. For those unfamiliar with the "overhead", it's basically a surcharge that the university passes to the government so that they can cover the ancillary costs, as biowatch mentioned.
So for every $1 in grant money that the NIH gives me, the university charges them $1.54.
However, I don't think the layers of paper-pushers at a biotech are as wide and diverse as they are at universities. The overhead costs extracted by universities are basically extorting taxpayers. I think at Harvard, the overhead is 80% or so now... ridiculous.
The average employee at a biotech makes less than 200K. Although management may be pulling in these numbers, many of the techs and entry level research assistants pull in the 60-70K range, give or take.
The costs to a biotech company must be largely a result of their clinical trial expenditures and behind that, their R&D.
Remember that for a patient in a clinical trial, the company foots the whole bill, not just the vial of drug that is supplied. I've heard numbers upwards of 10K per year per patient. Not sure how accurate that is, but if you have a large pivotal trial of about 600 patients ongoing, that's 6 mill for that trial alone.
For the R&D side, biotech research materials are outrageously expensive. And with companies requiring specialized scale-up of their proprietary compounds from third party manufacturers, I'm certain the non-salary portion of R&D costs add up. Real world example: For 200K a year, I would cover partial salary support for myself, full salary support for a research assistant and enough materials and equipment for 3 people (the extra graduate student has his/her salary supported from elsewhere). But note that our spending on materials is modest in comparison to a biotech company (they buy everything, even if it is cheaper to make it yourself). So if they had 100 employees, you're easily looking at 10 million a year just for pure R&D costs without any costs associated with the clinical trials.
Re: PEDF
Maybe that's all the targets that were left?
Notwithstanding the merits of limitations of PEDF, I think it's important to realize the deck of cards that Genvec has dealt itself by sticking to the adenovirus platform.
Although other companies are primarily interested in design antibodies and/or drugs to inhibit a specific signaling pathway, Genvec is limited to using endogenous proteins to antagonize a specific pathway.
Therefore, they're limited to trying to overcome the stimulatory effect of VEGF (for example) by using an endogenous protein that antagonizes the VEGF pathway. They do not have the option of making a direct inhibitor as a small molecule company or mAb company would..
Although a disadvantage in areas where you need inhibitors, the platform is a relative advantage in areas where you require augmented protein activity. For example, if a downregulation of protein X is implicated, then genvec's approach is advantageous in that it can introduce protein X into the cell to increase the aggregate activity. It is relatively difficult to design small molecule activators (especially if the protein is not a cell surface receptor and/or a kinase) and it is nearly impossible to stimulate the activity of intracellular proteins through mAbs.
It's a balancing act.
With the recent focus on the AMD field, it wouldn't surprise me if Genvec looked for an AMD candidate simply as a strategic play to capitalize on future market/funding trends.
The safety considerations for a replication competent virus and a purified protein do not have any relationship to each other, in my opinion.
I think that the "transgenic" label to GTCB's work provides it with more headaches than benefits. Really, they're simply a protein purification company. Some companies do it from bacteria or cancerous cells, GTCB does it in goats. Therefore, the safety concerns that the EMEA may have about GTCB's transgenic process must do with the absolute purity of the preparation such as trace viral contaminants, endogenous proteins from the goat's milk, etc... It can't *reasonably* have anything to do with the transgenic process of allowing the protein to be produced into the goat's milk.
Waiting for data from a US trial would be a reflection of the EMEA's skepticism about the clinical data to date, not a bona fide fear of transgenically derived protein.
I'm assuming that in this preliminary communique, they were told "we have some old questions and some new questions."
Otherwise, I'm not sure how they would know there are new questions if they've supposedly not received them.
right... now i recall that as well. I'm not very familiar with it.
As an aside for the AMD folk...
Genvec gave some sketchy details on their AMD candidate during today's Cowen talk. You can access the talk through the webcasts section of their homepage (genvec.com) if you're interested.
If I'm not mistaken, this program is also anecdotally called "compassionate use". It is rather widespread for investigational therapeutics.
I don't follow this company closely, but from the PR I could not determine if the accelerated approval route was withheld because the disease indication is ineligible or if the data were simply insufficient for consideration even under accelerated approval.
Any colour on this? I'd be interested in the implications of this decision.
As drbio pointed out, they do have enough funds to continue on for 3-4 years. That's attractive from my point of view as current investors have a legitimate shot as seeing the first phase III result (and bonus additional data from other programs) without worrying about significant near term dilution.
>How high must its chance of succeeding in the MI program be to make this EV justifiable on the basis of the MI program alone?<
Personally, that's somewhat difficult to gauge at this moment because I think much of the risk in decode will be defined by the actual phase III trial design for DG031. Unless they're completely unreasonable with the trial design (imo anything less than 500 total patients), I think the stock is a very fair value at its current levels in light of the high potential payoff for a successful post-MI drug. When it was trading over $10 per share it was overvalued given the state of the company, in my opinion.
P.S. To my knowledge, they've not outlined specifically the phase III trial design. I hope I'm not wrong on that point. Admittedly I've not listened to each and every one of their conference webcasts.
The initial data on myeloperoxidase (mpo) as a risk factor was based on all-comers who presented at the ER with chest pain. Decode looks like they want to use a marker like mpo (among others) as a means to zone in on patients that have a higher risk of a second MI. Presumably, this will allow them to recruit a "post-MI" population that will have a higher incidence of a second MI, allowing them to design trials requiring less patients and/or less follow-up time.
Therefore, I think there is ambiguity as to the predictive value of mpo following the first MI. I'm not convinced that a trial based in part on this marker is necessarily "predictable" insofar as the performance of the control arm. Also, the magnitude of events is really relatively small to begin with. As it stands, about 5% of patients per year have a second MI (ballpark). For 1000 patients in one arm, that's about 98 events in 2 years. They'll need to be able to enrich that population greatly (using mpo, creactive protein, leukotriene etc) to significantly cut down on the patient numbers and/or time to follow-up that they require in order to show benefit for the treatment arm.
Also, the post-MI population is a bit heterogenous insofar as the extent of insult from the first MI. I presume that they'll have a solid game plan in this regard, but I've not yet stumbled across any details. I'm sure i'll gain an education on this point in due time.
In sum, I think they're being a little cavalier in thinking that they can significantly cut down on the development time for a CV drug. Admittedly if they pull it off, then they're going to have every pharma company waiting at their door.