Replies to post #539 on Dendreon Corp fka DNDNQ

[walldiver]

Poorgradstudent...first of all, thanks for posting the conf call transcript here, that was very helpful.

As to your question regarding the CMC section of the BLA, the company has said all along that this will be the rate-limiting step to getting the BLA filed. To me, I believe they mean that it's the last step. However, IMO it looks more and more like the P-11 data will be a parallel "rate-limiting" final step of the BLA. It's taking longer for the number of PSA=3 events to occur than what was previously thought. Originally, upon the enrollment of the final patient they thought that topline data would be ready sometime in 1H 2006. Now, it looks to be sometime in Q4.

[bcblbrbm]

PGS - Sam here
Good day to you.
I don’t remember if you go for the theory that BigPharma is pulling the strings with much of the DNDN shorting going on. I am pretty well convinced that this is the case. I do not believe the pablum that Levinson has provided over the years about his total freedom to act as he chooses. He says Franz and the boys from Basel give him total autonomy as DNA CEO. Poppycock! I think that Roche is pulling the strings from afar, telling b. DNA to stop assisting (co-working small molecules) their future competiton, and a. hedge funds to keep DNDN on the griddle, looking like a failing company dependent on a one-trick pony. When I stop to take stock of where we are: Neuvenge is in the freezer (drop-kicked there by herceptin) and now the tainting of trp-p8 is being quietly debuted. Hell, yesterday Miller tried to get a light shining on that one, and we were all rewarded with something about an internal DNA decision. All we have left in the investing public’s eye is Provenge.

With that as the major portion of our sackful of woes, I am still an investor. Mitch still has a shot at the gold, and he seems to be on track. I would be even more of an investor, if I thought for one Beirut second that no one at the FDA can be convinced to make a choice counter to their true belief. My largest concern is that someone will cave (dollars, threats, jpg evidence of unlawful carnal knowledge of domesticated farm animals, etc., etc.) and the others will capitulate and DNDN will end up in a “do loop” of approvable letters, while Roche and DNA fatten up and invent/buy into new stuff to replace the items which DNDN threatens.
I bow to your earful of a world leader in drug pipelines and his considered opinion. I do not get to hear such items, unless provided by someone such as yourself. Did you just hear this, or have I missed it in your previous postings? I do not knowingly miss your words. If I become convinced that trp-p8 is a dead end, I will re-evaluate my investment horizon and amount. Right now, I would be very interested in your expanded view of the future of trp-p8.
Regarding your >> Are they purposefully refraining from saying "BLA" will be complete? Or is the CMC completion considered synonymous with BLA completion at this stage?<< I do not know if they are mincing words or not. sam

[nmstav]

PGS, you say:
"In reading the transcript, I'm also noticing that management is specific that the CMC section will be complete by the end of this year. Are they purposefully refraining from saying "BLA" will be complete? Or is the CMC completion considered synonymous with BLA completion at this stage?"

PGS, don't you think you're being more than disingenuous? Urdal clearly refers to BLA submission, with Clinical section being filed by August, and CMC section by yearend.
Are “purposefully” refraining from seeing the truth....


<<Dr. David Urdal - Dendreon Corp. - SVP, CSO

I am pleased to report that our BLA submission for PROVENGE remains on track. We continue to have a very collaborative and productive dialogue with the FDA. We plan to submit the clinical section of the BLA later this month as part of our rolling submission followed by the chemistry manufacturing and controls or CMC section by year-end. As most of you are aware, there are two key components to the CMC section. The first is the build-out of our commercial manufacturing facility in New Jersey and the second is the scale up of the recombinant protein antigen at Diosynth Biotechnology in North Carolina. We completed the build-out of our New Jersey facility last month and we are now in the process of validating and qualifying the facility to support the required pre-approval inspections by the FDA.

Likewise, we have made significant progress with activities to produce at commercial scale the recombinant protein antigen, one of the key raw materials used in the production of PROVENGE. Dendreon employees together with the team at Diosynth successfully manufactured a series of consecutive conformance lots of antigen, which is a required part of the CMC portion of the BLA submission. We feel very good about our progress, particularly with respect to manufacturing, which can be a stumbling block for many companies seeking FDA approval. I look forward to keeping you informed on our ongoing progress with the BLA and I'll now turn the call back over to Mitchell.>>

[rancherho]

1. Trp-p8 mRNA is overexpressed in ADPC and may be down regulated as hormone therapy gradually causes pc cells to become androgen independent. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_...

2. On 4/18/05 DNDN reported: “The data presented show that these potent agonists of Trp-p8 significantly inhibited the growth of Trp-p8 positive tumors in mice by as much as 77 percent over controls (p=<0.0001). The lead compounds presented selectively killed Trp-p8 expressing cells at a physiologically relevant temperature and at well tolerated doses” http://investor.dendreon.com/ReleaseDetail.cfm?ReleaseID=160508&Header=IR

3. DNA reportedly did not give DNDN the reasons that it chose to drop out of the Trp-p8 development program. However, if its utility as a pc target is limited to the ADPC stage of the disease, there could be several potential reasons for their decision: (a) hormone therapy is relatively inexpensive with competitive products already on the market; (b) the median duration of ADPC before transition to AIPC is only about 18 months; (c) ODAC and the FDA have not agreed upon any surrogate markers that could shorten the long periods required to establish statistical significance for clinical benefits in ADPC such as survival and metastases; (d) if a Trp-p8 agonist works against the same pathological channel as anti-androgen therapy it might not prove any more effective than hormone therapy, and even worse, might speed the transition to the AIPC stage. OTOH, when the FDA approves Provenge for use in AIPC, its earlier use in ADPC would be a logical expansion where its benefits against AIPC cells would start even before the number of those cells became the dominant pc cell type and ADPC cells were reduced in relative numbers.

4. Genentech’s forte is in monoclonal antibodies where there are certainly many additional unexploited targets, and where they are transitioning some of their best sellers from “naked” mabs that attract immunity attacks to kill cancer cells to conjugated mabs that bring their own cytotoxins to the cancer cells.

5. Adding to all of the above, the division of profits with DNDN in the event of the development of a successful Trp-p8 therapy would further reduce the desire to commit time and resources to development.

6. It would have taken many years to bring any Trp-p8 therapy through clinical trials and FDA approval. One may argue that its perhaps temporary elimination from DNDN’s pipeline is somehow material. However, it is becoming increasingly obvious that WS views investing in early stage biotech candidates as akin to hoping for success in wildcat oil and gas drilling. DNDN has a blockbuster in Provenge tantalizingly close to FDA approval and commercialization with the ability to generate one billion in annual sales just out of their NJ facility. CELG is just approaching the annual billion dollar sales figures now and has a $15 billion market cap. DNDN’s sole focus on bringing Provenge through FDA approval is just economic common sense.

Good luck to all DNDN longs.