Replies to post #126721 on Biotech Values

[mcbio]

PGNX - PSMA ADC additional Phase 1 data

http://biz.yahoo.com/e/110923/pgnx8-k.html

Form 8-K for PROGENICS PHARMACEUTICALS INC

23-Sep-2011

Other Events

Item 8.01. Other Events.
Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) today presented at the Prostate Cancer Foundation's annual Scientific Retreat preliminary results from the Company's ongoing phase 1 trial of its PSMA ADC antibody-drug conjugate for treatment of prostate cancer.

The presentation includes data from 26 patients who have received doses ranging from 0.4 mg/kg to 2.0 mg/kg. Antitumor activity, manifested as significant reductions in prostate-specific antigen (PSA), circulating tumor cells and/or bone pain, have been observed at 1.6 mg/kg and higher doses and appear to be dose related. Of the five patients who received 2.0 mg/kg doses of PSMA ADC, two exhibited a decline in serum PSA of 43% and 90%, respectively, following the first dose as measured at the end of the first three-week cycle following that dose, and three experienced stable PSA. The two patients exhibiting a PSA decline also reported a reduction in bone pain. An analysis of the level of circulating tumor cells (CTC) for these two patients was unavailable at the time of the presentation.

PSMA ADC has been generally well tolerated at doses up to and including 2.0 mg/kg (the most common clinical adverse event was fatigue, reported by 24% of patients at the higher dose levels, or 16% of all study patients), and a maximum tolerated dose has not been determined. Patient dosing at 2.0 mg/kg has concluded, and screening for a study cohort at a dose of 2.2 mg/kg has commenced.

PSMA ADC is an antibody-drug conjugate designed to selectively deliver chemotherapy to cells that express prostate-specific membrane antigen, a validated biomarker of prostate cancer. Progenics' phase 1, dose-escalation trial is studying PSMA ADC in patients with taxane-refractory metastatic prostate cancer.

Additional data and information from the trial are included in the presentation materials exhibited at the Prostate Cancer Foundation Retreat, and are available for the next 30 days on the Events page of Progenics' website, www.progenics.com.

[mcbio]

You may be right. At the MLNM gave no indication that they were working to improve the linker that they got form IMGN they way Genentech has. However, there was talk that one of the big factors for the failure of the PSMA drug was that the target is shed copiously into the circulation. As you can imagine, this can produce a kind of "sink" for the toxin-PSMA Ab construct, reducing the amount that gets to the tissue.

pgs: Curious if you have any comments on PGNX's early results for its PSMA ADC for prostate cancer that I posted on in #msg-67357499 and, most recently, #msg-71663954. Namely, do you find the early results encouraging and do you think they lend credence to the possibility that the prior failures of PSMA Abs may have been due to the specific drugs themselves, not the target? Also, how strongly do you think large drops in circulating tumor cells will correlate to a potential OS benefit? Note in the most recent Phase 1 ASCO GU update poster that while some patients seem to derive no benefit, there were also patients that saw large drops in their CTCs. Specifically, looks like 2/4 patients in the 2.0 mg/kg group and 2/3 patients in the 2.2 mg/kg group saw large and sustained drops in CTCs from baseline. Separately, PSA declines don't necessarily correlate as only 1 of those 4 patients that had a large drop in CTCs also had a large drop in PSA. I do believe that drawing conclusions based on PSA changes tends to be a bit controversial though. So, is the drop in CTCs the more important endpoint to focus on here?