OncoGenex Pharmaceuticals, Inc. Message Board

Here is a brief mention of this abstract

http://prostatecancerinfolink.net/2011/05/15/whats-hot-at-the-aua-annaul-meeting-sunday-morning/

A poster by Matsumoto et al. (see AUA abstract no. 125) shows the future potential of OGX-011 to be given in combination with MDV3100. This is one of the first papers we are aware of to show that two of the newer agents have the potential to be used in combination. While neither OGX-011 nor MDV3100 has been approved for the treatment of advanced prostate cancer as yet, Matsumoto et al. have been able to show that not only can they be given in combination, but that they appear to have a synergistic effect in an animal model of castration-resistant prostate cancer (i.e., they worked better in combination than either drug did on its own).

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Such research is also important for investors as it reduces the uncertainty of whether the SYNERGY study will be able to achieve the hazard ratio of the P2 study as in the P2 study OGX-011 did not interact with these new treatments.

Thought I'd repost the abstract since there were some words missing, including p-values, when I copied it earlier:

125: CLUSTERIN ANTISENSE INHIBITOR OGX-011 SYNERGIZES ACTIVITY OF SECOND GENERATION ANTI-ANDROGEN, MDV3100, IN CASTRATE RESISTANT PROSTATE CANCER MODEL
Hiroaki Matsumoto
Hidetoshi Kuruma
Amina Zoubeidi
Ladan Fazli
Martin Gleave
Vancouver, Canada


INTRODUCTION AND OBJECTIVES: Experimental evidence strongly implicate the AR and intra-tumoral androgen synthesis in promoting tumor cell survival and development of castrate resistant prostate cancer (CRPC). The new second generation AR antagonist, MDV3100, has shown activity in preclinical and clinical studies. Our previous studies link androgen ablation therapy with clusterin upregulation and castrate resistance, and we developed the antisense oligonucreotide, OGX-011, that synergistically enhances both castration and chemotherapies in prostate cancer (CaP) models. In this study, we tested whether OGX-011 sensitized MDV3100 and delayed castrate-resistant progression in LNCaP model. METHODS: Effects of single vs combination MDV3100 and OGX-011 regimens on AR-positive LNCaP cell growth rates, protein, and gene expression were analyzed using crystal violet assay, flow cytometry, western blotting and RT-PCR, respectively. AR transcriptional activity was measured by PSA-luciferase reporter assay, while AR degradation was assessed by cycloheximide chase assay. The effects combination treatment on castrate-resistant LNCaP tumor growth was assessed in castrated male athymic mice.

RESULTS:
Combination OGX-011 + MDV3100 showed synergistic effect and more potently suppressed LNCaP cell growth rates in a dose and time dependent manner compared to OGX-011 or MDV monotherapy. PARP cleavage, sub G0/G1 apoptotic fraction and repressed AKT phosphorylation was most enhanced with combined therapy. Interestingly, OGX-011 accelerated AR degradation and repressed AR transcriptional activity in combination with MDV3100. In vivo, combined OGX-011 + MDV3100 significantly delayed castration-resistant LNCaP tumor progression compared to scramble antisense oligonucreotide + MDV3100 (p<0.05 and p<0.05 at 12weeks, respectively).

CONCLUSIONS:
OGX-011 combined with MDV3100 down-regulated AR levels and activity and suppressed castrate resistant LNCaP cell growth in vitro and in vivo, providing pre-clinical proof-of-principle as a promising approach for AR targeting therapy in CRPC.

Here's the text of the abstract:

Sunday, May 15, 2011 8:00 AM-10:00 AM
Prostate Cancer: Basic Research
Moderated Poster
Source of Funding: none
125: CLUSTERIN ANTISENSE INHIBITOR OGX-011 SYNERGIZES ACTIVITY OF
SECOND GENERATION ANTI-ANDROGEN, MDV3100, IN CASTRATE RESISTANT
PROSTATE CANCER MODEL
Hiroaki Matsumoto
Hidetoshi Kuruma
Amina Zoubeidi
Ladan Fazli
Martin Gleave
Vancouver, Canada
INTRODUCTION AND OBJECTIVES: Experimental evidence strongly implicate the AR and
intra-tumoral androgen synthesis in promoting tumor cell survival and development of castrate
resistant prostate cancer (CRPC). The new second generation AR antagonist, MDV3100, has
shown activity in preclinical and clinical studies. Our previous studies link androgen ablation
therapy with clusterin upregulation and castrate resistance, and we developed the antisense
oligonucreotide, OGX-011, that synergistically enhances both castration and chemotherapies in
prostate cancer (CaP) models. In this study, we tested whether OGX-011 sensitized MDV3100 and
delayed castrate-resistant progression in LNCaP model. METHODS: Effects of single vs
combination MDV3100 and OGX-011 regimens on AR-positive LNCaP cell growth rates, protein,
and gene expression were analyzed using crystal violet assay, flow cytometry, western blotting and
RT-PCR, respectively. AR transcriptional activity was measured by PSA-luciferase reporter assay,
while AR degradation was assessed by cycloheximide chase assay. The effects combination
treatment on castrate-resistant LNCaP tumor growth was assessed in castrated male athymic mice.
RESULTS:
Combination OGX-011 + MDV3100 showed synergistic effect and more potently suppressed
LNCaP cell growth rates in a dose and time dependent manner compared to OGX-011 or MDV
monotherapy. PARP cleavage, sub G0/G1 apoptotic fraction and repressed AKT phosphorylation
was most enhanced with combined therapy. Interestingly, OGX-011 accelerated AR degradation
and repressed AR transcriptional activity in combination with MDV3100. In vivo, combined
OGX-011 + MDV3100 significantly delayed castration-resistant LNCaP tumor progression
compared to scramble antisense oligonucreotide + MDV3100 (p
CONCLUSIONS:
OGX-011 combined with MDV3100 down-regulated AR levels and activity and suppressed
castrate resistant LNCaP cell growth in vitro and in vivo, providing pre-clinical proof-of-principle
as a promising approach for AR targeting therapy in CRPC.

There are a couple of other abstracts on 011 and 427 on the same webpage.

Looks like OGXI will be presenting a poster with the same title on Sunday at the meeting of the American Urological Association:

http://www.aua2011.org/abstracts/process.cfm?ID=Martin%2FGleave&searchType=presenter&seachKey=Search+by+Presenter

At first I thought it was necessity -- i.e. enrollment was going slowly and this expands the patient pool -- since otherwise why didn't they try to do this right after Cabazitaxel was first approved last June? (Summer, if memory serves -- and maybe it doesn't -- you yourself proposed something along those lines at the time.) But then it occurred to me that it would have taken awhile for them to do some preclinical studies that the FDA would probably require to test the safety and PK effects of Custirsen in combination with Cabazitaxel. I still suspect that if they were close to completing enrollment they wouldn't hold things up to do this, but then again if the trial succeeds they'll get a much better label and a bigger market.

The only other news I caught in the CC was that the P1 bladder trial for 427 is still enrolling but that they expect to report results of some kind (not necessarily final results) in early 2012.

Also, they'll be presenting preclinical data at a urology conference later this month and at ASCO. I didn't know ASCO accepted preclinical data.

i told you this pos is dead in the water last year. Thick head ! $15 is $10 over priced. $5 stock is what you have!

I thought it was positive. Easier accrual means we stay on track for commercialization. I agree with you that a lack of news is good news. Right now we hear of no reason why company can't meet its estimates for unblinding of 011 results in prostate. Nothing else IMO will make this stock move up except for moving down that track on time.