For the moment, this will be the final installment of the BiotechDueDiligence AACR Annual Meeting preview..thanks for sticking with us. As always, see below for another collection of presentations from biotech companies covered on the website.
Preview Part 1 (SNTA, ASTX, NVS, INFI)
Preview Part 2
Preview Part 3 (ARRY, ASTX)
Preview Part 4 (ASTX, ARQL, BPAX)Preview Part 5 (TKMR, EXEL, PCYC, IMMU, VRTX)Preview Part 6 (CRIS INFI ISIS CLDX LGND PCYC)
OncoGeneX $OGXI has licensed its lead prostate and lung cancer drug custirsen to Teva Pharma. Any inkling that the partnership was in jeopardy would be a huge blow to the small Canadian biotech. Custirsen is an antisense drug targeting clusterin, using technology licensed from isis Pharma.
Teva Pharma 2q-2012 earnings transcript courtesy on Morningstar.
"And second, I'm not sure if Michael Hayden is on the phone, but if you guys are going through some of the strategic review of the key products you currently have in the pipeline, I was wondering if you can comment about where you are in terms of your thinking, specifically about things like DiaPep277, the oncology portfolio and perhaps Laquinimod now that it's being submitted in Europe?"
Well, thank you, Ronny, for that question. We are currently undergoing a very detailed review of every project that's part of the R&D portfolio. DiaPep is part of that, and we will be reporting on the outcome of all of this during our Investor Day in December. But let me just talk about one of the drugs you mentioned in the pipeline, which has been a wonderful and a very pleasant surprise for me is the drug, Laquinimod. As you know, showed very significant results in terms of its ability to reduce disability progression and also brain volume loss. In fact, what's really quite remarkable about this unique asset is that many of its mode of actions and its ability to prevent inflammatory changes are already potentially extrapolateable to some of the more common and more serious disorders for which there really are no therapies. These include some of the neurodegenerative disorders. And so I would say as part of this review, of course, we are very interested at the potential utilization of drugs in our portfolio for other indications which would match the mechanism of action, which then would very suitably match the cores and the pathways perturb in some of these other diseases. So we're looking at this. And I'd say Laquinimod is one of those that has been a wonderful surprise in terms of understanding more deeply as to mechanisms of actions and its potential utility in other diseases.
OncoGeneX $OGXI will present updated phase 2 prostate cancer data for OGX-427 at #ASCO2012 in June in an oral presentation. I am personally very excited to see the updated data set for this promising mid-stage cancer asset. OGXI also announced their intention to broaden phase 2 development beyond prostate and bladder cancer to include lung and pancreatic cancer.Abstract #4514 A randomized phase II study of OGX-427 plus prednisone (P) versus P alone in patients (pts) with metastatic castration resistant prostate cancer (CRPC). Kim N. Chi Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense oligonucleotide that inhibits Hsp27 expression with in vitro and in vivo efficacy and was well tolerated with single agent activity in phase I studies. Methods: Chemotherapy-naÔve pts with no/minimal symptoms were randomized to receive OGX-427 600 mg IV x 3 loading doses then 1000 mg IV weekly with P 5 mg PO BID or P only. Primary endpoint was the proportion of pts progression free (PPF) at 12 weeks (PCWG2 criteria). A 2-stage MinMax design (H0 = 5%, HA >20%, ±=0.1, ≤=0.1) with 32 pts/arm provides 70% power to detect the difference at 0.10 1-sided significance. Secondary endpoints include PSA decline, measurable disease response, and circulating tumour cell (CTC) enumeration. Results: 38 pts have been enrolled; 1st stage of accrual completed with 2nd stage accruing. In the 1st 32 pts randomized (17 to OGX-427+P, 15 to P), baseline median age was 71 years (53-89), ECOG PS 0 or 1 in 66% and 34% of pts, median PSA 66 (6-606), metastases in bone/lymph nodes/liver or lung was 75/56/9%, 31% had prior P treatment, and 93% had "e5 CTC/7.5 ml. Predominantly grade 1/2 infusion reactions (chills, diarrhea, flushing, nausea, vomiting) occurred in 47% of pts receiving OGX-427+P. One pt on OGX-427+P developed hemolytic uremic syndrome. A PSA decline of "e50% occurred in 41% of pts on OGX-427+P, and 20% of pts treated with P. A measurable disease partial response was seen in 3/8 (38%) evaluable pts on OGX-427+P and 0/9 pts on P. CTC conversion from "e5 to <5/7.5 ml occurred in 50% of pts on OGX-427+P and 31% treated with P. Thus far, in 26 evaluable pts the PPF at 12 weeks was 71% (95% CI: 42-92) in OGX-427+P treated pts and 33% (95% CI: 10-65) in pts on P. Conclusions: These data provide clinical evidence for the role of Hsp27 as a therapeutic target in prostate cancer and support continued evaluation of OGX-427 for pts with CRPC. Funded by a grant from the Terry Fox Research Institute.
ASCO:Oncogenex $OGXI will present updated (first data presentation was at ASCO-GU in early 2012) randomized phase 2 prostate cancer data for OGX-427 at ASCO 2012 - stay tuned as the abstract will be released May 16th.1q-2012 Partner Update:OGXI is partnered with Teva Pharma $TEVA for their lead cancer drug custirsen, with phase 3 trials ongoing in prostate cancer and proposed for non-small cell lung cancer. This program is virtually never mentioned on Teva webcasts, and that was again the case this quarter. However, it is important to note that following the acquisition of Cephalon by Teva, the combined research and development pipelines are ongoing a thorough review and re-prioritization led by the newly appointed CEO Jeremy Levin. Here is what he said about the process:"So let me just touch on the reviews. As I've said to you the -- we are conducting an extensive review. This is not just of pipeline, it's across the board, it's the business, it's the -- in the different geographies. It's also the manufacturing footprint. It's the pipeline, our capabilities in R&D and the individuals, the people that we have. This is part of a normal process that any CEO does. It's not something unusual to what -- is undergoing in Teva. We've identified a number of different processes that we'll undergo to look at that. And amongst those is the process to look hard at the pipeline. Now as you know, that pipeline was looked at last year, and I think at this stage it's premature to say that there's any changes whatsoever from that. But I anticipate as Michael comes on board and works with me and others around the table, we'll have a much clearer view of that a little later in the year."It goes without saying that if Teva abandoned the OGXI partnership, OncoGenex would be in deep trouble - they do not have nearly the required resources to fund and operate the global phase 3 program for custirsen. However, there is no immediate reason to worry about this outcome. If OGXI was truly on the chopping block, it would be an odd decision by Teva to commit to a brand new phase 3 overall survival prostate cancer clinical trial in combination with the second-line chemotherapy agent JEVTANA (cabazitaxel), rather than simply abandoning the SATURN pain palliation trial. In any case, it is a situation that bears monitoring for all OGXI investors.
Though not often covered on BiotechDueDiligence, both abiraterone (ZYTIGA from $JNJ) and MDV-3100 (developed by Astellas and Medivation $MDVN) are key emerging players in the treatment landscape for prostate cancer. The late-breaking abstracts below related to these drugs caught my eye. Note that Oncogenex $OGXI has evaluated (or plans to) its clinical candidates custirsen (OGX-011) and OGX-427 in combination with these androgen receptor (AR) pathway-targeting therapies.
- OncoGeneX announced 3q2011 earnings and held a conference call on 11/3/2011.
- Check out more OGXI company info and complete guide to upcoming biotech catalysts and webcasts, along with links to my notes.
- New feature - checked out the embedded link to listen to the conference call if interested - courtesy of EarningsCast.com
- As usual, see below for the notes from the webcast and Q&A session.
- OGXI is focused on addressing treatment resistance in cancer
- Phase 3 trial of OGX-011 in NSCLC is on track to initiate in 2011
- OGX-427 randomized phase 2 trial in metastatic bladder cancer will start later in 2011
- Cash on hand sufficient into 2014
- OGX-2310 is available for outlicensing because not related to treatment resistance focus- this is a formulation product of an existing drug
- Phase 3 trials have interim looks, mostly for safety and futility by DSMBs- OGXI has not disclosed the number of events (deaths) that trigger the interim analyses
- inhibit clusterin- fight off resistance and add to efficacy of other agents
- TV1011 is TEVA designation for OGX011
- SATURN trial initiated 2q10- bone mets is what are debilitating. primary endpt is pain paliation. 60% of p2 pts had paliation, 80% durable 12 wks of more-other agents reported about 10%
- SYNERGY trial in first line (follow on to randomized p2 design, combo w/ decoetaxel. 6.9m improvement 0.61 HR- cant find any imbalances, side biases, subsequent tx effects, etc to explain besides tx effect). SPA< OS primary endpt
- continue to enrol both above 011 trials thru 2011
- Upcoming NSCLC trial will be 950 pts, larger than previously thought (700), initiate 2h2011. chemotherapy-naive stage 4 patients. carbo-tax +/- 011. pfs, has 2 futility looks and one interim analysis. huge financial commitment by teva. (but no controlled p2 data). 14 month survival vs 8-11 m historical.
- cash into 2014- realize pc p3 trials and get 427 thru p2
- 427 bladder cancer randomized p2 start later 2011. 5th largest indication 160k in 7 largetst mkts. TTP 8 months, 13m median survival
- new therapies entering mkt are opportunities, not competitors
- AACR presentation: clusterin is survival mechanism that confers resistance. if you inhibit this, reduce hsp90 levels- could augment hsp90 inhibitors...Clusterin has direct role in EMT transition...migration and invasisveness/metastasis
- OGX-427: HSP27 interacts with AR and brings into nucleus, required for function. Knockdown leads to degration of receptor
- randomized p2 in prechemo space. Will test a combination w/ anti-androgen eventually
- superficial bladder cancer- direct infusion dose escalation
- 85m cash ye10, will burn $31-35m 2011, leaves cash at year end 2011 of $50-54m. 9.7m shares
- OGXI employed a creative p1 clinical design. early prostate cancer pts. dosed for 5 wks w/ hormone ablation, then prostatectomy. Were able to answer questions like- how much drug got into prostate? how much target knockdown? saw 92% reduced HSP27 in prostate, 98% in LN. Note: prostate doesnt like to admit charged drugs, similar blocking mechanism to blood brain barrier
- OncoGenex (click here for full OGXI research page) presented 9/20 at UBS conference, click here for all upcoming biotech events and links to my notes.
- Quick notes:
- Cash sufficient to middle of 2014
- metastatic bladder cancer randomized phase 2 trial will start by end of 2011, take about 18 months to complete enrollment, and have data in the beginning of 2014.
- Prostate cancer is "crowded field", but is the second leading cause of cancer death among men (justifying custirsen program)