(TSX: PRX.TO) applies genetic engineering techniques to createinnovative, targeted protein-based therapeutics which are focused onprostate conditions and cancer. The Company's clinical-stage pipelineis based on the PORxin and INxin technology platforms. Lead drugs inclinical development include PRX302 for the treatment of benignprostatic hyperplasia (BPH or enlarged prostate) and localized prostatecancer as well as PRX321 for primary brain cancer (glioblastomamultiforme / GBM and astrocytoma).
While many U.S. investors may not be familiar with Protox since it is based in Vancouver, Canada with its primary
stock
/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> listing on the Toronto Stock
Exchange/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> (TSX); that could soon change with pending Phase 2b results for PRX302 – which has the potential for blockbuster
sales/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> based on a new treatment approach (molecular surgery) for BPH that straddles existing
options/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" />for the condition (drugs and surgical procedures). The Pink Sheetlisting for the Company (PTXRF.PK) rarely trades, but the Company mayconsider a dual listing strategy (e.g. AMEX or
NASDAQ/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" />in addition to the TSX) for its stock to increase visibility andprovide liquidity to U.S. retail investors as the clinical developmentfor lead compound PRX302 progresses.
PRX302 is a genetically engineered version of a protein (proaerolysin)that is secreted by a specific type of bacteria (Aeromonashydrophilia). This protein contains two important regions thatcontribute to its unique mode of action as a type of molecular surgicalprocedure that involves (1) a binding site that allows the molecule toattach to the surface of a cell, (2) an activation tail that must beremoved before it is able to form a pore, and (3) once activated, thedrug punches holes in the cells causing the contents to leak out andcause cell death.
PRX302 is the Company's lead PORxin drug, which are pore-formingpro-drugs that are activated by specific proteases produced at elevatedlevels on the surface of target cells. PRX302 is activated byprostate-specific antigen (PSA), an enzyme that is over-produced inpatients suffering from BPH and prostate cancer. PRX302 represents apotentially new treatment option for BPH and other prostate conditionswith blockbuster potential based on $3 billion in annual sales for BPHdrugs (e.g. Flomax, Avodart, Proscar) and the 575,000 surgicalprocedures that are performed each year in the top seven marketsworldwide.
This approach avoids side effects and other negative factors of drugtherapy for BPH, including (1) the need for lifetime therapy on a dailybasis; (2) the potential for sexual dysfunction; (3) fatigue /dizziness / low blood pressure; (4) the potential for drug interactions.
In contrast to drug therapy andsurgical procedures, PRX302 is minimally invasive and administered as asingle treatment that involves a 10-minute procedure that can beconducted in a doctor's office with no catheterization required.Advantages for physicians include no capital
investment/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" />, ultrasound-guided delivery, and a short procedure time.
On 9/10/09, Protox announced positive 12-month data from its open-labelPhase 2 study of PRX302 in males with moderate to severe benignprostatic hyperplasia (BPH). The study results indicate that thosepatients who received an optimal dose of PRX302 continued todemonstrate significant symptomatic relief at 12 months following asingle treatment. The International Prostate Symptom Score (IPSS) is avalidated accepted clinical end-point used to assess the treatmentbenefit in BPH clinical studies. This
index/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> is measured on a 0-35 scale with 0 defined as having no problems and 35 defined as the high end of severe symptoms.
In this Phase 2 open-label volume optimization study, 13 of the 18patients received the optimum PRX302 dosing of (greater than)-1mL perdeposit. A total of 11 of the 13 patients were evaluable at 12-monthsand continued to show a statistically significant and sustainedimprovement in IPSS of 12.1 points (which is in a similar range tosurgical procedures and much better than drug therapy, which results inan improvement of about 4-7 points) representing a 55% improvement whencompared to screening.
No safety issues were identified in this study, as increasing volumesof PRX302 were seen to be well tolerated. No PRX302 related seriousadverse events or Grade 3 or greater adverse events have been reportedto date. The PRX302 related adverse events were mild to moderate,transient in nature (resolved within days) and localized to the urinarytract. In addition, no sexual dysfunction has been reported in any ofthe subjects dosed to date. Detailed 12-month results from this Phase 2open-label clinical trial will be presented at the 30th World Congressof the Societe Internationale d'Urologie from November 1-5, 2009.
On 9/8/09, Protox announced that it has completed patient enrollment ina multi-center, double-blinded, placebo-controlled Phase 2b study(TRIUMPH) of PRX302 in males with moderate to severe benign prostatichyperplasia (BPH), a common and bothersome urological condition thataffects more than 50 million men worldwide. The Company recentlyprovided guidance for reporting top-line results from the TRIUMPH studyduring 4Q09.
TRIUMPH is the third BPH clinical trial of PRX302 conducted by Protox.
In addition to being well-tolerated,the previous open-label Phase 2 study reported at the 2009 AnnualMeeting of the American Urological Association, showed an 11 pointimprovement in the International Prostate Symptom Score at the optimalPRX302 dose used in the TRIUMPH study.
The Company's lead INxin drug (PRX321) is a novel protein comprised ofinterleukin-4 (IL-4), which is a protein that stimulates the immunesystem, in combination with Pseudomonas exotoxin. The IL-4 portion ofPRX321 has been designed so that the molecule can bind with a very highlevel of specificity to IL-4 receptors on the surface of cancer cells.The IL-4 receptor is an attractive target since studies have shown itto be highly expressed in a large number of different types of cancercells.
The Pseudomonas exotoxin portion of PRX321 has been designed tominimize undesirable side effects by reducing its ability to bindnon-specifically to cells containing the Pseudomonas exotoxin receptor.Once internalized into the target cell, the toxin component of PRX321causes cell death by arresting protein synthesis and inducing apoptosisor cell death. The combined features of PRX321 allow for specifictargeting to IL-4 receptors on the surface of cancer cells whileretaining the high potency of the toxin component.
A Phase 2a clinical trial evaluating PRX321 (INxin) for the treatmentof primary brain cancer has been completed and the drug has receivedFast Track Designation and Orphan Drug Status from the US FDA and EMEA.Protox is also collaborating with the U.S. National Institutes of
Health/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> (NIH) on a
research/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> program focused on the discovery of next generation fully human targeted therapeutics.
As of mid-year, Protox had $5.6 million in cash with a low burn rate ofapproximately $600,000 per month with 84.4 million shares of common
stock/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" /> outstanding and 90.4 million fully diluted shares for a
market/75.102.2.27//Images/ZoomIn.gif" class="IntextAdLinkIcon" />cap that is under $50 million. The ownership profile of Protox includesabout 60% retail, 27% institutional, and 13% insider holders of commonstock. The commercial and stock price implications for the Company'spending Phase 2b results for PRX302 in the treatment of BPH will haveeven more impact due to the clinical trial results of another Canadianbio-pharmaceutical company for its experimental treatment for the samecondition.
On 8/17/09, Aeterna Zentaris (NASDAQ:
AEZS
: 1.15, 0.01)announced Phase 3 results for its North American efficacy trial Z-033and the safety trial Z-041 in benign prostatic hyperplasia (BPH), withits lead endocrinology compound for urology, cetrorelix pamoate. StudyZ-033 demonstrated no clear differences in overall efficacy with all 3groups showing an improvement in IPSS of approximately 4 points thatwas maintained throughout the 52 weeks. There was a slight advantage infavor of the main active treatment arm (Arm A) up to Week 46 of thefollow-up, which was no longer demonstrated at Week 52. However, thesedifferences did not achieve statistical significance.
Based on the results achieved for PRX302 thus far, which havedemonstrated similar efficacy to surgical procedures and the superiorsafety profile, the pending top-line Phase 2b results have a favorablerisk / reward profile as a major pending binary event for the Companythat is expected to occur before year-end.
Disclosure: No positions.