|Protox Therapeutics: A Molecular Approach to Surgery|
|Tuesday, 06 October 2009 09:07|
Protox Therapeutics (TSX: PRX.TO) applies genetic engineering techniques to create innovative, targeted protein-based therapeutics which are focused on prostate conditions and cancer. The Company’s clinical-stage pipeline is based on the PORxin and INxin technology platforms. Lead drugs in clinical development include PRX302 for the treatment of benign prostatic hyperplasia (BPH or enlarged prostate) and localized prostate cancer as well as PRX321 for primary brain cancer (glioblastoma multiforme / 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 listing on the Toronto Stock Exchange (TSX); that could soon change with pending Phase 2b results for PRX302 – which has the potential for blockbuster sales based on a new treatment approach (molecular surgery) for BPH that straddles existing options for the condition (drugs and surgical procedures). The Pink Sheet listing for the Company (PTXRF.PK) rarely trades, but the Company may consider a dual listing strategy (e.g. AMEX or NASDAQ in addition to the TSX) for its stock to increase visibility and provide liquidity to U.S. retail investors as the clinical development for lead compound PRX302 progresses.
PRX302 is a genetically engineered version of a protein (proaerolysin) that is secreted by a specific type of bacteria (Aeromonas hydrophilia). This protein contains two important regions that contribute to its unique mode of action as a type of molecular surgical procedure that involves (1) a binding site that allows the molecule to attach to the surface of a cell, (2) an activation tail that must be removed before it is able to form a pore, and (3) once activated, the drug punches holes in the cells causing the contents to leak out and cause cell death.
PRX302 is the Company’s lead PORxin drug, which are pore-forming pro-drugs that are activated by specific proteases produced at elevated levels on the surface of target cells. PRX302 is activated by prostate-specific antigen (PSA), an enzyme that is over-produced in patients suffering from BPH and prostate cancer. PRX302 represents a potentially new treatment option for BPH and other prostate conditions with blockbuster potential based on $3 billion in annual sales for BPH drugs (e.g. Flomax, Avodart, Proscar) and the 575,000 surgical procedures that are performed each year in the top seven markets worldwide.
This approach avoids side effects and other negative factors of drug therapy for BPH, including (1) the need for lifetime therapy on a daily basis; (2) the potential for sexual dysfunction; (3) fatigue / dizziness / low blood pressure; (4) the potential for drug interactions. In contrast to drug therapy and surgical procedures, PRX302 is minimally invasive and administered as a single treatment that involves a 10-minute procedure that can be conducted in a doctor’s office with no catheterization required. Advantages for physicians include no capital investment, ultrasound-guided delivery, and a short procedure time.
On 9/10/09, Protox announced positive 12-month data from its open-label Phase 2 study of PRX302 in males with moderate to severe benign prostatic hyperplasia (BPH). The study results indicate that those patients who received an optimal dose of PRX302 continued to demonstrate significant symptomatic relief at 12 months following a single treatment. The International Prostate Symptom Score (IPSS) is a validated accepted clinical end-point used to assess the treatment benefit in BPH clinical studies. This index 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 18 patients received the optimum PRX302 dosing of (greater than)-1mL per deposit. A total of 11 of the 13 patients were evaluable at 12-months and continued to show a statistically significant and sustained improvement in IPSS of 12.1 points (which is in a similar range to surgical procedures and much better than drug therapy, which results in an improvement of about 4-7 points) representing a 55% improvement when compared to screening.
No safety issues were identified in this study, as increasing volumes of PRX302 were seen to be well tolerated. No PRX302 related serious adverse events or Grade 3 or greater adverse events have been reported to date. The PRX302 related adverse events were mild to moderate, transient in nature (resolved within days) and localized to the urinary tract. In addition, no sexual dysfunction has been reported in any of the subjects dosed to date. Detailed 12-month results from this Phase 2 open-label clinical trial will be presented at the 30th World Congress of the Societe Internationale d'Urologie from November 1-5, 2009.
On 9/8/09, Protox announced that it has completed patient enrollment in a multi-center, double-blinded, placebo-controlled Phase 2b study (TRIUMPH) of PRX302 in males with moderate to severe benign prostatic hyperplasia (BPH), a common and bothersome urological condition that affects more than 50 million men worldwide. The Company recently provided guidance for reporting top-line results from the TRIUMPH study during 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 Annual Meeting of the American Urological Association, showed an 11 point improvement in the International Prostate Symptom Score at the optimal PRX302 dose used in the TRIUMPH study.
The Company’s lead INxin drug (PRX321) is a novel protein comprised of interleukin-4 (IL-4), which is a protein that stimulates the immune system, in combination with Pseudomonas exotoxin. The IL-4 portion of PRX321 has been designed so that the molecule can bind with a very high level of specificity to IL-4 receptors on the surface of cancer cells. The IL-4 receptor is an attractive target since studies have shown it to be highly expressed in a large number of different types of cancer cells.
The Pseudomonas exotoxin portion of PRX321 has been designed to minimize undesirable side effects by reducing its ability to bind non-specifically to cells containing the Pseudomonas exotoxin receptor. Once internalized into the target cell, the toxin component of PRX321 causes cell death by arresting protein synthesis and inducing apoptosis or cell death. The combined features of PRX321 allow for specific targeting to IL-4 receptors on the surface of cancer cells while retaining the high potency of the toxin component.
A Phase 2a clinical trial evaluating PRX321 (INxin) for the treatment of primary brain cancer has been completed and the drug has received Fast Track Designation and Orphan Drug Status from the US FDA and EMEA. Protox is also collaborating with the U.S. National Institutes of Health (NIH) on a research 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 of approximately $600,000 per month with 84.4 million shares of common stock outstanding and 90.4 million fully diluted shares for a market cap that is under $50 million. The ownership profile of Protox includes about 60% retail, 27% institutional, and 13% insider holders of common stock. The commercial and stock price implications for the Company’s pending Phase 2b results for PRX302 in the treatment of BPH will have even more impact due to the clinical trial results of another Canadian bio-pharmaceutical company for its experimental treatment for the same condition.
On 8/17/09, Aeterna Zentaris (NASDAQ:AEZS) announced Phase 3 results for its North American efficacy trial Z-033 and the safety trial Z-041 in benign prostatic hyperplasia (BPH), with its lead endocrinology compound for urology, cetrorelix pamoate. Study Z-033 demonstrated no clear differences in overall efficacy with all 3 groups showing an improvement in IPSS of approximately 4 points that was maintained throughout the 52 weeks. There was a slight advantage in favor of the main active treatment arm (Arm A) up to Week 46 of the follow-up, which was no longer demonstrated at Week 52. However, these differences did not achieve statistical significance.
Based on the results achieved for PRX302 thus far, which have demonstrated similar efficacy to surgical procedures and the superior safety profile, the pending top-line Phase 2b results have a favorable risk / reward profile as a major pending binary event for the Company that is expected to occur before year-end.
Disclosure: No positions.
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