|Protox Therapeutics Vital Phase 2b Results Coming Soon (PTXRF.PK / PRX:TSO)|
|By Terika Ray|
|Monday, 14 December 2009 12:00|
Protox Therapeutics (PTXRF) uses genetic engineering to transform naturally occurring proteins into novel targeted therapeutics for the treatment of prostate diseases and various cancers. In Late December 2009 / early January 2010, the future direction of the company will be determined on announcement of the lead drug PRX302 Phase 2b 3-month results for the treatment of benign prostatic hyperplasia (BPH, or enlarged prostate). PTXRF is a High Risk / High Reward investmentwith a possible value price at $1.30 - $1.80 from the current $.66 (Dundee Securities analysis) pending positive Phase 2b results. With successful Phase I and Phase 2a results, will PRX302 prevail Phase 2b to be a competitive treatment?
BPH, or prostate enlargement, is a very common condition affecting ~ 60 million men worldwide, and is characterized by increased levels of PSA enzyme secreted by prostate glands. More than half of all men will have symptoms of BPH by age 60 and as many as 90% may suffer from BPH after the age of 70; about half of the men with BPH require medical treatment. The cause is unknown, but the theory is that with age, changes in the ratio of male hormone (testosterone) and female hormone (estrogen) levels in men stimulate the prostate to grow.
If BPH blocks urine flow and is untreated, it can pose a serious health threat causing:
· Acute urinary retention (AUR): AUR is a sudden painful inability to urinate. To empty the bladder, a catheter must be inserted into the bladder through the penis.
· Bladder damage: This occurs when, over a long period of time, the bladder hasn't emptied completely. The muscular wall of the bladder stretches, weakens and no longer contracts properly.
· Kidney damage: This is caused by frequent infections and acute urinary retention.
Many patients ultimately fail existing medical therapy, leading to over 350,000 surgical procedures annually in the United States, despite the risks of serious surgical complications, including impotence.
There is a need for an effective treatment that can destroy abnormal growth cells without surgery and inhibit further growth without toxic effects to healthy cells, focusing on five main goals:
· Prostate reduction
· Normal Urine flow
· High symptom reduction International Prostate Symptom Score (IPSS)
· Long term treatment duration
· Minimal side effects
The Race for the cure
PTXRF’s PRX302 is a novel protein therapy which binds externally to the cell growth, and is activated by surrounding PSA to puncture a hole and destroy the cell without side effects. The advantage is the treatment can obsolete surgery, current oral therapies, and radiation therapies with a one-time treatment---the disadvantage is so can the key competitor product. With Aeterna Zentaris’ recent Phase III failure for cetrorelix pamoate hormone and Bioexell’s Elocalcitol Phase 2b failure, Nymox is the leading competitor. Nymox discovered naturally occurring Neural Thread Protein (NTP) peptides present in Alzheimer’s disease are an effective cell death inducing treatment for a wide range of diseases, including cancers and BPH. Nymox has been mysteriously secretive about disclosing the method of action for NX1207, but their patents suggest a modified NTP peptide specifically targets the abnormal cell and delivers the NTP to the cell interior causing cell disruption and death: “…over-expression of NTP can cause increased cell death of an apoptotic nature linked to oxidative stress (de la Monte et al., Alz. Rep., 2:327-332 1999).” As shown in the table below, both PRX302 and NX1207 yield similar results more effective than current therapies; the true success of the drugs will depend on positive clinical trials and a sound business strategy.
· PTXRF leveraged exclusive agreements with Johns Hopkins University and U.S Public Health Service for prostate and cancer technology aimed at killing abnormal growth cells, not just treating the symptoms. The focus is on three technology platforms: PORxin™ (BPH/Prostate Cancer), INxin™(Brain/Blood cancers, solid tumors), and HUMxin™ (pre-clinical phase for multiple indications)
· Large market opportunity: According to U.S. Benign Prostatic Hyperplasia Markets analysis
by Frost & Sullivan, the BPH treatment market is estimated to reach $3.40 billion in 2011 in the U.S. alone. The actual percentage of market share that can be achieved would depend on partnerships
· Positive PRX302 Phase 2b results would expose the company to partnerships with Industry leaders, especially with the recent failure of competing therapies, and advance the prostate cancer trials. Dundee securities speculates: “To achieve a double or triple valuation lift, we believe IPSS benefit in the PRX302 arm should be in the range of 10-12, statistically significant vs. placebo, and with good safety and tolerability. This may be a tall order at 3 months - and a lesser but still medically positive result (although market reaction may be mixed) would be an IPSS improvement of 8-10 points, which would be helped further if IPSS trajectory is positive”
· The technology would be covered by reimbursement: “Assuming PRX302 reaches commercialization, existing codes for intraprostatic injection and ultrasound provide reimbursement at $900 - it will be incumbent on Protox and/or its partner(s) to negotiate drug reimbursement for PRX302, possibly in the $1,200-$3,000 range based on competing drugs and procedures.”
· Assuming positive phase 2b results for PRX302 and commercialization of PRX321, PTXRF can leverage the BrainLAB partnership for product bundling opportunities to enhance brand equity and increase sales
· PRX302 can be engineered to form a variety of unique drug candidates that act on different types of cancers and other diseases. In the future, Protox plans to combine its own drug candidates with other targeted molecules such as antibodies or ligands in order to further increase the drug’s specificity. Such dual targeting may lead to even greater efficacy and safety than either approach alone.
· With Nymox NX1207 already in Phase III, PTXRF can follow a similar clinical trial design and use the NX1207 results as a comparison
· PTXRF is a small developing company with no revenue stream and minimal resources; It would be important for PTXRF to secure a partnership
· PTXRF’s license agreement payment obligations to John Hopkins, University of Victoria and U.S PHS with no revenue stream constrains finances: PTXRF will make cumulative milestone payments over the lifecycle of PRX302 of up to $2.9 million contingent upon the achievement of certain clinical and regulatory milestones and to pay low single digit royalties on commercial sales of resulting products; PRX321 -- cumulative milestone payments of up to US$4.0 million contingent upon the achievement of certain clinical and regulatory milestones and to pay low single digit royalties on commercial sales of resulting products; HUMxin™ -- cumulative milestone payments of up to US$4.8 million contingent upon the achievement of certain clinical and regulatory milestones (for at least three indications) and to pay low single digit royalties on commercial sales of resulting products.
· PTXRF’s focus on the pending Phase 2b trials places a hold on their product portfolio trial advancement and could impact continued funding
· The Phase 2a trials were not compared to a control group, and the Phase 2a IPSS may not be a reliable indicator for Phase 2b controlled study IPSS
· Long term duration results for PRX302 past 12 months have yet to be determined; PTXRF expects a 2 year evaluation in mid-2010
· Low company exposure in the U.S has resulted in low trading volume on the pink sheets. However, for some brokers, orders are routed to the Canadian stock exchange, taking advantage of the TSO larger volume without paying exchange rate fees.
· Failure of Phase 2b 3-month results could negatively impact product portfolio advancement, future funding and partnerships
· Threat of competition is high: The largest competitive threat is Nymox NX1207 which yields identical results to PTXRFand advanced to Phase III; the company has a revenue stream from marketed products. Maintaining secrecy regarding the technology behind NX 1207 challenges PTXRF’s positioning strength and product differentiation. However, patent literature can provide sufficient information for an estimated guess.
· Threat of substitutes is low-moderate: The growing technology trends in non-invasive drug delivery (transdermal patches, creams) and controlling genetic expression leaves ample opportunity to develop non-invasive prostate cancer cures in the near future.
PORxin™ Product (How it works)
PRX302, is an engineered version of proaerolysin, a protein secreted by the bacteria Aeromonas hydrophilia. Proaerolysin contains two important regions that allow it to exert its effect. The first is a binding site that allows the molecule to attach to the surface of a cell and the second is an “activation tail” that requires removal by PSA before it is able to form a pore. Prostate specific antigen (PSA), is an enzyme that is produced at high levels in the prostates of patients with prostate cancer and BPH. Once bound and activated, PRX302 combines with other activated PRX302 molecules to form a mushroom shaped structure that is able to perforate the cell membrane. The cell contents leak out through the resulting pore and the cell dies. PRX302 is injected locally into the prostate to treat prostate cancer and BPH.
.PTXRF is an emerging, developing company with many challenges and opportunities yet to come. Positive phase 2b results could position the company for strong partnerships and financial security to advance and commercialize its portfolio.