Protox Therapeutics Vital Phase 2b Results Coming Soon (PTXRF.PK / PRX:TSO) Print E-mail
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?

The Challenge

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.

Technology Comparison

Protox Therapeutics, Vancouver CA

Nymox, NJ and Montreal CA

Current FDA approved BPH therapy

Product

PRX302 injection, ultrasound guided

NX1207 injection, N/A

Alpha blocker & enzyme inhibitor oral drugs, surgery, TUMT microwave energy, TUNA radiofrequency therapy, ILT laser surgery

Product differentiation

Protoxin binds to the external cell growth and punches a hole in the cell activated by PSA causing cell contents to leak

It is assumed that NTP peptide targets the cell growth and is delivered to the cell interior, causing disruption and cell death

N/A

Trial Phase

Clinical trials initiated in 2007: Phase 2a completed (no placebo) / Phase 2b (placebo controlled) results pending

Clinical trials initiated in 2003: Phase 2 compared to Finasteride® (Merck) ; Phase III in process

FDA approved

Administration time

Within 15 min in doctors office

Within 15 min in doctors office

TMT, TUNA, surgery typically in a hospital setting

Dose

One time 0.009 mg - 0.072 mg for a prostate size range of 30.0g – 80.0 g (affecting 95% of the male population)

2.5 mg one time treatment

0.4mg – 10.0 mg once daily drug treatment

Drug efficacy – prostate reduction

Prostate volume at 12 months post-treatment decreased significantly by 29%.

N/A

N/A

Drug efficacy – normal urine flow

The average maximum urine flow rate (Qmax) increased from 10.7mL/sec at screening to 15.2 mL/sec at 12 months for a 42% improvement in patients receiving the optimum dose

N/A

N/A

Mean symptom reduction IPSS after 3 months/ 12 months

10.3-11.2 IPSS reduction after 3 months of treatment; after 12 months mean IPSS 12.1 reduction

10.5 mean IPSS reduction after 3 months of treatment, after 12 months mean IPSS 10.3 reduction

IPSS 3-6 pt. reduction for drugs, 10.6-11.6 reduction for TUMT

Treatment duration after optimal dose

12 months, beyond 12 months has yet to be determined

4.5 years with a mean IPSS 11.1 reduction

Typically temporary treatments, usually requires daily administration of drugs

Side effects

0% side effects

0% side effects

Impotence, painful urination, retrograde ejaculation, chemical castration, blood in urine

Trial size

Phase 2a: 18 patients / Phase 2b: 92 patients

Phase 2: 85 patients

N/A

Patent expiration

Europe & Canada (pending), U.S and Japan issued – composition patent:2021, method patent:2025

2005 issue date for 20050032704, 69246266 patents and estimated 2019 expiration date, possess various other patents

N/A

 

The Profitability

Business Strengths

· 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)


· PRX302 potency is a strong competitive advantage: “a grain of salt is enough to destroy a tumor the size of a golf ball”. Even for the worst case 80g prostate, PRX302 dosage required is less than 3% of Nymox NX1207 dosage. The benefits are realized in manufacturing and cost efficiency and could potentially lead to a price advantage. If commercialized with a powerful partner, the reduced COGS compared to competing companies could position them for fast growth

 


· PTXRF has a promising product portfolio for PRX302 to treat prostate cancer [based on PORxin™] ; PRX321, which treats brain cancer, obtained fast track designation and orphan drug designation by EMEA and FDA expediting development / FDA approval, enabling PTXRF to possibly sell PRX321 without competition for 7 – 10 years (if it’s the first approved drug) and receive clinical trial tax incentives / fee waivers [based on the INxin™].

 


· PRX302 composition and method are protected under patents until 2021 / 2025 with other patents pending. The ability to form a pore in the cell membrane externally “…eliminates the need and sometimes difficulty of getting a drug inside a cell. In addition, many cancer therapies rely on the fact that cancer cells are rapidly dividing—in the case of PORxin™, there is no requirement for cells to be growing so quickly. This is beneficial in particular for prostate cancer which is inherently a slower growing cancer.”

 


· PTXRF is in collaboration with the FDA under the terms of a Cooperative Research and Development Agreement (CRADA) for PRX321 which minimizes risk of clinical trial failure, optimizes resources, and expedites commercialization.  The collaborative research and development program will be conducted by the principal investigators Dr. Sam Denmeade, MD, Chief Scientific Officer of Protox and Dr. Raj Puri, MD, PhD, Director, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research at the FDA.

 


· PTXRF’s partnership with BrainLAB computer aided imaging systems in conjunction with the PRX321 brain cancer treatment can ensure success of clinical trials and yield profitable business opportunities if commercialized

 


· PTXRF has been able to raise ~C$26.6 MM since 2004, operates on a C$600,000/month burn rate and has strong institutional support. Ownership is about 60% retail, 27% institutional, and 13% insider holders of common stock. “The purchase of the Protox shares underscores our growing confidence in the company's technology platforms and products in development”, said Frank Holler from Lion Liquidity Investment Fund. “We believe that PRX302 has strong potential for the treatment of localized prostate cancer and BPH, and view the acquisition of the INxinTM program announced on July 20, 2006 as another positive step in the company's development”

 


· As of September 30 2009, PTXRF has C$4.1 MM in cash equivalents that should last through the end of April 2010 or longer

 


· In 2005, PTXRF was “…named to the 2005 TSX Venture 50™, the first ever ranking of Canada’s top emerging public companies listed on TSX Venture Exchange. The TSX Venture 50™ are the top 10 companies in each of five major industry sectors – mining, oil & gas, technology, life science and diversified industries – based on a ranking formula with equal weighting given to one-year revenue (last reported 12 months), return on investment, market cap growth and trading volume. All data was as of August 31, 2005.”


Marketing Opportunities

 

· 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



Business Weaknesses

· 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.


External Threats

· 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.

The Verdict

.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.

 


PRX302 could be a competitive BPH treatment, primarily due to its potency -- pending positive phase 2b results.

 


The choice is yours.

 


Terika Ray, PMP, M.S is a contributor to Biomedreports who brings 6 years of expertise in Marketing/ Product Management, Portfolio Management, Engineering & Biomedical Sciences


Disclosure: Long PTXRF




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