According to the American Cancer Society, prostate cancer is the second most common cancer diagnosed amongst American men and the second leading cause of cancer death.  One in six men will be diagnosed with prostate cancer in their lifetime and 1 in 36 will die from it.  In 2011 241,000 new cases will be diagnosed in the US and there will be almost 34,000 deaths (ACS Website).  Decision Resources reports that the total worldwide market for prostate cancer pharmaceutical agents was $4B in 2009 and it is expected to double in the next 10 years.   Currently, more than 80% of this market is for agents which target the hormone therapy pathway.

When prostate cancer recurs, either locally or distally, the first line of therapy usually is focused on the hormone pathway.  Agents are given to the patient that suppress androgen synthesis or block the androgen from activating the androgen receptor.  Often both forms of therapy are given simultaneously.  When this approach fails, then newer androgen-synthesis-suppressing agents like abiraterone are given and this newly approved therapy provides on average several months of additional protection against the return of aggressive disease.  After failure of all these hormone-related therapies, patients typically would be given a cytotoxic agent (Docetaxel or Mitoxantrone) which may provide an additional several month interruption of cancer progression or Provenge, a recently-approved immunotherapy which also provides several months (on average) of additional delay of cancer progression (Note: abiraterone is approved for treatment of Docetaxel failures, but is sometimes used pre-Docetaxel).  Ultimately, progression occurs and the patient will succumb to the disease.

In summary, it is a market in which hormone therapy is a very effective first-line treatment, but ultimately fails in almost all patients.  Similarly, cytotoxic agents and immunotherapeutic agents also are effective, but for shorter periods of time.  Each newly-approved therapy thus finds its window of usefulness because all current agents eventually fail.  Virtually all patients pass sequentially through each therapy.  And it is a market that often includes simultaneous use of different therapeutic, especially on the hormone pathway.

All of these characteristics point to the potential values of ESSA’s N-terminus blockers, because they should be effective long after current hormone therapeutics have failed, and they should be additive to current hormone therapies, given their different hormone-related target.

Prostate Cancer Epidemiology

• The aging population and increasing incidence across several of the major pharmaceutical markets in this report will contribute to an increase in the number of incident cases of prostate cancer from 500,000 in 2009 to more than 618,000 in 2019.
• In 2009, the base year of our forecast period, 52,000 cases were diagnosed with advanced (stage IV) disease, representing 10% of the total, while 376,000 cases were diagnosed with stage II disease, and representing 75% of the total. The increasing widespread use of PSA testing has led to a shift in the stage distribution of prostate cancer at diagnosis. Over the forecast period, late-stage disease (stages III and IV) will decrease from 24% in 2009 to 22% in 2019.
• The crude incidence of prostate cancer varies across the major pharmaceutical markets, with the highest rate in France (183 new cases per 100,000 men) and the lowest in Japan (80 new cases per 100,000 men).
• Widespread PSA screening, diagnosis at earlier disease states, increasing incidence, and improving survival rates contribute to the increase in the number of prevalent cases of prostate cancer from 3 million in 2009 to more than 4 million in 2019.
• The percentage of patients receiving drug treatment will not change substantially over the study period. There is a high drug-treatment rate because the majority of advanced-stage patients receive hormonal therapies; therefore, the percentage drug treated does not significantly increase after the launch of emerging therapies because the majority of patients will continue to receive hormonal therapies.

Current Prostate Cancer Treatments

Current treatments for prostate cancer include drug therapies, radiation therapies and surgical interventions.  Typically patients who are initially diagnosed with prostate cancer are treated with either surgery (removal of prostate) or radiation therapies.  In approximately 50% of these cases a complete cure is achieved, with no further recurrence, albeit at the cost of a significant incidence of sexual dysfunction and incontinence.  Recurrence when it occurs usually happens after several years and is typically treated with hormone therapy.  There are currently two broad classes of drugs which are used to treat such recurrences: drugs which suppress testosterone and related hormones, and drugs which block the androgen receptor (which is where testosterone binds in order to enable cancer growth).  Both of these approaches fail when castrate-resistant prostate cancer (“CRPC”) emerges, as it almost invariably does.  Patients are also treated with additional radiation therapy, or cytotoxic anti-cancer agents, or more recently immunotherapy (Provenge).  These approaches typically prolong life by months rather than years.

Initial Market Opportunity for ESSA

Given the mechanism of ESSA’s drug candidates, the entire spectrum of prostate cancer patients may ultimately be treatable with the drug, including potentially patients with their initial diagnosis of the condition.  But first the Company will focus on castrate-resistant prostate cancer (“CRPC”), for the following reasons:

1. This remains the market segment with the greatest unmet need;
2. It is potentially a very large market;
3. In this area, the benefits of the ESSA approach should be most immediately obvious (CRPC arises because of emergent cancer variants which do not require androgen-binding to activate the androgen receptor.  ESSA’s drugs are expected to be effective in this patient group because the mechanism directly blocks androgen receptor activation rather than the precursor event of androgen binding.   Initial animal studies clearly support this hypothesis.  Human clinical trials are of course required in order to unequivocally prove the hypothesis.)
4. Enrollment of patients in clinical studies required for approval should be straightforward, because there are many such patients and their unmet need is high.

Competition

The competition in this cancer market is very high, with several pharmaceutical therapies already approved, and literally dozens of new molecules being tested for their effect in this patient population.  Currently approved emergent therapies include:

Provenge (Dendreon)

Approved in metastatic androgen-independent prostate cancer.  Autologous immunotherapy.  Requires ex vivo processing of patients immune cells with prostatic acid phosphatase/GMCSF and reinfusion into patients.  Priced at approximately   $90,000 per course of treatment (3 infusions)

Abiraterone (JnJ)

Approved in post-Docetaxel setting but commonly prescribed to patients who are experiencing failure of first-line hormone therapy.  Approved in April 2011, and priced at approximately $60,000 per year, abiraterone is an oral therapy targeted at suppressing synthesis of androgen.  It provides an average 4.8 months delay of cancer progression.

Taxotere (BMS)

Docetaxel, approved for metastatic prostate cancer, cytotoxic, microtubule inhibitor – has gone generic in 2010.

Jevtana (Sanofi-Aventis)

Cabazitaxel approved for metastatic hormone refractory prostate cancer for injection with prednisone in patients previously treated with Docetaxel; microtubule inhibitor.  Showed a survival benefit of ~4 months.

ESSA Competitive Position

In this crowded arena, ESSA’s competitive position is very strong, because its drugs focus mechanistically on the approach to prostate cancer that has made the biggest difference to the survival of recurrent prostate cancer patients – blocking androgen receptor activation.

But EPI-001 blocks the N-terminus directly, so that it has the potential to overcome the resistance issues related to current hormone-related CRPC therapies.  If successful, this would be a huge step forward in the treatment of prostate cancer.

Key competing agents – even newer ones like abiraterone and MDV3100 – are expected to quickly lead to re-emergence of CRPC, and those re-emergent CRPC patients are precisely the population where ESSA drugs are expected to have the most impact.  As well, ESSA’s drugs have already showed evidence of synergy with existing drugs in animal testing, including tests using other androgen ablation therapies and with cytotoxic agents.

In summary, ESSA’s drugs are attractive treatments for CRPC because they act on a proven pathway, they hold the potential for greatly improved efficacy in CRPC patients, and they have clear potential to be used successfully as combination therapy with current drug classes.