MEDICAL NEED FOR NEW & EFFECTIVE ANTIFUNGAL
PAC-113 an anti-fungal, for the treatment of oral Candidiasis infections, began in a Phase IIb clinical program in late 2007. The Company expects to receive the results for this Phase IIb study in mid 2008.
Opportunistic growth of Candida occurs in people with defective immune systems, or as a result of salivary dysfunction, and can be life-threatening if not treated. Candida albicans is the most common fungal pathogen among immune-compromised, hospitalized patients, accounting for roughly 50-60% of all bloodstream fungal isolates. Localized Candida infections, if untreated, can spread from the primary site of infection through the blood stream to cause a disseminated infection. Disseminated fungal infections are associated with a high mortality rate.
Photomicrograph of Candida
albicans, the fungus responsible
for oral Candida infections
Current treatments for Candida infections are either only marginally efficacious, have poor patient compliance characteristics, can cause serious side effects, can lead to drug-resistance and/or have multiple drug interaction issues.
PAC-113 HAS A NOVEL MECHANISM OF ACTION
PAC-113 is a 12 amino-acid antimicrobial peptide derived from a naturally occurring histatin protein found in saliva. In vitro studies demonstrate that it has potent anti-fungal activity against the Candida albicans, including drug-resistant HIV patient isolates.
Modes of action:
1. PAC-113 is an amphipathic molecule that interacts with fungal cell membranes, altering permeability which causes cytoplasmic leakage and cell death.
2.PAC-113 also interacts with fungal mitochondria causing production of reactive oxygen species and fungal cell destruction. This activity is unique to histatin proteins.
In addition, PAC-113 is active against growing cells, stationary phase cells and fungal biofilms. Rapid fungal lysis of fungal cells in a wide range of growth states may affect a more rapid and complete clinical cure.
PAC-113 HAS SUPERIOR FORMULATION
The PAC-113 formulation is a sugar-free, pleasant tasting, non-viscous aqueous solution with a neutral pH. The prolonged half-life of PAC-113 in the saliva has the potential to extend the duration of the therapeutic effect.
High potency antifungal:
PAC-113 has a Minimum Inhibitory Concentration (MIC) of 1.6 - 4μg/ml against Candida spp. (vs fluconazole MIC ~ 16 - 32 μg/ml ).
CLINICAL DEVELOPMENT PLAN FOR NOVEL ANTI-FUNGAL
PAC-113 is a peptide-based anti-fungal targeting oral Candida infections in immunocompromised patients and patients with salivary dysfunction.
Phase I/II Study - Positive Results
In May 2007 Pacgen reported topline results from it’s Phase I/II clinical trial evaluating the safety and efficacay of PAC-113. Topline results show PAC-113 is generally safe, well tolerated, and active in the treatment of oral Candida infection with clinical cure rates comparable to the current standard of care.
Study Design:
- PAC-113 mouthrinse vs. Nystatin oral suspension
- Randomized, examiner-blinded, parallel design clinical trial
- 14-day treatment phase with a 14-day follow-up period & day 28 follow-up visit.
Treatment Arms:
Eligible subjects will be randomized to one of the following treatment arms:
a. 0.15% PAC-113 mouthrinse (5 mL, 4-times per day); or
b. Nystatin oral suspension (5 mL, 4-times per day).
Positive Results:
Complete or partial responses at day 14 were observed in 86% of PAC-113 patients and 85% of Nystatin patients. 44% of PAC-113 patients were assesed as clinically cured at day 14 compared to 40% of Nystatin patients.
Next Steps:
The Company has completed patient recruitment for its Phase IIb dose-ranging study in patients with oral Candidiasis, using a more efficacious formulation of PAC-113. Topline results from this study are expected in mid-2008
POSITIVE TOPLINE RESULTS
Pacgen reported positive proof of efficacy results from its Phase I/IIa trial of PAC-113 in the treatment of oral Candidiasis.
Topline results show PAC-113 is generally safe, well-tolerated, and active in the treatment of oral Candida infection with clinical cure rates comparable to the current standard of care.
A Phase IIb study to establish additional efficacy and safety data as well as determine the optimize dose and formulation of PAC-113 for treating oral Candidiasis was initiated in the fourth quarter of 2007. Patient recruitment for a Phase IIb dose-ranging study has been completed and the Company expects to receive results in mid 2008.
EXCELLENT SAFETY PROFILE
Established clinical safety in over 400 subjects. Data shows that PAC-113 is well tolerated with no drug related serious adverse events.
Safety data was generated from Phase I and Phase II trials conducted in the US by Periodontix prior to PAC-113 being in-licensed by Pacgen in 2005. These studies evaluated PAC-113 as an oral rinse and gel formulation for prevention of bacterial periodontal disease.
SOLID MARKET OPPORTUNITY
Pacgen estimates that the current worldwide market opportunity for a novel, safe and effective, oral candidiasis therapy is US $250 million.
In 2004, global sales of topical antifungal drugs represented nearly a US $1.6 billion dollar market. The market for antifungal is projected to grow to US $2.1 billion by 2009.
The growth of this market and demand for effective anti-fungals is driven by a rising incidence of immunocompromised patients populations including individuals with HIV, cancer, asthma and diabetes, among others.
TARGET PATIENT POPULATION
Asthma: Prolonged use of oral steroids causes a localized immunosuppression in the mouth, throat, and upper airways that leads to a high frequency of Candidiasis in asthma patients. Approximately half of the 15,000,000 asthmatics in the United States use inhaled steroids to manage their disease.
Cancer: Candidiasis occurs with high frequency in cancer patients due to either disease-related, or treatment-related immunosuppression. Both radiation and chemotherapy lead to a suppression of the immune system. The American Cancer Society statistics estimate 1.4 million new cases of cancer in 2005.
Diabetes: The Centers for Disease Control and Prevention report that there are about 21 million diabetics in the United States. Diabetics are predisposed to oral Candidiasis due in part to poor glycemic control providing a ready food source for candida and in part to a reduction in immune function.
HIV/AIDS: The frequency of oral candidiasis in AIDS patients varies with the disease state and is reflective of the underlying level of immune function. The frequency of OPC in HIV-infected individuals with good immune function is in the range of 7% to 48%, but rises to more than 90% in those with advanced disease. Furthermore, HIV patients frequently have a relapse of oral Candidiasis within 2 weeks to 3 months following completion of antifungal treatment. An estimated 1.1 million people are living with HIV/AIDS in the United States alone. In Asia, Japan and Western Europe, there are an additional 8.5 million HIV/AIDS patients.
Xerostomia: Dry mouth is a common side effect on a number of medications. Drugs causing this condition include many commonly used drugs such as: antidepressants, anticholinergics, antihypertensives, antipsychotics, anti- Parkinson agents, antihistamines, diuretics and sedatives. These medications are broadly prescribed exacerbate the development of Candidiasis.