MEDICAL NEED FOR NEW & EFFECTIVE ANTIFUNGAL
PAC-113, an anti-fungal for the treatment of oral Candidiasis infections, completed a Phase IIb clinical program 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 IIb Study - Positive Results
In June 2008 Pacgen reported results from its Phase IIb clinical trial evaluating the safety and efficacy of PAC-113. Results demonstrate that PAC-113 is generally safe, well tolerated, and is effective in the treatment of oral Candida infection.
- 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
Eligible subjects will be randomized to one of the following treatment arms:
a. 0.15% PAC-113 mouthrinse (5 mL, 4-times per day);
b. 0.075% PAC-113 mouthrinse (5 mL, 4-times per day);
c. 0.0375% PAC-113 mouthrinse (5 mL, 4-times per day);
d. Nystatin oral suspension (5 mL, 4-times per day).
The optimal dose of PAC-113 demonstrated a 34% increase in primary endpoint efficacy level (complete clinical cure rate at Day 19) for the Per Protocol analysis as compared to Nystatin, and a 50% increase in the corresponding Intent to Treat analysis.
Pacgen plans to meet with the FDA to discuss its proposed Phase III clinical development plan. The Company is currently seeking collaboration and commercialization partner for PAC-113.
EXCELLENT SAFETY PROFILE
Established clinical safety in over 600 subjects. Data shows that PAC-113 is well tolerated with no drug related serious adverse events.
Safety data was generated from Phase I/II and Phase IIb trials conducted by Pacgen, as well as Phase I and Phase II trials conducted in the US by Periodontix Inc. (subsequently acquired by Demegen, Inc.) prior to PAC-113 being in-licensed by Pacgen in 2005. The studies conducted by Periodontix/Demegen were in 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 and exacerbate the development of Candidiasis.