Despite the number of antifungal therapeutics available, mortality rates for severe systemic fungal infections remain extremely high; candidiasis can be as high as 47% and for aspergillosis, as high as 90%.
Aspergillosis, a lethal severe systemic fungal infection, is caused by the mold fungus Aspergillus fumigatus, which is commonly found in soil. Anyone spending time outdoors (gardening) or in a non-urban evironment is exposed to the fungus. The fungus reproduces through the production of conidia, which are spread by airborne dispersal. Their small size enhances their buoyancy allowing them to remain aloft. Because of its near ubiquitous airbone presence, inhalation is the primary mode of entry and an average indivdual, when outdoors, may inhale several hundred conidia a day. Normally, exposure to Aspergillus is not a health concern but when individuals are immunocompromised it can be life-threatening. Invasive pulmonary aspergillosis (IPA) is now a leading cause of death in recipients of bone marrow transplants and is a significant cause of death in cancer, HIV/AIDS, and solid organ transplant patients.
IPA’s lethality is primarily due to late state diagnosis of the disease, when symptoms are more evident. Thus when therapy is brought to bear, the Aspergillosis infection is often well established and poorly responsive to treatment. Lypro’s novel NanoDisk formulation of amphotericin B (AMB) is a fast-acting, broad sprectrum, fungicidal therapeutic. AMB is one of the most effective antifungal prescribed and importantly, despite decades of use, fungal resistance to AMB is virtually nonexistent. However, conventional AMB (AMB deoxycholate) is highly toxic. While lipid-formulations developed in the 1990’s have addressed toxicity concerns, this has been at the cost of antifungal potency. Lypro’s AMB formulation is as safe as lipid formulations, yet retains the high potency of AMB deoxycholate, with the added benefit of a faster onset of activity, critical to the treatment of late stage fungal infection. Our model system is generally thought to be predictive of human outcomes.
Lypro’s fast acting NanoDisk forumulation of AMB will provide the critical response to infection needed at the early stages of treatment, buying both patient and physician the vital time required for patient recovery. Lypro’s goal is to prevent this loss of life by enhancing AMB’s potency, rate of action, safety and specificity. Through this, we will address a lethal complication of blood transfusion, HIV/AIDS, cancer and solid organ transplant patients.
Lypro is well along the development path for AMB containing NanoDisks and are preparing for IND filing. Currently, experiments are aimed at finalizing validation of efficacy in murine models and will begin non-rodent species PK and Tox determination.