Treatment failures and resistance to current therapies has led Melanovus Oncology to search for and to identify pharmacological agents and formulations that will target multiple key pathways involved in melanoma development. These first in class agents are referred to as Multi-Target Inhibitorsâ„?(MTI).
Melanovus Oncology compounds uniquely attack the tumor by inhibiting PI3K(pAkt3), STAT(pSTAT3) and MAPK(pErk) signaling cascades and other key pathway(s) in melanoma development. Their effect on tumor cells is characterized by inhibition of proliferation, triggering of apoptosis, a reduction in migration and metastasis, and limiting tumor vascularization. This multifaceted approach could lead to slowing tumor growth, more effective tumor inhibition and a decrease in the probability of developing drug resistance. The ultimate goal is to change the course of disease progression.
By targeting the pathways that are primarily overactive in melanoma cells, these highly specific agents could provide better overall efficacy and less damage to surrounding/normal tissues. Nanolipolee-007 is a unique nanoliposomal formulation. The properties of the formulation allow for maximum permeability and retention (EPR effect) and greater accumulation of the active agent within the tumor.
In pre-clinical animal studies, Nanolipolee-007 has shown to be both safe and effective.
In the current phase of development, the remaining IND-enabling studies are being conducted to: (1) establish a method for measuring levels of leelamine in the serum or tissues of animals following intravenous administration to establish dosing for therapeutic efficacy, toxicokinetics, pharmacokinetic and pharmacokinetic studies; and (2) complete escalating dose and 10-day repeated intravenous dosing studies in multiple species followed by measurement of leelamine levels present in the serum and tissues of the animals. Collectively, these discoveries are expected to form a crucial portion of the foundation for obtaining Investigational New Drug (IND) status from the FDA for systemic Nanolipolee-007 treatment and will lead to initiating a phase I clinical trial.
The phase I trial will likely be a multi-center trial, with the Melanoma Center at Penn State University serving as the coordinating site. The Melanoma Centers at Thomas Jefferson University and the University of Pennsylvania may also participate in the trial. We expect that the trial will begin in the second half of 2013.
- Lead compound for treating advanced melanoma
- Nanoparticle based drug
- Contains Leelamine (isolated from the bark of pine trees)
- Delivered as an intravenous formulation
- Inhibits AKT3, STAT3, Erk and V600EB-RAF â€?important pathways in melanoma development
- Active against the mutant B-RAF and B-RAF resistant to other therapies
- Well tolerated with minimal toxicity
- Companion diagnostic being developed to help identify patients who may respond to the therapeutic