Lpath Inc., the industry leader in bioactive lipid-targeted therapeutics, has started dosing in a phase IIa single-arm trial where ASONEP is being investigated as a treatment for renal cell carcinoma (RCC) in subjects that have failed the standard of care treatment with FDA-approved agents that block VEGF signaling (e.g. Sutent/ sunitinib maleate) and the mTOR pathway (e.g. Afinitor/ everolimus).
ASONEP is a humanized antibody that binds to and neutralizes sphingosine-1-phosphate (S1P). S1P is a bioactive lipid that has been validated as a drug target in multiple sclerosis and that has been shown to contribute to progression of several cancer types.
Many scientific publications have concluded that S1P is a tumorigenic and angiogenic bioactive lipid that cancer cells use to escape therapy. In collaboration with Rupal Bhatt, MD, of Beth Israel Deaconess Medical Centre, Lpath has demonstrated that levels of S1P are upregulated in blood of subjects with RCC. Moreover, Dr Bhatt has demonstrated efficacy of Lpath's anti-S1P antibodies in treating mice with human RCC tumours after they had failed treatment with Sutent.
This current proof-of-concept phase II trial follows the successful completion of the ASONEP phase I safety study. The phase I study, conducted in subjects with solid tumours, showed that ASONEP was well tolerated across all doses, including the highest dose of 24 mg/kg. In addition, of the 21 subjects that completed the initial four treatments in the phase I study over a five-week period, 11 showed stable disease at the end of five weeks; eight had stable disease at two months, six had stable disease at three months and two were stable for longer than 12 months.
According to Datamonitor, there are currently about 225,000 new cases of renal cell cancer worldwide each year, a figure that is projected to approach 300,000 by the year 2020.
The phase I and phase IIa clinical trials of ASONEP are partially funded by a $3.0 million grant from the National Cancer Institute (NCI) under its Small Business Innovation Research (SBIR) Programme.
ASONEP, and its sister drug iSONEP, are different formulations of sonepcizumab, a first-in-class therapeutic antibody against S1P developed using Lpath's ImmuneY2 drug-discovery engine. Antibodies developed via this discovery engine are designed to target bioactive signaling lipids, such as S1P, that are involved in cancer, age-related macular degeneration (AMD), inflammatory and auto-immune disorders, and other diseases.
Lpath is also conducting a clinical trial called Nexus, which is a four-arm, double-blind phase II study where iSONEP is being evaluated for safety and efficacy in wet-AMD subjects. Lpath entered into an agreement with Pfizer in 2010 that provides Pfizer an exclusive option for a worldwide license to develop and commercialize iSONEP. As part of that agreement, Lpath has granted to Pfizer a time-limited right of first refusal for ASONEP.
Lpath, Inc., a therapeutic antibody company, is the category leader in lipid-targeted therapeutics.