Lpath Demonstrates Strong Safety Profile of Lead Drug Candidate,Sphingomab, in Non-Human Primates
SAN DIEGO, August 20, 2007 /PRNewswire-FirstCall/ -- Lpath, Inc. , the category leader in therapeutic agents against bioactive lipids, reported that a standard panel of safety tests was recently completed with the humanized version of Sphingomab(TM), and the findings indicate no safety concern for systemic dosing of the antibody to humans.
Sphingomab, generated by Lpath's proprietary ImmuneY2(TM) platform technology, is a monoclonal antibody against the bioactive lipid S1P (sphingosine-1-phosphate). S1P has been well validated as a stimulator of angiogenesis (new blood-vessel growth), a process that has been strongly implicated in the pathology of both cancer and AMD.
The safety tests included cardiovascular studies in Cynomolgus monkeys as well as tests to evaluate the potential of the antibody to elicit the release of cytokines or an Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) reaction. The cardiovascular study included evaluation of the effect of humanized Sphingomab treatment on blood pressure, heart rate, and respiratory rate. The cardiovascular, cytokine release, and ADCC tests with humanized Sphingomab were all negative at doses or concentrations well above those expected to be needed in man to provide an anti-angiogenic action.
The panel of tests also included a pivotal multiple-dosing 28-day study in Cynomolgus monkeys. This study featured intravenous administration of humanized Sphingomab at doses as great as 100 mg/kg every three days for 28 days (10 total doses). Parameters monitored during this study included mortality, body weight, organ weight, clinical observations, ophthalmology, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), and immune-phenotyping, both pre-treatment and on day 28 in all animals, and after one, two, three, and four weeks of recovery in a large sub- group of the animals.
No animal deaths occurred during the study. There were also no significant clinical changes observed during, or following dose administration of 0, 3, 10, 30 or 100 mg/kg. The few minor clinical changes observed were all considered either not related to the administration of humanized Sphingomab or not toxicologically significant. No findings were observed in clinical chemistry, hematology, coagulation or lymphocyte subpopulation measures except for a slight decrease in blood lymphocytes at the highest dose administered, and this effect could not be observed within one week after cessation of dosing.
The histopathology results from this 28-day toxicology study are expected later this quarter, but no negative findings of any significance are expected.
In conclusion, the preclinical safety profile of humanized Sphingomab was extremely favorable throughout a wide variety of studies at high multiples of anticipated human exposure.
"These are extremely encouraging results," said William Garland, Ph.D., Lpath's vice president of drug development. "The favorable findings will provide Lpath with considerable dosing flexibility in our upcoming Phase I clinical trials."
Lpath plans to file an IND in November of 2007 for clinical use of ASONEP(TM) (the systemic formulation of humanized Sphingomab) in the treatment of cancer patients. During the first quarter of 2008, Lpath plans to file a second IND, this one for clinical use of iSONEP(TM) (the ocular formulation of humanized Sphingomab) in the treatment of AMD patients.
Scott Pancoast, Lpath's president and CEO, commented, "The strong safety profile of Sphingomab bolsters not only our cancer program, but also our ocular program, because the drug substance is humanized Sphingomab in both cases."
Lpath, Inc., headquartered in San Diego, California, is the category leader in lipidomics-based therapeutics, an emerging field of medical science whereby bioactive signaling lipids are targeted for treating important human diseases. ASONEP(TM) (the systemic formulation of humanized form of Sphingomab(TM)) is an antibody against S1P that holds promise for the treatment of cancer and other diseases. A second product candidate, iSONEP(TM) (the ocular formulation of humanized Sphingomab), has demonstrated superior results in various preclinical AMD models. Lpath's third product candidate, Lpathomab(TM), is an antibody against LPA, a key bioactive lipid that has been long recognized as a valid disease target. The company's unique ability to generate novel antibodies against bioactive lipids is based on its ImmuneY2(TM) drug-discovery engine, which the company is using to add to its pipeline.
Except for statements of historical fact, the matters discussed in this press release are forward looking and reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond our control and may cause actual results to differ materially from stated expectations. For example, there can be no assurance that required clinical trials will be successful, necessary regulatory approvals will be obtained, or the proposed treatments will prove to be safe or effective. Actual results may also differ substantially from those described in or contemplated by this press release due to risks and uncertainties that exist in our operations and business environment, including, without limitation, our limited experience in the development of therapeutic drugs, our dependence upon proprietary technology, our history of operating losses and accumulated deficits, our reliance on research grants, current and future competition, and other risks described from time to time in our filings with the Securities and Exchange Commission. We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof.
Posted: August 2007