The Science: Technical Overview

Technical Overview of Lpath's Core Technology

Bioactive lipids as drug targets

Lpath is the category leader in lipid-based therapeutics, an emerging field of medical science whereby bioactive signaling lipids are targeted for treating important human diseases.

It was not long ago that certain lipids were determined to be bioactive in nature and therefore bona fide targets for rational drug design. It is now appreciated by key opinion leaders that changes in lipid metabolism can lead to cancer, diabetes, neurodegenerative disorders, immune function, pain, mental disorders, ocular disorders, and inflammation. Scientists believe that there are over 1,000 members of the functional lipidome, opening up a sizeable array of new potential targets for therapeutic interventions.

Lpath has two distinct advantages in this emerging field of lipid-based therapeutics:

  1. Because lipids are extremely small (~1/100 the size of proteins, on average) and are not water-soluble, they are challenging to study. Many of the tools that were developed over decades to analyze proteins simply do not work with lipids. Lpath was one of the first to recognize that bioactive lipid signaling molecules, like sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), were valid targets; as such, over the last 10+ years, we have developed a sophisticated repertoire of proprietary processes, know-how, and assays that enable us to study and analyze the performance characteristics of these challenging molecules.
  2. Lpath is the only company that has been successful in generating and advancing therapeutic antibodies against bioactive lipids. Using our proprietary ImmuneY2™ drug-discovery engine, we have now done it several times over, and we continue to apply our technology to new bioactive lipid targets.

Lpath has further widened the lead over the competition by submitting patent applications that the company believes will provide protection of several key aspects of the platform technology.

Sphingosine-1-phosphate (S1P), an important bioactive lipid

Sphingosine-1-phosphate (S1P) is a bioactive lipid that is a key component of the sphingolipid signaling cascade. S1P acts on a complement of five G-protein Coupled Receptors (GPCRs) to promote cell proliferation, migration, and protection from cell death (apoptosis). In pathological conditions, S1P has many actions that can promote inflammation, pathogenic fibrosis and dysregulated angiogenesis.

Schematic of Sphingosine-1-Phosphate
Schematic of Sphingosine-1-Phosphate

Lpath's antibody against S1P, Sphingomab™

Lpath has produced and optimized a monoclonal anti-S1P antibody (Sphingomab). After demonstrating proof-of-concept with Sphingomab in various animal models of cancer, Lpath then humanized the anti-S1P antibody. The humanized version of the antibody demonstrates the same selectivity and specificity, with picomolar affinity, as Sphingomab and can similarly absorb S1P from the extracellular fluid, thereby lowering the effective concentration of S1P.

Lysophosphatidic Acid (LPA)

Lysophosphatidic acid (LPA) is a key extracellular signaling mediator that has been linked to neuropathic pain, cancer, and fibrosis (pulmonary, renal, and liver fibrosis). In animal models, receptor-mediated LPA signaling is crucial in the initiation of neuropathic pain and in pathologic fibrosis. In addition, LPA1-receptor activation has been shown to stimulate macrophage recruitment and connective-tissue growth-factor expression.

Schematic of Lysophosphatidic Acid
Schematic of Lysophosphatidic Acid

Lpathomab™ (antibody against LPA)

Lpath has developed monoclonal antibodies that specifically recognize LPA with the aim of lowering the effective extracellular levels of LPA. In CNS disease, it is anticipated that neutralizing LPA would result in significant neuroprotection and in fibrosis, neutralizing LPA appears to decrease collagen deposition and inflammation.

  • Lpath has successfully generated several monoclonal antibodies to LPA.
  • The antibodies are highly specific to LPA; they do not appreciably cross react with other structurally similar bioactive lipid mediators, including S1P, ceramide (CER), sphingosine (SPH), sphingosylphosphoryl choline (SPC), lysophosphatidyl choline (LPC), or other bioactive lipids.
  • Lpath's antibodies to LPA have also shown prophylactic and intervention effects in animal models of neuropathic pain, diabetic neuropathy and traumatic brain injury.
  • Lpath has data suggesting that antibodies to LPA could have an effect in animal models of renal and pulmonary fibrosis.