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Will LPATH (LPTN.OB) Reap the Fruits Of Its Acknowledged Efforts

|Includes: Apollo Endosurgery (APEN)

      An early enthusiasm for Lpath science, technology and breakthrough treatments still in preclinical development at the time, has led to investors’ disappointment. LPTN.OB, which has descended to the penny stock zone, might be predestined for a comeback and even more. Lpath scientists were among few who recognized that bioactive lipid signaling molecules such as sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) were valid targets for therapeutics of cancer and other diseases. The firm did not stop at the discovery, but went further into developing proprietary processes, know-how, and assays, which enabled studying and analyzing the characteristics of the challenging lipid molecules and their effects. Consequently, the firm used its proprietary ImmuneY2™ drug-discovery engine to create what to our knowledge are the first therapeutic molecules (in this case antibodies) against the chosen bioactive lipid targets.  

     What brought this firm in mind were two press releases posted by the firm on Tuesday March 30.  In the first, Lpath announced positive results of phase 1 clinical trial of its drug ASONEP™ in a wide variety of solid tumors. In the second it demonstrated and explained its dissatisfaction with, and rejection of the decision by its exclusive worldwide licensee of ASONEP™, Merck KGaA (Germany), to extend its license agreement. The news about phase 1 trial Asonep™ informed that the trial has met its primary endpoint of identifying safe dose. The monoclonal antibody drug was well tolerated at all the dose-levels from 1 mg/kg to 24 mg/kg. These results erased doubts about safety evaluating Asonep as a single agent or overlapping toxicity when used in combination with standard therapies. With regard to the drug’s efficacy, the results demonstrate that more than half the patients who completed the initial four-treatment evaluation period showed stable disease, which has been durable in several cases. Important also was the finding that the lymphocyte counts in the vascular space were reduced in a drug dose-related fashion. These results have achieved an objective established by the licensee Merck KGaA (Darmstadt, Germany), which led to a $2 million payment.

      Lpath views these results as validating its drug Asonep™, its bioactive signaling lipid target and its ImmuneY2™ drug-discovery engine.  Lpath viewed them as adding a huge increase in the drug value, which led to reject Merck KGaA’s proposal to continue its partnership in Asonep™ program with the same financial terms, which is now viewed as not in its best interest or the best interest of its shareholders. As a result, Merck KGaA notified Lpath that it will terminate the License Agreement effective April 24, 2010 and return the rights to the cancer drug Asopnep’s program to Elpath. What’s next? First, Lpath promised its shareholders to aggressively seek to re-partner Asopnep™, but with a much favorable deal. Its compelling argument include: First, the strong efficacy signals from Asonep’s preclinical studies in animal models, which involved renal cell carcinoma, prostate cancer, neuroblastoma, ovarian cancer and lung cancer. Second, the successful completion of phase 1 clinical trial that was announced on Tuesday, which offered evidence of biological and therapeutic activity of the drug on human cancer patients.

Some Background About the Drug Target

     To begin with, besides Lpath’s drug, Asonep, no therapeutics exist that that target bioactive signaling lipids for treating human diseases. Validating the firm’s program is the current scientists’ acknowledgement of the fact that changes in lipid metabolism can cause cancers, heart disease, vascular diseases, diabetes, neurodegenerative disorders, immune diseases, pain, mental disorders, eye disorders, and inflammatory diseases. They insinuated that bioactive lipid signaling molecules would make good therapeutic targets.
     It was easy to say it, but not really easy to identify these targets, analyze them and develop drugs that target them. These lipids are minute in size and are not water-soluble, making them extremely hard to understand. Also, the tools usually used to analyze proteins do not work for lipids.
     Using the processes it developed over a substantial amount of time, and its proprietary ImmuneY2™ drug-discovery engine technology, Lpath was capable of breaking the barriers, identifying valid targets for therapeutics: Sphingosine-1-phosphate (S1P) and another one, lysophosphatidic acid (LPA), and develop drugs to target them.    

Sphingosine-1-phosphate (S1P) - a bioactive lipid (a key component of the sphingolipid signaling cascade) acts on a complement of five G-protein Coupled Receptors (GPCRs) to promote cell proliferation, migration, and protection from cell death (apoptosis) – all are characteristics of cancer. S1P has many actions, possibly causing many diseases, including inflammation, pathogenic fibrosis, and cancer. S1P is, in fact, a pleiotropic tumorigenic growth factor that promotes tumor growth by stimulating cell proliferation and metastasis. Recent studies indicate that S1P promotes tumor angiogenesis. Importantly, sphingosine kinase (SPHK), the enzyme responsible for S1P production, is an oncogenic protein, further suggesting that S1P is a potential therapeutic target for cancer.

Lpath Pipeline

Asonep™:     (Systemic formulation of humanized Sphingomab™)

Target:     Sphingosine 1 Phosphate (S1P)
Indications:     Cancer, Inflammation
Development:     Phase 1 Partnered with Merck-Serono

isonep™:     (Ocular formulation of humanized Sphingomab™)

Target:     Sphingosine 1 Phosphate (S1P)
Indications:     AMD, Diabetic Retinopathy, Glaucoma, Others
Development:     Phase 1


Target:     Lysophosphatidic Acid (LPA)
Indications:     Cancer, Fibrosis, Neuropathic Pain
Development;  Late Preclinical


Target:     (Other bioactive lipid targets)
Indications:     Inflammation, Cancer, Asthma, Sepsis, Others
Development:     In discovery

Sphingomab™: This Lpath’s monoclonal anti-S1P antibody functions as a therapeutic molecular sponge to selectively absorb S1P, thus lowering the effective extracellular concentrations of this tumor-facilitating factor. The drug is expected1 to reduce tumor volume and metastatic potential as well as cause blockage of new blood vessel formation that feed cancers. Lpath also hypothesize that the drug would reverse the ability of S1P to protect cells from apoptosis.
     Lpath has developed murine and humanized monoclonal antibodies to S1P. The MAb is highly specific to S1P. It does not cross react with other structurally similar bioactive lipid mediators. Utilizing BIAcore technology, the affinity (Kd) of Sphingomab™ for S1P has proven to be much higher than most therapeutic antibodies, particularly other molecular sponges.

1. The expectations are based on animal results where data have demonstrated compelling efficacy results. The drug has significantly reduced tumor volumes and weights in human models of lung cancer in mice, including ovarian, breast, lymphoma, myeloma, lung and melanoma cancers. It significantly reduced new blood vessel formation in mice cancer and significantly reduced circulating levels of the pro-angiogenic growth factors, VEGF, IL8, and IL6 in tumor mice. In cell culture, the ability of cancer cells to release these growth factors is reduced by Sphingomab™.  
 There is a lot of science, a lot of experimentations and a lot of hypothesis and good results. There are many promising results and promises by the company. There is a lot of effort spent, a lot of pain and a lot of patience. The concept is a breakthrough, as the targets are lipid instead of
proteins like usual. The drugs are the outcome of the efforts and capability of solving the problem of understanding the lipid targets, which is a hard task. Lpath is one of the few, it not rare, penny stocks that are so serious, so scientific and so promising. We wish its efforts would become fruitful.  The odds for a successful outcome are mounting.   

Disclosure: No Positions