Multiple New Mechanisms Of Action Greatly Expand Lpath's Ability To Treat Ocular Disease

Main Category: Eye Health / Blindness
Article Date: 13 Nov 2007 - 4:00 PDT

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The strength of recent pre-clinical data has given Lpath, Inc. (OTCBB: LPTN) a broader vision for its lead drug candidate, sonepcizumab, in the ophthalmic arena. As recognized category leader in therapeutic agents against bioactive lipids, Lpath now considers sonepcizumab as a potential treatment for a broad range of ocular diseases that extend well beyond "wet" Age-related Macular Degeneration (AMD).

Results of Lpath's ocular discovery program suggest that sonepcizumab may be a valuable therapeutic in the treatment of diabetic retinopathy, dry AMD, uveitis, and scar formation that results in the failure of a significant percentage of glaucoma-related surgery.

Lpath previously announced that sonepcizumab (the humanized version of Sphingomab™) mitigated almost completely the choroidal neovascularization (CNV) formation in mice with laser-induced choroidal damage, which mimics the pathologic angiogenesis (new blood-vessel formation) experienced by patients with the wet form of AMD. As a result, the company is planning to file an IND ("investigational new drug") application with the FDA in 2008 for use of sonepcizumab in wet AMD patients.

Recent studies suggest, however, that sonepcizumab is much more than a potent inhibitor of pathologic ocular angiogenesis. Other beneficial therapeutic effects of sonepcizumab in ocular applications include:

-- Anti-permeability: In a recent animal model of AMD whereby the Bruch's membrane was ruptured via laser, sonepcizumab strongly inhibited vascular leakage.

-- Anti-fibrosis (reduced collagen scar formation): In recent studies, Lpath first demonstrated that S1P (the bioactive lipid that sonepcizumab binds to and inhibits) promotes collagen deposition (scarring) in numerous ocular cell types and, moreover, that S1P strongly promotes the subretinal fibrosis that is associated with AMD. Consequently, the company examined the effects of sonepcizumab on subretinal fibrosis following laser rupture of Bruch's membrane and showed the drug candidate significantly attenuated collagen deposition within the CNV lesion area, resulting in a greater than three-fold decrease at the 28-day time-point. It is important to note that none of the currently available treatments for wet AMD strategies demonstrates an ability to inhibit subretinal fibrosis.

-- Anti-inflammatory (reduced macrophage infiltration): Lpath recently conducted models of ischemic retinopathy characterized by abnormal blood- vessel growth and demonstrated that sonepcizumab resulted in not only a marked inhibition of pathologic retinal angiogenesis but also a dramatic anti-inflammatory effect, as evidenced by a reduction in macrophage recruitment of over 80%.

This combination of mechanisms of action is potent and provides Lpath with a wide range of opportunities in the ophthalmology arena, as follows:

-- Lpath is now positioned extremely well in wet AMD: The three additional modes of action described above confirm the ability of sonepcizumab to mitigate multiple etiologies of wet AMD and suggest that sonepcizumab may have significant therapeutic advantages over singly targeted methods of treatment, such as anti-VEGF compounds.

-- Lpath may be first-to-market with a solution to decrease the failure rates of glaucoma filtration surgery: Almost one-third of trabeculectomy and valve implantation surgeries fail due to scarring that forms at the point of intervention. With its anti-fibrotic mechanism, sonepcizumab could be used before, during, and/or after surgery to prevent such scarring. This is currently an unmet need in ophthalmology.

-- Sonepcizumab's profound ability to inhibit the recruitment of macrophages may make it a valuable therapeutic agent for the treatment of dry AMD: The incidence of dry AMD is nearly nine times that of wet AMD, and yet there is no treatment available beyond vitamin and mineral supplements.

-- Sonepcizumab might have distinct competitive advantages in diabetic retinopathy: Inflammation appears to play a key role in the pathogenesis of diabetic retinopathy. Given sonepcizumab's best-in-class anti- inflammatory results, Lpath hopes to offer therapeutic promise to patients with diabetic retinopathy where there is currently no treatment available.

"This is exciting and novel research in the ophthalmology arena," said Glenn L. Stoller, M.D., head of Lpath's ocular therapies division, "as the presence and the effects of bioactive lipids in the eye was a complete unknown until just recently."

Added Scott R. Pancoast, Lpath's president and CEO, "Sonepcizumab has shown to be, at least in animal models, its own combination therapy. This has created a broad spectrum of opportunity and positions Lpath extremely well to be a leader in ophthalmology."

Sonepcizumab is a monoclonal antibody against S1P, an innovative target in cancer and in retinal pathology. It was the first monoclonal antibody ever developed against any lysolipid, an extremely important subcategory of lipids.

About Lpath

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™ (the systemic formulation of sonepcizumab) is an antibody against S1P that holds promise for the treatment of cancer and other diseases. A second product candidate, iSONEP™ (the ocular formulation of sonepcizumab), has demonstrated superior results in various preclinical AMD and retinopathy models. Lpath's third product candidate, Lpathomab™, 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™ drug-discovery engine, which the company is using to add to its pipeline. For more information, visit http://www.Lpath.com

Forward-Looking Statements

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.

http://www.Lpath.com