Competitive Landscape
Lpath has developed a monoclonal antibody (mAb) against an important tumor growth factor, S1P. We believe that this antibody will be effective in reducing the four major processes of cancer progression: tumor proliferation, tumor metastasis, tumor-associated angiogenesis, and protection from cell death. Most other mAbs on the market or in clinical trials have demonstrated efficacy in only one or two of these tumor-promoting processes (see summary table below). As such, Lpath believes that Sphingomab™ might well have a comparative therapeutic advantage over the antibody approaches currently on the market.
Most therapeutic monoclonal antibodies on the market and in clinical trials are directed against protein targets; Sphingomab™, however, is directed against a lipid, giving the antibody an abundant therapeutic advantage. Unlike protein targets, S1P has a single molecular structure which is conserved among species (from slime molds to human). This allows for a greater translation between animal efficacy studies and possible human applications. As a consequence, the conserved structure of the ligand would presumably reduce the optimization effort once humanization of the antibody has been achieved. As a single molecular species, S1P is not expected to change its chemical structure as do many protein targets when transformed cells attempt to resist a therapy by mutating the target. Consequently, the Company believes that patients with cancers who subsequently would undergo an anti-S1P therapy will not as easily experience resistance to therapy as occurs with most other therapeutics.
An additional competitive therapeutic advantage of Sphingomab™ is that S1P normally resides in the systemic circulation, giving the antibody easy accessibility to its target. We believe that, as Sphingomab™sponges S1P from the circulation, it may act as a concentration sink to draw S1P out from tumors where the local concentrations of S1P may be quite high.
We believe that Sphingomab™'s ability to create a concentration gradient may be particularly useful in drawing S1P out of brain tumors. Therapeutic antibodies, including Sphingomab™, usually have limited ability to cross the blood-brain barrier (BBB). Unlike circulating protein targets, S1P is a small lipid and can cross the blood brain barrier with ease. Consequently, Sphingomab™does not need to cross the BBB and could draw S1P from the cerebral fluid, depriving brain tumors of the S1P growth factor. For most other solid tumors, Sphingomab™ would presumably have accessibility to the tumor itself through the profuse blood supply characteristic of fast growing tumors. Regarding circulating tumors such as myelomas and leukemias, Sphingomab™ could reduce effective levels of S1P in the same compartment (i.e., blood) where the tumor cells commonly reside.
Another potential competitive advantage of Sphingomab™ over protein targets is that our target, S1P, does not suffer from this species-specificity problem, i.e., mouse S1P and human S1P are the same molecular form and there are no other isoforms. By contrast, Avastin®'s protein target, VEGF, has five isoforms and about the same number of splice variants, as well as all of the different mouse variants. Thus, animal studies performed with Sphingomab™ will more likely reflect success in human trials, all other things being equal. All things may not be equal, however, in that our target, S1P, is in the same compartment (i.e., blood) as is the highest concentration of antibody. So, the ability of Sphingomab™ to neutralize the target is made easier. This plus the fact that S1P is a lipid and is much smaller (379 Da) than VEGF (45,000 Da) may prove important in allowing Sphingomab™ to draw S1P out of tumors and tissues (e.g., brain) where the target might accumulate.
Note: Avastin® is a registered trademark of Genentech, Inc.
