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P529 is a non-steroidal, synthetic, small molecule drug created throughcomputational design, synthetic and medicinal chemistry, the result of threegenerations of Palomid design work. Palomid's broad activity as ananti-angiogenic and anti-proliferative agent is shown to reside in its abilityto target and inhibit the PI3K/Akt/mTOR signal transduction pathway as aTORC1/TORC2 inhibitor.
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The first of the two presentations, "Palomid 529, a Non-Steroidal SmallMolecule Anti-Angiogenic Agent Inhibits Retinal and SubretinalNeovascularization by Inhibiting the PI3K/Akt/mTOR Pathway", was given as anoral presentation by Dr. David Sherris, President and CEO of PalomaPharmaceuticals. The second presentation, "Muller Cell Proliferation andGlial Scar Formation Is Reduced Following Experimental Retinal DetachmentUsing Palomid 529, an Inhibitor of the Akt/mTOR Pathway", was given by theDrs. Geoffrey P. Lewis and Steven. K. Fisher, presented by Dr. Ethan A.Chapin, of the Neuroscience Research Institute, Neuroscience ResearchInstitute, MCD Biology, University of California-Santa Barbara, Santa Barbara,CA.
"Ocular diseases of both retinal and sub-retinal origin, namely diabeticretinopathy and age-related macular degeneration, are a significant problem inour aging population. In order to create a drug to optimally treat suchdiseases one needs to prevent or inhibit disease progression caused by thegrowth of pathological retinal vessels, improve current vision damaged byretinal or sub-retinal blood vessels, inhibit retinal fibrosis and finallyformulate for long term drug delivery as these ocular diseases are chronic innature. We have presented data to support each of these issues in our drugPalomid 529. Palomid 529 is a broad inhibitor of angiogenesis able to inhibitthe key pro-angiogenic cytokines (via their synthesis and ability to signal)shown to initiate pathological vessel growth in both age-related maculardegeneration and diabetic retinopathy. Our data shows Palomid 529's abilityto synergize with anti-VEGF antibody treatment and further to actually allownormal vessel growth to occur while concomitantly inhibiting abnormal vesselgrowth," says Dr. Sherris.
"A frequent complication of retinal detachment is the induction of cellproliferation, often leading to scar formation that can occur on eithersurface of the retina. When scars form between the epithelial layer andphotoreceptors, termed subretinal fibrosis, regeneration of the photoreceptorsis compromised resulting in blindness in that region. When scars occur on thevitreal surface, termed proliferative vitreoretinopathy (PVR), the cellsbecome contractile and cause re-detachment of the retina, again resulting inblindness. We show here using an animal model of retinal detachment that asingle intravitreal injection of Palomid 529 dramatically reduces theintraretinal proliferation induced by detachment and subsequently reducessubretinal glial scar formation to a degree not found in any other drugs wehave evaluated in our models. These findings suggest that inhibiting theAkt/mTOR pathway by Palomid 529 is a promising new strategy for treatingsubretinal fibrosis and perhaps the related disease, PVR", says Drs. Lewis andFisher.
About Angiogenesis and Retinal Vascular Diseases
15 million people in the United States alone have age-related maculardegeneration with 2 million new cases each year. About 21 million people inthe United State have diabetes. Of those, 15 million are diagnosed and over 6million are undiagnosed. Of patients who have
