Eva Pharmaceuticals, STTR Phase II Application, April 2007, Abstract Since their discovery, COX-2 inhibitors have dominated the market for non-steroidal anti-inflammatory agents (NSAIDs). In 2004, Vioxx(r), a major COX-2 inhibitor, was removed from the marketplace due to thromboembolic toxicity. Celebrex(r), the other major COX-2 inhibitor, now has almost no competition and therefore can remain inhibitively expensive. Celebrex also has a lower but still measurable rate of thromboembolic complications. There is therefore a powerful need for a new, less toxic, and less expensive NSAID. We have recently discovered that Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, has multifactorial anti-inflammatory activity and specifically inhibits COX-2 but not COX-1. Initial in vivo studies were aimed at reducing inflammation from ionizing radiation (IR), a common side effect of cancer treatment for which there is no satisfactory agent for prevention, mitigation, or therapy. Among the most common and symptomatic complications of therapeutic radiation are toxicity to the skin and to the lung. The impact of EsA, and its aglycoside analog, h-EsA, on IR induced inflammation is dramatic and substantially better than Celebrex. To the best of our knowledge there are no comparable modifiers of intermediate or late lung toxicities after irradiation. Thus h-EsA could prove to have substantial impact on public health. Animal experiments performed under the Phase I portion of this STTR confirmed that EsA has anti-inflammatory utility. Additionally we found that administration of EsA and h- EsA in mice reduced radiation-related pneumonitis and pulmonary fibrosis, in addition to reducing radiation effects in other soft tissue such as brain and skin. Our goals with this Phase II STTR are to develop the Good Laboratory Practices and Good Manufacturing Practices, quantify the benefit with respect to delay and alleviation of pulmonary toxicity (eg. dose modifying factors), determine the dose schedules for h- EsA, and establish the no adverse effect level (NOAEL dose). The proposed studies will provide the remaining components required for our FDA IND submission. Eva Pharmaceuticals STTR Phase II Grant Request Project Narrative We are pursuing the goal of commercializing EsA, a drug that, based on sound experimental data, promises to reduce the harmful side effects of nuclear radiation on people. There is currently nothing else available anywhere that has the equivalent combination of (a) efficacy on lungs, brain and skin tissue, (b) ease of storage, handling and oral consumption, and (c) most importantly, effectiveness when taken after the exposure. The potential value to society is huge, especially for the estimated 325,000 people yearly who receive radiation treatments for cancerous tumors, but also for the nation's first responders and for our armed services. ? ? ?
