Eboo Pharmaceuticals Inc. (EPI) is an emerging development-stage company building on over 20 years of chemistry and pharmacology R&D that originated in the Burroughs Wellcome laboratories of North Carolina. EPI is currently seeking funding and partnering opportunities to advance pre-clinical lead candidates through non-clinical, gold-standard, proof-of-concept studies and to drive viable candidates through IND-enabling programs and into early clinical studies. The company has access to over 750 compounds in the library of delta opioid agonists that have a variety of therapeutic targets. The most advanced current lead compounds are being developed for the treatment of Parkinson’s disease, depression and protection of cardiac tissue from reperfusion injury (cardioprotection) following myocardial ischemia. Additional areas with substantial research basis and ongoing lead selection include sexual dysfunction and wider areas of concern related to reperfusion injury.
Parkinson’s Disease and Depression
Background: The vast majority of patients with Parkinson’s disease are currently treated with L-DOPA or its analogues. While these drugs are effective initially, on-off periods, increased dose requirements and significant side-effects such as dyskinesia accrue with continued use. A non-dopaminergic therapeutic MOA is urgently needed in order to diversify the therapeutic arsenal of both monotherapy and L-DOPA adjunct therapy. EPI has clear evidence of anti-parkisonian efficacy for a number of compounds, with strong support for a concomitant potential to decrease the L-DOPA induced dyskinesia (LID) based on biased ligand activity across the opioid receptor family. In addition, there is support for a protective role of these compounds, delaying the onset of the disease through retention of dopaminergic cells.
Approximately half of all patients afflicted with Parkinson’s disease also have depression. SSRI treatment is the current standard of care for depression but the advent of an orally available, centrally acting delta agonist would avoid the need for poly-pharmacy and its attendant vagaries.
Compound Profiles: The lead candidate for Parkinson’s disease, a high potency delta agonist and mu antagonist, has demonstrated significant efficacy in both dopamine antagonist and neurotoxin rodent-models of Parkinson’s disease, restoring normal behaviors with no evidence of side-effects or toxicity. Further, the compound class and molecular target have been validated in the gold-standard non-human primate models of Parkinson’s disease (MPTP-lesioned macaques; Hille et al., Experimental Neurology 2001; 172:189-198). This compound, among others in the library, has also demonstrated significant activity in three acute rodent models of antidepressant activity (rat and mouse forced swim and the mouse tail suspension test, with faster onset than Wellbutrin® or Prozac® in the rat and no loss of activity with continued use (Jutkiewicz, Molecular Interventions (2006), 6:162-169). Clearly there is substantial potential for the development of an antidepressant indication separate from the Parkinson’s setting; however, EPI aims to provide diverse proof-of-concept with a limited clinical development cost.
Background: Patients who survive a heart attack often suffer from congestive heart failure related to ongoing tissue damage due to reperfusion injury to the cardiac muscle. Delta receptors have been widely demonstrated to potently inhibit multiple factors in the cell death cascades related to reperfusion injury following hypoxia or ischemia.
Compound Profile: The lead candidate for protection against reperfusion injury is a high affinity delta agonist administered intravenously/intramuscularly. This compound has been shown to significantly protect against tissue death and loss of function over time in rodent models of ischemia when administered prior to, during or after (at the initiation of reperfusion) the ischemic event. With the excellent safety profile seen with this agent and the clear benefit in an otherwise empty space, this compound has the potential to become a first line intervention in any suspected cardiac event that may have resulted in hypoxia or ischemia to the heart.
Intellectual Property: Eboo Pharmaceuticals Inc has licensed an extensive patent estate covering the compounds, the chemical genus, and methods of use extending to 2028.