R&D MODEL & PORTFOLIO
PROJECT START: March 2015 OVERALL OBJECTIVE: Develop a macrofilaricide effective
PROJECT START: March 2013 OVERALL OBJECTIVE: Develop emodepside as a new
against worm-symbiotic Wolbachia bacteria
macrofilaricidal treatment for patients suffering from onchocerciasis
Two derivatives of a veterinary antibiotic, which target the worm-symbiont Wolbachia bacterium, are currently in development for treatment of filarial diseases. These compounds can be delivered orally, induce a robust antiWolbachia effect in several in vivo models, demonstrate clear superiority over doxycycline, and are effective after a shorter dosing regimen. Preliminary safety and toxicology profiling of these compounds carried out in 2015 suggests a favourable safety profile. Upon successful completion of the necessary toxicology studies, expected in 2016, and development of an oral formulation, a Phase I single rising dose study in healthy human volunteers will be performed to determine the safety, tolerability, maximum tolerated dose, and pharmacokinetics of single oral doses of the selected compound. If appropriate pharmacokinetic characteristics are demonstrated and are suggestive of sufficient therapeutic margins, the safety, tolerability, and pharmacokinetics of multiple ascending doses of an oral formulation of the compound will be determined. To demonstrate proof of concept for filarial disease, a Phase Ib programme will be conducted in patients. This programme will be designed to provide data on which a collective decision can be made to proceed into Phase II studies in patients with either onchocerciasis or lymphatic filariasis.
MAIN PARTNERS: AbbVie, USA; Liverpool School of Tropical
• Complete pre-clinical package for first-in-human study • Progress emodepside into first-in-human study
Emodepside is a semi-synthetic product (originated by Astellas and out-licensed to Bayer for animal and human use); its precursor is synthesized by a fungus living in the leaves of Camellia japonica. It is a potent antihelminthic drug used in combination with praziquantel (as Profender®) and in combination with toltrazuril (as Procox®) for the treatment of parasitic worms in cats and dogs. DNDi and Bayer Pharma AG are jointly developing emodepside for the treatment of onchocerciasis patients. DNDi will be responsible for the pre-clinical and clinical development of emodepside and Bayer for the pharmaceutical development, manufacturing, registration, and supply of the drug at the lowest sustainable price. The pre-clinical package to start Phase I studies was completed and recruitment into a single-ascending dose study was initiated in December 2015.
MAIN PARTNER: Bayer HealthCare, Germany
Filling knowledge gaps
As is frequently the case with neglected diseases, there are a number of knowledge gaps. DNDi partners are carrying out modelling studies aiming to quantify and characterize the future needs of patients suffering from onchocerciasis and lymphatic filariasis, and to provide information on the size and profile of target populations for the new treatments in development. There is also a need for reliable biomarkers of disease evolution which can assess the effect of new treatments as an alternative to existing invasive skin biopsies and nodulectomies. A new medical optical imaging technique is being evaluated, which aims to find an optical signature of live versus dead O. volvulus worms in subcutaneous nodules.
PARTNERS: Erasmus University, the Netherlands; CEA-LETI(1),
France; REFODTE, Cameroon; Institut de Recherche pour le Développement, France.
(1) LETI a French state-owned research entity, (Commissariat à l’énergie atomique et aux énergies alternatives (CEA), Laboratoire d’Électronique et de Technologies de l’Information (LETI).
DNDi Annual Report 2015 › 43