Trio tackles translational research

Three-way collaboration tackles Parkinson’s disease

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DIJON, France—A year ago, a drug discoverycompany/pharmacology service provider (Oncodesign) partnered with apharmaceutical company (Ipsen) to discover and develop innovative LRRK2 kinaseinhibitors as potential therapeutic agents against Parkinson's disease (PD) andother therapeutic areas. A month ago, the collaboration added the expertise ofan academic group exploring the roles of LRRK2 and a-synuclein in PD.
Building on Oncodesign's January 2012 LRRK2 program with advancedNanocyclix lead molecules with Ipsen, Oncodesign is working in a researchcollaboration with the Laboratory for Neurobiology and Gene Therapy (LNGT) atthe department of neurosciences at the Katholieke Universiteit Leuven (KULeuven). The objective of the collaboration is to evaluate Oncodesign'scompounds in multiple pharmacology models for PD.
The Ipsen-Oncodesign collaboration emanated fromOncodesign's discovery of novel macrocyclic LRRK2 inhibitors with attractiveprofiles. Ipsen entered into an option-based collaboration on this target. Inthis collaboration, Oncodesign uses its Nanocyclix platform expertise toadvance the program, while Ipsen contributes its know-how in central nervoussystem (CNS) disorders.
"Our partnership with Ipsen on the discovery of noveltherapeutic agents in Parkinson's disease has advanced to a stage where we canuse further in-depth expertise and advanced pharmacology models to position ourleads," says Dr. Jan Hoflack, chief scientific officer and head of Oncodesign'sdiscovery activities. "We are very excited to collaborate with KU Leuven toadvance our understanding of both our inhibitors and the LRRK2 target."
According to Dr. Philippe Genne, CEO and founder ofOncodesign, "the group of Veerle Baekelandt at KU Leuven is an expert team inPD in general, and more specifically related to LRRK2 and alpha-synuclein. Thegroup was initially involved in a feasibility study of early Oncodesign LRRK2inhibitors in which the investigators confirmed the potency and selectivity ofthe compounds in advanced cellular models. Now that the Oncodesign/Ipsenprogram is advancing well, the group is again involved in testing the novelcompounds in advanced in-vitro and in-vivo models."
Oncodesign will be responsible for the partnership toadvance the drug discovery program. KU Leuven will perform the biologicalevaluation of the best compounds, in a non-exclusive way. Other externalpartnerships with key opinion leaders in PD are being set up related to theLRRK2 program, according to Genne.
The goal is to advance the science related to PD and LRRK2,especially related to a link with alpha-synuclein. In addition, thecollaboration will profile the Oncodesign compounds in advanced models toassess their potential in a translational manner.
The overall deliverables goal of the project is to select aLRRK2 inhibitor candidate compound for preclinical and clinical development bythe end of 2013. The next goal is to establish clinical proof of concept for aLRRK2 inhibitor in a Phase IIa study. Ipsen will do the clinical development.
"We are delighted that our partnership with Oncodesign ismoving forward as planned with the objective of developing therapeutics forParkinson's disease patients," says Dr. Claude Bertrand, executive vice presidentof R&D and chief scientific officer at Ipsen. "The Oncodesign collaborationwith LNGT will greatly accelerate the progress of this research program."
Bertrand adds, "Parkinson's disease is a serious conditionwith high unmet medical needs where patients are seeking improved care andquality of life. Today, there is no treatment targeting the underlyingpathogenetic mechanism leading to progressive deterioration in those patients."
According to Genne, "LRRK2 is one of the most exciting'drugable' targets for PD because of its genetic linkage with familial cases ofPD. Nevertheless, it is still an exploratory target that requires significantvalidation. The aim of the program is to create in first instance the moleculartools that allow the validation of LRRK2 as an attractive target in PD, and insecond instance LRRK2 inhibitors useful to treat the disease."
The collaborators estimate the commercial potential to bemedium to high, depending on the utility of LRRK2 inhibitors in sporadic PD aswell as in familial cases of PD.

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