No inhibitions about drug discovery

DIJON, France—Oncodesign and Ipsen are teaming up toresearch novel treatments for Parkinson's disease, collaborating on therapeuticagents that inhibit the LRRK2 protein, mutations of which increase the risk ofgenetically inherited Parkinson's.

Under the terms of the agreement, Ipsen is granted twoexclusive options to exclusively license Oncodesign's LRRK2 inhibitor program,notably upon successfully reaching clinical proof of concept, with worldwidedevelopment, manufacturing and commercialization rights.

Oncodesign is entitled to a technology access fee, fundingof the program's research and early development activities, and upon exerciseof the license options, opt-in fees and additional development, regulatory andcommercial milestone payments potentially totaling about $145 million for thedevelopment of molecules in two or more indications, as well as tieredroyalties on net sales.

According to Jan Hoflack, chief scientific officer atOncodesign, the companies worked together on the Resource Center forExperimental Cancer Models (CReMEC) program, which was initiated in 2005 byOncodesign and entailed the development and characterization of patient-derivedexperimental models of colon cancer.

"We are very proud and excited to have been selected byIpsen as partner on this innovative research collaboration," adds PhilippeGenne, CEO and founder of Oncodesign. "This agreement advances our strategy topartner on drug discovery activities in addition to our well-known preclinicalevaluation service activities in advanced oncology pharmacology."

Hoflack explains that the agreement allows his company toadvance its series of attractive LRRK2 inhibitors together with a partner withrecognized expertise in central nervous system (CNS) disease research.

"This is our first drug discovery partnership with a majorbiopharmaceutical company based on our Nanocyclix technology, validating ourability to identify uniquely potent and selective novel kinase inhibitors foruse in oncology, CNS and other therapeutic areas," he says.

Hoflack notes that Oncodesign recently started its drugdiscovery activities, following the in-licensing of a medicinal chemistrytechnology from Johnson & Johnson in April 2010.

"This technology is based on small-molecule macrocyclizationand has been strongly expanded and improved by Oncodesign," Hoflack says. "Itis the basis of its current portfolio of research programs."

Nanocyclix, as the technology is called, gives access topotent and selective kinase inhibitors with a strong IP position and gooddrug-like properties.

Hoflack says kinase inhibitors have high interest in thepharmaceutical industry, with an estimated 25 percent of global R&Dspending devoted to it. There are 518 kinases found in the human genome, ofwhich many are potential therapeutic targets.

"The major hurdles in kinase research are creating a strongintellectual property position, finding compounds that are selective amongkinase family members and combining potency and selectivity in the compoundswith good drug-like properties (notably PK and safety)," he explains. "The Nanocyclixtechnology addresses these challenges in a broadly applicable way."

The program that is partnered with Ipsen consists of aseries of molecules that are potent and selective inhibitors of LRRK2 but thatare very small in size.

"The high level of selectivity is extremely important, asthe application in Parkinson's disease requires compounds that are very safe asthey will be used as a chronic treatment," Hoflack says. "The small size of themolecules is essential to allow them to cross the blood-brain barrier."

Claude Bertrand, Ipsen's executive vice president of R&Dand chief scientific officer, says the deal was in line with Ipsen's newstrategy to increase its investment in R&D with external partners forcompounds outside its usual focus of peptides and toxins.

Parkinson's disease is the most common neurodegenerativemovement disorder, afflicting 1 percent of the population 65 years and older.Bertrand also explains why Parkinson's was chosen as one of the first areas toresearch as part of the strategy.

"In the field of neurology and movement disorders,Parkinson's disease is a serious condition with high unmet medical needs wherepatients are seeking improved care and quality of life," he said. "Today, thereis no treatment targeting the underlying pathogenetic mechanism leading toprogressive deterioration in those patients."

Hoflack says the short-term goals of the collaborationinclude advancing Oncodesign's Nanocyclix LRRK2 inhibitors to preclinical, in-vivo proof of concept in Parkinson'sdisease and other therapeutic applications, validating LRRK2 as a diseasetarget using the compounds as pharmacological tools and selecting a LRRK2inhibitor for preclinical and clinical development. For longer-term goals,however, the companies hope to identify Parkinson's and LRRK2 specificbiomarkers for patient selection, early diagnosis and treatment follow-up, andto investigate the potential of the selected LRRK2 inhibitor in Parkinson'spatients with activating LRRK2 mutations.

"Specific project milestones havebeen agreed from the start by the joint project team," he concludes. "Theadvancement of the compounds through the discovery and development phases andthe validation of LRRK2 as a therapeutic target within the program areimportant success factors."