New LRRK2 inhibitor for Parkinson’s disease selected for preclinical studies


Servier and Oncodesign have selected an LRRK2 inhibitor as the lead candidate for their Parkinson’s disease partnership program and plan to initiate regulatory preclinical safety studies in the near future.

A phase 1 clinical trial is expected to start in 2022.

“We are particularly happy and proud of these results obtained in collaboration with Servier, historical and major partner of our company since its creation and are confident in their ability to make the most of the significant potential of this program”, Philippe Genne, PhD, chairman, CEO and founder of Oncodesign, said in a Press release.

In March 2019, the companies entered into a research and development collaboration to develop novel LRRK2 inhibitors for Parkinson’s disease. Collaboration involves the use of Nanocyclix, Oncodesign’s proprietary technology for the design, manufacture and optimization of small molecules capable of inhibiting kinase activity. Kinases are proteins that modify other proteins so that they can perform their functions in the body.

Mutations in the leucine-rich repeat kinase 2 (LRRK2), which provides instructions for making a kinase called LRRK2 or dardarin, are one of the most common genetic causes of Parkinson’s disease. Even in the absence of a disease causing mutation, LRRK2 activity is increased in patients with idiopathic Parkinson’s disease (of unknown cause).

It is believed that blocking LRRK2 activity may have therapeutic potential in Parkinson’s disease.

“The selection of this drug candidate in collaboration with Servier reaffirms the relevance of our Nanocyclix technology,” said Genne.

A key first step of the collaboration was taken in early 2020. Today, the achievement of the second step triggered a payment of 2 million euros (nearly $ 2.4 million) to Oncodesign. Under the terms of the agreement, Servier could pay Oncodesign 320 million euros (approximately $ 381 million) in milestone payments, excluding royalties on sales. So far, Oncodesign has received a total of 13 million euros (approximately $ 15 million) in the form of upfront payment, milestone payments and research funding.

“The achievement of this major milestone illustrates the constructive nature of the collaboration initiated with Servier in 2019,” said Jan Hoflack, PhD, Scientific Director of Oncodesign and head of its Biotech Business Unit. “The selection of this molecule within the initially planned timeframe, despite the difficulties associated with the global COVID-19 pandemic, reflects a shared desire to test this new approach in humans as quickly as possible. “

Servier has an exclusive worldwide license option that can be exercised once the candidate molecule receives Investigational New Drug (IND) approval, which it expects in 2022.

“This intense and fruitful collaboration with Oncodesign underlines the synergistic nature of the experiences and approaches of our two companies, which allowed the rapid identification of a preclinical candidate and several follow-up compounds; we are very proud of this partnership, ”said Ross Jeggo, Global Head of Neurology and Immunoinflammation Therapeutics at Servier. “The next step is the regulatory toxicology phase, which we will begin shortly, after which we anticipate our first phase I clinical trial in 2022.”

“Parkinson’s disease is an important part of our strategic direction, with enormous medical need and for which there is currently no treatment that slows the progression of the disease. Inhibition of LRRK2 is a potentially disruptive mechanism that could impact and slow this progression, representing a very important hope for millions of patients worldwide, ”added Jeggo.

During the lead optimization phase, several other LRRK2 inhibitors were identified as rescue preclinical candidates. These could be used as alternatives if problems arise during the development of the first selected molecule.

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