Servier, Oncodesign Select LRRK2 Inhibitor for Preclinical Studies

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
LRRK2 inhibitor

LRRK2 inhibitor

Servier and Oncodesign have selected a LRRK2 inhibitor as their partnership program’s lead candidate for Parkinson’s disease and plan to start regulatory preclinical safety studies soon.

A Phase 1 clinical trial is expected to begin in 2022.

“We are particularly pleased with, and proud of, these results obtained in collaboration with Servier, a longstanding and major partner of our company since its creation and are confident in their ability to make the best use of this program’s substantial potential,” Philippe Genne, PhD, Oncodesign’s chairman, CEO, and founder, said in a press release.

In March 2019, the companies entered a research and development collaboration to develop new LRRK2 inhibitors for Parkinson’s disease. The collaboration involves the use of Nanocyclix, Oncodesign’s proprietary technology for designing, making, and optimizing small molecules that can inhibit the activity of kinases. Kinases are proteins that modify other proteins so that they can fulfill their functions in the body.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, 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, the activity of LRRK2 is increased in patients with idiopathic (of unknown cause) Parkinson’s disease.

It is thought that blocking the activity of LRRK2 could have therapeutic potential in Parkinson’s disease.

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

A first key milestone of the collaboration was reached in early 2020. Now, reaching the second milestone has triggered a payment of €2 million (almost $2.4 million) to Oncodesign. According to the terms of the agreement, Servier could pay Oncodesign €320 million (about $381 million) in milestone payments, excluding royalties on sales. So far, Oncodesign has received a total of €13 million (about $15 million) in an upfront payment, milestone payments, and research funding.

“Reaching this major milestone illustrates the constructive nature of the collaboration initiated with Servier in 2019,” said Jan Hoflack, PhD, Oncodesign’s chief scientific officer and head of its Biotech Business Unit. “The selection of this molecule within the initially-anticipated 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 global license option that may 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 our two companies’ experiences and approaches, which has enabled the rapid identification of a preclinical candidate and a number of follow-up compounds; we are very proud of this partnership,” said Ross Jeggo, Servier’s global head of the Neurology and Immunoinflammation Therapeutic Area. “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 focus, with a huge medical need and for which there are no disease progression-slowing treatments currently available. LRRK2 inhibition is a potentially disruptive mechanism that could impact and slow this progression, representing a very important hope for millions of patients worldwide,” Jeggo added.

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