GeNeuro, Servier Aim To Develop First Drug Addressing Causal MS Factor

Servier of France will progress Swiss biotech GeNeuro’s monoclonal antibody through Phase III trials aimed at the MSRV-Env protein which, if successful, could transform how multiple sclerosis is treated.

Early studies showing that the presence of the MS-associated retrovirus may trigger multiple sclerosis has prompted French pharma Servier SA to back the lead product of Swiss-based startup GeNeuro SA in Phase III testing, the companies said Dec 2.

There is no cure for the chronic demyelinating inflammatory and degenerative disorder of the central nervous system, with existing therapeutics mainly focusing on treating symptoms. But GeNeuro aims to find one, an outcome that would revolutionize MS treatment.

Servier is now backing that premise. [See Deal]

The French group will cover Phase III global development costs of GNbAC1 and pay GeNeuro up to $408 million in future development and sales milestones, along with royalties on future sales. Servier also will have the option to take an equity stake in GeNeuro as a minority shareholder in the next 12 months.

GNbAC1 is a humanized monoclonal antibody that targets the MSRV-Env protein expressed in brain lesions of MS patients and which is pro-inflammatory and blocks the remyelination process. It has successfully completed Phase IIa studies demonstrating a good safety profile and encouraging signs of efficacy in a first small cohort of patients.

The Swiss group – spun out of Switzerland’s Institut Merieux in 2006 – focuses on human endogenous retrovirus (HERV) expression associated with the central nervous system. Explaining its approach, the Swiss biotech notes that mobile genetic elements make up about half the human genome and around 8% of the human genome is represented by HERV, in which this genetic material is usually dormant. A member of the HERV family W, the Multiple Sclerosis-Associated Retrovirus or MSRV gene, encodes an envelope protein (Env) that GeNeuro says could activate the body’s immune system and play a key role in the pathogenesis of multiple sclerosis (Also see "GeNeuro SA" - Scrip, 1 Feb, 2011.).

“By blocking this protein, our antibody could act on the inflammatory and neurodegenerative components of MS,” Jesús Martin-Garcia, chairman of GeNeuro, said, and added that it might prove to be especially well-suited for progressive forms of the disease. “We believe this can be the missing link (between observation that viral infections are associated with the start of the disorder and expression of the MSRV-Env protein, which can then explain the inflammatory and demyelinating characteristics of MS),” he added.

He underscored the point that GNbAC1 does not affect the immune system. “MSRV-Env has no physical function. We are targeting a protein that is toxic, and has no physiological function, and that’s why this target is safe,” Martin-Garcia said in an interview.

Under terms of their agreement, GeNeuro, which has just 16 employees, will be responsible for developing GNbAC1 to completion of Phase IIb, after which Servier can exercise the option to license the antibody for all markets outside the U.S. and Japan. Servier will pay GeNeuro of $47 million to finance the completion of Phase IIb.

“We have a great partner in Servier,” Martin-Garcia said. “They have a strong, long-term commitment to CNS and long-term disorders, a broad network to support clinical development and commercialization, and are present in 140 countries. And what’s really valuable to us is that they value the independence of their partners – so they’ll bring us their input and their experience, but they value where GeNeuro has so far taken the antibody and will let us carry on leading it to the end of Phase II,” he added.

He said the Phase II trials should finish mid-2017 “and given what we learn there, we’ll then launch the Phase III and see whether it’s a three-, four- or five-year program.”

GeNeuro Says Causal Approach Might Work In Other Diseases

GeNeuro says its causal approach to MS potentially could be applied in other disorders also.

“An increasing amount of literature suggests the MSRV-Env protein and the HERV process are also involved in other diseases, such as CIDP [Chronic Inflammatory Demyelinating Polyneuropathy], some subsets in type 1 diabetes, and a sub-group of schizophrenia. But at the moment, we’re concentrating on MS,” said Martin-Garcia, who is a co-founder of GeNeuro.

“When we started down this path eight years ago, it was not very well understood, but today more and more literature is showing that that this mobile element in our genome can play an important role in pathogenesis and we’re the first company with a clear proposition in terms of pathogenesis in a major disease that is today poorly understood. We believe this approach can dramatically change the approach. If the Servier-led Phase III trials confirm this, then it could really block the progression of the disease,” Martin-Garcia said.