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Merck & Co has had mixed fortunes in neurological diseases of late, but remains committed to the category and has just bolstered its early-stage pipeline with a $576 million agreement to acquire Calporta Therapeutics.

The bolt-on deal gives Merck access to a series of preclinical-stage TRPML1 agonists which Calporta is developing as treatments for various lysosomal storage and neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease.

The deal – which includes an undisclosed upfront payment plus milestones – was announced by COI Pharmaceuticals, one of eight companies set up by venture capital group Avalon Ventures in partnership with GlaxoSmithKline in an alliance first drawn up in 2013.

GSK recently acquired coeliac disease specialist Sitari, one of the other companies from the partnership.

Calporta’s research programmes draw on TRPML1 research conducted by University of Michigan scientist Haoxing Xu. According to COI, the target – transient receptor potential cation channel, mucolipin subfamily to give it its full name – is found on lysosomes in cells, structures that are used to break down and recycle waste products.

TRPML is also thought to be a regulator of autophagy, the process by which the body disposes of damaged cells, and alterations in its activity have been linked to neurodegenerative diseases, including Alzheimer’s, that are linked to the accumulation of toxic lipids or proteins.

“Increasing evidence points to the accumulation of toxic proteins as a common mechanism in neurodegenerative conditions such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and Alzheimer’s,” said Merck’s head of neuroscience discovery Fiona Marshall.

“We look forward to conducting further research to evaluate the potential of TRPML1 agonists to activate a natural clearance mechanism the brain employs to clear toxic proteins,” she added.

Merck’s efforts to a develop a treatment for Alzheimer’s disease hit a wall when its BACE inhibitor verubecestat was abandoned last year, after an interim analysis found that it was unlikely to succeed in slowing the progression of the disease in its early stages.

The company has insisted it remains committed to neurodegenerative disease research, however, and it has had more luck developing its sleep disorder therapy Belsomra (suvorexant) for insomnia in patients with mild-to-moderate Alzheimer’s, which was filed for approval in the US in May.

Otherwise its neurosciences pipeline is fairly thin when it comes to clinical-stage candidates, with phase 2 schizophrenia candidate MK-8189 currently the most advanced project. Most of its R&D in neurodegenerative disorders is in early-stage development, such as its anti-tau partnership with Teijin.

By Phil Taylor

Source: Pharma Phorum