Merck has taken a stake in the neurodegeneration research field, following the acquisition of San-Diego, US-based Calporta.
Calporta is focused on the development of selective small molecule agonists to TRPML1, which is thought to play a key role in lysosomal function. The lysosome is a cellular compartment enzyme involved in breaking down and recycling cellular waste products, including fats, proteins and other macromolecules.
When these enzymes do not function properly, waste builds up and poisons healthy cells. These changes in TRPML1 function have been implicated in a number of neurodegenerative diseases.
By activating TRPML1 signalling with small molecules treatments, lysosomal processes can potentially be reestablished and cellular function restored. Therein becomes a possible treatment for diseases such as Alzheimer’s and Parkinson’s.
“This agreement with Merck is an important milestone towards the rapid development of a novel therapeutic approach that could help millions of people with degenerative disorders caused by toxic accumulation of proteins, fats, or other cellular macromolecules,” said Sanford Madigan, CEO of Calporta and senior vice president, business development, COI Pharmaceuticals.
Merck has offered Calporta a total potential consideration of $576m – this includes an undisclosed upfront payment and contingent milestone payments.
Calporta was one of eight San Diego-based biotechs created as part of a deal between venture capital firm Avalon Ventures and pharma giant GlaxoSmithKline.
COI Pharmaceuticals is the venture-pharma entity established by Avalon to support its portfolio companies. Since GSK did not exercise the option to purchase Calporta, Merck has been able to snap up the early-stage biotech.
“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 Fiona Marshall, vice president, neuroscience discovery, Merck Research Laboratories.
“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, among many big pharma players, has had its fair share of failure in the neurodegenerative research area – its lead BACE inhibitor verubecestat failed to show a clinical effect in Alzheimer’s disease. By expanding into other potential treatment mechanisms, Merck may be able to find success in a field that has been littered with disappointing results.
However, the pre-clinical nature of the research also makes it high-risk – the unknown upfront payment will likely reflect this fact, with larger payments coming later on if significant milestones are reached.