Sanford J. Madigan, PhD, CEO of Calporta and senior vice president, business development of COI Pharmaceuticals.

Merck & Co. has acquired Calporta, a developer of treatments for neurodegenerative and lysosomal storage disorders, for up to $576 million from an entity created by venture capital firm Avalon Ventures and GlaxoSmithKline (GSK) to nurture life science startups in San Diego.

That entity, COI Pharmaceuticals, announced the acquisition today.

Calporta develops selective small molecule agonists to transient receptor potential cation channel, mucolipin subfamily, member 1 (TRPML1), also called mucolipin-1, based on research from the lab of Haoxing Xu, PhD, at the University of Michigan.

TRPML1 is a key lysosomal ion channel that is believed to play a role in lysosomal function by promoting autophagy and lysosomal exocytosis. Alterations in TRPML1 function have been implicated in several neurodegenerative diseases and dystrophies, where intracellular accumulation of proteins or fats have been shown to be toxic to the cell.

Merck and Calporta reason that activating TRPML1 signaling with small molecules could reestablish lysosomal processes and restore cellular function, and that agonists of TRPML1 restore calcium efflux and normalize lysosomal trafficking and function.

Calporta’s preclinical stage TRPML1 agonists are being studied for their potential to treat Niemann-Pick C Disease (NPC) and other lysosomal storage diseases. The company is also studying its TRPML1 agonists as potential treatments for Alzheimer’s disease and Parkinson’s disease, among other neurodegenerative disorders.

“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.”

Merck agreed to acquire Calporta for up to $576 million consisting of an upfront payment and payments tied to achieving milestones, neither of which were detailed in the announcement.

“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,” stated Sanford J. Madigan, PhD, CEO of Calporta and senior vice president, business development of COI Pharmaceuticals.

“Community of innovation”

COI Pharmaceuticals (short for “Community of Innovation”) was launched in 2013 through the $495 million Avalon-GSK collaboration, with the goal of forming and funding up to 10 life science companies.

The partnership ended at eight companies following a change of leaders for GSK’s R&D operations, as Hal Barron, MD, succeeded Lon Cardon, PhD, who is now at BioMarin Pharmaceutical and was promoted last month to chief scientific strategy officer. In September, GSK acquired the first of the COI companies to be formed, celiac disease treatment developer Sitari Pharmaceuticals, leaving Avalon overseeing the other COI companies.

Originally, Avalon agreed to contribute $30 million from its $200 million Fund X, and provide executive leadership and operational management consistent with its current portfolio strategy. GSK agreed to provide up to $465 million in company seed funding, R&D support, and payments tied to preclinical and clinical milestones toward the 10 startups, each focused on the discovery of drugs against disease targets.

Avalon agreed to identify promising early-stage technologies across a variety of therapeutic areas, subject to approval by a joint management committee of Avalon and GSK, then followed by joint financing of the companies established to commercialize those technologies.

Each company launched by COI Pharmaceuticals was funded with $10 million in Series A financing and R&D support from Avalon and GSK. Calporta received its $10 million in June 2015.

Speaking with GEN in 2014, Jay Lichter, PhD, managing director of Avalon Ventures and president and CEO of COI Pharmaceuticals, said nurturing startups through COI “is more capital efficient. You can get senior people who are somewhat expensive to work on an early-stage company, but only spend maybe 10 or 20% of their time on it.”

A postdoc or senior researcher from the founder’s lab is brought in to drive science, under Avalon supervision “to make sure they’re doing product development as opposed to just research,” Lichter said at the time.

“As early as 2014, our scientists identified TRPML1 as an important target for improving lysosomal function. We saw the potential to treat a number of diseases by activating this ion channel, and we launched Calporta in early 2015,” Lichter said today in announcing the acquisition. “Now, four years later, we have an agreement with Merck, an industry leader in biopharmaceutical research and development, which is key to advancing these therapies to clinical trials and patients.”

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