It’s been 17 years in the making, but Acumen Pharmaceuticals hasn’t given up hope for its approach to a disease-modifying drug for Alzheimer’s disease. After restructuring to become a virtual biotech and raising a $20 million Series A, Acumen is marching forward with preclinical development of an antibody that binds and captures soluble oligomers of the amyloid beta peptide in the brain.
The company’s story dates back to 1996, when it was formed to protect patent filings of discoveries made by William Klein and Grant Krafft at Northwestern University and Caleb Finch at the University of Southern California.
At that time, it was common belief that Alzheimer’s was caused by a buildup of beta-amyloid plaques in the brain, said CEO Bill Goure. The team’s research, though, had led them to believe something else.
They found that soluble oligomers they called amyloid beta-derived diffusible ligands, or ADDLs, were toxic to neurons and proposed that ADDLs were important to the cause of Alzheimer’s disease. That was controversial at the time, Goure said, but as science evolved over the next decade, soluble oligomers became a key part of the Alzheimer’s conversation.
As a result of that paradigm shift in the science community, Acumen landed a drug development deal with Merck & Co. in 2004, Goure said. With the money from the deal, the company established an R&D center in California to advance other activities associated with those soluble oligomers.
But that was short lived; in 2008, the company pivoted and converted itself to a virtual company, shutting down that facility. Goure, then the chief operating officer, became CEO, leading the company through a financial restructuring under which it eliminated its debt and began the process of reacquiring its drug candidate from Merck, which was at the time merging with Schering-Plough.
“We were concerned that Merck wasn’t advancing our program as fast as we thought they should have,” Goure said.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Acumen reacquired all of its rights to ACU-193 in 2011, and in the meantime licensed rights for another small molecule that blocked the formation of soluble oligomers to Merz Pharmaceuticals GmbH in early 2010.
The next and most recent milestone in its restructuring was the close of a $20 million Series A round last month. With funding from BVF Partners, NeuroVentures Fund, Praxis Technologies, Glynn Ventures and other investors, Acumen plans to continue in-vivo efficacy studies in transgenic animal models and begin IND-enabling safety studies in the fourth quarter of the year.
Goure said he hasn’t been discouraged by the disappointing Phase 3 study results of two other antibodies for Alzheimer’s reported last year. “When we look at all the other AB immunotherapies being developed today, all of those other antibodies do not have selective binding to soluble oligomers — they target plaque or monomers,” he said. In other words, they are based on outdated assumptions about Alzheimer’s.
But if the soluble oligomer hypothesis is now widely accepted, are other drug companies getting on board? According to Acumen, although the toxicity of soluble AB oligomers has been well studied, there is limited data showing the effects of molecules interfering with their actions. Goure said Abbott Pharmaceuticals had a fairly robust program going, but appears to have shut it down. Cognition Therapeutics is taking a different approach, identifying a small molecule that’s designed to prevent the binding of toxic oligomers to receptors on the surface of neurons.
As Acumen marches forward with just two formal employees and a host of service provider partners, Goure said he has complete faith in the company’s new model.
“If you look today at skills necessary to develop a therapeutic, very few small companies can acquire those skills, and those that do can’t do it in a cost effective manner,” he said. “Those skills shift as you go from pre-clinical to IND to clinical studies. Small companies either find themselves hiring and firing to adapt their expertise, or trying to adapt their workforce to areas they don’t have skills for. It makes more sense to buy the skills and expertise you need when you need them.”
