EIP Pharma Closes $20.5 to Fund Alzheimer’s Studies
The monies raised will be used to advance development of neflamapimod for the treatment of Alzheimer’s disease. The oral small molecule inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38 alpha). P38 alpha is expressed in neurons during stress and disease, and irregular p38 alpha activity appears to contribute to synaptic dysfunction, a major driver in memory issues caused by Alzheimer’s disease.
In March, EIP released results from a three-month Phase IIa clinical trial of neflamapimod in patients with early Alzheimer’s disease. The study data was published in the Annals of Clinical and Translational Neurology. As a result of the findings, it initiated a six-month Phase IIb clinical trial (REVERSE-SD) to evaluate the drug’s activity in reversing synaptic dysfunction.
In the study, 16 patients received neflamapimod for 84 days (12 weeks). They were randomized to receive 40 mg or 125 mg twice a day. Brain scans were performed at baseline and at Day 84. Episodic memory was assessed using the Wechsler Memory Scale (WMS).
Brain scan results weren’t consistent. The company cited “no main group level effects,” although in the “prespecified responder analysis,” which was a 7 percent or greater reduction in 11C-PiB signal, there were three responders in the 40-mg group and one in the 125-mg group. However, there were statistically significant increases from baseline in the memory assessments that correlated with immediate recall and delayed recall.
The study’s interpretation was, “Selective p38alpha inhibition in patients with early AD may improve episodic memory and potentially impact beta-amyloid production. These preliminary clinical findings support conduct of a longer duration placebo-controlled study, particularly to confirm the effects on episodic memory function.”
Neflamapimod was discovered by Vertex Pharmaceuticals and licensed by EIP in 2014. Before the license agreement, Vertex had completed extensive non-clinical toxicity studies and a Phase I and initial Phase IIa clinical trial in non-CNS diseases.
“We are grateful for the support from Access Industries as they share our commitment to advancing neflamapimod given the encouraging Phase IIa results and the significant unmet medical need that remains in Alzheimer’s disease treatments,” said John Alam, chief executive officer of EIP Pharma, in a statement. “This new funding is earmarked to support our Phase IIb study, further exploration of other areas where neflamapimod may have therapeutic potential and expansion of our team.”
Earlier this year, the U.S. Food and Drug Administration (FDA) issued new draft guidance for preclinical trials in Alzheimer’s disease, which recognized three stages of pre-dementia sporadic AD and provided suggestions on how to measure trial results for each of them. It also recognized four different states of AD that could be useful for the design and evaluation of clinical trials. Some of those included pathophysiologic changes, but others focused on detectable abnormalities in neuropsychological measurements, particularly in comparison to changes in functional impairment.
This was partly the FDA’s way of saying that in early Alzheimer’s disease, it was difficult to show a drug’s effect on things like rates of nursing home admission, because that occurs later in the disease. But in early disease, memory function is important to patients, and clinical studies can focus on that as a part of clinical trial design.
If effective—a big “if” when it comes to Alzheimer’s disease—the drug may have potential for treating almost any CNS disorder because of its approach to synaptic dysfunction.