EIP Pharma closed a $20.5 million series B round to support the phase 2b program of its Alzheimer's treatment, neflamapimod. While the company's immediate focus is that study, the funding will also help it build out its team and support the exploration of other central nervous system disorders for which the drug might be useful.
Cambridge, Massachusetts-based EIP licensed neflamapimod from Vertex in 2014. It is an oral inhibitor of the enzyme p38 MAP kinase alpha, which is expressed in neurons in times of stress and disease, the company said in a statement. Problems with p38 alpha activity can contribute to synaptic dysfunction, one of the culprits behind memory deficits in Alzheimer's disease.
EIP is working in one of the most difficult and unforgiving spaces in biotech; Alzheimer's has not seen any tangible R&D advance in about 15 years, with many candidates showing early promise only to fall short in late-stage trials. What's different about neflamapimod is that it doesn't drug a suspected root cause of the disease, according to CEO John Alam, M.D. Instead, it targets the synaptic dysfunction that occurs in Alzheimer's regardless of its cause.
"[Neflamapimod] is somewhat indifferent to what the triggers are," Alam said. "The science in the last two, three, four years says that regardless of whether it is amyloid plaques, inflammation, tau, or any number of different initiating factors, it all meets in the synapse."
And it might turn out to be the solution for a field that has focused on warding off the formation of amyloid plaques for the better part of two decades: "What has been discovered in the past five to seven years is that amyloid plaque buildup happens years in advance of memory deficits and the cognitive symptoms of Alzheimer's," Alam said. "So, the approach of preventing buildup inherently cannot work in someone who has clinical symptoms."
With neflamapimod, EIP is hoping to reverse synaptic dysfunction and not just arrest or delay it. Three weeks of treatment reversed cognitive deficit in animals, while a pair of phase 2a trials that ran for six and 12 weeks led to improvement in episodic memory function, Alam said.
EIP aims to finish enrolling its phase 2b study by the end of the year and to read out by the end of 2019. The Reverse-SD study will involve about 150 patients, half of whom will take neflamapimod capsules daily, while the other half will receive placebo. It will run for six months, with a primary endpoint of improving episodic memory as measured by the Hopkins Verbal Learning Test. Its secondary endpoints include broader measures of cognition and function, as well as markers of neurodegeneration in the spinal fluid, Alam said.
Once it's got the trial fully enrolled and under way, EIP will investigate other indications. Neflamapimod could be applied to other CNS disorders, including Huntington and Parkinson's diseases, as well as some forms of autism spectrum disorder and Rett syndrome, Alam said. But the most logical step forward might be helping the brain heal itself after suffering a stroke. Lingering inflammation can lead to synaptic dysfunction and hinder the brain's ability to rewire itself, so targeting this process could significantly improve recovery, he said.