EIP Pharma Announces Presentation of Preclinical Data Demonstrating Effects of p38a Kinase Inhibitor Neflamapimod on the Neurodegenerative Process

CAMBRIDGE, Mass., July 17, 2019 /PRNewswire/ -- EIP Pharma, Inc., a CNS-focused therapeutics company, today announced that new preclinical data regarding neflamapimod were presented at the AAIC 2019 scientific meeting in Los Angeles, CA (July 14-18, 2019).

"The findings add to the growing body of evidence that inhibition of p38 alpha kinase has the potential to reverse synaptic dysfunction and treat the neurodegenerative process," said John Alam, MD, President and CEO of EIP Pharma.

The data were reported in two separate poster presentations at the Developing Topics (late-breaker) session at the meeting:

    --  Title: #P4-506 Role of p38  MAP kinase in amyloid-  derived diffusible
        ligand (ADDL) induced dendritic spine loss in hippocampal
        neuronsAuthors: Ladan Amin, PhD(1), Nhat Le, PhD(1), Robert C.C. Mercer,
        PhD(1), Ursula Germann, PhD(2), John Alam, MD(2) and David A. Harris, MD
        PhD(1), (1) Boston University School of Medicine (2) EIP Pharma,
        Inc.Summary & Conclusions: Neflamapimod reduced Amyloid-  derived
        diffusible ligand (ADDL)-induced dendritic spine retraction starting at
        the lowest concentration tested (10 nM) and fully blocked the effect at
        50 nM.  Consistent with a previous report from the Harris lab (Fang, et
        al 2018), neflamapimod reduced dendritic spine loss after exposure to
        purified PrPSc, the infectious form of the prion protein, starting at 25
        nM, and fully blocked spine retraction at 100 nM.  The authors conclude
        that the results suggest that A  oligomers and PrPSc may trigger
        overlapping synaptotoxic signaling pathways that have in common
        activation of p38  MAP kinase.


    --  Title: #P4-692 Effects of p38  MAP kinase inhibition on the
        neurodegenerative phenotype of the Ts2 Down Syndrome mouse modelAuthors:
        Ying Jiang, PhD(1,2), Philip Stavrides, MS(1), Sandipkumar Darji, MS(1),
        Dun-Sheng Yang, PhD(1,2), Cynthia Bleiwas, MS(1), John Smiley, PhD(1,2),
        Ursula Germann, PhD(3), John Alam, MD(3) and Ralph Nixon, MD, PhD(1,2),
        (1) Nathan Kline Institute for Psychiatric Research (2) NYU Langone
        Medical Center (3) EIP Pharma, Inc.Summary & Conclusions: Ts2 transgenic
        mice that model Down Syndrome and develop typical Alzheimer's disease
        pathology or wild-type (WT) mice were treated for 28 days with vehicle
        or neflamapimod in vehicle starting at 4.7-6.4 months of age, when
        endosomal pathology is evident and cholinergic neuronal loss is
        developing in Ts2 mice. At the end of treatment, Rab5 activation, Rab5+
        endosome size and the number of neurons staining positive for choline
        acetyltransferase (ChAT+ neurons; i.e. cholinergic neurons) were
        assessed by immunohistochemical analyses of the medial septal nucleus of
        the brain. In the Ts2 mice, treatment with neflamapimod reduced Rab5
        activation relative to vehicle-treatment and normalized Rab5+ endosome
        size (i.e. reversed endosomal pathology). Neflamapimod treatment also
        restored ChAT+ neuron number and normalized morphology (size) in Ts2
        mice. Specifically, the number of ChAT+ neurons by immunohistochemistry
        was reduced by approximately 30% in the medial septal nucleus in
        vehicle-treated Ts2 mice relative to WT mice, while similar numbers of
        ChAT+ neurons were seen in the MSN of wild-type (vehicle or neflamapimod
        treated) and neflamapimod-treated Ts2 mice. The authors conclude that
        the findings indicate that p38  antagonism could treat the
        neurodegenerative process beyond reversing synaptic dysfunction.

About neflamapimod
Neflamapimod is a brain-penetrant, oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38 ). P38 , which is expressed in neurons under conditions of stress and disease, plays a major role in inflammation-induced synaptic toxicity, leading to impairment of synaptic function. Synaptic dysfunction is known to be a major drive of the deficits in cognitive function that are defining characteristics of many CNS diseases. Neflamapimod is currently being studied in a Phase 2b trial for early Alzheimer's disease; and in separate Phase 2 trials in patients with Huntington's disease who have evidence of cognitive dysfunction and in mild-to-moderate dementia of Lewy bodies.

About EIP Pharma, Inc.
EIP Pharma, Inc. is a private, Cambridge, MA-based company advancing CNS-focused therapeutics to benefit patients with neurodegenerative diseases.

For more information, please visit www.eippharma.com.

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SOURCE EIP Pharma, Inc.