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“The holy grail in this indication is a centrally acting, non-narcotic, not-sedating drug”


- Peter Dicpinigaits, MD, Professor, Albert Einstein School of Medicine; Editor-in-Chief, Lung

    • Ifenprodil has been shown to inhibit cough counts by ~40% (p<0.01) and almost doubled the time to cough (p<0.05)

    • These reductions were achieved at doses <50% NR2B receptor occupancy dose (ED50), enabling higher dosing to increase cough count reductions. 

    • Ifenprodil has been shown to be safe at up to 8x-16x this dose level (NOAEL), enabling significant dose increases without causing toxicities.

    Ifenprodil significantly reduces cough count and time to cough in vivo in preclinical models

    • Ifenprodil has been shown to inhibit geometric mean cough counts by ~40% (p<0.01) at week 12 in an open-label clinical trial.

    • Post-hoc responder analysis showed clear separation between ifenprodil and integrated placebo data from all IPF-refractory chronic cough trials.

    • The VAS score, a patient-reported measure of cough severity, was improved by 37.4% (23.6 mm, p = 0.001).

    •  In the Global Rating of Change Scale, 58% of patients reported an improvement after 12 weeks; only 5% felt worse.

    •  In the Leicester Cough Questionnaire, scores improved over 12 weeks by 1.75 points (p = 0.017), and scores were improved in each domain.

    Ifenprodil significantly reduces 24-hour cough counts and VAS scores in Phase 2a clinical trials in difficult to treat (IPF) patients with cough

    • Ifenprodil safety was described in 15,018 subjects taking the same dose as was tested in our Phase 2a clinical trial.

    • AEs were reported in 2.26% (340 cases) of 15,018 cases.

    • The most common side effects were gastrointestinal 212 cases (1.41%), neuropsychiatric 68 cases (0.45%), hepatic 61 cases (0.41%), hypersensitivity 57 cases (0.38%), and cardiovascular 39 cases (0.30%).

    • No serious side effects (SAEs).

    • Importantly dose-limiting side effects associated with general NMDA channel blockers were absent in >99.5% of patients. 

NR2B receptor allosteric antagonist

Potential for a first- and best-in-class oral treatment for chronic cough

Ifenprodil is a small molecule allosteric antagonist of the NMDA receptor sub-type 2B, which reduces signaling through NMDA receptors that have NR2B subunits present. Ifenprodil is not a general NMDA channel blocker, which is important as NMDA receptors control myriad functions in the brain. 

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