NRx Pharmaceuticals, Inc. announced a statistically significant safety advantage of NRX-101 compared to the standard of care comparator in its recently completed clinical trial in patients with suicidal bipolar depression. Therefore, the Company believes that demonstration of reduced akathisia in the setting of comparable antidepressant efficacy constitutes a basis for Accelerated FDA Approval of NRX-101. The full clinical trial results will be presented at the upcoming meeting to the American Society of Clinical Psychopharmacology held May 28-31, 2024 in Miami.

NRx will gather Key Opinion Leaders to educate the public on the importance and potentially life-saving implication of this finding. Last week, the Company released preliminary top-line data as required by SEC disclosure rules. The Company believes that today's findings based on mixed model regression analysis as specified in the Company's Special Protocol Agreement with the FDA, when combined with the prior STABIL-B trial1, demonstrate a basis for seeking accelerated drug approval of NRX-101 based on improved safety related to akathisia and suicidality in the setting of comparable antidepressant efficacy.

Trial participants had identical mean scores on the Barnes Akathisia Rating Scale (BARS) at baseline with subsequent decrease in the NRX-101 treated group versus an increase in the lurasidone-treated group, yielding a 76% relative mean difference between the groups. The difference was apparent at the first post-randomization visit and continued throughout the trial. (Fig 1) Over the 42 days of observation, an effect size of 0.37 was identified with a statistically significant P value of 0.025 on the Mixed Model for Repeated Measures (MMRM) methodology agreed to with FDA in the 2018 Special Protocol Agreement.

Akathisia as ascertained by a 1 point increase in the BARS was seen in 11% of participants randomized to lurasidone (comparable to previous reports in the literature) and seen in only 2% of those treated with NRX-101, an akathisia level that was previously reported for the placebo arm of the lurasidone registration trial. Akathisia was a prespecified key safety endpoint of the Company's clinical trial. Hence this finding is not a "post-hoc" observation.

As previously noted, this clinical trial of 91 participants with suicidal bipolar depression who were not pre-treated with ketamine demonstrated that NRX-101 and lurasidone were comparable in their antidepressant effect. A 33% but statistically non-significant sustained decrease in suicidality was also seen favoring NRX-101. As noted above, improved antidepressant efficacy is not required to seek drug accelerated drug approval based on a statistically-significant safety benefit.

Based on this safety finding, NRx plans to seek Accelerated Approval of NRX-101 for treatment of bipolar depression in patients at risk for akathisia who are at highest risk of suicide, while continuing to develop evidence to support broader indications both in treatment of depression and schizophrenia. Should these data be confirmed in additional large scale trials, the Company believes that physicians and patients will universally prefer antidepressant and antipsychotic drugs with a reduced akathisia risk. The NRx patent portfolio supports the development of a broad range of combined NMDA/serotonergic drugs for treatment of depression and psychosis.

There is a recent regulatory precedent for the approval of psychiatry drugs that demonstrate comparable efficacy with improved safety. A combination of olanzapine and samidorphan (LYBALVI®) was approved based on comparable effect on schizophrenia symptoms with evidence of less weight gain favoring LYBALVI. Thus, public assertions by journalists and short-sellers that NRx has no path to market based on the finding of comparable efficacy in this trial are utterly baseless and may be designed to mislead investors.