NRX-101 First Antidepressant that Lowers Suicidality in Bipolar Depression, reveals research

NRX-101 is First Antidepressant that Lowers Suicidality in Bipolar Depression, confirms Double blind Controlled trial.

NRx Pharmaceuticals has today announced presentation of its Phase 2b/3 trial of NRX-101, entitled "A Randomized, Double-Blind Controlled Comparison of NRX-101 (D-cycloserine/lurasidone) to Lurasidone for Adults with Bipolar Depression and Subacute Suicidal Ideation or Behavior" at the American Society of Clinical Psychopharmacology (ASCP) in Miami Beach, FL. The lead author is Prof. Andrew Nierenberg, Director, Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital and Professor of Psychiatry, Harvard Medical School.

Akathisia rating by study day: a consistent effect is seen commencing at first post-randomization visit and continued throughout the study (Mixed Model for Repeated Measures Regression effect size =0.037, P=0.03)

"Presentation of these data at this highly respected conference is another important step toward bringing a life-saving product to patients in tremendous need," said Dr. Jonathan Javitt, Chairman and Chief Scientist of NRx. "We believe that NRX-101 may offer a paradigm changing approach to treatment of Bipolar Depression, with a product highly effective in both treating depression and reducing suicidality and associated side effects. We will continue working to bring hope to life with life-saving medications."

The presentation will be held at 11:15 AM, Wednesday May 29, 2024.

W89 A Randomized, Double-Blind Controlled Comparison of NRX-101 (D-cycloserine/lurasidone) to Lurasidone for Adults with Bipolar Depression and Subacute Suicidal Ideation or Behavior

CONCLUSIONS of the Poster are:

• NRX-101 and lurasidone both demonstrated > 50% response for treating bipolar depression with no difference seen on primary efficacy endpoint (MADRS)

• A clinically meaningful difference was observed on both primary and secondary safety endpoints favoring NRX-101

• NRX-101 was associated with 58% relative reduction in time to sustained remission from suicidality as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) when stratified by sex, mood stabilizer use, antipsychotic use, lifetime suicide event (P=0.05).

• NRX-101 was associated with a relative 76% reduction in symptoms of akathisia compared to lurasidone that was sustained over 42 days (Effect Size 0.37; P=0.03) on the Barnes Akathisia Rating Scale

• Akathisia was seen in 2% of participants treated with NRX-101 vs. 11% treated with lurasidone.

• NRX-101 showed superiority to lurasidone in akathisia starting at day 7 and continuing through day 42/ET.

• No treatment-related serious adverse event was observed in either group. No safety issues were detected except for MedDRA General disorders: NRX-101 - 18.2% vs lurasidone - 0% (p=0.002).

Based on these findings, together with the earlier STABIL-B trial, the Company believes that NRX-101 has potential to become a standard of care drug for treating bipolar depression, an addressable population of 7 million patients in the US and many times that around the world.

This study represents the second trial conducted under FDA Good Clinical Practices guidelines to demonstrate large and meaningful advantages of NRX-101 vs lurasidone on akathisia and suicidality and clears the path for a registration trial of NRX-101 vs. placebo to treat bipolar depression together with earlier accelerated approval for those with akathisia. An additional academic trial conducted by Chen and co-workers similarly demonstrated a statistically-significant reduction in suicidality associated with D-cycloserine, the active ingredient in NRX-101, compared to various standard of care antidepressants.

To the Company's knowledge, this trial and its prior STABIL-B study represent the only clinical trials in which an oral antidepressant has been demonstrated to cause meaningful reductions in suicidality and akathisia. All currently approved antidepressant drugs carry FDA-mandated "black box" warnings on their labels indicating that they may increase the risk of suicide. Similarly, akathisia-a side effect in which patients are agitated and frequently experience involuntary movement – is a side effect that occurs in 10-15% of patients who take the lurasidone class of drugs and is closely linked to suicide. As shown in the clinical trial, those randomized to lurasidone experienced a substantial increase in akathisia from baseline, whereas those randomized to NRX-101 demonstrated a statistically-significant reduction in akathisia.