Cyclurad (cycloserine/lurasidone) / NRx Pharma, Alvogen - LARVOL DELTA

NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (PRNewswire) - "Initiated filing of a New Drug Application ('NDA') to the FDA for NRX-100 (IV Ketamine) for the treatment of Suicidal Depression; planned filing of an NDA for Accelerated Approval under Breakthrough Designation and Priority Review of NRX-101 for the treatment of bipolar depression in people at risk of akathisia. Both have anticipated PDUFA dates prior to December 31, 2025."

FDA approval • FDA filing • Bipolar Disorder

NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Advances Relationship with Anson Funds with $8.9 Million Financing, Including Above the Market Equity and Senior Secured Debt (PRNewswire) - "NRx Pharmaceuticals...today announced that it has entered into a binding agreement for a registered direct offering of its common stock with expected gross proceeds of $3.5 million (the "Financing") with certain institutional investors. The Company also intends to issue certain senior secured convertible promissory notes (the 'Notes') with expected gross proceeds of $5.4 million to the same institutional investors pursuant to that certain securities purchase agreement dated August 12, 2024 (the 'Note Issuances'). The Company intends to use the net proceeds from the Financing and the Note Issuances to support, among other things, the New Drug Application filing of its two lead products, NRX-100 and NRX-101, the launch of HOPE Therapeutics, and the potential addition of new products to its pipeline."

Financing • Depression • Suicidal Ideation

HOPE Therapeutics, Inc. and NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Announce Dr. Jonathan Javitt and Dr. David Feifel to Present Keynote Address, Beyond Ketamine Monotherapy: Combined Interventional Treatment of Suicidal Depression and PTSD, at the 8th Annual Neuroscience Innovation Forum in San Francisco (PRNewswire) - "HOPE Therapeutics...and...NRx Pharmaceuticals, Inc...today announced that Jonathan Javitt MD MPH...and Prof. David Feifel MD PHD...will present the Keynote Address at the 8th Annual Neuroscience Innovation Forum on January 12, 2025, at the Marines' Memorial Club in San Francisco at 10:30am PT...The keynote will focus on the integration of NMDA-targeted drug therapy (such as ketamine) with other emerging modalities such as Transcranial Magnetic Stimulation (TMS) and Digital Therapeutics to produce synergistic therapeutic effects that will permanently alter the clinical trajectory of patients with suicidal depression, PTSD, and other debilitating neuropsychiatric conditions for which there is a great need for better treatments....Milestones: 1Q 2025 - Planned completion of NRX-100 filing with the FDA; 1Q 2025 - Targeted NDA filing for NRX-101 (Oral DCS/Lurasidone) for Accelerated Approval; 1Q 2025 - Further HOPE clinic acquisitions."

Clinical • Commercial • FDA filing • Bipolar Disorder • Depression • Suicidal Ideation

NRx Pharmaceuticals (NASDAQ:NRXP) to Proceed with Two New Drug Applications in 2024; NRX-101 has Been Returned to the Company for Filing (PRNewswire) - "NRx Pharmaceuticals, Inc...announced that advice from regulatory counsel, which includes former senior officials from the Food and Drug Administration, supports filing two New Drug Applications (NDAs) in 2024: an application for Accelerated Approval for NRX-101 to treat bipolar depression in patients with akathisia and an application for approval of NRX-100 (IV ketamine) for treatment of suicidal depression. While efficacy and safety data are now in hand, filing of the above applications is dependent upon completion of 12-month stability data in manufactured lots as required by FDA regulations."

FDA filing • Bipolar Disorder • CNS Disorders • Depression • Suicidal Ideation

MBD: NRX-101 for Bipolar Depression With Subacute Suicidal Ideation (clinicaltrials.gov) - P2/3 | N=74 | Completed | Sponsor: NeuroRx, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

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 (ASCP 2024) - P2/3 | "Database lock will occur in April 2024. Trial efficacy and safety data and rater congruence results will be presented for the first time at the ASCP."

Clinical • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Dementia • Depression • Mood Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

NRX-101 (D-Cycloserine + Lurasidone) Is Active against Drug-Resistant Urinary Pathogens In Vitro. (PubMed, Antibiotics (Basel)) - "Furthermore, lurasidone does not interfere with DCS's antimicrobial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infections."

Journal • Preclinical • Infectious Disease • Nephrology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis • Urology

MBD: NRX101 for Suicidal Treatment Resistant Bipolar Depression (clinicaltrials.gov) - P2/3 | N=74 | Active, not recruiting | Sponsor: NeuroRx, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P2 ➔ P2/3 | Trial completion date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Sep 2023 ➔ Feb 2024

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

SBD-ASIB: NRX-101 for Maintenance of Remission From Severe Bipolar Depression in Patients With Suicidal Ideation (clinicaltrials.gov) - P3 | N=72 | Active, not recruiting | Sponsor: NeuroRx, Inc. | Trial completion date: Sep 2023 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

NRx Pharmaceuticals, Inc. (Nasdaq: NRXP) Announces FDA Qualified Infectious Disease Product (QIDP) and Fast Track Designation of NRX-101 in Complicated Urinary Tract Infection and Pyelonephritis (PRNewswire) - "NRx Pharmaceuticals, Inc...announced that it has received Qualified Infectious Disease Product (QIDP) and Fast Track designation from the US FDA for NRX-101 in the treatment of complicated urinary tract infections (cUTI) and pyelonephritis. Receipt of QIDP designation confers Priority Review, and critically, five additional years of data-exclusivity to NRX-101's already strong Intellectual Property position. The FDA also granted NRX-101 Fast Track designation for cUTI, which additionally allows for rolling submission of the Company's New Drug Application. In addition to the marketplace protections conferred by QIDP designation in the US, NRx has composition of matter patent protection on NRX-101 through at least 2033 in all major global markets. The data that formed the basis of FDA's QIDP approval have been submitted for publication."

Fast track designation • Infectious Disease

NRX-101 for Complicated Urinary Tract Infection (UTI) Including Pyelonephritis (clinicaltrials.gov) - P2 | N=13 | Not yet recruiting | Sponsor: NeuroRx, Inc.

New P2 trial • Infectious Disease • Nephrology

NRx Pharmaceuticals Announces Submission of an Investigational New Drug (IND) Application for NRX-101 in the Treatment of Chronic Pain (PRNewswire) - "NRx Pharmaceuticals, Inc...announced submission an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for the use of NRX-101 to treat Chronic Pain. The IND application leverages pioneering research on the use of D-cycloserine (a key ingredient of NRX-101) in the treatment of chronic pain and the recent licensure by NRx of a US Patent for the use of D-cycloserine in the treatment of pain."

IND • Immunology • Pain

NRX-101 (D-cycloserine plus lurasidone) vs. lurasidone for the maintenance of initial stabilization after ketamine in patients with severe bipolar depression with acute suicidal ideation and behavior: a randomized prospective phase 2 trial. (PubMed, Int J Bipolar Disord) - P2 | "Sequential treatment of a single infusion of ketamine followed by NRX-101 maintenance is a promising therapeutic approach for reducing depression and suicidal ideation in patients with bipolar depression who require hospitalization due to acute suicidal ideation and behavior. On the basis of these findings, Breakthrough Therapy Designation was awarded, and a Special Protocol Agreement was granted by the FDA for a registrational trial."

Journal • P2 data • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

New Pharmacologic Approaches to the Treatment of Bipolar Depression. (PubMed, Drugs) - "Included are new atypical anti-psychotics, glutamate modulators (ketamine and cycloserine/lurasidone), neurosteroid modulators (zuranolone), anti-inflammatories and mitochondrial modulators, cannabidiol (CBD) and psilocybin. New atypical anti-psychotics lumateperone and cariprazine have demonstrated efficacy in large-scale, placebo-controlled, double-blind randomized controlled trials (RCT) in treatment of BD depression...While there are potentially efficacious, mechanistically novel agents on the horizon, they require further study and validation. Further investigation on how these agents may impact specific subgroups of patients will also advance the field."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

NRx Pharmaceuticals, Lotus Pharmaceuticals and Alvogen Inc. Announce Collaboration to Develop and Commercialize NRX-101 (GlobeNewswire) - "Lotus Pharmaceuticals...Alvogen...and NRx Pharmaceuticals Inc..announced a global collaboration agreement covering the development and commercialization of NRX-101 for suicidal treatment-resistant bipolar depression (S-TRBD) for global markets. Under the terms of the agreement, relating to NRX-101 for the U.S. market, NRx is entitled to receive an initial payment of $10 million upon achieving both a successful read-out from the ongoing Phase 2b/3 clinical trial in S-TRB and completion of a Type B meeting with the USFDA. NRx would receive an additional payment of $5 million upon receipt of FDA approval for NRX-101 as well as bonus milestone payments of increasing amounts up to $330 million based on reaching certain net sales targets. In addition to success-based payments, NRx is eligible to receive a royalty on net sales between 12% and 16% contingent on certain sales thresholds for the U.S. market and other success-based payments for markets outside of the U.S."

Licensing / partnership • Bipolar Disorder • CNS Disorders

NRX-101, a Rapid-Acting Anti-Depressant, Does Not Cause Neurotoxicity Following Ketamine Administration in Preclinical Models. (PubMed, Int J Toxicol) - "Neuronal necrosis, as expected, was seen in the MK-801 (positive control) group. We conclude that NRX-101, a fixed-dose combination of DCS/lurasidone, when administered with or without prior infusion of IV ketamine was tolerated and did not induce neurotoxicity, even at supratherapeutic doses of DCS."

Journal • Preclinical • CNS Disorders • Depression • Psychiatry

MBD: NRX101 for Suicidal Treatment Resistant Bipolar Depression (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: NeuroRx, Inc. | Trial completion date: May 2023 ➔ Nov 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

NRX-101 EA: NRX-101 Expanded Access (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: NeuroRx, Inc.

New trial • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

MBD: NRX101 for Bipolar Depression and Sub-acute Suicidal Ideation and Behavior (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: NeuroRx, Inc. | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

SBD-ASIB: NRX-101 for Maintenance of Remission From Severe Bipolar Depression in Patients With Suicidal Ideation (clinicaltrials.gov) - P3 | N=72 | Active, not recruiting | Sponsor: NeuroRx, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P2/3 ➔ P3 | Trial completion date: Apr 2022 ➔ Sep 2023 | Trial primary completion date: Mar 2022 ➔ Jun 2023

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

NRX-GLX: NRX101 Glx Biomarker Validation Study (clinicaltrials.gov) - P2/3 | N=8 | Completed | Sponsor: NeuroRx, Inc. | Withdrawn ➔ Completed

Biomarker • Trial completion • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

NRX-GLX: NRX101 Glx Biomarker Validation Study (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: NeuroRx, Inc. | N=24 ➔ 0 | Trial completion date: Feb 2022 ➔ Aug 2022 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: Dec 2021 ➔ Apr 2022

Biomarker • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents. (PubMed, Front Pharmacol) - "Esketamine for treatment-resistant major depression and brexanolone for post-partum depression are two exceptions from the monoaminergic model, although their use is still limited by high costs, unique way of administration (only intravenously for brexanolone), physicians' reluctance to prescribe new drugs, and patients' reticence to use them. Glutamatergic neurotransmission is explored based on the positive results obtained by intranasal esketamine, with subanesthetic intravenous doses of ketamine, and D-cycloserine, traxoprodil, MK-0657, AXS-05, AVP-786, combinations of cycloserine and lurasidone, or dextromethorphan and quinidine, explored as therapeutic options for mono- or bipolar depression. Sestrin modulators, cholinergic receptor modulators, or onabotulinumtoxinA have also been investigated for potential antidepressant activity. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost 7 decades of..."

Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

MBD: NRX101 for Bipolar Depression and Sub-acute Suicidal Ideation and Behavior (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: NeuroRx, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation

MBD: NRX101 for Bipolar Depression and Sub-acute Suicidal Ideation and Behavior (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: NeuroRx, Inc. | Phase classification: P2/3 ➔ P2 | N=150 ➔ 70 | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Suicidal Ideation