NRx Pharmaceuticals amends IND filing for NRX-101 to include use for TMS

NRx Pharmaceuticals (NRXP) amended its Investigational New Drug filing for NRX-101 to include the use of NRX-101 in association with Transcranial Magnetic Stimulation for the treatment of depression, including suicidal depression. In the third quarter, the Company identified a new indication for NRX-101 that potentially offers rapid path to commercialization for this Breakthrough Therapy-designated drug. Recent evidence suggests that NRX-101 may confer a significant added advantage to the clinical results of Transcranial Magnetic Stimulation. Cole and colleagues reported that patients randomized to D-cycloserine vs. Placebo concurrent with TMS using a standard protocol experienced a greater than two-fold benefit in terms of reduction in symptoms of depression. Clinical response of 75% and remission of 40% was seen in the DCS-treated group.1 A substantial body of nonclinical literature has been published in subsequent years demonstrating that DCS at low doses exerts a neuroplasticity effect and causes dendritic sprouting in areas of the brain associated with depression. On November 4, 2025, Real World Data were presented in conjunction with use of a modern Theta Burst FDA-cleared TMS device and a one day TMS protocol, combined with a single administration of oral DCS. The authors reported 87% clinical response and 72% remission manifesting at 6 weeks after a single day of treatment on the Hamilton Depression Rating Scale with similar findings on other standard test measures. Nonclinical evidence suggests that D-cycloserine acts to augment neuroplasticity in association with TMS. Should the findings of these two clinical studies be replicated in registration trials conducted to current regulatory standards, the Company anticipates D-cycloserine or similar medicines will become standard of care therapy in association with TMS. The response rate from TMS with cycloserine in these two studies compares favorably to the 30% success rate now reported in association with SSRI antidepressants, without the well known side effects of SSRI medications. In addition to containing D-cycloserine, NRX-101 contains a low dose of lurasidone, a medicine already approved for treatment of depression and known to have anti-hallucinatory properties. D-cycloserine by itself is well known to have a low, but measurable potential for inducing low-grade hallucinations, resulting in a labeled contraindication against the use of Seromycin in patients with depression. This contraindication originally led the founders of NRx to develop and patent the NRX-101 drug combination, which has now obtained composition of matter patent protection in all major jurisdictions. NRx believes that the clinical benefit demonstrated in these two published trials can be demonstrated in a well-controlled trials of approximately 120 participants. The Company is in partnership discussion with manufacturers of currently-marketed TMS devices to configure a joint clinical trial that will lead to drug registration and augmentation of FDA labeling of currently-approved TMS devices. Because TMS is already an approved and reimbursed therapy for patients with depression, the Company anticipates that such trials can be accomplished at modest expense.