NRx Pharmaceuticals to discuss new NRX-101 pipeline indication for augmentation of Transcranial Magnetic Stimulation

Rhea-AI Summary

NRx Pharmaceuticals (Nasdaq: NRXP) amended its Investigational New Drug filing for NRX-101 (D-cycloserine/lurasidone) to add use in combination with Transcranial Magnetic Stimulation (TMS) for treatment of depression, including suicidal depression, and will offer the protocol via clinical trial and Expanded Access.

Company holds >25,000 investigational doses, cites prior studies reporting 75% response/40% remission (Cole et al.) and real-world data with 87% response/72% remission at 6 weeks after a single-day TMS+DCS regimen, and says NRX-101 has composition-of-matter patents and Breakthrough Therapy designation.

Positive

• IND amended to include NRX-101 with TMS
• >25,000 manufactured investigational doses available
• Published studies report 75% response/40% remission with DCS+TMS
• Real-world data report 87% response/72% remission at 6 weeks
• NRX-101 has composition-of-matter patents in major jurisdictions
• Drug holds Breakthrough Therapy designation

Negative

• D-cycloserine has known low-grade hallucination risk and prior contraindication
• Efficacy must be replicated in registration trials (company cites ~120 participants)

Insights

Clinical-Regulatory & Commercial Strategist

NRx amended an IND to test NRX-101 with TMS, citing published and real-world signals that could speed registration if replicated.

NRX has expanded the NRX-101 indication to include use with Transcranial Magnetic Stimulation (TMS), and plans both clinical trial access and Expanded Access; the release cites published randomized data showing a clinical response of 75% and remission 40% with D-cycloserine plus TMS, plus real-world results reported Nov 4, 2025 with response 87% and remission 72%. The company reports over 25,000 manufactured investigational doses available, Breakthrough Therapy designation, and composition-of-matter patents for the NRX-101 combination (D-cycloserine + low-dose lurasidone).

The business mechanism is straightforward: pair a drug that may augment TMS-driven neuroplasticity with an already-approved, reimbursed device therapy to shorten path-to-market and broaden label-based use. Key dependencies include successful replication of the cited clinical signals under current regulatory standards, formal registration trial design (the company cites ~120 participants as a target), and any joint trial arrangements with TMS device manufacturers. Risks include the need to meet regulatory evidentiary standards in controlled registration trials and the safety balance around D-cycloserine's known low-rate hallucination signal, which NRX seeks to mitigate with low-dose lurasidone.

Concrete items to watch: initiation and design details of the planned registration trial (~120 participants), outcomes versus the published response/remission figures, any announced partnerships with TMS device manufacturers, and timing for potential labeling changes; expect these milestones over the typical clinical-registration timeframe (months to a few years depending on trial start and pace). The company’s existing inventory (>25,000 doses) and published Breakthrough status support near-term trial readiness and Expanded Access availability.

• As previously announced, low dose D-cycloserine has been associated with augmentation of the antidepressant and antisuicidal response achieved by Transcranial Magnetic Stimulation (TMS).
• NRx has amended its Investigational New Drug filing for NRX-101 (D-cycloserine/lurasidone) to include its use in association with TMS for the treatment of depression, including suicidal depression. This protocol will be available to patients both through a clinical trial and under NRx’s Expanded Access protocols.
• NRx currently has more than 25,000 manufactured investigational doses available
  

WILMINGTON, Del., Dec. 03, 2025 (GLOBE NEWSWIRE) -- NRx Pharmaceuticals, Inc. (Nasdaq: NRXP), a clinical-stage biopharmaceutical company, today announced that it has amended its Investigational New Drug filing for NRX-101 (D-cycloserine/lurasidone) to include the use of NRX-101 in association with Transcranial Magnetic Stimulation (TMS) for the treatment of depression, including suicidal depression.

In the third quarter, the Company identified a promising 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 (DCS) 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.²

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 (>80%) 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^® (D-cycloserine) 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.

Given current trends, the Company expects that more than 1 million Americans per year may be treated with TMS by the year 2030, creating a substantial new potential market for NRX-101 not previously anticipated. As required by law for Breakthrough Therapy drugs such as NRX-101, the Company has published an Expanded Access policy for this medication. Treating physicians who believe that their patients might benefit from NRX-101 in association with TMS may contact the Company for further information.

About NRx Pharmaceuticals, Inc.
NRx Pharmaceuticals, Inc. (www.nrxpharma.com), is a clinical-stage biopharmaceutical company developing therapeutics based on its NMDA platform for the treatment of central nervous system disorders, specifically suicidal depression, chronic pain, and PTSD. The Company is developing NRX-100 (preservative-free intravenous ketamine) and NRX-101, (oral D-cycloserine/lurasidone). NRX-100 has been awarded Fast Track Designation for the treatment of Suicidal ideation in Depression, including Bipolar Depression. NRX-101 has been awarded Breakthrough Therapy Designation for the treatment of suicidal bipolar depression. NRx has recently re-filed an Abbreviated New Drug Application (ANDA), and initiated a New Drug Application filing for NRX-100 with an application for the Commissioner’s National Priority Voucher Program for the treatment of suicidal ideation in patients with depression, including bipolar depression.

Notice Regarding Forward-Looking Statements
The information contained herein includes forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "plan," "believe," "intend," "look forward," and other similar expressions among others. These statements relate to future events or to the Company's future financial performance, and involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. The Company has reported regulatory milestones as they have been achieved but has not predicted the outcome of any future regulatory determination. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. Any forward-looking statement reflects the Company's current views with respect to future events and is subject to these and other risks, including uncertainties and assumptions relating to the Company's operations, results of operations, growth strategy, and, among other things, liquidity. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's most recent Annual Report on Form 10-K and other filings with the Securities and Exchange Commission. Investors and security holders are urged to read these documents free of charge on the SEC's website at http://www.sec.gov. Except as may be required by applicable law, the Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, whether as a result of new information, future events or otherwise.

For further information:

Matthew Duffy		Brian Korb
Chief Business Officer, NRx		Managing Partner, astr partners
(646) 335-5923		(917) 653-5122
mduffy@nrxpharma.com		brian.korb@astrpartners.com

¹ Cole J, et.al. Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022;79(12):1153–1161. doi:10.1001/jamapsychiatry.2022.3255
² Vaughn, Donald & Marino, Brooke & Engelbertson, Alex & Dojnov, Aleksandra & Weiss, Nick & Vila-Rodriguez, Fidel & Nanos, Georgine & Downar, Jonathan. (2024). Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplastogen-Enhanced techniques in Depression (ONE-D). 10.21203/rs.3.rs-5679327/v1.

FAQ

What did NRx (NRXP) announce on December 3, 2025 about NRX-101 and TMS?

NRx announced it amended the NRX-101 IND to include use with TMS for depression, including suicidal depression, and will offer treatment in trials and Expanded Access.

How many NRX-101 investigational doses does NRx (NRXP) currently have available?

The company stated it currently has more than 25,000 manufactured investigational doses available.

What clinical response rates were reported for D-cycloserine plus TMS cited by NRx (NRXP)?

The cited studies reported a 75% clinical response and 40% remission in one trial and 87% response and 72% remission in real-world data at 6 weeks.

Will NRX-101 be available outside clinical trials under NRXP's plan?

Yes; the company said the protocol will be available both through a clinical trial and under its Expanded Access policy.

Does NRX-101 include other drugs besides D-cycloserine in NRXP's regimen?

Yes; NRX-101 combines low-dose lurasidone with D-cycloserine and the company cites patent protection for the combination.

What further evidence does NRx (NRXP) say is needed for NRX-101 with TMS to become standard of care?

The company said the findings must be replicated in registration trials conducted to current regulatory standards, estimating trials of about 120 participants.