NRX Pharmaceuticals, Inc. · NASDAQ:NRXP

NRX Pharmaceuticals — Investor Presentation (July 2024)

51 slides from NRX Pharmaceuticals's investor presentation, July 2024

  1. Slide 1: Hope Science Life

    Hope Science Life NASDAQ: NRXP July 2024 © NRx - All rights reserved |

  2. Slide 2: Safe Harbor Statement

    Safe Harbor Statement This presentation (this “Presentation”) is provided for informational purposes only. No representations or warranties, express or implied are given in, or in respect of, this Presentation. To the fullest extent permitted by law in no circumstances will Hope Therapeutics, Inc. (

  3. Slide 3: Recent clinical developments enable FDA filing in 2024

    Hope Recent clinical developments enable FDA filing in Science 2024 with Potential for 2025 Commercial Revenue Life NASDAQ: NRXP o New Drug Application planned for NRX-100 (IV Ketamine) in Suicidal Depression Potential for $100 million+ revenue in 2025 with peak in excess of $1 billion o Accelerated

  4. Slide 4: NRx Clinical Programs – 2024/25 Upside Potential

    NRx Clinical Programs – 2024/25 Upside Potential NRX-100 NRX-101 HOPE (Ketamine) (DCS/Lurasidone) Therapeutics Interventional Psychiatry • Fast Track NDA filing • Statistically-significant Bipolar Depression • NRXP: spin out to be Suicidal Depression in 2H24 Phase 2 data: first majority owned; • App

  5. Slide 5: Suicidality is a National Crisis

    Suicidality is a National Crisis Suicidality kills ~50,000 Americans every year Disproportionately affecting people with Bipolar Disorder Suicidality takes our best and brightest https://www.cdc.gov/suicide/facts/index.html#:~:text=In%202021%2C%20an%20estimated%2012.3,and %201.7%20million%20attempte

  6. Slide 6: If you know two people with bipolar depression

    If you know two peopleNRX-101 for PTSD with bipolar depression One will attempt suicide 50,000 Americans die of suicide each year 22 Veterans and Soldiers die of suicide every day Loss of more troops to suicide than to contact with the enemy No antidepressant today If you know five people reduces th

  7. Slide 7: Potential to Reach 75 Million Lives

    Potential to Reach 75 Million Lives Suicidal Bipolar Depression Depression Chronic Pain PTSD Complex UTI 3.5 M 7M 51 M2 12 M3 3M • 1 M Bipolar1 • 1 M Suicidal Global Opioid Currently 2 90% of organisms • 2.5 M Other Depression1 Crisis indicated SSRI are resistant to forms of • 6 M Non- Congressional

  8. Slide 8: Our Pipeline

    Our Pipeline Leveraging our Multi-Billion Dollar NMDA Platform Product Phase 1 Phase 2 Phase 3 NDA Status Suicidal Depression HTX-100 (IV Ketamine) Suicidal Depression NDA Filing 2H24 | PDUFA est. 2025 *Collaboration Agreement with Study Leadership of two well-powered, academic clinical trials NRX-1

  9. Slide 9: NRX-100 (IV Ketamine) for Suicidal Depression

    NRX-100 (IV Ketamine) for Suicidal Depression © Hope 2024 - All rights reserved 9

  10. Slide 10: No FDA-Approved Medication Today for Acute Suicidality

    NRX-100 (IV Ketamine) No FDA-Approved Medication Today for Acute Suicidality Only FDA-approved therapy is IV Ketamine is used off-label Electro-Convulsive Therapy (ECT) But not FDA-approved Intranasal Ketamine (Spravato) is approved but majority practice remains IV Ketamine Recent panels at psychiat

  11. Slide 11: Why is IV Ketamine not approved for depression?

    Everyone is calling for approval of Ketamine Why is IV Ketamine not approved for depression? 1 No Company has applied for FDA approval of Ketamine to treat depression In order to seek drug approval, you need a manufactured drug in hand 2 (NRx has manufactured drug in hand) 3 In order to seek drug ap

  12. Slide 12: Growing Public Demand for an Approved IV Ketamine

    Growing Public Demand for an Approved IV Ketamine to treat Depression (off-label use of the current anesthesia-labeled version is not insurance reimbursable) © NRx - All rights reserved | © NRx 2024 - All rights reserved | 12

  13. Slide 13: NRx Has Safety and Efficacy Data to Support a Filing

    NRx Has Safety and Efficacy Data to Support a Filing 1 NIH-funded Ketamine dose-ranging trial establishing 0.5 mg/kg dose 2 French government-funded trial of 156 patients in 7 hospitals (P<.0001 on 1° endpoint) 3 NIH-funded Columbia University trial in 80 patients (P<.015 on 1° endpoint) 4 PCORI tri

  14. Slide 14: Overwhelming Efficacy in Three Well-Controlled Trials (1)

    Overwhelming Efficacy in Three Well-Controlled Trials (1) Abbar Study, funded by Gov’t of France and the Fondation Fondamental • 156 Patients, 7 Hospitals • Admitted with acute suicidality Ketamine vs Placebo in All Patients (n=156) • Randomized to Ketamine vs. Placebo 5 CSSRS Suicidal Ideation Scor

  15. Slide 15: Overwhelming Efficacy in Two Well-Controlled Trials (2)

    Overwhelming Efficacy in Two Well-Controlled Trials (2) Grunebaum (Columbia University), single center trial, N=80. Ketamine vs. Midazolam (effect size 0.76, P=.0015) • Initial Randomization to Ketamine vs. midazolam • Midazolam failures treated with open-label Ketamine • Note that open label Ketami

  16. Slide 16: Ketamine has advantages over ECT in treating depression

    Ketamine has advantages over ECT in treating depression Anand (Harvard Mass General), multi-center non-inferiority trial, N=420. Ketamine vs. ECT (14% superior, P=.001 for non-inferiority) 3 weeks of treatment: Ketamine 2x/week vs. ECT 3x/week • Superiority favoring Ketamine P=.007 (study designed f

  17. Slide 17: Broad Support within the Psychiatry Community

    Broad Support within the Psychiatry Community Viewpoint Viewpoint October 25, 2023 January 3, 2024 Choosing Between Ketamine and The Rapidly Shifting Ketamine Electroconvulsive Therapy for Landscape in the US Outpatients With Treatment-Resistant Depression—Advantage Ketamine? Sanjay J. Mathew, MD; M

  18. Slide 18: NRx Has Toxicity and Manufacturing Data in Support of NDA

    NRx Has Toxicity and Manufacturing Data in Support of NDA 1 NRx aligned with FDA on neurotoxicity protocol in 2016 – Data were accepted 2 2023: NRx implemented formulation of preservative-free Ketamine 3 2023: First stability batch in BFS (no glass) with modern container closure 4 2024: Initial manu

  19. Slide 19: Why Should Anyone Care about Preservative-Free Ketamine

    Why Should Anyone Care about Preservative-Free Ketamine Benzethonium Chloride is good for killing germs, not for treating patients • From the manufacturer’s data sheet • The current formulation of Ketamine (formulated in the 1960s) contains a preservative whose toxicity is now well-known. The preser

  20. Slide 20: NRX-100 Value Proposition

    NRX-100 Value Proposition 1 An approval of IV Ketamine depression yields FDA exclusivity for 3 years 2 Approval yields Reimbursement for approved indication(s) 3 Provide REMS (Risk Evaluation and Management Strategy) & support to prescribers Subsequent development of pH neutral Ketamine formulation

  21. Slide 21: NRX-101 for Bipolar Depression with suicidality or akathisia

    NRX-101 (Oral D-cycloserine/lurasidone) for Bipolar Depression with suicidality or akathisia the First Antidepressant to demonstrate reduced akathisia and suicidality In multiple clinical trials © Hope 2024 - All rights reserved 21

  22. Slide 22: NRX-101: Oral medication with potential for 2025 NDA filing

    NRX-101: Oral medication with potential for 2025 NDA filing First oral antidepressant shown to reduce Suicidality & Akathisia Current efficacy and safety data support filing an NDA for Accelerated Approval 1 in the narrow indication of patients with suicidal bipolar depression and akathisia 2 Market

  23. Slide 23: Akathisia occurs in up to 15% of patients on antidepressants

    Akathisia occurs in up to 15% of patients on antidepressants Akathisia is the side effect of antidepressants most closely linked to suicide • Stewart Dolin was a successful and well-liked partner at Reed Smith in Chicago. He developed an episode of depression and was treated with Paxil. That night,

  24. Slide 24: All Antidepressants Carry Black-Box Warnings for Suicidality and Akathisia

    All Antidepressants Carry Black-Box Warnings for Suicidality and Akathisia no antidepressant has ever improved either side effect © NRx 2024 - All rights reserved | 24

  25. Slide 25: NRX-101: the Patented NRx Discovery validated by 3 clinical trials

    NRX-101 (D-cycloserine & Lurasidone): the Patented NRx Discovery now validated by 3 clinical trials • Simultaneous Blockade of NMDA and 5-HT2A Blocks Known Side Effects • 90+ patents and patent applications globally - 48 Issued • Composition of matter patent issued on synergy of inhibition of NMDA a

  26. Slide 26: NRX-101 demonstrates reduced Akathisia and Time to Suicidality Remission

    NRX-101 demonstrates reduced Akathisia and Time to Suicidality Remission in Suicidal Bipolar Depression: No Ketamine Pre-treatment Phase 2b/3, randomized, double blind trial on NRX-101 vs Standard of Care (lurasidone) in Suicidal Treatment Resistant Bipolar Depression (n=93) Akathisia Rating by Stud

  27. Slide 27: Prior Phase 2 Success (2018): STABIL-B trial

    Prior Phase 2 Success (2018): STABIL-B trial Showed Superiority of NRX-101 vs Lurasidone in Reducing Depression (primary endpoint) after Ketamine Pre-treatment Patients received one infusion of IV Ketamine vs. placebo. Responders were randomized to NRX-101 vs lurasidone, a Standard of Care • Mean 7.

  28. Slide 28: Prior Phase 2 Confirmation (2019): Chen, et. al.

    Prior Phase 2 Confirmation (2019): Chen, et. al. Showed Reduction in Suicidality vs Placebo with DCS after Ketamine Pre-treatment (p<0.05) Patients with Treatment Resistant Depression (n=32, MDD & Bipolar) who responded to IV Ketamine enrolled • DCS was superior to placebo in HAMD item 3 (suicide),

  29. Slide 29: Potential Product Profile of NRX-101 in Suicidal Bipolar Depression

    Potential Product Profile of NRX-101 in Suicidal Bipolar Depression • NRX-101 reduces depression scores by ~50% -- similar to SoC • NRX-101 is the only drug to demonstrate clinically meaningful reduction in akathisia and suicidality vs SoC  We believe an antidepressant with this profile can become

  30. Slide 30: Potential for NRX-101 in Bipolar Depression

    Potential for NRX-101 in Bipolar Depression Bipolar Depression Patients - US 7,000,000 Market @3,000/pt $ 21,000,000,000 Market @7,500/pt $ 52,500,000,000 Revenue @$3,000/pt & 10% share $ 2,100,000,000 © NRx 2024 - All rights reserved | 30

  31. Slide 31: NRX-101: Robust Composition of Matter Patent Protection

    NRX-101: Robust Composition of Matter Patent Protection Patent Estate of 48 issued, 43 pending patents Enables a platform of CNS drugs based on NMDA / 5HT2A Synergy. • Five patent families, 90+ filed applications, 48 issued patents in US/EU/CN/JP/KR/AU. • Protects NRX-101 to at least 2033 with poten

  32. Slide 32: NRX-101: Commercial-Ready Manufacture

    NRX-101: Commercial-Ready Manufacture • GMP manufacturing initiated in the US in 2022 • Phase 3 drug, produced using expected Commercial Scale manufacturing process. • FDA Type C manufacturing meeting conducted in January 2022 with concurrence on CMC, stability, and etc. • 1 million phase 3 / commer

  33. Slide 33: But the recent trial did not meet its primary endpoint…

    Commonly heard “But the recent trial did not meet its primary endpoint…” • The trial did not demonstrate a superior antidepressant effect vs. a leading antidepressant (i.e. the declared primary efficacy endpoint) • The trial did meet both primary (suicidality) and secondary (akathisia) pre-declared

  34. Slide 34: © NRx 2024 - All rights reserved

    © NRx 2024 - All rights reserved | 34

  35. Slide 35: Path to 2024 Accelerated Approval filing for NRX-101

    Path to 2024 Accelerated Approval filing for NRX-101 in Patients with Bipolar Depression and Suicidality or Akathisia • For long term approval, NRX-101 will require an additional clinical trial vs. placebo in future years for broad, first line indication. Beating placebo is highly likely, given that

  36. Slide 36: HOPE Therapeutics: Why Spin Out a Separate Company?

    HOPE Therapeutics: Why Spin Out a Separate Company? Expected 2025 profitability NRx is a Biotechnology company focused on Research and Development 1 HOPE is a Care Delivery company focused on Ketamine and digital therapeutics 2 Acquisition of revenue generating Ketamine/interventional psychiatry cli

  37. Slide 37: HOPE Therapeutics

    HOPE Therapeutics A Ketamine-focused interventional psychiatry initiative © Hope 2024 - All rights reserved 37

  38. Slide 38: Hope Therapeutics Near-Term Investor Highlights

    Hope Therapeutics Near-Term Investor Highlights (note that acquisition financing is anticipated to be non-dilutive to NRXP shareholders) • Acquisition and management of ~30 Ketamine clinics in coming 24 months • Target $45 million/yr run-rate • HOPE Solutions – Comprehensive practice acceleration pr

  39. Slide 39: HOPE: Proprietary Digital Therapeutic

    HOPE: Proprietary Digital Therapeutic 1 The pharmacologic effect of Ketamine lasts for < 1 week 2 Patients need ongoing support and Cognitive Behavioral Therapy is insufficient Research sponsored by DARPA demonstrates measurable benefit of Digital 3 Therapeutic approach in reducing physiologic measu

  40. Slide 40: Example of Digital Therapeutic Use in US Navy Personnel

    Example of Digital Therapeutic Use in US Navy Personnel Methodology: � 71 personnel from US Navy Coastal and Riverine Expeditionary Group and Squadron � 8-week Digital Therapeutic Use compared to Control � Measures are Perceived Stress Scale, Patient Health Questionnaire and Usage Report 18 Control

  41. Slide 41: Hope Therapeutics Near-Term Benefits to NRXP

    Hope Therapeutics Near-Term Benefits to NRXP • NRXP to be majority shareholder after distribution additional investors would dilute HOPE, but not NRXP • Target $45 million/yr run-rate • Opportunity Zone (tax-advantaged investment) focus • HOPE is an asset - adds to the NRXP Balance Sheet • Increases

  42. Slide 42: Leadership Team

    Leadership Team Jonathan Javitt, MD, MPH – Founder & Chief Scientist Stephen Willard, JD – CEO & Director 40 years in pharmaceutical and medical device development. 30+ years of management of publicly traded biotechnology Blockbuster drug and device development programs with Allergan, companies. Ser

  43. Slide 43: NRx Scientific Advisory Board

    NRx Scientific Advisory Board Daniel Javitt, PhD, MD Vania Apkarian, PhD Professor of Psychiatry at Columbia University. Initial Professor of Physiology, Anesthesia, Surgery, and Neuroscience discovery on the role of NMDA antagonists in Institute, Northwestern University Feinberg School of Medicine.

  44. Slide 44: NRX-101 Additional Indications

    NRX-101 Additional Indications (no revenue projection prior to 2026) © NRx 2024 - All rights reserved | 44

  45. Slide 45: NRX-101: Why Chronic Pain?

    NRX-101: Why Chronic Pain? A Global Opioid Crisis and No New Drug Class in Decades Chronic Pain is at the heart of the Opioid Crisis with almost nothing on the horizon Congress is investing in new non-opioid treatments for Chronic Pain through 1. DOD Congressionally Directed Medical Research Program

  46. Slide 46: The NMDA Receptor is integral to Pain Signaling

    The NMDA Receptor is integral to Pain Signaling An NMDA antagonist mPFC can modulate pain signaling at each step Within the medial prefrontal cortex (mPFC), the NMDA receptor facilitates pain remembrance Thalamus 1 2 3 4 Pain perception Pain transmission Pain recognition Pain memory NMDA receptors h

  47. Slide 47: First Clinical Evidence of DCS effect on Chronic Pain

    First Clinical Evidence of DCS effect on Chronic Pain In an independent research study conducted at Northwestern University, 400 mg/day dosing of DCS was shown to achieve a significant reduction in chronic back pain from baseline Back pain intensity ratings over a six-week, dose escalating, placebo

  48. Slide 48: Confirmatory 200 person Trial Complete: NRX-101 IND Open

    Confirmatory 200 person Trial Complete: NRX-101 IND Open Data Release Pending • Five year $4.9 million trial funded by US Department of Defense • DCS vs. placebo at 400mg/day • Trial completed • Awaiting study results NRx research demonstrates a 25µg/ml dose at which DCS becomes an NMDA antagonist •

  49. Slide 49: Complicated UTI Affects 3 Million Lives each year

    Complicated UTI Affects 3 Million Lives each year More than 15,000 Lives Lost per Year - Antibiotics we’ve relied on for decades often fail • Congress established the Qualified Infectious Disease Product (QIDP) Program to reward innovation against resistant pathogens that underlie the crisis1 • Demo

  50. Slide 50: NRX-101 For Complicated UTI

    NRX-101 For Complicated UTI An old drug for a new problem DCS is uniquely concentrated in the urine and can address patients who otherwise require advanced and toxic Intravenous antibiotics © NRx 2024 - All rights reserved | 50

  51. Slide 51: Award of QIDP and Fast Track Designations

    Award of QIDP and Fast Track Designations © NRx 2024 - All rights reserved | 51

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