Nrx Pharmaceuticals, Inc. · NASDAQ:NRXP
Nrx Pharmaceuticals — Investor Presentation (June 2023)
34 slides from Nrx Pharmaceuticals's investor presentation, June 2023
Slide 1: Hope. Science. Life.
Hope. NASDAQ: NRXP Science. Life. NRx Pharmaceuticals, Inc. Corporate Presentation June 2023
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 NRx Pharmaceuticals, Inc.
Slide 3: We Bring Hope to Life
OUR MISSION We Bring Hope to Life Breakthrough Medicines for Life-threatening CNS Diseases with unmet medical needs Our medicines are based on new molecular targets for suicidal depression and PTSD that are not addressed by major pharmaceutical companies. 3
Slide 4: Investment Thesis
INVESTMENT THESIS NRX-101: First drug to enter FDA trials for Suicidal Bipolar Depression (SBD) Positive Phase 2 data*; ongoing Phase 2b/3 trial - data expected in 2023 Partnership with Alvogen on first indication (suicidal bipolar depression/SBD) • Up to $330 million in milestones • Double digit ro
Slide 5: Target Opportunities for Our NMDA Antagonist Platform
Target Opportunities for Our NMDA Antagonist Platform Opportunities ranging from Acute to Chronic Use Suicidal Bipolar Treatment-resistant Suicidal Bipolar Depression: Depression 2% Unmet medical need, ongoing phase 2b/3 clinical trial. Granted Breakthrough Therapy designation. Non-suicidal Bipolar
Slide 6: Understanding the NMDA Receptor
Understanding the NMDA Receptor The NMDA receptor is an ION Channel on the surface of Brain Cells At high levels of NMDA activity (i.e. the channel is wide open) thoughts are slowed substantially, NRx-101 patients ruminate on negative, frequently suicidal thoughts. Brain cells stop making new connec
Slide 7: First Indication: Suicidal Bipolar Depression (partnered with Alvogen)
First Indication: Suicidal Bipolar Depression (partnered with Alvogen) Currently No Approved Drugs for Suicidal Bipolar Depression Suicide is attempted every 27 seconds in the US Suicide kills ~50,000 Americans annually, disproportionately affecting people with bipolar depression • If you know two p
Slide 8: Suicidal Bipolar Depression: The Only Approved Treatment is ECT
Suicidal Bipolar Depression: The Only Approved Treatment is ECT No Approved Medicine No Good Choices Antidepressants (SSRIs) can increase suicidality. Ketamine provides strong proof of concept for NMDA inhibition, but is known to be neurotoxic, addictive, hallucinogenic, and can only be administered
Slide 9: NRx NMDA Antagonist Platform Pipeline
NRx NMDA Antagonist Platform Pipeline: Multi-Billion Dollar Potential in Psychiatry and Chronic Pain Indication Compound Preclinical Phase 1 Phase 2 Phase 3 Status Suicidal Bipolar Depression Severe Bipolar Depression with Recently NRX-100™ / FDA SPA, Breakthrough Therapy, Biomarker letter of Integr
Slide 10: "Re-wiring the Brain," as shown in the laboratory
“Re-wiring the Brain,” as shown in the laboratory High levels of NMDA activity are shown to damage the “dendrite spines” that connect brain cells to each other Loss of dendrite spines is associated with depression-related behavior NMDA blockade with ketamine is demonstrated to restore lost dendrite
Slide 11: NMDA inhibition offers greater benefit in suicidal bipolar depression than MDD
NMDA inhibition is shown to offer substantially greater benefit in suicidal bipolar depression than in major depressive disorder Inpatient trial in 8 French Hospitals enrolling acutely suicidal patients Clinical benefit of ketamine in blocking suicidal ideation was 9x greater in bipolar depression t
Slide 12: The Patented NMDA Discovery: Simultaneous Blockade of NMDA and 5-HT2A
The Patented NMDA Discovery: 90 Patents & Patent Applications Globally NRX-101: Simultaneous Blockade of NMDA and 5-HT2A Blocks NMDA Side Effects DCS (D-Cycloserine) Lurasidone blocks side-effects of 5HT2A Blocks side-effects of NMDA Psychosis Akathisia 13
Slide 13: Robust Composition of Matter Patent Protection
Robust Composition of Matter Patent Protection Patent Estate of 48 issued and 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 potential for p
Slide 14: Initial Clinical Evidence of Efficacy in Resistant Depression
Initial Clinical Evidence of Efficacy in Resistant Depression Improved antidepressant and anti-suicidal effect of D-Cycloserine (DCS) when added to 5HT2A / SSRIs DCS significantly improved DCS significantly improved symptoms of patients with R-MDD symptoms in patients with S-TRBD Treatment Resistant
Slide 15: Phase 2 Success: STABIL-B trial of NRX-101 vs Lurasidone
Phase 2 Success: STABIL-B trial showed superiority of NRX-101 vs Lurasidone in reducing Depression (primary endpoint) Patients enrolled with severe depression (MADRS>30) and acute suicidality (C-SSRS 4/5) Patients received one infusion of IV ketamine vs. placebo. Responders were randomized to NRX-10
Slide 16: First Evidence of Reduced Suicidality with an Oral NMDA Antagonist
First Evidence of Reduced Suicidality with an Oral NMDA Antagonist (Secondary Endpoint) 1.5 point advantage on Columbia Suicide Severity Rating Scale (P=.02) 2.9 point advantage on Clinical Global Impression Suicidality Scale (P=.02) No SAEs in the NRX-101 treated group Need CGI graph 3 SAEs with 2
Slide 17: Effect of D-cycloserine in reducing suicidality shown in independent trial
Effect of D-cycloserine in reducing suicidality has been demonstrated in an independent trial Chen et. al. All Subjects (MDD and Bipolar) Bipolar Subgroup Treatment Resistant MDD + Bipolar Depression treated with D- cycloserine after two iv. Ketamine infusions 32 patients total – placebo controlled
Slide 18: Current Phase 2b/3 Trial for Suicidal Treatment-Resistant Bipolar Depression
Current Phase 2b/3 Trial for Suicidal Treatment-Resistant Bipolar Depression Patients who have symptoms of Severe Depression and Suicidal Ideation despite treatment with currently approved drugs 70 Patients 2x BID No pre-treatment with ketamine or other 42 Days stabilization is required NRX-101 Prim
Slide 19: Phase 2b/3 Trial Expansion: Rationale for Success
Phase 2b/3 Trial for Expansion to Suicidal Treatment-Resistant Bipolar Depression: Rationale for Success NDMA MOA well established in clinical trials 5-HT2A MOA well established in clinical trials STABIL-B demonstrated the combination to be safe and highly effective in Suicidal Bipolar Depression Tr
Slide 20: The DSMB recommended that enrollment in the trial continue
Phase 2b/3 Trial for Suicidal Treatment-Resistant Bipolar Depression The DSMB recommended that enrollment in the trial continue • The DSMB has reviewed unblinded interim data from the trial • The Board found no futility signal at this stage of the trial; the failure to identify futility requires tha
Slide 21: FDA Approval Roadmap (1): NDA in 2023
FDA Approval Roadmap – Integrated Phase 2b/3 for Suicidal Treatment- Resistant Bipolar Depression (1) Agreed upon path Given the guidance from FDA regarding a broader indication, the to submit company plans further discussion with FDA on this pathway in a rolling review Breakthrough Therapy Designat
Slide 22: FDA Approval Roadmap (2): NDA in 2023
FDA Approval Roadmap – Integrated Phase 2b/3 for Suicidal Treatment- Resistant Bipolar Depression (2) This pathway would potentially allow registration of NRX-101 for Suicidal Treatment-Resistant Bipolar Depression, regardless of the mechanism of stabilization. Agreed upon path This broader indicati
Slide 23: Commercial Partnership with Alvogen
Commercial Partnership with Alvogen • Alvogen, Alvogen US, Lotus Pharma: Outstanding Global Partnership • NRX-101 in Suicidal Bipolar Depression; right of first negotiation in other fields • Established global R&D, manufacturing and commercial operations • Almatica in the US: CNS focused division of
Slide 24: NRX-101: US Market Opportunity in Bipolar Depression
NRX-101: US Market Opportunity in Bipolar Depression Patients in clinics and outpatient being treated for Bipolar Depression with Suicidality Adults With Bipolar Disorder 7,000,000 9-10% Patients With Suicidality 680,000 26% 74% $2.2 Billion ACUTE 180,000 Subacute Suicidality 500,000 Market Potentia
Slide 25: Technology and Manufacturing Transfer to USA
Path to Commercial Manufacture Technology and Manufacturing Transfer to USA completed in Q2 2022 Phase 3 drug, produced using expected Commercial Scale manufacturing process, released in October 2022 with FDA Module 3 filing Potential for Commercial Sales of NRX-101 by 2024; 26
Slide 26: NRX-101 for Additional Indications (Unpartnered)
NMDA Antagonist Platform: NRX-101™ for Additional Indications (Unpartnered) • Post Traumatic Stress Disorder • Chronic Pain in Depression • Chronic/Intermittent Bipolar Depression (i.e. without suicidality) 27
Slide 27: NRX-101 for PTSD
NRX-101™ for PTSD Rationale for treating PTSD: Ketamine (despite its challenges and side effects) has shown therapeutic benefit – supports NMDA mechanism Nonclinical data shows that D-Cycloserine (DCS), the NMDA component of NRX-101, reduces Fear Memory Phase 2 – Proof of Concept trial of NRX-101 fo
Slide 28: No Approved Medicine for PTSD Symptoms
No Approved Medicine for PTSD Symptoms Only two approved SSRI’s for PTSD-related Depression Both carry black box suicide warnings and neither have an effect on Fear MemoryUnmet Need 9+ Million 10% Have Suicidality EFFICACY • Higher % responders SAFETY/ TOLERABILITY 1/3 With Severe >30K Veteran Death
Slide 29: Use of DCS in the Treatment of PTSD
Use of DCS in the Treatment of PTSD Patents were issued based on nonclinical behavioral studies in models of PTSD using DCS-induced Reduced Fear Memory DCS as the NMDA Component in WKY Rodent model of PTSD PTSD symptoms are not the same as depression and no SSRI antidepressant has demonstrated benef
Slide 30: NRX-101 for Chronic Pain
NRX-101™ for Chronic Pain Rationale for treating Chronic Pain: DCS at NMDA-antagonist doses has demonstrated attenuation of pain in preclinical models In a human dose escalation trial, in post-hoc analysis, DCS was shown to achieve a significant reduction in chronic back pain from baseline at 400 mg
Slide 31: 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
Slide 32: Scientific Advisory Board
Scientific Advisory Board Daniel Javitt, PhD, MD – Chair Professor of Psychiatry at Columbia University. Initial discovery on the role of NMDA antagonists in psychiatric disorders. More than 760 publications in the field. Inventor of the NRx patent portfolio Philip Lavin, PhD – Lead Methodologist NR
Slide 33: Looking Forward
Looking Forward Data readouts Revenue Demonstrated expected in the Totalability Shares NRx Cash in potential next 12 months; Outstanding: Position: 2024 to execute in triggers $10 CNS space million from $24.5 million as ~67 million Alvogen w FDA of 6/30/2022 shares as ofPhase 2 Phase 2b/3 notes 8/1/
Slide 34: Hope. Science. Life.
Hope. NASDAQ: NRXP Science. Life. NRx Pharmaceuticals, Inc. Corporate Presentation June 2023
NRx Pharmaceuticals — Investor Presentation (June 2023) on 6ix