Slide 1: Targeting Major Advances in Treatment of CNS Disorders
Targeting Major Advances in Treatment of CNS Disorders March 7, 2022 I Nasdaq: RLMD 1
Slide 2: Disclosures
Disclosures Certain statements contained in this presentation or in other documents of Relmada Therapeutics, Inc. (the “Company”), along with certain statements that may be made by management of the Company orally in presenting this material, may contain “forward - lookin g statements.” These statem
Slide 3: Investment Highlights
Investment Highlights Highly Compelling Opportunity in REL - 1017 Multiple Catalysts Expected Over Next 18 Months CNS Focus with Lead Program in Major Depressive Disorder (MDD) CNS= Central Nervous System **Our fiscal year end is December 31. The periods referred to in this slide are calendar years
Slide 4: Major Depressive Disorder
Major Depressive Disorder & REL - 1017
Slide 5: Prevalence of Depression
Prevalence of Depression ~ 10M • 50% of patients in the US experiencing a major depressive episode in the last year received medication treatment 1 • 40% require combination Rx 2 ~ 19 . 3M • Individual adults in the US had at least one major depressive episode in 2019 1 > 280M from depression, globa
Slide 6: Limitations of Current Treatments for MDD
Limitations of Current Treatments for MDD ~65% MDD patients do not respond to first antidepressant treatment 1 Standard antidepressants, even when effective, may take up to 8 weeks to reach efficacy 1 MDD = major depressive disorder 1. Trivedi MH, et al. Am J Psychiatry. 2006;163:28 - 40; 2. Ashton
Slide 7: Unique Profile of Potential as a rapid, oral, once-daily antidepressant for MDD
Unique Profile of REL - 1017 7 Potential as a rapid, oral, once - daily antidepressant for MDD, if approved REL - 1017 * CH 3 CH 3 CH 3 O N 3 H C • Orally administered, once - daily tablet MDD = major depressive disorder; NMDAR = N - methyl - D - aspartate receptor *Diagram reflects chemical structu
Slide 8: Phase 2 Efficacy & Safety Data
REL - 1017 Ph 1 & 2 Efficacy & Safety Data
Slide 9: Phase 1 SAD & MAD Studies, Data Published 2019
Phase 1 SAD & MAD Studies for REL - 1017, Data Published 2019 PK = pharmacokinetics; PD = pharmacodynamics; MTD: =maximum tolerated dose; C max = maximum plasma concentration ; AUC 0 - inf = area under the curve 0 to infinite time; AUC t = area under the curve to the end of dosing period; N = number
Slide 10: Phase 2 Study: Primary Efficacy Endpoint MADRS change vs. placebo
Phase 2 Study REL - 1017: Primary Efficacy Endpoint 10 REL - 1017 showed rapid and sustained differences in MADRS change vs. placebo D a y 2 D a y 4 D a y 7 D a y 14 5 0 - 5 - 25 Least - Square Mean Change in MADRS - 15 - 20 P=0.0103; d=0.9 P=0.0039; d=1.0 P=0.0308; d=0.7 P=0.0122; d=0.8 P=0.0096; d
Slide 11: Phase 2 Study Efficacy: Response & Remission
REL - 1017 Phase 2 Study Efficacy: Response & Remission % of Subjects Achieving Remission (MADRS ≤10) Percent Subjects per ITT Group % of Subjects Achieving Response (≥ 50% MADRS Improvement from Baseline) 11 Day 14: last efficacy assessment, 7 days after last dose of study drug MADRS=Montgomery - A
Slide 12: Safety & Tolerability Findings from Phase 2
Safety & Tolerability Findings from Phase 2 Safety & Tolerability Comparable to Placebo • Only Mild and Moderate transient AEs – no SAEs • No increased prevalence of specifically relevant organ group AEs in treatment groups vs placebo • No evidence of opiate effects or withdrawal symptoms in treatme
Slide 13: Phase 2 Study Safety: Treatment Emergent Adverse Events
REL - 1017 Phase 2 Study Safety: Treatment Emergent Adverse Events Treatment - emergent adverse events by preferred term in patients with MDD in the safety analysis set * Variable Placebo (N = 23) REL - 1017 25 mg (N=19) REL - 1017 50 mg (N=21) All Patients (N = 62) N % N % N % N % Patients with a s
Slide 14: Human Abuse Potential (HAP) Studies: vs. Oxycodone vs. Ketamine
Human Abuse Potential (HAP) Studies: REL - 1017 vs. Oxycodone REL - 1017 vs. Ketamine
Slide 15: Human Abuse Potential (HAP) Studies
Human Abuse Potential (HAP) Studies of REL - 1017 15 HAP Studies, per FDA’s Guidance for Industry 1 : The HAP Program for REL - 1017 includes two studies: • Mu Opioid Agonist HAP • Oxycodone as active control • Completed in July 2021 • N M D A R ecep t o r A n t agon i st H AP • Ketamine as active c
Slide 16: Primary Endpoint – Drug Liking vs. Oxycodone, Completer Population
Primary Endpoint – “Drug Liking at This Moment” [Emax] REL - 1017 vs. Oxycodone, Completer Population* Statistic Parameter Placebo REL - 1017 25 mg REL - 1017 75 mg REL - 1017 150 mg O x y c odone 40 mg n 47 47 47 47 47 Mean 52.7 54.2 58.7 64.9 83.2 Median 50 50 50 58 85 SD 6.52 10.35 15.82 16.58 16
Slide 17: Primary Endpoint – Drug Liking vs. Oxycodone, Statistical Analysis
Primary Endpoint – “Drug Liking at This Moment” [Emax] REL - 1017 vs. Oxycodone, Completer Population* Treatment 1 Treatment 2 P - value Oxycodone 40 mg Placebo <0.001 Oxycodone 40 mg REL - 1017 25 mg <0.001 Oxycodone 40 mg REL - 1017 75 mg <0.001 Oxycodone 40 mg REL - 1017 150 mg <0.001 Statistical
Slide 18: HAP Studies vs. Oxycodone Primary Endpoint Summary
Human Abuse Potential (HAP) Studies of REL - 1017 vs. Oxycodone Primary endpoint, Drug Liking (Emax) Completer Population* • All REL - 1017 doses including 150 mg (6x therapeutic dose and MTD) were statistically different from oxycodone 40 mg (p<0.05) • All REL - 1017 doses including 150 mg (6x ther
Slide 19: Primary Endpoint – Drug Liking vs. IV Ketamine, Completer Population
Primary Endpoint – “Drug Liking at This Moment” [Emax] REL - 1017 vs. IV Ketamine, Completer Population Statistic Pa r ame t er Placebo REL - 1017 25 mg REL - 1017 75 mg REL - 1017 150 mg D ex t r o m e t ho r ph a n 300 mg Ketamine 0.5mg/Kg n 51 51 51 51 51 51 Mean 50.9 51.4 54.9 59.2 68.4 90 Media
Slide 20: Primary Endpoint – Drug Liking vs. IV Ketamine, Statistical Analysis
Primary Endpoint – “Drug Liking at This Moment” [Emax] REL - 1017 vs. IV Ketamine, Completer Population Treatment 1 Treatment 2 P - value Ketamine 0.5 mg/ Kg Placebo <0.001 Ketamine 0.5 mg/ Kg REL - 1017 25 mg <0.001 Ketamine 0.5 mg/ Kg REL - 1017 75 mg <0.001 Ketamine 0.5 mg/ Kg REL - 1017 150 mg <
Slide 21: HAP Studies vs. IV Ketamine Primary Endpoint Summary
Human Abuse Potential (HAP) Studies of REL - 1017 vs. IV Ketamine, Primary endpoint, Drug Liking (Emax) Completer Population* • All REL - 1017 doses including 150 mg (6x therapeutic dose and MTD) were statistically different from IV ketamine 0.5 mg/Kg (p<0.05) • All REL - 1017 doses including 150 mg
Slide 22: Exploratory Endpoint – Drug Liking Dextromethorphan, Statistical Analysis
Exploratory Endpoint – “Drug Liking at This Moment” [Emax] Dextromethorphan, Completer Population Treatment 1 Treatment 2 P - value Dextromethorphan 300 mg Placebo 0.001 Statistical Analysis SD = Standard Deviation; SE = Standard Error; IV = intravenous Source: Relmada data on file. 22 Dextromethorp
Slide 23: Exploratory Endpoint – Drug Liking Dextromethorphan Summary
Exploratory Endpoint – “Drug Liking at This Moment” [Emax] Dextromethorphan, Completer Population • Emax for “drug liking at this moment” for dextromethorphan 300 mg was statistically lower compared to ketamine (p<0.05) • Emax for “drug liking at this moment” for dextromethorphan 300 mg was statisti
Slide 24: Results of two human abuse potential studies support the DEA statement
The results of these two human abuse potential studies support the DEA statement below: 24 “ The d - isomer lacks significant respiratory depressant action and addiction liability.. .” US Drug E n f or c e m ent A d mi n i s t ra t i on December 2019 1 1.US DEA Statement on Methadone, December 2019
Slide 25: RELIANCE: The Phase 3 Program
RELIANCE: The Phase 3 Program for REL - 1017
Slide 26: Phase 3 Program for the Treatment of MDD
REL - 1017 Phase 3 Program for the Treatment of MDD 26 Two sister two - arm, placebo - controlled pivotal studies as adjunctive treatment for MDD: • In MD D pat i e n ts w i th i nade qua te r e s pon s e to 1 - 3 A D T (n= ~364 per study) • Primary Endpoint: Change in MADRS at Day 28 • Key Secondar
Slide 27: Pivotal Phase 3 Trial Design for Adjunctive Therapy
Screening confirms MDE with inadequate response to 1 - 3 ADT ADT + 25 mg REL - 1017 ADT + Matching Placebo Pivotal Phase 3 Trial Design for Adjunctive Therapy 27 1:1 randomization (n= ~364) 28 Days of Dosing (QD) Follow - Up Assessments & RELIANCE - OLS SAFER Interview* D 1 Start Do s i ng D 4 D 7 D
Slide 28: Pivotal Phase 3 Trial Design for Monotherapy
Screening confirms ≤ 1 prior use of ADT for current MDE 25 mg REL - 1017 Matching Placebo Pivotal Phase 3 Trial Design for Monotherapy 28 Primary Endpoint: • Change in MADRS at Day 28 Key Secondary Endpoints: • Change from baseline in CGI - S score at Day 28 • Change from baseline in MADRS score at
Slide 29: Relmada Development Programs & Timeline
Relmada Development Programs & Timeline* 29 MDD = Major Depressive Disorder; OLS = Open Label Study *Subject to FDA feedback **Our fiscal year end is December 31. The periods referred to in this slide are calendar years and quarters Pr og ram 4Q 21 1Q 22 2Q 22 3Q 22 4Q 22 REL - 1017 RELIANCE I: 1st
Slide 30: Neuroplastogen Program
Neu r o pl a s t o g e n TM Program
Slide 31: Pipeline of molecules with neural plasticity modulating activity
We have a pipeline of molecules with neural plasticity modulating activity for the treatment of CNS disorders 31 We are developing a novel psilocybin formulation and we are synthetizing psilocybin derivatives with promising activity for the treatment of CNS disorders We have synthesized a series of
Slide 32: Corporate Information
B Corporate Information
Slide 33: Financial Overview
Financial Overview Cash, Cash Equivalents & Short - Term Investments* (as of 9/30/2021) $88.1 m illi o n Warrants Outstanding (as of 9/30/21, weighted average exercise price, $16.08) ~3.2 million Operating Cash Burn 3Q21 $21.0 m illi o n Common Shares Outstanding** (as of 9/30/2021) ~17.5 m illi o n
Slide 34: Investment Highlights
Investment Highlights Highly Compelling Lead Product Opportunity in REL - 1017 Key Catalysts Expected Over Next 3 - 18 Months Focus on CNS diseases and Lead Program in Major Depressive Disorder (MDD) CNS= Central Nervous System;; MDD = major depressive disorder; MOA = mechanism of action **Our fisca