Trevena, Inc. · OTC:TRVN
Trevena — Investor Presentation (May 2020)
40 slides from Trevena's investor presentation, May 18, 2020
Slide 1: Innovating for Patients
INNOVATING FOR PATIENTS Nasdaq TRVN I May 2020
Slide 2: Forward-Looking Statements
Forward - Looking Statements To the extent that statements contained in this presentation are not descriptions of historical facts regarding Trevena, Inc . (the “Company” or “we”), they are forward - looking statements reflecting management’s current beliefs and expectations . Forward - looking stat
Slide 3: Trevena's Experienced Leadership Team
BOARD OF DIRECTORS Leon O. Moulder , Jr. Chairman Carrie L. Bourdow Julie H. McHugh Scott Braunstein, M.D. Jake R. Nunn Michael R. Dougherty Anne M. Phillips, M.D. Maxine Gowen, Ph.D. Barbara Yanni SENIOR MANAGEMENT Carrie L. Bourdow President & Chief Executive Officer Scott Applebaum SVP, Chief Leg
Slide 4: Trevena: Innovative CNS Company
Lead asset IV Oliceridine New MOA designed to improve intravenous (IV) moderate - to - severe acute pain management FDA considers submission complete PDUFA date: August 7, 2020 Large market, targeted launch 45M+ US hospital patients; 9M at higher risk for AEs (initial focus) $1 - 1.5B market opportu
Slide 5: Multiple Expected Catalysts
PRE - CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA EXPECTED CATALYSTS OLICERIDINE G protein - selective agonist (mu - opioid receptor) Aug 7, 2020: PDUFA date TRV250 G protein - selective agonist (delta receptor) PoC study data TRV734 G protein - selective agonist (mu - opioid receptor) PoC study data (NIDA
Slide 6: IV Oliceridine Value Proposition
IV Oliceridine Value Proposition 6 IV opioids are necessary for effective acute pain management NSAIDs = nonsteroidal anti - inflammatory drugs 1) IMS MIDAS sales audit 2017; IV NSAIDs and Ofirmev ®. 2) Healogix hospital physician market research (N=91), August ‘16. e.g. IV morphine, IV hydromorphon
Slide 7: Designed to Improve on Conventional IV Opioids
4 head - to - head clinical studies vs. morphine Designed to Improve on Conventional IV Opioids 7 If approved, Oliceridine is expected to be a CII controlled substance, as defined in the Controlled Substances Act of 1970. 1) 2032 composition of matter expiration does not include potential patent ext
Slide 8: Compelling Product Profile
Compelling Product Profile 8 If approved, oliceridine is expected to be a CII controlled substance, as defined in the Controlled Substances Act of 1970. Data based on Phase 1 - 3 clinical trials including comparisons of oliceridine to IV morphine. Unique MOA IV opioid - level efficacy Rapid onset No
Slide 9: Primary Efficacy Endpoint Achieved in Two Pivotal Studies
Soft tissue Primary Efficacy Endpoint Achieved in Two Pivotal Studies Oliceridine regimens: 1.5 mg loading bolus, with 0.1, 0.35, or 0.5 mg available on demand every 6 minutes. Displayed p - values ar e for oliceridine vs. placebo with Hochberg multiplicity adjustment. 1) Viscusi ER et al. J Pain Re
Slide 10: Well-Characterized Safety and Tolerability Profile
0.0 0.2 0.4 0.6 0.8 1.0 Respiratory safety burden, hours Placebo 0.1 0.35 0.5 Morphine Oliceridine Placebo 0.1 0.35 0.5 Morphine 0.0 0.2 0.4 0.6 0.8 1.0 Respiratory safety burden, hours Oliceridine - 73% - 40% Ph3 Respiratory Safety Burden Relative Risk Reduction Ph3: Hard Tissue Ph3: Soft Tissue We
Slide 11: Unique and Differentiated PK Profile
Unique and Differentiated PK Profile 11 PK = pharmacokinetic. Icons made by Freepik from www.flaticon.com IV oliceridine demonstrates: Fast onset (<5 min) + ~3 - hour duration Attractive for ER, hospital floor, and surgery centers No known active metabolites Simplifies dosing for predictable pain co
Slide 12: Safety / Tolerability Demonstrated in Real World Use Study
Safety / Tolerability Demonstrated in “Real World Use” Study 12 Broad range of surgeries / medical procedures with at - risk patients Trial modeled real - world use: usual patient care with oliceridine instead of standard IV opioid 0 50 100 150 200 250 Orthopedic Gynecologic Colorectal surgery Gener
Slide 13: Positive Feedback from Formulary Stakeholders
Positive Feedback from Formulary Stakeholders 1,2,3 13 1) Source: Quantitative Price - Access Survey (n=200), Charles River Associates 2017. 2) “Are the improvements in the following re spiratory/GI safety endpoints clinically meaningful?” Based on oliceridine Ph3 clinical trial data. 3) Source: Qua
Slide 14: Formulary Focus: Improve Outcomes and Decrease Costs
Formulary Focus: Improve Outcomes and Decrease Costs 14 ORAE = opioid - related adverse event; costs are per hospital stay 1) Kessler RE, Pharmacotherapy, 2013. 2) Oderda , GM, J Pain Palliative Care Pharm, 2019; data based on 5 surgical procedure categories including Cardiothoracic / vascular, Gen
Slide 15: Targeted Account Launch
PATIENTS HOSPITALS Targeted Account Launch 15 Initial focus: at - risk patients in 3 key surgical areas ~5,800 hospitals in the US ~600 hospitals Community Large regional systems Hospital outpatient Ambulatory surgical centers ~9M at - risk patients Co - morbidities Obese Renal impa irment Elderly P
Slide 16: Launch Strategy Allows for Growth
Procedure risk factors, e.g. Procedure Risk Patient Risk High High Low Launch Strategy Allows for Growth 16 * Assumes $60 - $100 / day price for oliceridine Low Initial launch focus Expand for peak share • Severe / prolonged pain • Ortho, colorectal, cardiothoracic • Co - morbidities • Obese • Renal
Slide 17: Multiple Expected Catalysts
PRE - CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA EXPECTED CATALYSTS OLICERIDINE G protein - selective agonist (mu - opioid receptor) Aug 7, 2020: PDUFA date TRV250 G protein - selective agonist (delta receptor) PoC study data TRV734 G protein - selective agonist (mu - opioid receptor) PoC study data (NIDA
Slide 18: Migraine Represents A Large Market Opportunity
Migraine Represents A Large Market Opportunity 18 Total migraine drug market = ~$3.5B All data from Decision Resources, Pharmacor migraine market landscape and forecast 2018. 1) Moven et al., J Neurol Neurosurg Psychiatry, 2016. Icons made by Freepik from www.flaticon.com 650M migraines treated each
Slide 19: TRV250: New MOA for Acute Treatment of Migraine
TRV250: New MOA for Acute Treatment of Migraine 19 Delta receptor: Untapped potential in CNS space Play important role in regulation of pain, mood, and anxiety Acute migraine proof - of - concept study initiated Delta receptors have unique distribution throughout the brain • Validated biomarker mode
Slide 20: TRV734: Maintenance Therapy for Opioid Use Disorder
TRV734: Maintenance Therapy for Opioid Use Disorder 20 Selective agonism at µ receptor: Potential for improved tolerability 1) Center for Behavioral Health Statistics and Quality. 2) NIDA data on file. Ongoing collaboration with National Institute on Drug Abuse (NIDA) >2.5M people in U.S. suffer fro
Slide 21: TRV045: Next-Generation S1P Modulator for CNS Disorders
Avoids Lymphopenia Reverses Pain Response TRV045: Next - Generation S1P Modulator for CNS Disorders 0 20 40 60 80 100 Fingolimod TRV045 21 New MOA at S1P, without associated lymphopenia CIPN mouse model: Paclitaxel 6 mg/kg, i.p. on Days 1, 3, 5, 7. Hyperalgesia measured as % non - response to 0.4 g
Slide 22: TRV027 NCE targeting the AT1 receptor in COVID-19
TRV027 NCE targeting the AT 1 receptor in COVID - 19 22
Slide 23: Interaction Between the AT1 Receptor and ACE2 in COVID-19
Interaction Between the AT 1 Receptor and ACE2 in COVID - 19 • Coronavirus binds to and downregulates angiotensin converting enzyme 2 (ACE2) 1 • Decrease in ACE2 elevates angiotensin II levels - Angiotensin II activates AT 1 receptor - No breakdown of angiotensin II into Ang(1 - 7) o Normally, Ang(1
Slide 24: AT1 Receptor Integral to COVID-19 Morbidity
AT 1 Receptor Integral to COVID - 19 Morbidity Acute lung damage Vasoconstriction Fibrosis 24 Coronavirus binds to and removes ACE2, elevating levels of angiotensin II 1) Gibson PG et al, Med J Aust, 2020. *In patients requiring ventilation. Improved pulmonary integrity Vasodilation Reduced inflamma
Slide 25: TRV027: A New MOA at the AT1 Receptor
TRV027: A New MOA at the AT 1 Receptor 25 TRV027 combats overactivation of AT 1 receptor while promoting reparative effects on lung tissue TRV027 provides a selective and targeted approach to treating acute lung injury in COVID - 19 patients Acute lung damage Vasoconstriction Fibrosis Improved pulmo
Slide 26: TRV027 is Ready to Enter Clinical Testing
TRV027 is Ready to Enter Clinical Testing 26 Safety / tolerability has been established in large patient population • Advanced through Phase 2b for acute heart failure • Studied in ~700 individuals • Well - characterized pharmacology • No significant safety issues during clinical trials TRV027 clini
Slide 27: Trevena: Innovative CNS Company
Lead asset IV Oliceridine New MOA designed to improve intravenous (IV) moderate - to - severe acute pain management FDA considers submission complete PDUFA date: August 7, 2020 Large market, targeted launch 45M+ US hospital patients; 9M at higher risk for AEs (initial focus) $1 - 1.5B market opportu
Slide 28: Appendix
APPENDIX 28
Slide 29: NDA Resubmission Considered Complete
NDA Resubmission Considered Complete NDA = New Drug Application 29 Completed healthy volunteer QT study Confirmed safety database supports maximum daily dose of 27 mg Validated bioassay and confirmed levels of inactive metabolite (‘9662) Completed drug product validation reports • No accumulation of
Slide 30: Robust Clinical Development Program
• No dosage adjustments for elderly / renally impaired • No known active metabolites Robust Clinical Development Program 30 # subjects exposed to oliceridine in Ph1 = 318 # patients treated with oliceridine in Ph2 and Ph3 = 1,535 Phase 1 Phase 2 Phase 3 4 head - to - head trials vs. morphine: • IV o
Slide 31: Oliceridine Delivers Rapid Analgesia
Oli 2 mg Morphine 4 mg Oli 1 mg Oli 3 mg Oliceridine Delivers Rapid Analgesia 31 Fast onset measured by two - stopwatch method Majority of patients achieved perceptible pain relief within 2 - 5 minutes after first dose 1 Time of onset after first dose 1) Viscusi ER, Pain, 2016.
Slide 32: Overview of Cardiac Safety Data
-15 -10 -5 0 5 10 15 20 0.04 0.20 1.00 5.00 25.00 Time (hours) Moxifloxacin 400mg (positive control) Overview of Cardiac Safety Data 32 Single - Dose tQT Study Single - dose Phase 1 tQT study 1 1) Design based on FDA E14 Guidance: Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythm
Slide 33: No Accumulation Despite Repeated Dosing
-15 -10 -5 0 5 10 15 20 0 2 4 6 8 10 12 14 16 18 20 22 24 Mean ΔΔ QTcI ( msec ) [90% CI] No Accumulation Despite Repeated Dosing 33 Multi - Dose tQT Study 3 subjects not dosed due to lack of venous access: 1 discontinuation due to a non - serious adverse event (asymptomatic non - sustai ned ventricu
Slide 34: Comprehensive Data Available at Launch
Comprehensive Data Available at Launch 34 Will support future commercialization and hospital formulary uptake *Expected to be published at time of approval / launch • First - in - class new mechanism of action • Fast, effective IV opioid - level pain relief • Clinical data in at - risk patients / ta
Slide 35: Consistent Respiratory Safety Profile
1.5 3 4.5 Respiratory safety superiority of oliceridine vs. morphine has not been established in randomized controlled clinical trials. Consistent Respiratory Safety Profile Phase 1: • Reduced impact on hypercapnic respiratory drive vs. morphine 1 35 *p < 0.05 vs. morphine. Hypoventilation: clinical
Slide 36: Favorable GI Tolerability and Safety Profile
Superiority of the GI safety and tolerability of oliceridine vs. morphine has not been established in randomized controlled clinical trials. Favorable GI Tolerability and Safety Profile Phase 2: • Reduced incidence of nausea and vomiting adverse events vs. morphine 1 36 GI = gastrointestinal; *p < 0
Slide 37: APOLLO 1: Most Common TEAEs
APOLLO 1: Most Common TEAEs 37 TEAE = treatment - emergent adverse event. “Most common” refers to TEAEs occurring in ≥ 10% of patients in any treatment group. Di scontinuations for safety/tolerability: 0 for placebo; 0, 1, and 4 for oliceridine 0.1, 0.35, and 0.5 mg; 6 for morphine Placebo Oliceridi
Slide 38: APOLLO 2: Most Common TEAEs
APOLLO 2: Most Common TEAEs 38 TEAE = treatment - emergent adverse event. “Most common” refers to TEAEs occurring in ≥ 10% of patients in any treatment group. Di scontinuations for safety/tolerability: 0 for placebo; 0, 4, and 4 for oliceridine regimens 0.1, 0.35, and 0.5 mg; 2 for morphine Placebo
Slide 39: Delta Receptor Agonists Have Unique Benefits
Delta Receptor Agonists Have Unique Benefits Triptans / Ditans • Target: serotonin receptors mediate vascular excitability (a ssociated CV risk) 1 • Migraine - specific treatment CGRPs • Target: CGRP receptors regulate neuronal structures involved in pain signaling 2 • Migraine - specific treatment
Slide 40: TRV250 PoC Study (acute migraine)
TRV250 PoC Study (acute migraine) 40 Study initiated Q4 2019 Study Outline n = ~120 migraineurs w/o aura Primary endpoint: • Reduction of sustained NTG - induced headaches @ 4hr Secondary Endpoints: • Pain response or pain freedom @ 6hr / 8hr • Anxiety symptom relief • Overall safety & tolerability