Trevena, Inc. · OTC:TRVN
Trevena — Investor Presentation (March 2023)
55 slides from Trevena's investor presentation, Mar 30, 2023
Slide 1: Innovating for Patients
INNOVATING FOR PATIENTS Nasdaq: TRVN I April 2023
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. (t he “Company” or “we”), they are forward - looking statements reflecting management’s current beliefs and expectations. Forward - looking state
Slide 3: Trevena's Experienced Leadership Team
BOARD OF DIRECTORS Leon O. Moulder , Jr. Chairman Marvin H. Johnson, Jr. Carrie L. Bourdow Jake R. Nunn Scott Braunstein, M.D. Anne M. Phillips, M.D. Michael R. Dougherty Barbara Yanni SENIOR MANAGEMENT Carrie L. Bourdow President & Chief Executive Officer Mark A. Demitrack , M.D . SVP, Chief Medica
Slide 4: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company 4 * PoC = Proof of Concept OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Please see Important Safety Information including BOXED WARNING at t
Slide 5: Multiple Expected Catalysts
PRE - CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST - APPR EXPECTED CATALYSTS OLINVYK® New chemical entity (mu - opioid receptor) TRV045 Selective S1P receptor modulator • Complete enrollment mid - 23 • Complete enrollment mid - 23 TRV250 G - protein selective agonist (delta receptor) • IND - enabling activ
Slide 6: Ex-US Royalty-Based Financing Highlights
Ex - US Royalty - Based Financing Highlights Blue Chip Investor R - Bridge Healthcare Fund affiliate of CBC Group (one of the largest and most active healthcare - dedicated investment firms in Asia) $40M Total Financing $15M upfront (received April 2022) $10M on commercial or financing milestone $15
Slide 7: Large Market Opportunity – Acute Pain
Large Market Opportunity – Acute Pain 7 45M patients receive IV opioids annually to treat acute pain 1 IV opioids have unrivalled analgesic efficacy Top surgeries: Total knee arthroplasty, colectomy, hernia repair, spine fusion, C - section 2 IV NSAIDS / acetaminophen US injectable analgesic hospita
Slide 8: OLINVYK: Differentiated Profile for Acute Pain
OLINVYK: Differentiated Profile for Acute Pain 8 OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate Please see Important Safety Information including BOXED WARNING at the end of p
Slide 9: OLINVYK Studied in Complex Surgeries & Patients
OLINVYK Studied in Complex Surgeries & Patients 9 Broad range of surgeries / medical procedures 0 50 100 150 200 250 Orthopedic Gynecologic Colorectal surgery General surgery Plastic surgery Urologic Neurologic Emergency Bariatric surgery Cardiothoracic Medical Number of patients 11 18 18 33 39 44 6
Slide 10: OLINVYK: Well-Characterized Safety / Tolerability
OLINVYK: Well - Characterized Safety / Tolerability 10 Placebo (N = 162) OLINVYK ≤ 27 mg (N = 316) Morphine (N = 158) Patients with any TEAE (%) 73 86 96 Nausea 35 52 70 Vomiting 10 26 52 Headache 30 26 30 Dizziness 11 18 25 Constipation 9 14 14 Hypoxia 3 12 17 Pruritus 6 9 19 Sedation 5 7 13 Somnol
Slide 11: VOLITION Clinical Outcomes Study w/ Cleveland Clinic
VOLITION Clinical Outcomes Study w/ Cleveland Clinic • Open - label, multi - site study led by experts at Cleveland Clinic and Wake Forest Baptist Health • N = 203 adults undergoing major non - cardiac surgery treated with IV OLINVYK • Initial topline data reported 1Q 23 11 Further characterizes res
Slide 12: ARTEMIS – EMR Clinical Outcomes Study
ARTEMIS – EMR Clinical Outcomes Study • 96 OLINVYK - treated patients at Wake Forest Baptist Health VOLITION site • 457 matched patients undergoing similar surgical procedures, treated with other IV opioids, at same site during VOLITION study - Based on 8 demographic/clinical characteristics (age, s
Slide 13: Respiratory Physiology Study
Respiratory Physiology Study Assessment of Respiratory Function: • Increase inhaled CO2 to experimentally induce respiratory drive • Impact of drug measured as change in minute ventilation • Greater reductions in minute ventilation indicate more respiratory depression • Validated method to estimate
Slide 14: Respiratory Physiology Study: Elderly / Overweight Subjects
Respiratory Physiology Study: Elderly / Overweight Subjects Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . 14 50 70 90 110 130 0 1 2 3 4 5 6 7 OLINVYK 0.5mg Morphine 2.0mg 50 70 90 110 130 0 1 2 3 4 5 6 7
Slide 15: Respiratory Physiology Study Observations
Respiratory Physiology Study Observations • Study population comprised elderly individuals (56 to 87 years, mean = 71.2) with BMI ranging from 20 to 34 (mean = 26.3) • Both OLINVYK and IV morphine achieved comparable levels of pain relief. A statistically significant reduced impact on respiratory fu
Slide 16: Top Line Data: OLINVYK vs IV Morphine Cognitive Function Study
Top Line Data: OLINVYK vs IV Morphine Cognitive Function Study 16 Clinical assessment of OLINVYK’s potential impact on cognitive function vs. IV morphine • Randomized, double - blind, placebo - controlled, crossover study • N = 23 subjects, 19 - 53 years old (median age 26), 13 females & 10 males •
Slide 17: OLINVYK Showed Reduced Impact on Neurocognitive Function
OLINVYK Showed Evidence of Reduced Impact on Neurocognitive Function Compared to IV Morphine 17 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . OLINVYK showed a statistically significant reduction in sedati
Slide 18: Secondary Endpoint Results
Secondary Endpoint Results • Reaction Time. Reduced impact on saccadic eye movement reaction time - M ain effect, P=0.0201 OLINVYK vs IV morphine, P=0.0273 • Postural Stability (Motor Function). Reduced body sway, a measure of motor function - M ain effect, P=0.0314 OLINVYK vs IV morphine, P=0.0951
Slide 19: OLINVYK: Ease of Dosing and Administration
OLINVYK: Ease of Dosing and Administration • Bolus Dosing: 1 mg and 2 mg vials (single dose) • PCA Dosing: 30 mg vial (single patient use) • OLINVYK 1 mg ≈ morphine 5 mg 1 27 mg cumulative daily dose limit Do not administer single doses greater than 3 mg 19 3 vials allow for flexible and tailored IV
Slide 20: OLINVYK vs IV Morphine Health Economic Models
OLINVYK vs IV Morphine Health Economic Models 20 Published 1 and available to formulary committees * As stated in the lable , these data are not an adequate basis for comparison of rates between OLINVYK treatment group and the morphine treatment gro up. The OLINVYK and morphine dosing regimens studi
Slide 21: Customer Engagement Strategy
Customer Engagement Strategy
Slide 22: Targeted Account Launch
Targeted Account Launch 22 Health Care Practitioners (HCPs) Anesthesiology, Colorectal, Critical Care physicians Targeted Accounts Over 50 % of IV opioid volume covered by customer facing team Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribin
Slide 23: Expanded Targets: ~150 Burn Center Accounts
Expanded Targets: ~150 Burn Center Accounts Targeted market opportunity • ~40k burn - related hospitalizations each year across 150 burn centers in US • Longer average in - patient stay: 8 - 9 days • Burn guidelines recommend use of IV opioids 23 Critical care / burn patients experience severe pain
Slide 24: OLINVYK: Significant Opportunity in Acute Pain Market
OLINVYK: Significant Opportunity in Acute Pain Market 24 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . Source: Definitive Healthcare; American Hospital Association. *Assumes ~$100 / day price for OLINVYK
Slide 25: TRV045 S1P Receptor Modulator: Novel MOA for Diabetic Neuropathic Pain
TRV045 S1P Receptor Modulator Novel MOA for Diabetic Neuropathic Pain
Slide 26: S1P Receptor – Novel Target for CNS Indications
S1P 1 Receptor – Novel Target for CNS Indications 1) Sim - Selley et al., Journal of Pharmacology & Experimental Therapeutics, 2018. 2) Sim - Selley et al, Journal of Neurochemistry, 2008. 3) Gol et al., European Journal of Pharmaceutical Sciences, 2017. 4) Leo et al, CNS & Neurological Disorders -
Slide 27: TRV045: Novel MOA, Selective S1PR
Avoids Lymphopenia TRV045: Novel MOA, Selective S1PR 27 1) CIPN mouse model: Paclitaxel 6 mg/kg, i.p. on Days 1, 3, 5, 7. Hyperalgesia measured as % non - response to 0.4 g Von Frey filament vs. baseline, tested 30’ after dosing on Day 13. Lymphocytes measured after 3 days of dosing. Data are mean “
Slide 28: TRV045 Phase 1 Study – Safety / Tolerability / PK
TRV045 Phase 1 Study – Safety / Tolerability / PK Randomized, double - blinded, placebo - controlled study 3 - parts: single dose (n=53), food effect (n=27), multiple dose (n=9) 28 • Favorable tolerability profile with no SAEs Well Tolerated Target Exposure Attractive PK Profile • Calculated free pl
Slide 29: POC Study: Single-dose Target Engagement
POC Study: Single - dose Target Engagement (Ph 1) Enrollment completion expected mid - 2023 Pharmacodynamic Endpoint Test and Outcome Pain Type Cold Pressor Pain detection (PDT), pain tolerance (PTT), post - test VAS Nociceptive (thermal) Electrical Pain Burst: PDT, PTT, PT - VAS Stair: PDT, PTT, PT
Slide 30: POC Study: Repeat-dose TMS Study
• Design: Randomized, double - blind, placebo - controlled, multiple dose, two - way cross - over study (n~24) - Placebo or TRV045 (250mg) for 4 days Pharmacodynamic Endpoint Test and Outcome Resting Motor Threshold % maximal machine output MEP Amplitude Peak - to - peak amplitude (P - PA) Short Int
Slide 31: Effect of TRV045 on Cytokine / Chemokine Release
Effect of TRV045 on Cytokine / Chemokine Release • Methods: • Primary mouse astrocytes in monolayer cell culture; incubated for 24 hrs w/ 5 m M TRV045 • Panel of 17 cytokines / chemokines * assessed by ELISA • Main Findings: • Net anti - inflammatory action on astrocyte cytokine / chemokine release
Slide 32: TRV045 Demonstrates Efficacy in Nonclinical Epilepsy Models
TRV045 Demonstrates Efficacy in Nonclinical Epilepsy Models • NIH - supported Epilepsy Therapy Screening Program • Acute seizure protection in max. electroshock model - Replicated in 3 independent experiments using either subcutaneous or oral administration • Efficacy demonstrated in two different p
Slide 33: TRV250: New MOA for Acute Treatment of Migraine; TRV734: Maintenance Therapy for Opioid Use Disorder
TRV250: New MOA for Acute Treatment of Migraine TRV734: Maintenance Therapy for Opioid Use Disorder
Slide 34: TRV250: New MOA for Acute Treatment of Migraine
TRV250: New MOA for Acute Treatment of Migraine 34 Delta receptor: Untapped potential in CNS space Migraine represents a large market opportunity; total migraine drug market = ~$3.5B 1) Data from Decision Resources, Pharmacor migraine market landscape and forecast 2018. 2) Moven et al., J Neurol Neu
Slide 35: TRV250: Well-Tolerated in Ph1 Healthy Volunteer PK Study
TRV250: Well - Tolerated in Ph1 Healthy Volunteer PK Study Well tolerated, with no SAEs across broad range of doses Predictable PK: dose - proportional between 0.1 mg to 30 mg SC Half - life consistent across all doses No EEG findings observed in any subject IND - enabling activities initiated for n
Slide 36: TRV734: Maintenance Therapy for Opioid Use Disorder
TRV734: Maintenance Therapy for Opioid Use Disorder 36 Selective agonism at µ receptor: nonclinical evidence of 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.
Slide 37: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company 37 * PoC = Proof of Concept OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Please see Important Safety Information including BOXED WARNING at
Slide 38: Appendix
38 JL: can will create a transition slide? Appendix
Slide 39: OLINVYK: Distinct From IV Morphine / Hydromorphone
Studied in >1,900 individuals Hydromorphone OLINVYK: Distinct From IV Morphine / Hydromorphone Morphine 39 OLINVYK IV morphine included as active comparator NCE with 2032+ COM patent 1 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Inform
Slide 40: OLINVYK: IV Opioid Efficacy and Rapid Onset
OLINVYK: IV Opioid Efficacy and Rapid Onset 40 • Efficacy achieved in hard tissue & soft tissue models • Rapid onset: perceptible pain relief within 1 - 3 minutes • OLINVYK efficacy data in peer - reviewed journals The Journal of Pain Research 1 and Pain Practice 2 Soft Tissue (SPID - 24) Rapid onse
Slide 41: Primary Efficacy Endpoint: Phase 3 Analgesic Responder Rate
41 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . These analyses were the prespecified primary endpoints for both studies. Section 14 of the Prescribing Information includes t he SPID - 24 and SPID - 48 ef
Slide 42: OLINVYK: IV Opioid Efficacy in 2 Phase 3 RCTs
0 1 2 3 4 5 6 7 8 9 10 0 4 8 12 16 20 24 28 32 36 40 44 48 0 1 2 3 4 5 6 7 8 9 10 0 4 8 12 16 20 24 Time (hours) Average NRS Pain Score OLINVYK: IV Opioid Efficacy in 2 Phase 3 RCTs Study 1 (Orthopedic – Hard Tissue) 3 PCA regimens studied (0.1, 0.35, 0.5 mg) vs. placebo; all doses P<0.01 vs. placeb
Slide 43: Robust Assessment of Respiratory Safety in Phase 3 RCTs
Robust Assessment of Respiratory Safety in Phase 3 RCTs 43 Data included in AMCP dossier used in formulary review 1) Figure 2 - 8, Section 2.2, OLINVYK Evidence Dossier for Formulary Consideration. 2) Figures 3 - 4 and 3 - 8, Section 3.1, OLINVYK E vidence Dossier for Formulary Consideration. • Pres
Slide 44: Robust Assessment of GI Tolerability in Phase 3 RCTs
Robust Assessment of GI Tolerability in Phase 3 RCTs 44 Data included in AMCP dossier used in formulary review P < 0.05 vs. morphine.1) Figure 2 - 10, Section 2.2, OLINVYK Evidence Dossier for Formulary Consideration. 2) Figure 2 - 11, Section 2.2, OLINVYK Evidence Dossier for Formulary Consideratio
Slide 45: Positive Feedback from Formulary Stakeholders
Positive Feedback from Formulary Stakeholders 1 45 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . 1) Qualitative Pricing research, Charles River Associates, April 2020. 2) “Are the improvements in respirat
Slide 46: Multi-Dose tQT Study
-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 46 Multi - Dose tQT Study Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at w ww. OLINVYK.com. 3
Slide 47: VOLITION: Initial Topline Results and Study Design
VOLITION: Initial Topline Results and Study Design • Real - world, o pen - label, multi - site, post - approval clinical outcomes study in 203 adult patients undergoing major non - cardiac surgery. • IV OLINVYK was dosed as the first - line analgesic during post - operative care, with a 1.5mg loadin
Slide 48: ARTEMIS: Initial Topline Results and Study Design
ARTEMIS: Initial Topline Results and Study Design • EMR - based analysis that compared the health outcomes of VOLITION study patients with a matched population of patients, who underwent similar surgical procedures but were treated with other IV opioids, at the same institutions and during the same
Slide 49: Stable IV Opioid Market Performance
Stable IV Opioid Market Performance 49 Despite the 20% decline in elective surgeries, IV opioid volume remained stable SOURCE: IQVIA DDD Data May 2022 Declines due to COVID - 19 across top surgical procedures: Total knee, Total hip, Hernia repair, Hysterectomy, Bariatric Pack Units (000s) CDC report
Slide 50: Hospital Inpatient Visits Below Pre-Pandemic Levels
Hospital Inpatient Visits Below Pre - Pandemic Levels • Monthly Volume Changes in 2022 remain below 2019 levels for each month of the year. • Through August each month in 2022 has shown a decline greater than was seen in 2021 50 Source: National Patient and Procedure Volume Tracker - Strata Decision
Slide 51: Diabetic Neuropathic Pain Represents a Large Market Opportunity
$0 $7,000 $14,000 $21,000 $28,000 $35,000 Diabetes only Diabetes with DNP Diabetic Neuropathic Pain 51 Diabetic neuropathic pain (DNP) represents a large market opportunity 1) IDF, www.diabetesatlas.org 2) Economic Costs of Diabetes in the U.S. in 2017, Diabetes Care 2018;41:917 – 928. 3) Shillo et
Slide 52: Epilepsy: One of the Most Common Neurological Diseases
Epilepsy 52 One of the most common neurological diseases in the world 1 1. World Health Organization. Epilepsy. https://www.who.int/news - room/fact - sheets/detail/epilepsy. Accessed November, 2021. 2. Epi lepsy Foundation. About Epilepsy: The Basics. https://www.epilepsy.com/learn/about - epilepsy
Slide 53: Important Safety Information
53 JL: can will create a transition slide? IMPORTANT SAFETY INFORMATION
Slide 54: Boxed Warning: Addiction, Abuse, and Misuse; Respiratory Depression
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE - THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS Addiction, Abuse, and Misuse OLINVYK exposes patients and other users to the ri
Slide 55: Warnings and Precautions
WARNINGS AND PRECAUTIONS Prolonged use of opioids during pregnancy can result in withdrawal in the neonate that may be life - threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using OLINVYK for a prolonged period of the risk