Slide 1: Innovating for Patients
INNOVATING FOR PATIENTS Nasdaq: TRVN I March 2022
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 statements a
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 Medical O
Slide 4: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company 4 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 presentation. F
Slide 5: Pipeline and Multiple Expected Catalysts
PRE-CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST-APPR EXPECTED CATALYSTS OLINVYK® New chemical entity (mu-opioid receptor) TRV027 AT1 receptor selective agonist TRV045 Selective S1P receptor modulator • Phase 1 complete 2H 22 TRV250 G-protein selective agonist (delta receptor) • IND-enabling activities (or
Slide 6: Ex-US Royalty-Based Financing Highlights
Ex-US S Royalty-Based d Financing g 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 $10M on commercial or financing milestone $15M on first commercial sa
Slide 7: Large Market Opportunity – Acute Pain
Large Market Opportunity – Acute Pain 7 45M patients receive IV opioids annually to treat acute pain1 IV opioids have unrivalled analgesic efficacy Top surgeries: Total knee arthroplasty, colectomy, hernia repair, spine fusion, C-section2 IV NSAIDS / acetaminophen US injectable analgesic hospital ma
Slide 8: Stable IV Opioid Market Performance
Stable IV Opioid Market Performance 8 Despite the 20% decline in elective surgeries, IV opioid volume remained stable SOURCE: IQVIA DDD Data August 2021 Declines due to COVID-19 across top surgical procedures: Total knee, Total hip, Hernia repair, Hysterectomy, Bariatric 5,000 10,000 15,000 20,000 2
Slide 9: OLINVYK: Differentiated Profile for Acute Pain
OLINVYK: Differentiated Profile for Acute Pain 9 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 10: OLINVYK Studied in Complex Surgeries & Patients
OLINVYK Studied in Complex Surgeries & Patients 10 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
Slide 11: OLINVYK: Well-Characterized Safety / Tolerability
OLINVYK: Well-Characterized Safety / Tolerability 11 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 Somnolen
Slide 12: New Respiratory Physiology Study – Topline Data
New Respiratory Physiology Study – Topline Data 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
Slide 13: Respiratory Physiology Study Topline Data Observations
Respiratory Physiology Study Topline Data Observations • In elderly, overweight subjects (mean age 71.2 years), at comparable levels of analgesia, oliceridine showed a significantly reduced effect on ventilatory drive over time compared to morphine (P<0.0001) • These data in elderly subjects replica
Slide 14: OLINVYK vs IV Morphine Cognitive Function Study
New OLINVYK vs IV Morphine Cognitive Function Study 14 Clinical assessment of OLINVYK’s potential impact on cognitive function vs. IV morphine • Phase 1 randomized, double-blind, placebo-controlled, crossover study • N = ~24 subjects, 18-55 years old • Topline data expected mid-2022 Cognitive functi
Slide 15: OLINVYK Safety Outcomes Study with Cleveland Clinic
OLINVYK Safety Outcomes Study w/ Cleveland Clinic • Open-label, multi-site study led by experts at Cleveland Clinic and Wake Forest Baptist Health • N = ~200 adults undergoing major non-cardiac surgery • Topline data expected in 2H 2022 15 Further characterizes potential respiratory, GI and cognitiv
Slide 16: 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 mg1 27 mg cumulative daily dose limit Do not administer single doses greater than 3 mg 16 3 vials allow for flexible and tailored IV
Slide 17: OLINVYK vs IV Morphine Health Economic Models
OLINVYK vs IV Morphine Health Economic Models 17 Published1 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 group. The OLINVYK and morphine dosing regimens studied
Slide 18: Customer Engagement Strategy
Customer Engagement Strategy
Slide 19: Targeted Account Launch
Targeted Account Launch 19 ~40 FTEs across Medical, Market Access and Sales deployed in focused segments Health Care Practitioners (HCPs) Anesthesiology, Colorectal, Burn physicians Targeted Accounts ~70% of IV opioid volume covered by customer facing team Please see Important Safety Information inc
Slide 20: 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 20 Critical care / burn patients experience severe pain and ar
Slide 21: OLINVYK: Significant Opportunity in Acute Pain
OLINVYK: Significant Opportunity in Acute Pain 21 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 2032 com
Slide 22: TRV027: NCE targeting the AT1 receptor in COVID-19
TRV027 NCE targeting the AT1 receptor in COVID-19
Slide 23: Multi-Organ Damage From Coronavirus
Multi-Organ Damage From Coronavirus 23 Elimination of ACE2 protein leads to critical hormonal imbalances SARS-CoV-2 ACE2 Coronavirus binds to and eliminates ACE21 • Leads to accumulation of angiotensin II: - Acute lung injury and abnormal blood clots - Can lead to ARDS / pulmonary embolism / stroke
Slide 24: TRV027: New MOA for COVID-19
TRV027: New MOA for COVID-19 24 Mechanism targeted to improve lung function and prevent abnormal clotting TRV027 β-arrestin AT1 receptor TRV027 is the only selective AT1 receptor agonist Safety / tolerability data in ~700 patients G protein Cell surface Cell interior Lung damage Abnormal blood clots
Slide 25: TRV027 COVID-19 Study - Imperial College London
TRV027 COVID-19 Study - Imperial College London • Randomized, double-blind, placebo-controlled proof-of-concept study • N = 30 COVID-19 patients enrolled - Hospitalized, non-ventilated - ≥18 years old - IV infusion of placebo or TRV027 for 7 days (12 mg/hr) • Primary endpoint: mean change from basel
Slide 26: Primary Endpoint (D-Dimer Reduction) – Bayesian Results
Primary Endpoint (D-Dimer Reduction) – Bayesian Results 1) Percentage change from baseline D-dimer per year of age. 92% probability that TRV027 has a potentially beneficial effect on D-dimer vs. placebo 26 TRV027 Probability of Effect on D-dimer (adjusted for age) Probability Density 10% 0% 20% 30%
Slide 27: Time to Initial Hospital Discharge
Time to Initial Hospital Discharge (Length of Hospital Stay) Full Analysis Set (excludes deaths) TRV027 (N=7)* Placebo (N=10) Difference Mean (days) Median Range 11.4 8 5, 32 23.3 12 5, 86 11.9 days 4 days A post-hoc analysis indicated that patients receiving TRV027 experienced ~12-day reduction in
Slide 28: Preliminary Conclusions
Preliminary Conclusions TRV027 was well-tolerated in hospitalized COVID-19 patients Primary endpoint: • Bayesian modeling predicted 92% probability for TRV027 having a potentially beneficial impact on D-dimer levels • TRV027 patients experienced 70% reduction in circulating D-dimer, vs. 27% of place
Slide 29: Multi-Arm Platform Trial with TRV027 in COVID-19 Patients
Multi-Arm Platform Trial with TRV027 in COVID-19 Patients1 29 TRV027 data expected in ~300 patients; NIH ACTIV-4 topline data expected 2H 2022 *ACTIV = Accelerating COVID-19 Therapeutic Interventions and Vaccines. 1.Patients with ARDS/Abnormal clotting associated with COVID-19 NIH ACTIV-4* (US) Supp
Slide 30: TRV045: Novel MOA for Diabetic Neuropathic Pain
TRV045: Novel MOA for Diabetic Neuropathic Pain 30 Selective S1PR with no lymphopenia – Expected Completion of Phase 1 2H 2022 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 Pha
Slide 31: TRV045 for Diabetic Neuropathic Pain
$0 $7,000 $14,000 $21,000 $28,000 $35,000 Diabetes only Diabetes with DNP TRV045 for Diabetic Neuropathic Pain 31 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) S
Slide 32: Avoids Lymphopenia: TRV045 Novel MOA
Avoids Lymphopenia TRV045: Novel MOA for Diabetic Neuropathic Pain 32 1) Rosenberger et al., Journal of Neural Transmission, 2020 and CDC National Diabetes Statistics Report, 2020. 2) Shillo et al., Current Diabetes Reports, 2019. 3) American Diabetes Association. 4) FDA product labels for Lyrica, L
Slide 33: TRV250: New MOA for Acute Treatment of Migraine
TRV250: New MOA for Acute Treatment of Migraine 33 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 34: 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 new oral
Slide 35: TRV734: Maintenance Therapy for Opioid Use Disorder
TRV734: Maintenance Therapy for Opioid Use Disorder 35 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 36: Pipeline and Multiple Expected Catalysts
PRE-CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST-APPR EXPECTED CATALYSTS OLINVYK® New chemical entity (mu-opioid receptor) TRV027 AT1 receptor selective agonist TRV045 Selective S1P receptor modulator • Phase 1 complete 2H 22 TRV250 G-protein selective agonist (delta receptor) • IND-enabling activities (or
Slide 37: Appendix
37 JL: can will create a transition slide? Appendix
Slide 38: New Respiratory Physiology Study – Topline 1Q '22
New Respiratory Physiology Study – Topline 1Q '22 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com. Results from Study in Normal Age / BMI Subjects New Study vs IV morphine: Effect of OLINVYK on respiratory ph
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 patent1 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Informa
Slide 40: Robust Clinical Development Program
No dosage adjustments for elderly / renally impaired No known active metabolites Robust Clinical Development Program 40 OLINVYK studied in > 1,900 individuals 4 head-to-head trials vs. IV morphine Phase 1 Phase 2 Phase 3 Please see Important Safety Information including BOXED WARNING at the end of p
Slide 41: OLINVYK: IV Opioid Efficacy and Rapid Onset
OLINVYK: IV Opioid Efficacy and Rapid Onset 41 • 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 Research1 and Pain Practice2 Soft Tissue (SPID-24) Rapid onset (2-5 m
Slide 42: Please see Important Safety Information including BOXED WARNING at the end of presentation. Full
42 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 the SPID-24 and SPID-48 efficacy
Slide 43: 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 44: Robust Assessment of Respiratory Safety in Phase 3 RCTs
Robust Assessment of Respiratory Safety in Phase 3 RCTs 44 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 Evidence Dossier for Formulary Consideration. • Prespecifie
Slide 45: Robust Assessment of GI Tolerability in Phase 3 RCTs
Robust Assessment of GI Tolerability in Phase 3 RCTs 45 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 Consideration. 3
Slide 46: Positive Feedback from Formulary Stakeholders
Positive Feedback from Formulary Stakeholders1 46 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 respirator
Slide 47: Omni-channel Approach for HCP Engagement
Omni-channel Approach for HCP Engagement 47 Communication across a full range of channels to maximize reach and impact Field directed: live, virtual & email HCP social media Professional Society Meetings & Congresses Olinvyk.com Virtual “on demand” Medical Education programs Please see Important Saf
Slide 48: 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 ΔΔQTcI (msec) [90% CI] No Accumulation Despite Repeated Dosing 48 Multi-Dose tQT Study Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com. 3 subject
Slide 49: Important Safety Information
49 JL: can will create a transition slide? IMPORTANT SAFETY INFORMATION
Slide 50: Boxed Warning: Addiction, Abuse, and Misuse
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 risk
Slide 51: 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