Trevena, Inc. · OTC:TRVN
Trevena — Investor Presentation (April 2022)
52 slides from Trevena's investor presentation, Apr 20, 2022
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. (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 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: Multiple Expected Catalysts
PRE - CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST - APPR EXPECTED CATALYSTS OLINVYK® New chemical entity (mu - opioid receptor) TRV027 AT 1 receptor selective agonist TRV045 Selective S1P receptor modulator • Phase 1 complete 2H 22 TRV250 G - protein selective agonist (delta receptor) • IND - enabling act
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 $10M on commercial or financing milestone $15M on first commercial
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: 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
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 Somnol
Slide 12: 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 13: 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 . 13 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 14: 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 15: OLINVYK vs IV Morphine Cognitive Function Study
New OLINVYK vs IV Morphine Cognitive Function Study 15 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 Cognitiv
Slide 16: 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 16 Further characterizes potential respiratory, GI and co
Slide 17: 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 17 3 vials allow for flexible and tailored IV
Slide 18: OLINVYK vs IV Morphine Health Economic Models
OLINVYK vs IV Morphine Health Economic Models 18 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 19: Customer Engagement Strategy
Customer Engagement Strategy
Slide 20: Targeted Account Launch
Targeted Account Launch 20 ~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 21: 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 21 Critical care / burn patients experience severe pain
Slide 22: OLINVYK: Significant Opportunity in Acute Pain
OLINVYK: Significant Opportunity in Acute Pain 22 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 co
Slide 23: TRV027 NCE targeting the AT1 receptor in COVID-19
TRV027 NCE targeting the AT1 receptor in COVID - 19
Slide 24: Multi-Organ Damage From Coronavirus
Multi - Organ Damage From Coronavirus 24 Elimination of ACE2 protein leads to critical hormonal imbalances SARS - CoV - 2 ACE2 Coronavirus binds to and eliminates ACE2 1 • Leads to accumulation of angiotensin II: - Acute lung injury and abnormal blood clots - Can lead to ARDS / pulmonary embolism /
Slide 25: TRV027: New MOA for COVID-19
TRV027: New MOA for COVID - 19 25 Mechanism targeted to improve lung function and prevent abnormal clotting TRV027 β - arrestin AT 1 receptor TRV027 is the only selective AT 1 receptor agonist Safety / tolerability data in ~700 patients G protein Cell surface Cell interior Lung damage Abnormal blood
Slide 26: 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
Slide 27: 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 27 TRV027 Probability of Effect on D - dimer (adjusted for age) Probability Density 10% 0%
Slide 28: 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
Slide 29: 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%
Slide 30: Multi-Arm Platform Trial with TRV027 in COVID-19 Patients
Multi - Arm Platform Trial with TRV027 in COVID - 19 Patients 1 30 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 associat ed with COVID - 19 NIH ACTIV
Slide 31: TRV045: Novel MOA for Diabetic Neuropathic Pain
TRV045: Novel MOA for Diabetic Neuropathic Pain 31 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
Slide 32: 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 32 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)
Slide 33: Avoids Lymphopenia
Avoids Lymphopenia TRV045: Novel MOA for Diabetic Neuropathic Pain 33 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 ,
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: Multiple Expected Catalysts
PRE - CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST - APPR EXPECTED CATALYSTS OLINVYK® New chemical entity (mu - opioid receptor) TRV027 AT 1 receptor selective agonist TRV045 Selective S1P receptor modulator • Phase 1 complete 2H 22 TRV250 G - protein selective agonist (delta receptor) • IND - enabling act
Slide 38: Appendix
38 JL: can will create a transition slide? Appendix
Slide 39: Head-to-Head Comparison of OLINVYK and IV Morphine
Head - to - Head Comparison of OLINVYK and IV morphine in Elderly/Overweight Subjects (N=18) 39 Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com . As with all opioids, serious, life - threatening, or fatal res
Slide 40: OLINVYK: Distinct From IV Morphine / Hydromorphone
Studied in >1,900 individuals Hydromorphone OLINVYK: Distinct From IV Morphine / Hydromorphone Morphine 40 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 41: Robust Clinical Development Program
No dosage adjustments for elderly / renally impaired No known active metabolites Robust Clinical Development Program 41 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
Slide 42: OLINVYK: IV Opioid Efficacy and Rapid Onset
OLINVYK: IV Opioid Efficacy and Rapid Onset 42 • 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 43: Primary Efficacy Results: Phase 3 Trials
43 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 44: 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 45: Robust Assessment of Respiratory Safety in Phase 3 RCTs
Robust Assessment of Respiratory Safety in Phase 3 RCTs 45 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 46: Robust Assessment of GI Tolerability in Phase 3 RCTs
Robust Assessment of GI Tolerability in Phase 3 RCTs 46 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 47: Positive Feedback from Formulary Stakeholders
Positive Feedback from Formulary Stakeholders 1 47 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 48: Omni-channel Approach for HCP Engagement
Omni - channel Approach for HCP Engagement 48 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 S
Slide 49: 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 49 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 50: Important Safety Information
50 JL: can will create a transition slide? IMPORTANT SAFETY INFORMATION
Slide 51: 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 ri
Slide 52: 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