Trevena, Inc. · OTC:TRVN
Trevena — Investor Presentation (April 2021)
50 slides from Trevena's investor presentation, Apr 21, 2021
Slide 1: Trevena: Innovating for Patients
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Slide 2: Forward-Looking Statements
Forward-Looking Statements Tothe.etent that statements contalnedin tis presentation are not descriptions othistorcal facts regaraing Trevena, In. the “Company” or"we). they are fonrara-ooking statements reflecting management’ current belefs and expectations. Forrardooking statements are subject to k
Slide 3: Trevena's Experienced Leadership Team
Trevena’s Experienced Leadership Team SENIOR MANAGEMENT Carte L. Bourdow President & Chief Execute Officer merck Scott Applebaum ‘SVP, Chief Legal & Regulatory offer Shire aristor myers Squibb Mark A. Dentrack, MD. ‘SVP, Chief Medical Officer weuronenics fag, ROWANT Barry Shin ‘SVP, Chief Financial
Slide 4: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company IV OLINVYK: NCE approved for the management of acute pain in adults Differentiated profile Commercial launch in Q1 2021; targeting 100 formulary wins by year-end Large market, 45M US hospital patients; 9M procedures is initial core focus targeted launch $1.5B+ market
Slide 5: Multiple Expected Catalysts
Multiple Expected Catalysts PRE-CLINICAL PHASE 1 PHASE2 PHASES NDA OLINVYK™ 121: New chemical entity Acutepain 1 APPROVED i ‘Commerciallaunch (mu-opioid receptor) Mabie ‘ARDS / abnormal clotting Collaborations with Transition to llaborations Novel AT, receptor coucemiae th Renapoae tal selective ago
Slide 6: OLINVYK: Differentiated Profile for Acute Pain
OLINVYK: Di ited Profile for Acute Pain COLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid and for whom are feren Data in complex patients Elderly / obese, multiple comorbidities New chemical entity Distinct from IV morphine Simplified, pr
Slide 7: OLINVYK: Broad Indication for Acute Pain
yr OLINVYK: Broad Indication for Acute Pain \ Large acute market opportunity — ~~ 45M patients receive IV opioids annually to treat acute pain’ BE Voricids _— + Unrivalled analgesic efficacy [Bl Local anesthetics ba! US injectable analgesic hospital market unit volume* 45% V Opioids [ll WNsAlDS/acet
Slide 8: OLINVYK: Well-Characterized Safety / Tolerability
OLINVYK: Well-Characterized Safety / Tolerability Adverse drug reactions reported in 25% of OLINVYK-treated Placebo (N= 162) Patients with i ficgauedla Key cost-drivers associated Nausea with IV opioids: Vorsiting Headache + Vomiting Dizziness " 18 25 - Can result in significant health Constipation
Slide 9: Real World Use: Complex Surgeries & Patients
Real World Use: Complex Surgeries & Patients Broad range of surgeries / medical procedures Cardiothoracic: + 32%2 65 years; 46% BMI 2 30 Bariatic surgery + Co-morbidities: diabetes, obstructive sleep apnea, Emergency COPD, chronic / cancer pain —— + Concomitant medications: antiemetics, antibiotics
Slide 10: OLINVYK: Ease of Dosing and Administration
OLINVYK: Ease of Dosing and Admi 3 vials allow for flexible and tailored IV dosing = No refrigeration/ reconstitution , + Bolus Dosing: 1 mg and 2 mg vials (single dose) + PCA Dosing: 30 mg vial (single patient use) + OLINVYK 1 mg = morphine 5 mgt 30 mL 27 mg cumulative daily dose limit Coen Do not
Slide 11: Customer Engagement Strategy
Customer Engagement Strategy revena
Slide 12: Targeted Account Launch
Targeted Account Launch Initial focus: complex patients in 3 key surgical areas <r . Inpatient & Physician specialties hospital outpatient ~4 specialties ~550 hospitals Anesthesiology ~500 ASCs Orthopedic ‘Community Colorectal Large regional systems Gynecologic Hospital outpatient Ambulatory surgica
Slide 13: Targeted Messaging and Resources
Targeted Messaging and Resources Key OLINVYK attributes focused on key customers os Health Care Practitioners (HCPs) Targeted Accounts Hospitals + OLINVYK: NCE, distinct from IV morphine + OLINVYK published safety data vs. IV morphine + Fast pain relief & no active metabolites + Published health eco
Slide 14: Robust Set of Peer-Reviewed Publications
Robust Set of Peer-Reviewed Publications Comprehensive overview of OLINVYK development program OLINVYK nonclinical / Phase 1 / Phase 2 data 45 publications OLINVYK Phase 3 trials & secondary analyses 9 publications pan on bor Sait rion lng BOXED WARHONG tao mein i Pectin ort ss OU, Wtrevena Baie - =
Slide 15: HECON Model Driven by Clinical Data
HECON Model Driven by Compelling Clinical Data Representative Inputs: Vorniting ‘Somnolence / sedation (©, saturation <90% AE rates ‘$8knausea / vomiting’ Govt / Cost of AES sources! §28k critical esp event? PULSES +47 days hospital stay? Publication of base and high-risk patient models expected 1H
Slide 16: Hospital Formulary Review Process
Hospital Formulary Review Process Epc ieee ‘Submits request for Conducts formal Reviews assessment/ Updates formulary, drug review assessmentofthe drug _votes to revise formulary protocols /ordersets YE 2021 target: 100 formulary wins Wtrevena 6
Slide 17: Differentiated Profile for Hospital Outpatient & ASCs
Differentiated Profile For Use in Hosp Outpatient & ASCs Separate reimbursement may provide lower access hurdle Physician trial in outpatient can accelerate inpatient uptake Gy No dosage adjustments for renally impaired Fast onset No known active (1-3 min median) metabolites Improves patient through
Slide 18: Learning from and Adapting to COVID-19 Challenges
We Continue to Learn from and Adapt to COVID-19 Challenges Transitioned into commercial organization with minimal business interruption + No delays in regulatory timelines; approval and DEA scheduling in 2H 2020 + Commercial supply of all 3 presentations made available to customers What we learned f
Slide 19: OLINVYK: Significant Opportunity in Acute Pain
OLINVYK: Significant Opportunity in Acute Pain ~45M patients g 2 Expanded areas offocus & (28m) : => ERE tia corefocus on (9m) 2032+ COM Patent Patient & Procedure Risk Wtrevena Initial core focus (9m) ~15M days of therapy itil foc + Hospitals / ambulatory surgical centers eee + "CORES! patient focu
Slide 20: TRV027
TRV027 NCE targeting the AT, receptor in COVID-19 Wtrevena 20
Slide 21: Multi-Organ Damage From Coronavirus
Multi-Organ Damage From Coronavirus Elimination of ACE2 protein leads to critical hormonal imbalances Coronavirus binds to and eliminates ACE2" + Leads to accumulation of angiotensin Il: ~ Acute lung injury and abnormal blood clots sans.cova - Can lead to ARDS / pulmonary embolism / stroke | * 66% -
Slide 22: TRV027: New MOA for COVID-19
TRV027: New MOA for COVID-19 Mechanism targeted to improve lung function and prevent abnormal clotting Angiotensin It <a “ AT, receptor Cell surface Cell interior Lung damage Lung repair Abnormal blood clots. Anti-inflammatory TRV027 is the only selective AT, receptor agonist Safety / tolerability e
Slide 23: TRV027 COVID-19 Study - REMAP-CAP
TRV027 COVID-19 Study - REMAP-CAP REMAP-CAP is a global clinical trial network led by experts in pandemic response + Multi-site, adaptive, Phase 2 / 3 trial in COVID-19 patients + 200 - 300 COVID-19 patients - Hospitalized patients, including those admitted to ICU = 218 years old + TRV027 being admi
Slide 24: Multiple Expected Catalysts
Multiple Expected Catalysts LINICAL PHASE 1 PHASE 2 HASE3 NDA OLINVYK New chemical entity Acute pain Vv ‘APPROVED oa : Commerciallaunch (mu-opicid receptor) TRVO27 ‘ARDS / abnormal clotting Collaborations with Transition Novel AT; receptor selective agonist 4H21: Gane ing ct (delta receptor) IND-ena
Slide 25: TRV250: New MOA for Acute Treatment of Migraine
TRV250: New MOA for Acute Treatment of Migraine Delta receptor: Untapped potential in CNS space Migraine represents a large market opportunity; total migraine drug market = ~$3.5B. Delta receptors have unique distribution Play important role in regulation of pain, mood, and anxiety throughout the br
Slide 26: TRV250: Well-Tolerated in Ph1 Healthy Volunteer PK Study
TRV250: Well-Tolerated in Ph1 Healthy Volunteer PK Study Subcutaneous doses up to 30 mg studied; no SAEs observed Single dose pharmacokinetics + Well tolerated, with no SAEs across broad of TRV250 given by SC injection range of doses 1000) + Predictable PK: dose-proportional between 0.1 mg to 30 mg
Slide 27: TRV734: Maintenance Therapy for Opioid Use Disorder
TRV734: Maintenance Therapy for Opioid Use Disorder Selective agonism at y receptor: Potential for improved tolerability Ongoing collaboration with National Institute on Drug Abuse (NIDA) Nonelinical evidence of improved tolerability with TRV734 >2.5M people in NIDA study demonstrated reduced drug-s
Slide 28: TRV045: Selective S1PR With No Lymphopenia
TRV045: Selective S1PR With No Lymphopenia Uniquely selective for S1P-subtype 1 receptor S1P, receptors are expressed broadly in the CNS Potential role in the treatment of: Epilepsy Chronic neuropathic pain + Neuroprotective effects! « Inhibits pain sensation® + Modulates permeability of BBB, ainnat
Slide 29: TRV045: Engages S1PR Without Lymphopenia
TRV045: Engages S1PR Without Lymphopenia S1P receptor activation conventionally associated with lymphopenia / immunosuppression + In animals, TRVO45 reversed paclitaxel-induced hyperalgesia without immune-suppressing activity = Fingolimod reduced lymphocytes by 78% = TRVO045 had no effect on lymphoc
Slide 30: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company IV OLINVYK: NCE approved for the management of acute pain in adults Differentiated profile Commercial launch in Q1 2021; targeting 100 formulary wins by year-end Large market, 45M US hospital patients; 9M procedures is initial core focus targeted launch $1.5B+ market
Slide 31: Appendix
APPENDIX revena
Slide 32: OLINVYK: Distinct From IV Morphine / Hydromorphone
OLINVYK: Distinct From IV Morphine / Hydromorphone H,C0 individuals IV morphine included as active comparator a - NCE with —_ Beat oe = 2032+ COM patent! Pinas ta porn Say rtn kl HED WAPUONS sted eres Pl Pesci oman a ne OLM com Wtrevena 2
Slide 33: Robust Clinical Development Program
Robust Clinical Development Program OLINVYK studied in > 1,900 individuals Phase 1 Phase 2 Phase 3 T T 4 head-to-head trials vs.IV morphine: + IV opioid efficacy + No dosage adjustments for elderly / renally impaired + No known active metabolit + Rapid onset of action + Well-characterized respirator
Slide 34: OLINVYK: IV Opioid Efficacy and Rapid Onset
OLINVYK: IV Opioid Efficacy and Rapid Onset Hard Tissue Soft Tissue + Efficacy achieved in hard tissue (SPID-48) (SPID-24) & soft tissue models Superior pain relief vs. Superior pain relief vs. placebo (p<0.01) placebo (p<0.02) + Rapid onset: perceptible pain relief within 2-5 minutes * OLINVYK effi
Slide 35: Primary Efficacy Endpoint Achieved in Two Pivotal Studies
Primary Efficacy Endpoint Achieved in Two Pivotal Studies OLINVYK achieved IV opioid efficacy 80. P< 0.0001 2 Zot | 2 Publishedin £ a. TheJournalof | PainResearch | = 3 2 < o. Placebo 0.1 0.35 0.5 Morphine (170) Oiiceriaine Ph3: Hard Tissue Surgery Mean baseline pain = 6.7 80: 0. Placebo 0.1 0.35 P=
Slide 36: OLINVYK: IV Opioid Efficacy in Phase 2 RCTs
OLINVYK: IV Opioid Efficacy in 2 Phase 3 RCTs & Pracedo (0-79) © OLINVYK 0.1m (n=76) © OUNWYK 035mg (0-79) © OLINWK 05mg (9-79) 0 4 8 4246 20 24 28 32 96.40 46 48 Study 1 (Orthopedic - Hard Tissue) 3 PCA regimens studied (0.1, 0.35, 0.5 mg) vs. placebo; all doses P<0,01 vs. placebo Eee ES ess Averag
Slide 37: Robust Assessment of Respiratory Safety in Phase 3 RCTs
Robust Assessment of Respiratory Safety in Phase 3 RCTs Data included in AMCP dossier used in formulary review Ph3 Respiratory Safety Events? + Prespecified secondary endpoint: Respiratory Safety Burden (RSB) (conpenetn athe nte eaten) = Calculated based on incidence and cumulative duration of respi
Slide 38: Robust Assessment of GI Tolerability
Robust Assessment of GI Tolerability i Data included in AMCP dossier used in formulary review + Phase 3 pivotal trials included measurements of nausea J vomiting rates and rescue antiemetic use + Additional exploratory post-hoc analysis was conducted using a “complete Gi response” endpoint? + Fullch
Slide 39: Customer Facing Organization
Customer Facing Organization Partnering with Syneos Health to provide “best in class” commercial support © Syneos. Health + Allows for execution speed and flexibility in deployment + Full range support: source, hire, train and deploy customer-facing roles + Ability to flex as business needs evolve 4
Slide 40: Launch Team: Top Talent with Hospital Experience
Launch Team: Top Talent with Hospital Experience Role ighlights Medical Science Liaisons Regional Sales Managers Key Account Managers Representatives Wtrevena SS a 100% with Advanced degrees 100% with Health Econ background 100% with hospital and launch experience 20+ Years experience Buy & Bill Hos
Slide 41: Feedback from Formulary Stakeholders
e Feedback from Formulary Stakeholders’ Majority of stakeholders view IV morphine as likely to be replaced by OLINVYK: Likely toRepacein Practice (noo; maple responses permit) ~75% of formulary stakeholders find OLINVYK’s published data clinically meaningful:? 1V morphine 66 Key Endpoint (vs. IV mor
Slide 42: Omni-channel Approach for HCP Engagement
Omni-channel Approach for HCP Engagement Communication across a full range of channels to maximize reach and impact Customize mix across channels Olinvyk.com Virtual “on demand” Medical Education programs Field directed: live, virtual & emai Professional Society Meetings & HCP social media Congresse
Slide 43: "Now Available" Campaign
“Now Available” Campaign “Now Available” Website + Order/Reimbursement/Dosing Guides + Connect with Medical Affairs and/or Sales Rep “Now Available” Drivers + Programmatic Banner Ads - Banner ad messaging to connect HCPs through digital journey + Journal Ads ~ Ads will run in American Journal of Hea
Slide 44: No Accumulation Despite Repeated Dosing
No Accumulation Despite Repeated Dosing Multi-Dose tQT Study Olceridine Moxiforacin + Zorg every 2st dthng ponte 20) Ginaman coor) N = 68healthy volunteers 02 4 6 8 10 12 16 16 18 20 22 24 Time (hours) Key results No accumulation through 24 hrs Mean QTcl <10ms at22 of 24 points No categorical QTc ou
Slide 45: Interaction Between the AT2 Receptor and ACE2 in COVID-19
Interaction Between the AT, Receptor and ACE2 in COVID-19 Downregulation of ACE2 by coronavirus indirectly promotes activation of the AT, receptor * Coronavirus binds to and downregulates angiotensin converting enzyme 2 (ACE2)' + Decrease in ACE2 elevates angiotensin II levels ~ Angiotensin Il activ
Slide 46: TRV027 COVID-19 Study - Imperial College London
TRVO027 COVID-19 Study - Imperial College London Interim review by DMSC' supports transition to REMAP-CAP trial + Randomized, double-blind, placebo-controlled proof-of-concept study + N= ~60 (30 per arm) COVID-19 patients = Hospitalized, non-ventilated = 218 years old + IV infusion of placebo or TRV
Slide 47: Delta Receptor Agonists Have Unique Benefits
Delta Receptor Agonists Have Unique Benefits Potential utility for a variety of CNS indications Triptans / Ditans + Target: serotonin receptors > mediate vascular excitability (associated CV risk)* * Migraine-specific treatment CGRPs * Target: CGRP receptors > regulate neuronal structures involved i
Slide 48: Important Safety Information
IMPORTANT SAFETY INFORMATION revena
Slide 49: 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 preserbing OLINVYK, and monitor al patients regularly forthe development behavi
Slide 50: Warnings and Precautions
[WARNINGS AND PRECAUTIONS + Aswith alot OLECUYK ay cause spas ofthe sphincter of 44; andmay caseincesesin FE nies te Stone ‘orang Aévvepapamevonen ungOLLWTE. ire plengedpesod ceo . in seat ‘pod nthe! sare anders tatappopat etme! besa re cena + Rl dn pin een oa dnthy edt cenit c Ou i thes Seaiay shoc