Trevena, Inc. · OTC:TRVN
Trevena — Corporate Update (November 2023)
34 slides from Trevena's corporate update, Nov 14, 2023
Slide 1: Innovating for Patients
INNOVATING FOR PATIENTS Nasdaq TRVN I November 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. (the “Company” or “we”), they are forward-looking statements reflecting management’s current beliefs and expectations. Forward-looking statements a
Slide 3: Trevena Overview
Trevena Overview 3 Focused on Innovative Medicines For CNS Disorders Olinvyk IV* Approved NCE for the management of acute pain in adults* Proven track record of Trevena internal discovery and development through approval S1P Modulator Program Novel S1P1R modulator with differentiated MOA (lead asset
Slide 4: TRV045: Innovative Clinical-Stage S1P1R Modulator
TRV045: Innovative Clinical-Stage S1P1R Modulator TRV045: Selective S1PR Modulator Compelling Clinical POC Data1 Differentiated Product Profile Large Addressable Target Indications Novel Family of S1PR Modulators S1PR: Validated target for multiple blockbusters (fingolimod / siponimod / ozanimod / p
Slide 5: S1P1 Receptor – Novel Target for CNS Indications
S1P1 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 - Drug
Slide 6: TRV045 MOA (1): Rapid Receptor Recycling
TRV045 MOA (1): Rapid Receptor Recycling β-arrestin2 S1P1 receptor Gβγ GRK ↑I Internalization KAch ligand Gαi ↓cAMP ↓ Ca++ (via IcaL) Reduces surface receptor, which leads to lymphopenia (Gilenya, etc) Receptor Recycling Maintains surface receptor and avoids lymphopenia, allowing free lymphocyte egr
Slide 7: TRV045 MOA (2): S1PR Subtype-1 Selectivity
Highly expressed in key CNS / brain cells TRV045 MOA (2): S1PR Subtype-1 Selectivity • S1P acts on 5 distinct subtypes of receptors (S1P1-5) • TRV045 is potent and selective for S1P subtype-1 receptor - S1P1R is highly expressed on astrocytes / other glial cells - May play role in central pain signa
Slide 8: TRV045 MOA (3): Anti-Inflammatory Effect (nonclinical)
1) P<0.05 v vehicle 2) Full cytokine / chemokine panel studied: (Inflammatory markers) – TNFa, IL-6, IL-1b, IL-17, IL-23, IL-33, CCL1, CCL2, CCL20, CXCL5, CXCL12, CX3CL1, IFNg, Csf2, Substance P; (Anti-inflammatory markers) – IL-10, IL-4. (Trevena, Inc., data on file) TRV045 MOA (3): Anti-Inflammato
Slide 9: TRV045 Proof-of-Concept Study Program – Highlights
TRV045 Proof-of-Concept Study Program – Highlights • Target Engagement. Demonstrated CNS penetration and target engagement • Neuropathic Pain. Statistically significant, dose-dependent effect in validated model of neuropathic pain • EEG Spectral Power. Statistically significant increases in brain wa
Slide 10: TRV045 POC Study Program – Overall Objectives
TRV045 POC Study Program – Overall Objectives • Provide evidence of CNS penetration and target engagement via pharmacodynamic effects on validated experimental study endpoints in humans, using: - Battery of acute and chronic pain models (characterize ‘analgesic phenotype’ for TRV045) - EEG and EMG m
Slide 11: Target Engagement (PainCart®) POC Study Design
Target Engagement (PainCart®) POC Study Design • Pharmacodynamic Endpoints: - Mechanical allodynia (Von Frey hair testing on capsaicin-treated skin), pressure pain, heat pain (capsaicin-treated, UVB-exposed, and unexposed skin), cold pain (CPT), electrical pain (stair, burst conditions), conditioned
Slide 12: TRV045 Significantly Reduced Mechanical Allodynia
TRV045 Significantly Reduced Mechanical Allodynia 12 1% capsaicin-treated dominant volar forearm – Von Frey filament allodynic area (CFB, mm2) Change from Baseline (mm2) -1200 -1000 -800 -600 -400 -200 0 200 400 600 Baseline Hr 1 Hr 2 Hr 4 Hr 6 Hr 8 Hr 10 Total Allodynic Area Placebo 50mg 150mg 300m
Slide 13: Effect Size Comparison: TRV045 v Other Analgesics
Effect Size Comparison: TRV045 v Other Analgesics 13 Favors Placebo Favors Active • Studies for comparators conducted at same lab (CHDR) conducting TRV045 studies • Single highest result for each comparator provided (cold pressor) from a battery of CHDR tests conducted - Mechanical allodynia test wa
Slide 14: Target Engagement (PainCart®) Study
Source: Trevena data on file Target Engagement (PainCart®) Study • Statistically significant, dose-dependent, treatment effect in model of capsaicin-induced mechanical allodynia provides evidence of the therapeutic potential of TRV045 in neuropathic pain - Recognized and validated study index of cen
Slide 15: TMS POC Study Design
TMS POC Study Design • TMS-EEG Pharmacodynamic endpoints: - Resting qEEG power spectral analysis (eyes open/eyes closed): Alpha, Beta, Delta, Gamma, Theta bands - TMS-evoked EEG response (single and paired-pulse TMS) • TMS-EMG Pharmacodynamic endpoints: - Motor-evoked potential (MEP), resting motor
Slide 16: EEG Shifts in Alpha, Beta, Gamma, Delta Power Spectra
EEG Shifts in Alpha, Beta, Gamma, Delta Power Spectra -5 0 5 10 Delta Theta Alpha Beta Gamma TRV045 Placebo 16 Resting qEEG Power Spectral Analysis – Eyes Open, Day 4 TRV045 v Placebo All Bands -5 0 5 10 Delta Theta Alpha Beta Gamma TRV045 Placebo -5 0 5 10 Delta Theta Alpha Beta Gamma TRV045 Placeb
Slide 17: TRV045 Effect on Cortical Excitability vs AEDs
TRV045 Effect on Cortical Excitability vs AEDs* Mean change from baseline in MEP on Day 1 with TRV045 comparable in magnitude to MEP reductions seen with known AEDs, including levetiracetam, valproic acid, and lorazepam, performed in the same laboratory 17 Mean change from baseline in motor-evoked p
Slide 18: Safety and Tolerability Summary
Safety and Tolerability Summary • No AEs assessed as probably / definitely related to study drug; no AEs reported as severe; no SAEs - 98% of AEs (102 of 104) in PainCart® study reported as mild - 99% of AEs (79 of 80) in TMS study reported as mild • Screening / follow-up physical exams (including o
Slide 19: Safety and Tolerability Summary
Safety and Tolerability Summary • AEs with incidence of ≥10% for any TRV045 dose shown below (none deemed drug related) • No clinically signficant difference (vs placebo) in any AEs including: Sedation Balance Disorders Attention Disturbances Nausea Dry Mouth Blurred Vision • 19 Generally well toler
Slide 20: Overall Conclusions
Overall Conclusions • Target Engagement. Demonstrated CNS penetration and target engagement • Neuropathic Pain. Statistically significant, dose-dependent effect in validated model of neuropathic pain • Epilepsy. Promising evidence of early reduction in cortical excitability Statistically significant
Slide 21: TRV045: Broad Potential Applicability
TRV045: Broad Potential Applicability Potential fields for development may include: Seizure treatment (anticonvulsant) Prevention of seizure (epileptogenesis) Pain (DPN, CIPN) Autoimmune (MS, RA, UC, Crohn’s Disease) Neuropsychiatric / neurodegenerative (MDD, schizophrenia, AD, PD) Potent and select
Slide 22: TRV045: Innovative Clinical-Stage S1P1R Modulator
TRV045: Innovative Clinical-Stage S1P1R Modulator TRV045: Selective S1PR Modulator Compelling Clinical POC Data1 Differentiated Product Profile Large Addressable Target Indications Novel Family of S1PR Modulators S1PR: Validated target for multiple blockbusters (fingolimod / siponimod / ozanimod / p
Slide 23: TRV045 Prior FIH Phase Study
TRV045 Prior FIH Phase 1 Study
Slide 24: TRV045 Phase 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) 24 Well Tolerated • Favorable tolerability profile with no SAEs Target Exposure Attractive PK Profile • Calculated free plasma c
Slide 25: TRV045 Nonclinical Data - Epilepsy
TRV045 Nonclinical Data - Epilepsy
Slide 26: Dose-dependent protection in corneal-kindled seizure models
TRV045 demonstrated dose-dependent protection in seizure risk in corneal-kindled seizure models Corneal-kindled Seizure Model TRV045: Dose Dependent Seizure Protection (nonclinical) 26 Corneal kindled mouse Subcutaneous 0 20 40 60 80 100 1 2.5 5 7.5 10 % protected TRV045 mg/kg Corneal kindled mouse
Slide 27: TRV045: Improved Seizure Burden / Freedom in Nonclinical Model
B ase line Ve hicle T RV045 0 4 8 1 2 1 6 2 0 Seizure B urden S core * 15 mg/kg * # 0 25 50 75 % Seizure Freedom Baseline Vehicle TRV045 B ase line Ve hicle T RV045 0 4 8 1 2 1 6 2 0 Seizure B urden S core * 10 mg/kg ** 0 25 50 75 % Seizure Freedom Baseline Vehicle TRV045 TRV045 demonstrated a dose-
Slide 28: TRV045: Protection from Acute Seizures in Nonclinical Model
TRV045 demonstrated protection from acute seizures in three replicated experiments TRV045: Protection from Acute Seizures in Nonclinical Model 28 Maximal Electroshock Model 0 5 1 0 1 5 2 0 2 5 3 0 3 5 0 2 0 4 0 6 0 8 0 TR V045 m g/kg s.c. % of rats protected Maximal electroshock Subcutaneous 0 1 0 2
Slide 29: TRV045 Nonclinical Data – Non-opioid Pain Indications
TRV045 Nonclinical Data – Non-opioid Pain Indications
Slide 30: TRV045 Efficacy in Nonclinical Chronic Pain Models
0 1 2 3 4 5 6 Fingolimod TRV045 No Lymphopenia TRV045 Efficacy in Nonclinical Chronic Pain Models (w/ no Lymphopenia) 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 20.
Slide 31: TRV045: Reversed Hyperalgesia in Nonclinical Model
Rat diabetic peripheral neuropathic pain (STZ) model TRV045: Reversed Hyperalgesia in Nonclinical Model 31 Veh 1 0 3 0 6 0 gabap 0 5 1 0 1 5 2 0 2 5 50% W ithdraw al Threshold (g) STZ TR V 045 (m g/kg, p.o.) Effective on thermal pain endpoint Effective on mechanical pain endpoint Source: Trevena dat
Slide 32: Important Safety Information
32 IMPORTANT SAFETY INFORMATION
Slide 33: 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 risk
Slide 34: 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