Trevena, Inc. · OTC:TRVN
Trevena — Investor Presentation (March 2025)
36 slides from Trevena's investor presentation, March 2025
Slide 1: Innovating for Patients
INNOVATING FOR PATIENTS OTC Pink Open Market: TRVN I March 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements Any statements in this presentation about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candi
Slide 3: Innovative Pipeline in Areas with Significant Unmet Needs
Innovative Pipeline in Areas with Significant Unmet Needs PRE-CLIN PHASE 1 PHASE 2 PHASE 3 NDA POST-APPR EXPECTED CATALYSTS PoC – pain / target engagement Chronic, non-opioid pain. • Data reported TRV045 PoC - epilepsy • Data reported Selective S1P receptor modulator Epilepsy Epilepsy indications. •
Slide 4: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company S1PR: Validated target for blockbusters (fingolimod / siponimod / ozanimod / ponesimod) TRV045: Selective S1PR1 New chemical entity; potent & selective for subtype 1; developed in-house with strong IP (2038) Agonist Unique profile (with potential for no lymphopenia) f
Slide 5: TRV045 Overview
VW Trevena TRV045 Overview
Slide 6: TRV045: S1P1 Receptor – A Novel Target for CNS Indications
TRV045: S1P1 Receptor – A Novel Target for CNS Indications S1P1 receptors are highly expressed on key central nervous system cells involved in neuroinflammation Potential therapeutic role in seizures and pain signaling Epilepsy Neuropathic pain • Neuroprotective effects1 • Inhibits pain sensation4 •
Slide 7: TRV045 MOA: Rapid Receptor Recycling
TRV045 MOA: Rapid Receptor Recycling Maintained (rather than degraded) S1P receptors on cell surface ligand S1P1 receptor Gβγ GRK No lymphopenia Gαi β-arrestin2 reported in prior Phase 1 FIH study ↓cAMP ↑IKAch ↓ Ca++ Internalization (via IcaL) Other S1PR Drugs TRV045 Receptor Degradation Receptor Re
Slide 8: TRV045 MOA: S1PR Subtype-1 Selectivity
TRV045 MOA: S1PR Subtype-1 Selectivity Subtype-1 is broadly expressed in the CNS and may avoid effects associated with other subtypes • S1P acts on 5 distinct subtypes of receptors (S1P1-5) • TRV045 is potent and selective for S1P subtype-1 receptor - EC50 ~32 nM for G-protein signaling; EC50 ~2 µM
Slide 9: TRV045 MOA: Anti-Inflammatory Effect (nonclinical)
TRV045 MOA: Anti-Inflammatory Effect (nonclinical) Anti-inflammatory actions (cytokines / chemokines) on astrocytes in cell culture • Main Findings: Net anti-inflammatory action (statistically Anti-inflammatory significant) on astrocyte cytokine / chemokine release IL-10 markers - Increased all anti
Slide 10: NIH Epilepsy Therapy Screening Program (ETSP) Study Results – New Data
NIH Epilepsy Therapy Screening Program (ETSP) Study Results – New Data Summary and Main Findings • TRV045 has completed a broad range of ETSP anticonvulsant screening studies • Identification and Differentiation phase work largely complete • Data provide replicated evidence of TRV045 as an acute ant
Slide 11: Mouse 6Hz Electrical Stimulation Model (IP Administration) – NEW
Mouse 6Hz Electrical Stimulation Model (IP Administration) – NEW Positive dose-effect relationship – ED50 = 98.13 mg/kg 80 30 mpk 70 60 mpk 150 mpk 60 200 mpk 50 • TRV045 administered by IP route • N=8 animals / group 40 • Tested 1 hr post dose • ED50 est. 98.13 mpk 30 • ED50 for toxicologic dose >5
Slide 12: Rat MES Model (IP administration) – NEW
Rat MES Model (IP administration) – NEW Positive dose-effect relationship – ED50 = 17.47 mg/kg 100 10 mpk 90 15 mpk 20 mpk 80 30 mpk 70 60 • TRV045 administered by IP route • N=8 animals / group 50 • Peak effect 1 hr post dose 40 • ED50 est. 17.47 mpk • ED50 for toxicologic dose >500 mpk 30 • IP for
Slide 13: Study Design: Intra-amygdala kainate (IAK) model (IP, mouse) – NEW
Study Design: Intra-amygdala kainate (IAK) model (IP, mouse) – NEW Differentiation model of mesial temporal lobe epilepsy (MTLE) • Late stage ETSP model used to screen for drug-resistant seizures and disease prevention/modification • Microinjection of kainic acid into amygdala; results in emergence
Slide 14: Study Design: Intra-amygdala kainate (IAK) model (IP, mouse)
Study Design: Intra-amygdala kainate (IAK) model (IP, mouse) Differentiation model of mesial temporal lobe epilepsy (MTLE) Statistically significant reduction in seizure frequency and seizure burden CONFIDENTIAL
Slide 15: NYMC Study Results – Cryptogenic Infantile Spasms Model (IP, rat)
NYMC Study Results – Cryptogenic Infantile Spasms Model (IP, rat) Summary and Main Findings • On the primary endpoint, final analysis shows that TRV045 demonstrates a statistically significant, dose- dependent reduction in the number of NDMA-triggered spasms at both 2 hours and 4 hours pre-treatment
Slide 16: Efficacy of TRV045 in a Validated Model of Infantile Spasms
Efficacy of TRV045 in a Validated Model of Infantile Spasms PRIMING TRIGGER TRV045 Dosing Schedule Betamethasone NMDA IP (Pretreatment time prior to NMDA spasm trigger) 2x 0.4 mg/kg IP 7.5 mg/kg G22-23 P12 Test Compound 2 hour 4 hour G0 G15 Gestation Post-natal development Vehicle* X X delivery TRV0
Slide 17: Efficacy of TRV045 in a Validated Model of Infantile Spasms
Efficacy of TRV045 in a Validated Model of Infantile Spasms Two Hour Pre-treatment Four Hour Pre-treatment P=0.498 P=0.044 120 120 Primary Outcome: # of Spasms # of Spasms 100 P=0.020 100 P=0.015 Reduction in number 80 80 of spasms 60 60 40 40 20 20 0 0 10 mg/kg 30 mg/kg 60 mg/kg Vehicle 10 mg/kg 30
Slide 18: TRV045 Proof-of-Concept Study Program – Highlights
TRV045 Proof-of-Concept Study Program – Highlights Phase 1 Human Healthy Volunteers • Target Engagement. Demonstrated CNS penetration and target engagement • EEG Spectral Power. Statistically significant increases in brain waves (alpha, beta, gamma) associated with arousal, alertness, cognitive proc
Slide 19: TMS POC Study Design in Healthy Volunteers
TMS POC Study Design in Healthy Volunteers • Design: Randomized, double-blind, placebo-controlled, multiple dose, two-way cross-over (n=25 male subjects; mean age 31.5 years, range 21-55) - Placebo or TRV045 (250mg) for 4 days; post-dose assessments performed at 4 hours • TMS-EEG Pharmacodynamic end
Slide 20: EEG Shifts in Alpha, Beta, Gamma, Delta Power Spectra
EEG Shifts in Alpha, Beta, Gamma, Delta Power Spectra qEEG Power Spectral Analysis (TRV045 minus placebo) Eyes Closed Alpha: Significant increase across all regions % CFB [TRV045 – Placebo] * Beta/Gamma: Significant increase in frontal region * Associated with alertness / arousal / memory / learning
Slide 21: TRV045 Effect on Cortical Excitability vs AEDs
TRV045 Effect on Cortical Excitability vs AEDs* Mean change from baseline in motor-evoked potential (MEP) measured by peak-to-peak amplitude 1000 Pre-dose 900 859.0 840.1 4h post-dose Mean Peak Amplitude (µV) 782.0 800 700 605.4 600 500 400 300 200 100 0 Placebo Day 1 TRV045 Day 1 Estimated differen
Slide 22: Safety and Tolerability Summary
Safety and Tolerability Summary POC data generally consistent with FIH study • 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 • Scre
Slide 23: Safety and Tolerability Summary
Safety and Tolerability Summary Generally well tolerated and consistent with FIH study • AEs with incidence of ≥10% for any TRV045 dose shown below (none deemed drug related) Placebo TRV045 50mg TRV045 150mg TRV045 300mg PainCart Study N (%) Events N (%) Events N (%) Events N (%) Events General Diso
Slide 24: Overall Conclusions
Overall Conclusions TRV045 Proof-of-Concept Study Program • Target Engagement. Demonstrated CNS penetration and target engagement • Epilepsy. Promising evidence of early reduction in cortical excitability Statistically significant increases in brain waves (alpha, beta, gamma) associated with arousal
Slide 25: TRV045 Development Program: Key Milestones
TRV045 Development Program: Key Milestones • Nonclinical - DART studies; 3-month toxicology data (COMPLETE) - Nonclinical data package will support advancing to Phase 2 development - Strong support for epilepsy indications from ETSP (adult pharmaco-refractory epilepsy) and NYMC (orphan infantile spa
Slide 26: TRV045: Broad Potential Applicability
TRV045: Broad Potential Applicability Unique MOA Produces Compelling Profile Potent and selective S1P1R target engagement anti-inflammatory and nociceptive effects No lymphopenia (in FIH study) potentially limits other S1PR modulators May avoid AEs associated with approved S1PR drugs cardiac / pulmo
Slide 27: TRV027: New Chemical Entity Targeting the AT1 Receptor
TRV027: New Chemical Entity Targeting the AT1 Receptor Beta-arrestin biased action, with no G-protein signalling TRV027 Angiotensin II AT1 receptor Cell surface Cell interior G protein β-arrestin • No AT1R G protein activation • Potent recruitment of beta-arrestin • Antagonizes A-II G protein signal
Slide 28: 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 bra
Slide 29: 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 of TRV250 given by SC injection Well tolerated, with no SAEs across broad range of doses Predictable PK: dose-proportional between 0.1 mg to 30 mg SC Half-li
Slide 30: TRV734: Maintenance Therapy for Opioid Use Disorder
TRV734: Maintenance Therapy for Opioid Use Disorder Selective agonism at µ receptor: nonclinical evidence of improved tolerability Ongoing collaboration with National Institute on Drug Abuse (NIDA) NIDA study demonstrated reduced drug-seeking behavior in animal model of relapse2 >2.5M NIDA-funded pr
Slide 31: Trevena: Innovative CNS Company
Trevena: Innovative CNS Company S1PR: Validated target for blockbusters (fingolimod / siponimod / ozanimod / ponesimod) TRV045: Selective S1PR1 New chemical entity; potent & selective for subtype 1; developed in-house with strong IP (2038) Agonist Unique profile (with potential for no lymphopenia) f
Slide 32: Appendix
Appendix WE Trevena
Slide 33: TRV045: PainCart POC Study in Healthy Volunteers
TRV045: PainCart® POC Study in Healthy Volunteers • Design: Randomized, double-blind, placebo-controlled, single dose, four-way cross-over (N=25 subjects; 8F/17M, mean age 37.6 years, range 18-53) - Placebo or TRV045 (50/150/300mg) • Pharmacodynamic Endpoints: - Mechanical allodynia (Von Frey hair t
Slide 34: TRV045 Significantly Reduced Mechanical Allodynia
TRV045 Significantly Reduced Mechanical Allodynia 1% capsaicin-treated dominant volar forearm – Von Frey filament allodynic area (CFB, mm2) 300mg TRV045 v Placebo; P=0.0023 300mg TRV045 v Placebo; P=0.0001 150mg TRV045 v Placebo; P=0.0022 150mg TRV045 v Placebo; P=0.0002 Secondary Allodynic Area Tot
Slide 35: Effect Size Comparison: TRV045 v Other Analgesics
Effect Size Comparison: TRV045 v Other Analgesics Favors Placebo Favors Active Hedges' g -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 Mechanical Allodynia TRV045 (300mg) Cold Pressor Pain Test Pregabalin (300mg) Cold Pressor Pain Test VX-150 (1250mg) Cold Pressor Pain Test Effect Size: +0.2 – small effec
Slide 36: Summary: PainCart Study in Healthy Volunteers
Summary: PainCart® Study in Healthy Volunteers PainCart observations • 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