Sensorion Sas · EURONEXT:ALSEN
Sensorion Sas — Sensorion — J.P. Morgan Healthcare Conference 2025
47 slides from Sensorion Sas's conference presentation, January 2025
Slide 1: Unlocking The Potential Of Advanced Therapies For Hearing Loss
SENSORION Unlocking The Potential Of Advanced Therapies For Hearing Loss January 2025
Slide 2: Disclaimer
DISCLAIMER • This document has been prepared by Sensorion (the “Company”) and is provided for information • This document contains certain forward-looking statements. These statements are not guarantees purposes only. This document does not purport to contain comprehensive or complete information of
Slide 3: Establishing Global Leadership In Hearing Loss With Strong And Diversified Pipeline
Sensorion Establishing Global Leadership In Hearing Loss With Strong And Diversified Pipeline • Unmet clinical need: 1.5bn people affected by hearing loss (HL) • Multiple causes: genetic, environmental, idiopathic • Modality agnostic approach to hearing loss disorders • World-leading and exclusive p
Slide 4: Portfolio Of Advanced Hearing Loss Therapies
Sensorion Portfolio Of Advanced Hearing Loss Therapies Milestones Product Indication Discovery In-vivo POC Preclinical Phase 1 Phase 2 Phase 3 (estimated) 2nd Cohort SENS-501* Otoferlin Deficiency Phase 1/2 Completed in H1 2025 Gene Therapies Adult Onset CTA/IND Enabling GJB2-GT* RESTORE (presbycusi
Slide 5: Best-In-Class Partners And Internal Capabilities To Transform Standard Of Care
Sensorion Best-In-Class Partners And Internal Capabilities To Transform Standard Of Care TRANSLATIONAL CLINICAL DIAGNOSIS AND RESEARCH RESEARCH PATIENT JOURNEY PARTNERS GLOBAL CLINICAL CENTERS OF EXCELLENCE IN-HOUSE PRECLINICAL - CMC GENE THERAPY PATIENT ACCESS SMALL MOLECULES & CLINICAL EXPERIENCE
Slide 6: Gene Therapy Programs
1 GENE THERAPY PROGRAMS 6
Slide 7: Gene Therapy Programs Target Rare Auditory Diseases
Sensorion Gene Therapy Programs Target Rare Auditory Diseases FIRST PROGRAMS RESULTING FROM THE INSTITUT PASTEUR COLLABORATION OTOFERLIN DEFICIENCY GJB2-RELATED HEARING LOSS • Pediatric patients with mutations in OTOF suffer from severe to profound We have identified three forms of hearing loss asso
Slide 8: Otoferlin Deficiency
2 OTOFERLIN DEFICIENCY 8
Slide 9: SENS-501 Long-Term Hearing Recovery In A Standardized Translational Model
SENS-501 Long-Term Hearing Recovery In A Standardized Translational Model Of Otoferlin Deficiency Long-Term Hearing Restoration Hearing Restoration Correlates with de novo OTOF Expression AAV-mOTOF injected in mice before hearing onset SENS-501 injected in mice after hearing onset * 10 months after
Slide 10: SENS-501 Dedicated Surgical Approach for Gene Therapy
SENS-501 Dedicated Surgical Approach for Gene Therapy Non-Human Primates injected through the round window membrane (RWI) with or without stapedotomy (stap) 1 Fenestration Used for cochlear implant • Overpressure Surgical approach • Limited volume • Backflow • Irregular transduction rate • Surgical
Slide 11: Raising The Bar With The SENS-501 Audiogene Study
SENS-501 Raising The Bar With The SENS-501 Audiogene Study We wanted to generate a compelling value story showing that SENS-501 treatment is able to: • Demonstrate by itself hearing restoration in toddlers • Enable infants to have normal language acquisition and development • Improve Patient Reporte
Slide 12: SENS-501 Phase 1/2 Audiogene Study
SENS-501 Phase 1/2 Audiogene Study Audiogene, a Phase 1/2 clinical trial in homogenous population of infants and toddlers, aged 6 to 31 months, naive of cochlear implants, to assess safety, tolerability, and efficacy of SENS-501 following unilateral injection into the cochlea DMC Dose escalation DMC
Slide 13: SENS-501 Audiogene Study Status
SENS-501 Audiogene Study Status • First cohort of infants and toddlers (3 patients) injected in H2 2024 • Surgical administration procedure was uneventful in the 3 patients FIRST • Initial safety reported in first two patients COHORT - No dose-limiting toxicities, no Serious Adverse Events INJECTED
Slide 14: GJB2-Related Hearing Loss
3 GJB2-RELATED HEARING LOSS 14
Slide 15: Leveraging SENS-501 Program For GJB2-GT Program Success
GJB2-GT Leveraging SENS-501 Program For GJB2-GT Program Success SENS-501 Is Paving The Way For GJB2-GT SENS-501 GJB2-GT Aiming To Develop Best-In Class And First-In Class Gene Therapy • AAV capsid selected for high-level of target cells specificity • GT product showing high level of target cells tra
Slide 16: Connexin 26 Is A Gap-junction Protein Encoded By GJB2 Gene
GJB2-GT Connexin 26 Is A Gap-junction Protein Encoded By GJB2 Gene And Is Responsible For Tissue Homeostasis Mutations in the GJB2 gene Lead to Deafness GJB2 Expression in the Cochlea • GJB2 is the gene encoding for the Connexin 26 protein; one of 20 known connexins • Cx26 and Cx30 proteins are the
Slide 17: Lead Candidate Can Deliver Cx26 In The Appropriate Target Cells
GJB2-GT Lead Candidate Can Deliver Cx26 In The Appropriate Target Cells Correct Delivery Of Cx26 Using Lead Candidate Flag In Non-Human Primate Cochlea Cell Types Claudius Cells Deiters Cells Great Epithelial Ridge Cells Hensen Cells Inner Border Cells Inner Hair Cells Inner Phalangeal Cells Pilar C
Slide 18: GJB2-GT Lead Candidate Demonstrates Adequate Safety and Biodistribution Profile
GJB2-GT Lead Candidate Demonstrates Adequate Safety and Biodistribution Profile - Including Long-Term Local Tolerability in Mice and NHP Acute toxicity in WT Mice - High Dose IV injection • Study performed in preparation of upcoming GLP-toxicity in mice after IV injection • GJB2-GT does not interfer
Slide 19: Lead Candidate Prevents Hearing Loss In Relevant Mouse Model
T+7w - 1X GJB2-GT 100 ABR Threshold (dB SPL) Lead Candidate Prevents Hearing Loss In Relevant Mouse Model 80 60 Proof Of Concept In Mice with Progressive Hearing Loss Proof Of Concept In Mice with Congenital 40 Hearing Loss Example of One Mouse Injected After Hearing Onset T+7w - 1X 20 ABR threshold
Slide 20: GJB2-GT Program Status
GJB2-GT Program Status Update on Ongoing Ongoing Additional European Natural History IND/CTA Clinical Trial PoC Efficacy Natural History Study Enabling Applications and Safety Data Study in Collaboration Studies H2 2025 Oct 2024 OTOCONEX with Sonova (ESGCT) Copyright by Sensorion - 2025 - All Rights
Slide 21: SENS-401 Programs
4 SENS-401 PROGRAMS Multiple Indications To Treat And Prevent Hearing Loss 21
Slide 22: SENS-401 To Preserve Residual Hearing After Cochlear Implantation
CI SENS-401 To Preserve Residual Hearing After Cochlear Implantation COMBINATION OF COCHLEAR IMPLANT WITH SENS-401 TO PREVENT CELL-DEATH POST COCHLEAR IMPLANT PROCEDURE HEALTHY AGEING KEY FIGURES Growing understanding of the link between healthy hearing and healthy ageing 48,040 Implants sold by Coc
Slide 23: Residual Low Frequency Hearing Benefits for Cochlear Implant Users
CI Residual Low Frequency Hearing Benefits for Cochlear Implant Users Initial Initial shift* shift* Second shift* (2-4 weeks (2-4 weekspostoperative) postoperative) (3-6 months postoperative) between surgery between andand surgery initial activation initial activationofofthe thedevice device Attribu
Slide 24: SENS-401 CI Study Design - Study completed
CI SENS-401 CI Study Design - Study completed A Phase 2a, Multicenter, Randomized, Controlled, Open-label Study SCREENING PERIOD EVALUATION PERIOD W-6 W-1 W0 6 W6 8 W14 weeks weeks Randomization End of treatment D105 Start D49 D8 of treatment D1 Arm A n=18 A Phase 2a, Multicenter, SENS-401 Randomize
Slide 25: SENS-401 Provides Hearing Protection 6 & 14 Weeks Post-Cochlear Implantation
CI SENS-401 Provides Hearing Protection 6 & 14 Weeks Post-Cochlear Implantation LS Mean change from baseline of hearing threshold Mean of the 3-frequency average (250-750 Hz) hearing values at 6 and 14 weeks post CI threshold values at baseline, 6 weeks and 14 weeks post CI 0 40 Treated group (n=16)
Slide 26: SENS-401 Provides Residual Hearing Preservation 6 & 14 Weeks Post-CI
CI SENS-401 Provides Residual Hearing Preservation* 6 & 14 Weeks Post-Cochlear Implantation W6 Post-CI W14 Post-CI Complete: HP>75% Partial: HP of 25 to 75% 27% 3-frequency average (250-750 Hz) 14% 53% 29% • Patients in the SENS-401 treated group are twice as likely to show complete or partial heari
Slide 27: SENS-401 CI Final Results - Conclusion
CI SENS-401 CI Final Results - Conclusion SENS-401 can cross the labyrinthine barrier to target cochlear hair cells in all patients sampled, confirming primary endpoint is met. SENS-401, present in the perilymph fluid, reaches concentrations that are pharmacologically active. A complete hearing pres
Slide 28: Cisplatin Administration For Chemotherapies Damages The Inner Ear
CIO Cisplatin Administration For Chemotherapies Damages The Inner Ear And Leads To Hearing Loss, Tinnitus And Dizziness WHAT IS CIO? Hearing loss caused by cisplatin administration as chemotherapeutic treatment. Risk factors include young age as well as individual and cumulative cisplatin doses. CIO
Slide 29: SENS-401 Phase 2a Proof-Of-Concept Study NOTOXIS
CIO SENS-401 Phase 2a Proof-Of-Concept Study NOTOXIS Positive Preliminary Safety Data A Phase 2a, Multicenter, Randomized, Controlled, Open-label Study to Evaluate the Efficacy of SENS-401 to Prevent the Ototoxicity Induced by Cisplatin in Adult Subjects with a Neoplastic Disease SCREENING PERIOD RA
Slide 30: Preliminary Results Show Patients with High Exposure to Cisplatin May Benefit Most
CIO Preliminary Results Show Patients with High Exposure to Cisplatin May Benefit the Most from SENS-401’s Otoprotective Effects : SENS-401 (n=7) : CONTROL (n=9) Groups n Variables Mean SD Maximum mean PTA change for 3 most severe consecutives frequencies* (dB) Cisplatin dose 305 110.0 Contro
Slide 31: Key Takeaways From Preliminary Study Data
CIO Key Takeaways From Preliminary Study Data Cumulative dose of cisplatin is a key factor of ototoxicity severity SENS-401 has a favorable safety profile when administered continuously for up to 23 weeks in adult patients undergoing cisplatin-based chemotherapy Recruitment is progressing well Based
Slide 32: Conclusion
Sensorion Conclusion • Developing hearing loss therapeutics to treat, prevent and restore hearing – an area of high unmet clinical need • Combining extensive internal capabilities with world-leading exclusive partnerships • Advancing a robust and diversified pipeline with multiple upcoming milestone
Slide 33: Thank You
THANK YOU E:contact@sensorion-pharma.com 33
Slide 34: Appendix
_ . © Sensorion Appendix
Slide 35: Hearing Loss
HEARING LOSS 35 35
Slide 36: Access And Clarity Are Mandatory For Optimal Outcomes
HEARING Access And Clarity Are Mandatory For Optimal Outcomes (Hz) (dB HL) O = Right ear threshold Normal X = Left ear threshold Slight th f p s Mild t Hearing aid fitting range* z v h g k m d b ch j n o sh Moderate i a ng r Adults* e u Moderately-severe Children O Severe > 2 years* X O X O O O X O
Slide 37: Gene Therapy Programs Back-Up
GENE THERAPY PROGRAMS BACK-UP 37
Slide 38: OTOF Gene Encodes Otoferlin, a Key Ca2+ Sensor Protein
SENS-501 OTOF Gene Encodes Otoferlin, a Key Ca2+ Sensor Protein Increase in Ca2+ SNARE Proteins VAMP Ca2+ Ca2+ Ca2+ Ca2+ Vesicle Ca2+-Channel Otoferlin Pre-synaptic membrane neurotransmitters release restricted SNARE interaction Otoferlin SNARE interaction SNARE-complex binding primed vesicle contai
Slide 39: SENS-501 Leads to Restoration of Efficient Sound Processing in Behavioural Test
SENS-501 Leads to Restoration of Efficient Sound Processing in Behavioural Test Behavior Test Based on Hearing Recovery Implemented in Mouse White noise pulse (2-20 kHz, 115 dB) Wild type Non-injected Otof ko/ko Restored Otof ko/ko Olivier et al. ASGCT 2023 Copyright by Sensorion - 2025 - All Rights
Slide 40: SENS-401 Programs Back-Up
SENS-401 PROGRAMS BACK-UP Multiple Indications To Treat And Prevent Hearing Loss 40
Slide 41: SENS-401: A Pipeline In A Product Mechanism Of Action
SENS-401: A Pipeline In A Product Mechanism Of Action Disrupted Ca2+ Calcineurin INSULT homeostasis Activation Neurodegenerative cascades: Excitotoxicity Neuro Inflammation • NFAT translocation: oxidative stress, survival, inflammation pathways • Cell death pathways: BAD, mPTP, AIF, caspases activat
Slide 42: SSNHL
SSNHL Sudden Sensorineural Hearing Loss 42
Slide 43: Sudden Sensorineural Hearing Loss Is a Severe Disease Affecting 200,000 Patients Per Year
Sudden Sensorineural Hearing Loss (SSNHL) is a Severe Disease Affecting more than 200,000 Patients Per Year WHAT IS SSNHL? The sudden onset of a significant hearing loss due to dysfunction of the cells of the cochlea and central auditory structures. Hearing loss develops over less than 72 hrs, heari
Slide 44: SENS-401 SSNHL Program: AUDIBLE-S Phase 2 Design
SSNHL SENS-401 SSNHL Program: AUDIBLE-S Phase 2 Design A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL 50 clinical sites globally 1 Primary endpoint +/- oral corticosteroids Audiometry 15 dB improvement vs. Placebo +/- oral corticosteroids 115 patients enrolled Timing Q1 2019 June
Slide 45: SENS-401 Plasmatic Exposure
SSNHL SENS-401 Plasmatic Exposure PLASMATIC CONCENTRATION (Pre-dose at Day 14 and Day 28) Legend ng/mL SENS-401 High dose SENS-401 Low dose Placebo Copyright by Sensorion - 2025 - All Rights Reserved 45
Slide 46: SENS-401 Induces Complete PTA Recovery In 50% Of Patients
SSNHL SENS-401 Induces Complete PTA Recovery In 50% Of Patients COMPLETE PTA RECOVERY Complete PTA p=0.1452 p=0.0230 Placebo High Dose Low Dose * recovery (n/n total) 70 % patients with complete PTA 60 p=0.1230 p=0.2707 Day 28 9/28 12/23 13/26 50 recovery 40 Day 84 8/26 8/18 14/22 30 20 Legend SENS-
Slide 47: SENS-401 SSNHL Phase 2 Results Summary
SSNHL SENS-401 SSNHL Phase 2 Results Summary AUDIBLE-S SECONDARY ENDPOINT RESULTS • Complete PTA recovery is achieved in 50% of the SENS-401 treated patients • SENS-401 shows a clinically meaningful and statistically significant effect on PTA change (at least 10 dB) over time in a large homogeneous