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Sensorion Sas — Sensorion — Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration Symposium 2025
55 slides from Sensorion Sas's conference presentation, Apr 26, 2025
Slide 1: Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration
Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration Symposium April 26, 2025
Slide 2: Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration
Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration April 26, 2025 - 11:30 am to 12:15 pm (UTC+1) Moderator: Nawal Ouzren, Chief Executive Officer, Sensorion • Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401 Prof. Yann Nguyen, Department of Otolaryngology-He
Slide 3: Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401
Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401 Yann Nguyen AP-HP, GHU « Sorbonne Université » ; site Pitié Salpêtrière ; DMU « ChIR » Chirurgie Innovation et recherche, Service ORL, Paris. IHU Institut Reconnect, équipe TI2S « Technologies innovantes et thérapies translationnel
Slide 4: SENS-401 as a Potential Otoprotective Agent
SENS-401 AS A POTENTIAL OTOPROTECTIVE AGENT SENS-401 Acts as A Specific Antioxydant Agent in the Cochlea Through A Dual Mechanism SENS-401 (® Azasetron) Disrupted Ca2+ Oxydative Stress Homeostasis Calcineurin Therapeutic Class Selective 5-HT3 receptor antagonist & Excitotoxicity Activation Cell Deat
Slide 5: SENS-401 as a Potential Otoprotective Agent
SENS-401 AS A POTENTIAL OTOPROTECTIVE AGENT SENS-401 Acts as A Specific Antioxydant Agent in the Cochlea Through A Dual Mechanism SENS-401 (® Azasetron) Disrupted Ca2+ Oxydative Stress Homeostasis Calcineurin Therapeutic Class Selective 5-HT3 receptor antagonist & Excitotoxicity Activation Cell Deat
Slide 6: SENS-401 as a Potential Otoprotective Agent
SENS-401 AS A POTENTIAL OTOPROTECTIVE AGENT SENS-401 Acts as A Specific Antioxydant Agent in the Cochlea Through A Dual Mechanism SENS-401 (® Azasetron) Disrupted Ca2+ Oxydative Stress Homeostasis Calcineurin Therapeutic Class Selective 5-HT3 receptor antagonist & Excitotoxicity Activation Cell Deat
Slide 7: Cisplatin-Induced Ototoxicity Mechanism of Action
CISPLATIN-INDUCED OTOTOXICITY MECHANISM OF ACTION Cisplatin-Induced Cochlear Inflammation & Oxydative Stress Uptake Accumulation Overload ROS Damage to cellular DNA, lipids & proteins Inflammation & apoptosis Cisplatin-induced inflammation & oxydative stress lead to hair cell death Domingo IK, Latif
Slide 8: Cisplatin-Induced Ototoxicity Mechanism of Action
CISPLATIN-INDUCED OTOTOXICITY MECHANISM OF ACTION Cisplatin-Induced Cochlear Inflammation & Oxydative Stress Uptake Accumulation Overload ROS Damage to cellular DNA, lipids & proteins Inflammation & apoptosis Cisplatin-induced inflammation & oxydative stress lead to hair cell death Domingo IK, Latif
Slide 9: Study Design & Objectives
STUDY DESIGN & OBJECTIVES A Phase IIa, 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 RANDOMIZATION EVALUATION PERIOD (max 31 weeks) Control group
Slide 10: Study Design & Objectives
STUDY DESIGN & OBJECTIVES A Phase IIa, 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 RANDOMIZATION EVALUATION PERIOD (max 31 weeks) Control group
Slide 11: Study Design & Objectives
STUDY DESIGN & OBJECTIVES SCREENING PERIOD RANDOMIZATION EVALUATION PERIOD (max 31 weeks) Control group Follow-up • Adults ≥ 18 years n=9 Cisplatin only No treatment Follow-up - No treatment • Adequate hearing levels Up to 18 weeks (max 6 cycles of 3 weeks) 4 weeks 8 weeks • Neoplastic disease plann
Slide 12: Patient Characteristics
PATIENT CHARACTERISTICS Demographic Characteristics at Baseline SENS-401 Control Total Patients Demographic Data Group Group (n=16) (n=7) (n=9) Male (n) 7 7 14 (87.5%) Gender Female (n) 0 2 2 (12.5%) Mean Age 57.3 56.1 56.6 (years) (Extraction date 31 July 2024) Mainly urological and head & neck can
Slide 13: Patient Characteristics
PATIENT CHARACTERISTICS Demographic Characteristics at Baseline & Cisplatin Exposure SENS-401 Control Average Total Patients Number Demographic Data Group Group Group n Cis. Cumulative Dose (n=16) of Cycles (n=7) (n=9) (mg/m2) Male (n) 7 7 14 (87.5%) Gender Control 9 305.6 3.3 Female (n) 0 2 2 (12.5
Slide 14: Patient Characteristics
PATIENT CHARACTERISTICS Demographic Characteristics at Baseline & Cisplatin Exposure SENS-401 Control Average Total Patients Number Demographic Data Group Group Group n Cis. Cumulative Dose (n=16) of Cycles (n=7) (n=9) (mg/m2) Male (n) 7 7 14 (87.5%) Gender Control 9 305.6 3.3 Female (n) 0 2 2 (12.5
Slide 15: Maximum Change From Baseline in PTA 4 Weeks After Last Cisplatin Dose
STUDY DESIGN & OBJECTIVES Maximum Change From Baseline in PTA 4 Weeks After the Last Cisplatin Dose As the cumulative dose of cisplatin increases, Maximum mean PTA change for 3 most severe consecutives frequencies* (dB) severity of ototoxicity observed in the control group escalates r=0.42 : SENS-40
Slide 16: Maximum Change From Baseline in PTA (Primary Endpoint)
STUDY DESIGN & OBJECTIVES Maximum Change From Baseline In PTA 4 Weeks After the Last Cisplatin Dose (Primary Endpoint) Mean effect in the Groups n Variables Mean SD Maximum mean PTA change for 3 most severe consecutives frequencies* (dB) control group for a cisplatin dose of 306 mg/m² Mean effect in
Slide 17: Conclusions
CONCLUSIONS Cumulative dose of cisplatin is a key factor of ototoxicity severity Based on preliminary data, no significant difference observed on ototoxicity measured by PTA change or CTCAE grading, however SENS-401 treated group received higher cumulative dose of cisplatin compared to control
Slide 18: Various Mechanisms Result in Residual Hearing Loss
VARIOUS MECHANISMS RESULT IN RESIDUAL HEARING LOSS Mechanical disrupture of intracochlear structures Mechanical disrupture of intracochlear structures (basilar membrane, spiral ligament, modiolar wall,spiral osseous lamina) Inflammatory process (fibrosis in perilymphatic space) and secondary apo
Slide 19: Residual Hearing Preservation in Adults: Study Design
RESIDUAL HEARING PRESERVATION IN ADULTS Study Design & Objectives A Phase 2a, Multicenter, Randomized, Controlled, Open-label Study to Evaluate the Presence of SENS-401 in the Perilymph after 7 days of Repeated Oral Administration in Adult Participants Scheduled for Cochlear Implantation SCREENING P
Slide 20: Patient Characteristics at Baseline
RESIDUAL HEARING PRESERVATION IN ADULTS Patient Characteristics at Baseline Treated Group (n=17) Control Group (n=10) Age (mean) Female 11 (65%) 6 (60%) Gender (n) (%) Male 6 (35%) 4 (40%) Mean PTA Hearing Threshold 67 61 (dB HL) at 500 Hz Cochlear implant indications were genetic/hereditary (n=5, 1
Slide 21: Perilymph Sampling Protocol
PERILYMPH SAMPLING PROTOCOL Perilymph sampling technique with the courtesy of Pr Steven O’Leary Cochlear CI622 array insertion (CHU Pitié Salpêtrière, AP-HP)
Slide 22: Primary Endpoint: Presence of SENS-401 in the Perilymph
RESIDUAL HEARING PRESERVATION IN ADULTS Primary Endpoint: Presence of SENS-401 in the Perilymph Treated with SENS-401 (n=16) n (%) SENS-401 levels ≤ LLOQ 0 SENS-401 levels > LLOQ 14*(100) *Among the 16 participants who underwent surgery, 15 have a perilymph samples and 14 samples were analyzable *LL
Slide 23: Secondary Endpoint: PTA Change at Week 6 & 14 Post-CI
RESIDUAL HEARING PRESERVATION IN ADULTS Secondary Endpoint: PTA Change at Week 6 & 14 Post-CI 250 Hz ■ After 7 weeks of SENS-401 treatment (6 weeks post-CI), reduction in residual hearing loss is consistently better across all frequencies in the SENS-401 treated group ■ This protective effect is mai
Slide 24: Secondary Endpoint: PTA Change at Week 6 & 14 Post-CI
RESIDUAL HEARING PRESERVATION IN ADULTS Secondary Endpoint: PTA Change at Week 6 & 14 Post-CI PTA 250-750 Hz Treated Group (n=15) Control Group (n=7) ANCOVA analysis and descriptive statistics p-value of 0.0567 (LS mean difference of -14.40 between Arm A and Arm B change from baseline suggested a tr
Slide 25: Conclusions
RESIDUAL HEARING PRESERVATION IN ADULTS Conclusions ■ Primary objective achieved: SENS-401 crosses the labyrinthine barrier and reaches the perilymph fluid ■ Clinically relevant reduction of residual hearing loss in SENS-401 treated group compared to the control group at 6 weeks after cochlear impla
Slide 26: Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration
Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration April 26, 2025 - 11:30 am to 12:15 pm (UTC+1) Moderator: Nawal Ouzren, Chief Executive Officer, Sensorion • Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401 Prof. Yann Nguyen, Department of Otolaryngology-He
Slide 27: Advancing Gene Therapy for OTOF-Related Hearing Loss in Young Children
Advancing Gene Therapy for OTOF- Related Hearing Loss in Young Children Natalie LOUNDON ENT Department Necker Enfants malades Hospital, Paris, France 27 Audinnove project
Slide 28: Consultant for Sensorion
Consultant for Sensorion ‘ SOREL Ssenr ee — PASTEUR 7 2ensorion rea
Slide 29: Gene Therapy in Human
Gene Therapy in Human In Vivo or Ex Vivo In Vivo: The vector carrying the therapeutic DNA is directly injected into the subject Ex Vivo: The cells to be treated are extracted and reinjected once treated (onco-hematology) Pathologies treated with GT using Associated Adenovirus (AAV) as vector
Slide 30: Gene Therapy for the Inner Ear
Gene Therapy for the Inner Ear The inner ear is a good target for GT Isolated organ Limited diffusion Limited off target effect Surgical routes The approaches Cochleostomy/Round, Oval window/Canalostomy Combined routes Volume 40-150μl (15 drops) Omichi et al., Hum Mol Genet., 201
Slide 31: Associated Adenovirus (AAV)
Associated Adenovirus (AAV) Vector Non-pathogenic Low immunogenicity 12 serotypes & combinations Target cells, tolerance ITR Promoter Transgene ITR AAV AAV gene therapy principle Hair Cells (CC) Usher, Otoferlin, Stereocilin Stria Vascularis Cells (SV) Waardenburg Work on mice mo
Slide 32: Auditory Neuropathy Spectrum Disorder
Auditory Neuropathy Spectrum Disorder Clinical aspects 2-10% Sensorineural Hearing loss (Berlin et al. 2010) Mild to profound hearing loss (Pure Tone Audiometry) Poor speech intelligibility rate Desynchronized Auditory Brainstem Responses Preserved Oto-Acoustic Emissions (30-83%) Stand
Slide 33: DFNB9: Current Candidate for GT Treatment
DFNB9: Current Candidate for GT Treatment Audinnove project Isolated synaptic dysfunction Preserved inner ear fine structures 1 Patient cohort Relevant mouse model 2 DFNB9 Effective GT in mature mice Preclinical validation PATIENTS 3 Phase 1/2 Clinical trial 2019/ S. Safieddine 33 Audinnove
Slide 34: Audiogene Clinical Trial (Sensorion)
Audiogene Clinical Trial (Sensorion) April 2024 (Europe and Australia) Clinical trial accepted in Europe (France first center) and Australia Candidates and study Infants aged 6 to 31 months with DFNB9 confirmed (bi-allelic otoferlin mutation) Severe to profound bilateral HL No cochlear i
Slide 35: Audiogene Clinical Trial (Sensorion)
Audiogene Clinical Trial (Sensorion) 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 D
Slide 36: Audiogene Clinical Trial: Cohort Demographics
Audiogene Clinical Trial (Sensorion) Cohort 1 demographics and clinical characteristics of enrolled patients (SENS-501 low dose) Patient 1 Patient 2 Patient 3 Sydney Cochlear Implant Paris Necker Hospital, Sydney Cochlear Implant Site Location Centre, Australia France Centre, Australia Age of Dosing
Slide 37: Audiogene Clinical Trial Status
Audiogene Clinical Trial Status • Patient recruitment as planned: first cohort of 3 infants and toddlers injected in H2 - 2024 • In the first 3 patients, good initial safety: FIRST • No dose-limiting toxicities, no Serious Adverse Events COHORT • Vestibular function and Otoacoustic Emissions (OAEs)
Slide 38: Impact on our Practice
Impact on our Practice Pediatrician, ENT Specialist, Speech Therapist, Audiologists 38
Slide 39: How does those GT trials impact our practice?
How does those GT trials impact our practice? Counselling: Hearing loss due to OTOF mutations GT described as an alternative to cochlear implantation in infants and toddlers Early parental counselling: algorithm rehabilitation program (ENT/Audiologists) Setting a specific screening program f
Slide 40: What should we get prepared for in a near future?
What should we get prepared for in a near future? Patients with DFNB9 Babies with profound HL: discuss GT rather than CI Older children/ Adults with congenital profound HL and unilateral CI: wait for future GT indications Progressive HL forms: GT could be an alternative to CI 40
Slide 41: What should we get prepared for in a near future?
What should we get prepared for in a near future? Other causes of Hearing loss: possible GT trial in few years from now? GJB2 USH2 STRC 41
Slide 42: Rehabilitation VS Restoration
Rehabilitation VS Restoration Are we here Yet? Life-changing advances Hope for natural hearing restoration 42
Slide 43: Thank you for your attention!
Thank you for your attention! 43
Slide 44: Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration
Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration April 26, 2025 - 11:30 am to 12:15 pm (UTC+1) Moderator: Nawal Ouzren, Chief Executive Officer, Sensorion • Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401 Prof. Yann Nguyen, Department of Otolaryngology-He
Slide 45: Developing Novel Gene Therapy for Hereditary Hearing Loss in Patients with GJB2 Mutations
Developing Novel Gene Therapy for Hereditary Hearing Loss in Patients with GJB2 Mutations Presentation Laurent DÉSIRÉ, Ph.D, Head of Preclinical Development, Sensorion
Slide 46: GJB2-GT for DFNB1A
GJB2-GT For DFNB1A Connexin 26 is Encoded by GJB2 Gene and is Responsible for Tissue Homeostasis Mutations in the GJB2 Gene Lead to Deafness GJB2 Expression in the Cochlea • Biggest cause of congenital deafness, around 50% of autosomal recessive non syndromic hearing loss cases are thought to result
Slide 47: GJB2-GT Lead Candidate Selected to Answer Specific Development Criteria
GJB2-GT Lead Candidate was Selected to Answer Specific Development Criteria CRITERIA LEAD CANDIDATE Natural and synthetic AAV capsid libraries screening for broad coverage of target cells. Expression cassette design for high-level of target cells transduction, correct cellular localization. Avoiding
Slide 48: Sensorion's Proprietary GJB2-GT Candidate
Expression Assay HEK293 HeLa DH GJB2-GT Sensorion’s Proprietary GJB2-GT Candidate Cx26 HSP90 AAV capsid Hemichannel Assay HeLa DH 60 Hela DH Hela DH GJB2-GT % PI + cells 40 Hela DH GJB2-GT CBX 100µm 20 0 Gap Junction Assay Control GFP candidate (+ Reg S1) HeLa DH vector • Synthetic AAV capsid with b
Slide 49: Lead Candidate can Deliver Connexin 26 in Appropriate Target Cells
GJB2-GT Lead Candidate can Deliver Connexin 26 in the Appropriate Target Cells Correct Delivery Of Connexin 26 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
Slide 50: Lead Candidate Prevents Hearing Loss in DFNB1A cKO Mouse Model
GJB2-GT Lead Candidate Prevents Hearing Loss in DFNB1A cKO Mouse Model Proof Of Concept in Mice with Progressive Hearing Loss Proof of Concept in Mice with Congenital Hearing Loss Mouse model provides congenital and Progressive Model progressive hearing loss Injected After Hearing Onset Congenital m
Slide 51: Adequate Safety and Biodistribution Profile in Mice and NHP
GJB2-GT 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 interfere with normal growth and don’
Slide 52: GJB2-GT is Now in IND/CTA Enabling Studies
Summary GJB2-GT is Now in IND/CTA Enabling Studies Early safety Cell-specific & biodistribution IND/CTA Clinical Trial expression of Enabling Applications Efficacy in DFNB1 Studies active hCx26 Q1 2026 mouse models Copyright by Sensorion - 2025 - All Rights Reserved 52
Slide 53: Thank You
THANK YOU Laurent.desire@sensorion-pharma.com Lise BARROT Pauline LIAUDET Crystel BONNET Christine PETIT Audrey BROUSSY Guillaume OLIVIER Amrit ESTIVALET Muriel SUDRES Rafik BOUDRA Anais PAGES Anne-Valérie HÉRITIER Virginie WONG JUN TAI Emilie BOUSQUET Géraldine PETIT Ghizlène LAHLOU Selma DADAK San
Slide 54: Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration
Hearing Loss Innovation: Expanding Frontiers in Protection & Restoration April 26, 2025 - 11:30 am to 12:15 pm (UTC+1) Moderator: Nawal Ouzren, Chief Executive Officer, Sensorion • Protecting Hair Cells, Preserving Hearing: The Potential of SENS-401 Prof. Yann Nguyen, Department of Otolaryngology-He
Slide 55: Thank You
= © Sensorion THANK YOU