Slide 1: Unlocking the potential of advanced therapies for hearing loss
Unlocking the potential of advanced therapies for hearing loss September 20, 2024
Slide 2: Sensorion
1 SENSORION Our vision is to help people with inner ear hearing disorders to live life with unlimited connections Copyright by Sensorion - 2023 - All Rights Reserved
Slide 3: Disclaimer
DISCLAIMER • This document has been prepared by Sensorion (the “Company”) and is provided for • This document contains certain forward-looking statements. These statements are not information purposes only. This document does not purport to contain comprehensive guarantees of the Company’s future pe
Slide 4: Establishing Global Leadership In Hearing Loss With Strong And Diversified Pipeline
Sensorion: Establishing Global Leadership In Hearing Loss With Strong And Diversified Pipeline • Untapped opportunity with 1,5 bn people affected by hearing loss (HL); 0,5 bn suffer from disabling HL • Multiple causes: genetic, environmental, idiopathic • Modality agnostic approach leveraging unpara
Slide 5: Together With Best-In-Class Partners We Can Transform The Current Standard of Care
Together With Best-In-Class Partners We Can Transform The Current Standard of Care • EU reference center for monogenic forms of deafness • Natural History Study currently running for TRANSLATIONAL CLINICAL all monogenic forms of deafness; extension • Interdisciplinary approach to the RESEARCH mechan
Slide 6: Sensorion's Portfolio Of Advanced Hearing Loss Therapies
Sensorion’s Portfolio Of Advanced Hearing Loss Therapies Upcoming Product Indication Discovery In-vivo POC Preclinical Phase 1 Phase 2 Phase 3 Milestones (estimated) 1st cohort completed SENS-501* Otoferlin Deficiency Phase 1/2 by end of 2024 Adult Onset Preclinical CTA/IND RESTORE GJB2-GT* (presbyc
Slide 7: We Have Established Internal Capabilities To Ensure Successful Execution
We Have Established Internal Capabilities To Ensure Successful Execution PRECLINICAL - CLINICAL CMC GENE THERAPY REGULATORY PATIENT SMALL MOLECULES & EXPERIENCE FACILITIES EXPERTISE ACCESS GT PROGRAMS • Cell Model Platform: assays • 400 subjects enrolled in • Process development: non- • Develop regu
Slide 8: Gene Therapy Programs
2 GENE THERAPY PROGRAMS Copyright by Sensorion - 2023 - All Rights Reserved
Slide 9: Sensorion's Gene Therapy Programs Target Rare Auditory Diseases
Sensorion’s 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 We have identified three forms of hearing loss associated
Slide 10: Aiming To Develop Best-In Class And First-In Class Gene Therapy
SENS-501 Aiming To Develop Best-In Class And First-In Class Gene Therapy CRITERIA SENSORION AAV capsid selected for high-level of target cells specificity GT product showing high level of target cells transduction Limited off-target tissue biodistribution Surgical approach developed and mastered by
Slide 11: Gene Therapy Pediatric Indications Have Blockbuster Sales Potential
SENS-501 Gene Therapy Pediatric Indications Have Blockbuster Sales Potential SENS-501 (OTOF-GT) is the Perfect Pilot Program • SENS-501 will be the pilot program demonstrating that GT is a relevant • Well understood biology and pathology of the otoferlin medical approach for the inner ear deficiency
Slide 12: OTOF Gene Encodes Otoferlin, A Key Ca2+ Sensor Protein
SENS-501 OTOF Gene Encodes Otoferlin, A Key Ca2+ Sensor Protein Iow Ca2+ 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 vesic
Slide 13: SENS-501 Leads to Long-Term Hearing Recovery in a Translational Model of Otoferlin Deficiency
SENS-501 SENS-501 Leads to Long-Term Hearing Recovery in a 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 aft
Slide 14: SENS-501 Leads to Restoration of Efficient Sound Processing in Behavioural Test
SENS-501 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 link Copyright by Sensorion - 202
Slide 15: 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 Surgical approach • Overpressure • Limited volume • Backflow • Surgical procedure is similar to cochle
Slide 16: Phase 1/2 Audiogene Study (SENS-501)
SENS-501 Phase 1/2 Audiogene Study (SENS-501) Audiogene, a Phase 1/2 clinical trial in children aged 6 to 31 months to assess safety, tolerability, and efficacy of SENS-501 following unilateral injection into the cochlea DMC Dose escalation DMC Dose selection SENS-501 low dose Primary endpoint: Prim
Slide 17: Audiogene (SENS-501) Study Status
SENS-501 Audiogene (SENS-501) Study Status First Patient Injected • First Patient Injected in Q3 2024 • Initial safety data reported at 4 weeks - No dose-limiting toxicities, no Serious Adverse Events - Vestibular function remained intact and unchanged from baseline - Oto Acoustic Emissions (OAEs) r
Slide 18: SENS-501 (OTOF) Gene Therapy Program Status
SENS-501 SENS-501 (OTOF) Gene Therapy Program Status Pediatric Investigational Plan CTA Approval in Various Countries agreed in EU 1st Cohort Completed First Patient Communication H2 2024 2nd Cohort Completed H1 2025 Copyright by Sensorion - 2024 - All Rights Reserved 18
Slide 19: Connexin 26: A Gap-junction Protein Encoded By GJB2 Gene
Connexin 26: A Gap-junction Protein Encoded By GJB2 Gene and GJB2-GT Responsible For Tissue Homeostasis Mutations in the GJB2 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 dominating
Slide 20: Lead Candidate Was Selected to Answer Specific Development Criteria
Lead Candidate Was Selected to Answer GJB2-GT Specific Developement 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, active g
Slide 21: 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 22: 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 • GT-GJB2 does not interfer
Slide 23: GJB2-GT Lead Candidate Prevents Hearing Loss in Relevant Mouse Model
GJB2-GT Lead Candidate Prevents Hearing Loss in Relevant Mouse Model Proof Of Concept In Progressive Mouse Model Conditional knock-out mouse model leading to 2 phenotypes ABR threshold - 1 month after birth ABR threshold - 6 months after birth Hearing Loss Prevention Correlates With Connexin 26 Expr
Slide 24: GJB2 Gene Therapy Program Status
GJB2-GT GJB2 Gene Therapy Program Status Ongoing European Natural History Ongoing Natural History Study Study OTOCONEX in Collaboration with Sonova Preclinical IND/CTA Enabling Update on Additional PoC Efficacy Studies and Safety Data Oct 2024 (ESGCT) Clinical Trial Applications H2 2025 Copyright by
Slide 25: SENS-401 Programs
3 SENS-401 PROGRAMS Multiple Indications To Treat And Prevent Hearing Loss Copyright by Sensorion - 2023 - All Rights Reserved
Slide 26: 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 36,450 Implants sold by Coc
Slide 27: SENS-401 CI Study Design
CI SENS-401 CI Study Design Study completed A Phase 2a, Multicenter, Randomized, Controlled, Open-label Study SCREENING PERIOD EVALUATION PERIOD D1 D8 D49 D105 CI switch on Randomization SENS- Treated Arm: SENS-401 b.i.d Follow-up 401 Arm A COCHLEAR up to IMPLANTATION EFFICACY EFFICACY SENS-401 in 1
Slide 28: Primary Endpoint of the Phase 2a Clinical Study Has Been Met
CI Primary Endpoint of the Phase 2a Clinical Study for Residual Hearing Preservation Has Been Met Perilymph Concentrations Data 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 an
Slide 29: Residual Low Frequency Hearing Benefits for Cochlear Implant Users
CI Residual Low Frequency Hearing Benefits for Cochlear Implant Users Initial shift* Second shift* (2-4 weeks postoperative) (3-6 months postoperative) between surgery and initial activation of the device • Attributed to perioperative factors • Attributed to intracochlear fibrosis, excitotoxic chang
Slide 30: SENS-401 Provides Hearing Protection 6 & 14 Weeks Post-Cochlear Implantation
SENS-401 Provides Hearing Protection 6 & 14 Weeks CI Post-Cochlear Implantation LS Mean change from baseline of hearing threshold values Mean of the 3-frequency average (250-750 Hz) hearing threshold values LS Meanat 6 andfrom change 14 baseline weeks post CI threshold values of hearing at baseline
Slide 31: SENS-401 Provides Residual Hearing Preservation 6 & 14 Weeks Post-Cochlear Implantation
SENS-401 Provides Residual Hearing Preservation* 6 & 14 Weeks CI Post-Cochlear Implantation % of participants with Hearing Preservation (HP) % of participants with Hearing Preservation (HP) at 6 weeks post CI at 14 weeks post CI 100 100 Complete: HP > 75% 14% Complete: HP > 75% Partial: HP of 25 to
Slide 32: 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 33: Cisplatin Administration Damages The Inner Ear And Leads To Hearing Loss
Cisplatin Administration For Chemotherapies Damages The Inner CIO 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 34: SENS-401 Phase 2a Proof-Of-Concept Study NOTOXIS Positive Preliminary Safety Data
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 35: 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 Groups n Variables Mean SD Maximum mean PTA change for 3 most severe consecutives frequencies* (dB) Cisplatin dose 305.6 110.0 Control 9 PTA change 26.1 13.6 Cis
Slide 36: 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 37: SENS-401 Programs Status
CI & CIO SENS-401 Programs Status SENS-401 with cochlear implants – SENS-401 CIO NOTOXIS Full Data Readout Sept 20, 2024 - Preliminary Results S2 2023 SENS-401 CIO NOTOXIS SENS-401 with cochlear implants – - Preliminary Safety and Efficacy Data Final Results Sep 20, 2024 SENS-401 NOTOXIS – Completio
Slide 38: Sensorion Newsflow [Estimated Timelines]
Sensorion Newsflow [Estimated Timelines] H2 2024 – Audiogene enrollment completion of the first cohort SENS-501 Gene Therapy Program H1 2025 – Audiogene enrollment completion of the second cohort October 2024 (ESGCT) – GJB2-GT: Update on additional POC efficacy and safety data GJB2 Gene Therapy Prog
Slide 39: Thank You
THANK YOU E: contact@sensorion-pharma.com
Slide 40: Hearing Loss
Hearing Loss Copyright by Sensorion - 2023 - All Rights Reserved
Slide 41: Access And Clarity Are Mandatory For Optimal Outcomes
Access And Clarity Are Mandatory For Optimal Outcomes (Hz) O = Right ear threshold (dB HL) X = Left ear threshold Normal f th Mild p s t z v h g k m d b ch j n o sh Moderate i a Hearing aid fitting range* ng r Adults* e u Moderately-severe Children O Severe > 2 years* X O X O Cochlear implant candid
Slide 42: SENS-401
SENS-401 Copyright by Sensorion - 2023 - All Rights Reserved
Slide 43: SENS-401 Mechanism Of Action
SENS-401 Mechanism Of Action Disrupted Ca2+ Calcineurin Neurodegenerative cascades: INSULT homeostasis Activation NFAT translocation: oxidative stress, survival, inflammation Excitotoxicity pathways Neuro Inflammation Cell death pathways: BAD, mPTP, AIF, caspases activation Structural degeneration,
Slide 44: SSNHL
SSNHL Copyright by Sensorion - 2023 - All Rights Reserved
Slide 45: Sudden Sensorineural Hearing Loss (SSNHL) is a Severe Disease Affecting more than 200,000 Patients Per Year
SSNHL 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,
Slide 46: 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 Control group
Slide 47: 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 - 2024 - All Rights Reserved 47
Slide 48: SENS-401 Induces Complete PTA Recovery In 50% Of Patients
SSNHL SENS-401 Induces Complete PTA Recovery In 50% Of Patients Complete PTA Recovery 70 p=0.1452 * p=0.0230 Complete PTA p=0.1230 p=0.2707 Placebo High Dose Low Dose 60 recovery (n/n total) % patients with complete PTA 50 Day 28 9/28 12/23 13/26 40 recovery 30 Day 84 8/26 8/18 14/22 20 10 Legend 0
Slide 49: SENS-401 SSNHL Phase 2 Results Summary
SSNHL SENS-401 SSNHL Phase 2 Results Summary Seeking Partners For Late-Stage Development And Commercialization 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 effec