Slide 1: Unlocking the potential of advanced therapies for hearing loss
Unlocking the potential of advanced therapies for hearing loss August 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: Our Vision: A Global Franchise Establishing Leadership In The Hearing Space
Our Vision: A Global Franchise Establishing Leadership In The Hearing Space Portfolio Product Pipeline (Institut Pasteur, Other…) GJB2-GT SENS-501 SENS-401 Ecosystem • EU Natural History Key Opinion Centers of Patient Groups Partners • US Studies Leaders Excellence • ROW Copyright by Sensorion - 202
Slide 6: 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 7: Sensorion Is Well Positioned To Transform the Hearing Landscape
Sensorion Is Well Positioned To Transform the Hearing Landscape - Institut Pasteur Partnership Feeds GT Pipeline GENE THERAPY SMALL MOLECULE: SENS-401 Otoferlin deficiency (SENS-501) Sudden Sensorineural Hearing Loss (SSNHL) Audiogene Ph1/2 study approved in France; AUDIBLE-S Ph2 Randomized and Cont
Slide 8: 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) Communication on SENS-501* Otoferlin Deficiency Phase 1/2 First Patient H2 2024 Adult Onset CTA/IND enabling RESTORE GJB2-GT* (presbyc
Slide 9: 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 10: Our Team Has Significant Experience In Gene Therapy Clinical Development
Our Team Has Significant Experience In Gene Therapy Clinical Development The team has been involved in 15+ programs … using different technologies… from preclinical to BLA filing… 10 4 1 15 1 1 Preclinical Clinical BLA filing Gene therapy Cell Gene editing (AAVs / LVs) therapy … across different org
Slide 11: Gene Therapy Programs
2 GENE THERAPY PROGRAMS Copyright by Sensorion - 2023 - All Rights Reserved
Slide 12: 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 13: 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 14: Gene Therapy Pediatric Indications Have Blockbuster Sales Potential
SENS-501 Gene Therapy Pediatric Indications Have Blockbuster Sales Potential SENS-501 CTA Approved In France 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 appro
Slide 15: 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 16: 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 17: 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 18: 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 19: Phase 1/2 Audiogene Study (SENS-501) Approved In France
SENS-501 Phase 1/2 Audiogene Study (SENS-501) Approved In France First Patient Communication Anticipated In H2 2024 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 Audiogene
Slide 20: Otoferlin Audinnove Consortium Provides Privileged Access To Patients And Surgeons
SENS-501 Otoferlin “Audinnove” Consortium Provides Privileged Access To Patients And Surgeons Audinnove consortium received Hospital-University Research (RHU) prize: • The consortium is eligible to receive up to €9.7m to develop a Gene Therapy program addressing otoferlin deficiency AUDINNOVE CONSOR
Slide 21: SENS-501 (OTOF) Gene Therapy Program Status – Progressing
SENS-501 SENS-501 (OTOF) Gene Therapy Program Status – Progressing Injection device system Preclinical package completed development completed GMP Drug product successfully CTA Approval in France manufactured Submission European Natural First Patient Communication History Study OTOCONEX H2 2024 Copy
Slide 22: 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 23: 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 24: 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 25: Lead Candidate Demonstrates Adequate Safety And Biodistribution Profile
Lead Candidate Demonstrates Adequate Safety And Biodistribution GJB2-GT Profile - Including Long-Term Local Tolerability In Mice And NHP ABR Thresholds in WT Mice Following Lead Candidate Injection 15 days after injection 3 months after injection 6 months after injection 120 120 ABRT+2m LE AAVDJ-smC
Slide 26: 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 27: GJB2 Gene Therapy Program Next Steps
GJB2-GT GJB2 Gene Therapy Program Next Steps Submission of European Natural Submission of Natural History Study History Study OTOCONEX in collaboration with Sonova Candidate selection Q2 2023 Preclinical IND enabling studies Clinical Trial Applications Mid-Year 2025 Copyright by Sensorion - 2024 - A
Slide 28: Small Molecule Programs
3 SMALL MOLECULE PROGRAMS Copyright by Sensorion - 2023 - All Rights Reserved
Slide 29: SENS-401: Multiple Indications To Treat And Prevent Hearing Loss
SENS-401: Multiple Indications To Treat And Prevent Hearing Loss Product Indication Discovery In vivo POC Preclinical Phase 1 Phase 2 Phase 3 Hearing preservation PREVENT SENS-401 after cochlear implantation Cisplatin SENS-401 Induced Ototoxicity TREAT Sudden SENS-401 Sensorineural Hearing Loss* *”P
Slide 30: SENS-401 - A Portfolio With Potential Blockbuster Value
SENS-401 - A Portfolio With Potential Blockbuster Value CI + SSNHL CIO For treatment And prevention Blockbuster Potential SENS-401 SSNHL clinical data and insight derisk further development of SENS-401 in other indications Copyright by Sensorion - 2024 - All Rights Reserved 30
Slide 31: 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 32: SENS-401 CI Study Design Primary Endpoint Met
CI SENS-401 CI Study Design Primary Endpoint Met 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
Slide 33: 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 Rat Guinea Pig Cat Human Minimal perilymph concentration in animals • Presence of SENS-401 in the perilymph is confirmed in 100% of the patients sampled following cochlear
Slide 34: 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 35: SENS-401 Provides Medically Significant Hearing Protection 6 Weeks Post-Cochlear Implantation
CI SENS-401 Provides Medically Significant Hearing Protection 6 Weeks Post-Cochlear Implantation Average Change From Baseline In 500 Hz Hearing Average Change From Baseline Of The Mean Hearing Thresholds Threshold (PTA) At 6 Weeks Post CI (PTA) At Frequencies 250, 500 And 750 Hz At 6 Weeks Post CI S
Slide 36: The Hearing Protection Provided By SENS-401 Continues For Up To 8 Weeks
CI The Hearing Protection Provided By SENS-401 Post-Cochlear Implantation Continues For Up To 8 Weeks After End Of Treatment Average Change From Baseline In 500 Hz Hearing Average Change From Baseline Of The Mean Hearing Thresholds Threshold (PTA) at 14 Weeks Post CI (PTA) At Frequencies 250, 500 An
Slide 37: SENS-401 CI Conclusion Primary Endpoint Met
CI SENS-401 CI Conclusion Primary Enpoint Met SENS-401 can cross the labyrinthine barrier to target cochlear hair cells in all patients sampled, confirming primary endpoint is met. Six and Fourteen weeks post-cochlear implantation, the residual hearing loss whether assessed at 500 Hz or across an av
Slide 38: Cisplatin Administration Damages The Inner Ear And Leads To Hearing Loss, Tinnitus And Dizziness
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 39: 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 40: SENS-401 Program Key Milestones, Data Readouts in 2024
CI & CIO SENS-401 Program Key Milestones, Data Readouts in 2024 SENS-401 with cochlear implants (CI) SENS-401 with cochlear implants (CI) - Positive Preliminary Results Reported - Primary Endpoint Readout H1 2024 SENS-401 CIO NOTOXIS SENS-401 CIO NOTOXIS - Preliminary Safety and Efficacy Data - Prel
Slide 41: Sensorion Newsflow [Estimated Timelines]
Sensorion Newsflow [Estimated Timelines] H2 2024 - First Patient Communication SENS-501 Gene Therapy Program H1 2025 – Enrollment completion of the first two cohorts Ongoing – Preclinical IND/CTA enabling studies GJB2 Gene Therapy Program Mid-Year 2025 – Clinical Trial Applications Sept 2024, during
Slide 42: Thank You
THANK YOU E: contact@sensorion-pharma.com
Slide 43: Hearing Loss
Hearing Loss Copyright by Sensorion - 2023 - All Rights Reserved
Slide 44: 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 45: SENS-401
SENS-401 Copyright by Sensorion - 2023 - All Rights Reserved
Slide 46: 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 47: SSNHL
SSNHL Copyright by Sensorion - 2023 - All Rights Reserved
Slide 48: 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 49: 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 50: 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 50
Slide 51: 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 52: SENS-401 SSNHL Phase 2 Results Summary Seeking Partners For Late-Stage Development And Commercialization
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