Slide 1: May 2022
| © Sensorion
Slide 2: Disclaimer
DISCLAIMER • This document has been prepared by Sensorion (the "Company") and is provided for information purposes only. This document does not purport to contain comprehensive • This document contains certain forward-looking statements. These statements are not guarantees of the Company’s future pe
Slide 3: Sensorion
1 SENSORION Copyright by Sensorion - 2022 - All Rights Reserved 3
Slide 4: Investment Highlights
Investments Highlights • Sensorion is focused on innovative treatments that can restore, treat and prevent hearing loss − Two gene therapy programs, OTOF-GT and GJB2-GT, targeting monogenic forms of deafness: • caused by a mutation of the gene encoding for Otoferlin • related to mutation in GJB2 gen
Slide 5: The inner ear: one of the most delicate organs in the human body
The inner ear: one of the most delicate organs in the human body Inner Ear Biology Limited number of hair cells: KEY FACTS • 3,500 Inner Hair Cells • 12,000 Outer Hair Cells Hair cells do not naturally regenerate According to the WHO*: ~ 400m people affected by disabling hearing loss worldwide inclu
Slide 6: Our strategy: Restore, Treat & Prevent hearing loss
Our strategy: RESTORE, TREAT & PREVENT hearing loss Causes of hearing loss GENE THERAPY APPROACH • Exclusive collaboration signed with Institut Pasteur in Gene Therapy to Idiopathic RESTORE auditory functions 25% • Program to RESTORE hearing in Otoferlin deficiency (DFNB9 deafness), Genetic one of t
Slide 7: Our critical strategic alliances from bench to bedside
Our critical strategic alliances from bench to bedside French Military Biomedical Research Institute CLINICAL • Access to a military population at risk of noise-induced hearing loss • EU reference center for monogenic forms of deafness RESEARCH • Strong medical network, strict monitoring and precise
Slide 8: Our pipeline: a comprehensive portfolio to restore, treat & prevent hearing loss
Our pipeline: a comprehensive portfolio to RESTORE, TREAT & PREVENT hearing loss Next milestones Product Indication Discovery In-vivo PoC Pre-clinical Phase 1 Phase 2 Phase 3 (estimated timelines) Otoferlin Clinical Trial OTOF-GT* deficiency Application H1 2023 GJB2-related GJB2-GT* early Candidate
Slide 9: An experienced team, board of directors and SAB
An experienced team, board of directors and SAB NAWAL OUZREN GÉRALDINE HONNET NORA YANG OTMANE BOUSSIF STEPHANIE FILIPE Chief Executive Officer Chief Medical Officer Chief Scientific Officer Chief Technical Officer Head of PMO SENSORION SENSORION SENSORION SENSORION SENSORION (Since 2017) (Since 202
Slide 10: We have established internal capabilities to ensure successful execution
We have established internal capabilities to ensure successful execution PRECLINICAL CAPABILITIES CLINICAL EXPERIENCE CMC GENE THERAPY REGULATORY EXPERTISE FOR SMALL MOLECULES FACILITIES & GT PROGRAMS • In Vitro platform: assays • 400 people enrolled in • Process development lab: • Multiple regulato
Slide 11: Gene Therapy
2 GENE THERAPY RESTORE Copyright by Sensorion - 2022 - All Rights Reserved 11
Slide 12: Strategic R&D collaboration with Institut Pasteur on genetics of hearing
RESTORE Strategic R&D collaboration with Institut Pasteur on genetics of hearing 2 PROGRAMS INITIATED UNDER THE COLLABORATION AGREEMENT WITH INSTITUT PASTEUR Rare disease, high unmet medical need Master Research Project Agreement “OTOF” Sensorion Agreement has an option Project Agreement “GJB2” on a
Slide 13: Sensorion's first gene therapy programs to treat rare auditory diseases
RESTORE Sensorion’s first gene therapy programs to treat rare auditory diseases 2 PROGRAMS INITIATED UNDER THE STRATEGIC COLLABORATION AGREEMENT WITH INSTITUT PASTEUR OTOFERLIN DEFICIENCY GJB2-RELATED HEARING LOSS We have identified three forms of hearing loss associated • Patients with mutations in
Slide 14: OTOF gene encodes Otoferlin, a key Ca2+ sensor protein
RESTORE RESTORE 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 primed vesicle containing restricted SNARE interaction Otoferlin SNARE interaction S
Slide 15: Dual AAV-OTOF resulted in durable hearing restoration in mature DFNB9 mice
Dual AAV-OTOF targeting IHCs resulted in durable hearing RESTORE restoration in mature DFNB9 mice HEARING RESTORATION TROPISM • Data showing 5-months AAV-OTOF efficacy in DFNB9 mouse model: the expression of Otof protein in mature Otof-/- • The chosen capsid of AAV-OTOF targets mice injected with du
Slide 16: AAV-OTOF vector transduces IHCs with high efficiency in mature NHP cochlea
RESTORE AAV-OTOF vector transduces IHCs with high efficiency and specificity in mature NHP cochlea 1 4 IHC 2 5 • The AAV-OTOF delivers transgenes to IHCs and not OHCs in non-human-primates • Transduction efficiency reaches more than 50% along the Apex to Base axis in the cochlea • The surgical proce
Slide 17: Otoferlin Audinnove consortium provides privileged access to patients and surgeons
Otoferlin “Audinnove” consortium provides privileged RESTORE 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 • Audio
Slide 18: OTOF gene therapy program status
RESTORE OTOF gene therapy program status PoC data in mouse PoC data in mouse & Submission of PoC preliminary data in European natural history NHPs study OTOCONEX Product development and Production of toxicological manufacturing agreement batches mid-2022 Advice from regulatory Clinical Trial Applica
Slide 19: Connexin 26: a gap-junction protein encoded by GJB2 gene
CONNEXIN 26: a gap-junction protein encoded by GJB2 gene RESTORE responsible for tissue homeostasis Mutations in the gene leads to deafness • GJB2 is the gene encoding for the Connexin 26 protein; one of 20 known connexins in humans and almost endemic to the cochlea (together with Cx30); a hexamer o
Slide 20: GJB2 gene therapy program next steps
RESTORE GJB2 gene therapy program next steps PoC data in mouse Submission of European Natural Submission of natural history study History Study OTOCONEX in collaboration with Sonova Candidate selection mid-2022 Preclinical IND enabling studies Copyright by Sensorion - 2022 - All Rights Reserved 20
Slide 21: SENS-401
3 SENS-401 TREAT AND PREVENT Copyright by Sensorion - 2022 - All Rights Reserved 21
Slide 22: 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 PREVENT Hearing preservation SENS-401 after cochlear implantation Cisplatin-Induced SENS-401 Ototoxicity TREAT Sudden SENS-401 Sensorineural Hearing Loss* *Pa
Slide 23: Sudden Sensorineural Hearing Loss SSNHL
Sudden Sensorineural Hearing Loss SSNHL 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, hearing sensitivity is reduced by at least 30 dB (1.000 fold) in the affe
Slide 24: SENS-401 SSNHL Program Phase 2 design
TREAT TREAT SENS-401 SSNHL Program Phase 2 design A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL 50 clinical sites globally 1 Primary endpoint Audiometry 15 dB improvement vs. Placebo 115 patients enrolled Timing Q1 2019 June 2020 Q1 2022 center Positive Final openings DSMB result
Slide 25: SENS-401 shows a clinically meaningful effect in a large sub-population
SENS-401 shows a clinically meaningful effect at Day 84 TREAT in a large sub-population PTA improvement from baseline compared to placebo on per protocol idiopathic SSNHL 5 Estimate PTA change from baseline (dB) Legend 0 SENS-401 High dose vs Placebo SENS-401 Low dose vs Placebo * 1 p < 0,05 * 2 p =
Slide 26: SENS-401 effect is more pronounced in a profound hearing loss sub-group
TREAT SENS-401 effect is more pronounced in a profound hearing loss sub-group (PTA ≥ 80 dB) PTA improvement from baseline compared to placebo Analysis from profound hearing loss sub-group (PTA ≥ 80 dB) 0 Estimate PTA change from baseline (dB) -5 Legend SENS-401 High dose vs Placebo -10 SENS-401 Low
Slide 27: Responder rate is always better in the treated groups compared to placebo
TREAT Responder rate is always better in the treated groups compared to placebo Responder analysis on ITT population Legend SENS-401 High dose SENS-401 Low dose Placebo Responder rate calculated with the data available at each visit n Day 7 Day 14 Day 28 Day 84 High Dose 13 19 21 17 Low Dose 13 21 2
Slide 28: SENS-401 induces complete PTA recovery in 50% of patients
TREAT SENS-401 induces complete PTA recovery in 50% of patients Complete PTA recovery (ITT, n = 94) 70 p=0.1452 * p=0.0230 Legend 60 p=0.1230 p=0.2707 SENS-401 High dose complete PTA recovery 50 SENS-401 Low dose % patients with Placebo 40 30 20 Complete PTA 10 Placebo High Dose Low Dose recovery (n
Slide 29: SENS-401 SSNHL phase 2 results summary
RESTOR TREAT E SENS-401 SSNHL phase 2 results summary Exploring partnering opportunities AUDIBLE-S SECONDARY ENDPOINT RESULTS • Safe and well tolerated in 115-patient SSNHL study; primary endpoint not met • SENS-401 shows a clinically meaningful and statistically significant effect on PTA change ove
Slide 30: Cisplatin-Induced Ototoxicity can lead to permanent disabling hearing loss
Cisplatin-Induced Ototoxicity can lead to permanent disabling hearing loss 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 leads to permanent inner ear problems in 50-
Slide 31: SENS-401 CIO NOTOXIS: Working on CTA amendment submission
SENS-401 CIO NOTOXIS PREVENT Working on CTA amendment submission SIGNIFICANTLY REDUCES CISPLATIN-INDUCED HEARING LOSS AND OUTER HAIR CELL DEATH IN PRE-CLINICAL MODELS TREATMENT PROTOCOL SENS-401 6.6 mg/kg, 13.2 mg/kg or placebo were administered Significant improvement versus placebo to rats once-da
Slide 32: SENS-401 clinical study submission to preserve residual hearing post cochlear implantation
PREVENT SENS-401 clinical study submission to preserve residual hearing post cochlear implementation COMBINATION OF COCHLEAR IMPLANT WITH SENS-401 TO PREVENT CELL-DEATH POST COCHLEAR IMPLANT PROCEDURE HEALTHY AGEING Growing understanding of the link between healthy hearing and healthy ageing 36,450
Slide 33: SENS-401 program next steps
RESTORE SENS-401 program next steps CTA approval for SENS-401 study to preserve residual hearing post cochlear implementation H1 2022 First patient enrolled in for SENS-401 study to preserve residual hearing post cochlear implantation mid-2022 SENS-401 CIO NOTOXIS CTA amendment submission H2 2022 SE
Slide 34: Sensorion potential newsflow
Sensorion potential newsflow [estimated timelines] • H1 2022 – CTA approval for SENS-401 study to preserve residual hearing post cochlear implantation • Mid-2022 – First patient in for SENS-401 study to preserve residual hearing post cochlear implantation • Mid-2022 – GJB2-GT candidate selection • M
Slide 35: Thank you
THANK YOU Nawal Ouzren Chief Executive Officer E: contact@sensorion-pharma.com 30