A WORLD IN WHICH THE PRIVILEGES OF HEARING AND BALANCE ARE AVAILABLE TO ALLTM

Citi Virtual BioPharma Conference

September 2020

CONFIDENTIAL | 1 Hearing & Balance: Significant Needs, Life-Changing Medicines

Focused Approach: Restore Functional Hair Cells to Inner Ear

Integrated Platform: Single cell genomics, Therapy

Experienced Team: Inner Ear Biology, Drug Hunting Leading Company Emerging Field Sustainable Value Creation: Platform, Pipeline, Intellectual Property Significant Unmet Needs: Hearing and Balance Disorders

CONFIDENTIAL | 3 Hair Cells in Inner Ear: Key Transducers of Mechanical Signals Loss of HCs in Cochlea/Vestibule is Major Cause of Hearing & Balance Disorders

Stereocilia

Vestibule / Balance Function Hair cell Aging and chemical insults cause loss of functional hair cells in the vestibule

Nerve ending

Cochlea / Hearing Function Aging, noise, and genetics cause loss of functional hair cells in the cochlea

CONFIDENTIAL | 4 Decibel Platform: Restoring Hair Cell Functionality

Restoration of Hearing and Balance

Restoration of Hair Cell Functionality

Rare Genetic Disorders Common Disorders Gene Replacement Hair Cell Regeneration

Single-cell Genomics Precision Gene Therapy Inner Ear Expertise

CONFIDENTIAL | 5 Gene Therapy: Ideal Modality For the Ear Strong parallels to the eye

Ideal Organ Decibel Proprietary Gene Regulatory Elements Manufacturing Enable Precise Spatial and Temporal Regulation • Tiny volume, enclosed • ~100x lower product compartment, high requirement vs systemic titers All Hair Cells • Local delivery, no systemic exposure • Access validated Inner Hair Cells delivery/surgery route • Immuno-privileged Outer Hair Cells Systemic Otic Vestibular >5,000L Process ~200L Process Supporting Cells scale for scale for commercial commercial

CONFIDENTIAL | 6 Targeted Delivery of Otic Therapy Platform links key gene targets to proprietary products Genomics & Computation Platform Therapeutic Delivery

Epigenome Gene Therapy: Proprietary target/ Non- ATACseq; Cut&Run functional

Transcriptome Therapeutic Target

scRNAseq; NucSeq Small Molecule: Spliceosome Validated Target Restore Functionality

PacBio IsoSeq

CONFIDENTIAL | 7 Decibel’s Strategies for Restoration of Hair Cell Functionality Drugs to complement genetic mutations or to regenerate hair cells

Immature Cochlear Hair Cell Regeneration Supporting Cell

Gene Outer Inner Hair Cell Replacement Hair Cell

Vestibular Regeneration

Type I Type II Hair Cell Hair Cell Supporting Cell CONFIDENTIAL | 8 Pipeline 2020: Decibel Retains 100% of Commercial Rights

PROGRAM TARGET/MOA TARGET ID/VALIDATION DRUG DISCOVERY CLINICAL TESTING NEXT MILESTONE Gene Therapy for Congenital Deafness

DB-OTO Otoferlin REGENERON IND Q4’21 Co-development; Decibel AAV.103 Undisclosed commercializes DC

Regenerative Medicines: Hair Cells

DB-ATO ATOH1/Vestibule IND 1H’22

AAV.RF301 Cochlea DC

Discovery Vestibule/Cochlea DC

Discovery Vestibule/Cochlea DC

Otoprotection

DB-020 Cisplatin Inactivation POC 2021* *Registrational Trial Gene Therapy Small Molecule 2022

CONFIDENTIAL | 9 DB-OTO for congenital genetic hearing loss DB-OTO for Congenital OTOF Deficiency

• Biology: Otoferlin is a calcium sensor at base of inner hair cell • Patient Phenotype: Profound deafness • Identification: Newborn testing; OTOF genetic test • Epidemiology: Estimated US & EU5 prevalence of 9,000 – 36,000; incidence of ~115 – 450 / year • Treatable OTOF Mutations: Single gene transfer • DB-OTO: Differentiated vs competition – Precision gene therapy; proprietary, selective expression of otoferlin in hair cells – Clinical strategy leverages unique relationship with largest characterized patient cohort

CONFIDENTIAL | 11 Dual AAV.OTOF Delivery Rescues Normal Hearing Sensitivity in Congenitally Deaf Mice

OTOFQ828X/+ OTOFQ828X/Q828X OTOFQ828X/+ OTOFQ828X/Q828X OTOFQ828X/Q828X Treated

Dual AAV-OTOF Delivery

Expression of OTOF Transgene: Selective expression, robust functional recovery

CONFIDENTIAL | 12 DB-OTO: Proprietary Regulatory Element Provides Cell-Specific Expression and Enables Improved Prolonged Efficacy

Durable efficacy in rodents vs ubiquitous Cell-selective dual AAV expression promoter (competition) in non-human primates

Myo7a AAV-smCBA-hOTOF Hair Cells (Target) DAPI GFP

Sensitivity DB-OTO

Normal Range

Weeks After AAV Injection

Emerging safety data in eye confirms importance of cell-selective transgene expression. Xiong et al (2019) PNAS

CONFIDENTIAL | 13 DB-OTO Clinical Development Expedited path through committed partnership with largest characterized OTOF cohort

149 Patients with Confirmed Biallelic Timeline To Clinical POC OTOF Mutations Identified in Spain 2020 2021 2022

CMC, Process, Analytical, Stability, Supply, Centralized Genetic Manufacturing Distribution Diagnosis with PI CTA GLP Tox IND Profound Congenital Deafness Clinical Trials

Patient registry

Natural History Study Ongoing with Patients

CONFIDENTIAL | 14 Regenerative Medicines Atoh1+/+ Atoh1-/-

Vestibule DB-ATO for Regeneration of Vestibular Hair Cells F-actinAtoh1+/+ Product: DB-ATO is an AAV gene therapeutic; deliver ATOH1 Atoh1+/+ Atoh1-/- • with proprietary support-cell promoter • Biology: ATOH1 is a bHLH factor expressed in

Myo7a (HC marker) developing hair cells, required for hair cell differentiation F- -/- Atoh1 • Mechanism: DB-ATO converts supporting cells into hair cells • Indications: Balance disorders caused by chemicals or age – Severe Indication: Bilateral Vestibulopathy

Myo7a (HC marker) – 80% loss of vestibular hair cells; 130K in US, EU5 – Broad Indication: Age-related balance disorders DB-ATO SC-specific ATOH1 WPRE polyA – 15M in US

CONFIDENTIAL | 16 Vestibule DB-ATO Robustly Regenerates Type 2 Vestibular Hair Cells In Vivo Support cell- selective expression Hair Cell Regeneration w DB-ATO Control + DB-ATO Off-target region Contralateral ear Treated ear HC marker Pou4f3 (nucleus) C57Bl/6 mice 6-9 wko males

Pou Utricle Hair4f3 cells GFP • Vestibular hair cells killed w IDPN Off-target • 14d after IDPN, DB-ATO delivered region unilaterally • 14d after DB-ATO, hair cells were

assessed Crista

CONFIDENTIAL | 17 Vestibule DB-ATO Development Path to IND, Clinical Trials

Efficacy in rodent models Identical tests in humans

Electrophysiology Physiology

VOR VOR In Vivo DC Q121 Regeneration IND 1H22 Q4 19

Balance Function Mobility and Vision

CONFIDENTIAL | 18 Cochlea Regeneration of Cochlear Outer Hair Cells for Restoration of Hearing AAV.RF301 Converts IHCs to OHCs Single-cell genomics defines targets AAV.RF301 Overexpresses RF301 and to direct outer hair cell fate converts IHCs to OHC fate

Hdac3 1 Kdm4a Mtpn Htatip2 Dnmt3a Mlxip Foxo3 Foxn3 0.8 Prnp Sall1 Pknox2 Klf9 Untreated Ear Rora Six2 Trps1 0.6 Actn4 Mef2a Pdcd11 Nfkb1 Hlcs Zfp410 Banp 0.4 Zbtb7b Esrra AAV.RF301 Zfp740 Zkscan3 Creb3l1 Ighm 0.2 Zfp324 Arnt Lig1 Elk3 Zbtb40 Crem Smarca2 0 Nfatc2 Rest Nfib Zfp608 Nfix Smad7 Mafk Adarb1 Irf6 Nacc2 Rorb Bhlhe40 Ikzf2 Jun Zfp423 OHCs Nr3c1 Tppp RF301 Cat Zfp637 Zfp777 Kmt2a Nr2f2 Zfp592 Pura Zfp365 Zbtb46 Zfp654 BC005561 Zfp516 Cic Zhx3 Rxra Zfp106 OHC Zfp277 Thra Tmem33 Zc3h7a Srrm3 Pds5a Zbtb4 Ube2k Ctbp2 Id4 Srebf1 Nfat5 candidates Ddit3 Sall3 Mdm2 Srebf2 Gtf2i Prdx5 Smap2 Zbtb7a Zfp618 Gata3 Prestin IHCs Irf9 Mef2d Taf1 Zfp523 Kdm2a Abcf2 Zfp398 Zfp638 Hmg20a Msi2 Phalloidin Nmral1 Tead1 Tead2 H2afy Irx3 Ezh2 Rfxap Sox9 Tgif2 Egr4 Egr3 Npas4 Sox11 Fhl2 Prox1 Cers2 Gm10093 Dazap1 Dnajc21 AAV-RF301 Treated Ear Isl1 Ran Ebf1 Atoh1 Hes6 Rpl35 Rps10 Psma6 Akr1a1 Barhl1 Smarca5 Ruvbl1 U2af1 Gtf2a2 Transcription factors Transcription Zfp428 Ssbp3 Zfp326 Nuak1 Pknox1 Cyb5r1 Tceal5 Msra Cers6 Hdac3 Zmat4 1 Bcl11b Kdm4a Npdc1 Mtpn Bcl2 Ybx1 Htatip2 Stub1 Zmat2 Dnmt3a Zfp667 Mlxip Yeats4 Tfdp2 Foxo3 Hnrnpa1 Foxn3 Tfdp1 0.8 Rbm17 Prnp Hmgn3 Sall1 Lhx3 Cers4 Pknox2 Ugp2 Klf9 Bax Mrps25 Rora H1fx Six2 Nap1l1 Pax2 0.6 Trps1 Traf4 Actn4 Mcm6 Neurod6 Mef2a Rab2a Cd59a Pdcd11 Ptcd1 Nfkb1 Klf7 Las1l Hlcs Cdk2ap1 Zfp410 Mycl Nono 0.4 Banp Zfp330 Zbtb7b Insm1 Irx2 Esrra Id1 E2f3 Id2 Magoh Zfp740 Nr2f6 Zkscan3 Zbtb20 Diablo Creb3l1 Gar1 Ighm Snrpb2 0.2 Rps4x Zfp324 Zmiz1 Hnrnpc Arnt Nr2f1 Lig1 Rbpj Elk3 Lsm6 Hmgb2 IHCs expressing the Zbtb40 Crem Tbpl1 Smarca2 0 Nfatc2 Rest Nfib Zfp608 Nfix OHC marker, Prestin Smad7 Mafk Adarb1 Pseudotime Irf6 Nacc2 Rorb Bhlhe40 Ikzf2 Jun Zfp423 Nr3c1 Tppp CONFIDENTIAL | 19 Cat Zfp637 Zfp777 Kmt2a Nr2f2 Zfp592 Pura Zfp365 Zbtb46 Zfp654 BC005561 Zfp516 Cic Zhx3 Rxra Zfp106 Zfp277 Thra Tmem33 Zc3h7a Srrm3 Pds5a Zbtb4 Ube2k Ctbp2 Id4 Srebf1 Nfat5 Ddit3 Sall3 Mdm2 Srebf2 Gtf2i Prdx5 Smap2 Zbtb7a Zfp618 Gata3 Irf9 Mef2d Taf1 Zfp523 Kdm2a Abcf2 Zfp398 Zfp638 Hmg20a Msi2 Nmral1 Tead1 Tead2 H2afy Irx3 Ezh2 Rfxap Sox9 Tgif2 Egr4 Egr3 Npas4 Sox11 Fhl2 Prox1 Sox2 Cers2 Gm10093 Dazap1 Dnajc21 Isl1 Ran Ebf1 Atoh1 Hes6 Rpl35 Rps10 Psma6 Akr1a1 Barhl1 Smarca5 Ruvbl1 U2af1 Gtf2a2 Zfp428 Ssbp3 Zfp326 Nuak1 Pknox1 Cyb5r1 Tceal5 Msra Cers6 Zmat4 Bcl11b Npdc1 Bcl2 Ybx1 Stub1 Zmat2 Zfp667 Yeats4 Tfdp2 Hnrnpa1 Tfdp1 Rbm17 Hmgn3 Lhx3 Cers4 Ugp2 Bax Mrps25 H1fx Nap1l1 Pax2 Traf4 Mcm6 Neurod6 Rab2a Cd59a Ptcd1 Klf7 Las1l Cdk2ap1 Mycl Nono Zfp330 Insm1 Irx2 Id1 Id2 Magoh Nr2f6 Zbtb20 Diablo Gar1 Snrpb2 Rps4x Zmiz1 Hnrnpc Nr2f1 Rbpj Lsm6 Hmgb2 Tbpl1 DB-020 for ototoxicity DB-020 for Cisplatin Ototoxicity: Clear Path to Value Inflections POC in ~40 Patients; Single Registration Study “Better than dead? At this point, I’m wondering…..hearing loss and DB-020 Provides Broad Protection against Cisplatin-induced this constant tinnitus is life- changing, far more than having Hearing Loss cancer.” • 260k cisplatin patients/year in US/EU5/ Japan • ~80% adults, >50% children – permanent hearing loss; tinnitus, hyperacusis, balance loss • Validated mechanism: sodium thiosulfate inactivates cisplatin; 100% hearing protection in preclinical models • Office-based injection; proprietary formulation

CONFIDENTIAL | 21 DB-020 Program: Fast Path to Human POC and Product Registration 2019 2020 2021 2022

I.A. LPO

Phase 1A Phase 1B POC (AU/US) Registration trial

Phase 1A, Human PK, Safety, Phase 1B, Human POC Tolerability • DB-020 administered 3hrs before • DB-020 administered locally, cisplatin feasibly • Placebo in contralateral ear • Well tolerated, mild TEAEs, no auditory findings • IV cisplatin, 21-28d • Systemic exposure 20x below • Any tumor type cisplatin efficacy inhibition • Safety, tolerability • Opportunity for strong audiometric efficacy signal

CONFIDENTIAL | 22 Decibel Therapeutics: Leading Company, Emerging Field

• Major opportunities in hearing and balance • Differentiated precision gene therapy platform: state-of-art for ear – Gene replacement – Regenerative medicines • Restoration of hair cell functionality: cellular focus of pathology, validated mechanisms • Demonstrated drug development and delivery capabilities for inner ear diseases

CONFIDENTIAL | 23