#1AKOUOS CONFIDENTIAL June 2020#2Cautionary Note and Disclaimer 1 Akouos, Inc. (the "Company") has filed a registration statement (including a preliminary prospectus) with the SEC for the offering to which this presentation relates. The registration statement has not yet been declared effective, and the Company's common stock may not be sold, nor may offers to buy be accepted, prior to the time the registration statement becomes effective. You should read the preliminary prospectus contained in the registration statement and other documents the Company has filed or may in the future file with the SEC for more information about the Company and this offering. You can obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus may be obtained from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (631) 592-5973 or by email at PostSale Manual [email protected]; or Piper Sandler & Co. at (866) 805-4128 or email at [email protected]. Cautionary Note Regarding Forward-Looking Statements This presentation includes express and implied "forward-looking statements." In some cases, you can identify forward-looking statements by terms such as "anticipate," "believe," "contemplate," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," "would," or the negative of these terms, and similar expressions intended to identify forward-looking statements. However, not all forward-looking statements contain these identifying words. These statements may relate to our strategic plans or objectives, revenues or earnings projections, or other financial items. By their nature, these statements are subject to numerous uncertainties, including factors beyond our control, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. 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Market & Industry Data Projections, estimates, industry data and information contained in this presentation, including the Company's general expectations and market position and market opportunity, are based on information from third-party sources and management estimates. Although the Company believes that its third party-sources are reliable, the Company cannot guarantee the accuracy or completeness of its sources. The Company's estimates are derived from third-party sources, publicly available information, the Company's knowledge of its industry and assumptions based on such information and knowledge. The Company's estimates have not been verified by any independent source. All of the projections, estimates, market data and industry information used in this presentation involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such information. In addition, projections, estimates and assumptions relating to the Company's and its industry's future performance are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including, but not limited to, those described above, that could cause future performance to differ materially from the Company's expressed projections, estimates and assumptions or those provided by third parties. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. AKOUOS#3Offering Summary Issuer / Ticker Common Stock Offered Estimated Gross Proceeds Over-Allotment Option Price Range Use of Proceeds Lock-Up Period Bookrunners Co-Manager • Akouos, Inc., AKUS (NASDAQ) • 8,333,333 shares (100% Primary) . $125 million at the midpoint 15% (100% Primary) $14-$16 • Advance the clinical development of AK-OTOF for the treatment of OTOF-mediated hearing loss through the report of preliminary clinical data from our planned Phase 1/2 clinical trial; • Initiate clinical development of our additional product candidates, anti-VEGF, CLRN1, and GJB2; • Continue preclinical development of our other product candidates and development programs, including our autosomal dominant hearing disorder and our hair cell regeneration programs, and to continue development of our platform; • Establish internal manufacturing capabilities of 250-liter capacity; The remainder for working capital and other general corporate purposes 180 days for Akouos, directors, executive officers, and existing security holders • BofA Securities, Cowen and Piper Sandler & Co. BTIG AKOUOS#4Agenda Akouos Background & Introduction to Hearing • The Akouos Genetic Medicine Platform Product Candidate Pipeline 3 Manufacturing • Financial Overview CONFIDENTIAL AKOUOS#5The Akouos Mission: Healthy Hearing Available to All AKOUOS "Akouos," from the Greek verb Akoúw: to listen, to learn, to understand. We are a precision genetic medicine company dedicated to the development of gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for people worldwide who live with disabling hearing loss CONFIDENTIAL#6Genetic Medicine Platform Focused on Inner Ear Disorders Attractive Market with High Unmet Need Multimodal Precision Genetic Medicine Platform Potential for Rapid Advancement of Lead Program, AK-OTOF Focused Pipeline Expansion with Access to Multiple Cell Types Value-Add Capabilities and Infrastructure ~466mm people worldwide with disabling hearing loss, including ~34mm children Building a platform that enables development of multiple vector-mediated genetic medicine modalities utilizing proprietary AAVAnc vectors and a novel delivery approach to target a broad range of inner ear disorders AKOUOS AK-OTOF has generated promising preclinical data and has the potential for rapid clinical readout using auditory brainstem response (ABR) as an objective, clinically accepted efficacy endpoint, potentially leading to platform validation Disciplined indication and target selection: suitability for locally delivered AAV, clearly defined mechanism of action/promising in vivo data, potential for rapid clinical readout, and high unmet need / meaningful addressable patient population Developing internal CGMP manufacturing with capabilities to supply vector for clinical trials World-Class Management Team with Team has expertise in auditory anatomy and physiology, otopathology, human genetics, inner ear drug Broad Expertise delivery, gene therapy, and rare disease drug development and commercialization CONFIDENTIAL#7Experienced Management Team with Otology, Genetic Medicine, and Rare Disease Drug Development Expertise 6 Emmanuel Simons, Ph.D., M.B.A. Founder, Chief Executive Officer Rabia Gurses Ozden, M.D. Chief Development Officer Morgan Molloy Chief Corporate Development Officer Jennifer Wellman SVP, Regulatory & Quality AM PIVOTAL Voyager nightstar &agtc gsk Spark genzyme Biogen Spark of Philadelphi AVIGEN Broad Base of Top Tier Investors EcoR1 CAPITAL COWEN HEALTHCARE INVESTMENTS RACAPITAL CONFIDENTIAL Michael McKenna, M.D. Founder, Chief Medical Officer Gregory Robinson, Ph.D. Chief Scientific Officer Karoline Shair, Ph.D., J.D. General Counsel John Connelly SVP, Portfolio Strategy, R&D Operations Fidelity SOFINNOVA NEA SURVEYOR AKOUOS HARVARD nightstar agilis Shire Biogen Takeda VA Voyager genzyme#8Deep Pipeline Highlights Breadth of Platform 7 Product Candidate or Development Program (Indication) Hair Cells AK-OTOF (OTOF-Mediated Hearing Loss) CLRN1 / Usher Type 3A Autosomal Dominant Hearing Disorder Supporting Cells GJB2 Hair Cell Regeneration Secreted Proteins AK-antiVEGF (Vestibular Schwannoma) AAV-Enabled Modalities: Estimated Prevalence (US and EU) 20.000 2,000 Pending Target Selection 200,000 Pending Target Selection 200,000 Gene Transfer Discovery Gene Transfer + Knockdown Stage of Development CONFIDENTIAL Preclinical Phase 1/2 Therapeutic Protein Expression Pivotal Next Planned Milestone AKOUOS IND Submission Candidate Selection Target Announcement Candidate Selection Target Announcement Pre-IND Meeting#9How We Hear Oval Window Ear Drum Round Window Membrane ("RWM") Spiral Ganglion Cells Auditory Nerve 1 Sound enters the ear through the external auditory canal of the outer ear, where it vibrates the ear drum 2 The sound vibrations are then relayed through the middle ear where they articulate with the cochlea at the oval window The cochlea contains a long, coiled, ribbon-like epithelial membrane that is suspended between two cochlear fluid compartments 4 Sensory cells, called hair cells, sense the movement of fluid and convert the fluid waves into nerve impulses that are sent along the auditory nerve to the brain CONFIDENTIAL Inner Border Cells Spiral Ganglion Cells Pillar, Cells AKOUOS Inner Hair Cells Hensen's Cells Claudius Cells Outer Hair Cells#10Diagnosis of Hearing Loss Soft Hearing Loss (dB HL) Loud NORMAL MILD MODERATE MODERATELY- SEVERE SEVERE PROFOUND Low Pitched 125 i md b 250 ng Y 500 E 1000 2000 Frequency (Hz) High Pitched feth 4000 8000 An individual with this audiogram would be unable to hear sounds at lower dB levels above the circles and Xs AKOUOS • Clinical diagnosis of sensorineural hearing loss depends on the demonstration of reduced hearing sensitivity by auditory testing Children with Severe to Profound hearing loss cannot perceive typical speech sounds and are unlikely to develop verbal language • Hospitals typically use either ABR or otoacoustic emission (OAE) testing to identify hearing loss in newborns ▪ ABR testing reflects how the cochlea, auditory nerve, and auditory pathways in the brain are working CONFIDENTIAL OAE testing reflects whether outer hair cells in the cochlea respond to sound#11Cochlear Implants Are Currently the Only Intervention Available for Individuals with Some Forms of Severe to Profound Sensorineural Hearing Loss 10 Transmitter Speech processor & microphone Receiver/Stimulator Electrode array AKQUOS Shortcomings Requires invasive surgical procedure and permanent indwelling hardware; destructive to inner ear cells • Provides impoverished auditory signal compared to physiologic hearing • Requires extensive speech-language therapy following implantation for children to develop verbal language • Recipients often have difficulty understanding speech in real-world situations • Device failures and surgical revision are not uncommon; routine device maintenance required Only ~10% of eligible individuals receive a cochlear implant CONFIDENTIAL#12Overview of Genetically-Driven Hearing Loss • Tens of millions of children with monogenic hearing loss worldwide • Congenital hearing loss recognized as neurodevelopmental emergency by American Academy of Pediatrics . • Some of the most common forms of monogenic deafness affect an estimated ~200,000 individuals in the U.S. and Europe 11 No drugs currently approved for the treatment of sensorineural hearing loss 1 of 500 newborns has disabling hearing loss Complex Etiology (20%) Recessive (80%) Genetic Causes (80%) Nonsyndromic (75-80%) Dominant (19%) Syndromic (15-20%) Mitochondrial & X-Linked (1%) Autosomal Recessive Autosomal Dominant Note: Syndromic hearing loss means, in addition to hearing loss, the individual has other symptoms of medical importance CONFIDENTIAL Nonsyndromic AKOUOS >75 genes >48 Syndromic >30 genes >10#13The Anatomy and Biology of the Inner Ear Are Ideal for One-Time Genetic Medicines 12 Opportunity to Leverage Learnings from Development of Genetic Medicines for the Eye and Brain Eye . Brain Inner Ear CONFIDENTIAL . AKQUOS Unique Advantages of the Inner Ear • Fewer target cells and smaller delivery volume → less vector required for meaningful transgene expression Enclosed compartments → opportunity for local, targeted delivery Reduced immune surveillance → lower impact of neutralizing antibodies Non-dividing target cells → potential for one-time delivery to provide life-long benefit Anatomy is fully developed at birth more favorable benefit-risk profile in pediatric populations While the unique anatomical challenges of delivering to the inner ear have hindered genetic medicine development for hearing disorders, we believe Akouos is uniquely positioned to overcome these delivery challenges#1413 CONFIDENTIAL AKQUOS Our Platform • Novel, minimally invasive surgical delivery • Access to proprietary library of ~38,000 novel AAVAnc capsids Multiple vector-mediated modalities#15The Akouos Precision Genetic Medicine Platform 14 Novel Delivery Approach Proprietary AAV Vector Library CONFIDENTIAL Multimodal Capabilities AKOUOS Gene transfer targeting loss-of- function mutations Gene knockdown or editing targeting toxic gain-of-function or dominant negative mutations Therapeutic protein expression (e.g., monoclonal antibody) targeting disease pathways responsible for non-monogenic hearing loss#16Novel, Minimally Invasive Delivery Approach Designed to Enable Efficient Access to Target Cells and Controlled Distribution of Product Candidates Throughout the Cochlea 15 0.00 8 0 Oval Window Round Window Membrane (RWM) Akouos Device in RWM CONFIDENTIAL 20 Uncoiled Cochlea Oval Window Base Injected fluid path Designed to allow for the safe and effective delivery of product candidates through the RWM Minimally invasive device delivers product candidates in a fixed volume and at a controlled flow rate • Design allows for distribution of product candidates across the full length of the cochlea AKOUOS Apex 1 8.0 2.0 0.5 Frequency Distribution Along the Cochlea 0.02 kHz#17Novel AAV Vector Platform with Library of ~38,000 AAVAnc Vectors 16 0.05 Anc80Lib Anc81 Anc80 Anc83 Anc84 Anc82 Anc113 Anc127 Anc126 10 10 43 rh 10 AAV8 rh 43 rh 8 Anc110 cy 2 AAV7 AAV3 AAV38 ch5 hu13 2 AAV6 AAV2 42 2 hu48 hu43 AAV9 AAV1 hu 31 hu 32 rh32 rh33 rh34 AAVA AAV5 Exclusive licenses to a library of approximately 38,000 AAVAncs for the potential treatment of inner ear and hearing related disorders • AAVAnc80, a member of this library, has shown significant advantages over commonly used AAV vectors: AKOUOS CONFIDENTIAL Broad tropism across inner ear cell types, which further expands target landscape Superior transduction efficiency in inner ear cells, which paves the way for dual vector delivery of large transgenes and more available. targets Tropism and transduction advantages open new opportunities to address broader target landscape#18AAVAnc80 Exhibits High Transduction Efficiency Compared to Other AAV Capsids 17 Capsid Dose OHCs IHCS AAVAnc80 Transduces Cochlear Hair Cells More Efficiently than Other AAV Capsids AAV8 7x %GFP* IHCs 100 80 60 40 20 0 AAV1 21x AAV1 AAV2 AAV6 AAV8 AAV2 3.5x 8 AAVANC80 Apex Base %GFP* OHCs CONFIDENTIAL 100 80 60 40 20 0 ∞∞ AAV1 AAV2 AAV6 AAVAnc80 1x AAV8 9 AAVAnc80 AKOUOS Landegger et al. (2017), Nature Biotechnology 35, 280-284 Multiple independent investigations have shown increased hair cell transduction efficiency of AAVAnc80 relative to other AAV capsids in mouse and non-human primate models OHCS = outer hair cells; IHCS = inner hair cells; GFP = green fluorescent protein#19Multi-Dose Tropism Study in Cynomolgus Macaque Showed Efficient Inner Hair Cell Transduction at Three Weeks 18 Percentage of Inner Hair Cells Expressing GFP Three Weeks Following Administration of an AAVAnc80 Vector Encoding GFP 100 Inner Hair Cell Transduction (%) 80 60 40 20 0 Dose 2.4E11 vg 6.0E10 vg 71.5E10 vg 0.06 0.5 4 Cochlear Frequency Position (kHz) 32 OHCS = outer hair cells; IHCS = inner hair cells; SC = supporting cells 6.0E10 vg 2.4E11 vg 1.5E10 vg AAVAnc80-GFP Expression in Cynomolgus Macaque Cochlea Across Frequencies and Doses (in Vector Genomes (vg) per Cochlea) 4 kHz 32 kHz 0.125 kHz SC OHC IHC AKOUOS 75-100% of inner hair cells (IHCS) express transgene at 6E10 vg/ cochlea in the cynomolgus macaque CONFIDENTIAL#20The High Transduction Efficiency of AAVAnc80 Coupled with Local Delivery to the Inner Ear Compartment Allows for a Dual Vector Approach for Larger Transgenes ITR 25 ITA الے promoter 5 GFP cDNA promoter 5' GFP cDNA SD ITR ITR SA Transduction ITR t ITR SA DNA sequence alignment Recombination Transcription Splicing polyA TR 3º GFP cDNA H 3* GFP cDNA GFP mRNA Translation polyA ITR Percentage of Inner Hair Cells Expressing Transgene Threel Weeks Following Administration of Dual AAVAnc80 Vectors Inner Hair Cell Transduction (%) 100 80- 60 40- 20- 0- 7.2E11 vg 0.06 Monkey 1 Monkey 2 Monkey 3 Monkey 4 0.5 4 32 Cochlear Frequency Position (kHz) AKOUOS Functional protein Ability to deliver transgenes that are larger than 5 kb in size creates the potential for broader treatment of genetically-driven hearing loss CONFIDENTIAL#21AAVAnc80 Efficiently Transduces Multiple Cell Types in the Inner Ear 20 • Conducted preclinical studies across three different non-human primate models using GFP as a reporter gene delivered by AAVAnc80 • AAVAnc80 can efficiently transduce multiple target cell populations throughout the cochlea in the primate inner ear • Pre-existing neutralizing antibodies, even at relatively high levels in serum, did not inhibit cochlear cell transduction following intracochlear delivery CONFIDENTIAL Treated Untreated Hensen's Cells Outer Hair Cells Pillar Cells Inner Hair Cells Inner Border Cells GFP Hensen's Cells Outer Hair Cells Pillar Cells Inner Hair Cells Inner Border Cells b Myo7a GFP Outer Hair Cells Pillar Cells Outer Hair Cells Pillar Cells Satellite Glial Cells AKOUOS GFP Hoescht GFP Tu#22Access to Multiple Cell Types Opens Large Target Landscape 21 Inner Border Cells Spiral Ganglion Cells Inne Ha Inner Hair Cells Outer Hair Cells Claudius Cells Inner Hair Cells CONFIDENTIAL OTOF SLC17AB SERPINB6 MY07A, POU4F3, CDH23, ESPN, USHIC, TRIOBP, TMC1, MYO1SA, ACTG1, MY06, RDX WHRN, LOXHD1, TMHS.... PJVK KONOA Spiral Ganglion Cells Outer Hair Cells STRC, SLC26A5 AKQUOS Supporting Cells GJB2, GLB3, GJB6, SLC26A4 Different genes are associated with the different cell types in the ear, including inner hair cells, outer hair cells, and supporting cells#23Multimodal Capabilities Create Potential to Address a Broad Range of Monogenic and Non-Monogenic Inner Ear Disorders. Akouos Precision Genetic Medicine Platform Gene Editing 22 Modality Target Hair Cells Supporting Cells Secreted Proteins Gene Transfer Single Vector CLRN1 GJB2 Dual Vector OTOF Gene Knockdown RNA-interference Hair Cell Regeneration Nuclease- based Undisclosed autosomal dominant indications Non- nuclease- based CONFIDENTIAL AKOUOS Therapeutic Protein Expression Vestibular Schwannoma Initial pipeline spans multiple vector-mediated modalities and cochlear targets to potentially address inner ear disorders affecting hundreds of thousands of individuals in the U.S. and Europe#24The Global Sing (Sensorineural Genetic) Hearing Loss Registry Observational Research Study Focused on Understanding the Life-Long Impact of Genetically Caused Sensorineural Hearing Loss (SNHL) To support the identification, diagnosis, and characterization of participants with a genetic SNHL To understand epidemiology and incidence / prevalence of genetic SNHL • To further understand long-term genotype / phenotype relationships to assist with clinical prognosis, participant care, and treatment outcomes 23 • To generate untreated or comparative intervention (e.g., Cls) data for potential use as comparator data for new treatment options • To understand longitudinal outcomes for treatment options and interventions. CONFIDENTIAL sing REGISTRY AKQUOS#2524 3 CONFIDENTIAL AKQUOS Our Product Candidates Core focus on gene therapy for inner ear disorders • Disciplined candidate selection criteria • Utilize learnings from lead program to drive future candidate selection#26Our Disciplined Candidate Selection Criteria Allow Us to Focus Resources on Promising Targets Covering a Range of Inner Ear Disorders Patient populations with high unmet need 25 Promising preclinical data Large potential market. opportunity Hair Cell Targets Supporting Cell Targets Secreted Proteins Clear endpoints with potential for rapid. clinical read-out CONFIDENTIAL AKOUOS Leverage platform established in AK-OTOF to utilize learnings to mitigate development risk Demonstrate platform breadth and balanced risk profile at portfolio level#27Deep Pipeline Highlights Breadth of Platform 26 Product Candidate or Development Program (Indication) Hair Cells AK-OTOF (OTOF-Mediated Hearing Loss) CLRN1 / Usher Type 3A Autosomal Dominant Hearing Disorder Supporting Cells GJB2 Hair Cell Regeneration Secreted Proteins Ak-antiVEGF (Vestibular Schwannoma) AAV-Enabled Modalities: Estimated Prevalence (US and EU) 20.000 2,000 Pending Target Selection 200,000 Pending Target Selection 200,000 Gene Transfer Discovery Gene Transfer + Knockdown Stage of Development CONFIDENTIAL Preclinical Phase 1/2 Therapeutic Protein Expression Pivotal Next Planned Milestone AKOUOS IND Submission Candidate Selection Target Announcement Candidate Selection ■ Target Announcement Pre-IND Meeting#28AK-OTOF Overview 27 AK-OTOF Prevalence Indication Delivery Method Mechanism of Action Progress and Status AK-OTOF encodes otoferlin, a protein that enables the sensory cells of the ear to release. neurotransmitter vesicles, activating auditory neurons Estimated 20,000 cases of OTOF-mediated hearing loss in the US and EU • Treatment of sensorineural hearing loss due to mutations in the otoferlin, or OTOF, gene • Mutations in the OTOF gene are a major cause of genetic nonsyndromic hearing loss Use AAVAnc80 as a delivery vehicle for the OTOF gene Administer product candidate directly into the inner ear AKOUOS Encodes otoferlin to enable release of neurotransmitter vesicles to activate auditory neurons in response to sound • Auditory neurons then carry electronically encoded acoustic information to the brain allowing: us to hear Promising preclinical data in representative mouse models Pre-IND meeting with FDA. • Executing on agreed IND-enabling preclinical studies • Designing a Phase 1/2 trial for AK-OTOF and plan to file an IND in 2021 CONFIDENTIAL#29AK-OTOF Has the Potential to Address an Unmet Need for Individuals with OTOF-Mediated Hearing Loss • Patients typically born deaf • Currently no approved pharmacologic therapies to address OTOF-Mediated hearing loss 28 Only treatment option is cochlear implants Hair Cell Neuron Vesicle CONFIDENTIAL Hair Cell Synapse Neuron Neurotransmitter AKQUOS Vesicle Otoferlin --SL Synapse. Otoferlin is required for the release of neurotransmitters at the junction of the inner hair cells and the spiral ganglion neurons, which carry acoustic information to the brain#30Dual Vector Delivery of AK-OTOF Led to Restoration of ABR Thresholds and Long-Term Hearing Recovery in Mice 29 Restoration of ABR Thresholds in Otof Knock-Out Mice Receiving a Dual AAV Vector Expressing OTOF Click ABR threshold (db SPL) 90 80 70 60 50 40 30 20 10 0 25 4 10 15 Weeks Post-Injection 30 Otof/-(n=6) Otof (5' alone; n=3) Otof (5'+3'; n=8) Wild-type (n=8) Click ABR threshold (db SPL) CONFIDENTIAL Intracochlear Delivery of AK-OTOF Resulted in Significant, Long-term Hearing Recovery in Otof Knock-Out Mice 100 80 60 40 20 0 1 mo AKOUOS Untreated Otof(n=5) Wild-Type (n=6 at 1 mo; n-3 at 10 mo) Otof/ + AAVAnc80-hOTOF (n=3 per group) 3 mo 7 mo 10 mo Approximate Age at ABR Test (Administration at 1 week old) AK-OTOF utilizes a dual vector approach to restore long-term hearing in knock-out mouse models - one AAVAnc80 vector carries the 5' fragment of OTOF gene and the other AAVAnc80 vector carries the 3' fragment of the OTOF gene#31A Single Dose of AK-OTOF Restored Cochlear Function in Mature Mice Lacking Otoferlin 30 Click Level (dB SPL) 100 90 80 70 60 50 Wild-Type Vehicle Control 40 www Time re Click Onset (msec) Otoferlin KO + Vehicle Control Click Level (dB SPL) 100 90 80 70 60 50 40 Time re Click Onset (msec) CONFIDENTIAL Otoferlin KO + AAVAnc80-hOTOF Click Level (dB SPL) 100 90 80 70 50 40 www www www است www. Time re Click Onset (msec) In a preclinical study, a single dose of AK-OTOF restored cochlear function in mice lacking otoferlin AKOUOS#32Planned AK-OTOF Phase 1/2 Clinical Trial 31 Part A Dose Escalation Assess: Safety, tolerability, and bioactivity Key Eligibility Administration Efficacy Endpoints Timing Up to 5-year clinical follow-up Individuals with OTOF-mediated hearing loss • Amenable to surgical delivery and potential for benefit • May enroll children as young as one year old in the expansion phase (¹) Part B Cohort Expansion Assess: Safety and effectiveness Administered to trial participants through a single unilateral intracochlear injection • Objective and clinically relevant ABR testing and age appropriate behavioral assessment (1) Based on pre-IND meeting with FDA in September 2019. Submit IND in 2021 • Intend to file the delivery device along with the investigational product as a combination product(¹) CONFIDENTIAL AKQUOS#33Deep Pipeline Highlights Breadth of Platform 32 Product Candidate or Development Program (Indication) Hair Cells AK-OTOF (OTOF-Mediated Hearing Loss) CLRN1 / Usher Type 3A Autosomal Dominant Hearing Disorder Supporting Cells GJB2 Hair Cell Regeneration Secreted Proteins AK-antiVEGF (Vestibular Schwannoma) AAV-Enabled Modalities: Estimated Prevalence (US and EU) 20.000 2,000 Pending Target Selection 200,000 Pending Target Selection 200,000 Gene Transfer Discovery Gene Transfer + Knockdown Stage of Development CONFIDENTIAL Preclinical Phase 1/2 Therapeutic Protein Expression Pivotal Next Planned Milestone AKOUOS IND Submission * Candidate Selection Target Announcement Candidate Selection Target Announcement Pre-IND Meeting#34USHER SYNDROME IS THE MOST COMMON HEREDITARY DEAF- BLIND DISORDER#35CLRN1 Overview 34 CLRN1 Prevalence Indication Delivery Method Mechanism of Action Progress and Status • Deliver a functional version of the CLRN1 gene to cochlear hair cells in patients with Usher syndrome 3A . Estimated 2,000 cases in the US and EU Treatment of sensorineural hearing loss due to mutations in the CLRN1 gene • Mutations of CLRN1 gene cause syndromic genetic hearing / vision loss, characterized by progressive sensorineural hearing impairment and progressive vision loss Uses AAVAnc80 as a delivery vehicle for the CLRN1 gene Administer product candidate directly into the inner ear AKOUOS Mutations in CLRN1 gene reduce the production and localization of CLRN-1 protein to hair cell membranes • Encodes Clarin-1, which plays a role in communication between neurons in the inner ear and in the retina, and may be important for the function of synapses • Published data: AAV delivery of mouse Cirn1 rescues the phenotype in newborn mice • Preclinical data (AAVAnc80) in collaboration with Case Western Reserve University demonstrated restoration of hearing in a mouse model CONFIDENTIAL#36Proof of Concept Data: AAV-Mediated Delivery of CLRN1 Recovered Hearing in a Knock-Out Mouse Model 35 Preclinical data demonstrated hearing preservation in the KO-TgAC1 mouse model, which recapitulates the auditory phenotype observed in human USH3A patients •AAV delivery of mouse Clrn1 with its endogenous UTR preserves hearing levels near wildtype animals • Early preclinical data show that AAVAnc80 encoding human Clarin-1 can rescue hearing in mature KO-TgAC1 mice Restoration of Hearing Thresholds in CLRN1 KO Mouse Model Click ABR Threshold (dB SPL) 86 dB SPL 81 dB SPL. 76 dB SPL 71 dB SPL 66 dB SPL 61 dB SPL 56 dB SPL 51 dB SPL. 46 dB SPL 41 dB SPL 36 dB SPL 31 dB SPL CONFIDENTIAL 49 60 70 80 90 100 110 117 160 Days Postnatal WT At UTR=untranslated region ABR Waveforms KO-TRAC1 AAV AKOUOS Untreated AAV + UTR Wild-Type Cim1 - TgAC1 KO-TRAC1+Clrn1 + UTR#37Our Disciplined Candidate Selection Criteria Allow Us to Focus Resources on Promising Targets Covering a Range of Inner Ear Disorders Patient populations with high unmet need 35 Promising preclinical data Large potential market opportunity Hair Cell Targets Supporting Cell Targets Secreted Proteins Clear endpoints with potential for rapid. clinical read-out CONFIDENTIAL AKQUOS Leverage platform established in AK-OTOF to utilize learnings to mitigate development risk Demonstrate platform breadth and balanced risk profile at portfolio level#38Deep Pipeline Highlights Breadth of Platform 37 Product Candidate or Development Program (Indication) Hair Cells AK-OTOF (OTOF-Mediated Hearing Loss) CLRN1 / Usher Type 3A Autosomal Dominant Hearing Disorder Supporting Cells GJB2 Hair Cell Regeneration Secreted Proteins Ak-antiVEGF (Vestibular Schwannoma) AAV-Enabled Modalities: Estimated Prevalence (US and EU) 20.000 2,000 Pending Target Selection 200,000 Pending Target Selection 200,000 Gene Transfer Discovery Gene Transfer + Knockdown Stage of Development CONFIDENTIAL Preclinical Phase 1/2 Therapeutic Protein Expression Pivotal Next Planned Milestone AKOUOS IND Submission Candidate Selection Target Announcement Candidate Selection Target Announcement Pre-IND Meeting#39AK-antiVEGF Overview 38 AK-antiVEGF Prevalence Indication Delivery Method Mechanism of Action Progress and Status AK-antiVEGF encodes a secreted inhibitor of vascular endothelial growth factor (VEGF) to treat vestibular schwannomas Estimated 200,000 cases in the US and EU AKOUOS Treatment of sporadic vestibular schwannoma, a common intracranial tumor • Current standard of care consists of surgical removal and/or radiation, both of which typically result in lost hearing and can be associated with significant morbidity Uses AAVAnc80 as a delivery vehicle to achieve local, sustained anti-VEGF protein at tumor site Administer product candidate directly into the inner ear Systemic anti-VEGF has been shown to reduce tumor volume and improve hearing in some patients with vestibular schwannoma • Local delivery may avoid the systemic side effects of high dose intravenous VEGF inhibitor infusion and could remove or reduce the need for other interventions Preclinical data in wild-type mice confirming anti-VEGF protein expression and tolerability • Completed dosing for a pilot non-human primate tolerability study and preparing to request a pre-IND meeting with FDA in 2H:20 CONFIDENTIAL#40AK-antiVEGF for the Treatment of Vestibular Schwannoma Human Data Demonstrate Ability of Systemic VEGF Inhibitor to Improve Hearing and Reduce Tumor Volume in Some Patients with Vestibular Schwannomas The NEW ENGLAND JOURNAL MEDICINE 39 Hearing Improvement after Bevacizumab in Patients with Neurofibromatosis Type 2 ORIGINAL ARTICLE S Neuro-Oncology 12(1):14-18, 2010 dox 10.1093/neuonc nopo10 Fre Advance Access publication October 20, 2009 Al Victor-Felix Carsten Bo NEURO-ONCOLOGY Bevacizumab induces regression of vestibular schwa neuro 10.1007/11060015-1828-8 CLINICAL STUDY Department Bevacizumab decreases vestibular schwannomas growth rate Neuropatholo Center Man in children and teenagers with neurofibromatosis type 2 Audrey Hochart- Vianney Gaillard-Mare Baroncini Nicolas Andre Jean-Pierre Vannier Matthieu Vinchon Frederique Dubrulle². Jean-Paul Lejeune-Christophe Vincent Véronique Neve Hélène Sudour Bonnange Nicolas Xavier Bonne" - Pierre Leblond CONFIDENTIAL Preliminary Data Demonstrate Delivery of AK-antiVEGF Results in Therapeutic Protein Expression with Preserved Anatomy and Physiology in Mice and NHPs Percent Missing Cells (Normalized) AAVAnc80-antiVEGF in Mouse ABR Threshold Shift in NHP Anti-VEGF and Actin Anti-VEGF 8 3 8 2 8 8 10 40 30 20 10 0 -20 -30 -40 AKQUOS Molith 15 Distance from Apex (mm) Month 2 NHP Cytocochleogram 2 months after AK-antiVEGF Delivery Cell Types AVG_OHC IHC Month3 20#4140 CONFIDENTIAL AKQUOS Manufacturing • Internal capabilities with potential to generate research-grade vector • Building internal CGMP manufacturing infrastructure and capabilities to support our clinical development programs#42Key Advantages to Our Manufacturing Process 41 Well characterized HEK293 cell suspension and 250 L bioreactor system Potential to expand beyond Phase 1/2 Exclusive access to AAVAnc Vectors for inner ear provides opportunity to optimize production process and secure additional competitive advantage CONFIDENTIAL AKOUOS Low dose requirements given small size of the inner ear Targeted delivery and high transduction efficiency alleviate the need for large scale production#43Internal Manufacturing Capabilities May Provide Competitive Advantage 42 Expertise in Gene Therapy and Gene Editing Building In-House cGMP Manufacturing Capabilities Current Supply from a Well-Established CMO Expertise covers development from vector design through drug product manufacture Developing scalable manufacturing capabilities, which may allow for significant control over process development timelines and cost • Internal capabilities to process gene therapy batches to support activities through Phase 1/2 clinical trials Plans to leverage single use, disposable, closed system operations aligned to genetic medicine platform to promote both flexibility and cost-effectiveness Internal analytical and process development • 250 L single-use bioreactor system using suspension HEK293 cells Agreement with Lonza, which has performed toxicology manufacturing supply for AK-OTOF program and will conduct CGMP manufacturing to support clinical development AKOUOS CONFIDENTIAL#4443 CONFIDENTIAL AKQUOS Conclusion#45Financial Overview 44 Funding History Current Cash & Cash Equivalents Series Seed: $7.6 million • Series A: $50 million. • Series B: $105 million • Total invested capital:~$163 million • $120.1 million as of March 31, 2020 AM VENTURES 5A Fidelity PIVOTAL COBIGBANTAESET MANAGEMENT FIOVENTURE PARTNERS SOFINNOVA CONFIDENTIAL Investors NEA COWEN HEALTHCARE INVESTMENTS POLARIS SURVEYOR AKOUOS EcoR1 CAPITAL PARTNERS FUND INNOVATION RACAPITAL 双湖资本 WU CAPITAL#46Genetic Medicine Platform Focused on Inner Ear Disorders 45 AKQUOS Attractive Market with High Unmet Need Multimodal Precision Genetic Medicine Platform Value-Add Capabilities and Infrastructure Potential for Rapid Advancement of Lead Program, AK-OTOF AKQUOS Focused Pipeline Expansion with access to Multiple Cell Types World-Class Management Team with Broad Expertise CONFIDENTIAL#4745 CONFIDENTIAL AKQUOS Appendix#48Board of Directors and Scientific Advisory Board 47 Ed Mathers Board of Directors Vicki Sato, Ph.D. Board of Directors Arthur Tzianabos, Ph.D. Board of Directors Luk Vandenberghe, Ph.D. Founder Michael McKenna, M.D. Founder, Chief Medical Officer NEA Ra Pharma Medimmune VIR A ARCH KENTURE HOMOLOGY Shire HARVARD HARVARD Manches Board of Directors Kush Parmar, M.D., Ph.D. Board of Directors Emmanuel Simons, Ph.D. Founder & Chief Executive Officer Scientific Advisory Board Richard Smith, M.D. Founder 5AM CONFIDENTIAL HOMOLOGY VOR Harvard University MIT THE UNIVERSITY DE TOWA Jean Bennett, M.D., Ph. D. Penn Medicine Heather Preston, M.D. Board of Directors Chris Smith Board of Directors AKOUOS PIVOTAL TPG J.P.Morgan Orlto Cinca Dugostes Cochlear HARVARD William Sewell, Ph.D. Founder Aaron Tward, M.D., Ph. D. UCSF