Frequency Therapeutics Corporate Overview - September 2020

 
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Frequency Therapeutics Corporate Overview - September 2020
Frequency Therapeutics
    Corporate Overview

    September 2020

Copyright Frequency Therapeutics, Inc.   1
Frequency Therapeutics Corporate Overview - September 2020
FORWARD-LOOKING STATEMENTS AND OTHER DISCLAIMERS

  This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do
  not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the treatment potential of FX-322, the design
  and enrollment of the Phase 2a clinical trial of FX-322, the timing of top-line data from the Phase 2a clinical trial and timing of presentation of results of the exploratory study in Germany,
  the novelty of the exploratory study in Germany, the implications of the results of the exploratory Germany study in combination with our other trials, the therapeutic levels of FX-322
  predicted in the exploratory Germany study, the results and implications of the Phase 1/2 durability of response data, the timing of the FX-322 clinical study in patients with age related
  hearing loss, the ability of our technology platform to provide patient benefit, the impact of COVID-19 on the Company’s on-going and planned clinical trials and business, future
  milestone and royalty payments under the license and collaboration agreement with Astellas Pharma Inc. (“Astellas”), the sufficiency of the Company’s cash, cash equivalents and short-
  term investments, estimates of the size of the hearing loss population and population at risk for hearing loss, the timing of the remyelination program, and the potential application of
  the PCA platform to other diseases.

  These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks,
  uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements
  expressed or implied by the forward-looking statements, including, but not limited to, the following: Frequency Therapeutics (the “Company”) has incurred and will continue to incur
  significant losses and is not and may never be profitable; need for additional funding to complete development and commercialization of any product candidate; the Company’s
  dependence on the development of FX-322; the unproven approach of the PCA platform; the lengthy, expensive and uncertain process of clinical drug development and regulatory
  approval; limited experience successfully obtaining marketing approval for and commercializing product candidates; the results of earlier clinical trials not being indicative of the results
  from later clinical trials; differences between preliminary or interim data and final data; adverse events or undesirable side effects; disruptions at the FDA and other regulatory agencies;
  the impact of the COVID-19 impact; failure to identify additional product candidates; new or changed legislation; failure to maintain Fast Track designation for FX-322 and such
  designation failing to result in faster development or regulatory review or approval; costly and damaging litigation, including related to product liability, intellectual property or brought
  by stockholders; dependence on Astellas for the development and commercialization of FX-322 outside of the United States; misconduct by employees or independent contractors;
  reliance on third parties, including to conduct clinical trials and manufacture product candidates; compliance with laws and regulations, including healthcare and environmental, health,
  and safety laws and regulations; failure to obtain, maintain and enforce protection of patents and other intellectual property; security breaches or failure to protect private personal
  information; attracting and retaining key personnel; and ability to manage growth.

  These and other important factors discussed under the caption “Risk factors” in the Company’s Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 12, 2020
  and its other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such
  forward-looking statements represent management’s estimates as of the date of this presentation. While the Company may elect to update such forward-looking statements at some
  point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing
  the Company’s views as of any date subsequent to the date of this presentation.

Copyright Frequency Therapeutics, Inc.                                                                                                                                                               2
Frequency Therapeutics Corporate Overview - September 2020
Frequency Today
                    FX-322 program for sensorineural hearing loss in Phase 2a clinical development
                      •   Phase 2a study ongoing, fully enrolled; read out in Q2 2021
                      •   Phase 1/2 results provided evidence of hearing restoration; favorable safety profile
                      •   Planning for near-term FX-322 studies in additional patient populations
                      •   FDA Fast Track designation
                      Additional opportunities across multiple degenerative diseases
                      • Multiple sclerosis program advancing toward IND; target submission H2 2021
                      • Broad IP portfolio in hearing and additional applications
                    Operating runway into 2023
                      • $195.4 million in cash, cash equivalents and short-term investments (as of June 30, 2020)
                      • $40.1 million in net proceeds raised in private placement in July 2020
                      • Potential development milestones related to Astellas ex-US FX-322 collaboration including $90M
                        at first Phase 2b dosing in Europe & Asia and $140M for the first Phase 3 dosing in Europe & Asia
Copyright Frequency Therapeutics, Inc.                                                                                      3
Frequency Therapeutics Corporate Overview - September 2020
Key Recent Advances in FX-322 Clinical Development
                                                               Data presented
                                                               Sept. 13, 2020
                   Demonstration of
                   effective delivery to the                     Preliminary evidence of
                   target tissue                                 longer-term durability
• Exploratory study of patients undergoing cochlear     • Post P1/2 study word recognition (WR) data
  impact surgery to determine if cochlear drug            obtained in five patients 13- 21 months following
  levels can be directly measured                         administration
                                                        • 4/5 subjects maintained improvements in WR
Key findings:                                             scores
 • Measurement of cochlear fluid confirmed              • Three of four patients who responded to FX-
   successful drug delivery to cochlea in all samples     322 maintained stat sig benefit
   analyzed
                                                          • 87% average increase from original baseline
 • Drug levels predicted to result in                   • Same three subjects showed 10-15 dB
   therapeutic activity                                   improvements at 8kHz

 Copyright Frequency Therapeutics, Inc.                                                                       4
Frequency Therapeutics Corporate Overview - September 2020
Origins of Frequency Therapeutics
Tissue-Specific, Pre-programmed Stem Cells

            Decoding Intestinal          Enabling Cochlear                   Frequency
            Regeneration                 Regeneration                        Therapeutics
            Langer and Karp publish      Same cues reactivate                Small molecule
            small molecules activate     normally inactive                   therapeutics show clinical
            intestinal progenitors       progenitors in the cochlea          proof of concept

            Niche-independent high-      Clonal Expansion of Lgr5-Positive
            purity cultures of Lgr5+     Cells from Mammalian Cochlea and
            intestinal stem cells and    High-Purity Generation of Sensory
            their progeny                Hair Cells

Copyright Frequency Therapeutics, Inc.                                                                    5
Frequency Therapeutics Corporate Overview - September 2020
Regenerative Approach with Broad Potential
                                         Brain

                                 Ear               Eye

                           Lung                          Skin   Progenitor cells are stem cells
                                                                that are pre-programmed to
                       Intestine                      Bone      perform a specific activity

                                Muscle           Cartilage

                         Potential to address a range
                          of degenerative diseases

Copyright Frequency Therapeutics, Inc.                                                            6
Frequency Therapeutics Corporate Overview - September 2020
Frequency Progenitor Cell Activation (PCA) Approach

                                                                                         Inactive Progenitor Cell

                        Inactive                    ACTIVATED
                       Progenitor                   Progenitor

                                                                         Asymmetric
                                                                        division using
                                                                       native programs
                                                                                         Functional Target Cell

                                         Combinations of small molecules
                                         designed to activate progenitor cells
Copyright Frequency Therapeutics, Inc.                                                                              7
Frequency Therapeutics Corporate Overview - September 2020
Reducing the Complexity of Regenerative Medicine

              Harnessing                      No Change                  Ease of
            Innate Biology                    To Genome                Manufacturing
             Progenitors already         Activating native programs,       Use of small
            located within target         reducing safety concerns     molecules: no need to
                   tissue                                              remove or grow cells
                                                                              ex vivo

Copyright Frequency Therapeutics, Inc.                                                         8
Frequency Therapeutics Corporate Overview - September 2020
Our Pipeline

                                         DISCOVERY   PRECLINICAL   PHASE 1   PHASE 2   PHASE 3

      Sensorineural hearing
      loss (FX-322)

                                         DISCOVERY   PRECLINICAL   PHASE 1   PHASE 2   PHASE 3

      Multiple Sclerosis

Copyright Frequency Therapeutics, Inc.                                                           9
Frequency Therapeutics Corporate Overview - September 2020
Hearing Restoration Program:
  Preclinical Validation

Copyright Frequency Therapeutics, Inc.   10
Cochlear Function: Hearing Different Frequencies

                                                                    Healthy Cochlea »

                                         Oval window base

                                                                          Schematic of
                                                                        expanded cochlea

                                                                                                               Apex

                                          Round window

                                                             20,000 Hz           1,500 Hz             20 Hz
                                                         (high frequency)   (medium frequency)   (low frequency)

Copyright Frequency Therapeutics, Inc.                                                                                11
Impact of Damage to Cochlear Hair Cells
    Healthy Cochlea                                                  Damaged Cochlea

      Inner Hair Cells (IHCs)
      Outer Hair Cells (OHCs)

       “Analysis of hair cells, auditory nerve fibers and strial tissues … shows that the degree of hearing loss is
       well predicted from the amount of hair cell loss.” Journal of Neuroscience, July 2020
Copyright Frequency Therapeutics, Inc.                                          DOI: https://doi.org/10.1523/JNEUROSCI.0937-20.2020   12
Profound, Unexpected Synergy
                                         Cochlear Progenitor Proliferation (Lgr5-GFP)

                                                                           Culture Media
Strong synergy
seen between                                                               Wnt Activation
                                                                           (glycogen synthase kinase-3
pathways activated                                                         (GSK3) Inhibitor; NCE)

by small molecules
                                                                           HDAC Inhibition
                                                                           (sodium valproate)

                                                                           Wnt Activation and
                                                                           HDAC inhibition
HDAC = Histone deacetylase                                                 HIGH SYNERGY
In vitro mouse model testing
NCE = new chemical entity

Copyright Frequency Therapeutics, Inc.                  Cell Rep. 2017 Feb 21;18(8):1917-1929. doi: 10.1016/j.celrep.2017.01.066   13
FX-322 Program: Aiming to Repair Underlying Pathology

• Progenitors in place
  despite loss of hair cells
• FX-322 molecules aim
  to activate genetic
  pathways to regenerate
  missing hair cells

Copyright Frequency Therapeutics, Inc.                  14
Strong Pre-Clinical Validation

            Test                           Outcome
            In vitro

            Adult human inner ear tissue   Created new hair cells

            In vivo
                                           Restored hair cells and hearing across all
            Adult deafened mice
                                           frequencies

                                           Achieved active levels in the cochlea
            Therapeutic drug levels
                                           in multiple species

Copyright Frequency Therapeutics, Inc.                                                  15
Clinical Program

Copyright Frequency Therapeutics, Inc.   16
FX-322 Administration and Concentration

    Quick intratympanic injection into the middle ear                                                             FX-322 concentrates in the highest
                                                                                                                  frequency region, critical for sound clarity

                                                                                                                                                     1,000 Hz         2,000 Hz

                                                                      Inner ear                                                        500 Hz
                                                                                                                                                                                 3,000 Hz
                                                                       Cochlea                                                  250 Hz
                                              Middle ear

                                                                                                               20,000 Hz

                                         Needle                                                                                                                                    4,000 Hz

                                         Outer ear                                                                 16,000 Hz
                                                     Ear drum
                                                         Round window                                                  14,000 Hz
                                                                                                                         12,000 Hz
                                                              Eustachian tube
                                                                                                                            10,000 Hz
                                                                                                                                              8,000 Hz          6,000 Hz

                                    US Phase 1/2 Study FX-322-201

Copyright Frequency Therapeutics, Inc.                                            Analysis in partnership with Mass Eye and Ear Institute Temporal Bone Bank                                  17
Hearing is Measured Using Validated Tests
                                    Audibility (Loudness)                       Intelligibility (Clarity)
                                         measured with pure tones   measured with word recognition and words-in-noise tests

                                                                             Word Recognition Test:
                                                                             • List of 50 monosyllabic words
                                                                             • Single words played in quiet

                                                                             Words-in-Noise Test:
                                                                             • Standard, clinically accepted
                                                                               measure
                                                                             • Background noise from
                                                                               multiple voices
                                                                             • Played at different signal-to-
                                                                               noise ratios

Copyright Frequency Therapeutics, Inc.                                                                                        18
Critical Information Lost at High Frequencies

                        “Oh say can you see … by the dawn’s early light”
                   20

                   16

                                                                                                                                                          Spectrogram
 Frequency (kHz)

                   12
                                                                                                                                                          of Sound

                    8

                    4

                                 0.5     1                1.5                        2                      2.5                        3
                                                           Time (Secs)

Copyright Frequency Therapeutics, Inc.       Source: Monson et al (2014) The perceptual significance of high-frequency energy in the human voice. Frontiers in Psychology, 5, 587   19
Successful Phase 1/2 Study Completed

                                           Screening NIHL/SSNHL
                                          Mild to Moderately Severe
      Study Overview
       • Safety in patients with
                                                                             Single       No
         sensorineural hearing loss                                        Injection   Injection
                                         FX-322                  Placebo
       • Stable patients                 N = 15                   N=8       15 drug,     All 23
                                                                           8 placebo    patients
       • Assessed hearing by word
                                                  Day 1 | Dose
         testing and pure tones

                                              Follow-up Visits
                                             Days 15, 30, 60, 90

Copyright Frequency Therapeutics, Inc.                                                             20
Clinically Meaningful Improvement in Word Recognition

         Mild Hearing Loss                     Moderate to Moderately Severe
                                               Hearing Loss
          • 14 patients (5 placebo)
                                               • 9 patients (3 placebo)
          • Typically very high word
            recognition scores (45+ words)     • All treated subjects showed increases
                                                 in word recognition
          • Ceiling effect: Limited room for
            improvement                        • 4 of 6 showed statistically significant
                                                 and clinically meaningful improvement
                                               • No change in placebo
                                               • No change in untreated ear

Copyright Frequency Therapeutics, Inc.                                                     21
Clinically Meaningful Improvements in Word Recognition

                                                Absolute Word Recognition Scores
     50

                                                                                     47 *

     40                                                                                                                   Clarity of Sound
                                                                39 *                                    38                Used word tests
     30
                         34 *                                                                                             in a quiet background
                                                                                                  29
                                                                              26
     20                                                                                                                       Baseline – Correct
                                                         20                                                                   words out of 50
                                               16 *
                 14
     10                                                                                                             12        Day 90 – Correct
                                                                                                                              words out of 50
                                         7                                                                    8

      0                                                                                                                   Test/retest variability is one
                 Patient 1               Patient 2        Patient 3            Patient 4          Patient 5   Patient 6   standard deviation, which for a 50-
                                                                                                                          word list is ~ 3 words

          *Statistically significant and clinically meaningful improvements in word recognition

Copyright Frequency Therapeutics, Inc.                                                                                                                          22
Statistically Significant Improvement in Sound Clarity

                                                                  Word Recognition
                                         50

                                         40
                                                                                                             Clarity of Sound
  Improvement

                                         30                                                                  Used word tests
                % Change from Baseline

                                                                                                             in a quiet background
                                         20                                                                  [all patients]

                                         10
                                                                                                                    Placebo

                                          0                                                                         FX-322

                                         -10                                                                 p=0.010

                                         -20
                                               0   Day
                                                     15 15   Day
                                                               3030       45         Day
                                                                                       6060   75   Day9090

Copyright Frequency Therapeutics, Inc.                                                                        US Phase 1/2 Study FX-322-201   23
Clear Improvement Trend in Words-in-Noise

                                                                             Words-in-Noise
                                         40

                                                                                                                                 Clarity of Sound
  Improvement

                                         30

                                                                                                                                 Used word tests
                % Change from Baseline

                                         20                                                                                      in a noisy background
                                                                                                                                 [all patients]
                                         10

                                                                                                                                        Placebo
                                          0
                                                                                                                                        FX-322

                                         -10
                                                                                                                                 p=0.211

                                         -20
                                               0   10 Day 15   20       30
                                                                    Day 30      40      50    Day 6060   70   80   Day 90   90

Copyright Frequency Therapeutics, Inc.                                                                                            US Phase 1/2 Study FX-322-201   24
Pure Tone Improvements at Highest Tested Frequency

                           Percent of Patients with 10dB
                             Improvement at 8000 Hz
                                                                                    4 / 13
 35%                                                                                subjects
 30%
                                                                                               Loudness of Sound
                                                                                               measured pure tones
 25%

 20%
                                                                                               • Standard frequency range was
 15%                                                                                             measured (500 – 8000 Hz)
 10%                                                                                           • Consistent pure tone
                                  0/7                                                            improvements observed at
   5%
                               subjects                                                          8000 Hz in only FX-322 subjects
   0%
                                 Placebo                                             FX-322

Analysis includeds subjects with a measurable baseline hearing deficit at 8000 Hz

Copyright Frequency Therapeutics, Inc.                                                                       US Phase 1/2 Study FX-322-201   25
New Data Show Sustained, Clinically Meaningful
Improvements in Word Recognition
                                            Absolute Word Recognition Scores
   50
                                                                                                             50W                                        Clarity of Sound
                                                                                                              47
                                                                                50W
                                                                                                                                                        Used word tests
   40                                                                                                              25W*
                                                                                 39
                                                                                                                                         50W
                                                                                                                                                        in a quiet background
                     50W                                                              50W                              38                 38
                      34    25W*
                                                                                          35
   30                                                                                                                             50W
                                                                                                                                                            Baseline – Correct
                               30                                                                    50W                          29           50W          words out of 50
                                                                                                      26
                                                                        50W                                                                                 Day 90 – Correct
   20                                                                                                                                              22       words out of 50
                                                  50W                    20
             50W
                                                   16    50W                                                                                                1-2 years – Correct
              14                                                                                                                                            words out of 50
   10                                                       12
                                          50W

                           Month            7            Month                        Month                        Month                       Month    Test/retest variability is one
                           16**                          21**                         19**                         13**                        21**     standard deviation, which for a 50-
     0
                                                                                                                                                        word list is ~ 3 words
                   Subject 1                    Subject 2                     Subject 3                    Subject 4                   Subject 5

          *25W = 25 Word test performed outside an official study site at 13-18 months after dosing; results scaled to 50 words
          50W = 50 Word test performed under a formal protocol at original study site at 18-21 months after dosing
          **Since FX-322 dosing

Copyright Frequency Therapeutics, Inc.                                                                                                                                                        26
New Data Show Sustained, Clinically Meaningful
    Improvements in Word Recognition

•       Follow-up study data presented at Sept. 2020 American
        Academy of Otolaryngology (AAO) Annual Meeting

•       Hearing signal observed in subjects from previous Phase
        1/2 study appears to be maintained

        •        4/5 subjects maintained improvements in WR scores

        •        3/4 subjects showed Thornton-Raffin improvements and had
                 an 87% average increase from original baseline

•       These same 3 subjects showed 10-15 dB improvements
        at 8kHz

    Copyright Frequency Therapeutics, Inc.                                  27
Clinical Data Confirms FX-322 Delivery to Cochlea

 • Exploratory study in Germany to see if cochlear
   drug levels can be directly measured
 • Patients undergoing cochlear implant
   surgery receive standard FX-322 injection
 • Cochlear fluid (perilymph) obtained

Key findings:
 • Measurement of cochlear fluid confirmed
   successful drug delivery to cochlea in all
   samples analyzed
 • Drug levels predicted to result in
   therapeutic activity
    Taken together with Phase 1/2 study, we believe this is the first known evidence of a
  pharmacokinetic / pharmacodynamic effect of a potential hearing restoration therapeutic
Copyright Frequency Therapeutics, Inc.                                                      28
Key Elements in FX-322 Development:

                                         Leadership in Hearing Drug Development

         Effective                            Favorable      Clinically meaningful   Preliminary evidence
      delivery to the                       safety profile     improvements in          of longer-term
       target tissue                                           hearing function            durability

Copyright Frequency Therapeutics, Inc.                                                                      29
Phase 2a Study – Objectives

          Further establish                Evaluate      Clarify endpoints and
           hearing signal                repeat dosing    patient population

Copyright Frequency Therapeutics, Inc.                                           30
FX-322 Study - Phase 2a Design

                                                Screening NIHL/SSNHL
                                               Mild to Moderately Severe                     • Double-blind, placebo-controlled,
                                                                                               multi-center, adults ages 18-65
                                                                                                  • All subjects have meaningful
                                                   Randomize 1:1:1:1
                                                                                                    word recognition deficits
                                                                                             • Efficacy and exploratory endpoints
                                                                                                • Word recognition
           FX-322                           FX-322                  FX-322         Placebo
                                                                                                • Words-in-noise
             1X                               2X                      4X              4X
           N = 24                           N = 24                  N = 24          N = 24      • Pure tone audiometry (0.25-16kHz)
                                                                                                • Tinnitus questionnaire
                                                                                                • QoL questionnaires

                                                    Follow-up Visits
                                         Days 15, 30, 60, 90, 120, 150, 180, 210

Copyright Frequency Therapeutics, Inc.                                                                                                31
Hearing Loss Overview

Copyright Frequency Therapeutics, Inc.   32
Improvement in Hearing Clarity is the Major Unmet
Need Among Hearing Loss Patients

        “I can hear you…
         I just can’t understand you.”

Copyright Frequency Therapeutics, Inc.              33
Opportunity to Treat Substantial Patient Population (US)

                                                                                                           2018 Hearing Loss Prevalence – US Adults
• ~40m SNHL patients – expected                                                                    30
                                                                                                                 26
  to grow by 20% by 2030                                                                                                                 = not treated

                                                                                                                                         = treated with hearing aids
• Opportunity to treat patients

                                                                             Patients (millions)
                                                                                                   20
  both with and without hearing                                                                                                               15
  aids
                                                                                                   10
• Significant opportunity to
  expand treatment rate among
  mild patients                                                                                     0
                                                                                                              Mild                    Moderate / Severe
• No restorative therapies exist to                                                                        Hearing Loss                 Hearing Loss

  treat underlying cause of SNHL
              Notes: Prevalence based on self-reported hearing loss; sensorineural accounts for >90% of hearing loss
              Source: National Health Interview Survey (sample size of 35,000 households); Census Bureau; NIH; NCBI

Copyright Frequency Therapeutics, Inc.                                                                                                                                 34
Commercial Overview
Introduction of an injectable therapeutic for hearing loss will require ear, nose and throat (ENT) doctors for prescription
and administration, while continuing to drive diagnosis and monitoring through audiologists

                               CURRENT STATE                                               FUTURE STATE

                                                                                 •      FX-322 aims to improve hearing for
                         • Hearing aids are the primary treatment
                                                                                        those with acquired SNHL including
                           for hearing loss; limited in reaching
                                                                                        overall sound clarity, a major unmet
                           frequencies that impact sound clarity
                                                                                        need for hearing loss patients
                         • ENTs have no approved treatment
                           interventions to offer mild, moderate, or                 • Procedure would be integrated into
                           moderately severe hearing loss patients                     existing ENT office practices for patients
                                                                                       with or without hearing aids
                         • Audiologists are the primary source of
                                                                                     • Audiologists role in diagnosing hearing
                           diagnosis, treatment and monitoring
                                                                                       loss and patient engagement likely to
   Only half of hearing loss pts have                                                  grow with increased treatment options
   been formally diagnosed/treated in
   part due to a lack of available
   treatment options*

 Frequency’s focus includes market insight generation, planning & development, and stakeholder engagement
Confidential
  Copyright | Frequency Therapeutics, Inc.                             35                                           *CDC/NCHS       35
Hearing Health Impacts Brain Health
                                          July, 2020
                                                               Risks Associated with
Hearing loss is the largest potentially modifiable risk
          factor for developing dementia                      Untreated Hearing Loss

                                                                      50%                                                  41%

                                                              DEMENTIA                                         DEPRESSION

                                                                                                   JAMA Nov 8, 2018
                                                          Deal J, et al. Incident Hearing Loss and Comorbidity. A Longitudinal Administrative Claims Study.

 Copyright Frequency Therapeutics, Inc.                                                                                                                       36
Broad Potential of
  Progenitor Cell Activation Approach

Copyright Frequency Therapeutics, Inc.   37
Remyelination Program for Multiple Sclerosis

       Building on strong progenitor             Target IND submission
       biology foundation                        in 2H21
         • Scripps Institute applied PCA         • Building on expertise in discovering
           approach to brain progenitors           and developing synergistic
                                                   combinations of small molecules
         • Validated in multiple animal models
                                                 • Worldwide license and ongoing
         • Clinically validated using a single
                                                   research partnership with Scripps
           agent (Lancet Dec ’17)

Copyright Frequency Therapeutics, Inc.                                                    38
Moving Forward

Copyright Frequency Therapeutics, Inc.   39
Summary
                                         +                                  +
                       Hearing Signal Established                   Large Market
                     Potential first-in-class regenerative         Addressable market
                        treatment to restore hearing         of >30 million people in the U.S.

                                          +                                 +
                                  Ex-US Partnership               Platform Potential
                           Global development and              PCA platform with potential
                        commercial partner; substantial      to treat patients with numerous
                           royalties and milestones,              degenerative diseases
                              U.S. rights retained

Copyright Frequency Therapeutics, Inc.                                                           40
Appendix

Copyright Frequency Therapeutics, Inc.   41
Uniqueness of Our PCA Approach

                                 Previous approaches                                   Frequency’s PCA approach

                                                      Stem cell
Pluripotent

Multipotent

                                                                  Yamanaka 4 factors
                                                                                                Partial reprogramming
Bipotent
                               Transdifferentiation

Fully
differentiated

                               Hair           Progenitor                                 Hair           Progenitor
                               cell              cell                                    cell              cell

Copyright Frequency Therapeutics, Inc.                                                                             Based on Conrad Waddington’s Epigenetic Landscape   42
Progenitors in Place to Replace Hair Cell Loss

                                Human Cochlear Cross-section                                                     Audiogram

                                                                                                          Hearing loss
                                                                                                          correlates
                                                                                                          with hair cell
                                                                                                          loss

                                                                                                                    Normal Ion Transport

                           Despite Hair Cell Loss, Progenitor Cells Remain                                         Normal Nerve Function

                                                 47 Year Old Male with Occupational Noise Deafness
Copyright Frequency Therapeutics, Inc.                                                      Analysis in Partnership with Mass Eye and Ear Institute Temporal Bone Bank   43
Astellas Collaboration
    • Development and commercialization collaboration for FX-322, including lifecycle improvements
    • Astellas has ex-US rights; Frequency retains US rights to FX-322
    • Payments of up to $625mm which included $80mm upfront
           – Development milestone payments to Frequency of $65.0 million and $25.0 million upon the first
             dosing of a patient in a Phase 2b clinical trial for SNHL in Europe and Asia, respectively
           – $100.0 million and $40.0 million upon the first dosing of a patient in a Phase 3 clinical trial for
             SNHL in Europe and Asia, respectively
    • Development & commercialization:
       – Astellas responsible for execution and costs of ex-US clinical development and commercialization

                                                   • Strategic commitment to invest in ENT as a
                                                     therapeutic area
                                                   • Research focus in regenerative medicine
                                                   • Global footprint in major markets and
                                                     distributorship model in Africa/ME and LATAM
Copyright Frequency Therapeutics, Inc.                                                                             44
Proven Leadership Team

    David Lucchino                                    Chris Loose, Ph.D.                                   Carl Lebel, Ph.D.
    President, CEO & Co-Founder                       Chief Scientific Officer & Co-Founder                Chief Development Officer
    Former CEO of Entrega Bio (PureTech). Co-         Co-founder/CTO of Semprus BioSciences through        Chief Scientific Officer of Otonomy (2009 to
    founder/CEO of Semprus BioSciences (acquired),    FDA/CE clearance and acquisition. Princeton, MIT,    2016). Executive Director, Amgen. Scientific
    Polaris Partners. MIT Sloan Fellow.               Hertz Fellow and Yale Faculty.                       fellow of the American Academy of
                                                                                                           Otolaryngology.

    Dana Hilt, M.D.                                   William Chin, M.D.                                   Will McLean, Ph.D.
    Chief Medical Officer                             EVP, Clinical & Translational Science                VP, Biology & Regen. Med, Co-Founder
    Neurologist and neuroscientist with two decades   SVP, Discovery Research and Clinical Investigation   15 years experience in inner ear biology.
    in biopharma and CNS drug development.            at Eli Lilly, EVP at PhRMA, Executive Dean for       Discovered specific stem cells that make hair
    Amgen, Lysosomal, Forum Pharma.                   Research at Harvard Medical School.                  cells and neurons. Harvard-MIT Health
                                                                                                           Sciences and Technology Program.

Copyright Frequency Therapeutics, Inc.                                                                                                                     45
Hearing Clinical Advisory Board

                Dan Lee, M.D.                  Rene Gifford, Ph.D.                Steve Rauch, M.D.                Ruth Litovsky, Ph.D.
                Director, Pediatric Otology    Associate Director of              Director, Vestibular Division,   Professor, Communications
                and Neurotology,               Pediatric Audiology, Director      Medical Director, Mass. Eye      Sciences and Disorders and
                Mass Eye and Ear               of Cochlear Implant Program,       and Ear Balance and              Surgery Division of Otolaryngology,
                                               Vanderbilt University              Vestibular Center                University of Wisconsin

                Chris Runge, Ph.D.              David Friedland, M.D., Ph.D.      Julie Arenberg, MS, Ph.D.        Joni Doherty, MD, Ph.D.
                Chief of the Division of        Vice-Chair of the Department of   Associate Director of Clinical   Assistant Professor of Clinical
                Communication Sciences,         Otolaryngology and                Audiology for Research and       Otolaryngology-Head and Neck
                Medical College of Wisconsin    Communications Sciences,          Education, Mass Eye and Ear      Surgery, Keck School of Medicine
                                                Medical College of Wisconsin                                       of USC.

Copyright Frequency Therapeutics, Inc.                                                                                                                   46
Regenerative Medicine Advisory Board

Jeff Karp, Ph.D.                            Robert Langer, SC.D.                  Robin Franklin, Ph.D.                  Sheng Ding, Ph.D.
Associate Professor at                      David H. Koch Institute Professor     Professor of Stem Cell Medicine,       Senior Investigator, Gladstone
Brigham and Women’s Hospital,               at the Massachusetts Institute        Wellcome Trust-MRC Cambridge           Institute of Cardiovascular Disease
Harvard Medical School                      of Technology                         Stem Cell Institute

Sean J. Morrison, Ph.D.                      Siddhartha Mukherjee,                 Amy Wagers, Ph.D.
Director of the Children's Medical Center    M.D., D.Phil.                         Forst Family Professor of
Research Institute,                          Assistant Professor of Medicine,      Stem Cell and Regenerative Biology,
UT Southwestern                              Columbia University Medical Center    Harvard University

Copyright Frequency Therapeutics, Inc.                                                                                                                         47
Frequency Therapeutics
    Corporate Overview

    September 2020

Copyright Frequency Therapeutics, Inc.   48
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