Full Press Release Details
Frequency Therapeutics Corporate Presentation September 2022
Forward-Looking Statements and Other Disclaimers This presentation
contains forward-looking statements within the meaning of the dependence on the development of FX-322; the unproven approach of the PCA Private Securities Litigation Reform Act of 1995. All statements contained in this platform; the lengthy,
expensive and uncertain process of clinical drug presentation that do not relate to matters of historical fact should be considered development and regulatory approval; limited experience successfully obtaining forward-looking statements, including
without limitation statements regarding the marketing approval for and commercializing product candidates; the results of design of Frequency Therapeutics' (the "Company") Phase 2b trial of FX-322, earlier clinical trials not being
indicative of the results from later clinical trials; including the type of SNHL that the enrolled patients will have and the ability of differences between preliminary or interim data and final data; adverse events or design features to reduce
bias, the timing of the Company's trials, including the undesirable side effects; disruptions at the FDA and other regulatory agencies; Phase 2b trial of FX-322, Phase 1b trial of FX-345, and Phase 1 trial in the failure to identify additional
product candidates; new or changed legislation; multiple sclerosis ("MS") remyelination program, the interpretation and failure to maintain Fast Track designation for FX-322 and such designation failing implications of the results and
learnings of previous FX-322 clinical studies, the to result in faster development or regulatory review or approval; costly and acceptance by the FDA of particular endpoints in the Company's trials, the damaging litigation, including related
to product liability, intellectual property or treatment potential of FX-322, FX-345, and the novel approach for remyelination brought by stockholders; dependence on Astellas Pharma Inc. for the in MS, the timing and progress of the FX-345 and
remyelination programs, the development and commercialization of FX-322 outside of the United States; sufficiency of the Company's cash, cash equivalents and short-term investments, misconduct by employees or independent contractors; reliance
on third parties, estimates of the size of the hearing loss population and population at risk for including to conduct clinical trials and manufacture product candidates; hearing loss, estimates of the size of the population with MS, estimates of
the compliance with laws and regulations, including healthcare and environmental, commercial opportunity of FX-322, FX-345, and the novel approach to health, and safety laws and regulations; failure to obtain, maintain and enforce remyelination, the
impact on existing treatment paradigms, the potential for payor protection of patents and other intellectual property; security breaches or failure reimbursements for treatment, the ability of our technology platform to provide to protect private
personal information; attracting and retaining key personnel; patient benefit, and the potential application of the progenitor cell activation and ability to manage growth. ("PCA") platform to other diseases. These and other important
factors discussed under the caption "Risk factors" in These forward-looking statements are based on management's current the Company's Form 10-Q filed with the Securities and Exchange Commission expectations. These statements
are neither promises nor guarantees, but involve (SEC) on August 9, 2022 and its other reports filed with the SEC could cause known and unknown risks, uncertainties and other important factors that may actual results to differ materially from those
indicated by the forward-looking cause actual results, performance or achievements to be materially different from statements made in this presentation. Any such forward-looking statements any future results, performance or achievements expressed or
implied by the represent management's estimates as of the date of this presentation. While the forward-looking statements, including, but not limited to, the following: the impact Company may elect to update such forward-looking statements at
some point in of COVID-19 on the Company's ongoing and planned clinical trials, research and the future, it disclaims any obligation to do so, even if subsequent events cause development and manufacturing activities, the Company's
business and financial its views to change. These forward-looking statements should not be relied upon markets; the Company has incurred and will continue to incur significant losses as representing the Company's views as of any date
subsequent to the date of and is not and may never be profitable; need for additional funding to complete this presentation. development and commercialization of any product candidate; the Company's Frequency Therapeutics, Inc. |
Vision A new approach to regenerative medicine Using small
molecules to activate the body's innate regenerative potential Applicable to many other degenerative diseases with large patient populations Opportunity The first drug candidate shown to improve hearing Potential to transform
treatment for millions Key clinical readout in Q1 2023 Frequency Therapeutics, Inc. | 3
Significant Near-Term Clinical Milestones and Data Readouts Capitalized
to Achieve Major Milestones FX-322 FX-345 Development Candidate Lead Second MS Remyelination Hearing Program Hearing Program Program Phase 2b 208 Phase 1b Advance to study readout readout Phase 1 Study Q1 2023 H2 2023 H2 2023 Lead hearing
restoration study in New hearing restoration candidate Small-molecule therapeutic to sudden sensorineural and noise- explores impact of broader activate oligodendrocyte induced hearing loss cochlear drug distribution precursor cells to restore
myelin Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. || 4 4
Transforming the Standard of Care for Hearing Loss FX-322 for Hearing
Restoration SIGNIFICANT POTENTIAL PARADIGM- UNMET NEED CHANGING THERAPY There are no solutions to Enhancing speech perception address the underlying biological - the greatest need for millions cause of hearing loss of individuals with hearing
loss Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. || 5 5
FX-322: A Small Molecule Candidate to Address the Underlying Pathology
Combination of pathways aims to activate progenitor cells and regenerate sensory cells in the cochlea Frequency Therapeutics, Inc. | 6
FX-322: Directly Targeting the Regeneration of Sensory Hair Cells in the
Cochlea The injection concentrates FX-322 FX-322 is administered via a standard in the cochlear region critical for intratympanic injection, a routine speech intelligibility procedure performed by ENTs Frequency Therapeutics, Inc. |
Clinical Impact of a 5-word Improvement for Hearing Loss Patient
5-word increase out 50 of 50 (10% absolute) is clinically meaningful 5-word improvement 40 can allow individual to Speech perception delay/avoid Impacts treatment range of procedure recommendation cochlear implant 30 candidate 29
Individuals with stable 26 hearing loss do not 20 spontaneously improve 16 14 10 7 0 Frequency Therapeutics, Inc. | 8 Number of Words Correct ( out of 50)
Speech Perception Improvements with FX - 322 Data from FX-322 -
201 Phase 1/2 Study More than 30% of 50 subjects had a greater 47 than 5-word 40 improvement in speech 39 38 perception scores 34 30 Some subjects 29 26 more than doubled their scores 20 Baseline - 20 Correct words out of 50 16
Some maintained 14 Day 90 - 10 Correct words improvements one to out of 50 two years later 7 Statistically Significant 0 Subject 1 Subject 2 Subject 3 Subject 4 Subject 5 Published in Otology and Neurotology, February 2021 Improved
Speech Intelligibility in Subjects with Stable Frequency Therapeutics, Inc. | 9 Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study (W.J. McLean, et. al.) Number of Words Correct ( out of 50)
Outcomes from Five FX-322 Studies Building a Clinical Path for a
Hearing Therapeutic Sudden and Sudden and Age-related, no sudden or Severe, all etiologies All etiologies noise-induced SNHL noise-induced SNHL noise-induced FX-322-201 FX-322-202 FX-322-111 FX-322-112 FX-322-113 Double blind Double blind Open label
study Double blind Double blind Placebo controlled Placebo controlled Placebo controlled Placebo controlled Mild-to-mod. severe Mild-to-mod. severe Mild-severe Mild-to-mod. severe Severe hearing loss Aged 18-65 Aged 18-65 Aged 18-65 Aged 66-85 Aged
18-65 N=23 N=96 (4x injections) N=33 N=30 N=31 Statistically significant, High percentage of Statistically significant, Limited response in treatment Hearing improvements clinically meaningful responses in untreated and clinically meaningful group.
Study excluded older shown in multiple subjects improvement in placebo ears improvement in individuals with noise-induced using signal-to-noise speech perception in speech perception in and sudden hearing loss measures treatment group treatment
group No Drug-Related Serious Adverse Events >200 Subjects Dosed Hearing signal No change between placebo and treated groups Inconsistent baselines undermined data Frequency Therapeutics, Inc. | 10
Pooled FX-322 Data Across Studies Shows Pattern of Response Studies
201, 111, 112 & 113 20 Exceeds 95% Confidence Interval 10 +5 words 0 -5 words -10 Treated Untreated Placebo 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007). Frequency
Therapeutics, Inc. | 11 Word improvement to reach 95% confidence interval depends on starting performance. Change in Words
Pooled Single-Dose Studies Defined Etiology/Severity for 208 Study
Moderately- Moderate Mild Severe Severe Noise 0% 0% 33% 17% (18-65 years) Sudden 0% 27% 40% 8% (18-65 years) Placebo and untreated ears had a 3% response rate 208 Trial Age-related 0% 7% 0% (65+ years) 94 subjects, single dose Circle size = # of
people tested Color = % of responders Frequency Therapeutics, Inc. | 12
Substantial and Growing Need within Target Population Moderately-
Moderate Mild Severe Severe Noise 33% 33% (18-65 years) 208 study: Target population 7-10 million Sudden 40% 27% 27% 40% people in the U.S. (18-65 years) 208 Trial Age-related (65+ years) 94 subjects, single dose Circle size = # of people tested
Color = % of responders Frequency Therapeutics, Inc. | 13
FX-322-208 Phase 2B Study Powered to show statistically significant
improvement in speech perception 124 Subjects, SSNHL and NIHL, Ages 18-65 3 screenings to enter lead-in Pure tone average 35-85 dBHL Rigorous Study Design Start of 1-Month Lead-in Day -30 Lead-in phase with multiple baseline measures Lead-in Day -15
Ability to disqualify subjects based on test stability Baseline Day 1 All sessions recorded and monitored Randomize Sites and patients masked FX-322 Placebo to qualifying test results Placebo 1X 1X 1X N = 62 N = 62 N = 62 Follow-up Visits: Days 30,
60, 90 Frequency Therapeutics, Inc. | 14
Clearly Defined Criteria for FX-322-208 Study Success Pre-specified,
FDA-aligned clinical endpoints Powered to detect Pre-Specified Responder efficacy over placebo Definition Responders have statistically significant Study powered to show greater and clinically meaningful improvements responder rate in FX-322 treated
(Exceed 95% confidence interval on patients than placebo (p<0.05)* speech perception test*) *80% power assuming 20% effect size *Speech perception test used as a primary endpoint is pre-specified but not publicly disclosed to keep clinicians and
patients blinded Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. || 15 15
Clear Commercial Path First Potential Therapy for Millions of People
with Hearing Loss Small molecule Established ENT Path to approach physician channel reimbursement - Not gene or cell therapy- Medicine would enable - Existing reimbursement ENTs to offer intervention to (and CPT code) for -
Favorable safety profile patients with SNHL trans-tympanic injection - Ease of manufacturing and - Standard trans-tympanic - ENTs are currently drug delivery injection reimbursed for many hearing interventions Fre
Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. || 16 16
Hearing Loss Can Have a Significant Impact on Overall Health July, 2020
November, 2018 Increased risks with untreated hearing loss "Hearing loss is the largest potentially modifiable risk factor 50% 41% for developing dementia" Dementia Depression JAMA Nov 8, 2018, Deal J, et al. Incident Hearing Loss and
Comorbidity. A Longitudinal Administrative Claims Study. Frequency Therapeutics, Inc. | 17
Opportunities Enabled by a Positive FX-322-208 Study Outcome Regulatory
Defined path to registrational studies Potential for FX-322-208 to be considered a pivotal study One additional study for approval Potential for Breakthrough Therapy designation FX-322 Partner Milestones $625m for ex-US development
and commercialization AST Development milestone payments to Frequency $90 million for Phase 2b start in Europe and Asia $140 million for Phase 3 start in Europe and Asia Frequency Therapeutics, Inc. | 18
Pipeline Expansion Frequency Therapeutics, Inc. | 19
New Regenerative Program What if we were able to get greater drug
distribution in the cochlea? Frequency Therapeutics, Inc. | 20
FX-345 Working to Achieve Broad Exposure Through the Cochlea
Second hearing restoration program Enables coverage of a large portion of the cochlea Potential to address additional SNHL patient types Formulation enabling evaluation of a range of dose levels Developing in addition
to FX-322. Clinical data will drive commercial positioning Frequency Therapeutics, Inc. | 21
FX-345 Creating Effective Drug Levels Through Large Portion of Cochlea
Frequency Therapeutics, Inc. | 22
New Regenerative Program What if we could extend our approach to other
degenerative diseases? Frequency Therapeutics, Inc. | 23
Novel Frequency Small Molecule Inhibitors Drive Oligodendrocyte
Differentiation Lead Optimization generated FREQ-162 Highly potent Highly efficacious Orally bioavailable Brain penetrant Novel chemical entity Patent application filed Frequency discovered a novel and highly effective target 1 3 10 30 100 Developed
novel chemical nM nM nM nM nM entities that are highly potent inducers of oligodendrocyte differentiation FREQ-162 Frequency Therapeutics, Inc. | 24 % Newly Differentiated Oligodendrocytes Vehicle Negative Control
FREQ-162 Outperforms Literature Compounds In Vivo Adult mice received 3
doses of comparator compounds or a single dose of FREQ-162 Brains were stained for a marker of newly generated oligodendrocytes Single dose FREQ-162 induces more OPCs to differentiate than comparator compounds Vehicle T3 / Thyromimetic -Lingo
Antibody Clemastine / Anti-Muscarinic FREQ-162 x 3 days 10 mg/kg x 3 days 5 mg/kg x 3 days 75 mg/kg x 3 days 5 mg/kg, Single Dose FREQ-162 induces formation -Lingo antibody: Clemastine: Thyroid Hormone: of newly differentiated Blocking
antibody Anti-Muscarinic Class Thyromimetic Class oligodendrocytes in both white and gray matter Frequency Therapeutics, Inc. | 25
The Cuprizone Model of Chronic Demyelination Healthy Control Cuprizone,
Vehicle Cortex Corpus Callosum Adult mice were demyelinated via 17 months of cuprizone Striatum administration Elderly mice with long term demyelination Myelin Basic Protein Myelin Basic Protein Frequency Therapeutics, Inc. |
FREQ-162 Outperforms Published Compounds In Vivo Adult mice received up
to 10 daily doses of comparators or a single dose of FREQ-162 Brains were stained for Myelin Basic Protein (green) Single dose FREQ-162 induces more remyelination than comparator compounds Vehicle T3 / Thyromimetic -Lingo Antibody Clemastine /
Anti-Muscarinic FREQ-162 x 10 doses 10 mg/kg x 10 doses 5 mg/kg x 3 doses 75 mg/kg x 10 doses 5 mg/kg, Single Dose FREQ-162 induces formation -Lingo antibody: Clemastine: Thyroid Hormone: of new myelin in white and Lingo inhibitor
Anti-Muscarinic Class Thyromimetic Class gray matter Animals demyelinated for 17 months via cuprizone treatment Frequency Therapeutics, Inc. | 27
Frequency NCEs Outperform Competitors: High Magnification FREQ-162