UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
| Item 2.02. | Results of Operations and Financial Condition. |
On November 9, 2021, Frequency Therapeutics, Inc. (the “Company”) announced that its unaudited cash, cash equivalents and marketable securities totaled $160.5 million as of September 30, 2021, which does not include Restricted Cash.
| Item 7.01. | Regulation FD Disclosure. |
On November 9, 2021, the Company posted an updated corporate slide presentation and a slide presentation from its R&D Event to be held today, Tuesday, November 9, 2021 at 8:00 a.m. Eastern Time (R&D Event) in the “Investors & Media” portion of its website at www.frequencytx.com. Copies of the slide presentations are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K (the “Current Report”).
The information in this Item 7.01 of this Current Report, including Exhibits 99.1 and 99.2, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly provided by specific reference in such filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibits 99.1 and 99.2.
| Item 8.01. | Other Events. |
On November 9, 2021, the Company announced the following highlights to be disclosed during its R&D Event:
FX-322
| • | Clinical data review from four completed FX-322 clinical studies, including 169 subjects with a range of hearing loss severities and sensorineural hearing loss (SNHL) etiologies (sudden, noise-induced, age-related). |
| • | Analysis of statistically significant and clinically meaningful patient responses following a single FX-322 administration, establishing the range of severity and etiologies that will be explored in the upcoming FX-322-208 study. |
| • | Review of design of ongoing FX-322-208 study, including use of multiple lead-in hearing measures implemented to reduce study bias and baseline variability. |
| • | Alignment with the U.S. Food and Drug Administration around speech perception measures as a primary efficacy endpoint and the importance of speech perception as the key unmet need for individuals with SNHL. |
FX-345
| • | Introduction of new SNHL investigational therapeutic program, including a more potent GSK3 inhibitor designed to achieve broader exposure of the cochlea. |
| • | Preclinical pharmacokinetic measures and human modeling data have indicated that therapeutically active FX-345 drug levels could be reached in areas of the cochlea corresponding to a wider range of hearing frequencies. |
| • | Potential to benefit an expanded SNHL patient population. |
| • | Investigational New Drug application submission anticipated in Q2 2022. |
Remyelination in Multiple Sclerosis
| • | Identified novel therapeutic target that drives oligodendrocyte progenitor cell differentiation and myelination. |
| • | FREQ-162, preclinical stage lead compound, showed substantial remyelination in preclinical studies. |
| • | FREQ-162 being advanced in preclinical safety studies toward the initiation of clinical development. |
Forward-Looking Statements
This Current Report contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this Current Report that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the design of the new Phase 2 trial of FX-322, including the type of SNHL that the enrolled patients will have and the ability of design features to reduce bias, the interpretation and implications of the results and learnings of other FX-322 clinical studies, the acceptance by the FDA of particular endpoints in the Company’s trials, the treatment potential of FX-322, FX-345, and the novel approach for remyelination in multiple sclerosis, the timing and progress of the FX-345 and remyelination programs, the topics to be discussed during the R&D event, the ability of our technology platform to provide patient benefit, the ability to continue to develop our Progenitor Cell Activation (PCA) platform and identify additional product candidates, 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: the impact of COVID-19 on the Company’s ongoing and planned clinical trials, research and development and manufacturing activities; the Company has incurred and will continue to incur significant losses and is not and may never be profitable; the Company’s 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; the Company’s 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; 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; ability to seek and receive Breakthrough Therapy designation for FX-322; the Company’s ability to enroll and retain patients in clinical trials; costly and damaging litigation, including related to product liability or intellectual property or brought by stockholders; dependence on Astellas Pharma Inc. 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 changing laws and regulations, including healthcare and environmental, health, data privacy and safety laws and regulations; failure to obtain, maintain and enforce protection of patents and other intellectual property rights covering product candidates; security breaches or failure to protect private personal information; attracting and retaining key personnel; and the Company’s 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, 2021 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 Current Report. Any such forward-looking statements represent management’s estimates as of the date of this Current Report. 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 Current Report.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following exhibits relate to Items 7.01, and shall be deemed to be furnished, and not filed:
| Exhibit |
Description | |
| 99.1 | Frequency Therapeutics, Inc. Corporate Slide Presentation as of November 9, 2021 | |
| 99.2 | Frequency Therapeutics, Inc. R&D Event Slide Presentation | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| FREQUENCY THERAPEUTICS, INC. | ||||||
| Date: November 9, 2021 | By: | /s/ David L. Lucchino | ||||
| Name: | David L. Lucchino | |||||
| Title: | President and Chief Executive Officer | |||||
Exhibit 99.1 Pioneering a New Category in Regenerative Medicine Frequency Therapeutics Corporate Presentation
Forward-Looking Statements and Other Disclaimers This presentation contains forward-looking statements within the meaning of the process of clinical drug development and regulatory approval; limited experience Private Securities Litigation Reform Act of 1995. All statements contained in this successfully obtaining marketing approval for and commercializing product presentation that do not relate to matters of historical fact should be considered candidates; the results of earlier clinical trials not being indicative of the results forward-looking statements, including without limitation statements regarding the from later clinical trials; differences between preliminary or interim data and final timing and design of the new Phase 2b trial of FX-322, including the type of data; adverse events or undesirable side effects; disruptions at the FDA and other SNHL that the enrolled patients will have and the ability of design features to regulatory agencies; failure to identify additional product candidates; new or reduce bias, the interpretation and implications of the results and learnings of changed legislation; failure to maintain Fast Track designation for FX-322 and other FX-322 clinical studies, the acceptance by the FDA of particular endpoints such designation failing to result in faster development or regulatory review or in the Company’s trials, the treatment potential of FX-322, FX-345, and the novel approval; costly and damaging litigation, including related to product liability, approach for remyelination in multiple sclerosis, the timing and progress of the intellectual property or brought by stockholders; dependence on Astellas Pharma FX-345 and remyelination programs, the sufficiency of the Company’s cash, cash Inc. for the development and commercialization of FX-322 outside of the United equivalents and short-term investments, estimates of the size of the hearing loss States; misconduct by employees or independent contractors; reliance on third population and population at risk for hearing loss, estimates of the commercial parties, including to conduct clinical trials and manufacture product candidates; opportunity of FX-322 and the impact on existing treatment paradigms, the ability compliance with laws and regulations, including healthcare and environmental, of our technology platform to provide patient benefit, and the potential application health, and safety laws and regulations; failure to obtain, maintain and enforce of the PCA platform to other diseases. protection of patents and other intellectual property; security breaches or failure to protect private personal information; attracting and retaining key personnel; These forward-looking statements are based on management’s current and ability to manage growth. expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may These and other important factors discussed under the caption “Risk factors” in cause actual results, performance or achievements to be materially different from the Company’s Form 10-Q filed with the Securities and Exchange Commission any future results, performance or achievements expressed or implied by the (SEC) on August 12, 2021 and its other reports filed with the SEC could cause forward-looking statements, including, but not limited to, the following: the impact actual results to differ materially from those indicated by the forward-looking of COVID-19 on the Company’s ongoing and planned clinical trials, research and statements made in this presentation. Any such forward-looking statements development and manufacturing activities, the relocation of the Company’s represent management’s estimates as of the date of this presentation. While the offices and laboratory facilities, the Company’s business and financial markets; Company may elect to update such forward-looking statements at some point in Frequency Therapeutics (the “Company”) has incurred and will continue to incur the future, it disclaims any obligation to do so, even if subsequent events cause significant losses and is not and may never be profitable; need for additional its views to change. These forward-looking statements should not be relied upon funding to complete development and commercialization of any product as representing the Company’s views as of any date subsequent to the date of candidate; the Company’s dependence on the development of FX-322; the this presentation. unproven approach of the PCA platform; the lengthy, expensive and uncertain © Frequency Therapeutics, Inc. | 2
A Vision Built on Regeneration Since 2014, Frequency has focused on developing therapeutics by activating a person’s innate regenerative potential, within the body, to repair tissue and restore human function. © Frequency Therapeutics, Inc. | 3
Power of the Progenitor Cell Activation (PCA) Platform Ease of No Change to Harnessing Manufacturing Genome Innate Biology Use of small Activating native Progenitors molecules: no need programs, already located to remove or grow reducing safety within the cells ex vivo concerns target tissue © Frequency Therapeutics, Inc. | 4 © Frequency Therapeutics, Inc. | 4
A Series of Firsts in Hearing Restoration First PK/PD First clinical First speech First to show shown for a studies to show perception sustained hearing therapeutic hearing improvements improvements candidate improvements measured and continued improvements over time © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 5 5
FX-322: A Small Molecule Candidate to Address the Underlying Pathology Synergy between 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. | 7
Four FX-322 Completed Studies: 169 Subjects Favorable Safety Profile with No Treatment-Related SAEs SINGLE-DOSE 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 2 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 3 112 MULTIPLE-INJECTION STUDY SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 4 202 = Data Readout © Frequency Therapeutics, Inc. | 8
FX-322-201 and FX-322-111 Single-Dose Safety Studies with Hearing Improvement Signal SINGLE-DOSE 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 2 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 3 112 MULTIPLE-INJECTION STUDY SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 4 202 = Data Readout © Frequency Therapeutics, Inc. | 9
Two Independent Studies (FX-322-201, FX-322-111) Show Hearing Improvements with Single Dose Day-90 Word Recognition Scores Across Studies Phase 1/2 Study Phase 1b Study FX-322-111 FX-322-201 Overview Overview FX-322-201 Phase 1/2 FX-322-111 Phase 1b • Placebo-controlled, multi-center, • Compared different FX-322 40% randomized study administration conditions • Mild to moderately severe subjects, • Open-label, multi-center, age 18-65 (n=23) randomized study • NIHL/SSNHL• Mild to severe subjects, age 30% 18-65 (n=33) Study Results Study Results 20% • 33% of subjects achieved 10% or • 34% of subjects achieved 10% or greater absolute improvement in greater absolute improvement in word word recognition in treated ear recognition (WR) in treated ear 10% • Statistically significant and clinically • Statistically significant and clinically meaningful improvements in WR meaningful improvements in WR • No meaningful changes in • Favorable safety profile placebo group 0% • Favorable safety profile Placebo FX-322 Untreated FX-322 *Total of 33 patients enrolled in study, 32 subjects * * completed 90-day clinical assessment period (n=8) (n=15) (n=32) (n=32) © Frequency Therapeutics, Inc. | 10 % Exceeding Absolute 10%
FX-322 Phase 1/2 Durability Data: Patients Show Sustained Hearing Improvements 13-21 Months After Initial Dosing 50 50W Month 16** Month 21** Month 19** Month 13** Month 21** 47 Key Findings 50W 40 Preliminary evidence *25W 50W 39 indicating a durable benefit 38 38 50W 50W of hearing clarity 35 34 *25W 50W 30 30 29 50W Baseline - Correct words out of 50 26 50W Day 90 - Correct words out of 50 50W 22 20 20 1-2 Years - Correct words out of 50 50W 50W 16 50W 14 Three patients who had durable 12 10 improvements in intelligibility also had 50W pure tone audiometry improvements 7 of 10 – 15 dB at the highest frequency tested (8k Hz) 0 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 © Frequency Therapeutics, Inc. | 11
Follow up of FX-322-111 Subjects Show Additional Hearing Improvements at Later Time Points Conducted longer-term follow-up of FX-322-111 study subjects • 25 of 33 study subjects evaluated at 8-12 months following FX-322 dosing Results show some FX-322 dosed subjects accumulated hearing benefits over time • 4 subjects that had shown improvement trends in word recognition scores at day 90, achieved statistically significant scores when tested at the later time points To date, 9 of 32 evaluated study subjects have shown statistically significant improvements in speech perception scores in treated ears between 90 days and 1 year • No change observed in untreated ears © Frequency Therapeutics, Inc. | 12
Pooled FX-322 Data Shows Patterns of Response Single-dose Studies (201, 111, 112) Exceeding 95% Confidence Interval, Suggesting Inconsistent Baseline Value Measures % Exceeding Single-dose Studies Single-dose Studies 95% Confidence Interval (201, 111, 112) (201, 111 & 112) 25% 20 Exceeds 95% Confidence Interval 20% 14.1% 10 15% +10% 10% (5 words) 0 -10% (5 words) 5% 2.5% 2.1% 0% -10 Untreated Literature* Treated Treated Untreated Placebo and Placebo n = 71 n = 84 n = 13 n = 71 n = 97 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 13 Change in Words
FX-322-202 Multiple Injection Study to Assess Safety of Increased FX-322 Exposure SINGLE-DOSE 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 2 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 3 112 MULTIPLE-INJECTION STUDY SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 4 202 = Data Readout © Frequency Therapeutics, Inc. | 14
Comparing Pooled Data to Multiple-Injection Study FX-322-202 Placebo-Treated and Untreated Ears are Outside 95% Confidence Interval % Exceeding % Exceeding Single-dose Studies Multiple Injection Study 95% Confidence 95% Confidence Interval Interval (201, 111, 112) (202) 25% 25% 21.2% 20% 20% 15.4% 14.1% 15% 15% 10% 10% 5% 5% 2.5% 2.5% 2.1% 0% 0% Untreated Untreated Literature* Treated Literature Treated and Placebo and Placebo n = 71 n = 66 n = 104 n = 97 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 15
Clinical Study Data Informs New FX-322 Phase 2b Study © Frequency Therapeutics, Inc. | 16
New Clinical Study FX-322-208 Designed to Advance Drug Candidate to Pivotal Trials Built upon insights Sufficient sample Reduce from trials with hearing size to demonstrate potential restoration signal efficacy for bias Etiology, severity, Multiple baseline Approach based baseline speech measures on pooled data perception Primary endpoint of Multiple speech speech perception perception tests © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 17 17
U.S. Patients Pooled Single-Dose Studies (201, 111, 112) Data Suggest Patterns Between Etiology/Severity and Response Moderately- Moderate Mild Severe Severe 71 Treated with single-dose of FX-322 Noise The size of each circle represents the 0% 0% 33% (18-65 years) number of people tested per group The color of the circle represents the percentage of responders Sudden 208 Trial: Target Population 0% 27% 40% (18-65 years) 7-10 Million U.S. patients 208 Trial FX-322: Extended Population Age-related 0% 7% 0% (65+ years) 15+ Million U.S. patients © Frequency Therapeutics, Inc. | 18
Multiple Design Features Have Been Added to Mitigate Bias And Demonstrate Greater Separation Between Signal and Placebo Lead-in phase with multiple Start of 1-Month Lead-in baseline measures Day -30 Lead-in Sites and patients masked to Day -15 qualifying test results Baseline Day 1 All sessions recorded and monitored Ability to disqualify subjects based on symptom stability © Frequency Therapeutics, Inc. | 19
New FX-322 Placebo-Controlled Phase 2b Study Commenced First patient dosed in FX-322-208 Study in October 2021 Subjects Screened to Enter Lead-in Pure tone average 35-85dB 124 Subjects Start of 1-Month Lead-in Day -30 Subjects will have diagnosed Lead-in period with noise induced or sudden 3 visits determines Lead-in sensorineural hearing loss trial candidacy based Day -15 on consistency of audiologic testing Ages 18 – 65 Baseline Day 1 Randomize 124 subjects assumes 10% attrition Study powered at 80% FX-322 Placebo Effect size 20% over placebo Placebo 1X 1X Significance level is 0.05 1X N = 62 N = 62 N = 62 Follow-up Visits: Days 30, 60, 90 © Frequency Therapeutics, Inc. | 20
FDA Type C Meeting Held to Gain Alignment ALIGNMENT Primary Endpoint Gained alignment with FDA on speech perception as the primary endpoint 208 Study Design FDA reviewed and commented on 208 study, comments were incorporated into study protocol Patient Reported Outcomes (PRO) FDA feedback provided on novel PRO development called RADIAL; special meeting granted for further discussion © Frequency Therapeutics, Inc. | 21
Today’s Hearing Loss Market Has No Restorative Treatments Only ~$10 ~41 $980 20% Billion Million Billion Market US hearing aid Individuals Lost annually due penetration for market annual with SNHL to untreated hearing hearing aids sales in U.S. loss globally* *Source: World Health Organization © Frequency Therapeutics, Inc. | 22
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. | 23
Pipeline Expansion © Frequency Therapeutics, Inc. | 24
Two New Regenerative Programs What if we were able to get drug deeper into the cochlea? © Frequency Therapeutics, Inc. | 25
FX-345 Working to Achieve Broad Exposure Through the Cochlea • Second clinical program focused on regrowth of sensory cells • Enables coverage of large portion of cochlea • Potential to address additional SNHL patient types • Formulation enabling evaluation of a range of dose levels • Developing in addition to FX-322, and clinical data will drive commercial positioning © Frequency Therapeutics, Inc. | 26
FX-345 – A New Development Candidate Creating Effective Drug Levels Through Large Portion of Cochlea © Frequency Therapeutics, Inc. | 27
FX-345 Path to Clinic IND planned for H1:2022 for a Phase 1b study in patients with SNHL Enables us to clinically evaluate increased cochlear coverage across range of doses in multiple patient populations Candidate IND-enabling IND FIH clinical selection GLP tox Submission study On-going Q2 2022 H2 2022 © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 28 28
Two New Regenerative Programs What if we could extend our approach to other degenerative diseases? © Frequency Therapeutics, Inc. | 29
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. | 30 % 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 α-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 α-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. | 31
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 α-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 α-Lingo antibody: Clemastine: Thyroid Hormone: of new myelin in white and Lingo inhibitor Anti-Muscarinic Class Thyromimetic Class gray matter © Frequency Therapeutics, Inc. | 32
Frequency NCEs Outperform Competitors: High Magnification FREQ-162 Vehicle Cortex Cortex High Magnification view reveals that FREQ-162 Corpus Callosum Corpus Callosum yields myelination • in both white and gray matter • In the appropriate orientation and location Striatum Striatum 5 mg/kg x 1 dose Myelin Basic Protein © Frequency Therapeutics, Inc. | 33
FREQ-162: Highly Reproducible Increases in Myelination All 8 out of 8 mice treated with FREQ-162 showed robust increases in myelination in both white and gray matter tracts Vehicle #1 #2 #3 #4 #5 #7 #6 #8 FREQ-162 #7 #1 #2 #3 #4 #5 #6 #8 Myelin Basic Protein © Frequency Therapeutics, Inc. | 34
Freq-162 Induces Robust 6000 Increases in Myelination Myelin Basic Protein 5000 • Forebrain myelin basic protein levels 4000 quantitated • A single dose of a Frequency compound induces robust remyelination 3000 2000 Dose Fold Compound # of doses P= (mg/kg) change α-Lingo antibody 5 3 0.9 x 0.99 Clemastine 75 10 1.7 x 0.70 1000 Thyroid Hormone (T3) 10 10 1.4 x 0.95 FREQ-162 5 1 7.7 x <0.0001 0 Healthy Vehicle T3 Lingo Ab Clemastine FREQ-162 (10 mg/kg) (5 mg/kg) (75 mg/kg) (5 mg/kg) Naive © Frequency Therapeutics, Inc. | 35 MBP (Intensity Weighted Pixel Count)
Remyelination: Path Forward Discovered novel target Generated multiple compounds Induced high levels of oligodendrocyte differentiation and remyelination in vivo Initiating IND enabling studies © Frequency Therapeutics, Inc. | 36
Our Path Forward We believe FX-322 restores hearing. We know characteristics of FX-322 responders. Learnings from previous trials informed new trial design with strong controls and FDA approved clinical endpoints. We have a compelling new hearing program that will allow us to explore the impact of going deeper into the cochlea. We also have an exciting remyelination program in multiple sclerosis with a novel target and a strong response in vivo. We are a well capitalized company with resources to deliver innovation for patients and value for investors. • $160.5m in cash and cash equivalents*, runway into 2023 • Ex-US partnership with Astellas, significant milestones and royalties *Number reflects unaudited Cash, Cash Equivalents, and Marketable Securities as of 9/30/21, and does not include Restricted Cash © Frequency Therapeutics, Inc. | 37
Appendix
Broad Potential of Progenitor Cell Activation Approach 3 © Frequency Therapeutics, Inc. | 39 9
Origin of Frequency Therapeutics Tissue-Specific, Pre-programmed Stem Cells Decoding Enabling Frequency Intestinal Cochlear Therapeutics Regeneration Regeneration Small molecule Langer and Karp publish Same cues reactivate therapeutics show small molecules activate normally inactive clinical proof intestinal progenitors progenitors in the cochlea of concept Niche-independent high-purity cultures of Clonal Expansion of Lgr5-Positive Cells Lgr5+ intestinal stem cells and their progeny from Mammalian Cochlea and High- Purity Generation of Sensory Hair Cells © Frequency Therapeutics, Inc. | 40
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 © Frequency Therapeutics, Inc. | 41
Uniqueness of Our PCA approach Previous Approaches Frequency’s PCA Approach Pluripotent Multipotent Yamanaka 4 Factors Partial Reprogramming Bipotent Transdifferentiation Fully Differentiated Hair Progenitor Hair Progenitor Cell Cell Cell Cell © Frequency Therapeutics, Inc. | 42
Our Approach: Activation of Progenitors to Replace Hair Cell Loss Despite Hair Cell Loss, Progenitor Cells Remain Audiogram Human Cochlea Cross-section 47 Year Old Male with Occupational Noise Deafness © Frequency Therapeutics, Inc. | 43
Can we re-draw charts Profound Synergy Between Pathways to Regenerate Cells Culture Media Wnt Activation (glycogen synthase kinase-3 Cochlear Progenitor (GSK3) Inhibitor; NCE) Proliferation (Lgr5+ – GFP) HDAC Inhibition (sodium valproate) Wnt Activation + HDAC inhibition PROFOUND SYNERGY HDAC = Histone deacetylase NCE = new chemical entity In vitro mouse model testing © Frequency Therapeutics, Inc. | 44
Footnote? FX-322 Agents Induce Protein Expression Consistent with Fully Functional Sensory Hair Cells Hair cells Hair cells Hair cells Hair bundles Transducing cell dye Synapses Sensing Sound Creating Signal Transmitting Signal Generating intricate Producing functional Synaptic proteins to communicate hair bundles ion channels with nerve are present McLean et al., 2017, Cell Reports 18, 1917–1929 February 21 © Frequency Therapeutics, Inc. | 45 http://dx.doi.org/10.1016/j.celrep.2017.01.066
Images Showing Cellular Regeneration In Vivo Hearing Loss Model VEHICLE CONTROL TREATED WITH FX-322 HAIR CELLS NUCLEI HAIR CELLS NUCLEI Representative of n=7; Numbers correspond to frequencies; 30 days after treating © Frequency Therapeutics, Inc. | 46
Strong FX-322 Pre-Clinical Validation Test Outcome In vitro Adult human Created new hair cells inner ear tissue v In vivo Restored hair cells and hearing Adult deafened mice across all frequencies Achieved active levels in the Therapeutic drug levels cochlea in multiple species © Frequency Therapeutics, Inc. | 47
Clinically Meaningful: 10% Means Needing Audiologic Help Words 100% 50 May get by with 90% 45 consumer technology and lifestyle changes. Difficult communication, 80% 40 +10% especially in noise. Challenges to home 70% 35 and work relationships. 60% 30 Can no longer communicate Needs help. -10% in person or on phone 50% 25 without professional audiologic help. 40% 20 30% 15 20% 10 10% 5 0% 0 © Frequency Therapeutics, Inc. | 48
Clinically Meaningful: 10% Means Functional Deafness or Need for Implant Words 100% 50 90% 45 80% 40 70% 35 Can communicate using hearing aids and 60% 30 accommodations at home Unable to communicate, and work. 50% 25 +10% even with hearing aids. At risk for depression 40% 20 due to impact on home 30% 15 -10% and work. Cochlear implants 20% 10 or functionally deaf. 10% 5 0% 0 © Frequency Therapeutics, Inc. | 49
Externally-Led (HLAA) Patient Focused Drug Development Program on Sensorineural Hearing Loss Top two needs for new drug or device Improved hearing 80% Hearing restoration 72% Top two hearing loss concerns Trouble hearing with 92% background noise Sounds are muffled 66% Credit: Hearing Loss Association of America (HLAA) © Frequency Therapeutics, Inc. | 50
Astellas Collaboration: Ex-US Development and Commercialization of FX-322 • Development and commercialization collaboration for FX-322, including lifecycle improvements • Astellas has ex-US rights; Frequency retains US rights to FX-322 Strategic commitment to invest in • Payments of up to $625mm which included $80mm upfront ENT as a therapeutic area - Development milestone payments to Frequency of ————— $65.0 million and $25.0 million upon the first dosing of a Research focus in regenerative patient in a Phase 2b clinical trial for SNHL in Europe and medicine Asia, respectively ————— - $100.0 million and $40.0 million upon the first dosing of a Global footprint in major markets patient in a Phase 3 clinical trial for SNHL in Europe and and distributorship model in Asia, respectively Africa/ME and LATAM • Development & commercialization: Astellas responsible for execution and costs of ex-US clinical development and commercialization © Frequency Therapeutics, Inc. | 51
Proven Leadership Team David Lucchino Chris Loose, Ph.D. Peter Pfreundschuh President, CEO Chief Scientific Officer Chief Financial Officer & Co-Founder & Co-Founder CFO of numerous public life sciences companies including UroGen and Former CEO of Entrega Bio Co-founder/CTO of Semprus Sucampo, as well as business (PureTech). Co-founder / CEO of BioSciences through FDA / CE development and finance leadership Semprus BioSciences (acquired), clearance and acquisition. Princeton, positions at Astra Zeneca and J&J. Polaris Partners. MIT Sloan Fellow. MIT, Hertz Fellow and Yale Faculty. Dana Hilt, M.D. Carl Lebel, Ph.D. Sue Stewart, J.D., LLM Chief Medical Officer Chief Development Officer Chief Regulatory Officer Neurologist and neuroscientist Chief Scientific Officer of CRO at numerous biopharma with two decades in biopharma Otonomy (2009 to 2016). companies including Kaleido and CNS drug development. Executive Director, Amgen. Biosciences, Candel Therapeutics, Amgen, Lysosomal, Forum Scientific fellow of the American and regulatory leadership roles at Pharma. Academy of Otolaryngology. Tokai Pharma, Transmolar and Genzyme Corp. Wendy Arnold Quentin McCubbin, Ph.D. Chief People Officer Chief Manufacturing Officer HR leader with extensive life science Led pharmaceutical sciences and experience including senior leadership process chemistry at Takeda / roles at Kaleido Biosciences, Millennium and headed technical Moderna, Celgene Avilomics operations Cerevel Therapeutics. Research, and Inotek Pharmaceuticals © Frequency Therapeutics, Inc. | 52
Scientific Advisory Board Clinical Advisory Board Jeff Karp, Robert Langer, Robin Franklin, Sheng Ding, Dan Lee, Rene Gifford, Steve Rauch, Ruth Litovsky, Ph.D. SC.D. Ph.D. Ph.D. M.D. Ph.D. M.D. Ph.D. Associate Professor at David H. Koch Institute Professor of Stem Senior Investigator, Director, Pediatric Associate Director of Director, Vestibular Professor, Brigham and Women’s Professor at the Cell Medicine, Gladstone Otology and Pediatric Audiology, Division, Medical Communications Sciences Hospital, Harvard Massachusetts Institute Wellcome Trust-MRC Institute of Neurotology, Mass Director of Cochlear Director, Mass. Eye and Disorders and Surgery Medical School of Technology Cambridge Cardiovascular Eye and Ear Implant Program, and Ear Balance and Division of Otolaryngology, Stem Cell Institute Disease Vanderbilt University Vestibular Center University of Wisconsin Sean J. Siddhartha Amy Wagers, Chris Runge, Joni Doherty, Julie Arenberg, David Friedland, Morrison, Ph.D. Mukherjee, Ph.D. Ph.D. MD, Ph.D. MS, Ph.D. M.D., Ph.D. M.D., D.Phil. Director of the Forst Family Professor Chief of the Division Assistant Professor Associate Director Vice-Chair of the Children's Medical of Stem Cell and of Communication of Clinical of Clinical Audiology Department of Assistant Professor Center Research Regenerative Biology, Sciences, Medical Otolaryngology-Head for Research and Otolaryngology and of Medicine, Institute, Harvard University College of Wisconsin and Neck Surgery, Education, Mass Eye Communications Sciences, Columbia University UT Southwestern Keck School of and Ear Medical College of Medical Center Medicine of USC. Wisconsin © Frequency Therapeutics, Inc. | 53
Pioneering a New Category in Regenerative Medicine Frequency Therapeutics Corporate Presentation
Exhibit 99.2 Pioneering a New Category in Regenerative Medicine Frequency Therapeutics Virtual R&D Event November 9, 2021
Strategic Overview David L. Lucchino Chief Executive Officer © Frequency Therapeutics, Inc. | 2
Forward-Looking Statements and Other Disclaimers This presentation contains forward-looking statements within the meaning of the candidates; the results of earlier clinical trials not being indicative of the results Private Securities Litigation Reform Act of 1995. All statements contained in this from later clinical trials; differences between preliminary or interim data and final presentation that do not relate to matters of historical fact should be considered data; adverse events or undesirable side effects; disruptions at the FDA and other forward-looking statements, including without limitation statements regarding the regulatory agencies; failure to identify additional product candidates; new or timing and design of the new Phase 2b trial of FX-322, including the type of changed legislation; failure to maintain Fast Track designation for FX-322 and SNHL that the enrolled patients will have and the ability of design features to such designation failing to result in faster development or regulatory review or reduce bias, the interpretation and implications of the results and learnings of approval; costly and damaging litigation, including related to product liability or other FX-322 clinical studies, the acceptance by the FDA of particular endpoints intellectual property or brought by stockholders; dependence on Astellas Pharma in the Company’s trials, the treatment potential of FX-322, FX-345, and the novel Inc. for the development and commercialization of FX-322 outside of the United approach for remyelination in multiple sclerosis, the timing and progress of the States; misconduct by employees or independent contractors; reliance on third FX-345 and remyelination programs, the ability of our technology platform to parties, including to conduct clinical trials and manufacture product candidates; provide patient benefit, the ability to continue to develop our Progenitor Cell compliance with laws and regulations, including healthcare and environmental, Activation (PCA) platform and identify additional product candidates, the potential health, and safety laws and regulations; failure to obtain, maintain and enforce application of the PCA platform to other diseases, and the sufficiency of the protection of patents and other intellectual property; security breaches or failure Company’s capital resources. to protect private personal information; attracting and retaining key personnel; and ability to manage growth. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve These and other important factors discussed under the caption “Risk factors” in known and unknown risks, uncertainties and other important factors that may the Company’s Form 10-Q filed with the Securities and Exchange Commission cause actual results, performance or achievements to be materially different from (SEC) on August 12, 2021 and its other reports filed with the SEC could cause any future results, performance or achievements expressed or implied by the actual results to differ materially from those indicated by the forward-looking forward-looking statements, including, but not limited to, the following: the impact statements made in this presentation. Any such forward-looking statements of COVID-19 on the Company’s ongoing and planned clinical trials, research and represent management’s estimates as of the date of this presentation. While the development and manufacturing activities, the Company’s business and financial Company may elect to update such forward-looking statements at some point in markets; the Company has incurred and will continue to incur significant losses the future, it disclaims any obligation to do so, even if subsequent events cause and is not and may never be profitable; the Company’s need for additional its views to change. These forward-looking statements should not be relied upon funding to complete development and commercialization of any product as representing the Company’s views as of any date subsequent to the date of candidate; the Company’s dependence on the development of FX-322; the this presentation. 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 © Frequency Therapeutics, Inc. | 3
Overview Pioneering a New Category of Regenerative Medicine Developing the First Therapeutic for Acquired Sensorineural Hearing Loss © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 4 4
Two New Regenerative Programs What if we were able to get drug deeper into the cochlea? What if we could extend our approach to other degenerative diseases? © Frequency Therapeutics, Inc. | 5
Agenda Pioneering a new category in regenerative medicine David L. Lucchino President and CEO Dr. Robert Langer, PhD Scientific co-founder of Frequency David H. Koch MIT Institute Professor Advancing the first hearing restoration drug candidate Carl LeBel, PhD Chief Development Officer — Pooled FX-322 data show clear improvement in speech perception Kevin Franck, PhD — Well-designed and powered FX-322 Phase 2b study SVP, Strategic Marketing and New Product Planning — Clear understanding of hearing loss types that may benefit — FDA alignment on primary endpoints Sumit Dhar, PhD KOL perspectives Hugh Knowles Professor of Hearing Science, — Why FX-322 data align with how the inner ear is expected Northwestern University to respond Steven D. Targum, MD — Strength of new FX-322 study design Scientific Director, Signant Health Expanding regenerative pipeline with two new programs Chris Loose, PhD Chief Scientific Officer — FX-345 in hearing restoration Sanjay Magavi, PhD — FREQ-162 for remyelination in MS VP, Myelination Research © Frequency Therapeutics, Inc. | 6
Execution and Pipeline Expansion Team and resources to advance these programs to the millions in need of new treatment options. © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 7 7
Pioneering a New Category in Regenerative Medicine Dr. Robert Langer Frequency Therapeutics Co-founder and MIT Institute Professor © Frequency Therapeutics, Inc. | 8
Key Learnings from FX-322 Hearing Restoration Program Carl LeBel, PhD Chief Development Officer © Frequency Therapeutics, Inc. | 9
A Series of Firsts in Hearing Restoration First PK/PD First clinical First speech First to show shown for a studies to show perception sustained hearing therapeutic hearing improvements improvements candidate improvements measured and continued improvements over time © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 10 10
FX-322 Agents Induce Protein Expression Consistent with Fully Functional Sensory Hair Cells Hair cells Hair cells Hair cells Hair bundles Transducing cell dye Synapses Sensing Sound Creating Signal Transmitting Signal Generating intricate Producing functional Synaptic proteins to communicate hair bundles ion channels with nerve are present McLean et al., 2017, Cell Reports 18, 1917–1929 February 21 © Frequency Therapeutics, Inc. | 11 http://dx.doi.org/10.1016/j.celrep.2017.01.066
Images Showing Cellular Regeneration In Vivo Hearing Loss Model VEHICLE CONTROL TREATED WITH FX-322 HAIR CELLS NUCLEI HAIR CELLS NUCLEI Representative of n=7; Numbers correspond to frequencies; 30 days after treating © Frequency Therapeutics, Inc. | 12
First to Prove FX-322 Delivery to the Human Cochlea FX-322 Clinical signal achieved with drug localized in the high frequency region © Frequency Therapeutics, Inc. | 13
Four FX-322 Completed Studies: 169 Subjects Favorable Safety Profile with No Treatment-Related SAEs 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 14
FX-322-201 Single-Dose Safety Study With First Hearing Improvement Signal 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 15
FX-322-202 Multiple Injection Study to Assess Safety of Increased FX-322 Exposure 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 16
FX-322 Clinical Strategy Evaluate Etiologies and Severities to Understand FX-322 Activity 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Moderately- Mild Moderate Severe Mild-Moderately Severe [66-85 y/o] Study (201-2) Severe 1 201 Noise ? ? ? (18-65 years) ? SSNHL and NIHL Study (202) Understand FX-322 [Mild-Moderately Severe [66-85 y/o] Activity on Different 2 202 Patient Populations Sudden ? ? ? (18-65 years) ? Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-related ? ? ? ? (65+ years) Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 17
FX-322-111 Second Single-Dose Safety Study with Hearing Improvement Signal 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 18
FX-322-112 Single-Dose Safety Study in Older Patients without NIHL or SSNHL 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 19
Pooling Data From Three Single-Dose FX-322 Trials Evaluate Characteristics of Responders 2018 2019 2020 2021 2022 STUDIES Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SSNHL and NIHL Study (201) Phase 1/2 Durability Mild-Moderately Severe [66-85 y/o] Study (201-2) 1 201 SSNHL and NIHL Study (202) [Mild-Moderately Severe [66-85 y/o] 2 202 Study of Administration Conditions (111) All Etiologies, Mild-Severe [18-65 y/o] 3 111 Age-Related Hearing Loss Study (112) Mild-Moderately Severe [66-85 y/o] 4 112 = Data Readout © Frequency Therapeutics, Inc. | 20
Pooled FX-322 Data Shows Patterns of Response Single-dose Studies (201, 111, 112) Using a Responder Definition 20 10 +10% (5 words) 0 -10% (5 words) -10 Treated Untreated Placebo n = 71 n = 84 n = 13 © Frequency Therapeutics, Inc. | 21 Change in Words
Pooled FX-322 Data Shows Patterns of Response Single-dose Studies (201, 111, 112) Exceeding 95% Confidence Interval % Exceeding Single-dose Studies 95% Confidence Interval (201, 111, 112) 25% 20% 14.1% 15% 10% 5% 2.5% 2.1% 0% Untreated Literature* Treated and Placebo n = 71 n = 97 *95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 22
Comparing Pooled Data to Multiple-Injection Study FX-322-202 Placebo-Treated and Untreated Ears are Outside 95% Confidence Interval % Exceeding % Exceeding Single-dose Studies Multiple Injection Study 95% Confidence 95% Confidence Interval Interval (201, 111, 112) (202) 25% 25% 21.2% 20% 20% 15.4% 14.1% 15% 15% 10% 10% 5% 5% 2.5% 2.5% 2.1% 0% 0% Untreated Untreated Literature* Treated Literature Treated and Placebo and Placebo n = 71 n = 66 n = 104 n = 97 *95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 23
Clear Speech Perception Improvements from FX-322 in High Frequency Range of Cochlea 20 10 +10% (5 words) 0 -10% (5 words) -10 Treated Untreated Placebo n = 71 n = 84 n = 13 © Frequency Therapeutics, Inc. | 24 Change in Words
Externally-Led (HLAA) Patient Focused Drug Development Program on Sensorineural Hearing Loss Top two needs for new drug or device Improved hearing 80% Hearing restoration 72% Top two hearing loss concerns Trouble hearing with 92% background noise Sounds are muffled 66% Credit: Hearing Loss Association of America (HLAA) © Frequency Therapeutics, Inc. | 25
FDA Type C Meeting Held to Gain Alignment ALIGNMENT Primary Endpoint Gained alignment with FDA on speech perception as the primary endpoint 208 Study Design FDA reviewed and commented on 208 study, comments were incorporated into study protocol Patient Reported Outcomes (PRO) FDA feedback provided on novel PRO development called RADIAL; special meeting granted for further discussion © Frequency Therapeutics, Inc. | 26
Summary Developed a novel, locally delivered, drug-drug combination that regenerates cochlear function preclinically First hearing restoration signal observed in humans Second independent trial shows hearing restoration signal Favorable safety profile Alignment with FDA on primary endpoint for 208 and future FX-322 studies © Frequency Therapeutics, Inc. | 27
FX-322 Clinical Data and Real-World Impact of Speech Perception Improvements Kevin Franck, PhD SVP, Strategic Marketing and New Product Planning © Frequency Therapeutics, Inc. | 28
Clinically Meaningful: Words 100% 50 90% 45 80% 40 70% 35 60% 30 50% 25 40% 20 30% 15 20% 10 10% 5 0% 0 © Frequency Therapeutics, Inc. | 29
Clinically Meaningful: 10% Means Needing Audiologic Help Words 100% 50 May get by with 90% 45 consumer technology and lifestyle changes. Difficult communication, 80% 40 +10% especially in noise. Challenges to home 70% 35 and work relationships. 60% 30 Can no longer communicate Needs help. -10% in person or on phone 50% 25 without professional audiologic help. 40% 20 30% 15 20% 10 10% 5 0% 0 © Frequency Therapeutics, Inc. | 30
Clinically Meaningful: 10% Means Functional Deafness or Need for Implant Words 100% 50 90% 45 80% 40 70% 35 Can communicate using hearing aids and 60% 30 accommodations at home Unable to communicate, and work. 50% 25 +10% even with hearing aids. At risk for depression 40% 20 due to impact on home 30% 15 -10% and work. Cochlear implants 20% 10 or functionally deaf. 10% 5 0% 0 © Frequency Therapeutics, Inc. | 31
10% Absolute Change is Clinically Meaningful 50 Speech 45 Perception 40 35 10% absolute change is 30 considered clinically meaningful 25 20 15 10 5 0 0 10 20 30 40 50 Baseline WR (words) 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 32 90-Day WR (words)
10% Absolute Change is Clinically Meaningful 50 Speech 45 Perception 40 35 10% absolute change is 30 considered clinically +/-10% meaningful 25 (5 words) 20 15 10 5 0 0 10 20 30 40 50 Baseline WR (words) 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 33 90-Day WR (words)
10% Absolute Change is Clinically Meaningful 50 Speech 45 Perception 40 35 10% absolute change is 30 considered clinically +/-10% meaningful 25 (5 words) 20 15 10 5 0 0 10 20 30 40 50 Baseline WR (words) 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 34 90-Day WR (words)
Statistical Significance Sets a Higher Bar 50 Speech 45 Perception 40 35 2.5% 10% absolute change is 30 considered clinically meaningful 25 95% 20 A 95% confidence interval can show patients with 15 statistical improvement 10 2.5% from their starting point 5 0 0 10 20 30 40 50 Baseline WR (words) 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007) © Frequency Therapeutics, Inc. | 35 90-Day WR (words)
Study 201 Responders Shown within 95% Confidence Interval 50 45 40 35 30 25 20 15 Normal 10 Mild Moderate 5 Moderate-severe 0 FX-322 0 10 20 30 40 50 Baseline WR (words) 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007). Test used Maryland CNC word lists. © Frequency Therapeutics, Inc. | 36 McLean et al O&N 2021 90-Day WR (words)
Study 201 Responders Shown within 95% Confidence Interval 20 Exceeds 95% Confidence Interval 10 +10% (5 words) 0 -10% (5 words) -10 No Norma rmall Treated Mi Mild ld n = 15 Mo Moderate derate Mo Moderate derate- -severe severe FX FX- -322 322 95% confidence intervals established by Thornton & Raffin (1978) and modified by Carney & Schlauch (2007). Test used Maryland CNC word lists. © Frequency Therapeutics, Inc. | 37 McLean et al O&N 2021 Change in Words
Study 201 Responders Shown within 95% Confidence Interval Study 201 20 20 Exceeds 95% Confidence Exceeds Interval 95% Confidence 10 Interval 10 +10% (5 words) 0 -10% (5 words) +10% (5 words) -10 0 -10% Treated Untreated Placebo (5 words) n = 15 n = 23 n = 8 -10 Treated Untreated Placebo n = 15 n = 23 n = 8 © Frequency Therapeutics, Inc. | 38 Change in Words Change in Words
Study 201 Responders Shown within 95% Confidence Interval Single-dose Studies Study 201 Studies 111 & 112 (201, 111 & 112) 20 20 Exceeds 95% Confidence Interval Exceeds Exceeds 95% Confidence 95% Confidence Interval Interval 10 10 +10% +10% (5 words) (5 words) 0 0 -10% -10% (5 words) (5 words) -10 -10 Trea Treate ted d Untrea Untreate ted d Plac Placebo ebo Treated Untreated Placebo n = n = 71 15 n = n = 23 84 n = n = 13 8 n = 56 n = 61 n = 5 © Frequency Therapeutics, Inc. | 39 Change in Words Change in Words
Pooled Single-Dose Studies (201, 111, 112) Highlights 202 Anomalies Single-dose Studies Multiple Injection Study - 202 (201, 111 & 112) Exceeds 20 20 Exceeds 95% Confidence Interval 95% Confidence Interval 10 10 +10% +10% (5 words) (5 words) 0 0 -10% -10% (5 words) (5 words) -10 -10 Treated Untreated Placebo Treated Untreated Placebo n = 71 n = 84 n = 13 n = 66 n = 85 n = 19 © Frequency Therapeutics, Inc. | 40 Change in Words Change in Words
U.S. Patients Pooled Single-Dose Studies (201, 111, 112) Data Suggest Patterns Between Etiology/Severity and Response Moderately- Moderate Mild Severe Severe 71 Treated with single-dose of FX-322 Noise The size of each circle represents the 0% 0% 33% (18-65 years) number of people tested per group The color of the circle represents the percentage of responders Sudden 208 Trial: Target Population 0% 27% 40% (18-65 years) 7-10 Million U.S. patients 208 Trial FX-322: Extended Population Age-related 0% 7% 0% (65+ years) 15+ Million U.S. patients © Frequency Therapeutics, Inc. | 41
Cochlear Pathology and the Impact of High Frequencies on Speech Perception Sumit Dhar, PhD Hugh Knowles Professor of Hearing Science and Associate Provost for Faculty at Northwestern University 42
Disclosures Honorarium from Frequency TX to review all clinical data from past studies and assess planned clinical trial. Participated on external panel of KOL’s on auditory science. Primary employment at Northwestern University. Parts of my salary are paid by the NIH and PCORI. I receive royalty and consulting fees from Plural Publishing. I receive licensing fees from Etymotic Research. I serve on the Board of Directors of the American Auditory Society. I serve on the Board of Directors of LeAP (Language Empowers All People). 43
Why Treat the High-Frequency Region of the Cochlea? 44
Common Forms of Hearing Loss is Dominant in the Highest Frequencies 20.5 dB @ 18kHz in 20-24 yo 56.5 dB @ 15kHz in 44-49 yo 65 dB @ 15kHz in 60-64 yo Current limit of clinical tests N=976; Lee et al., 2012; Hunter et al., 2020 45 45
How Does High Frequency Cochlear Function Influence Speech Perception? 46
Speech Perception Influenced by Cochlear Function in High-Frequency Regions N = 921 DPOAE levels between 12.5 – 16 kHz drive speech perception in noise scores 2 (p = 0.047, R = 0.017) more than audibility. Speech perception is the complaint that leads patients to seek treatment. Speech perception is the the long-standing gold standard in determining functional outcomes of any treatment for hearing loss. Current limit of clinical tests Stiepan et al., 2020 47 47 Threshold (dB FPL)/OAE Level (dB SPL)
Should We Expect Heterogeneity in Treatment Outcomes? 48
Response Variability Predicted by Cochlear Heterogeneity Heterogeneity of response magnitude and response timeline is the reality of all hearing loss treatments • Decades of data from cochlear implants and hearing aids definitively demonstrate heterogeneity in response • Likely driven by varying damage and rates of plasticity in the auditory system. 49
Impact of Heterogeniety on Clinical Study Planning Etiology and duration of pathology is heterogenous across individuals. Frequency TX’s approach of exploring various etiologies and pathologies in early studies was the necessary approach to identify target responder populations. The design and controls put in place for the next study represent the best path forward. 50
Takeaways Treating the HF region of the cochlea is critical. Function of the HF region can influence speech perception. Heterogeneity of response is a reality of all treatments for hearing loss. 51
208 Section for R&D Event Clinical Development Path for Hearing Restoration Program Carl LeBel, PhD Chief Development Officer © Frequency Therapeutics, Inc. | 52
New Clinical Study FX-322-208 Designed to Advance Drug Candidate to Pivotal Trials Built upon insights Sufficient sample Reduce from trials with hearing size to demonstrate potential restoration signal efficacy for bias Etiology, severity, Multiple baseline Approach based baseline speech measures on pooled data perception Primary endpoint of Multiple speech speech perception perception tests © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 53 53
U.S. Patients Pooled Single-Dose Studies (201, 111, 112) Data Suggest Patterns Between Etiology/Severity and Response Moderately- Moderate Mild Severe Severe 71 Treated with single-dose of FX-322 Noise The size of each circle represents the 0% 0% 33% (18-65 years) number of people tested per group The color of the circle represents the percentage of responders Sudden 208 Trial: Target Population 0% 27% 40% (18-65 years) 7-10 Million U.S. patients 208 Trial FX-322: Extended Population Age-related 0% 7% 0% (65+ years) 15+ Million U.S. patients © Frequency Therapeutics, Inc. | 54
Pooled Single-Dose Studies (201, 111, 112) Data Show Clear Subset of Patients Responding to FX-322 Observed consistent response in two major etiologies – Noise-induced Hearing Loss – Sudden Sensorineural Hearing Loss Observed consistent response in specific range of SNHL severity – Moderate to lower end of severe Study powered at 80% Effect size 20% over placebo Significance level is 0.05 Sample size is 124 subjects (assumes 10% attrition) © Frequency Therapeutics, Inc. | 55
Multiple Design Features Have Been Added to Mitigate Bias And Demonstrate Greater Separation Between Signal and Placebo Lead-in phase with multiple Start of 1-Month Lead-in baseline measures Day -30 Lead-in Sites and patients masked to Day -15 qualifying test results Baseline Day 1 All sessions recorded and monitored Ability to disqualify subjects based on symptom stability © Frequency Therapeutics, Inc. | 56
New FX-322 Placebo-Controlled Phase 2b Study Commenced First patient dosed in FX-322-208 Study in October 2021 Subjects Screened to Enter Lead-in Pure tone average 35-85dB 124 Subjects Start of 1-Month Lead-in Subjects will have diagnosed Day -30 noise induced or sudden Lead-in period with sensorineural hearing loss 3 visits determines Lead-in trial candidacy based Day -15 on consistency of Rigorous bias management audiologic testing controls in place Baseline Day 1 Ages 18 – 65 Randomize Primary endpoint: Speech perception FX-322 Placebo Placebo (in agreement with FDA) 1X 1X 1X N = 62 N = 62 N = 62 Follow-up Visits: Days 30, 60, 90 © Frequency Therapeutics, Inc. | 57
Confidence in Path Forward for FX-322 FX-322 shows hearing signal in speech perception; aligns with FDA endpoint FREQ has unparalleled dataset providing extensive insight into responder profiles Learnings from trials have provided critical insight into mitigating bias through multiple trial design components Phase 2b study optimized to confirm that FX-322 can restore hearing in targeted study population © Frequency Therapeutics, Inc. | 58
Addressing Placebo Response in Clinical Trials: Best Practices Steven D. Targum MD Clinical Consultant Scientific Director, Signant Health 59
Steven D. Targum MD Disclosures Scientific Director, Signant Health Clinical consultant/Scientific Advisory Board activities (past 3 years): • Acadia Pharmaceuticals Inc., Alkermes Inc., AZ Therapies, BioXcel Therapeutics Inc., Denovo Biopharma, EMA Wellness, Epiodyne, Frequency Therapeutics, Functional Neuromodulation LLC, Johnson and Johnson PRD, Karuna Pharmaceuticals, Methylation Sciences Inc., Merck Inc., Navitor Pharmaceuticals, Neurim Pharmaceuticals, Neurocrine, Pax Neuroscience, Resilience Therapeutics, Sunovion Inc., Takeda Pharmaceuticals, XR Health, Yale University school of medicine. 60
The Inherent Challenge of Clinical Trials: Reliability • Challenges to study reliability include: • Misplaced enrollment incentives • Expectation bias • Pre-randomization symptom fluctuation • Lack of ratings precision and consistency 61
The Frequency Experience in FX-322-202 Can Inform the Next Study • Post-hoc review of the FX-322-202 trial found: • Inflation of hearing deficits at screen • Subjects under-reported the number of words they could understand from the word recognition test in order to achieve study eligibility. • Open communication about eligibility criteria • Some clinical trial site staff shared with subjects the reasons that they were excluded from the trial. • Frequency vocally communicated the requisite hearing deficits necessary to enter the trial and the intended primary endpoint. • Social media • Some subjects shared their information on social media platforms that are routinely used by subjects with hearing loss. 62
Experience Informs the Next Study: FX-322-208 Best Practices to Optimize Trial Outcome and Mitigate the Placebo Response • A protocol that blinds the key eligibility metric criteria from both staff and subjects (masking) and employs multiple hearing assessment measures • Blinding mitigates the risk of intentional inflation of hearing loss deficits • Multiple measures distract subjects from the “true” eligibility criteria • Blinding mitigates the risk of site staff sharing specifics about the study • Employ a protocol addendum for the masked criteria • FX-322-208 Unmasked Addendum is not seen by the trial site • Add an interim visit to assess symptom stability • Add rater training and site-independent monitoring as quality assurance layers to assure ratings precision 63
Regenerative Medicine: The Path Forward David L. Lucchino Chief Executive Officer © Frequency Therapeutics, Inc. | 64
Delivering FX-322 as the First Therapeutic to Restore Hearing © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 65 65
Regenerative Medicine: Expanding and Extending Our Pipeline Two New Regenerative Programs © Frequency Therapeutics, Inc. | 66
Two New Regenerative Programs Restoring hearing across more and different types of patients New remyelination program aimed at repairing the underlying cause of MS © Frequency Therapeutics, Inc. | 67
New Regenerative Programs from Continued Progenitor Cell Activation (PCA) Research Chris Loose, PhD Chief Scientific Officer © Frequency Therapeutics, Inc. | 68
Power of the PCA Platform Ease of No Change to Harnessing Manufacturing Genome Innate Biology Use of small Activating native Progenitors molecules: no need programs, already located to remove or grow reducing safety within the cells ex vivo concerns target tissue © Frequency Therapeutics, Inc. | 69 © Frequency Therapeutics, Inc. | 69
Two New Regenerative Programs What if we were able to get drug deeper into the cochlea? How do we extend this approach to other degenerative diseases? © Frequency Therapeutics, Inc. | 70
FX-322 High Frequency Exposure in the Cochlea Demonstrated hearing signal when FX-322 reaches the highest frequency region of the cochlea © Frequency Therapeutics, Inc. | 71
FX-345 Working to Achieve Broad Exposure Through the Cochlea • Second clinical program focused on regrowth of sensory cells • Enables coverage of large portion of cochlea • Potential to address additional SNHL patient types • Formulation enabling evaluation of a range of dose levels • Developing in addition to FX-322, and clinical data will drive commercial positioning © Frequency Therapeutics, Inc. | 72
Profound Synergy Between Pathways to Regenerate Cells Culture Media Wnt Activation (glycogen synthase kinase-3 Cochlear Progenitor (GSK3) Inhibitor; NCE) Proliferation (Lgr5+ – GFP) HDAC Inhibition (sodium valproate) Wnt Activation + HDAC inhibition PROFOUND SYNERGY HDAC = Histone deacetylase NCE = new chemical entity In vitro mouse model testing © Frequency Therapeutics, Inc. | 73
Pioneering Advanced Tools Unique in Hearing Restoration Activating and Proliferating Lgr5+ Progenitor Cells Lgr5+ Clusters of Lgr5+ Progenitor Cells proliferating as organoids More potent compound found © Frequency Therapeutics, Inc. | 74
Pioneering Advanced Tools Unique in Hearing Restoration Cochlear Drug Sampling and Modeling Perilymph Sampling FX-322 was dosed in animals and humans, and perilymph was sampled C ochlear Perforate A queduct 1 2 3 4 Scala Tym pani A pex B ase 1 2 3 4 CSF 2 3 4 CSF Improved Speech Intelligibility in Subjects with Stable Laryngoscope. 2007 Jul; 117(7): 1191–1198. Sensorineural Hearing Loss Following Intratympanic Dosing doi: 10.1097/MLG.0b013e318058a06b (S.K. Plontke, et. al.) of FX-322 in a Phase 1b Study (W.J. McLean, et. al. 2021) © Frequency Therapeutics, Inc. | 75
FX-345 – A New Development Candidate Creating Effective Drug Levels Through Large Portion of Cochlea © Frequency Therapeutics, Inc. | 76
FX-345 Path to Clinic IND planned for H1:2022 for a Phase 1b study in patients with SNHL Enables us to clinically evaluate increased cochlear coverage across range of doses in multiple patient populations Candidate IND-enabling IND FIH clinical selection GLP tox Submission study On-going Q2 2022 H2 2022 © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 77 77
Two New Regenerative Programs What if we were able to get drug deeper into the cochlea? How do we extend this approach to other degenerative diseases? © Frequency Therapeutics, Inc. | 78
Progenitor Cell Activation: Remyelination Identified Novel Target Developed Multiple NCEs Established in vivo efficacy © Frequency Therapeutics, Inc. | 79
Remyelination for Multiple Sclerosis: Discovery of a Novel Target with Exceptional in vivo Activity Sanjay Magavi, PhD VP, Myelination Research © Frequency Therapeutics, Inc. | 80
Frequency Discovered a Novel Remyelination Target Progenitor Cell Activation Bioinformatics Target 1 Target 2 Target 3 Target 4 Target 5 © Frequency Therapeutics, Inc. | 81
Frequency Discovered a Novel Remyelination Target Target 14 Blocking Antibody Treated OPCs Target 14 Blocking Antibody Treatment Control Target 14 Antibody Myelin Basic Protein Myelin Basic Protein Control Target 14 Target 14 blocking antibodies increase myelin basic protein expressing cells in vitro. Discovery of target allowed rapid screening for novel small molecule drugs. © Frequency Therapeutics, Inc. | 82 % Myelin Basic Protein + Cells
Small Molecule Target 14 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 Frequency developed novel chemical nM nM nM nM nM entities that are highly potent inducers of oligodendrocyte differentiation FREQ-162 © Frequency Therapeutics, Inc. | 83 % 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 Vehicle T3 / Thyromimeticα-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 induced formation α-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. | 84
Frequency NCEs Outperform Competitors: High Magnification FREQ-162 Vehicle Cortex Cortex Corpus Corpus Callosum Callosum Striatum Striatum © Frequency Therapeutics, Inc. | 85
FREQ-162 Drives More Oligodendrocyte Differentiation than Competitor Mechanisms Newly Generated Oligodendrocytes Adult mice received • Three Daily doses of anti-Lingo antibody, Clemastine, or Thyroid Hormone (T3) • A single dose of FREQ-162 Newly Generated Oligodendrocytes were quantitated via automated AI image analysis A single dose of a Frequency Compound induces more oligodendrocyte differentiation than multiple doses of comparators Dose # of Compound Fold change P= (mg/kg) doses α-Lingo antibody 5 3 1.1 x 0.99 Clemastine 75 3 1.5 x 0.60 Thyroid hormone (T3) 10 3 5.7 x <0.0001 FREQ-162 5 1 23.2 x <0.0001 Vehicle Lingo Ab Clemastine T3 FREQ-162 (One Way ANOVA, n ≥ 7) (5 mg/kg) (75 mg/kg) (10 mg/kg) (5 mg/kg) © Frequency Therapeutics, Inc. | 86 2 Newly Generated Oligodendrocytes / mm
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. | 87
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) Vehicle T3 / Thyromimeticα-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 induced formation α-Lingo antibody: Clemastine: Thyroid Hormone: of new myelin in white and Lingo inhibitor Anti-Muscarinic Class Thyromimetic Class gray matter © Frequency Therapeutics, Inc. | 88
Frequency NCEs Outperform Competitors: High Magnification FREQ-162 Vehicle Cortex Cortex Corpus Callosum Corpus Callosum Striatum Striatum 5 mg/kg x 1 dose Myelin Basic Protein © Frequency Therapeutics, Inc. | 89
FREQ-162 Robustly Induces Remyelination All 8 out of 8 mice treated with FREQ-162 showed robust increases in myelination in both white and gray matter tracts Vehicle #7 #1 #2 #3 #4 #5 #6 #8 FREQ-162 #7 #1 #2 #3 #4 #5 #6 #8 Myelin Basic Protein © Frequency Therapeutics, Inc. | 90
Freq-162 Induces Robust 6000 Increases in Myelination Myelin Basic Protein 5000 • Forebrain myelin basic protein levels 4000 quantitated • A single dose of a Frequency compound induces robust remyelination 3000 2000 Dose Fold Compound # of doses P= (mg/kg) change α-Lingo antibody 5 3 0.9 x 0.99 1000 Clemastine 75 10 1.7 x 0.70 Thyroid Hormone (T3) 10 10 1.4 x 0.95 FREQ-162 5 1 7.7 x <0.0001 0 Healthy Vehicle T3 Lingo Ab Clemastine FREQ-162 (10 mg/kg) (5 mg/kg) (75 mg/kg) (5 mg/kg) Naive © Frequency Therapeutics, Inc. | 91 MBP (Intensity Weighted Pixel Count)
Remyelination: Path Forward Discovered novel target Generated multiple compounds Induced high levels of oligodendrocyte differentiation and remyelination in vivo Initiating IND enabling studies © Frequency Therapeutics, Inc. | 92
Our Path Forward David L. Lucchino Chief Executive Officer © © Fre Frequenc quency y Th Thera erapeuti peutics, cs, Inc. Inc. | | 93 93
Our Path Forward We believe FX-322 restores hearing. We know characteristics of FX-322 responders. Learnings from previous trials informed new trial design with strong controls and FDA approved clinical endpoints. We have a compelling new hearing program that will allow us to explore the impact of going deeper into the cochlea. We also have an exciting remyelination program in multiple sclerosis with a novel target and a strong response in vivo. We are a well capitalized company with resources to deliver innovation for patients and value for investors. © Frequency Therapeutics, Inc. | 94
Pioneering a New Category in Regenerative Medicine Frequency Therapeutics Virtual R&D Event November 9, 2021