UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 22, 2021
FREQUENCY THERAPEUTICS, INC.
(Exact name of Registrant as Specified in Its Charter)
| Delaware | 001-39062 | 47-2324450 | ||
| (State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
19 Presidential Way, 2nd Floor
Woburn, MA 01801
(Address of principal executive offices) (Zip Code)
(866) 389-1970
(Registrant’s telephone number, include area code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2 below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading |
Name of each exchange | ||
| Common stock, par value $0.001 per share | FREQ | The Nasdaq Global Select Market |
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).
Emerging growth company ☒
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 7.01. | Regulation FD Disclosure. |
On February 22, 2021, Frequency Therapeutics, Inc. (the “Company”) issued a press release announcing the publication of its FX-322 Phase 1/2 study results in Otology & Neurotology, a leading peer-reviewed Otolaryngology journal focused on disorders of the ear. The Company also provided a summary of its development program for FX-322. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K (the “Current Report”).
Also on February 22, 2021, the Company posted an updated corporate slide presentation in the “Investors & Media” portion of its website at www.frequencytx.com. A copy of the slide presentation is attached as Exhibit 99.2 to this Current Report.
The information in Item 7.01 of this Current Report, including Exhibits 99.1 and 99.2 attached hereto, 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 (the “Securities Act”), or the Exchange Act, except as expressly set forth 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 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following exhibits relate to Item 7.01, and shall be deemed to be furnished, and not filed:
| Exhibit No. |
Description | |
| 99.1 | Publication Press Release issued on February 22, 2021 | |
| 99.2 | Frequency Therapeutics, Inc. Corporate Slide Presentation as of February 22, 2021 | |
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: February 22, 2021 | By: | /s/ Michael D. Bookman | ||
| Name: Michael D. Bookman | ||||
| Title: General Counsel and Secretary | ||||
Exhibit 99.1
Frequency Therapeutics Announces Publication of Phase 1/2 Data Showing Hearing Improvements in Acquired Sensorineural Hearing Loss Patients Receiving FX-322
Results Published in Leading Peer-Reviewed Otolaryngology Journal, Otology & Neurotology
Statistically Significant Improvements Observed in Word Recognition Tests in Quiet and in Noise; Suggests Potential to Improve Speech Intelligibility, a Major Unmet Need for Individuals with Hearing Loss
Company Expects Interim FX-322 Phase 2a Study Data Later this Quarter
WOBURN, Mass., February 22, 2021 – Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage biotechnology company focused on harnessing the body’s innate biology to repair or reverse damage caused by a broad range of degenerative diseases, today announced the publication of its FX-322 Phase 1/2 study results in Otology & Neurotology, a leading peer-reviewed journal focused on disorders of the ear. The data show hearing improvements in adults with acquired sensorineural hearing loss (SNHL) and the first-known linkage of pharmacokinetics and pharmacodynamics for a potential hearing restoration therapy.
Findings from the Phase 1/2 study of FX-322, the company’s lead product candidate to treat SNHL, showed statistically significant increases in word recognition (WR) and words-in-noise (WIN) scores. Individuals with stable SNHL that received a single dose of FX-322 showed improvements in the number of words recognized in quiet from baseline to day 90 in the WR test (p=0.029) and the level of background noise in which words could be identified in the WIN test (p=0.012). There were no meaningful changes in the WR and WIN scores of the placebo group. FX-322 was also shown to be well tolerated. The publication includes data demonstrating consistent cochlear drug delivery in both preclinical and human studies. FX-322 is currently being evaluated in a larger Phase 2a study, with results anticipated later this quarter.
The study data will be presented today at the leading international hearing research conference, the Association for Research in Otolaryngology 44th Annual MidWinter Meeting.
“Healthy hearing is not just about the volume of sound, but about the broader ability to communicate. The most frequent complaint from patients with hearing loss is their inability to understand speech, which is due to a lack of clarity and loss of intelligibility where patients can’t recognize words and follow conversations, particularly in background noise,” said Christina Runge, Ph.D., a professor in the Department of Otolaryngology and Communication Sciences at the Medical College of Wisconsin, Director of the Koss Cochlear Implant Program, a
member of the Company’s clinical advisory board and an author on the publication. “These Phase 1/2 data are the first to show a potential therapeutic solution to address intelligibility, a key unmet need for those with SNHL.”
SNHL accounts for more than 90 percent of all hearing loss and results from damage to auditory sensory hair cells due to chronic noise exposure, aging, certain viral infections or from toxic medications. SNHL impacts more than 40 million people in the U.S. and hundreds of millions of people globally.
“Having a treatment that regenerates sensory hair cells would have a profound impact on the field, providing physicians with a meaningful intervention for restoring hearing loss,” said Ravi N. Samy, M.D., FACS, Professor of Otolaryngology & Neurosurgery and Chief of the Division of Otology/Neurotology at the University of Cincinnati / Cincinnati Children’s. “These exciting early clinical data begin to show the potential of a localized approach to repairing the cochlea, the ability to deliver a treatment to an area of the body that historically has been impossible to access and restore, and above all, clinically meaningful hearing improvements in patients.”
Hearing loss typically begins in higher frequencies and often impacts the ability to hear and distinguish between certain consonants, making it difficult to understand words, especially in noise. Hearing aids amplify sound but do not improve hearing clarity in higher frequencies or repair the underlying damage to the inner ear. FX-322, an injectable treatment candidate made up of two small molecules, is designed to activate progenitor cells (pre-programmed stem cells) to regenerate auditory hair cells in the cochlea and restore hearing function.
“These Phase 1/2 study data build upon the favorable word recognition performances that we previously reported, while bolstering the trends we saw in words-in-noise scores,” said Will McLean, Ph.D., Frequency’s Vice President of Biology and Regenerative Medicine, a Company co-founder and the lead author on the paper. “Increases in speech intelligibility and improvements when listening in noisy environments can have a significant impact on quality of life, and we are excited about the potential of our approach for patients and to advance the field of hearing restoration.”
FX-322 Development Program
FX-322 is Frequency’s lead product candidate for the treatment of acquired SNHL. The Phase 1/2 study was a randomized, double-blind, placebo-controlled, single-dose, multi-center study to assess the safety of FX-322 in 23 patients with stable SNHL. Patients received an intratympanic injection of FX-322 or placebo in one ear during an office-based procedure. In the study, 15 patients received a single dose of FX-322 in one ear while eight patients received placebo.
Of the six patients treated with FX-322 who had baseline word recognition in quiet scores of below 90 percent, four showed clinically meaningful improvements. Also,when assessed at the group level, patients treated with FX-322 outperformed the placebo group in word recognition in a quiet background when averaged across all time points.
The FX-322 Phase 2a study is a randomized, double-blind, placebo-controlled, single- and repeat-dose study in which the Company enrolled 95 patients aged 18 to 65 with mild to moderately severe SNHL. The study uses validated measures of hearing function including WR, WIN and pure tone audiometry.
Tinnitus and quality-of-life measures will be evaluated using the Tinnitus Functional Index and the Hearing Handicap Inventory for Adults, respectively, and the study also includes testing of extended high frequencies (up to 16 kHz). The Phase 2a study has four dose cohorts, and hearing function will be regularly tested over the course of seven months following the first dosing.
The Company is conducting Phase 1b clinical studies to evaluate the potential of FX-322 in additional patient groups, including patients with age-related hearing loss and with severe SNHL. The Company is also conducting an open-label safety study looking at the administration conditions for FX-322.
A link to the publication, Improved Speech Intelligibility in Subjects with Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study (W.J. McLean, et. al.) can be found here. The Editor-in-Chief of Otology and Neurotology is Lawrence Lustig, M.D., Chair, Department of Otolaryngology - Head & Neck Surgery at Columbia University.
About Frequency Therapeutics
Frequency Therapeutics is a leader in the development of medicines designed to activate progenitor cells within the body to treat degenerative diseases. The Company’s progenitor cell activation (PCA) approach stimulates progenitor cells to create functional tissue with the aim of developing disease modifying therapies. The Company’s lead product candidate, FX-322, is designed to regenerate auditory hair cells to restore hearing function. FX-322 is being evaluated in multiple ongoing clinical studies in patients with sensorineural hearing loss. The Company also is evaluating additional diseases where its PCA approach could create functional tissue, including in a pre-clinical program in multiple sclerosis.
Headquartered in Woburn, Mass., Frequency has an ex-U.S. license and collaboration agreement with Astellas Pharma Inc. for FX-322, as well as additional collaboration and licensing agreements with academic and nonprofit research organizations including Massachusetts Eye and Ear, Mass General Brigham, the Massachusetts Institute of Technology, The Scripps Research Institute and Cambridge Enterprises Limited. For more information, visit www.frequencytx.com and follow Frequency on Twitter @Frequencytx.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the Phase 2a clinical trial, the timing of top-line data from the Phase 2a clinical trial, the timing and results of top-line data from the Phase 1b studies in age-related hearing loss and severe SNHL, the implications of the results of the Phase 1/2 data, the timing and results of the open-label safety study evaluating the administration conditions for FX-322, the ability of our technology platform to provide patient benefit, estimates of the size of the hearing loss population and population at risk for hearing loss, the Company’s ability to advance its hearing program and further diversify its portfolio 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 relocation of the Company’s offices and laboratory facilities, the Company’s business and financial markets; 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; 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; 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 laws and regulations, including healthcare and environmental, health, and safety laws and regulations; failure to obtain, maintain and enforce protection of patents and other intellectual property; security breaches or failure to protect private personal information; attracting and retaining key personnel; and ability to manage growth.
These and other important factors discussed under the caption “Risk factors” in the Company’s Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 16, 2020 and its other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. 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 press release.
###
Contacts:
Investor Contact:
Carlo Tanzi, Ph.D.
Kendall Investor Relations
Tel: 617-914-0008
ctanzi@kendallir.com
Media Contact:
Suzanne Day
Frequency Therapeutics
Tel: 781-496-2211
Email: sday@frequencytx.com
Exhibit 99.2 REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021Exhibit 99.2 REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021
Forward-Looking Statements and Other Disclaimers This presentation contains forward-looking statements within the meaning of the including related to product liability, intellectual property or brought by Private Securities Litigation Reform Act of 1995. All statements contained in this stockholders; dependence on Astellas for the development and commercialization of presentation that do not relate to matters of historical fact should be considered FX-322 outside of the United States; misconduct by employees or independent forward-looking statements, including without limitation statements regarding the contractors; reliance on third parties, including to conduct clinical trials and treatment potential of FX-322, the Phase 2a clinical trial of FX-322 and the Phase 1b manufacture product candidates; compliance with laws and regulations, including studies in age-related hearing loss and severe SNHL patients, design, pace and timing healthcare and environmental, health, and safety laws and regulations; failure to of enrollment for the Phase 1b studies in age-related hearing loss and severe SNHL, obtain, maintain and enforce protection of patents and other intellectual property; the timing and completeness of data from the Phase 2a clinical trial and Phase 1b security breaches or failure to protect private personal information; attracting and studies in age-related hearing loss and severe SNHL, the results and implications of retaining key personnel; and ability to manage growth. the Phase 1/2 durability of response data, the timing and results of the open-label safety study evaluating the administration conditions for FX-322, the timing of end of These and other important factors discussed under the caption “Risk factors” in the phase 2 meetings with the FDA and future pivotal studies, the ability of our Company’s Form 10-Q filed with the Securities and Exchange Commission (SEC) on technology platform to provide patient benefit, the impact of COVID-19 on the November 16, 2020 and its other reports filed with the SEC could cause actual results Company’s on-going and planned clinical trials and business, future milestone and to differ materially from those indicated by the forward-looking statements made in royalty payments under the license and collaboration agreement with Astellas this presentation. Any such forward-looking statements represent management’s Pharma Inc. (“Astellas”), the sufficiency of the Company’s cash, cash equivalents and estimates as of the date of this presentation. While the Company may elect to short-term investments, estimates of the size of the hearing loss population and update such forward-looking statements at some point in the future, it disclaims any population at risk for hearing loss, estimates of the commercial opportunity of FX- obligation to do so, even if subsequent events cause its views to change. These 322 and the impact on existing treatment paradigms, the timing of the remyelination forward-looking statements should not be relied upon as representing the program, and the potential application of the PCA platform to other diseases. Company’s views as of any date subsequent to the date of this presentation. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: Frequency Therapeutics (the “Company”) has incurred and will continue to incur significant losses and is not and may never be profitable; need for additional funding to complete development and commercialization of any product candidate; the Company’s dependence on the development of FX-322; the unproven approach of the PCA platform; the lengthy, expensive and uncertain process of clinical drug development and regulatory approval; limited experience successfully obtaining marketing approval for and commercializing product candidates; the results of earlier clinical trials not being indicative of the results from later clinical trials; differences between preliminary or interim data and final data; adverse events or undesirable side effects; disruptions at the FDA and other regulatory agencies; the impact of the COVID-19 impact; failure to identify additional product candidates; new or changed legislation; failure to maintain Fast Track designation for FX-322 and such designation failing to result in faster development or regulatory review or approval; costly and damaging litigation, c Frequency Therapeutics, Inc. 2Forward-Looking Statements and Other Disclaimers This presentation contains forward-looking statements within the meaning of the including related to product liability, intellectual property or brought by Private Securities Litigation Reform Act of 1995. All statements contained in this stockholders; dependence on Astellas for the development and commercialization of presentation that do not relate to matters of historical fact should be considered FX-322 outside of the United States; misconduct by employees or independent forward-looking statements, including without limitation statements regarding the contractors; reliance on third parties, including to conduct clinical trials and treatment potential of FX-322, the Phase 2a clinical trial of FX-322 and the Phase 1b manufacture product candidates; compliance with laws and regulations, including studies in age-related hearing loss and severe SNHL patients, design, pace and timing healthcare and environmental, health, and safety laws and regulations; failure to of enrollment for the Phase 1b studies in age-related hearing loss and severe SNHL, obtain, maintain and enforce protection of patents and other intellectual property; the timing and completeness of data from the Phase 2a clinical trial and Phase 1b security breaches or failure to protect private personal information; attracting and studies in age-related hearing loss and severe SNHL, the results and implications of retaining key personnel; and ability to manage growth. the Phase 1/2 durability of response data, the timing and results of the open-label safety study evaluating the administration conditions for FX-322, the timing of end of These and other important factors discussed under the caption “Risk factors” in the phase 2 meetings with the FDA and future pivotal studies, the ability of our Company’s Form 10-Q filed with the Securities and Exchange Commission (SEC) on technology platform to provide patient benefit, the impact of COVID-19 on the November 16, 2020 and its other reports filed with the SEC could cause actual results Company’s on-going and planned clinical trials and business, future milestone and to differ materially from those indicated by the forward-looking statements made in royalty payments under the license and collaboration agreement with Astellas this presentation. Any such forward-looking statements represent management’s Pharma Inc. (“Astellas”), the sufficiency of the Company’s cash, cash equivalents and estimates as of the date of this presentation. While the Company may elect to short-term investments, estimates of the size of the hearing loss population and update such forward-looking statements at some point in the future, it disclaims any population at risk for hearing loss, estimates of the commercial opportunity of FX- obligation to do so, even if subsequent events cause its views to change. These 322 and the impact on existing treatment paradigms, the timing of the remyelination forward-looking statements should not be relied upon as representing the program, and the potential application of the PCA platform to other diseases. Company’s views as of any date subsequent to the date of this presentation. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: Frequency Therapeutics (the “Company”) has incurred and will continue to incur significant losses and is not and may never be profitable; need for additional funding to complete development and commercialization of any product candidate; the Company’s dependence on the development of FX-322; the unproven approach of the PCA platform; the lengthy, expensive and uncertain process of clinical drug development and regulatory approval; limited experience successfully obtaining marketing approval for and commercializing product candidates; the results of earlier clinical trials not being indicative of the results from later clinical trials; differences between preliminary or interim data and final data; adverse events or undesirable side effects; disruptions at the FDA and other regulatory agencies; the impact of the COVID-19 impact; failure to identify additional product candidates; new or changed legislation; failure to maintain Fast Track designation for FX-322 and such designation failing to result in faster development or regulatory review or approval; costly and damaging litigation, c Frequency Therapeutics, Inc. 2
2021 – A Year of Data and Growth LEADERSHIP MOMENTUM CLARITY Understanding the broadest patient Bringing focus to Speech Late Q1 2021: day-90 read out of population that can be helped by FX- Intelligibility as the major unmet FX-322 Phase 2a study 322. New Phase 1b studies in age clinical need for hearing loss Late Q2 2021: end-of-study related and severe hearing loss patients readout of FX-322 Phase 2a study Developing extensive HCP, patient Publication of clinical data in Continued partnership with Astellas and payor insights to guide strategy Otology & Neurotology Setting the standard - Creating the regulatory and clinical path forward c Frequency Therapeutics, Inc. 32021 – A Year of Data and Growth LEADERSHIP MOMENTUM CLARITY Understanding the broadest patient Bringing focus to Speech Late Q1 2021: day-90 read out of population that can be helped by FX- Intelligibility as the major unmet FX-322 Phase 2a study 322. New Phase 1b studies in age clinical need for hearing loss Late Q2 2021: end-of-study related and severe hearing loss patients readout of FX-322 Phase 2a study Developing extensive HCP, patient Publication of clinical data in Continued partnership with Astellas and payor insights to guide strategy Otology & Neurotology Setting the standard - Creating the regulatory and clinical path forward c Frequency Therapeutics, Inc. 3
Frequency Therapeutics: Pioneering a New Mode of Medicine Lead program, FX-322, showed first evidence of a hearing signal and hearing restoration in a clinical study; potential to treat tens of millions of patients Clinical-stage company Clinical-stage company that uses small molecules to activate progenitor cells within the body to that uses small molecules to activate progenitor cells within the body restore damaged cells and tissue Transformative approach to regenerative medicine potentially for a broad range of degenerative nd diseases, including a 2 program in multiple sclerosis c Frequency Therapeutics, Inc. 4Frequency Therapeutics: Pioneering a New Mode of Medicine Lead program, FX-322, showed first evidence of a hearing signal and hearing restoration in a clinical study; potential to treat tens of millions of patients Clinical-stage company Clinical-stage company that uses small molecules to activate progenitor cells within the body to that uses small molecules to activate progenitor cells within the body restore damaged cells and tissue Transformative approach to regenerative medicine potentially for a broad range of degenerative nd diseases, including a 2 program in multiple sclerosis c Frequency Therapeutics, Inc. 4
Frequency Therapeutics: A Vision Built on Regeneration Since 2014 Frequency has Hearing loss: the been developing a powerful 4th largest cause new therapeutic approach to address a condition for which of disability there has been limited innovation in decades. globally Source: Wilson, et al. Lancet. (2017) c Frequency Therapeutics, Inc. 5Frequency Therapeutics: A Vision Built on Regeneration Since 2014 Frequency has Hearing loss: the been developing a powerful 4th largest cause new therapeutic approach to address a condition for which of disability there has been limited innovation in decades. globally Source: Wilson, et al. Lancet. (2017) c Frequency Therapeutics, Inc. 5
Large Hearing Loss Market: No Restorative Treatments Only 20% market ~$10 Billion ~41 Million $750 Billion penetration for US hearing aid market SNHL patients in US Lost annually due to Hearing Aids annual sales untreated hearing loss globally c Frequency Therapeutics, Inc. 6Large Hearing Loss Market: No Restorative Treatments Only 20% market ~$10 Billion ~41 Million $750 Billion penetration for US hearing aid market SNHL patients in US Lost annually due to Hearing Aids annual sales untreated hearing loss globally c Frequency Therapeutics, Inc. 6
Intelligibility - The Major Unmet Clinical Need I’M NOTICING AND UNDERSTANDING WHAT YOU’RE SAYING.Intelligibility - The Major Unmet Clinical Need I’M NOTICING AND UNDERSTANDING WHAT YOU’RE SAYING.
High Frequencies are Critical for Intelligibility For someone with high-frequency hearing loss, words may be indistinguishable – impacting their ability to understand and communicate.High Frequencies are Critical for Intelligibility For someone with high-frequency hearing loss, words may be indistinguishable – impacting their ability to understand and communicate.
40% of the words in English rely on the use of High Frequency Consonants 42% Of the words in Mandarin 55% Of the words in Spanish c Frequency Therapeutics, Inc. 940% of the words in English rely on the use of High Frequency Consonants 42% Of the words in Mandarin 55% Of the words in Spanish c Frequency Therapeutics, Inc. 9
Hearing Loss May Have a Significant Impact on Overall Health Increased risks with untreated hearing loss “Hearing loss is the largest potentially modifiable risk 50% 41% factor for developing dementia” July, 2020 DEMENTIA DEPRESSION JAMA Nov 8, 2018 Deal J, et al. Incident Hearing Loss and Comorbidity. A Longitudinal © CO OP 2021 Administrative Claims Study.Hearing Loss May Have a Significant Impact on Overall Health Increased risks with untreated hearing loss “Hearing loss is the largest potentially modifiable risk 50% 41% factor for developing dementia” July, 2020 DEMENTIA DEPRESSION JAMA Nov 8, 2018 Deal J, et al. Incident Hearing Loss and Comorbidity. A Longitudinal © CO OP 2021 Administrative Claims Study.
The Problem: Missing Sensory Hair Cells in the Cochlea Missing Sensory Hair Cells “Analysis of hair cells, auditory nerve fibers and strial tissues … shows that the degree of hearing loss is well predicted from the amount of hair cell loss.” Sensory Hair Cells - Journal of Neuroscience, July 2020 Progenitor Cells 11The Problem: Missing Sensory Hair Cells in the Cochlea Missing Sensory Hair Cells “Analysis of hair cells, auditory nerve fibers and strial tissues … shows that the degree of hearing loss is well predicted from the amount of hair cell loss.” Sensory Hair Cells - Journal of Neuroscience, July 2020 Progenitor Cells 11
Solution: A Therapy to Address the Underlying Pathology Activating progenitor cells to regenerate sensory hair cells in the cochlea 12Solution: A Therapy to Address the Underlying Pathology Activating progenitor cells to regenerate sensory hair cells in the cochlea 12
Solution: Directly Targeting Regenerating Sensory Hairs in the Cochlea FX-322 is administered via a standard The injection concentrates FX-322 in the cochlear region that intratympanic injection, a common procedure detects extended high-frequency sounds, critical for speech ENTs perform routinely intelligibility c Frequency Therapeutics, Inc. 13Solution: Directly Targeting Regenerating Sensory Hairs in the Cochlea FX-322 is administered via a standard The injection concentrates FX-322 in the cochlear region that intratympanic injection, a common procedure detects extended high-frequency sounds, critical for speech ENTs perform routinely intelligibility c Frequency Therapeutics, Inc. 13
Increasing Focus on Higher-Level Hearing Benefit Intelligibility (Clarity) Audibility (Loudness) measured with word recognition and measured with pure tone test words-in-noise tests (Standard, Validated Tests) Word Recognition Test • List of 50 monosyllabic words • Single words played in quiet Words-in-Noise Test • Background noise from multiple voices • Played at different signal-to-noise ratios c Frequency Therapeutics, Inc. 14Increasing Focus on Higher-Level Hearing Benefit Intelligibility (Clarity) Audibility (Loudness) measured with word recognition and measured with pure tone test words-in-noise tests (Standard, Validated Tests) Word Recognition Test • List of 50 monosyllabic words • Single words played in quiet Words-in-Noise Test • Background noise from multiple voices • Played at different signal-to-noise ratios c Frequency Therapeutics, Inc. 14
Recap: Completed FX-322 Phase 1/2 Safety Study Study Design • FX-322 shown to have a favorable safety profile Key Findings – no serious AEs Absolute Word Recognition Scores 50 Single No Injection 40 Injection • Clinically meaningful improvement in word All 23 30 15 drug, patients recognition scores in patients with measurable 8 placebo 20 word recognition deficits 10 0 % Change from Baseline in Word Recognition Scores • Statistically significant improvement in word recognition scores (words in quiet/sound clarity) Injection only in one ear creating an p = 0.010 additional control % Change from Baseline in Words-in-Noise Scores • Safety study • Patients with mild to moderate SNHL; • Improvement trend in words-in-noise permanent NIHL/SSNHL for at least 6 months • Majority of patients did not have measurable p = 0.211 impairment in WR FX-322 PlaceboRecap: Completed FX-322 Phase 1/2 Safety Study Study Design • FX-322 shown to have a favorable safety profile Key Findings – no serious AEs Absolute Word Recognition Scores 50 Single No Injection 40 Injection • Clinically meaningful improvement in word All 23 30 15 drug, patients recognition scores in patients with measurable 8 placebo 20 word recognition deficits 10 0 % Change from Baseline in Word Recognition Scores • Statistically significant improvement in word recognition scores (words in quiet/sound clarity) Injection only in one ear creating an p = 0.010 additional control % Change from Baseline in Words-in-Noise Scores • Safety study • Patients with mild to moderate SNHL; • Improvement trend in words-in-noise permanent NIHL/SSNHL for at least 6 months • Majority of patients did not have measurable p = 0.211 impairment in WR FX-322 Placebo
FX-322 Patients Show Sustained Hearing Improvements 13-21 Months After Initial Dosing 50 50W 47 Key Findings 50W 50W 40 *25W 39 38 38 50W • Preliminary evidence indicating a 50W 35 durable benefit of hearing clarity 34 *25W 50W 30 30 29 50W 26 Baseline - Correct words out of 50 50W 50W Day 90 - Correct words out of 50 22 20 20 1-2 Years - Correct words out of 50 50W 50W 16 50W 14 Three patients who had durable 12 10 50W improvements in intelligibility also had pure tone audiometry improvements of 7 10 – 15 dB at the highest frequency tested Month 16** Month 21** Month 19** Month 13** Month 21** (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 c Frequency Therapeutics, Inc. 16 • **Since FX-322 dosingFX-322 Patients Show Sustained Hearing Improvements 13-21 Months After Initial Dosing 50 50W 47 Key Findings 50W 50W 40 *25W 39 38 38 50W • Preliminary evidence indicating a 50W 35 durable benefit of hearing clarity 34 *25W 50W 30 30 29 50W 26 Baseline - Correct words out of 50 50W 50W Day 90 - Correct words out of 50 22 20 20 1-2 Years - Correct words out of 50 50W 50W 16 50W 14 Three patients who had durable 12 10 50W improvements in intelligibility also had pure tone audiometry improvements of 7 10 – 15 dB at the highest frequency tested Month 16** Month 21** Month 19** Month 13** Month 21** (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 c Frequency Therapeutics, Inc. 16 • **Since FX-322 dosing
FX-322 Clinical Data Published in Leading Journal FX-322 Phase 1/2 and drug delivery studies • Improved Speech Intelligibility in Subjects with Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study (W.J. McLean, et. al.) • Peer-reviewed • Pre-eminent journal in the field • Editor: Larry Lustig, M.D. Chair, Department of Otolaryngology - Head & Neck Surgery at Columbia University DOI: 10.1097/MAO.0000000000003120 c Frequency Therapeutics, Inc. 17FX-322 Clinical Data Published in Leading Journal FX-322 Phase 1/2 and drug delivery studies • Improved Speech Intelligibility in Subjects with Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study (W.J. McLean, et. al.) • Peer-reviewed • Pre-eminent journal in the field • Editor: Larry Lustig, M.D. Chair, Department of Otolaryngology - Head & Neck Surgery at Columbia University DOI: 10.1097/MAO.0000000000003120 c Frequency Therapeutics, Inc. 17
FX-322 Study - Phase 2a Design, Single and Multiple Doses Screening NIHL/SSNHL Mild to Moderately Severe • Double-blind, placebo-controlled, multi-center, adults ages 18-65 Randomize 1:1:1:1 • All subjects have meaningful word recognition deficits • Efficacy and exploratory endpoints • Word recognition FX-322 FX-322 FX-322 Placebo • Words-in-noise 1X 2X 4X 4X • Pure tone audiometry (0.25- N = 24 N = 24 N = 24 N = 24 16kHz) • Tinnitus questionnaire • QoL questionnaires Weekly Dosing Follow-up Visits Days 15, 30, 60, 90, 120, 150, 180, 210 Study Enrollment Completed Sept. 2020 c Frequency Therapeutics, Inc. 18FX-322 Study - Phase 2a Design, Single and Multiple Doses Screening NIHL/SSNHL Mild to Moderately Severe • Double-blind, placebo-controlled, multi-center, adults ages 18-65 Randomize 1:1:1:1 • All subjects have meaningful word recognition deficits • Efficacy and exploratory endpoints • Word recognition FX-322 FX-322 FX-322 Placebo • Words-in-noise 1X 2X 4X 4X • Pure tone audiometry (0.25- N = 24 N = 24 N = 24 N = 24 16kHz) • Tinnitus questionnaire • QoL questionnaires Weekly Dosing Follow-up Visits Days 15, 30, 60, 90, 120, 150, 180, 210 Study Enrollment Completed Sept. 2020 c Frequency Therapeutics, Inc. 18
Phase 2a Study objectives Further establish Evaluate Clarify endpoints hearing signal repeat dosing and patient population for registration FX-322 impact on secondary Improvements in measures including ultra-high key intelligibility measures frequency pure tones, tinnitus such as word recognition and and QOL measures words in noise c Frequency Therapeutics, Inc. 19Phase 2a Study objectives Further establish Evaluate Clarify endpoints hearing signal repeat dosing and patient population for registration FX-322 impact on secondary Improvements in measures including ultra-high key intelligibility measures frequency pure tones, tinnitus such as word recognition and and QOL measures words in noise c Frequency Therapeutics, Inc. 19
Collecting Key Data to Inform Clinical Program Phase 1/2 Study Phase 2a Study Overview N= 23 N= 95 Hearing restoration signal observed Further establish signal & validate potential endpoints Word recognition/Words-in-noise Word recognition/Words-in-noise Pure tone audiometry at 8kHz (0.25-8kHz) Pure tone audiometry /extended frequencies (0.25-16kHz) Tinnitus questionnaire QoL questionnaires Entrance criteria limited participation of subjects with meaningful Entrance criteria required all subjects have meaningful word word recognition/words-in-noise deficits recognition deficits Single dose Single and multiple doses Studies are double-blind, placebo-controlled, multi-center, in adults ages 18-65Collecting Key Data to Inform Clinical Program Phase 1/2 Study Phase 2a Study Overview N= 23 N= 95 Hearing restoration signal observed Further establish signal & validate potential endpoints Word recognition/Words-in-noise Word recognition/Words-in-noise Pure tone audiometry at 8kHz (0.25-8kHz) Pure tone audiometry /extended frequencies (0.25-16kHz) Tinnitus questionnaire QoL questionnaires Entrance criteria limited participation of subjects with meaningful Entrance criteria required all subjects have meaningful word word recognition/words-in-noise deficits recognition deficits Single dose Single and multiple doses Studies are double-blind, placebo-controlled, multi-center, in adults ages 18-65
Phase 2a Readouts Day-90 FX-322 day-90 group-level data review (late Q1 2021): • Speech intelligibility as measured by WR and WIN testing • Pure Tone Audiometry measures at frequencies from 0.25 kHz to 16 kHz • Partial data on measures of FX-322 on tinnitus, impact on QoL • Safety profilePhase 2a Readouts Day-90 FX-322 day-90 group-level data review (late Q1 2021): • Speech intelligibility as measured by WR and WIN testing • Pure Tone Audiometry measures at frequencies from 0.25 kHz to 16 kHz • Partial data on measures of FX-322 on tinnitus, impact on QoL • Safety profile
Phase 2a Readouts End of Study FX-322 end-of-study group- and individual- level data readout (late Q2 2021): • Full (7 month) intelligibility and audibility data. • Seven-month durability data (all patients) • Full study data on measures of FX-322 on tinnitus, impact on QoL • Safety profilePhase 2a Readouts End of Study FX-322 end-of-study group- and individual- level data readout (late Q2 2021): • Full (7 month) intelligibility and audibility data. • Seven-month durability data (all patients) • Full study data on measures of FX-322 on tinnitus, impact on QoL • Safety profile
Building on Existing Treatment Paradigms ENT treatment role in diagnosis, cochlear ENT Without implant or bone- anchored hearing aid Therapeutics (Current State) Audiologist Empowers ENT’s with a therapeutic intervention Patient Diagnosis Treatment Monitoring Journey Anticipate Audiologists will see increased patient Audiologist flow With Increased patient flow to Hearing aid still Need for on-going Therapeutics AUD for diagnosis dispensed by AUD monitoring by AUD (Future State) Diagnosis, therapeutic ENT administered by ENT c Frequency Therapeutics, Inc. 23Building on Existing Treatment Paradigms ENT treatment role in diagnosis, cochlear ENT Without implant or bone- anchored hearing aid Therapeutics (Current State) Audiologist Empowers ENT’s with a therapeutic intervention Patient Diagnosis Treatment Monitoring Journey Anticipate Audiologists will see increased patient Audiologist flow With Increased patient flow to Hearing aid still Need for on-going Therapeutics AUD for diagnosis dispensed by AUD monitoring by AUD (Future State) Diagnosis, therapeutic ENT administered by ENT c Frequency Therapeutics, Inc. 23
Understanding the Broader potential of FX- Phase 1b Study 322 evaluating ages 18- 65 with severe 5M severe hearing loss Each SNHL Type Being Studied in FX-322 clinical program represents a significant patient population Phase 1b Study evaluating ages 66-85 with mild to moderately severe age- related 16M mild to moderate, age 65+ hearing loss Phase 2a Study evaluating ages 18 – 65 with noise induced and sudden mild to 20M mild to moderate, age 18-65 moderately severe SNHL Source: NCHS Survey Data 2016-18; NCHS 2017; NCHS 2016; c Frequency Therapeutics, Inc. 24Understanding the Broader potential of FX- Phase 1b Study 322 evaluating ages 18- 65 with severe 5M severe hearing loss Each SNHL Type Being Studied in FX-322 clinical program represents a significant patient population Phase 1b Study evaluating ages 66-85 with mild to moderately severe age- related 16M mild to moderate, age 65+ hearing loss Phase 2a Study evaluating ages 18 – 65 with noise induced and sudden mild to 20M mild to moderate, age 18-65 moderately severe SNHL Source: NCHS Survey Data 2016-18; NCHS 2017; NCHS 2016; c Frequency Therapeutics, Inc. 24
Program Momentum and Expansion Sensorineural Hearing DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Loss (SNHL) FX-322 Phase 2a – 202 Study Fully enrolled; Day-90 data analysis planned for late Q1 2021 Study of noise induced and sudden SNHL patients with mild with end of study read out in late Q2 2021 to moderately severe acquired SNHL, ages 18 – 65 FX-322 Phase 1b – 112 Study First patient dosed October 2020, Study of mild to moderately severe age-related hearing read out planned for Q2 2021 loss patients, ages 66 - 85 FX-322 Phase 1b – 113 Study Study commenced in Q4 2020, read out planned for Study of patients with severe SNHL, Q3 2021 ages 18 – 65 DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Remyelination in Regulatory submission Multiple Sclerosis planned for H2 2021 *The Company is also conducting an open-label Phase 1 safety study looking at the administration conditions for FX-322 c Frequency Therapeutics, Inc. 25Program Momentum and Expansion Sensorineural Hearing DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Loss (SNHL) FX-322 Phase 2a – 202 Study Fully enrolled; Day-90 data analysis planned for late Q1 2021 Study of noise induced and sudden SNHL patients with mild with end of study read out in late Q2 2021 to moderately severe acquired SNHL, ages 18 – 65 FX-322 Phase 1b – 112 Study First patient dosed October 2020, Study of mild to moderately severe age-related hearing read out planned for Q2 2021 loss patients, ages 66 - 85 FX-322 Phase 1b – 113 Study Study commenced in Q4 2020, read out planned for Study of patients with severe SNHL, Q3 2021 ages 18 – 65 DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Remyelination in Regulatory submission Multiple Sclerosis planned for H2 2021 *The Company is also conducting an open-label Phase 1 safety study looking at the administration conditions for FX-322 c Frequency Therapeutics, Inc. 25
Regenerative Approach with Broad Potential Brain Ear Eye Lung Skin Progenitor cells are stem cells that are pre- programmed to perform a specific activity Bone Intestine Muscle Cartilage Potential to address a range of degenerative diseases c Frequency Therapeutics, Inc. 26Regenerative Approach with Broad Potential Brain Ear Eye Lung Skin Progenitor cells are stem cells that are pre- programmed to perform a specific activity Bone Intestine Muscle Cartilage Potential to address a range of degenerative diseases c Frequency Therapeutics, Inc. 26
Remyelination Program for Multiple Sclerosis Remyelination is the major Target Regulatory submission - unmet need in MS 2H21 • Little room to improve • Single agents have current immunomodulators demonstrated signal in early Phase 2 MS studies • Patients still decline due to lack of myelination • Frequency has secured rights across multiple key classes of • Target population for molecules remyelination represents 50% of MS patients • Building on Frequency expertise in synergistic combinations of small molecules c Frequency Therapeutics, Inc. 27Remyelination Program for Multiple Sclerosis Remyelination is the major Target Regulatory submission - unmet need in MS 2H21 • Little room to improve • Single agents have current immunomodulators demonstrated signal in early Phase 2 MS studies • Patients still decline due to lack of myelination • Frequency has secured rights across multiple key classes of • Target population for molecules remyelination represents 50% of MS patients • Building on Frequency expertise in synergistic combinations of small molecules c Frequency Therapeutics, Inc. 27
Summary and Financial Profile Addressing Broadest Potential FX-322 Near-Term Data Ex-US Partnership with Strong SNHL Market Readouts Potential Milestones and Royalties Studies across all major SNHL Continued clinical validation and types development progress towards pivotal studies Addressable market of >40 million people in the US Platform Potential $224.2 Million in Cash and Cash Well capitalized for advancement Equivalents of pivotal trials. Runway into 2023 PCA platform with potential to treat patients across numerous *As of Sept. 30, 2020. Excludes restricted degenerative diseases cash 28 c Frequency Therapeutics, Inc.Summary and Financial Profile Addressing Broadest Potential FX-322 Near-Term Data Ex-US Partnership with Strong SNHL Market Readouts Potential Milestones and Royalties Studies across all major SNHL Continued clinical validation and types development progress towards pivotal studies Addressable market of >40 million people in the US Platform Potential $224.2 Million in Cash and Cash Well capitalized for advancement Equivalents of pivotal trials. Runway into 2023 PCA platform with potential to treat patients across numerous *As of Sept. 30, 2020. Excludes restricted degenerative diseases cash 28 c Frequency Therapeutics, Inc.
REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021
APPENDIX c Frequency Therapeutics, Inc. 30APPENDIX c Frequency Therapeutics, Inc. 30
Broad Potential of Progenitor Cell Activation Approach c Frequency Therapeutics, Inc. 31Broad Potential of Progenitor Cell Activation Approach c Frequency Therapeutics, Inc. 31
Origin of Frequency Therapeutics Tissue-Specific, Pre-programmed Stem Cells Decoding Intestinal Enabling Cochlear Frequency Therapeutics Regeneration Regeneration Small molecule therapeutics show Langer and Karp publish small Same cues reactivate normally molecules activate intestinal inactive progenitors in the clinical proof of concept progenitors cochlea Clonal Expansion of Lgr5-Positive Niche-independent high-purity Cells from Mammalian Cochlea cultures of Lgr5+ intestinal stem and High-Purity Generation of cells and their progeny Sensory Hair Cells c Frequency Therapeutics, Inc. 32Origin of Frequency Therapeutics Tissue-Specific, Pre-programmed Stem Cells Decoding Intestinal Enabling Cochlear Frequency Therapeutics Regeneration Regeneration Small molecule therapeutics show Langer and Karp publish small Same cues reactivate normally molecules activate intestinal inactive progenitors in the clinical proof of concept progenitors cochlea Clonal Expansion of Lgr5-Positive Niche-independent high-purity Cells from Mammalian Cochlea cultures of Lgr5+ intestinal stem and High-Purity Generation of cells and their progeny Sensory Hair Cells c Frequency Therapeutics, Inc. 32
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 c Frequency Therapeutics, Inc. 33Frequency 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 c Frequency Therapeutics, Inc. 33
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 c Frequency Therapeutics, Inc. 34Uniqueness 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 c Frequency Therapeutics, Inc. 34
Frequency: Developing a Platform Approach that Reduces the Complexity of Regenerative Medicine Harnessing Innate No Change to Ease of Biology Genome Manufacturing Progenitors already Activating native Use of small located within target programs, reducing molecules: no need to tissue safety concerns remove or grow cells ex vivo c Frequency Therapeutics, Inc. 35Frequency: Developing a Platform Approach that Reduces the Complexity of Regenerative Medicine Harnessing Innate No Change to Ease of Biology Genome Manufacturing Progenitors already Activating native Use of small located within target programs, reducing molecules: no need to tissue safety concerns remove or grow cells ex vivo c Frequency Therapeutics, Inc. 35
Progenitors in Place to Replace Hair Cell Loss Human Cochlea Cross-section Audiogram Despite Hair Cell Loss, Progenitor Cells Remain 47 Year Old Male with Occupational Noise Deafness c Frequency Therapeutics, Inc. 36Progenitors in Place to Replace Hair Cell Loss Human Cochlea Cross-section Audiogram Despite Hair Cell Loss, Progenitor Cells Remain 47 Year Old Male with Occupational Noise Deafness c Frequency Therapeutics, Inc. 36
Profound Synergy Between Pathways to Regenerate Cells Cochlear Progenitor Proliferation (Lgr5-GFP) Culture Media Wnt Activation (glycogen synthase kinase-3 (GSK3) Inhibitor; NCE) HDAC Inhibition (sodium valproate) Wnt Activation + HDAC inhibition HDAC = Histone deacetylase NCE = new chemical entity PROFOUND SYNERGY In vitro mouse model testing c Frequency Therapeutics, Inc. 37Profound Synergy Between Pathways to Regenerate Cells Cochlear Progenitor Proliferation (Lgr5-GFP) Culture Media Wnt Activation (glycogen synthase kinase-3 (GSK3) Inhibitor; NCE) HDAC Inhibition (sodium valproate) Wnt Activation + HDAC inhibition HDAC = Histone deacetylase NCE = new chemical entity PROFOUND SYNERGY In vitro mouse model testing c Frequency Therapeutics, Inc. 37
Strong FX-322 Pre-Clinical Validation Test Outcome In vitro Adult human inner ear tissue Created new hair cells In vivo Restored hair cells and hearing across Adult deafened mice all frequencies Achieved active levels in the cochlea Therapeutic drug levels in multiple species c Frequency Therapeutics, Inc. 38Strong FX-322 Pre-Clinical Validation Test Outcome In vitro Adult human inner ear tissue Created new hair cells In vivo Restored hair cells and hearing across Adult deafened mice all frequencies Achieved active levels in the cochlea Therapeutic drug levels in multiple species c Frequency Therapeutics, Inc. 38
FX-322 Program Advances and Global Opportunity c Frequency Therapeutics, Inc. 39FX-322 Program Advances and Global Opportunity c Frequency Therapeutics, Inc. 39
FX-322: Robust Clinical Phase 1/2 Design Screening NIHL/SSNHL Mild to Moderately Severe Single Study Overview No Injection Injection All 23 • Assess safety in 15 drug, patients patients with 8 placebo sensorineural hearing FX-322 Placebo loss N = 15 N = 8 • Stable patients Day 1 | Dose • Evaluated hearing by word testing and pure tones Follow-up Visits Injection only in one ear creating an Days 15, 30, 60, 90 additional control c Frequency Therapeutics, Inc. 40FX-322: Robust Clinical Phase 1/2 Design Screening NIHL/SSNHL Mild to Moderately Severe Single Study Overview No Injection Injection All 23 • Assess safety in 15 drug, patients patients with 8 placebo sensorineural hearing FX-322 Placebo loss N = 15 N = 8 • Stable patients Day 1 | Dose • Evaluated hearing by word testing and pure tones Follow-up Visits Injection only in one ear creating an Days 15, 30, 60, 90 additional control c Frequency Therapeutics, Inc. 40
FX-322: Successful Phase 1/2 Study Completed Key Findings Screening NIHL/SSNHL Mild to Moderately Severe Exploratory Endpoints - Evaluating Hearing Signal • Favorable safety profile • No change in placebo patients Mild SNHL patients (9 treated w/FX-322; 5 placebo) • No change in untreated ears • Baseline WR typically 45+ FX-322 Placebo word out of 50 (ceiling effect) N = 15 N = 8 Moderate SNHL patients (6 Day 1 | Dose treated w/FX-322; 3 Placebo) • Could be assessed for hearing improvement Follow-up Visits Days 15, 30, 60, 90 41 c Frequency Therapeutics, Inc.FX-322: Successful Phase 1/2 Study Completed Key Findings Screening NIHL/SSNHL Mild to Moderately Severe Exploratory Endpoints - Evaluating Hearing Signal • Favorable safety profile • No change in placebo patients Mild SNHL patients (9 treated w/FX-322; 5 placebo) • No change in untreated ears • Baseline WR typically 45+ FX-322 Placebo word out of 50 (ceiling effect) N = 15 N = 8 Moderate SNHL patients (6 Day 1 | Dose treated w/FX-322; 3 Placebo) • Could be assessed for hearing improvement Follow-up Visits Days 15, 30, 60, 90 41 c Frequency Therapeutics, Inc.
First Drug Candidate to Show Clinically Meaningful Improvements in Word Recognition Absolute Word Recognition Scores 50 47* Clarity of Sound 40 Used word tests in a quiet background 39* 38 34* Baseline - Correct words out of 50 30 29 Day 90 - Correct words out of 50 26 Test/retest variability is one standard deviation, which for a 50-word list is ~ 3 20 words 20 16* *Statistically significant and clinically 14 12 meaningful improvements in word 10 recognition 8 7 0 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 c Frequency Therapeutics, Inc. 42First Drug Candidate to Show Clinically Meaningful Improvements in Word Recognition Absolute Word Recognition Scores 50 47* Clarity of Sound 40 Used word tests in a quiet background 39* 38 34* Baseline - Correct words out of 50 30 29 Day 90 - Correct words out of 50 26 Test/retest variability is one standard deviation, which for a 50-word list is ~ 3 20 words 20 16* *Statistically significant and clinically 14 12 meaningful improvements in word 10 recognition 8 7 0 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 c Frequency Therapeutics, Inc. 42
Sustained Improvements in Sound Clarity Statistically Significant Improvement Clear Improvement Trend in Sound Clarity (words in quiet) in Words-in-Noise p = 0.010 p = 0.211 FX-322 Placebo c Frequency Therapeutics, Inc. 43 Improvement % change from baseline % change from baselineSustained Improvements in Sound Clarity Statistically Significant Improvement Clear Improvement Trend in Sound Clarity (words in quiet) in Words-in-Noise p = 0.010 p = 0.211 FX-322 Placebo c Frequency Therapeutics, Inc. 43 Improvement % change from baseline % change from baseline
Clinical Data Confirms FX-322 Delivery to Cochlea Exploratory study to see if cochlear drug levels can be directly measured in patients undergoing cochlear implant surgery following FX-322 injection Key Findings: • Measurement of cochlear fluid confirmed successful drug delivery to cochlea in all samples analyzed • Drug levels predicted to result in therapeutic activity Taken together with the Phase 1/2 study, we believe this is the first known clinical evidence of a pharmacokinetic / pharmacodynamic effect of a potential hearing restoration therapeutic c Frequency Therapeutics, Inc. 44Clinical Data Confirms FX-322 Delivery to Cochlea Exploratory study to see if cochlear drug levels can be directly measured in patients undergoing cochlear implant surgery following FX-322 injection Key Findings: • Measurement of cochlear fluid confirmed successful drug delivery to cochlea in all samples analyzed • Drug levels predicted to result in therapeutic activity Taken together with the Phase 1/2 study, we believe this is the first known clinical evidence of a pharmacokinetic / pharmacodynamic effect of a potential hearing restoration therapeutic c Frequency Therapeutics, Inc. 44
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 • Payments of up to $625mm which included $80mm upfront - Development milestone payments to Frequency of $65.0 million and $25.0 million upon the first dosing of a patient in a Phase 2b clinical trial for SNHL in Europe • Strategic commitment to and Asia, respectively invest in ENT as a therapeutic area - $100.0 million and $40.0 million upon the first dosing of a patient in a Phase 3 clinical trial for SNHL in Europe • Research focus in and Asia, respectively regenerative medicine • Development & commercialization: • Global footprint in major Astellas responsible for execution and costs of ex-US markets and distributorship clinical development and commercialization model in Africa/ME and LATAM c Frequency Therapeutics, Inc. 45Astellas 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 • Payments of up to $625mm which included $80mm upfront - Development milestone payments to Frequency of $65.0 million and $25.0 million upon the first dosing of a patient in a Phase 2b clinical trial for SNHL in Europe • Strategic commitment to and Asia, respectively invest in ENT as a therapeutic area - $100.0 million and $40.0 million upon the first dosing of a patient in a Phase 3 clinical trial for SNHL in Europe • Research focus in and Asia, respectively regenerative medicine • Development & commercialization: • Global footprint in major Astellas responsible for execution and costs of ex-US markets and distributorship clinical development and commercialization model in Africa/ME and LATAM c Frequency Therapeutics, Inc. 45
LEADERSHIP c Frequency Therapeutics, Inc. 46LEADERSHIP c Frequency Therapeutics, Inc. 46
Proven Leadership Team David Lucchino Chris Loose, Ph.D. Carl Lebel, Ph.D. President, CEO & Co-Founder Chief Scientific Officer & Co-Founder Chief Development Officer Former CEO of Entrega Bio (PureTech). Co-founder/CTO of Semprus BioSciences through FDA/CE Chief Scientific Officer of Otonomy (2009 to 2016). Co-founder/CEO of Semprus BioSciences (acquired), clearance and acquisition. Princeton, MIT, Hertz Fellow Executive Director, Amgen. Scientific fellow of the Polaris Partners. MIT Sloan Fellow. and Yale Faculty. American Academy of Otolaryngology. Dana Hilt, M.D. William Chin, M.D. Will McLean, Ph.D. Chief Medical Officer EVP, Clinical & Translational Science VP, Biology & Regen. Med, Co-Founder Neurologist and neuroscientist with two decades in SVP, Discovery Research and Clinical Investigation at Eli 15 years experience in inner ear biology. Discovered biopharma and CNS drug development. Amgen, Lilly, EVP at PhRMA, Executive Dean for Research at specific stem cells that make hair cells and neurons. Lysosomal, Forum Pharma. Harvard Medical School. Harvard-MIT Health Sciences and Technology Program. Wendy Arnold Peter Pfreundschuh Chief People Officer Chief Financial Officer HR leader with extensive life science experience including CFO of numerous public life sciences companies including senior leadership roles at Kaleido Biosciences, Moderna, UroGen and Sucampo, as well as business development and Celgene Avilomics Research, and Inotek Pharmaceuticals finance leadership positions at Astra Zeneca and J&J. c Frequency Therapeutics, Inc. 47Proven Leadership Team David Lucchino Chris Loose, Ph.D. Carl Lebel, Ph.D. President, CEO & Co-Founder Chief Scientific Officer & Co-Founder Chief Development Officer Former CEO of Entrega Bio (PureTech). Co-founder/CTO of Semprus BioSciences through FDA/CE Chief Scientific Officer of Otonomy (2009 to 2016). Co-founder/CEO of Semprus BioSciences (acquired), clearance and acquisition. Princeton, MIT, Hertz Fellow Executive Director, Amgen. Scientific fellow of the Polaris Partners. MIT Sloan Fellow. and Yale Faculty. American Academy of Otolaryngology. Dana Hilt, M.D. William Chin, M.D. Will McLean, Ph.D. Chief Medical Officer EVP, Clinical & Translational Science VP, Biology & Regen. Med, Co-Founder Neurologist and neuroscientist with two decades in SVP, Discovery Research and Clinical Investigation at Eli 15 years experience in inner ear biology. Discovered biopharma and CNS drug development. Amgen, Lilly, EVP at PhRMA, Executive Dean for Research at specific stem cells that make hair cells and neurons. Lysosomal, Forum Pharma. Harvard Medical School. Harvard-MIT Health Sciences and Technology Program. Wendy Arnold Peter Pfreundschuh Chief People Officer Chief Financial Officer HR leader with extensive life science experience including CFO of numerous public life sciences companies including senior leadership roles at Kaleido Biosciences, Moderna, UroGen and Sucampo, as well as business development and Celgene Avilomics Research, and Inotek Pharmaceuticals finance leadership positions at Astra Zeneca and J&J. c Frequency Therapeutics, Inc. 47
Hearing Clinical Advisory Board Dan Lee, M.D. Rene Gifford, Ph.D. Steve Rauch, M.D. Ruth Litovsky, Ph.D. Director, Pediatric Otology and Associate Director of Pediatric Director, Vestibular Division, Professor, Communications Sciences and Neurotology, Mass Eye and Ear Audiology, Director of Cochlear Medical Director, Mass. Eye and Disorders and Surgery Division of Implant Program, Vanderbilt Ear Balance and Vestibular Center Otolaryngology, University of Wisconsin University Chris Runge, Ph.D. David Friedland, M.D., Ph.D. Julie Arenberg, MS, Ph.D. Joni Doherty, MD, Ph.D. Chief of the Division of Vice-Chair of the Department of Otolaryngology Associate Director of Clinical Audiology for Assistant Professor of Clinical Communication Sciences, and Communications Sciences, Medical College of Research and Education, Mass Eye and Ear Otolaryngology-Head and Neck Surgery, Medical College of Wisconsin Wisconsin Keck School of Medicine of USC. c Frequency Therapeutics, Inc. 48Hearing Clinical Advisory Board Dan Lee, M.D. Rene Gifford, Ph.D. Steve Rauch, M.D. Ruth Litovsky, Ph.D. Director, Pediatric Otology and Associate Director of Pediatric Director, Vestibular Division, Professor, Communications Sciences and Neurotology, Mass Eye and Ear Audiology, Director of Cochlear Medical Director, Mass. Eye and Disorders and Surgery Division of Implant Program, Vanderbilt Ear Balance and Vestibular Center Otolaryngology, University of Wisconsin University Chris Runge, Ph.D. David Friedland, M.D., Ph.D. Julie Arenberg, MS, Ph.D. Joni Doherty, MD, Ph.D. Chief of the Division of Vice-Chair of the Department of Otolaryngology Associate Director of Clinical Audiology for Assistant Professor of Clinical Communication Sciences, and Communications Sciences, Medical College of Research and Education, Mass Eye and Ear Otolaryngology-Head and Neck Surgery, Medical College of Wisconsin Wisconsin Keck School of Medicine of USC. c Frequency Therapeutics, Inc. 48
Scientific Advisory Board Jeff Karp, Ph.D. Robert Langer, SC.D. Robin Franklin, Ph.D. Sheng Ding, Ph.D. Associate Professor at David H. Koch Institute Professor at Professor of Stem Cell Medicine, Senior Investigator, Gladstone Brigham and Women’s Hospital, Harvard the Massachusetts Institute of Wellcome Trust-MRC Cambridge Institute of Cardiovascular Disease Medical School Technology Stem Cell Institute Sean J. Morrison, Ph.D. Siddhartha Mukherjee, Amy Wagers, Ph.D. M.D., D.Phil. Director of the Children's Medical Center Forst Family Professor of Research Institute, Stem Cell and Regenerative Biology, Assistant Professor of Medicine, UT Southwestern Harvard University Columbia University Medical Center c Frequency Therapeutics, Inc. 49Scientific Advisory Board Jeff Karp, Ph.D. Robert Langer, SC.D. Robin Franklin, Ph.D. Sheng Ding, Ph.D. Associate Professor at David H. Koch Institute Professor at Professor of Stem Cell Medicine, Senior Investigator, Gladstone Brigham and Women’s Hospital, Harvard the Massachusetts Institute of Wellcome Trust-MRC Cambridge Institute of Cardiovascular Disease Medical School Technology Stem Cell Institute Sean J. Morrison, Ph.D. Siddhartha Mukherjee, Amy Wagers, Ph.D. M.D., D.Phil. Director of the Children's Medical Center Forst Family Professor of Research Institute, Stem Cell and Regenerative Biology, Assistant Professor of Medicine, UT Southwestern Harvard University Columbia University Medical Center c Frequency Therapeutics, Inc. 49
REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021REIMAGINING THE TREATMENT OF HEARING LOSS Corporate Overview February 2021