Full Press Release Details
August 2021 Exhibit 99.2
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the interpretation and implications of the results of the Phase 2a study as well as the FX-322-112 and the FX-322-111 studies, the timing and results of top-line data from the Phase 1b study in severe SNHL, the initiation, timing and design of the new Phase 2 trial of FX-322, including the ability of study design to address study bias, the design and timing of future studies of and clinical development path for FX-322, the results and implications of the Phase 1/2 durability of response data, the ability of our technology platform to provide patient benefit, the impact of COVID-19 on the Company's on-going and planned clinical trials and business, future milestone and royalty payments under the license and collaboration agreement with Astellas Pharma Inc. ("Astellas"), the sufficiency of the Company's cash, cash equivalents and short-term investments, estimates of the size of the hearing loss population and population at risk for hearing loss, estimates of the commercial opportunity of FX-322 and the impact on existing treatment paradigms, the timing and progress of the remyelination program, and the potential application of the PCA platform to other diseases.
These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: 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; 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; failure to identify additional product candidates; new or changed legislation; failure to maintain Fast Track designation for FX-322 and such designation failing to result in faster development or regulatory review or approval; costly and damaging litigation, including related to product liability, intellectual property or brought by stockholders; dependence on Astellas 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 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 presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While the Company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presentation.
Forward-Looking Statements and Other Disclaimers 2
Leading the field of hearing restoration First ever known clinical studies demonstrating hearing improvements 3 Frequency Today: Guided by a Clear Signal
Defining the Target, Expanding the Pipeline Learnings from exploratory studies support new Phase 2 trials and help define path forward Working to expand our pipeline for hearing therapeutics and for other degenerative diseases 4
5 Today's Hearing Loss Market Has No Restorative Treatments $980 Billion Only 20% market penetration for Hearing Aids Lost annually due to untreated hearing loss globally* ~41 Million Individuals with SNHL in U.S. ~$10 Billion US hearing aid market annual sales *Source: World Health Organization
July, 2020 "Hearing loss is the largest potentially modifiable risk factor for developing dementia" Hearing Loss Can Have a Significant Impact on Overall Health DEMENTIA DEPRESSION Increased risks with untreated hearing loss 50% 41% JAMA Nov 8, 2018
Deal J, et al. Incident Hearing Loss and Comorbidity. A Longitudinal Administrative Claims Study.
7 Since 2014 Frequency has been driving a powerful new approach to tissue and cellular regeneration aimed at developing new therapeutics for conditions where there are no treatment options. Frequency Therapeutics:
A Vision Built on Regeneration
8 "Analysis of hair cells, auditory nerve fibers and strial tissues shows that the degree of hearing loss is well predicted from the amount of hair cell loss." - Journal of Neuroscience July 2020 Sensory Hair Cells Progenitor Cells Missing Sensory Hair Cells The Problem:
Missing Sensory Hair Cells in the Cochlea
A Therapy to Address the Underlying Pathology Synergy between pathways aims to activate progenitor cells and regenerate sensory cells in the cochlea
Intelligibility of Speech and Sound -
A Major Unmet Clinical Need For those with sensorineural hearing loss, words may be indistinguishable -
impacting their ability to understand and communicate
11 of words in English
rely on the use of fricative consonants of words in Mandarin of words in Spanish 40% 42% 55%
12 Increasing Focus on Hearing Clarity Intelligibility (Clarity)
measured with word recognition and words-in-noise tests Word Recognition Test
List of 50 monosyllabic words
Single words played in quiet Words-in-Noise Test
Background noise from multiple voices
Played at different signal-to-noise ratios Audibility (Loudness)
measured with pure tone test "When you develop SNHL, the issue is not just that you can't hear soft sounds. That's why if you ever talked to anyone who has a hearing loss, what they'll say is it's not that I can't hear you it's I can't understand you."
- Dr. Frank Lin from Externally-Led Patient Focused Drug Development program on SNHL, June 2021
13 FX-322: Directly Targeting the Regeneration
of Sensory Hair Cells in the Cochlea FX-322 is administered via a standard intratympanic injection,, a routine procedure performed by ENTs The injection concentrates FX-322 in the cochlear region critical for speech intelligibility
14 Two Independent Studies (FX-322-201, FX-322-111) Show Hearing Improvements with Single Dose Phase 1b Study FX-322-111 Overview Compared different FX-322 administration conditions
Open-label, multi-center, randomized study
Mild to severe subjects, age 18-65 (n=33) Study Results 34% of subjects achieved 10% or greater absolute improvement in word recognition (WR) in treated ear
Statistically significant and clinically meaningful improvements in WR
Favorable safety profile Phase 1/2 Study FX-322-201 Overview Placebo-controlled, multi-center, randomized study
Mild to moderately severe subjects, age 18-65 (n=23)
NIHL/SSNHL Study Results 33% of subjects achieved 10% or greater absolute improvement in word recognition in treated ear
Statistically significant and clinically meaningful improvements in WR
No meaningful changes in placebo group
Favorable safety profile *Total of 33 patients enrolled in study, 32 subjects completed 90-day clinical assessment period
15 FX-322 Phase 1/2 Durability Data: Patients Show Sustained Hearing Improvements 13-21 Months After Initial Dosing 7 Baseline - Correct words out of 50 Day 90 - Correct words out of 50 1-2 Years - Correct words out of 50 *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 Three patients who had durable improvements in intelligibility also had pure tone audiometry improvements of 10 - 15 dB at the highest frequency tested (8k Hz) Key Findings
Preliminary evidence indicating a durable benefit of hearing clarity
DOI: 10.1097/MAO.0000000000003120 16 FX-322 Clinical Data Recently 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. 2021)
Pre-eminent, peer-reviewed journal in the field
FX-322 Clinical Profile Informed by Broad Range of Learning Studies [Detail from subjects across all single-dose studies will provide key insights into potential responders] Enrolled
Next Steps for Continued FX-322 Clinical Development Important learnings informing continued FX-322 development
Understanding specific populations where FX-322 demonstrates benefit
Lead-in baseline assessments and other controls may mitigate study design bias
Build off totality of study subject data Plan to commence an additional FX-322 Phase 2 placebo-controlled study in Q4 2021
Continuum of data will further inform understanding of the patients and conditions where FX-322 may have the greatest impact
Clinical data demonstrate potential of FX-322 as a restorative treatment for SNHL
Two FX-322 single administration studies have demonstrated treatment benefit
Favorable safety profile
19 Repair of neurological damage is the major unmet need in MS
Currently approved immunomodulators do not restore myelin
Remyelination of damaged neurons has potential reverse neurological damage
Target population for remyelination represents 50% of MS patients Using PCA approach to address restoration in MS patients
Pre-clinical data has demonstrated potential to remyelinate with proprietary small molecule combinations
Research efforts underway to confirm optimal combination of molecules for clinical program
Strong IP portfolio Remyelination Program for Multiple Sclerosis
20 Harnessing Innate Biology
Progenitors already located within target tissue Frequency: Developing a Platform Approach that Reduces the Complexity of Regenerative Medicine No Change to Genome
Activating native programs, reducing safety concerns Ease of Manufacturing
Use of small molecules: no need to remove or grow cells ex vivo
21 Summary and Financial Profile Ex-US Partnership with Strong Potential Milestones and Royalties $175.5 Million in Cash and Cash Equivalents*
*As of March. 31, 2021.
Excludes restricted cash Defining FX-322 Development Path and Advancing New Studies Continued clinical validation and development progress Two Single Dose FX-322 Studies Show Hearing Improvements Statistical significance in key measures of hearing clarity
24 Broad Potential of Progenitor Cell Activation Approach
25 Origin of Frequency Therapeutics Tissue-Specific, Pre-programmed Stem Cells Decoding Intestinal Regeneration Langer and Karp publish small molecules activate intestinal progenitors Enabling Cochlear
Regeneration Same cues reactivate normally inactive progenitors in the cochlea Frequency Therapeutics Small molecule therapeutics show clinical proof of concept Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells
26 Frequency Progenitor Cell Activation (PCA) Approach Inactive
Progenitor ACTIVATED
Progenitor Asymmetric division using native programs + Functional Target Cell Inactive Progenitor Cell Combinations of small molecules designed to activate progenitor cells
27 Uniqueness of Our PCA approach Previous Approaches Frequency's PCA Approach Progenitor
Cell Pluripotent Multipotent Bipotent Fully Differentiated Yamanaka 4 Factors Transdifferentiation Partial Reprogramming
28 Our Approach: Activation of Progenitors 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
29 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
PROFOUND SYNERGY HDAC = Histone deacetylase
NCE = new chemical entity
In vitro mouse model testing
30 Strong FX-322 Pre-Clinical Validation
31 FX-322 Program Advances and Global Opportunity
Assess safety in patients with sensorineural hearing loss
Evaluated hearing by word testing and pure tones FX-322: Robust Clinical Phase 1/2 Design Screening NIHL/SSNHL
Mild to Moderately Severe Follow-up Visits
Days 15, 30, 60, 90 FX-322
N = 8 Single Injection
8 placebo No Injection
All 23 patients Day 1 | Dose Injection only in one ear creating an additional control
Recap: Completed FX-322 Phase 1/2 Safety Study Single Injection
8 placebo No Injection
All 23 patients Safety study
Patients with mild to moderate SNHL; permanent NIHL/SSNHL for at least 6 months
Majority of patients did not have measurable impairment in WR