Frequency Therapeutics Redesigns Study, Announces New Drug Pipeline

Frequency Therapeutics: Advancements and Future Directions

Frequency Therapeutics has experienced both successes and challenges since its inception. A recent Research and Development (R&D) event showcased a series of announcements detailing the progress of its leading hearing loss drug and outlining future strategies.

A Regenerative Approach to Hearing Loss

Established in 2015, Frequency Therapeutics is dedicated to a regenerative medicine strategy for addressing hearing loss. This approach concentrates on reactivating progenitor cells, which ultimately develop into the crucial hair cells responsible for sound transmission within the cochlea.

The loss or damage of these hair cells is a primary cause of sensorineural hearing loss, the most prevalent form of hearing impairment.

Updates on FX-322

During Tuesday’s event, the company presented several updates concerning FX-322, its primary drug candidate for hearing loss.

Frequency Therapeutics emphasized combined data from initial trials, indicating potential clinical advantages. They also posited that unfavorable outcomes from a Phase 2 study stemmed from deficiencies in the study’s methodology.

New Programs Unveiled

In addition to the FX-322 updates, Frequency Therapeutics introduced a novel product targeting hearing loss.

Furthermore, the company announced the initiation of a new research program focused on developing a treatment for multiple sclerosis.

These announcements collectively demonstrate Frequency Therapeutics’ commitment to innovation in regenerative medicine and its expanding pipeline of therapeutic candidates.

Re-evaluation of the FX-322 Clinical Trial Protocol

Sensorineural hearing loss is commonly addressed through interventions like cochlear implants or hearing aids. Individuals experiencing abrupt hearing decline may explore steroid therapies; however, currently, no pharmaceutical treatments are approved for the treatment or reversal of this condition.

Initial investigations into FX-322 yielded promising results. A Phase 1b study, involving 15 participants receiving the drug and eight receiving a placebo, revealed no significant adverse effects. Notably, four participants in the treatment group demonstrated measurable improvements in their ability to discern specific words.

It is important to note that Frequency Therapeutics assesses drug efficacy based on “speech perception” – the ability to understand spoken language – rather than simply detecting sounds. This endpoint has been utilized in trials for cochlear implants, and the company’s Chief Scientific Officer, Chris Loose, confirms alignment with the FDA regarding its relevance in evaluating hearing loss treatments.

Long-term follow-up data continues to support these initial findings, according to Carl LeBel, Frequency’s chief development officer. Unpublished data from five participants monitored for one to two years indicates that three continue to exhibit statistically significant improvements.

LeBel stated that this suggests some patients are capable of sustaining the benefits observed, potentially for a period of one or two years. Further monitoring of patients demonstrating improvement is necessary to ascertain whether this indicates a disease-modifying effect.

However, the positive outlook for FX-322 has been moderated by subsequent trial results. A Phase 2a clinical trial failed to demonstrate any significant improvement in hearing loss compared to the placebo group.

This study enrolled 95 participants, with half receiving four injections of the drug and the other half receiving placebos. Improvements were limited across both groups, and the company reported “no discernible benefit” from the drug in this trial.

Following the announcement of these results, Frequency’s stock price plummeted from $36 to $7 and has remained substantially below its previous peak. Consequently, shareholders initiated a class-action lawsuit, alleging that company leadership misrepresented information regarding FX-322 in earnings calls, press releases, SEC filings, and presentations prior to March 23, 2021.

Company leadership now contends that the Phase 2a study was compromised by potential bias. LeBel explained that patients may have underestimated their hearing abilities to qualify for the trial, and the study design did not adequately address this possibility.

“Inconsistencies were observed between patients’ historical speech perception scores and those recorded at the study’s baseline visit,” LeBel explained to TechCrunch.

Jason Glashow, Frequency’s senior vice president of corporate affairs, clarified that the company views this as a “design issue” inherent to the trial’s methodology.

Glashow emphasized that while bias was present in the study, it was not attributable to the participants themselves.

During a recent R&D presentation, Frequency presented pooled data from three Phase I studies to support the claim that FX-322 demonstrates a consistent pattern of response, and that the Phase 2a study was an anomalous outlier.

The potential impact of this information on the ongoing legal proceedings remains uncertain. However, the experience has influenced the design of future studies evaluating FX-322.

Frequency has initiated a new Phase 2b clinical trial for FX-322, enrolling 124 participants. This study incorporates a one-month “lead-in” period to monitor participants’ hearing before baseline measurements are taken.

The trial will also refine the focus on specific types of hearing loss, targeting individuals with diagnosed noise-induced or sudden sensorimotor hearing loss. This represents a subtle shift in the parameters of the therapy’s target population. (It is worth noting that noise-induced hearing loss affects between 10 and 40 million people annually, according to CDC estimates).

Novel Drug Candidate and Expanded Research Program

Beyond FX-322, Frequency Therapeutics is strategically diversifying its pipeline, venturing beyond a single product focus for the first time. The company intends to evaluate a new therapeutic, designated FX-345, which represents an enhanced iteration of the small molecule utilized in FX-322.

This increased potency, as noted by Loose, is expected to facilitate greater penetration of the drug into the cochlea.

An Investigational New Drug (IND) application for FX-345 is planned for submission in the second quarter of the following year.

Multiple Sclerosis Program Development

Frequency Therapeutics is concurrently engaged in the development of FREQ-162, a drug targeting multiple sclerosis. This initiative aligns with the company’s previously stated objective of broadening its focus to encompass regenerative medicine.

Preliminary data from murine studies, as presented to TechCrunch, indicates the drug’s potential to stimulate oligodendrocyte production. These cells are crucial for generating the myelin sheath, which is damaged in individuals affected by multiple sclerosis.

The company has not yet revealed a specific schedule for future clinical trials.

Currently, the primary emphasis remains on FX-322 and the redesigned trials aimed at resolving existing uncertainties.