Pipeline

GW-TT1
GW-TT2
GW-TT3
GW-TT5

GW-TT1:

An Oral Formulation of Zonisamide to Prevent
Noise-Induced Hearing Loss (NIHL)

Zonisamide is an FDA-approved anticonvulsant medication, specifically blocking T-type calcium channels. With the support of the US Department of Defense, we have initiated a Phase 2 clinical trial with Washington University School of Medicine to assess the safety and efficacy of GW-TT1 for the treatment of acute noise-induced hearing loss.

Back view of a woman with blonde hair in a ponytail, wearing black clothing and red and black noise-canceling headphones, raising her index finger.

Noise-Induced Hearing Loss (NIHL) is the second most common cause of sensorineural hearing loss, affecting nearly 26 million U.S. adults aged 20-69

GW-TT1 was evaluated in a double-blind, placebo-controlled trial designed to study the drug in adults exposed to loud noise associated with drilling during skull surgery. Unfortunately, this trial was terminated due to low patient enrollment that coincided with the COVID-19 pandemic.

Excessive calcium signaling affects many physiological processes in the inner ear, including sound transduction, ionic balance in inner ear fluids, and blood flow. By inhibiting T-type calcium channels, particularly CaV3.1, present in outer hair cells (OHCs) of the cochlea, GW-TT1 may prevent overexcitation of signaling pathways, which could otherwise lead to cell death.

Diagram of inner ear anatomy showing cochlea, nerve fibers, hair cells, semicular canals, and inside the cochlea.

Despite the termination of this key clinical trial due to challenges of running a trial during the COVID-19 pandemic, the concept of repurposing zonisamide for NIHL remains a subject of great interest to benefit high-risk individuals, such as military personnel, factory workers, and those undergoing certain surgical procedures.

An infographic explaining vertigo in the inner ear, showing normal and vertigo-affected structures with labeled parts, and a woman experiencing vertigo.

GW-TT2:

A Novel Nasal Formulation That Delivers Relief to Recent Onset Tinnitus

This unique nasal formulation of an FDA-approved drug for the treatment of tinnitus and other inner ear disorders allows targeted drug delivery to the brain at 20x concentration relative to oral delivery. This enables lower drug doses, faster action and fewer systemic side effects.

A woman with curly hair holding a large shell up to her face on a beach.

Tinnitus, often described as a ringing in the ear, affects approximately 15% of the population

Recent onset tinnitus, defined as tinnitus that has arisen within the last two years, affects over 8 million people in the US alone, with no FDA-approved drugs on the market. For millions, tinnitus can disrupt sleep, concentration, and quality of life. It is also a symptom of many inner ear disorders, including Meniere's disease, sudden sensorineural hearing loss, and vestibular migraines.

Excessive calcium signaling affects many physiological processes in the inner ear, including sound transduction, ionic balance in inner ear fluids, and blood flow. By reducing active signaling, GW-TT2 may reduce inflammatory responses and neural signals that generate a tinnitus percept.

Close-up of a woman holding a nasal spray bottle near her nose.

We are currently completing preclinical safety studies with the goal of moving to human clinical studies in 2026. These initial studies will provide safety and efficacy data in healthy adults and patient populations

Diagram of the human ear showing parts involved in hearing and how tinnitus affects hearing, including labels for the brain, cochlea, auditory nerve, ear canal, ear drum, auditory tube, earlobe, sound waves, healthy hair cells, and damaged nerve cells.

GW-TT5:

A First-in-Class Gene Therapy for Chronic Tinnitus

Previous medical reports have documented a dramatic reduction in tinnitus loudness following electrical stimulation of the caudate nucleus (CN) in patients. GW-TT5 was developed to transpose CN-targeted deep-brain electrical stimulation to a safer and more effective drug-based neuromodulation using chemogenetic gene therapy.

A starfish resting on wet sandy beach, with ripples in the water around it.

Approximately 2 million Americans suffer from severe, debilitating tinnitus

These individuals have a higher risk of experiencing other debilitating comorbidities, including suicidal ideation, resulting in greater functional impairment and a decrease in quality of life. Despite its high prevalence, there are no drugs approved by the FDA for the treatment of tinnitus. If successful, the outcomes of the GW-TT5 program will lead to new gene therapies.

GW-TT5 uses chemogenic tools to insert special proteins within inhibitory neurons of the CN that, when activated, may suppress the tinnitus percept. Specifically, designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tools enable precise and selective neuronal targeting of the gene therapy. Therapeutic effects of DREADD-expressing inhibitory CN neurons can be achieved through oral drugs that selectively activate DREADD proteins.

A person holding an orange prescription pill bottle with white pills spilling onto their palm.

Our proof-of-concept work supports successful brain delivery and neuronal targeting of AAV-based DREADDs with confirmed auditory perceptual effects. A phase 1 clinical study is currently in development.

Diagram of tinnitus inside the cochlea showing healthy and damaged hair cells, nerve fibers, semicircular canals, and the cochlea.

GW-TT3:

A New Small Molecule Therapy to Treat Tinnitus

GW-TT3 is a new chemical entity that shows potential in the treatment of tinnitus. Animal pharmacodynamic and pharmacokinetic studies are currently underway to examine the efficacy of GW-TT3 in the treatment of tinnitus.