Develop innovative therapeutic solutions for inner ear disorders

Our approach around three pillars

Restore / Treat / Prevent

Through these 3 pillars, we are developing a portfolio of potential therapeutic solutions addressing unmet medical need in inner ear disorders.

Aim

Restore hearing

One of our objectives is to restore hearing by developing innovative gene therapies for genetic forms of hearing loss that have been hitherto untreatable. Sensorion is developing two products: OTOF-GT targeting Otoferlin deficiency, USHER-GT to address Usher Syndrome Type 1 and GJB2-GT targeting GJB2-related hearing loss.

collaboration

Collaborations with Institut Pasteur

In May 2019, Sensorion signed a partnership framework agreement with Institut Pasteur on gene therapy programs targeting hearing loss. Sensorion is the preferred partner for Institut Pasteur’s research programs in the field of genetic inner ear diseases, with rights to establish research and development collaborations. In the first three programs from this collaboration, Sensorion and Institut Pasteur are investigating deafness caused by Otoferlin deficiency and by Usher Syndrome Type 1 and by mutations in the GJB2 gene.

Our approach

Otoferlin deficiency

Introduction

What is Otoferlin deficiency ?

Sensorion’s OTOF-GT gene therapy product development program aims to restore hearing in people with Otoferlin deficiency, one of the most common forms of congenital deafness. This rare genetic disease is caused by mutations in the OTOF gene, typically leading to severe to profound deafness in both ears.

The Otoferlin protein is essential in transmitting sound information at auditory hair cell synapses.

Audinnove project

Sensorion is the sole industrial partner in the « AUDINNOVE » consortium together with three clinical and research partners – Necker-Enfants Malades Hospital, Institut Pasteur, the Fondation pour l’Audition. The objective is the development of a gene therapy for patients suffering from Otoferlin deficiency.

The consortium funding (up to €9.7m), will advance the program to the enrolment of the first patient in the clinical study.

Membership of this consortium keeps Sensorion at the forefront of the epidemiology of Otoferlin deficiency and emerging gene therapies.

This project notably involves:

-A database compilation with genotypic and phenotypic characterization of children with congenital hearing loss

-A natural history study allowing for clinical evaluation and selection of patients

-A Phase 1 clinical study

This consortium is key to the understanding of the epidemiology and to build awareness of the emerging gene therapies.

This project is financed by the French state, via the National Research Agency through the “Investing for the future” program (ref: ANR-18-RHUS-0007).

Key figures

Key information

  • Otoferlin defiency is responsible for up to 8% of all congenital hearing loss
  • Prevalence: around 20 000 patients in the USA and EU
  • Incidence: around 1100 new patients per year in the USA and EU.

Our approach

Usher syndrome type 1

syndrome

Sensorion launched the USHER-GT gene therapy product development program to restore inner ear function in patients suffering from Usher Syndrome Type 1.

Usher Syndrome Type 1 is the most severe form of Usher syndrome, characterized by a profound congenital deafness and balance dysfunction. Progressive vision loss also appears during childhood, leading to blindness.

Usher Syndrome Type 1 stems from disruptive variations in one of several proteins, each influencing a protein complex that plays a key role in the formation or maintenance of the electromechanical transduction apparatus of sensory inner hair cells.

Key figure

Key information

  • Usher Syndrome Type 1 represents around 40% of all cases of Usher Syndrome
  • Prevalence of Usher Syndrome: around 4-17 per 100,000 people – around 13k to 55k patients in EU and around 13k to 56k patients in the USA

Notre approche

GJB2-related hearing loss

What is GJB2-related hearing loss?

What is GJB2-related hearing loss?

Sensorion’s GJB2-GT gene therapy product development program aims to address hearing loss in people with mutations in the GJB2 gene, the most common form of childhood deafness. This rare genetic disease in congenital forms typically leads to severe to profound deafness in both ears.

The Connexin 26 protein, encoded by the GJB2 gene, is essential in the formation of gap junctions in the cochlea, which are key for intercellular exchanges of molecules.

We have identified three forms of hearing loss associated with GJB2 gene mutations:

  • Early onset of severe presbycusis: Institut Pasteur established that GJB2 mutations caused early onset forms of severe presbycusis in adults, appearing to be monogenic types of hearing loss potentially treatable by gene therapy
  • Childhood onset: Hearing loss can progress in a subset of patients with GJB2 mutations during childhood, worsening over time.
  • Congenital onset: Hearing loss is present at birth and is typically severe to profound

Key figure

Key information

  • 100,000 patients between 30 and 69 years old tought to be affected by a monogenic form of presbycusis due to GJB2 mutations.
  • Prevalence of congenital and childhood onset forms are estimated to be around 200,000 patients as around 50% of autosomal recessive non syndromic hearing loss cases are thought to be from GJB2 mutations.

Aim

Treat hearing disorders

One of our objectives is to treat hearing disorders by developing innovative therapeutic solutions. SENS-401 SSHNL is our lead candidate to treat sudden sensorineural hearing loss.

Causes

Sudden Sensorineural Hearing Loss (SSNHL)

Sudden Sensorineural Hearing Loss is due due to dysfunction of the cells of  the cochlea and central auditory structures. It is characterized by a sudden hearing loss appearing instantly or in less than 72 hours, typically unilateral, and a sound perception reduced 1,000 fold (meaning a hearing sensitivity loss of at least 30 decibels).

The hearing loss can be accompanied by tinnitus and frequent vertigo. Complications experienced can be through difficulties in communicating, social isolation and cognitive decline.

Key figures

Key information

  • More than 70% of cases are idiopathic, known causes include noise/head trauma, ischemia, infection, …
  • More than 50% of patients suffer from permanent disabling hearing loss

Prevention

Prevent hearing disorders

One of our objectives is to prevent hearing loss in different indications such as cisplatin induced ototoxicity or hearing loss due to cochlear implantation. We launched two programs with our SENS-401 compound: SENS-401 CIO and SENS-401 Cochlear, addressing those two indications.

Treatment

Prevent cisplatin induced ototoxicity

Platinum based agents such as cisplatin (often used as first line option in chemotherapies), carboplatin and oxaliplatin, alone or in combination, are often used to treat a wide variety of cancers. However, cisplatin induced ototoxicity leads to permanent inner ear problems in 50 to 60% of cases, causing:

-Problems in language acquisition and learning for pediatric patients

-Difficulties in communicating, social isolation, cognitive decline

Risk factors include young age as well as individual and cumulative cisplatin doses received.

Causes

Prevent hearing loss due to cochlear implantation

Cochlear implants are highly effective in treating severe to profound hearing loss. But preserving acoustic hearing in patients with less severe forms of hearing loss who receive cochlear implants could provide a substantial benefit to this population.

We have initiated a partnership with Cochlear LTD in order to combine cochlear implantation with SENS-401, with the aim of preventing cell death. Cochlear LTD invested €1.6m in Sensorion equity, receiving in exchange a right of first negotiation for a global license to use SENS-401 in combination with its implantable devices.