Resources for clinicians
Rinri Therapeutics was founded in 2018 by Marcelo Rivolta, Professor of Sensory Stem Cell Biology at the University of Sheffield (UK). The company receives senior leadership and strategic direction from a number of clinical key opinion leaders who are frontline clinicians, passionate about improving outcomes for hearing loss patients across the spectrum of hearing conditions.
We are committed to driving responsible improvement, responding to new evidence and new ways of working, and working collaboratively with the clinical community to ensure we deliver the care our patients need.
We have prepared below some responses to frequently asked questions to help you understand our mission, and how you and your patients might be able to get involved.
Since Rinri’s lead product candidate, Rincell-1, aims to regenerate auditory neurones, individuals with presbycusis or Auditory Neuropathy will be treated first, as these conditions are are associated with the loss and/or dysfunction of auditory neurones.
While initially focusing on patients with auditory neurone-related hearing loss, we will continue to consider a broad range of aetiologies and populations to better understand the individuals our therapeutic candidate may treat.
Rinri has capitalised on its unique deep understanding of developmental and auditory biology to build protocols to produce auditory neuron progenitor cells. These cells have been engineered to match natural cochlear phenotypes and functional physiological characteristics.
Under the right conditions, we have shown that these progenitor cells are able to mature into functional auditory neuron cells which exhibit the same morphology and electrophysiology as native cells of the inner ear.
Our preclinical studies have clearly demonstrated that when we deliver our cells to the damaged cochlea, they survive, engraft, mature, and re-establish neural connections to auditory hair cells and the wider auditory neural architecture. In models of auditory neuropathy these cells result in a reversal of hearing loss and a ~40% improvement in the ABR hearing threshold 1.
1 Chen, W., Jongkamonwiwat, N., Abbas, L. et al. Restoration of auditory evoked responses by human ES-cell-derived otic progenitors. Nature 490 (2012). https://doi.org/10.1038/nature11415
The human inner ear contains minute three-dimensional neurosensory structures that are deeply embedded within the skull base, rendering them relatively inaccessible to regenerative therapies for hearing loss. Rinri has worked with an international consortium of clinicians, surgeons and anatomists to establish a viable and safe delivery route for therapeutic intervention into the cochlea. In 2022 we reported our initial work providing a detailed characterisation of the functional architecture of the space that hosts the cell bodies of the auditory nerve 2. We used synchrotron phase-contrast imaging which offers the required microscopic soft-tissue contrast definition while simultaneously displaying precise bony anatomic detail. Using volume-rendering software we constructed highly accurate 3-dimensional representations of the inner ear. Modelling data from temporal bones enabled the definition of a safe trajectory for therapeutic access while preserving the cochlea’s internal architecture. We validated the approach through surgical simulation, anatomical dissection, and micro-radiographic analysis.
2 Li, H., Agrawal, S., Rohani, S.A. et al. Unlocking the human inner ear for therapeutic intervention. Sci Rep 12 (2022). https://doi.org/10.1038/s41598-022-22203-2
Cochlear health can be broadly defined as a cochlea free from disease, illness or injury as evidenced by good hair cell and spiral ganglion function, aligned with a lack of evidence of inflammation. It is important to better understand the influence of cochlear health on hearing loss treatment outcomes and to assess the safety and efficacy of future novel treatments for deafness that will be administered as adjunctive therapies to cochlear implantation.
Until recently, it has been notoriously difficult to measure cochlear health. However, due to technological advances, an additional advantage of an adjunctive approach is that post-operative monitoring of cochlear health can be performed telemetrically using the cochlear implant (CI) electrode. Unlike other assessment methods, the CI electrode provides direct access to the cochlea, enabling cochlear health parameters to be continuously recorded. Rinri has been working with an international consortium to evaluate the feasibility of using a CI to assess cochlear health and examined patterns of electrode impedances, electrically-evoked compound action potentials (eCAPs) and electrocochleography (ECochGs), over time. We recently published this data which demonstrated that it is feasible for CI users to independently record CH measurements using their CI, and electrode impedances and eCAPs are promising measurements for objectively assessing cochlear health3.
3 Mushtaq F., Soulby A., Boyle P. et al. Self-assessment of cochlear health by cochlear implant recipients. Front. Neurol 13 (2022). https://doi.org/10.3389/fneur.2022.1042408
Following our ground-breaking proof of concept data, significant progress has been made to refine and optimise our process technology, improving yield, efficiency, potency and purity, and build a robust preclinical safety data package to the high level required to gain regulatory authorisation to enter first-in-man clinical trials. We are currently finalising our clinical protocol and aim to be recruiting patients within the next 2 years. Further details will be uploaded to our website and social media accounts but for more information, please contact clinical@rinri-therapeutics.com