Process and non-clinical development of a stem cell therapy for hearing loss

Half a billion people in the world have disabling hearing loss resulting in enormous personal, social and economic hardship. The vast majority of hearing loss cases are produced by the loss of sensory hair cells and/or their associated neurons. Mammals in general, and humans in particular, do not have the ability to restore these cells. We are born with a complement of cells that should last a lifetime. When these are damaged, permanent deafness ensues. The current standard of care is based on hearing devices, such as hearing aids and cochlear implants. However, these devices do not address the underlying problem of cell loss. Currently, no treatments that can regenerate or restore cells exist for hearing loss.
Rinri Therapeutics is developing a new treatment, 'Rincell-1', a cell therapy with the potential to replace dead or damaged nerve cells in the inner ear and restore hearing. In order to reach clinical trials, Rinri needs to adapt the methods to generate the relevant cells currently used in a research lab to an industrial standard that fulfils the stringent manufacture and safety regulations.
Rinri have been working with its founder and creator of the original technology at the University of Sheffield, translating the research from the academic lab and making it compatible with a cell manufacture organization. We request funds for the secondment of Dr. Leila Abbas, a researcher with expertise in hearing loss and stem cell technology working at the University of Sheffield, to Rinri, in order to manage and accelerate the development of these industrial processes. This secondment will prove directly beneficial to Leila, Rinri, the University of Sheffield and the hearing loss scientific community. Specifically, Leila will learn about the strategies, challenges and regulations involved in the manufacture of a cell-drug product. Along with her existing research skills, this will provide her with an almost unique skillset in the biotech industry in the hearing field that could be applied to the development of other novel hearing therapies in the future, which are desperately needed to address the global burden of hearing loss. Likewise, Rinri will gain from Leila's extensive knowledge of the fundamental biology underpinning hearing and deafness, the behaviour of stem cells along with her unique understanding of hearing scientists and Rincell-1's target population: people with hearing loss. Ultimately, this secondment will enhance the exchange of ideas between Rinri and the University of Sheffield towards the development of a revolutionary new treatment for hearing loss.

Disabling hearing loss has a devastating effect on communication, education and employment. Sensorineural hearing loss is produced mostly by damage to the hair cells and/or their associated neurons. Hearing aids and cochlear implants (CIs) are the only therapeutic option and, although many have benefited from their use, they are not suitable for every patient and cannot fully restore normal hearing.
To address these deficiencies, Rinri Therapeutics is developing a first-in-class, stem-cell-derived therapy, Rincell-1, which aims to restore hearing by replacing damaged cochlear neurons. This should provide a true regenerative, biological therapy to patients affected by auditory neuropathy.
Work performed at the Rivolta Lab at the University of Sheffield generated protocols to drive the differentiation of human pluripotent stem cells into otic neuroprogenitors and established proof of concept for functional restoration. Further work identified cellular markers to purify the relevant cell types, and is demonstrating the cells biosafety. However, there is now the need to move these processes from the academic lab into an industrial setting. We are requesting funds to support the seconding of Dr Leila Abbas, a highly experienced postdoctoral researcher from the Rivolta lab with expertise in hearing loss and otic stem cells, into Rinri.
Rinri has designed a GMP cell manufacture strategy, analytical and quality control (QC) procedures as well as identified key elements to be developed in the preclinical and safety path. Dr Abbas will refine and adapt them to the requirements of cell manufacturing organizations, generating new data. She will help to manage and incorporate outcomes from several work packages into the broader product development plan and interact with process development/CMC, non-clinical safety, regulatory and other clinical advisors at Rinri to build a unified and coherent approach leading to Rinri's first-in-human clinical trial authorisation.