Public Funding for Drishti Discoveries LTD.

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that causes death in patients within 3-5 years of diagnosis. Riluzole is the only approved drug in the UK that extends survival by 6 months. Increasing research in the pathophysiology of ALS has led to a deeper understanding of molecular mechanisms underlying the disease progression. Recently several exciting targets have been identified. Many of these targets are not druggable using the conventional small molecule and monoclonal antibody-based approach. RNA targeting gene therapy has emerged as a promising modality, extending druggable targets for the treatment of ALS. Drishti Discoveries is an Advanced Therapy company developing disease-modifying gene therapy for rare diseases using a proprietary miRNA-adapted shRNA technology. We are applying this RNA-targeting technology to develop a long-term treatment for ALS. Our data so far show we can significantly silence our gene of interest and rescue motor functions in an acute ALS mouse model. In this project, we aim to further progress the programme. We will confirm the efficacy of our candidates in an independent ALS mouse model to bring our innovative gene therapy product one step closer to the clinic for patients in urgent need.

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that causes death in patients within 3-5 years of diagnosis. Riluzole is the only approved drug in the UK that extends survival by 6 months. Increasing research in the pathophysiology of ALS has led to a deeper understanding of molecular mechanisms underlying the disease progression. Recently several exciting targets have been identified. Many of these targets are not druggable using the conventional small molecule and monoclonal antibody-based approach. RNA targeting gene therapy has emerged as a promising modality, extending druggable targets for the treatment of ALS. Drishti Discoveries is an Advanced Therapy company developing gene therapy for rare diseases using a proprietary miRNA-adapted shRNA technology. We are applying this RNA-targeting technology to develop a long-term treatment for ALS. Our data so far show we can significantly silence our gene of interest. In this project, we aim to develop a multi-target candidate. We will undertake a technical evaluation of our multi-target gene therapy concept, and perform proof-of-concept studies in an in-vitro model of ALS to bring our innovative gene therapy product one step closer to the clinic for patients in urgent need.

Retinitis Pigmentosa (RP) is one of the leading causes of blindness worldwide. RP is a highly heterogeneous disease caused by mutations in one of over 60 genes. Due to the genetic nature of the disease, in-vivo gene therapy is considered to be the most promising approach to treating RP. However, the challenge of developing gene therapies for RP is that many of the underlying gene mutations are ultra-rare making them unattractive for therapeutic development. An approach that allows the development of a single precision therapy that would benefit a larger patient population irrespective of the underlying genetic cause is highly desirable. The proposed project will develop a proof of concept for a gene agnostic therapy for RP that will benefit a broader patient population.