Public Funding for Senisca Ltd

Here we propose a highly innovative RNA medicine project that will leverage the previous work carried out by SENISCA on the identification of a new and druggable set of target genes to enable significant senescence reversal effect in primary human cell lines. This project is a step forward towards the most innovative and fruitful avenue for novel therapeutics for Idiopathic Pulmonary Fibrosis (IPF), capable, for the first time, of attenuating the disease mechanism and with the potential to reverse the disease rather than mitigating symptoms only. IPF is the most common and aggressive form of interstitial lung disease, which can't be cured, reversed or stopped and current treatment options offer only a palliative solution, as they can only mildly slow disease progression and only in certain patients. Data shows that both incidence and prevalence of IPF are rising sharply and are predicted to continue to do so, leading to a crisis for healthcare systems. A strong team and advisory board have been established to carry out this project, which will ultimately lead to clinical trials of a new drug to stop advancement of the disease or potentially even reverse the fibrotic deposition that occurs during its progression. The expected outcomes are novel oligonucleotide therapeutics capable of reversing senescence in IPF-specific tissues. These new drugs will drive extension of the business strategy and scientific achievement of SENISCA which will contribute to the future generation of revenues and operational growth and strengthen the competitive position of SENISCA as a UK-based RNA medicine biotech. We expect significant benefits for the healthcare system (decrease of annual NHS costs up to ≈£2.5m in 3 years post launch), the UK economy (a reduction of working days lost because of IPF by ≈0.1%, with overall saving of estimated £32m for the UK economy) and a significant improvement of care outcome that will enable better quality of life and care for patients with IPF.

At SENISCA we have discovered a new way by which cells age; loss of alternative splicing, a form of fine-tuning of gene expression. We can restore this process to 'turn back the ageing clock' in old (senescent) human cells. This presents a possible solution to many of the healthcare challenges faced by our ageing society, offering restorative, as well as potentially preventative treatments for common diseases of ageing.  Realisation of the full potential of our technology requires a set of robust and accurate outcome measures with which to measure the rejuvenative effect of our interventions in vitro and in vivo. One such measure will be a multi-tissue 'alternative splicing clock' specific to senescence which can be linked to cellular age.  With this project, we will create a multi-tissue senescence signature for 2 different disease relevant cell types (relevant to cardiovascular and lung function) by growing cells to senescence in culture. Results will also be integrated with data from blood to provide a tissue-relevant clock from an accessible tissue. Samples will be collected at multiple time-points for a full battery of cell ageing measurements alongside the collection of an 'RNA barcode' comprising every splicing event in the cells under test. This dataset will allow us to develop an accurate picture of the gene expression changes that occur during cellular ageing. We will perform a variety of exploratory analyses including differential expression and gene set enrichment to build a network model of cellular ageing, leading to the identification of a minimal-viable set of genes with sufficient power to predict biological age. We will then correlate expression of this subset of genes to the cellular phenotype data, followed by evaluation of their predictive power in a human cohort.  To our knowledge, this will be the first time globally that a multi-tissue transcriptomic biological clock has been mapped specifically to both cellular senescence and chronological age in human samples. This work will produce a number of cell type specific molecular clocks that are specific to senescence. These will be an integral part of SENISCA's toolkit of evaluation measures for our emerging therapeutics, but will have inherent and commercial value of their own. Specific biomarkers for senescence are currently lacking, and the production of a series of tissue specific senescence-specific clocks would be of great interest to other companies striving to attenuate age-related disease by senotherapies and to consumers looking to monitor their biological age.

SENISCA is a biotech spinout company from the University of Exeter, founded in 2020 and dedicated to the development of new approaches to reverse cellular senescence (senotherapeutics). Our founders are world leaders in molecular and cellular biology and have patent-protected an innovation for the reversal of cell aging. This innovation works by restoring the ability of cells to 'fine tune' the expression of their genes to rejuvenate aged cells. At SENISCA, we are using this knowledge, concerning how and why cells become senescent, to develop a new generation of oligonucleotide-based interventions, to turn back the ageing clock in old cells and to target the diseases and aesthetic signs of ageing. Because oligonucleotide therapeutics is one of the fastest-growing therapeutic sectors globally, cutting edge cell delivery technologies are in constant and fast-moving development. To stay abreast of these developments, SENISCA needs to dedicate a strong internal team to the task of securing world leading partnerships for oligonucleotide synthesis and cell delivery in-licensing. This will be a key success factor in our ability to reach Phase 1 to Phase 3 clinical-testing stage for our drug pipeline, and ensure that SENISCA becomes a leading Oligonucleotide therapeutics company globally. The success of these partnerships will also provide a solid foundation to bid for collaborative EU-based grant opportunities and open the door to future co-development pharmaceutical partnerships. We will be assigning research tasks to members of the SENISCA team, sub-contracting research to a drug development market specialist, and sourcing a pharmaceutical partnering agency to assist us with our partner search. We also aim to attend at least one networking event/conference in early 2022 (either online or in person) to increase our international network and visibility. This project will lead to innovation within the senescence field. SENISCA is proposing effective treatments (and potentially cures) for age-related diseases such as Idiopathic Pulmonary Fibrosis (IPF), Osteoarthritis (OA) and Age-related Macular Degeneration (AMD). These diseases currently have limited treatment and no cure. By starting the search for global partners, we will allow for the exchange of scientific knowledge and expertise, and we will accelerate SENISCA's R&D and route towards commercialisation.

Ageing is a universal phenomenon and the primary risk factor for most common, chronic human diseases. Our company, SENISCA, is a spin-out from the University of Exeter, initially focussing on developing molecules suitable for treatment of skin ageing, followed by a wider vision to deliver innovative, effective pharmaceutical treatments for age-related diseases. Ageing occurs at the cell and tissue level because of failure of a few basic health maintenance mechanisms. The research leading to SENISCA's patent-protected innovation has identified a novel molecular mechanism of ageing that can be manipulated for cellular rejuvenation. SENISCA's existing data, showing that rejuvenation of senescent cells is possible, gives rise to the possibility of developing treatments for any age-related disease or condition with a senescence component. This project will focus on identifying combinations of naturally occurring or FDA-approved compounds with anti-ageing properties and obtaining primary safety and toxicity data in preparation for out-licensing to the skin ageing market.