SUMMIT: SiRNAs Utilising Mergo? delivery for post-Myocardial Infarction Treatment

点击翻译按钮获取中文摘要

SUMMIT aims to develop and validate Sixfold's oligonucleotide delivery system, Mergo?, for delivery of (simultaneously developed) short-interfering RNA (siRNA) gene silencing cargo to a specific tissue type (undisclosed). SUMMIT combines multidisciplinary partners with highly complementary expertise and experience in delivering successful projects, with rapid scientific and commercial progress towards early-stage R&D collaboration.Compared to small molecule and antibody-based drugs, siRNAs can act on virtually unrestricted choice of--otherwise "undruggable"--therapeutic targets, with high specificity and potency; while their easy manufacturing facilitates rapid lead optimization\[1\]. Therefore, siRNAs have the potential to effectively treat numerous diseases. Initial regulatory approvals of Alnylam's siRNA therapies for liver disorders in 2018-19 \[1-2\] validated clinical and commercial opportunity for such therapies. However, the major limiting factor for further success remains the lack of effective platforms for systemic delivery of siRNAs to specific diseased cells\[4\]. Current approaches, primarily GalNAc-conjugates, lipid nanoparticles and viral vectors, are sub-optimal given their limited cell targeting specificity, cargo loading capacity, high toxicity, and complex/expensive manufacturing that limit the addressable disease indications.Mergo? addresses this challenge through its modular design based around a central RNA nanoscaffold. This can be functionalised with therapeutics and targeting molecules that recognise biomarkers on specific cells of interest only. This allows the platform to target only diseased cells, thus significantly reducing toxic side-effects from the therapy in other cells and tissues. Although previous Mergo? data demonstrated promising _in vitro_ and _in vivo_ results, highly competitive safety and favourable cost profiles, further validation of mechanism-of-action is required for specific tissue types.SUMMIT will develop an in-house siRNA targeted towards a specific extrahepatic tissue, and exploit the versatility of Mergo? using nucleic acid chemistry to improve delivery via tissue targeting. This will generate an in-house asset(s), speed candidate development, and act as a demonstrator for application of Mergo? to deliver diverse cargo (mRNAs, CRISPR therapeutics) and to target other indications. Consequently, Mergo? represents an attractive opportunity to capture a significant portion of the thriving gene therapy and delivery markets and could accelerate other Advanced Therapy Medicinal Products (ATMPs), through improved safety, efficacy and reduced cost of goods, especially compared to viral technologies.Pharmidex and MDC's unique expertise in advanced preclinical screening and imaging enables generation of preclinical data-pack for rapid commercialization and clinical advancement via licensing.Sixfold's broad IP portfolio and licensing strategy engages the entire biopharmaceutical supply chain, providing diverse benefits to the wider UK life sciences sector.\[1\]Lam\_J.K.W\_et\_al.\__Mol\_Ther\_Nucleic\_Acids_\_2015\_4(9):e252\. \[2\]Alnylam\_Press\_release\_10\_August\_2018\.\[3\]Payne\_D\__Nature_\_574\_S1\_2019\.