Public Funding for Elasmogen Limited

no public description

To develop new targeted nanomedicines for the treatment of cancers with unmet clinical need using variable New Antigen Receptor technology.

To develop the knowledge and capability to design, construct and test new and efficacious bi-specific drugs for liver disease; a 'silent-epidemic' driven by growing levels of obesity and diabetes and where no effective drugs currently exists.

"Despite marked improvements in outcomes for cancer patients, 35% will succumb to the disease. First line chemotherapy treatments generally rely on the sensitivity of fast-growing cancers being more susceptible to toxic agents than ""normal"" healthy cells. The unpleasant side-effects of this treatment, together with a poor prognosis means there is an urgent need for new targeted therapeutics to improve patient health. Developments to-date have included the targeted delivery of drugs to cancer cells as a way of limiting toxic side effects on healthy tissues. Targeted therapies based on monoclonal antibodies have been used with some success. However, their ""killing power"" can be ineffective against larger solid tumours. To ramp-up their potency, tumour targeting antibodies have been conjugated with highly potent cytotoxic drugs, and antibodies have been engineered that simultaneously target two different cancer proteins in order to improve tumour selectivity. Whilst these antibody drug conjugates (ADCs) and bi-specific antibody approaches show promise, the large size and complexity of antibodies limits their tumour penetrating ability and the ability to engineer therapeutic improvements. Furthermore, the cost of manufacture and off-target side effects are still significant problems for these agents. Consequently, next generation approaches using 'smaller' protein therapeutics with improved tumour penetration, increased stability and less toxicity hold great promise. To meet this challenge, the aim of this project is to build a platform technology for the accelerated development and optimisation of novel oncology medicines based on antibody-like single domain receptors found in sharks (VNARs). Shark VNAR domains are the smallest naturally occurring antigen binding domain in the animal kingdom and their properties are potentially advantageous for cancer therapy. In an initial collaboration between Almac Discovery and Elasmogen, we have shown that high affinity VNARs can be generated to an oncology target and that these VNARs can be site-specifically modified using a bio-conjugation technology developed by Almac Discovery. The aim is to build on this initial proof-of-concept research by combining Elasmogen's expertise in the generation and screening of VNAR proteins, with Almac Discovery's expertise in protein engineering and oncology drug discovery. The idea is to develop a modular VNAR ""plug-and-play"" platform for the accelerated development of innovative VNAR cancer drugs. Successful development of a platform technology that can overcome the limitations of full-length antibodies, and rapidly deliver VNAR therapeutic candidates with improved efficacy, will enable the full potential of these next-generation approaches to be realised and significantly improve human health."

Elasmogen’s technology is a unique soloMER™ drug platform exploiting the power of proteins (biologics) as drugs but in small, simple and stable formats. Elasmogen have a pipeline of products in pre-clinical development for the treatment of inflammatory diseases of the eye. Current first-line therapies for these diseases are corticosteroids, but up to one third of patients fail to respond with many more suffering side-effects and the real risk of going blind. The use of targeted protein-based approaches have shown benefits, and particularly in this group of unresponsive patients. There remain however, significant efficacy limitations to the current use of biologics. Their large molecular weight and “fragile nature” limits routes of drug administration to injection into the blood stream or directly into the eye. This funding will progress our existing “next-generation” biologic therapies that, despite their size, are potently anti-inflammatory but are also stable, soluble and therefore amenable to non-invasive, site-specific, topical delivery (eg modified eye drops).

Even though there has been a marked improvement in the outcomes for cancer patients, 35% will still eventually succumb to the disease. Treatments still require clinicians to balance the administration of anti- cancer toxins with extreme patient side-effects. Therefore, there remains a significant need for more specific cancer therapies, providing opportunities for innovative drug development. This proposal combines the power of proteins call soloMERs™ (produced by the lead organisation Elasmogen Ltd), that can bind specifically to tumours, with microscopic drug filled (nano)particles (produced by Queen’s University Belfast), to target toxic payloads directly into cancerous cells, minimising the insult to surrounding healthy tissue. soloMERs™ small size and robust nature makes them ideal “escort” proteins suitable for joining to and decoration of the surface of nanoparticles. It is hoped that this approach could deliver 1000 times more drug than competing technologies with these first sNaPs™ having the potential to be a new platform approach to the treatment of solid cancer masses.ject Summary