Project background

The Receptor for Advanced Glycation End products (RAGE) is a type I cell-surface transmembrane receptor member of the immunoglobulin superfamily, and has been observed to show increased expression in certain cancers. RAGE expression in healthy tissue is in general absent or very low with the exception of lung, making it an ideal target for ADC therapy. As proof of concept, in vitro and in vivo studies confirmed the toxicity and specificity of our ADCs for ovarian and endometrial cancer cells. Additionally, our ADCs are more efficacious in vitro than an ADC equivalent to the clinically approved ADC, Kadcyla®.

Technology summary

We have significantly advanced the pre-clinical development of our ADCs by using a proof-of-concept IgG2-ADC and undertaking in vivo and ex vivo distribution and toxicology studies. The successful completion of this initial project has confirmed that (1) our ADCs have no systemic toxicity confirming previous observations that the target is non-essential to life, (2) The tissue distribution profile following intravenous administration of the ADC, confirms it accumulates in the tumour of tumour-bearing animals and in the reproductive organs (endometrium and ovaries) of non-tumour and tumour-bearing animals, (3) the ADC molecules has the ability to penetrate tumours and reduce the effectively reduce the tumour volume when tested in a xenograft model of endometrial cancer (in vivo animal study) (J Immunother Cancer.2019 Oct 29;7(1):280. doi: 10.1186/s40425-019-0765-z).

Benefits/Advantages

Antibody Drug conjugates (ADCs) are among the first generation of targeted therapies with the potential to transform cancer treatment. These novel therapeutic agents are armed antibodies with lethal cytotoxin payloads targeting cancer cells while sparing healthy cells and reducing side effects. These target-seeking molecular missiles have proven very effective in oncology applications, and are exemplified by Adcentris and Kadcyla, currently in the market. To date, a total of ten ADCs have been approved by the FDA, of which 6 have been approved in the last 18th months. Aiming to develop novel therapeutics against these gynaecological cancers, we have identified a novel target for ovarian and endometrial cancer therapies and developed a therapeutic modality based on antibody drug conjugates (ADCs).

Market application

At a similar cost to Avastin, £25,000 for a 7-month course, RAGE-ADC this could translate to a market of £177 million in the UK alone, and around £1.6Bn in Europe, with an expected higher market in Asia. Even if the drug were restricted to those who presented with advanced disease, this represents around 80% of all new diagnoses, due to the absence of symptoms in early-stage disease of disease. This represent a strong clinical and commercial case for development of a novel RAGE antibody drug conjugate targeting ovarian cancer. The potential market value of an ADC is given by the uniqueness of its target. The ADC market is avid of new molecules as evidenced by the increased amount of partnership and licensing agreements. We aim to approach major ADC development companies as our engagement strategy for the RAGE ADC programme.

IP status

Granted as EP3209694, US 10,406,124, and pending applications CA 2963744 and US 16/541,107

Ways of collaboration

· Joint technical collaboration

· Technology commercialization in China

· Capital seeking