Posters

We have developed RxNfinity™ as a new structure-based screening platform for the hierarchically docking and subsequent elaboration of synthon libraries in the context of the binding site of the target structure, allowing for the sampling of more than 1 trillion compounds. RxNfinity™ uses a Monte Carlo sampling method to overcome the limitations of hierarchical docking and identify optimum fragment-like first round binders with favourable interaction energies. These initial hits are further elaborated and refined within the context of the binding site through a library of codified chemical reactions, generating high quality and synthetically tractable drug-like hits. In contrast to conventional in silico approaches, the RxNfinity™ platform allows for the rapid exploration of dynamic chemical space in the context of the target structure through iterative rounds of molecular editing towards an objective function. This new approach has been successfully validated on a wide range of different target classes for the identification of novel synthetically tractable bioactive compounds. Herein, we present a case study for the human G protein-coupled receptor, GPR183, where RxNfinity™ was successfully deployed to identify several chemically distinct drug-like hit series with higher hit rates and potencies than those observed for the same target using a conventional virtual screening approach. These results demonstrate that RxNfinity™ can be used to generate novel synthesisable starting points for drug discovery projects by rapidly sampling ultra large and synthetically tractable chemical space in the context of the target binding site.

We have engineered and constructed the Galaxy® antibody library that underpins our proprietary platform. Our ‘glass spleen’ approach incorporates the learnings of the in vivo selection process and allows us to access a far greater fraction of relevant antibody space. Based on the principle of ‘smart randomness’, the Galaxy® library harnesses the incredible diversity found within human B cells in a focused way, maximising the proportion of correctly folded functional antibodies. This process results in potent antibodies without the need for excessive mutational load. The Galaxy® platform is geared for generation of ‘clinic ready’ antibodies straight out of the library. Furthermore, the design provides the potential to rapidly generate cheap to manufacture bispecifics without the need for any special technology or engineering. At RxBiologics our capabilities extend to screening for desired specificity and cross-reactivity, NGS analysis, in silico developability and immunogenicity screening, profiling for functional activity, antibody production, affinity determination, epitope and biophysical characterisation.

NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) mice are severely immunocompromised and require careful handling and strict biosafety protocols to maintain their health status.

Despite their genetic mutations, NSG mice typically do not display any gross physical or behavioural abnormalities (JAX, 2024). However, in recent years, we have observed a subset of NSGs (~30%) in our research labs developing a progressive tarsal lesion phenotype similar to that previously reported by MacLeod et al. (2017) in huNOG mice and Campagna et al. (2021) in NSG mice.

The phenotype initially presents as either unilateral or bilateral rounding of the hock, progressing to swelling and reddening of the tarsal joint, eventually advancing to ulceration of the skin. Toe curl, grip strength and gait are typically also impacted in the affected limb(s).

Using one of our internal R&D studies, we developed a scoring system and treatment plan to support affected animals through the acute phase, and subsequently collected samples to investigate the pathological changes occurring in the affected hocks.

For eight years Methuselah Health UK Ltd worked on developing a label-free proteomics platform that was as precise as possible to enable quantitative analysis of posttranslational modifications. Following the acquisition of Methuselah Health by RxCelerate in September 2022 the platform was launched as ProQuant® and is available right now with the power to speed up and derisk multiple phases of the drug development pipeline.

The ProQuant® platform is based on a standard bottom-up proteomics protocol, with a number of key enhancements that drive the analytical performance. These include optimisations to the sample preparation, changes to the way the mass spectrometer collects data and improved data analytics. We also use machine learning to improve peptide identification and reduce artefacts. Importantly, all these processes are unsupervised, eliminating bias related to the biological question being introduced into the data.

In 2022, 2.3 million women were diagnosed with, and 670,000 women died from breast cancer globally (WHO, 2024). Breast cancer is therefore the most prevalent cancer in women. Although localised conditions have a survival rate of 85%, the survival rate drops to 23% for women with distant metastases (Iorns et al., 2012). RxCelerate has previously designed and used bespoke cancer models for specific clients. However, the aim of this internal study was to develop and validate a model that mimicked the earlier stages of breast cancer, to eventually offer clients an ‘off-the-shelf’ metastatic model to test cancer drugs against.