Cambridge, UK – July 20, 2022. Healx, the AI-powered, patient-inspired technology company pioneering the next generation of drug discovery for rare diseases, shared promising data about several AI-predicted candidates for the management of fragile X syndrome (FXS) in a poster and oral presentation at the National Fragile X Foundation’s International Conference in San Diego, California (July 14 – 17, 2022).

Download the poster here. 

Fragile X syndrome is a rare genetic neurodevelopmental condition that affects around 1 in 4,000 males and 1 in 8,000 females, and causes a range of learning difficulties. Individuals affected by FXS also exhibit social, language, attentional, emotional, and behavioural challenges. There are currently no approved therapies for the condition.

In the presentations, titled Discovery of multiple clinical candidates for treatment of fragile X syndrome using AI-enabled drug discovery, Healx shared how their AI drug discovery platform, Healnet, had identified several compounds that could be used as potential medications for FXS. 

Healnet uses sophisticated artificial intelligence (AI) and natural language processing (NLP) methods to analyse millions of drug and disease data points and then rapidly identify completely novel connections between diseases and compounds, without being limited to a single target. For the FXS programme, Healnet leveraged three drug matching methods: 

• DGEM (Disease-Gene Expression Matching), which compares the gene expression profile for a disease with gene expression profiles from Healx’s curated drug database to predict which drugs will be effective based on the most differentially expressed genes in the profiles;
• PRISM (Prediction of Repurposed Indications with Similarity Matrices), which predicts connections based on compound and disease similarities;
• KBC (Knowledge Base Completion), which discovers new drug-disease connections by virtue of graph structure.

The compounds HLX-0201 and HLX-0205 were identified by these methods as lead candidates and were then validated in two preclinical models of FXS, where they were found to modify behaviours similar to those exhibited in people with the condition. Notably, the compounds were able to effectively reverse several behavioural phenotypes, including hyperactivity, stereotypy, cognitive deficits, anxiety, impaired social recognition and aggression. These results were confirmed by three independent contract research organisations (CROs). Another compound, HLX-0206, was also predicted by Healx’s proprietary combination methods (not listed above) to be effective in reducing symptoms of fragile X syndrome, and has been previously tested as a monotherapy for the condition by a third party. 

HLX-0201, HLX-0205 and HLX-0206 all have distinct mechanisms of action targeted towards different pathophysiological pathways. Based on these promising preclinical findings, Healx has initiated a Phase 2a clinical trial to evaluate these candidates in individuals diagnosed with FXS in order to identify a combination therapy that could target different disease processes and pathways. The IMPACT-FXS study (which stands for Investigating Multiple Pathways And Combined Treatments for FXS) is the world’s first umbrella trial for the investigation of therapies for FXS, and will evaluate several compounds first as monotherapies and then as combination therapies in order to identify the best medication. 

Commenting on the data presented, Wayne Chadwick, Principal Pharmacologist at Healx, said: “It is wonderful to be able to share this exciting and promising data with the fragile X community. We are proud to have identified several potential novel candidates for the management of fragile X syndrome, and we are looking forward to evaluating the compounds in a clinical setting in the coming months.”