Healx to Trial Repurposed Drug for Fragile X Syndrome | News

Fragile X Syndrome: A New Clinical Trial Offers Hope

Currently, a definitive cure for Fragile X syndrome – the most prevalent inherited cause of intellectual disability – remains elusive. Existing therapeutic strategies focus on symptom management, addressing conditions like anxiety, obsessive-compulsive disorder, and, infrequently, seizures. However, a novel clinical trial is poised to commence through a U.K.-based startup.

Healx Gains FDA Approval for Phase 2a Trial

On Wednesday, Healx, a drug discovery company, announced receiving FDA investigational new drug status. This approval paves the way for a Phase 2a clinical trial evaluating a repurposed medication for Fragile X syndrome. According to clinicaltrials.gov, the study, assessing the impact of a non-steroidal anti-inflammatory drug on individuals with Fragile X, is scheduled to begin by January 2022.

AI-Driven Drug Development and Healx’s Funding

Healx is at the forefront of companies leveraging artificial intelligence for drug development and identification. To date, the company has secured approximately $67 million in funding, with a recent $56 million Series B round closed in October 2019. Investors include Atomico, Balderton Capital, Amadeus Capital Partners, Intel, Global Brain, btov partners, and Jonathan Milner.

Healnet: Healx’s Machine Learning Platform

Healx’s core technology is its platform, Healnet. This system employs machine learning to analyze data related to existing drugs and potential disease targets, uncovering new therapeutic connections. Healnet can process both structured and unstructured data, including information found in scientific publications.

“The platform ingests all available data into a knowledge base, which then empowers our algorithms to identify potential drug matches,” explains Dr. Anthony Hall, Healx’s chief medical officer, in an interview with TechCrunch. “These algorithms seek correlations between diseases and drugs, guiding our selection for preclinical and clinical trials.”

The Rise of AI in Pharmaceutical Research

AI-driven drug development is rapidly gaining prominence within the broader AI landscape. Funding for this field surged to $13.5 billion between March 2020 and 2021, representing a 4.5-fold increase compared to 2019, as reported in The AI Index 2021 Annual Report by Stanford University. While the COVID-19 pandemic likely contributed to this increase, significant funding rounds, such as Insilico Medicine’s $255 million Series C in June, demonstrate sustained interest. Furthermore, numerous companies have established deals with major pharmaceutical firms.

Focus on Rare Diseases

Healx currently concentrates its efforts on rare diseases. Beyond Fragile X syndrome, the company has potential treatments for Pitt Hopkins syndrome in clinical planning, with an additional 11 candidates undergoing preclinical development.

Hall adds, “We have several other programs progressing through the pipeline.”

Collaboration with FRAXA

Throughout its research, Healx has maintained a close partnership with FRAXA, a nonprofit research foundation dedicated to Fragile X syndrome. Michael Tranfaglia, FRAXA’s chief scientific officer and medical director, emphasizes that Healx and FRAXA collaborated from the outset, even before the typical involvement of patient organizations in clinical trial processes.

“Our involvement has been comprehensive throughout the entire process,” he states to TechCrunch. “We’ve provided crucial information that has aided the company in curating relevant datasets.”

Drug Repositioning: A Cost-Effective Approach

Healx’s strategy centers on identifying existing drugs for new applications, rather than developing novel compounds – although Hall notes that future development of new drugs is not excluded. Utilizing existing drugs, known as drug repositioning, offers advantages, particularly in the realm of rare diseases. It reduces development costs and is considered a viable method to accelerate research in areas often overlooked due to limited potential for profit.

A 2021 review published in Trends in Pharmacological Sciences indicates that repurposed drugs can reach patients in three to twelve years, compared to the ten to fifteen years typically required for new drugs.

From Serendipity to Systematization

Historically, drug repurposing relied heavily on chance discoveries. However, a 2011 paper highlighted the need for a more “systematized and rational” approach, moving beyond mere serendipity.

Healx’s approach leverages artificial intelligence to address this challenge.

Future Clinical Trials and Adaptive Study Design

Healx’s upcoming clinical trial for Fragile X syndrome will be its first to evaluate a repurposed drug. The company envisions this trial as the initial phase of an adaptive clinical study, continuously incorporating and testing additional drugs identified by Healnet and validated through preclinical testing.

Hall reveals plans to include two more drugs in the trial, withholding their names to prevent off-label use. He clarifies that these three drugs target distinct mechanisms related to Fragile X syndrome.

Evaluating Cognitive and Anxiety-Based Endpoints

The trial will assess the drugs’ effectiveness across two primary categories of endpoints in Fragile X research: cognitive function and anxiety-related measures.

Shifting Perspectives on Autism and Fragile X

Within autism research – as individuals with Fragile X are often also diagnosed with autism – the pursuit of a “cure” has become less central. For some, autism is viewed as a natural variation in human experience, not a condition requiring eradication. Alternative perspectives suggest that societal barriers, rather than biological factors, hinder the well-being of neurodivergent individuals.

Research indicates that therapies and supportive environments are beneficial for individuals with Fragile X. While drug-based treatments can manage symptoms like hyperactivity or anxiety, Tranfaglia notes that current options can be ineffective or cause undesirable side effects.

He explains, “Treating hyperactivity with medication can sometimes exacerbate anxiety.”

“It’s a constant cycle of addressing one symptom with a drug, only to have it create new problems elsewhere,” he says.

A Multi-Pronged Approach to Treatment

The upcoming study involving three different drugs reflects a multifaceted approach. Hall describes it as “putting multiple shots on goal.” Tranfaglia adds that this strategy aligns with the understanding that addressing complex rare diseases like Fragile X will likely require a combination of therapies.

“Our ultimate goal is to identify the optimal two or three drug combinations for each of the 7,000 rare diseases, utilizing these 1 or 200 repurposing candidates,” Tranfaglia states.

A Promising First Step

This study represents an initial step, but it underscores a growing trend in rare disease treatment: the potential of existing drugs, previously undiscovered due to a lack of appropriate tools.