Partnering with EpicentRx

Bryan Oronsky and Scott Caroen from US pharmaceutical company EpicentRx presented to the OneTRI Conference via Zoom on October 3, 2023. Here an adaptation of that presentation.

The Imitation Game

Drug development is not for the faint of heart. It takes 10-15 years to bring a new drug to market with an average cost of $1-2 billion. Add to this the more than 90 per cent of drugs in development that fail and it is not hard to see why many pharmaceutical companies prefer to modify or upgrade what is already there. It takes nerve to set a new course and direction. It is much simpler, safer and cheaper to follow a path that has already been cleared of obstacles, make a few - usually minor - improvements or tweaks along the way, and then patent them.

Meanwhile, many different disorders lack effective therapies - and options for patients are few and far between.

Liftoff

Not at all content to play this imitation game was a successful Silicon Valley venture capitalist and long-time pharma executive.

Having decided to flip the imitative drug development script, they put his resources behind a team that eventually became EpicentRx, a California biopharmaceutical company. Their mandate was to form a partnership with the American aerospace and defense industry to screen several high-energy rocket propellants for anticancer activity and to create truly novel therapeutic categories in the process. The expectation was that these propellants would decompose to form tumor-damaging free radicals, which synergize well with radiation. A problem immediately presented itself. Nitrogen-rich rocket propellants are explosive. Fortunately, hundreds and hundreds of them were available to screen.

Still, it was no surprise that the word “explosive” was not a big selling point with investors—or with the FDA. The solution was to replace one or more of the explosive side groups on these compounds with non-explosive ones. In the case of the small molecule that came to be known as RRx-001 (and the generic name nibrozetone), a nitro group was replaced with an acyl bromide group, rendering it non-explosive.

And just like that, EpicentRx achieved liftoff.

Beyond Cancer

EpicentRx announced that it planned to develop nibrozetone as a radiosensitizer, meaning a drug that partnered with radiation therapy and made it better.

But it was also much, much more. Which presented a problem of sorts. Because small pharmaceutical companies such as EpicentRx are funded to develop one molecule in one indication, not one molecule in several. The company didn’t have the resources or the bandwidth to expand. Fortunately, EpicentRx managed to find investors and financial support. The company expanded almost overnight from five fulltime employees to 15.

Nibrozetone showed promise in neuroinflammation and neurodegenerative diseases such as Parkinson’s, Alzheimer’s and motor neurone disease. However, EpicentRx was a company with anti-cancer - not neurodegenerative - expertise. CEO Dr Tony Reid is a Stanford University-trained gastrointestinal oncologist and virologist. For all the experience in and with cancer, Dr Reid and the rest of the EpicentRx team were out of their depth when it came to the treatment of neurodegenerative diseases. EpicentRx needed a partner.

EpicentRx meets QLD Researchers

Enter Richard Gordon, an associate professor from QUT and TRI. During its due diligence, EpicentRx consistently came across a landmark research paper authored by Dr Gordon and collaborators in the journal Science Translational Medicine. Data from the work, conducted while Dr Gordon was based at The University of Queensland, was foundational to demonstrate that the inflammasome was a druggable pathway that can be targeted with drugs to switch off the master regulator of inflammation and thereby treat the progression of devastating neurological diseases such as Parkinson’s and Alzheimer’s disease. 

A preclinical collaboration with Dr Gordon and QUT kicked off via Zoom in 2020, during the COVID lockdown. To date, it has yielded two sought-after grants with significant funding from the Michael J. Fox Foundation, Shake It Up Australia and Fight MND, as well as high-impact publications. A/Prof. Gordon's team at TRI has generated promising data that shows nibrozetone can block the master regulator of inflammation in the brain, suggesting that it could have potential to be developed for neurological diseases in the future.

QUT, TRI and Beyond

Given the promising results to date from their QUT and TRI collaboration, EpicentRx has ambitious plans to establish a satellite research facility in Brisbane to develop new treatments for devastating neurological diseases, by progressing nibrozetone and other promising molecules in their pipeline for these devastating conditions. The first clinical trial of nibrozetone for Parkinson’s disease is planned for early 2025 - and is due to be conducted in Brisbane.