Most people know someone who has gone through chemotherapy. Though the treatment helps rid a person of cancer, patients often suffer from a slew of unwanted side effects. One of the most common of these is chemotherapy-induced peripheral neuropathy (CIPN). This is where nerves in the arms, legs, hands, and feet are damaged, leading to sensory numbness, muscle weakness, and pain. Sylvain Celanire, CEO of Augustine Therapeutics, explains:
“About 60% of people who receive chemotherapy are affected by CIPN, the symptoms become chronic for 30%–40% of patients. This side effect severely affects many people’s quality of life, even after they’ve gone into remission from the cancer.”
Augustine Therapeutics is developing a compound to not only alleviate the symptoms of CIPN, but also to reverse the nerve damage at the axonal level (axonopathy) altogether. The company traces its origins back to the VIB-KU Leuven lab of Prof. Ludo Van Den Bosch, where researchers discovered that molecules inhibiting the HDAC6 enzyme have the capacity to repair damaged axons and neurons, and restore nerve conduction defects.
Van Den Bosch realized that HDAC6 inhibitors could have therapeutic applications in a range of diseases in both the central and peripheral nervous system. So in 2019, he founded Augustine Therapeutics with a seed financing round of €4.2 million supported by VIB, V-Bio Ventures, and other investors.
Read this article on how VIB Discovery BioSciences helped Augustine Therapeutics bridge the ‘Valley of Death’!
Prevention: even better than a cure
The company’s initial therapeutic focus was on developing HDAC6 inhibitors for the treatment of Charcot-Marie-Tooth (CMT), a debilitating genetic disorder where peripheral nerves become damaged over time. Now, studies have shown that their proprietary HDAC6 inhibitors have a huge therapeutic potential in both CMT and CIPN.
“The huge advantage is that our HDAC6 inhibitors are able to not only reverse the axonal damage, but also prevent it from happening in the first place,” says Celanire. “We’ve unambiguously demonstrated this in animal models and human tissue models for CMT, and now validated it for CIPN. Both nerve function and axonal damage is rescued through electromyography and biomarker measures, that are routinely monitored in patients . The protective aspect would be especially valuable for chemotherapy patients – many of whom will develop CIPN during the course of their cancer treatments – and could last for months or years.”
“The real blockbuster potential of our lead candidate lies in its ability to both prevent disease but also reverse the damage already done.” – Sylvain Celanire
A large number of companies have tried to develop first generation of HDAC6 inhibitors in the past, but faced liabilities due to a chemical functionality known to be genotoxic. This precluded further development for chronic diseases such as CMT, which require life-long treatments. While several biotech companies have now shifted to alternative chemical series, limitations have arisen, including modest efficacy on critical motor function parameters and signs of chemical instability, states Celanire:
“Our company is developing a completely novel class of HDAC6 inhibitors that are selective, specific, orally available and extremely well tolerated over weeks of treatment in preclinical disease models. Our robust intellectual property portfolio comprises patent applications not only on composition of matter but also on the use of HDAC6 in CMT, granted in Europe and other countries. This gives us a lot of traction from local and international investors as well as pharmaceutical companies, with several already in active due diligence.”
Read this article to find out more about Augustine Therapeutics’ work on CMT.
Moving into the clinic
Augustine Therapeutics is now working towards the first clinical trials in both CMT and CIPN. To support the next phase of activities, a Clinical Advisory Board has been set up with global experts on small-molecule therapy trials in CMT, CIPN, and neurodegenerative disorders (e.g. ALS). In anticipation of future clinical work, the company has also established close connections with CMT patient advocacy groups in Europe (the European CMT Federation) and US, as well as with local and European clinical centers, to facilitate patient enrollments and trials.”
“With a pipeline-in-a-product approach, our drug presents a potentially life-changing breakthrough for patients around the world.” – Sylvain Celanire
Recently, Augustine Therapeutics appointed Gerhard Koenig – CEO of Arkuda Therapeutics in the US – as Chair of the Board. The company is also expanding the team and its biology platform, aiming to move into offices and labs in the new bioincubator in Leuven by the end of 2022. To support all this growth and development, the company is currently raising a Series A financing round. Celanire has high hopes for the future:
“With a pipeline-in-a-product approach, our drug presents a potentially life-changing breakthrough for patients around the world. Though we’re initially targeting CMT and CIPN, there are many other disorders of the peripheral and central nervous systems where our approach may be of use. We have recently discovered novel HDAC6 inhibitors capable of reaching the brain to treat severe life-threatening diseases such as ALS. The real blockbuster potential of our lead candidate lies in its ability to both prevent disease but also reverse the damage already done.”