In August 2020, V-Bio Ventures announced their investment in Biodol Therapeutics, a French start-up looking to make a difference to people suffering from chronic pain. The company is developing a drug to treat neuropathic pain by addressing the interplay between nerves and the immune system. In a billion-dollar market dominated by ineffective and dangerous painkillers, their unique approach could reduce the suffering of millions.
By Amy LeBlanc
Everyone knows the feeling of pain. Whether from a papercut, bruise or serious injury, we’ve all experienced how distracting and consuming the sensation can be. For many unfortunate people, pain has become a part of their everyday existence, limiting their daily activities and overall quality of life. Chronic pain, defined as lasting more than three months, can be a debilitating experience and affects over 225 million people in the world today.
For many, their condition is treated with opioids analgesics, which can in themselves lead to even greater issues such as addiction. But for others, such as the 30% of chronic pain patients suffering from neuropathic pain, even opioids aren’t effective. Instead, patients with neuropathic pain are limited to taking repurposed drugs such as antidepressants and antiepileptics to try to calm their firing nerves. These repurposed drugs are less than ideal: only one in two patients find their pain reduced by even 30%, and one in every three experiences side effects. Chronic pain remains an unsolved public health and societal problem with a huge medical need for better treatment options.
Connecting nerves and immunology
A striking feature of the $23 billion chronic pain market is that most drugs only address symptoms, without attempting to solve the root cause of the problem. For two thousand years, since the Roman medical writer Aulus Cornelius Celsus first described the four hallmarks of inflammation (redness (rubor), heat (calor), swelling (tumor), and pain (dolor)), we have known of the connection between the immune system and pain. However, it is only recently that the neuro-immunology link has been examined more closely.
It wasn’t until 2018 that the underlying cause of the [neuropathic pain] cascade was uncovered by the scientists who would go on to found Biodol Therapeutics. – Fabien Granier
The link between immunology and neurology is precisely what French start-up Biodol Therapeutics is looking to address. This company aims to develop the first-ever specific treatment for neuropathic pain and believes its technology will also be able to address other forms of chronic pain. It’s an example of true innovation, where a small company is looking at a longstanding challenge from a different angle. Biodol CEO Fabien Granier explains how the company came to be:
“Neuropathic pain occurs when a nerve has been damaged, through a lesion or by a treatment like chemotherapy, but the pain response persists even after the original injury has been healed. The cascade of events from nerve damage to neuropathic pain has long been known, but it wasn’t until 2018 that the underlying cause of the cascade was uncovered by the scientists who would go on to found Biodol Therapeutics. Their research, published in Nature Communications (1), found that the underlying cause of the cascade was an interaction between immune cells and the nervous system which led to the stimulation of a receptor called FLT3 on the damaged nerve. This in turn triggers the events that lead to the development of neuropathic pain.”
Old target, new possibilities
The FLT3 receptor has long been known as a target for another disease: cancer. There are multiple types of leukemia treatments that work by blocking FLT3 receptors. These treatments, only used in the deadly scenario of blood cancer, are “dirty” therapies with a range of side effects, only tolerated due to the high-risk profile of the disease they are being used to combat. However, Granier believes that FLT3 inhibitors may nevertheless be the solution neuropathic pain patients have been waiting for:
“At Biodol, we are developing a small molecule drug that works by inhibiting FLT3 receptors. This has never been done for pain, as it wasn’t until the seminal work by Biodol’s scientists that we even knew this receptor might be a target for chronic pain. We are also confident that we can overcome the side effects and long-term use issues of oncological FLT3 inhibitors, as they target the intracellular part of the receptor. Our small molecule compounds are instead targeting the extracellular part of FLT3. This makes them more selective and safe for continual use, which is necessary for a chronic condition like neuropathic pain.”
Using FLT3 inhibitors in combination with opioids eliminates the buildup of opioid resistance in animal models. A combination therapy in humans may therefore be a safer and more sustainable alternative to current opioid treatments for inflammatory pain. – Fabien Granier
Granier also tells us there is an indication that FLT3 inhibitors also have the potential to play a vital role in the global opioid crisis:
“Our researchers have found that using FLT3 inhibitors in combination with opioids eliminates the buildup of opioid resistance in animal models. A combination therapy in humans may therefore be a safer and more sustainable alternative to current opioid treatments for inflammatory pain.”
Read this previous BioVox article for more on the global opioid epidemic.
Taking a chance on change
The company is still in the early stages of drug development, working on the chemistry and lead optimization in preclinical studies. Granier is however confident they will find a good candidate for the clinic by 2023 at the latest. At that point, he believes pharmaceutical companies will be immensely interested in the treatment they’ve developed. Ward Capoen, Principal at V-Bio Ventures, agrees:
“Pain is an interesting market to tackle, because people are a bit afraid of the field. It’s considered a difficult area to work in, because there have been a couple of famous failures on safety lately, mostly related to one target. This is because any pain drugs need to be clean and safe for long-term use. Interestingly, in terms of risk management and likelihood of approval, pain is generally in the same range as oncology.
We decided to take the leap and invest in this company’s vision. It’s what V-Bio does best: we support young companies with good science, who are simply too early-stage for others, and nurture them through to the next stage of their journey. – Ward Capoen
When Biodol approached us, they had a lot of interest from other investors and pharma, who thought the target had a huge potential but were still too hesitant to get involved. Unlike them, we decided to take the leap and invest in this company’s vision. It’s what V-Bio does best: we support young companies with good science, who are simply too early-stage for others, and nurture them through to the next stage of their journey.”
According to Capoen, Biodol now has the funds to progress through the preclinical phases and get their lead to the clinic. Once the FLT3 inhibitor is ready for in-human trials, he is confident the interest from pharma will be intense.
One thing is for sure: early-stage or not, Biodol’s neuro-immunology based approach to pain management is in line with a general scientific trend towards tackling medical challenges in a more holistic manner. The aim is not to treat symptoms in isolation, but rather to understand the whole system and address the root cause of the disease. At Biodol, they aren’t just attempting to develop a new and better drug; they’re trying break the pain cycle.
(1) Rivat et al., Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice. Nat Commun, (2018) 9:1042.
