Targeting Alopecia with Plant Power

I often say to people, “Try to catch a cat, and it will run away. But try to catch a tree and you win every time.” Confused? Plants cannot run and hide from predators – and because they are vulnerable, they have, through evolution, developed many interesting bioactive molecules to protect themselves. Nature is very well “made”.  As we humans have evolved alongside plants, consuming them. Not only do we tolerate most of them very well, but their bioactive molecules are transferred to us, with a potential therapeutic effect, which varies depending on the dosage and combination of plants used.

Many of the pharma industry’s early drugs were derived from plants, including codeine, quinine, and digoxin. In these instances, one bioactive is extracted from the plant, identified, and then synthesized chemically. But it is also possible to use the full plant extract to develop a botanical drug. For example, instead of taking one compound from an apple, you would use the full apple. Prescription botanical drugs are a relatively new class in drug development; the FDA and EMA both only established a guidance in 2004. These drugs use the full plant (or a combination of plants), with every molecule that is found in the plant found in the drug. These multi-molecule drugs offer the potential to hit multiple therapeutic targets at the same time.

At first, regulators believed that botanical drugs would fit within the same regulations as other drugs; however, nature is not a factory and does not make things identical. If you pick the same plants from the same field on the same day and process them into two bottles of tablets, there will be slight differences between the medicines. In the world of pharma, variability is generally not accepted.

In 2016, the FDA introduced updated guidance for industry after recognizing that things would need to be adapted to reality if botanicals were ever to reach the market. Now, regulators are asking for quality control measures to be implemented throughout the process, from collection of the plant to manufacturing, so that despite the natural variability, efficacy and safety is ensured. There are very few botanical drugs approved for marketing as prescription drugs, but improvements in regulations should now make development of botanical drugs more viable.

It is important to stress that botanical drugs are not the same as traditional herbal supplements. Many herbal supplements are available in the US, but these have not been approved by regulators to treat disease. Botanical drugs require clinical data demonstrating safety and efficacy to treat a disease.

Surviving the VC gauntlet
 

I was born in Morocco where many people use both allopathic drugs and plant-based remedies (many of the plant-based remedies are homemade, which makes for some crazy variability!). In fact, this duality is normal in many countries. When I arrived in Europe, I found it strange that, whenever I needed a treatment, the only option on prescription was a synthetic chemical agent.

While I was working in the pharma industry, I was very interested when regulations around botanical drugs started to appear – and I saw it as an opportunity to launch a company. However, finding funding was almost impossible. I approached many peers and VCs without luck, which led us to pivot our development plans. Developing a drug that is to be taken orally is very expensive. A topically-applied drug is a little cheaper, so this is the path we decided to pursue.

As for the therapeutic area, we decided to focus on alopecia, which pharma was not yet interested in at the time. The initial clinical data were nice, so we approached consumer companies who helped our product reach the market as a haircare product that did not claim a therapeutic effect (which you can do since it’s plant-based). Over 2.5 million units of this product have been sold during this period. 

We used the profits to fund R&D of what we hope will become an approved botanical drug. We are now at the filing stage. In June 2023, the EMA validated our marketing authorization application for the treatment of moderate to severe alopecia areata in children and adolescents. The drug is now under review.

Our drug, Coacillium, is made from four plants – Allium cepa, Citrus lemon, Theobroma cacao, and Paullinia cupana Kunth. All of these are considered “GRAS” (generally regarded as safe). In other words, they are edible.

Autoimmune conditions, such as alopecia areata, have been difficult for drug developers to address. In autoimmune conditions, T cells attack the body in a coup. You can’t simply send them back to the barracks and lock them in because you need them for self-defense also. Until recently, there weren’t any approved treatments for alopecia areata, but now JAK inhibitors have come to the market. These drugs work well – the patient’s hair will grow back; however, when patients stop taking the treatment, their hair falls back again. And since these are immunosuppressant drugs, patients may not use them forever. In other words, there is a real need for other options, in addition to the fact that they are restricted to the most severe patients, while everyone needs treatment.

We’ve seen positive results for our drug so far 91), and it has been reported about it. Even when treatment was stopped for six months, the hair kept growing, suggesting there is a long-term action of the drug on the physiopathological process that is causing alopecia. Importantly, patients also indicated that they felt much better after treatment. Hopefully patients will be able to take the drug, have their hair back and feel better – and then they can discontinue use until they have a flare up. It’s a complete shift in disease management for this condition. We don’t know the exact mechanism of action of the drug, but it does seem to work. And it is doing so without the negative side effects often seen with immunosuppressants. It’s exciting and it shows that some plants have a lot of potential.

Botanical drugs may not suit every disease or be the most relevant for acute events, but there is certainly room for more investigation especially for chronic conditions. Here, artificial intelligence (AI) can help; there is a great deal of knowledge about diseases in the world, including their mechanisms and pathophysiology. Separately, there is also a lot of knowledge about plant biology, including the molecules they contain. From there, you can use AI to help answer a relatively straightforward question: “Are there molecules in plants that could address a druggable disease target?”

We’ve spent more than 10 years developing our drug – with the discovery aspect taking 3-4 years. We’re now looking at how AI can speed up projects because it allows us to simultaneously look at over a thousand drugs and then pick the ones most likely to be winners.

The natural choice?
 

Not all plants are safe – and there are some that are more poisonous than many chemicals. But if your starting point consists of plants that are known to be safe for human use, the likelihood of side effects or long-term toxicity should be close to nil. And that means patients could take them for a chronic condition over a long period of time without the fear of doing more damage in the long run.

I am not advocating for us to move away from synthetic drugs – these are effective therapies, and we need them. The COVID-19 vaccines demonstrate the power of traditional drug development. But we also shouldn’t disregard plants. 

People are living longer – and we all want to live healthier lives. Many of us will end up with certain conditions and may be taking drugs for 20 to 30 years of our lives. We want these drugs to treat our diseases and be mindful of our overall health. The combination of plants in Coacillium often surprises people, which is probably why we’ve faced a lot of disbelief. But doesn’t it also make you think about what else might be possible with plants? Our moonshot project is to eventually look at the potential of botanical drugs for Alzheimer’s disease… 

And why not give patients more choice? Today, there is a growing trend for more natural products. With clinical trials and more research, we could give patients options for pharmaceuticals too. If you have a synthetic drug and a botanical drug – both of which are approved by health authorities with clinical evidence that shows both are effective – many people may choose the botanical option, as surveys have shown.

I don’t expect the pharma industry and venture capitalists to instantly go crazy on botanical drugs. But I do hope our story can serve as inspiration. Botanical products shouldn’t be limited to nutraceuticals or supplements – they should be researched for their potential as pharmaceutical drugs, for the treatment of diseases, particularly for chronic conditions.