Last month, DeFloria Inc.—a joint venture between Ajna BioSciences PBC and Charlotte’s Web Holdings Inc.—announced a milestone in its development of an oral multi-cannabinoid drug for the treatment of symptoms of autism spectrum disorder (ASD). In a first for botanical drug development, not just cannabinoid drugs, DeFloria received FDA Investigational New Drug (IND) application clearance for the systemically absorbed drug AJA001 to proceed with Phase 2 clinical trials.
To better understand the significance of this development and the forces behind it, Cannabis Business Times spoke with Joel Stanley, CEO of Ajna BioSciences and DeFloria Chairman of the Board, and Jared Stanley, CEO of DeFloria.
Editor’s note: This interview was edited for length and clarity.
Jolene Hansen: You were both co-founders of Charlotte’s Web. What roles do your current companies play in the development of this new multi-cannabinoid botanical drug AJA001?
Joel Stanley: It was really what we learned at Charlotte’s Web, honestly, that informed us how powerful plant medicine can be for people. In 2021, I stepped off the board of Charlotte’s Web to specifically start Ajna Biosciences, which is the botanical drug development company that’s now partnered back with Charlotte’s Web to carry some of Charlotte’s Web’s very valuable plant genetics into drug development.
Charlotte’s Web is a dietary supplement company. Ajna is a botanical drug development company. So we’ve combined this partnership to take what Charlotte’s Web has in plant medicine to that next level, which is through the FDA, so that the product has clinical data, physicians can advocate for it, and you can find it, eventually, in pharmacies and hopefully covered by insurance for many people. That’s really what a lot of plant medicines lack.
There’s only four FDA-approved botanical drugs to date. It’s a new regulatory pathway. Honestly, how you take a complex botanical with multiple molecules, standardize it to a reproducible therapeutic experience, and then characterize all of the molecules in it, so that the FDA will allow it to be a pharmaceutical-grade botanical—that’s the trick.
What we saw with Charlotte’s Web was that you could make a very viable plant medicine that works for many people, but without the clinical data, without the FDA approval, without physicians advocating for it, very few people are really going to try it—very few of the people that could benefit from it.
DeFloria is the partnership, the joint venture between Charlotte’s Web and Ajna. DeFloria specifically works with Charlotte’s Web’s assets to develop a drug for autism. It would be the third drug [FDA-approved, of any kind] for autism.
One thing that’s very important to understand about Ajna: It’s a botanical drug development platform. It’s not just about cannabinoids or psychedelics or formerly prohibited substances. It just so happens that those substances are some of the lowest-hanging fruit that we know are highly efficacious and have strong pharmacological safety signals. But Ajna’s drugs in the pipeline in perpetuity may come from plants, shrubs, trees, roots that have nothing to do with any level of psychoactivity.
Hansen: I was surprised to learn that 1 in 36 children have an ASD diagnosis. What inspired you to target ASD with AJA001’s development?
Joel Stanley: Well, Charlotte’s Web and really the entire CBD movement started with stories like Charlotte’s, of children with severe epilepsy. Back in 2013, Sanjay Gupta told the story. Back then, hemp had not been federally legal yet, so you had families moving to Colorado to access Charlotte’s Web. The community that was built around it was largely pediatric epilepsy in the very beginning.
With pediatric epilepsy diagnoses, about 50 percent of those are also accompanied with an autism diagnosis. So we’ve seen signals [of efficacy] in seizure disorders as well as autism, as well as other neurological disorders.
Cannabinoid medicines are very diverse. Which indication you choose when you have a diverse drug is a bit of an intricate process. But we chose autism largely for these two reasons: One, we do have a strong historical signal for the genetics we’re using in this drug. … Two, because there’s only two FDA-approved drugs for autism spectrum disorder, and both of them have terrible side effects. This is really an important option for the autism community—a much safer option, we believe, and one that’s been lacking.
The two drugs that are approved in autism are both atypical antipsychotics. They can work if you’ve got a child that’s self-injurious, highly withdrawn, banging their head against the wall—these are the types of cases. These two drugs are last-resort drugs because of their horrific side effects. Knowing that we have a strong signal and that the autism population is really left wanting, the FDA really needs to take drugs like this very seriously for that community.
Hansen: What can you share about the new drug, its development process and the genetics behind it?
Jared Stanley: First of all, it’s a new formulation, but the baseline genetics are the same genetics that we saw in the Charlotte Figi phenomenon. When you had a phenomenon like Charlotte, you vow not to change that product. We had a 15,000-client waiting list. We had consumers that we vowed could rely on that product in perpetuity.
What we didn’t realize at the time was that the 15 years that we’ve spent building Charlotte’s Web—I was COO of Charlotte’s Web when Joel was CEO—we were building the very foundation of what would become DeFloria in the future.
In order to get the FDA IND clearance into Phase 2, we have to meet the rigorous Chemistry, Manufacturing and Controls [CMC] from the FDA. We have to prove that we can get this same consistent product every time. So this new drug is an oral solution, cannabinoid formulation from the baseline genetics that we’ve used.
It’s a utility patent, which is really a moat of intellectual property, protecting the product. Then we’ve used all of our 15 years of experience and methods in breeding, consistent seed supply, stabilized genetics, cultivation, harvest, extraction, manufacturing. All of these processes combined are then a method-of-use patent, protecting how we make the drug to ensure its consistency, to meet those CMC requirements.
Joel Stanley: When you look at plant-based dietary supplements, what Charlotte’s Web did by using the same genetics of plant that express the same phytochemical fingerprint over and over, the level of standardization of that plant before it ever gets extracted is really the highest standard that I know of anywhere. That’s not just in hemp or CBD. That’s in supplements in general.
For us to take it to the next level, to the pharmaceutical level, we’ve been preparing for this. … The barriers to entry to make this standardized botanical product are substantial, and I don’t know of anyone else with that capacity. All of our history kind of led us to this. I don’t want to call it Round 2, but it is in large part a completion of something we’ve been working on for almost 15 years now.
Hansen: You announced Phase 1 trial results in December 2024. What have you learned so far about how the drug works and its potential impact?
Jared Stanley: Two very key findings: The number one finding, we were looking at safety and tolerability of AJA001, and we found our upper limit—the highest limit of AJA001 that we can dose at. We’re very pleased with our upper limit. But not only did we look at upper limit, we did a SAD, Single Ascending Dose, study and a MAD, Multiple Ascending Dose, study, and we tested the blood plasma concentrations of cannabinoids through different dosing, starting low, going high.
What we saw was very consistent. As the dosing increased, so did blood plasma concentrations of our target cannabinoids. It sounds simple, but that’s a really good sign to us that we can monitor dosing, that dosing works for how we’re metabolizing what we believe are the efficacy parts of AJA001.
In essence, those are the two major things we learned, and that is what now informs our dosing for our Phase 2, and our whole protocol is established based off the safety.
Hansen: The FDA reviewed your IND application and cleared the way for Phase 2. Why is this so significant, particularly for the development of botanical drugs from cannabis and hemp in the U.S.?
Joel Stanley: It’s certainly significant for cannabis medicine, hemp medicine, for sure. But I’d say even larger than that, it’s significant for the future of botanical drugs. The four drugs that have been FDA-approved botanical drugs, three of those are topical, which are relatively easy to get through. You don’t have to do as much work on Chemistry, Manufacturing and Controls, because it’s not systemically absorbed. Then one of those four is still not systemically absorbed—it is an oral, but it coats the [gastrointestinal] GI tract.
This will be the first systemically absorbed—what we think of as pharmaceuticals—botanical drug to have the clearance into Phase 2. A lot of people debated whether botanical drug development to this level was going to be possible. Can you characterize the molecules? Do we even have the technology to characterize a drug substance to be allowed to go into pediatric efficacy trials?
What it shows is that we’ve cracked that code. The Chemistry, Manufacturing and Controls, which is the hardest part of botanical drug development, is doable. It’s not easy, but it’s a doable process.
For us, this marks one of the largest milestones for botanical drugs, in general, and should send a signal to the biotech industry, as well as those who’d like to see more natural pharmaceuticals in Western medicine, that these are coming. This is really the first of its kind.
There are so many people out there that are self-medicating with cannabis products. They don’t have a lot of direction from their physicians. Some physicians are willing to look into it and recommend, but they can’t legally prescribe. What we see is a level of clinical data that the everyday physician, not the rare ones that are willing to work with cannabis, but the everyday physician can look at this drug, take it very seriously, just like they do all of the synthetic drugs, and offer it as an option.
This is a huge first. Not that many people are really willing to go against the grain and buy some of these plant medicines. The majority of people want their doctor on board, especially when they’re diagnosed with a serious illness. So this is a huge milestone for botanical drugs and for cannabinoid medicine in general.
Hansen: Your Phase 2 clinical trials are planned for mid-2025. What will those involve and what are your specific goals?
Jared Stanley: First of all, what we’re doing isn’t a new strategy. We’re starting with two Phase 2 open-label studies. These are not placebo-controlled studies. These are meant to inform our double-blinded Phase 3 placebo-controlled study. We plan on learning a lot from these Phase 2 trials.
We will do a U.S. study in young adolescent and adult. We will conduct a pediatric and young adolescent study in Australia. And we will look at different dosing titrations going up to our upper limit. They’re a 12-week study with a three-week titration schedule and a nine-week maintenance period.
The point of this study is to inform how we dose, how we titrate, and look for efficacy signals on our target endpoints. This will help inform our Phase 3 and clinical trial design for Phase 3 to ensure maximum effectiveness and that we meet our goals for our Phase 3.
Joel Stanley: When we have Phase 2 results, we can then approach the FDA with a trial design for the pivotal study—that’s Phase 3, the blinded, placebo-controlled that they call the pivotal trial.
You basically update your Investigational New Drug application with the new clinical trial you’re looking to go into. Oftentimes, the agency can have feedback. They say, “OK, we think this is good, except we’d like you to look at these and these.” That’s the process.
One thing to note, even though the Chemistry, Manufacturing and Controls, the standardizing of the drug, the characterizing the drug, is very different than the single-molecule drugs, the rest of this process is the exact same. The clinical trials are run the same. Everything else is just normal drug development from here on out.
Hansen: This is bigger than cannabis, but what does this mean for the cannabis industry specifically? What impact might rescheduling have on your work?
Joel Stanley: Ajna has a DEA Schedule I manufacturing registration, and that’s to be able to also work with high-THC cannabis—this drug is not high-THC cannabis—but certainly to work with psilocybin. As far as I know, Ajna is the only DEA manufacturing registration that is working with botanical Schedule I controlled substances. … So, for Ajna, that question is not highly relevant because we were able to obtain the license. That says a lot about our team and our experience and what we put together.
For the DeFloria drug and joint venture, because it comes from hemp, we really aren’t beholden to the Controlled Substances Act, so it doesn’t impact it directly. However, we do have opinions on it, because we were born from the cannabis industry. I think we kind of pioneered there.
I think rescheduling, when it does go to Schedule III, which is what it looks like is going to happen, is a very important move. Now I’d love to see an even bigger move, but I think it’s a very important move in which now you’ve got millions of Americans that will be in possession of a plant under their state program, and they won’t be in possession of a mandatory felony at that point. Just from a human perspective, can’t wait to see it happen.
I think a lot of people would say, “No, it needs to be descheduled, regulated like alcohol.” I feel that—I’m not a prohibitionist in any way, shape or form. But we’ll take what we can get. I do think it is going to Schedule III.
I think that’s going to signal something, especially to pharma. Larger companies, larger institutions, will be willing to invest in the further development—development like we’re doing—of cannabinoid therapies, which I think is very important. … Going to Schedule III just opens the doors for researchers, large funds, the largest biotech investors, the largest biotech companies, to start moving in the space. Maybe that’s M&A activity. It’s certainly going to mean a lot for investment. But all of that equals advancement of the science in my mind, and advancement of better products within cannabinoid products.
Jared Stanley: Just to add to that, Charlotte Figi blew down the door on the accepted medicinal benefit of cannabis. We all saw that. DeFloria is taking 15 years of our observations and turning them into clinical data and answers that physicians can rely on to garner physician advocacy. I believe we’ve already opened our eyes, and we know that this plant has accepted medicinal benefit and is moving from Schedule I. But I believe the work we’re doing at DeFloria continues to substantiate that position and open our eyes further to what can be done with this plant.
Hansen: Is there anything else you would like the readers of Cannabis Business Times to know?
Jared Stanley: When Joel came off the [Charlotte’s Web] board in 2021, Joel knew that this was the future and the greatest good for what we were doing within our life’s work within cannabinoids. … [Charlotte’s Web was] doing a great job as a supplement company, but it wasn’t a pharmaceutical development company.
So when Joel went and built that lab and that clinical expertise and that team, while I was building the supply chain and operations at Charlotte’s Web, that’s how these came together. … We truly have the world’s A+ Who’s Who team that have come together around this because they understand how meaningful this is and that it’s a clear shot on goal to a much-needed ASD community.
Joel Stanley: For us, this all goes back to [when] I met Charlotte Figi in February 2012. Of course, her results, her life story was just phenomenal, and that had a huge impact on the world, huge impact on access. The team that Ajna was able to put together is some of the Who’s Who within pediatric neurology, some of the Who’s Who within drug development.
One of our team members, Jinhui Dou, spent 17 years inside the FDA. He is the primary author for the FDA’s botanical drug guidance. He literally wrote the rule book that you use to move a botanical drug through the FDA. … One more human asset, Dr. Orrin Devinsky was Charlotte’s highest-level doctor. He ran the neurology department at NYU. He was also the lead principal investigator for Epidiolex, which is the only [FDA-approved] cannabis-derived CBD drug. … Dr. Devinsky was the lead principal investigator on their Phase 2 and Phase 3 clinical trials. So, he’s the only human that has designed clinical trials through the FDA for a CBD drug.
What’s come together around us in these brilliant people really are all the puzzle pieces to get this through. The reason why that happened, to be honest, is the powerful story of Charlotte Figi, the Figi family and what happened there, Sanjay Gupta telling the story.
Had all of that phenomenon not come together, had we not done a really good job building Charlotte’s Web … none of them would have taken it seriously. But when we went and asked them, “Do you want to do this project with us?” They said, “Absolutely.” They jumped on board. Without those folks, and without the entire perfect storm of events the last 15 years, none of this would be happening.
Jolene Hansen is an award-winning freelance writer and editor specializing in the commercial horticulture, cannabis and CEA industries. Reach her at [email protected].
In ‘huge first,’ systemically absorbed oral cannabinoid AJA001 from Charlotte’s Web genetics receives FDA clearance for Phase 2 clinical trials. Read More
