Subscribe
Share
Share
Embed
Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
We hear the term AI all the time, but what is it actually doing? Today, we learn how AI was used by one company to discover a drug now approved by the FDA. The company's AI has already gone on to discover other drugs as well. Doctor Vimal Mehta is the CEO of BioXcel Therapeutics. Well, doctor Mehta, welcome to the program.
Dr. Vimel Mehta:Thank you very much. I'm very happy to be here.
Dr. Moira Gunn:Now this is a very interesting interview for me because it's not just about the drug candidates, the treatments you're working on, but it's also about a a different and advanced approach or a new approach to drug discovery, how you come to identify what would make a good drug candidate. The scientist is looking to create this intervention in the body, is looking to figuring out how to deliver it. And, and in doing so, they they read everything they can in the literature and along the way they form experiments and continue to work on what might be possible and, you know, as they learn, they evolve that. So when we look at this approach, the first limiting factor is the scientist's knowledge based on reading everything in the literature. Why is this a limiting factor?
Dr. Vimel Mehta:There are 50,000,000 publications and there's a overload of information. It's very difficult for a scientist to digest all the information. That's where we applied artificial intelligence and machine learning approaches to make the information digestible for the scientist. Because reading one publication at a time will not get you, where you need to be assimilate all the information. So machine come in, they can read 50,000,000 publication and they never get tired.
Dr. Vimel Mehta:And scientists will get tired. So, ultimately, machines can really help us find insight which are not possible by just reading one publication.
Dr. Moira Gunn:Well, there's also an old adage in networking that says, it's it's not just who you know, it's who who you know knows. And a scientist reading a publication takes that information and just adds it on to himself, but there's a there's a deeper aspect to what artificial intelligence can learn.
Dr. Vimel Mehta:Artificial intelligence in a unbiased man, manner creates a knowledge graph or a as you said, network of information, which no scientist can do. So it can bring all the information that may exist in one part of the world or the other part of the world and bring it together and create some unique insights, which are network maps. So you can look at first degree connection, which a scientist can identify by reading a book. But second, 3rd degree connections are very difficult to assimilate because information is so complex. So that's where the artificial intelligence platform, machine learning technique helps us sort out and bring the efficiency that we need to enhance our drug discovery and development process.
Dr. Moira Gunn:So it's not just who you know, it's who who you know knows, and who they know, and it knows. And so it's a much deeper understanding than just the paper at hand or what they're looking for at hand. So, that that kinda brings together. It's like, oh, it it it enables you to know far more. Now you're not just looking for the information.
Dr. Moira Gunn:You are also looking for those same capabilities among already approved drugs. Why is that?
Dr. Vimel Mehta:The reason we are trying to take advantage of the existing knowledge because there is a 100 of years of knowledge available about the disease. There are so many molecules that either make it to the market and never their full biology has been understood or it has been exploited or leverage. And there are molecules which fail after phase 2, and they get stuck in phase 2 and phase 3. So we go with the unbiased approach. We try to see that what is the underlying disease drivers.
Dr. Vimel Mehta:Do we understand them? What are the cause causal drivers for the disease? If we understand, then we try to relate that to the drugs and their underlying biology and the mechanism, what exists, and then try to correlate and see, can we find a novel way of treating that, patient population. And, that's exactly the underlying foundation for our drug candidates at BioXcel Therapeutics.
Dr. Moira Gunn:Well, this was certainly the example of your first drug, Igalmi, and let me spell it for pea for listeners. It's I g a l m I, Igalmi, which was approved last spring and it's a drug to treat agitation associated with schizophrenia and bipolar 1 and 2. This was a drug that had been approved originally for a different medical condition. What was it originally approved for?
Dr. Vimel Mehta:It was originally approved as a sedative and assertive given in a surgical unit.
Dr. Moira Gunn:Now obviously, if you're trying to settle down agitation in someone, you say, well, let's just pull the IV out. That's not going to happen. You had to develop a new delivery method. What did you do?
Dr. Vimel Mehta:So we converted this drug into a sublingual thin film because you want some sort of a treatment that is patient centric and friendly for the patient. They don't feel threatened. If you go at a patient with a needle, they can feel threatened and they can hurt you also if you're trying to go, to them with a needle. So that was fundamental reason that we converted this drug into a sublingual thin film. It's green in color.
Dr. Vimel Mehta:It's a minty in taste. You put it under the tongue. It has a muco adhesive and it starts onset of action immediately. That was the important factor for the doctor that once you give the drug, you have a rapid onset of action. Because you want to calm the patient, as soon as possible.
Dr. Vimel Mehta:We are doing microdosing, because that's what we realized. That's what is needed to calm the patient. So, film, we believe was the ideal treatment delivery option for these patient and we are seeing that in the real market since we have launched the Calmi in the marketplace.
Dr. Moira Gunn:And if you took a pill, if you got the person to take a pill, they're pretty agitated at this point. It would take a long time to get into their system.
Dr. Vimel Mehta:It will because it will go through the stomach and, our drug that we are using on Egalmi, it has some sort of a metabolism. So it won't get to the blood level to we need within a short amount of time. So that's part of the reason we did the sublingual delivery so that drug can reach to the blood levels and it can start treating the patient. There's another problem to that. If you give bill, sometimes these patient cheek it, they and then when the doctor leave, they spit it out.
Dr. Vimel Mehta:So with the film, with the mucradysy, they can do that.
Dr. Moira Gunn:A drug candidate that was original right from the lab bench, never previously used, would take 12 to 15 years to become approved. This was already approved. What territory did you not have to revisit because it was already approved?
Dr. Vimel Mehta:First is that we knew so much about the drug. The fundamental properties of the drug because it has been in humans for over 20 years in 10,000,000 patient, there are 10,000 publications already. So that gives us a very good base. The biggest advantage was that we had a very good understanding of the safety for this drug because it has been used in the human. So that's, that key characteristic that you look into the drug, like, what is the pharmacokinetics, what is the pharmacodynamics, what is the safety, that's already established.
Dr. Vimel Mehta:We need you to figure out what those and what is the delivery mechanism and what smart trial we need to design to prove it. And that's exactly what we did. That's part of the reason we have were able to go from our IND all the way to the approval within a 3.5 year rather than taking the, 12 to 15 year cycle. And there has been no innovation in this area. So it's a highly innovative drug from those perspectives.
Dr. Moira Gunn:So for those of you listening who are outside the drug development field, IND is investigational new drug. That means you tell the FDA, this is what we wanna do. So that's day 1 in a in a drug like this. And from there too, it was actually approved with just three and a half years instead of the 12 to 15. And you had a lot more confidence because so much more was done.
Dr. Vimel Mehta:Certainly. It gives us a high level of confidence, a derisk opportunity, for our stakeholders because we have a high level of degree of confidence that we can bring it, in the clinic and we can if clinical data is good, we can bring it to the regulators to get approved. So those were the fundamental reason for forming BioXcel Therapeutics and initiating this agitation program, massive program where there are 140,000,000 episodes. And it's a huge use societal problem. So we are very pleased with the outcome we had with the IgALMIA.
Dr. Vimel Mehta:And as you and I speak today, it's already helping the patient.
Dr. Moira Gunn:You said a 140,000,000 episodes. Do you mean a 140,000,000 episodes per year?
Dr. Vimel Mehta:That's right.
Dr. Moira Gunn:And what was the what's the current treatment for that before Igal may showed up?
Dr. Vimel Mehta:So let me just divide that. So agitation happens because of schizophrenia, bipolar 1 and 2, and agitation happens in dementia patient or Alzheimer's patient. So there are about 40,000,000 episode that happened for schizophrenia, bipolar 1 or 2 patient, and there are about 100,000,000 episode that happened for Alzheimer's and dementia patient. So currently, there's no approved therapy for Alzheimer's related agitation. They give them antipsychotic.
Dr. Vimel Mehta:They give them Benzodiazepine. But what our treatment options are more tranquilizing and they are black box warning. So they have not been, there is no approved therapy as of today. In bipolar, schizophrenia, arena, there are few approved therapies, but they don't work that well. And some of them are I'm injections.
Dr. Vimel Mehta:And they have, like, in a long effect in patients sedating the patient or tranquilizing the patient. So what we have come over is a very ideal option to treat a patient agitation and involve the patient in the care and making a treatment choice. So physician can tell them I have this I'm injection or I have this innocuous film to treat your agitation. What do you want to take? And some of these patients had this experience that they come to the emergency room multiple times so they know they did not like the drugs or choices they were on before because they were tranquilized for a long time.
Dr. Vimel Mehta:So patient really know what the side effects were. So with a new drug like a galmi, they have a new treatment option. And, same for the health care providers and the physicians.
Dr. Moira Gunn:Now I know you're also studying, bringing eigalmi at home. Right now, you would have to go you'd have to be in a facility of some sort or go to the ER to get this. How do you study it at home?
Dr. Vimel Mehta:We just initiated that program last year, our pivotal phase 3 program. We call it as a serenity 3. And we it has two parts to it. One part is efficacy. We are testing the efficacy in a medical supervised setting like we did before.
Dr. Vimel Mehta:Like, where we got approval of the economy. Just we are using a lower dose. So in our economy, we got 120 microgram and 180 microgram, 2 doses approved across the spectrum, mild, moderate, and severe agitation. And now we are using half the dose 60 and showing the efficacy. Once we demonstrate efficacy under the same condition as our previous trial, Then second part of safety will be done at home.
Dr. Vimel Mehta:And it's no different than any other drug that is being developed. They test the safety at home. So we will be using the same where patient will be reporting how he feels. Does he feel any safety or, issues or his informant will be providing that information. So it's no different than the regular drug development.
Dr. Moira Gunn:And you're also studying Alzheimer's as well. Right?
Dr. Vimel Mehta:That's right. That's that's a very very large opportunity and very high unmet medical need. So our, like, you know parents or grandparents, they end up in the assisted living facilities or nursing home not because of the Alzheimer's or dementia. They end up there because agitation cannot be controlled by their family member. They really don't know how to manage that.
Dr. Vimel Mehta:Because whenever agitation happen, they send them to the emergency room. So it's a huge unmet medical need. There's no approved therapy, and we have a breakthrough therapy designation from the FDA using our phase 2 data. So we are in a good place and now we are running pivotal trials. We call them tranquility 23 to show that we can, help these patient and then if data is positive, be able to get approval from the FDA.
Dr. Vimel Mehta:And there are about 100,000,000 episodes related to just Alzheimer's related agitation.
Dr. Moira Gunn:Now since AI engines will search for whatever you're asking for, I know you're also working in immuno oncology. Keytruda, of course, is well known as as leading immuno oncology drug, and it works for many cancers, but it doesn't work for all cancers. Here's where you're operating. Right?
Dr. Vimel Mehta:That's right. So we are working on tumor that are hard to treat. What I mean by that hard to treat tumors is these tumors by definition are also called as cold tumors where immunotherapy doesn't work. If you change the microenvironment inside the tumor and make them hard, there is a high likelihood that KEYTRUDA will provide better benefit to the patient. So that's exactly what we are doing with our lead product that was, again, identified using our AI platforms.
Dr. Vimel Mehta:We are combining with Keturah. We are presenting a data next week at Escogu, full 28 patient data to show how well, it can help the patient. So that data will be presented by our principal investigator. And currently, KEYTRUDA responses are really, really low, like, under 5% in these rare forms of the prostate cancer. So if you can enhance the response rate into the mid twenties, like, you know, that's a big win, for, these patients because, and also if you can stabilize the disease and you can have a durable response.
Dr. Moira Gunn:And is your drug one that was previously approved as well?
Dr. Vimel Mehta:This drug had a different story. So this drug has gone to the phase three trial in other tumor types, and it has done multiple phase two trials. It was a biotech company. They spend a 100 of 1,000,000 of dollar, but it was stuck. Using AI, we identified that this drug, which was tried before the immunotherapy revolution in early 2000 where everything combination was a chemotherapy.
Dr. Vimel Mehta:Chemotherapy and the drug, this drug didn't work. With the new information about the immunotherapy and our AI platform being able to identify that, that it's a innate immunity activator, and this could be a relevant candidate to combine. So we have published the mechanism. It's a completely novel mechanism for this drug. We have established the safety with Keytruda and now, efficacy with Keytruda.
Dr. Vimel Mehta:So this will give us a good path to double up how to bring this drug to the marketplace.
Dr. Moira Gunn:It occurs to me that you just don't walk up to your AI engine and say, hey. We need another drug. You've gotta have data and you've got to be able to ask the question, you know, or the questions to get it down to those things that are usable, actions that are usable. Tell us about that.
Dr. Vimel Mehta:You're absolutely right. There's no magical solution. And in terms of the question, we decide that we want to work in this, medical condition. Our experts, they design question that can be as long as 500 to 5000 word queries, and we feed in the machine. Then machine reads whatever information is available and create what we call as a network map or a knowledge graph.
Dr. Vimel Mehta:These are dynamic. It's not a database. These are dynamic network maps or a knowledge graph, which we can update as new information will come. And we use that to see what are the key insights we can drive using the machine learning. Like, how can we figure out something that's not easily accessible to the human brain because there is so much information.
Dr. Vimel Mehta:So it's a quite a process, and we have built this over a now, 15 years. The parent company of BioXcel Therapeutics, BioXcel Corporation started as a big data company, developed the algorithm, did this work for the pharmaceutical company for over, like, in a 200 companies, and then applied this to create BioXcel Therapeutics pipeline, which are our current drugs. So we are a very patient centric organization. We like to make societal impact, and that's exactly what we like to do as a team at BioXcel Therapeutics.
Dr. Moira Gunn:Well, with this telling of your journey, your motto for the company could be one thing leads to another, and it certainly does. Doctor Mehta, thank you so much for joining me. I hope you'll come back and see us again.
Dr. Vimel Mehta:Certainly. Thank you very much for hosting us. I appreciate that.
Dr. Moira Gunn:Doctor Vimal Mehta is the CEO of BioXcel Therapeutics. More information is available at bioexcel.com. That's bio, the letter x, and c elbioexcel.com.