Dr. Robert Risinger, BioXcel Therapeutics, On Developing An Innovative Therapy to Treat Agitation

DocWire News recently spoke with Dr. Robert Risinger, MD, the Chief Medical Officer, Neuroscience at BioXcel Therapeutics, a biopharmaceutical company that uses artificial intelligence (AI) to identify drug targets and develop drugs in neuroscience and immuno-oncology.

BioXcel’s leading product is IGALMI™, a sublingual film used to treat agitation associated with schizophrenia or bipolar disorder. It was approved in April 2022 and is currently on the market. Dr. Risinger spoke about more about the company, the benefits of IGALMI, and other products in the BioXcel pipeline.

DocWire News: Talk to us about your professional background.

Dr. Robert Risinger: Sure. I am a neuropsychiatrist by training. I was a professor, trained at Pittsburgh, then Emory, NIH for fellowship, in the military, a professor of psychiatry at the Medical College of Wisconsin, mid-career moved to pharma, and I joined BioXcel, actually, about the time that we went first into human with this now approved sublingual film.

Talk to us about BioXcel Therapeutics. What is the number one challenge the company is looking to solve?

We have a variety of means through artificial intelligence to scour literature and look at old molecules and new indications and repurpose, as well as reformulate, even molecules that never have made it to humans. And one of the things that fell out, we were very much interested in stress, the stress axis, and agitation. And so people often call people under stress a fight-or-flight reaction. And so this fell out of the artificial intelligence engines. We identified a very potent alpha-2 agonist, which is dexmedetomidine.

It acts at the locus coeruleus, which is the seat or the origin of the sympathetic nervous system. It releases norepinephrine, or the other word for that is adrenaline. And adrenaline drives a fight-or-flight reaction in people. And so, we believe that the molecule helps patients who are agitated become less agitated by a very potent alpha-2 receptor agonism, and that diminishes the sympathetic tone. And what we’re seeing in clinical trials is it decreases the level of agitation.

How big a role does AI currently play in drug development?

Well, it’s become sort of a buzzword. A lot of different companies are using it. It’s been in pharmaceutical development for more than a decade. And so we actually are the first company to literally use artificial intelligence to take molecules to the market. This is the first molecule where we’ve done this. We have another molecule in backup in neuroscience for stress and the stress axis. We also have a molecule that is doing very well in oncology in a couple of different rare orphan diseases or rare cancers. And so we’re shooting two for two so far using artificial intelligence.

It’s a different way to develop molecules than other pharmaceutical companies. And I think it’s catching on that this is a valuable means to look at the literature and everything that we know about how the body works and cells. We know the brain is incredibly complex, and nobody can capture every level like a computer can. So we’re using this as a tool to benefit mankind.

Talk to us about your leading product, IGALMI.

IGALMI is a sublingual film. It was approved for the treatment of acute agitation associated with schizophrenia or bipolar 1 or bipolar 2 disorder. The film was engineered to have mucoadhesive properties. So it’s kind of like a Listerine film-type shape. It’s green, and it has some dots on it, which is the actual dexmedetomidine or the active pharmaceutical ingredient. It has physical-chemical properties so that when someone puts it under their tongue, it is absorbed directly through the oral mucosa. And the film, the backing actually dissolves over six to eight minutes, but the dexmedetomidine appears in the bloodstream about five minutes after the film is placed in the mouth.

And then we see clinical effects that are very clear. It acts very rapidly. It’s the fastest-acting oral treatment for agitation. We see a separation from placebo as early as 20 minutes. And we’ve run very large 750 patient trials. One for patients with schizophrenia, one for patients with bipolar disorders, 1 or 2. And each study showed clinically meaningful and statistically significant reductions through two hours and beyond.

What other products does the company have in early development?

Early development, we’re calling this molecule, the IGALMI, is BXCL501. We have ongoing studies. We have a study of daily dosing. We have a study in combination with an antidepressant in healthy volunteers. We have a study of this molecule or BXCL501 in agitation associated with Alzheimer’s. We, in fact, have two studies, one that is due to report out the first half of this year. And for that, we received Breakthrough Therapy from the FDA because this is a very novel mechanism of action. And we’ve demonstrated robust efficacy in a smaller trial but with five different measures. We’ve been working closely with the FDA on a breakthrough status and, hopefully, an accelerated approval for this indication. That’s still in the works.

We also have a follow-up molecule for the stress axis. We haven’t announced what the actual molecule is, not quite yet. And we have a home-use study for BXCL501. So patients, we know, they appear in the hospital, emergency rooms, or inpatients agitated, but we know they get agitated at home. And so, we’re studying the potential use of IGALMI or BXCL501 at home. And then, we also have the oncology agent. That’s called BXCL701. And that is looking at, for example, prostate cancer, a form of treatment-resistant prostate cancer.

What are some key takeaways you want to leave our audience with today?

Well, I think that as a physician, I treated many patients in the emergency room, and I really hated to have to give patients, for example, an injection. And I know that it can be disheartening for the patient and potentially even dangerous to the patient or providers. And so I really like the fact that this is a new option available to physicians. IGALMI for acute agitation, especially in these situations where patients can be hostile or aggressive, potentially even violent, I think it really helps a lot of both providers and patients.