A Second Chance for an ALS Drug... Dr. Ari Azhir, Founder & CEO, Neuvivo
This is the biotech equivalent of an old story, the one which starts with a guy walks into a bar. However, this being the biotech equivalent, it goes something like this. A promising new biotech with a very new approach gets significant funding. Its drug fails after two phase two trials, and they shut their doors. It's unfortunate.
Dr. Moira Gunn:It's expensive, but it happens. And then what? Normally, nothing, unless the original founder scientists just don't believe that the drug could fail. Doctor Ari Asher is the founder and CEO of NuVivo. She tells us about the regenesis of this promising ALS drug, how it was reacquired, how they figured out what the problem was, how they went back and got even more data from the same patients, and about its new drug application recently submitted to the FDA.
Dr. Moira Gunn:Additionally exciting, this drug has other potential. Neuvivo is ready to initiate phase two studies in Huntington's Alzheimer's disease and vascular dementia. Doctor Azhir, welcome.
Dr. Ari Azhir:Glad to be here, Moira.
Dr. Moira Gunn:Now we're gonna be talking about a lot today. Yes. There are medical conditions that, NuVivo is working on and has had some success in, such as ALS, Huntington's, muscular dystrophy, frontotemporal dementia, and more, but we're also talking about how biotech companies can take out what we'll call it perhaps a misstep or a missing of the opportunity, and this is one for the books, I must say. Let's start with Neuvivo's lead compound, n p zero zero one, and there already is a good story there. Those of you in biotech know that a company develops a number of drug candidates, all somewhat different, and they're numbered from one to however many drug compounds they're working on.
Dr. Moira Gunn:Normally, a company's very first drug that they would take into human trials might be number six ten or number three zero two if they were just a start up and and had just working on variations on their one drug. But this is the very first time that I've seen it. Neuvivo's first drug in clinic is number one. And why? Because you, doctor Azhir, started Neuvivo by purchasing this drug from another company where it had failed in human trials.
Dr. Moira Gunn:And you purchased the drug, and all its human data and all its intellectual property because you knew the drug. How did you know the drug?
Dr. Ari Azhir:Well, I know this drug because I actually started a company called Noreltos, and this was the drug that I was one of the founders and have the patent holder, and I developed it in Noreltos. So we took it up to phase one and phase two human clinical trial. And it was very exciting data, and the company decided they wanted to have somebody from big pharma running the company after me. I was a CEO and a founder of the company at that time, and then I left.
Dr. Moira Gunn:Uh-huh. So we needed somebody from the big pharmaceutical area, and you had to exit. So no longer with the company. Yes. How long ago was that?
Dr. Ari Azhir:I left in 02/2011.
Dr. Moira Gunn:So that's thirteen years ago. Very exciting. Very exciting. Now by my count, they went through five CEOs in the meantime before you purchased the drug, and we'll return to that story. So listener put a pin in it.
Dr. Moira Gunn:But now we're gonna talk about ALS as the drug was developed to treat ALS. So describe what ALS is like for people with the condition. What is it?
Dr. Ari Azhir:ALS is neurodegenerative disease. That means gradually within two to four years after diagnosis, the patient die. They it can start from top, you know, from the speech pattern, gradually different muscles lose function, and so on. So it's a very heart disease, and the duration is very short.
Dr. Moira Gunn:I understand that it's very difficult to diagnose.
Dr. Ari Azhir:Well, because as I told you, it starts from different part of the body. And the diagnosis at the moment, I think, is still a challenge for people. So people come and they have sort of hand, tremble. So they don't know whether it's ALS or something else. And they have a speech problem.
Dr. Ari Azhir:They don't know whether it's ALS or something else, and they have to go to neurologist to be able to be able to diagnose. They start with normally, you know, general practitioner, and then they will go to neurologist.
Dr. Moira Gunn:How many people have ALS? How is this very widespread?
Dr. Ari Azhir:No. It's an orphan drug. There is a at the moment, they said it's thirty thousand people. And thirty thousand people, I think there's a lot of people who are misdiagnosed. The problem is more than that.
Dr. Ari Azhir:The the first time it was diagnosed was Lou Gehrig eighty years ago. And since then, there has never been any, therapy for treatment of ALS.
Dr. Moira Gunn:So if you're diagnosed with it and they're sure it is, then within several years, you just can't expect to recover.
Dr. Ari Azhir:Yes. Within two to four years, you probably die, unfortunately.
Dr. Moira Gunn:And the drug that we're talking about, was it a pill, an injection? How how would the patients take it?
Dr. Ari Azhir:Oh, it's an injection. They take it. The first month, they take five days in a row. And then after that, three treatments a month for six months. That was the study that we have conducted.
Dr. Moira Gunn:Now how is this drug different from other approaches to treating ALS?
Dr. Ari Azhir:Oh, this is wonderful. Because I think everybody else has tried to figure out what is missing, which neuron is damaged, and try to figure out the, healing that neuron. We our approach is very different. We think, ALS starts in immune system. So if we can regulate immune system, we can stop any attack, and the body can automatically recover from any attack it takes, whether it's a neuro damage, whether it's extra proteins, whether it is, viruses or bacteria infection.
Dr. Ari Azhir:If we can regulate the immune system, it recurs from all these attacks.
Dr. Moira Gunn:Now what exactly is wrong with the immune system in the case of ALS?
Dr. Ari Azhir:There is because it's been attacked very intensely, it is missing a molecule which normally uses for recovery of the immune system. This molecule is called toluene. So we provide this molecule so the the system can recover, has the ability to recover.
Dr. Moira Gunn:So you're not in the brain. You're in the immune system treating ALS.
Dr. Ari Azhir:Yes. Correct.
Dr. Moira Gunn:So let me get this straight. That company took this drug through phase one, phase two a, two b, you know, two trials there in tube in phase two. And it's a failure. It doesn't work. Right?
Dr. Ari Azhir:Yes. But we didn't believe it.
Dr. Moira Gunn:So along with the drug trial failure, the company failed. And and usually, that's that. But you acquired it, and now you could really take a look at the protocols of the trials, at the data that had been collected and had been looked at, you know, which which had determined that the drug had failed. Some 200,000 pages of paper, which is just shocking to anyone. What did you learn when you looked at all this?
Dr. Ari Azhir:So what we learned, first, we were surprised because usually when you do another trial, you repeat what you find the first time. So they didn't do that. So we start looking at the data very extensively from all direction. We found there was a programming, mistake, so we fixed that. And then we start looking at the data to understand how our molecule works.
Dr. Ari Azhir:So we have looked at many different ways of understanding the way that the molecule works. And also in this process, we were lucky because the science has also came up and we have some other supporting other scientists telling us our way of looking at immune system is the right way. So we looked at the molecule. We understood it under it impacts the ability to breathe. The the reason these people die is because we stop.
Dr. Ari Azhir:They have a breathing problem. And so we said, oh my god. The ability to breathe. And then we understood why does it, the ability of breathe, where does it impact? It was a diaphragm, so it's a muscle impact.
Dr. Ari Azhir:So we decided to look at other muscle functions in the body. You know, we added both trial together. There were two phase two trials. We added together, and we looked at the impact on functionality of how different muscles and, function impacted in ALS, like the ability to talk, the ability to eat, the ability to walk, the ability to breathe, the ability to putting a jacket on. So we looked at every single muscle function, and we saw that it improves.
Dr. Ari Azhir:The totality of the data shows it significantly, impacts for people mainly 65 years and younger. The the reason is, like, you know, like anything, after 65 years old, you know, our muscle deteriorates, our skin is, as not as good as when we were younger. Also, immune system declines. So these people, 65 youngers, their immune system was still able to engage, to be able to get re the molecule n p zero zero one and recover from any attack that the body has been under.
Dr. Moira Gunn:So here you are. You've got all this data from phase two a and phase two b, the the two phase two trials, and you've reprogrammed it. So you get the true results here showing very positive results. And let's not forget that this is, an orphan drug, so, you don't need to do a big phase three trial. If this had been successful the first time out in phase two a and b, you would go right to a new drug application, an NDA to say, great.
Dr. Moira Gunn:We're ready to go to a new drug applying to the FDA. And so what do you do then? You've got this positive data. What do you do then?
Dr. Ari Azhir:That's a really good question. So we went we told, okay. We have an impact on respiratory function, so we need to know whether it's a survival benefit. So we had the patients, but we hadn't collected how long did they live after they took the treatment. So we hired this contract research organization.
Dr. Ari Azhir:They went back to all the clinical investigators who had enrolled this patient and in a blinded fashion. So we didn't know who was on a a drug and who was on a placebo. And they collected the last state that these patients were alive. This was eleven years of tracking every single patient. And then we did the survival study, which was statistically significant for patient 65 years old.
Dr. Ari Azhir:So we got obviously very excited, and now we decide to put the new drug application. So for the entire population, the extension of survival was four four months. There is nothing in the, in the pipeline that any treatment extends the survival more than two and three months. Then we looked at 65 years and younger. And in that patient population, the extension of survivor was seventeen point one month, which is unheard of after six months of treatment, just after six months of treatment.
Dr. Ari Azhir:So we thought, okay. Now we have a drug. So we decided to put a new drug application package together, and we took us, like, six months to put the package together as, Moira said it took 200,000 pages, and we submitted to FDA about six weeks ago. And we are hoping to get approval in summer or spring next year.
Dr. Moira Gunn:This is very exciting. Now, obviously, this will help somewhat people 65, but 65, this is phenomenal news, you know, a year and a half more, just with six months of treatment. Now the question that I have is, like, why wasn't it any better for people 65?
Dr. Ari Azhir:Well, the people 65, their immune system has declined, so they are not necessarily able to engage in recovery. So it is too much further down because of other diseases. Some people have diabetes. Some people have cancer. Some people have cardiovascular.
Dr. Ari Azhir:So the inflammation is far more than just ALS inflammation.
Dr. Moira Gunn:Now I know you're also working on other medical conditions, Huntington's, muscular dystrophy, frontotemporal dementia, and others. Is it the same drug you are using?
Dr. Ari Azhir:Yes. We are hoping to use the same drug, and might be different formulation. And, so the the orphan drug like Huntington, we think with one study, we can actually apply for new drug application for that disease as well. But for bigger drugs, you know, an indication like Alzheimer's, Parkinson, front you know, that might be different. We might need to do two two studies.
Dr. Moira Gunn:But as we said earlier, this is a whole new approach. You're not looking at the neurons and the neurological part to treat. You're backing it up to the immune system and the missing molecule that is the recovery molecule.
Dr. Ari Azhir:Yes. It I mean, that's why it's so exciting because we're getting the body to act as a healthy body that they can recover by themself. And that's really what is so exciting about our findings.
Dr. Moira Gunn:Well, yours is an exceptional journey. What would you say to entrepreneurs out there, biotech and otherwise?
Dr. Ari Azhir:I would say, first of all, more important, you need to understand your data, and your data can be understood by scientists, medical profession who knows the science behind the drug, and also the disease, how the disease works. So you really need to look at every single data point that you have. And, you know, we call it in in our profession biomarkers. Like, how do we know the muscle is improving? There when you go to clinical labs, there is something that's called creatinine.
Dr. Ari Azhir:You they measure it, and that tells you that your muscle is working, your kidney is working. Very simple. You don't really need to do much. And you we had this data. We just needed to analyze.
Dr. Moira Gunn:Well, I think that the lesson is if doctor Ashir is looking to buy a company, stand next to her and and buy some of it too.
Dr. Ari Azhir:But thank you.
Dr. Moira Gunn:Doctor Azhir, thank you so much for joining us, and I hope you'll come back and see us again.
Dr. Ari Azhir:Thank you, Moira. It was a pleasure. I'm you know, I love to share my experience so other people can learn from it and not give up so soon.
Dr. Moira Gunn:Doctor Ari Azhir is the founder and CEO of Neuvivo. More information is available on the web@neuvivo.com. That's neuvivo, neuvivo Com.
