Hier noch das Transkript zum Fireside Chat. Dabei hat mir KI geholfen.
So newron is 25 years of innovation in CNS diseases goes back to a spin off from pharmacia to a group that worked on a compound class, which is called a voltage gated sodium charm blockers, which usually everybody would develop in epilepsy. But these chaps decided that, due to its very specific characteristics, they would take those compounds into indications like Parkinson's and pain and schizophrenia. The Parkinson drug, by the way, is on the market for 10 years in Europe and eight years in the United States. And we know from that drug number one, not only how to take drugs to the market get over all the hurdles, but we also know that class of compounds is extremely safe in patients. And number three, it works in the brain. So the Parkinson's drug, then the pain compound, is ready to start a phase three study in often pain times. But the real game changer is a evenamide in schizophrenia, because that combines a truly unique mechanism of action, the one and only glutamatergic mechanism. It will be the one and only drug that is developed for treatment resistant schizophrenia and pour responders, which is the majority of all schizophrenia patients for which there is no treatment, effective and safe treatment today, and it will be the first add on therapy ever in schizophrenia, because, as per the fact that all today's medications are autopaminergic, FDA has decided there's no good in add on. So our mission is on the compound side, that with the next pivotal study that was start a few weeks time and reports results by Q 3 next year, we should be able to submit an NDA and the email is maa by next year, and we should get that drug into patients very soon. If we look at the mission for our shareholders, that is clearly building value towards the level where all our peers who have been acquired lately we are, in fact, the most advanced schizophrenia asset and one of the very few independent companies left in the space. We want to get to a valuation that is comparable to our peers who have been acquired for multi billion dollars in the last 18 months, absolutely
Question:
All right, so let's talk more about schizophrenia. So this is an indication this is not only a US problem. It's a global problem. Roughly 1% of all adults in the entire world, they have schizophrenia. That's roughly 25 million or so across the world, and roughly 3 million or so just in the United States. So and if you look deep, deeper into this disease, does this three sub segment of population people who have positive symptoms or negative symptoms and then cognitive symptoms. So I'm curious, what's your clinical strategy? Are you specifically targeting a subdomain within schizophrenia? Or how should we think about your approach?
SW
I think you have to go back to how the first schizophrenia interrupt was invented, thoracine, which was used by a French doctor who wanted to put somebody on a sedative. And he found, pre surgically, he found that that guy improved psychosis here, and that was a dopamine blocker, receptor blocker. And since then, all approved drugs have followed that path, which means that today we have and we can talk about Clozapine, on which we don't know what the mechanism is, and we
talk about the cobenfy and the like,
who claim they are different. But in reality, all those drugs except Clozapine do work by dopamine. There's a huge unmet medical need because those drugs do not work in all patients. From the very beginning, we have 20% patients who are treatment resistant, they don't respond to dopamine because there is no dopamine imbalance in their brains, then we have that large number of patients growing more and more as they go through their lifelong career, schizophrenics who are losing the benefits of their dopaminergic treatment and become poor responders and ultimately treatment resistant. So the majority of schizophrenic patients today does not have a medium term, long term treatment that works much less is safe, because the side effects are terrible. Count, weight gain per week, sexual dysfunction, hormonal changes, Parkinson like symptoms because we reduced dopamin. So what we need, urgently need is a drug that works by a completely new mechanism of action that works in treatment resistant and poor responders and the first add on therapy, because if you have an adult therapy, you don't have to take patients off medication. You don't have relapses, hospitalization, no increased suicidality. That's exactly where we put evinamide, the regulatory strategy is developed for treatment resistant schizophrenia, so 50% of the patients, but as all the other approved drugs, it will expire into Bible depression, Alzheimer's, like symptoms,
Question
So let's delve deeper into the mechanism. So it's a voltage gated sodium channel blocker. And then, can you tell us what preliminary evidence you have? You can even. To talk about your phase two data, and what gives you more confidence, you know, to continue this program?
SW
knowledge building for more than a decade that there is something about glutamate in the brain. And I will say we tested our compound early pre clinically in all models of psychosis, psychiatry, mood disorders, anxiety, depression, and in all those models, it worked when we gave it as monotherapy or as an add on to current dopamine drugs, there is very exciting new know how, built by the professor Grace at the Pittsburgh University, and he says that, as per his research, schizophrenia starts at the hippocampus, but all today's drugs pulmonary drugs work and kick in five levels down, which means they are not hitting the target directly, and they have probably much more side effects than they should have if they are not targeting and you know what he found? He says there's one drug with one mechanism that works straight at hippocampus, that's glutamate, a drug that reduces the excessive availability of glutamate on hippocampus, and that's exactly evenamide. And not only that, he has established what I believe would soon be the gold standard model, the MAM model in schizophrenia. What he has found is that evenamide completely normalizes the glutamatergic imbalances at the hippocampus. It improves cognition, it improves negative symptoms, and perhaps most importantly, evenamide works, and the benefits keep on working way after the drug is out of the system, that means we have a process which explains our phase 2 to a phase 3 results and which indicate that this drug improves plasticity in the brain, which means a process of Slowly repairing the damage done in the brain of schizophrenia patients and putting things right again. And that's exactly what we saw in our phase 2 study. We have done a one year label I will admit study in treatment resistance schizophrenic patients. What we saw was a very slow start of the efficacy measured by panns total directly to young point. But it didn't matter, CGI, s, CTIC level function, whatever we looked at, we saw a continuous improvement from six weeks to one year with anything not only the mean change, we also saw that the responder rates, so minimum improvement levels doubled and tripled up to one year, we saw at the end of the one year, we had 50% of patients no longer qualifying as treatment resistance. They would not have been allowed to get into that study after one year of treatment. And 25% something never reported before. 25% of those patients were in remission, free from symptoms from minimally six months and all that, with no safety issues. Now I said this was open label, and it was 90% patients and more in India. So there was quite a bit of criticism, lot of excitement by KOLs, but criticism. So it was very important that just four months later, we had a phase three study in poor respondents, 70% overlap with the treatment resistant patients. And after four weeks, we could exactly confirm all the findings, highly statistically significant. All the endpoints mean change responder rates. Take the endpoint that you like, we still ever increasing improvement up to day 29 so now I can say, because the P values were like point 0,006 not 0.005, I can say it is obvious that this drug works what it needs, and that's our regulatory strategy. Is one study sufficiently positive that has per agreement with the FDA and the Europeans and the Canadians, one sufficiently positive phase three study to confirm these claims and the results we saw on the phase two, and then we can submit the NDA. Great, that's exactly what we intend to
Question
I just wanted to tell everybody that, you know, it's not quite common to do only one phase three schizophrenia. So I think you're one of the lucky ones who don't have to do two phase three studies, because that would be very, financially, very extensive,
SW
Yes, I would say one thing, though, because we are an add on treatment, right? Our patients do not need to be hospitalized, and that translates into substantially lower cost, but it also shows the substantial and the systematic advantage of our drug, you do not take patients off medication. In our case, you keep them on the best drug the doctor can give them, and then you add evenamide and you get the incremental benefits. And you get no incremental side effects, the worst side effects. We had in 3% patient was nasal pharyngitis. I tell you, this morning at the pool, I had another foreign guidance. I prefer that anytime over today's medication side effects. So it's, it's the perfect drug as an add on therapie, absolutely,
Question
all right, so let's talk about your Phase Three design. So can you tell us the degree of alignment between your randomized Phase Three versus the open label you've already done and it showed positive data, and what endpoints matter the most for the FDA, as well as for other regulators? So
SW
if this study would in the end, let me start with the end. If this study would confirm what we saw on the phase two or anything close to it. It will be a landmark study for a long period of time, because what we do is a one year double blind, placebo controlled study. We will measure all the endpoints, the primary endpoint with the panns total, which is the regulatory endpoint around the world. Yes, we do not necessarily be if it's the best endpoint, but there's no discussion and where we have met it in both studies. So no issue. And the key secondary endpoint will be the CGis, we will measure those endpoint and all the others at 12 weeks, which is the agreement with FDA after 12 weeks. Given what we know from the phase two and the phase three study, we should see a very remarkable improvement in the panns total, but we will go on that will be enough to submit the NDA. But we will go on up to 26 weeks, and that will be the long term efficacy that we will show to EMA, because that helps them waive the relapse prevention study, a very costly and long term study you have to do in Europe if you want to get a schizophrenic drug approved. We don't have to do it because we show long term efficacy, and then we will still go on for 52 weeks now. Importantly, the phase three study we just reported a few months ago did show the lowest placebo response in many years in schizophrenia, we had a 7% procedure response. You're used to 12 to 15. So why is that? And what are we going to do to replicate that super performance? One key topic that nobody has done before is that we looked in patients who said, I'm taking this or that, and they took the best selling anty psychotics in the world. And I should mention that in our phase three study, this included also patients of clozapine. And while everybody says you never combine closure with any other antipsychotic, because the efficacy will be reduced, we show an improvement in clozapine. So we can claim that our drug works with every other drug on the market, and every other drug will work with ours and will produce a benefit. What we did, and that was remarkable. We found, when we took blood samples of the patients, that 30% of the patients who wanted to join our study with the support of their doctor, did not take the medication, nor the dose. They claimed they took no medication, two medications, different medications. The doctors were wondering where those patients got the drug from. So what we did is we took them out. And that's exactly what we will do in the pivotal study. In the one year study, we will have six weeks of screening everybody and three times blood samples. Everybody who is not having the drug in the blood at the levels where it should be would be excluded, would not even be randomized to the study. And we will do another four blood samples during the 12 month treatment period. And we'll do the same so very rigid on the patients that make it. We will be absolutely rigid on the training of the raters, who will be all psychiatrists. We will have an independent global gremium, led by John kane, of the real KOLs in treatment resistant schizophrenia, who will review every single patient and make sure that he fully fulfills the trip criteria for treatment resistant schizophrenia, and we will try to have lower number of study centers with more patients to reduce reliability. If that all works like it worked in the phase two study, then we have a landmark study, and there's no doubt that this drug
should be approved.
Question
Great. So I have couple of questions with respect to your phase three data expectations. So let me start from efficacy first, during your interactions with the agency, how they said that? Oh, this is the panns total we were looking for. Let's say like between 8 to 10 improvement in panns score. Is there an efficacy bar that you set just to show that your drug could work better. That's the first one, and then second one in terms of safety angle, one of the thing that concerns me the most was schizophrenia is the discontinuation, right? You know, patients start a treatment within 12 months or so, 60 to 70% of them, they discontinue, they move to a new therapy, hoping that they want to see something different. Then, but that doesn't happen exactly within one year or 12 months or so, they again discontinue the treatment, and they go off the third medication, and then the vicious cycle continues. So tell me about your expectations for discontinuation rate with respect to your drug
SW.
Let's start with that one, because that is one of the most exciting findings within our phase two. Sure they were patients with treatment resistant schizophrenia, diagnosed. They had failed on each and any new drug. They had reached all the drug criteria. And our expectation was that within the six weeks we would lose 25 to 30% of patients, because that is the way it goes in treatment resistant schizophrenia. And we did absolutely not see that we had 90% of patients who completed the first six weeks. Then we said, Okay, guys, we don't know exactly why. It seems there must be some effect and there must be a very moderate, mild, side effect profile. Otherwise that would not have happened. Would you want to go on for the full one year? And practically everybody decided to go on, and after one year, we still had more than 80% of patients in the study. One year in treatment resistant patients, and that was the first message from the key opinion leaders when they reviewed the data. This might be open labeled no placebo, but you know what? No way in the world we can explain why a treatment resistant patient would stay in a study for one year if there was no effect, and if there were material side effects. So we can assume the drug works, and we can assume it is extremely safe, as we know from the class of compounds on the efficacy. Yes, it would be perfect to have 8, 9, 10, points of pans improvement, and that's possible if we look at the treatment size and the benefits we saw in the one year study. Now in the four week study, in the phase three, we had substantially less, and that's fair, because what we see is that gap starts opening at day 8 to 15, between day 8 and 15, and it widens rapidly to day 29 that's exactly what we saw in the one year study. It goes continuously up. So if we do a kind of analysis of where the improvement would be after 12 weeks, and that's one of the reasons why we have chosen 12 weeks, FDA would have been okay with 8. We said we would go for 12 weeks. Then they said, Fine, okay, that then we will see a very significant effect on the panns. Keep in mind, this is us comparing to monotherapy. If you develop a monotherapy, it's a kind of, should I say? Funny thing, you have a patient on a dopaminergic drug, which works. You take that drug away,
and you give him your dopaminergic drug and wonder, wonder it works. What we do is something completely different. We have patients who are on the best medication the doctor can give them, and they get all the benefit from their current medication. We are not replacing we are giving incremental benefit. That is number one, why it is much more challenging to get to eight nine points, okay? And the second topic is those patients are treatment resistant, they are not expected to get any incremental benefit. So that's why it is much more challenging for us to get to those eight nine points. And the FDA has clearly indicated it will not need eight nine points. Okay, the current expectation is that anything more 4 points will do,
Question
Thanks so much for the clarification. All right, so let's move to market opportunity. So this is a very big population, and then how are you planning to commercialize the drug? You can tell us, you know, because there's already some three dozen schizophrenia drugs that already approved, and some of them are offered once a day. Som of them twice a day. Some of them are extended release formulation. So how are you thinking to position your drug and maximize your advantage?
SW:
I have to come back to unmet medical need, okay, all those three dozen drugs, okay? And I would go so far now to say that will apply to cobenfy, because if you rented psychiatric times of last week, what they say is, look, this drug has huge potential, and I've no doubt that BMS would make billions of sales with that drug. No doubt because each and any new patent protected drug in the space does a billion minimum, and they are certainly very good in commercializing it. So it would be billions. What psychiatric times rightfully says is this drug is doing what the other drugs do indirectly dopaminergic benefit, but it promises to be substantially better on the side effects, and it could improve the integration of our patients back into society. So if you're a patient and you're gaining weight, like a pound a week, you're socially isolated. If you have sexual dysfunction, you withdraw from anything. And if Cobenfy should indeed not have those side effects, and it seems no, because the data don't say so. So that would be a major, major step forward. But don't go too far. That's also what psychiatric Times says. It's a cholinergic mechanism, and it was put on the shelf by Lily many years ago because of its massive cholinergic gi side effects. It has been modulated and improved, but still, if you have like 30, 40% of patients with nausea, vomiting, diarrhea, that is neither, something very like so today's treatments are still all dopaminergic. They still have one on the other side, handful of side effects. There's the huge medical need of those patients who really need a add on treatment, which combines to a existing drug on the market, and I see only one that would be our drug, which means that the doctor can give it to his patient if he can. After 18 months, he comes back and see, I need a new medication. Doesn't work any longer, but the side effects are unbearable. So for the first time, the doctor can say, I give you a drug with a completely different mechanism of action. First approved, add on therapy, additional benefits, no additional side effects, no risk of relapse, which is a risk for the doctor, hospitalization and increased suicide. So that's number one, first approved add on, then we have that huge number of patients who are treatment resistant, who are just swapping from sweeping from one drug to another, because the doctor needs to give them something. There's plenty of polypharmacy in this space. Not a single study has ever shown any good of polypharmacy the doctors does it anyway because he wants to give the patient something new. There's no evidence of improvement. Here comes the first drug that shows it works in all those patients because of its completely different mechanism of action, glutamide. So there is no doubt there will be a huge market for this drug. It's the one and only drug with a really, completely different mechanism. It's glutamate
Question
All right, great. So there's one. Maybe I have two questions, but let's get to that very quickly. Let's talk about m&a. Schizophrenia is a very, very hottest topic. It's one of the important topics everybody's paying attention to it. Part of the reason is because, you know, only this year, JJ acquired a intracellular for 14.6 billion. And not so long ago, BMS acquired Coronavirus for $14 billion so clearly, you know, people are very paying close attention to schizophrenia. So what is it you are doing to maximize your chances of being acquired, or maybe at least to get more partnership interest?
SW:
Yes, so the first step we did is we wanted to validate, we wanted to start closing the gap between us and our peers. And that is when, three months ago, we signed a deal with the ESIAI group in Japan. And what we wanted was we wanted to validate the mechanism, the positioning, the market potential. We wanted to get a huge amount of money to pay for our next study, and we wanted to get an indication of the intrinsic value of the project. And we succeeded nicely. I think nobody will dispute his eyes competence in CNS, they have innovated Aricept, the dementia drug, and they have been the inventor of the second generation Alzheimer's drug, for which Biogen gave up their own program. So no doubt EISAI is one of the top players in CNS, and the deal covers only 10% of the globe, but the value we got was $120 million and that's RPD, so make your math. That was step number one, but the market cap is still at $200 million dollars. So what does it need? If we want to go where Karuna was made, was acquired, they have submitted the NDA, yep, that will be enough next year. So if that takes us to $14 billion nice. But the other thing that's missing is a listing at the number one stock exchange in the world for biopharma, and that's NASDAQ. You know that we are listed on the stock exchange, so by the time that we will get the pivotal study results that qualify us to submit the NDA, this company should be listed on NASDAQ. And that's exactly our objective. And on the way there, we want to take on some first class crossover investors, institutions from the US or Europe, and that is the next task. So in order to prepare, we will do institutional investors on board, list our stock on NASDAQ, and when the results come, we will be happy to submit the NDA. And then we might, and our shareholders might well decide if they want to go the Karuna path or the intracellular path, because Cheryl, mates, with all my respect for her, has launched her own compound in the US for five years, got 16 times sales on Nasdaq and then sold it for another 60% premium to JJ. I love all those patent cliffs. I. Love Big Pharma coming back like walls with Wall Street Journal yesterday said Big Pharma is back in psychiatry.
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Robbi30 schrieb am 27.03.2025 22:50 Uhr
