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95. Bull, Bear & Beyond – Newron Pharmaceuticals: executive interview
7 Plays7 months ago
In this video, we speak with Stefan Weber, CEO of Newron Pharmaceuticals. We discuss the company’s registrational ENIGMA-TRS Phase III programme, the setting that evenamide is targeting and the licensing deals Newron has secured. Stefan also summarises the key milestones and catalysts that investors should watch out for across the next couple of years.
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About ‘Bull, Bear & Beyond’
Bull, Bear & Beyond': features candid conversations with senior executives and from our own team of experts from across industries, exploring strategy, innovation, and the opportunities shaping their markets and 60-second pieces are a compressed summary of content designed to convey our message in a single, easily shareable hit.
About Edison:
Edison is a content-led IR business. We believe quality investment content should inform all investors, not just brokers. Our mission: engage and build bigger, better-informed investor audiences for our clients.
Edison covers 50+ investment trusts, read about them here: https://www.edisongroup.com/equities/investment-companies/
Original interview published on 13/06/2025 and reposted as a podcast
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Transcript
Introduction of Episode and Guest
00:00:07
Speaker
Hello everyone and welcome to Edison TV. My name is Aaron Atkar and I'm a healthcare care analyst here at Edison. We're joined today by Stefan Weber, CEO of Neuron Pharmaceuticals. Neuron is a specialist in CNS drug developments with its lead clinical asset gearing up for a registration phase three programme in schizophrenia.
00:00:25
Speaker
Welcome Stefan. Thank you, Aaron, for having us. It's my absolute pleasure to join you. Excellent.
Enigma TRS Phase 3 Program Launch
00:00:31
Speaker
So to jump straight into it, Neuron's launching its registrational Enigma TRS phase three program in treatment resistant schizophrenia. So can you provide an overview of the trial designs, the endpoints agreed upon with regulators and the expected timelines for the program?
00:00:47
Speaker
Oh, absolutely. i think we are really proud that after last year's phase two and phase two slash three results, ah we got the agreement with all the key regulators, US, Europe and around the world to start our pivotal program.
00:01:02
Speaker
And that is very special because Avenomide, our compound, is the first drug in schizophrenia that works by a glutamatergic mechanism of action. um which supports and helps the vast majority of today's schizophrenic patients, those who are treatment resistant and those who are poor responders to any of today's medications.
00:01:21
Speaker
And it will still and confirmed to be the only add-on therapy ever to be approved in schizophrenia after the late phase 3 failure of the Comanfi. So to to get the buy-in from all the key regulators to take this into a phase three regulatory program that could support a submission of an NDA by end of next year is a key achievement.
Trial Design and Patient Criteria
00:01:44
Speaker
So this Enigma TIS program consists of two pivotal studies. Enigma TIS 1. will be a was a double-blind placebo-controlled study, a version of the phase two study that we had last year. So it is the first ever one-year pivotal program in treatment-resistant schizophrenia. 52 weeks.
00:02:09
Speaker
Double-blind placebo-controlled study will be performed in study centers in Europe, Asia, Latin America, and Canada. What we will do is we will take in patients who are diagnosed as treatment resistant schizophrenics according to the TRIP criteria.
00:02:25
Speaker
Those patients will have BPRS, which is the Pre-Psychiatric Rating Scale, score of at least 45. They will have a CGIS of mildly to severely ill, means three to six.
00:02:38
Speaker
And they will have prominent symptoms as per the BPRS. So these are the inclusion criteria. Each and any of those patients will be on a stable dose of either an oral or an injected current antipsychotic. The best choice at a therapeutic dose, the best choice of medication, standard of care the doctor can give them.
00:02:59
Speaker
Now, what we will do is, and that's very important, we did that also in the phase three study last year. Before we randomize the patient, we start with about 900 candidates who we put into a 42-day screening period.
00:03:16
Speaker
And we will check obviously for the confirm confirmation of the treatment resistance and meeting the criteria. But very importantly, what we will do is we will take three times plasma levels of the current antipsychotics because in our phase three study last year, we saw that more than 30% of patients who wanted to get into the study were not compliant.
00:03:37
Speaker
They took whatever medication, no medication, due medications, but they didn't take the one drug at the levels they should have taken them. We will make sure any patient who wants to be randomized will meet the inclusion criteria and will take the drug that he
Trial Phases and Regulatory Requirements
00:03:52
Speaker
claims to take. And then we will have a final choice of an international eligibility committee, which is headed by John Kane.
00:04:00
Speaker
Those guys will look at each and any patient's data and by you by the same criteria on everybody in all the territories will take a final decision if that patient is allowed in.
00:04:11
Speaker
So those patients will then be randomized. We will take them into an add-on treatment and we will have patients either placebo added to their current medication or low dose 15 mg BID or high dose 30 mg BID as an add-on to their current standard of care. After 12 weeks, we will have the first readout and the primary efficacy endpoint will be the PANS total, which is the regulatory endpoint, nothing to dispute.
00:04:39
Speaker
And the key secondary endpoint will it be the CGIS, the change from baseline. um That readout after 12 weeks will be what we need to start submitting the NDA.
00:04:52
Speaker
because the FDA endpoint is 12 weeks. But we will go on, double-blind perceived control, no re-randomization after 12 weeks. We will go on for up to 26 weeks and we'll have the second, the maintenance endpoint, which is very important because on the basis of a positive outcome, the European Medicines Agency has agreed that we will not have to do a relapse prevention study, which is, by the way, completely unethical in
Schizophrenia Market and Avenomide's Unique Position
00:05:15
Speaker
TRS. s And we will again measure the efficacy endpoint being the PANs total change.
00:05:22
Speaker
And then we will still go on for the full 52 weeks, never done before by any company in treatment-resistant schizophrenia, but based on those extremely promising results we had in the phase two in treatment-resistant when we saw ever-increasing efficacy up to one year.
00:05:37
Speaker
That is enigmaia as one Enigma Enigma TRS-2 will be the second pivotal study While Enigma TRS1 has already been initiated, TRS2 will be initiated around October. This study will be 12 weeks only.
00:05:54
Speaker
So absolutely in line what with what the FDA expects to submit an NDA. And it will be 400 patients only. And it will be 200 placebo.
00:06:05
Speaker
added to their current standard of care and 200 at 15 milligram BID added to their current standard of care. Everything else will be exactly like in TRS-1. TRS-2 will be starting in US study centers, which is obviously very important.
00:06:20
Speaker
And it will be expanded to the other territories and become thus an international study as we get more proceeds on board. On the timelines for both studies, we expect that in fourth quarter and end 2026, we would have the 12 weeks results and would get ready to submit an NDA, which obviously is extremely important and a key milestone then on our ends.
00:06:45
Speaker
I think that's fairly representing the pivotal program might have taken slightly more longer than it should have, but I think that was necessary. It is an extraordinary program, first drug ever, and if it could confirm anything close to what we saw in that phase two study up to one year, that would be just making a landmark study.
00:07:10
Speaker
Absolutely. It's great to hear all the details. ah You touched upon it, but schizophrenia has sort of been more in the headlines since the approval of BMS's CoBenphy. But we understand that Evanamide is targeting a slightly different population.
00:07:23
Speaker
So can you tell us a bit more about the setting that Neuron is targeting and then the market opportunity for this for this space? Let me start with the schizophrenia market as it
Impact of Avenomide and Market Opportunities
00:07:33
Speaker
is today. I mean, we are speaking about 1% of the global population suffering from schizophrenia. That's an enormous number.
00:07:41
Speaker
Now, you could say, well, we have dozens of drugs on the market. Everything should be fine. Now, the problem with the treatments we have on the market today is that the efficacy is limited, both to the level of improvement and time-wise.
00:07:55
Speaker
And at all today's medications, if it is the first or second generation, or if we now talk about cobenfee being something different, slightly different, doesn't matter. The side effects are terrible. We have a pound weight gain per week of treatment. We have sexual dysfunction. We have hormonal changes, Parkinson's a like symptoms.
00:08:14
Speaker
Now, the good news is that Cobenphi doesn't have plenty of that. But Cobenphi being a cholinergic receptor drug, even if it is amended and improved and those side effects are ameliorated by adding drospium, we still have about 40% of patients with nausea, vomiting, diarrhea, constipation, which is bad enough.
00:08:43
Speaker
ah so But the real point is, we have about one third of the population that nicely responds to today's monotherapy and psychotics, whichever drug it is. One third responds nicely.
00:09:00
Speaker
On the other hand, we have 30 to 50% of patients who are treatment resistant. 30% are those who are diagnosed, and 50% is what, if you speak to doctors, is the real number. If you ask them, why are those 20% not diagnosed, doctors would say, well, I have nothing to offer but Clozapine, a drug from the 80s, which is completely underused. Only 5% of the US TRS patients will take the only approved drug, which is Clozapine. Now, in between those patients who are well cared off, taken care of, and those who are treatment resistant, we have that large chunk of patients who we call poor responders.
00:09:43
Speaker
That is a group of patients which initially got the benefits from today's antipsychotics, but then they are fading in towards treatment resistance. And that is nicely documented by the CATI study, which shows that once you are into the disease for a number of years, your response to the medications gets worse and worse. And on average, every 18 months, 72% of patients will change their medication. It's just switching from one monotherapy anti-psychotic to another.
00:10:15
Speaker
It's just a switching of drugs and slightly side effects, but there has never been any single study which shows that this switching or an add-on of label does any good. We see plenty of polypharmacy without any evidence that this is really helping patients.
Research Findings and Mechanism of Action
00:10:34
Speaker
So there's a huge unmet medical need for a drug with a truly differentiated mechanism.
00:10:40
Speaker
and a first add-on therapy. Why is there no add-on in schizophrenia? Because the FDA rightfully says all drugs are working by dopaminergic mechanism, and though an add-on is just an increase of dose, there is no good to it. Here comes the only and the first drug working by glutamate.
00:10:58
Speaker
So that is why avenomide is different. And this is nicely documented by late research done by the Pittsburgh University and Dr. Grace, and that will be published also in the next few months. So what Dr. Grace has found is that schizophrenia is really a disease that starts at the hippocampus.
00:11:18
Speaker
Now, unfortunately, all today's drugs work four levels down on the dopaminergic pathway. So they are not targeted to the origin of the disease.
00:11:29
Speaker
And obviously the side effects are widespread if you don't hit the real target. Now, ah Dr. Grace has executed the MAM model, which is well known and will probably become the gold standard in schizophrenia. And what he has shown is that in the hippocampus, you see a major impact of this disease on the neuronal activity on cognition and negative symptoms.
00:11:51
Speaker
and avenomide was the only drug when given in his model did improve all of those right at the source at the hippocampus avenomide acts at the hippocampus it reverses the neuron hyperactivity it normalizes the bta dopamine neuron activity it impacts the lateral bta dopamine and Importantly, what we saw is that the time that avenomide worked, the benefits it had, went on for hours and hours after the drug was no longer in the body. And that is part of the magic behind that one-year improvement that we have seen in the Phase II study.
00:12:30
Speaker
And avenomide normalized cognition and it normalized social approach and behavior in those animals. So there's plenty of evidence here that avenomide is a truly differentiated drug. And that avenamide does not only help patients who are treatment resistant and poor responders, which is, as i have to say again, the vast majority of
Phase 2 Study Insights and Results
00:12:51
Speaker
patients. So if you want to see how avenamide is different, well, you have those drugs, which are all today's antipsychotics, including Copenfi.
00:13:00
Speaker
who work directly, indirectly via dopamine, and they do well on 30% patients. And you have 70% patients who urgently need a new medication, and that is Venomoid.
00:13:13
Speaker
So the market opportunity is huge. Being the only add-on therapy, it can be added to each and any antipsychotic, and very importantly, this is the first drug ever when added to glozipine has shown improvement on top and with glozipine.
00:13:29
Speaker
So that's the advantage and the promise of aveniment. Excellent. So we see that there's a lot of enthusiasm and optimism there from Neurons Management Team. And that's based on this encouraging track record of Evanamide in the clinic. So can you share some more details on some of the clinical highlights?
00:13:47
Speaker
Yes. So let me guide you through the key points that we found in our Phase 2 and Phase 2 slash 3 study, which have been published last year and have been Also scientifically published, so the publications are available by now. So the first study was the phase two study in 161 patients who were treatment resistant diagnosed.
00:14:05
Speaker
And what we did in those patients, we gave them avenomide on top of their current standard of care, whatever the doctor believed was the right therapy, and we did that for one year.
00:14:16
Speaker
And the first absolutely stunning thing we saw was that patients were staying in that study because usually what you see in TIS ah studies is that after four weeks, six weeks, a drove of patients like 30% leaves the study because A, the side effects on Beryl or B, there is just no benefit. As treatment resistant patients, you do not expect any more improvement. You have tried everything.
00:14:41
Speaker
So patients stayed in the study for six weeks. And then we asked patients, you want to go on up to one year? And 90% of those patients who were still in said, yes, we want to go on. And at the end of one year, we still had more than 80% of patients in the study completing it.
00:14:58
Speaker
That was the first major, major exciting news, because it tells you this drug is safe, We had no not a single relapse in that one year, not one.
00:15:10
Speaker
and ah And the drug shows some benefit because no patient in that population would stay for one year if he doesn't see improvement. Then we looked at the regulatory endpoints, perhaps so PANS total obviously, and the CGIS, the CGIC and level of functioning.
00:15:30
Speaker
And what we saw after six weeks was a kind of moderate improvement, like 12% improvement on the pants total. And people said, yeah, but look, this this could be a typical placebo effect. So 10%, 12%, 15% is the standard placebo response we see in schizophrenia studies lately.
00:15:49
Speaker
And we said, yeah, that's fair. So we looked again after six months. And importantly, the efficacy went up to 16%.
00:16:00
Speaker
And when we looked at the responder race, because you want to look at responders to be sure that it's not just a few super performers who spoiled the mean change. So responders was even more impressive because the number of patients who improved by at least 20%, which is the regulatory requirement in TRS, went from 15 to 30%, so doubled.
00:16:19
Speaker
So patients who saw an improvement, stayed and kept the improvement. And other patients who had not responded after six weeks, after six months were responders.
00:16:29
Speaker
And that percentage of patients tripled to almost triple to 43% at one year. And when we looked at the clinical global impression of change, we saw exactly the same picture and level of functioning the same. So the stunning thing is completely unexpected and not explainable and never seen before in treatment resistance. We saw one year improvement, permanent stable improvement up to one year. And it obviously doesn't stop there. It's just that we stopped the study there. Then we looked at the inclusion criteria. So the key criteria which we used to include patients and we looked how many of the patients would by end of one year still fulfill the criteria. And it was 50% who did no longer fulfill the criteria after one year.
00:17:15
Speaker
And then we went one step ahead and we said, look, the final LACMUS test, that's really the level of symptoms no longer being visible. So do we have patients in remission, which is not described in treatment-resistant schizophrenia as a consequence of being given a drug?
Significance of Phase 2 and Phase 3 Setup
00:17:32
Speaker
And we saw, regardless of which criteria, the toughest one requires that patients should be for six months practically without symptoms. And 25% of our patients fulfilled that top criteria. So 25% of our patients in that one-year study were free from symptoms for at least six months.
00:17:55
Speaker
Now we got a lot of beating for that study because there were two caveats. Number one, it is was mostly performed in Indian study centers because of COVID. And the number two was, well, it was not placebo controlled.
00:18:07
Speaker
And yes, everybody said, look, ah we we we cannot explain how placebo would create that effect. And what we can tell you is if those results can be repeated in double-blind placebo-controlled studies, they are unseen and unheard of.
00:18:22
Speaker
So it was very important that just a few months later, in April and May, we had two disclosures on a phase 2-3 double-blind placebo-controlled study with avenomide as an add-on treatment to current standard care standard of care in patients who were poor responders.
00:18:40
Speaker
So on average, not yet treatment resistant, but on their way, like 70% overlap of patients between poor responders and treatment resistant. That study was only four weeks long, which is what FDA says these days. After four weeks, you see if an antipsychotic works or not.
00:18:58
Speaker
And this study was run in 11 countries and 291 patients. So fulfilling all the criteria that you want. And what we saw was absolutely confirming, even in four weeks, what we saw in that one-year open-label study.
00:19:14
Speaker
Because in the Phase 2, 3, double-blind perceived control study, 11 countries, what we saw is when we added Avenomide to the best-selling antipsychotics of this world. And we included 14% patients on clozopine.
00:19:27
Speaker
What we saw was highly statistically e highly statistically significant efficacy on all the key endpoints. PANSTOTAL, CGI-S, CGI-C.
00:19:39
Speaker
And we saw highly statistically significant responder rates. And what we saw exactly like in the one-year study, even better after four weeks compared to the six weeks readout from the open-label study, we saw responder rates slowly and steadily differentiating from placebo and the gap always widening up to day 20 So with those results, we decided it was time to go to the regulators in the US, Europe and around the world and say, look, we want phase three program that will be good to get to the NDA level.
00:20:18
Speaker
And as you know, TRS is seen as an area of high unmet medical need. And in principle, it would be sufficient if you had one sufficiently positive phase three study in order to get this drug approved.
00:20:32
Speaker
That was our plan initially. But I would say that we have decided to go for two parallel pivotal studies just to make absolutely sure there is no risk here. And there's no chance of any delay because we might have to repeat one study which barely misses whatever the regulators deemed to be sufficiently positive. That's why we go for two studies in parallel.
00:20:53
Speaker
One is that landmark study, double blind placebo controlled one year, and one will be just a standard 12-week study, still if sufficiently positive enough to submit and get this drug approved.
Strategic Licensing and Financial Implications
00:21:07
Speaker
Excellent. So this positive sentiment seems to be shared given that Neurom has already secured some licensing deals. So can you give us an overview of these, touch upon the financial support that they provide and maybe cover what the commercial strategy might look like if successful with with approval?
00:21:23
Speaker
Yes, look, Aaron, I mean, we we have been telling this story for a number of years, and there's so much level of innovation in here, the glutamatergic mechanism, first of all, then going for the treatment resistant population where nothing has worked. And Clozapine is just not used for its massive side effects and administrative load for doctors and the the problems for patients.
00:21:46
Speaker
And there's no add-on treatment. So three promises of highly innovation, highly high level of innovation. And there was just some kind of disbelief. I mean, we are swimming against the the the river. We have 60 years now of dopaminergic drugs.
00:22:02
Speaker
We see Cobenphy being the revolution in schizophrenia, even if it's just indirectly dopaminergic drug. So Who would believe us, a small Italian biotech company, not even NASDAQ listed?
00:22:17
Speaker
So it was very important for us to get some first validation. And that is why we said, let us go to territories that we don't deem strategic. And let's be clear, the only ah territory we deem strategic is the United States, because that is 50% of the world market.
00:22:35
Speaker
So let us go to a territory where we get a top 10 PharmaPlayer with some absolute excellence in CNS space, respected in CNS. Let us get enough money from down payment and non-conditional milestones, let's call it like that, enough money to pay for a substantial chunk of that pivotal program and get it started.
00:22:58
Speaker
And let us try to get a first indication of the intrinsic value of the project, because our market cap is at $150 million. dollars Our peers, let's say by end of next year with positive results, our peer would have been Corona, because that is the time when they were acquired.
00:23:14
Speaker
So how do we close that gap? Well, we need a first indication of intrinsic value. So we run that process and I would say the process had an absolutely outstanding outcome in December last year because we got a deal signed with EA Pharma's ESAI Group.
00:23:31
Speaker
And ESAI Group we don't have to discuss. Azelect and Lekanamab is evidence of their outstanding excellence in CNS. They understand what they are doing. They have done a nine months due diligence. They know everything about the mechanism.
00:23:45
Speaker
the positioning, the market potential. And they signed that deal with us. And this deal gives them the rights to develop and commercialize Avenamide in Japan and some, for us not relevant Asian to territories, in total about 7% of the world market.
Commercial Strategy and Market Impact
00:24:04
Speaker
But what we got was 44 cash upfront, 44 million euros cash upfront, plus 11 million called milestones, but in reality support of the first pivotal study with no conditions of relevance. So 55 million euros of cash to pay for our pivotal program. Another 62 million euros up to, I should say, for regulatory ah and commercial milestones, including several indications. So, IZI, as we, does absolutely believe believe that this drug should not only be developed in TRS, but also in poor responders and depression, bipolar, and we believe it should work also in cognition in Alzheimer's-like patients, where all current psychotics are not allowed to be taken for massive side effects, risk of death. So,
00:24:58
Speaker
so Huge amount of money on top of those 170 million euros up to double digit tiered royalties. So a typical deal and on top is I will run the Japanese program at their own expense.
00:25:16
Speaker
And when our guys did, the Jefferies who supported us in the transaction, did the RNPV, Risk Adjusted Net Present Value, and we got a number of about $120 million. dollars for 7% of the world markets. That makes it easy to come to a first conclusion on what the intrinsic value of this project is. And that means we have we have hit all the click boxes, all the buttons with that deal.
00:25:43
Speaker
Then there was a second deal. i will mention that as well, that a deal for South Korea, which came within very short time after the first. and That is when Mee-yung-In, which is the number one CNS specialist in South Korea, said, look, we have gone through all this process with you. We are the number one CNS specialist in South Korea.
00:26:00
Speaker
Why don't we partner on South Korea? And we said, yeah, that's fine. And we got the usual financial terms, which we didn't or couldn't disclose. And then we said, but what is it that you really add to this? Which is the unique point that you bring to the table?
00:26:16
Speaker
And what Mee-yung-in said is, look, we have all the competence and resources here in South Korea. We'll add 10% of your 600 patients to your first pivotal study.
00:26:28
Speaker
And that is when it made click and we said, that's the deal. So what we will do, we will do more deals like that, like territories like LATAM, China, India, perhaps ultimately even Europe.
00:26:43
Speaker
before or around the time when we get the phase three results by Q4 end of next year. We will keep the US rights. And then by end of next year, let's assume we get the results in a way that they would allow us to submit an NDA and an MAA in Europe.
00:27:02
Speaker
Then we are still the owners of the US rights. And then the capital markets conditions and our shareholders will have to take a tough decision Probably if they want to sell the company around the US s rights and we know from intracellular what the value of US s rights in schizophrenia can be.
00:27:21
Speaker
Or if shareholders say, yes, we like that intracellular story very much, so why does Neuron not build up a management team for a US commercialization?
00:27:33
Speaker
sell it itself for a number of years, take it to some key value, like $500, $600 million dollars of sales as intracellular did, and then sell it to somebody like the big farmers who bought intracellular.
00:27:47
Speaker
So that's the optionality. If things go well, and those pivotal studies show what they should show and what we saw in the phase two study, then I guess we have plenty of options and our shareholders will have some very good days.
00:28:03
Speaker
Sounds good. Thanks very much, Stefan. Just before we wrap up, could you summarize for us some of the key milestones and catalysts that investors should watch out for across the next couple of years then?
00:28:14
Speaker
Oh, absolutely.
Upcoming Milestones and Investor Catalysts
00:28:15
Speaker
So let's start with the additional partnering deals that you might see as we go. It could be as early as in the next few months and it could spread over the next 15 months until we get close to those results. And those deals should add additional cash,
00:28:31
Speaker
because any cache is welcome to improve and broaden our database for the NDA. Any of the safety studies that we need to run, ah integrating efficacy endpoints on bipolar, on depression, or on Alzheimer's will strengthen our our documentation um and additional validation.
00:28:57
Speaker
Now, there's one thing that obviously in the current times sounds a bit strange, which our peers had at the time when they were acquired. They were all NASDAQ listed.
00:29:08
Speaker
I understand NASDAQ right now is not today. It's not the place where you must be. But in the end, look, Nasdaq is the largest market for capital and biotech assets.
00:29:21
Speaker
We are happy with our Swiss listing, but we are missing a number of investors who do not access European or Swiss listed companies. And we want everybody in the world who is interested in top biotech to have the chance to buy neural shares. And that is why we intend to at a certain point in time and obviously if the market allows it to uplist our shares to Nasdaq.
00:29:45
Speaker
So there is no click box on left by the time that we get those phase three results and our shareholders can benefit from the true value of this compound. So a lot of news flow, a lot of challenges as usual in our industry.
00:30:02
Speaker
But look, we have an absolutely outstanding unique compound. We have very exciting phase two results. We have confirming first phase three results and we have a validation from a top CNS player. We are really looking forward to those next 15, 18 months. And then if positive results, well, the door is wide open to everything that biotech shareholders dream of.
00:30:28
Speaker
Excellent. Stefan, thanks very much for the insightful discussion. I'm very much looking forward to following the progress of the Enigma TRS program. For more information and analysis, we direct our audience to the Edison website where our research is freely available.
00:30:42
Speaker
Stefan, thanks again for your time today. Thank you, Aaron. Have a good day.