Conference Transcript - NAMS 2026-06-03

Dennis Deng, Analyst — Jefferies

Hi, good morning. Welcome to the Jefferies Healthcare Conference. My name is Dennis Dane, biotech analyst here at Jefferies. I have the wonderful pleasure of having Michael Davidson, CEO of New Amsterdam Pharma, here with us. Welcome.

Michael Davidson, CEO

Thank you. Before we kind of go into the fireside, we'd love to give you the opportunity to just make some opening comments around New Amsterdam, just some of the incredible progress that you guys have made over the last several years sure thank you thanks everyone thanks for joining uh this morning um of course we feel uh it's been a really great year of progress for us at new amsterdam uh we um we filed in europe for approval and um we announced just a few weeks ago that you know based on you know what we're seeing in prevail and tracking Broadway you know first-year events now we're seeing lower events than expected even if you impute a certain decay in the placebo arm which is what you can expect we really feel encouraged by a reduction in in all all endpoints across the board in our second year and then tracking even beyond the second year you know we feel and we're in a good spot to have an interim analysis that would maybe stop the trial a year before otherwise completing so we want to make sure we don't anyway jeopardize the results of the overall trials we've done a lot of digging into you know when do you see the best results and it's roughly year three to four it's we're right in that in that point because then you have to worry about study maintenance and retention and drop in drop out so we feel we're in a really good spot whether the interim is the successful and we we're optimistic about that or we need to go the full you know the full four plus years to to get the the ultimate number of events that we want to make sure we power the study down to a 15 percent for the primary endpoint if necessary, which we know has been the benchmark for all the other LDL trials. So if you look at all the LDL trials last decade, it's ranged from 9 percent to 19 percent. So we feel that we want to make sure we can capture that benefit because that still gives us an exceptionally good overall MACE benefit that we can then utilize our other benefits of ovocetrapib in our differentiation in the marketplace. So we feel in a good spot, and we're moving forward with Rubens and Rembrandt, our other important trials for labeling. And so in general, we're very excited about who we are. We are going to announce the, I've been saying, we're going to announce the start of our new Alzheimer's trial. And we're presenting at the Alzheimer's meeting in July a number of exciting insights into our Broadway data still that continues to give us more and more excitement about what Obacetropib is doing in patients that are at risk for Alzheimer's. And also, at the same time, we're seeing the field of Alzheimer's itself evolve in that there's now very much recognition that it's a disease process that begins 20 years before symptoms, in other words, cognitive decline. And so if we can intervene earlier, you have a much greater chance of showing a benefit Because once neurodegeneration kicks in, it's really a very difficult disease to modify. And so we feel we're in the right spot with the right drug to make a big difference for that devastating disease. And our data is, again, getting a lot of traction among the key opinion leaders in Alzheimer's and a very large support for what we're trying to do with our next study. And more to come on that when we officially launch the trial in a few months.

Dennis Deng, Analyst — Jefferies

So it sounds to me like, you know, if I take a step back, it's really more than just about LDL-C, right? You guys have shown an LPL-A benefit, some, you know, benefit in diabetes. You guys are starting an Alzheimer's trial to try to tease out some of these benefits. Like, I guess biologically, like, what is really driving that level of LDL-plus sort of benefits? Like, do you have a hypothesis about that?

Michael Davidson, CEO

So first and foremost about ovacetrapib that I think is not really appreciated as much as it should is how well-tolerated and no difference in the side effect profile of placebo in our phase 3 trials. And that really resonates very well with patients and clinicians. That's important differentiating, number one, because, listen, and I don't know if you talk to your friends about their medical issues, but as you know, many people are on statins, and I guess I'm probably got a biased view as a cardiologist, but almost everybody that I see socially complains about their statin and what it does to their muscles and side effects. Of course, in my lipid clinic, it's a nonstop. I don't want to take a statin. I don't want to get diabetes. I don't want to get muscle aches. I don't want to get Alzheimer's disease. All those things are unfortunate about how statins are being perceived in the marketplace. However, it sets up to be really well differentiated from any other LDL drug when it becomes available because it does whatever statins do that people don't like, it does the opposite. So it lowers the risk of diabetes, lowers LPL-A, It lowers the risk of Alzheimer's disease based on our Broadway biomarker data, and it lowers the small particles which statins don't really address in residual risk patients with cardiometabolic disease. So in many ways, it's exactly the right drug at the right time for the majority of patients who want something to address their LDL initially, but also if we can address all these other factors that they're highly motivated about addressing, we feel that we're going to get the lion's share of either the drug to add to statins or, as often the case, people want to prefer a different drug than a statin. And so we feel very, very optimistic about, you know, how this drug's going to go when it starts getting utilized after launch.

Dennis Deng, Analyst — Jefferies

Yeah. So then, you know, you guys are obviously running Prevail, CVOT, almost a 10,000 patient trial, and we just crossed the two-year mark for all these patients. So maybe comment a little bit about, you know, the event rates that you have seen on a blinded basis and how does that track relative to your internal expectations, and also touch a little bit about the new statistical protocol that you guys implemented.

Michael Davidson, CEO

Right. So when you start a trial, you use a certain predicted event rate from other trials that you can look at. And the one that's the most utilized is the Fourier trial by Repatha, because it's a chronic heart disease population. LDL 90, about a third have diabetes. so it's you know we looked at prevail getting started we felt this was going to be the right you know kind of base to judge our outcomes on so that that's where we started from and then it says one that's one range and then if you look at you know many other trials there's been 15 CVOTs done in the last decade, and you can match with AI in particular. You can look at all the different placebo event rates over time in all these trials and come up with what you believe would be a good estimate range for placebo event rates. And that's, we've done that, of course. And then, which I think is even a better way of thinking about it, is that Broadway was designed as to be a mini prevail in other words basically the same inclusion criteria the same sites the same dsmb the same steering committee the same course investigators and coordinators so you could not ask for a better like mini de-risking study uh for prevail than broadway and so So when we saw that the first-year event rates in Broadway track the first-year event rates in Prevail very, very closely, not just four-point, but also three-point, and then every single component, we look at everything, non-fatal MI, stroke, revascularization, death, of course, all those things tracked very, very well with Prevail, which means that our 21% relative risk reduction that we saw between placebo and active in Broadway, that could be exactly what could be applied to Prevail as well, assuming the placebo arms are going to be the same. And again, there's no reason to believe they would not be. Then we look at year two and three now, follow up, and you expect a little bit of decay in the placebo arm over time. and that's again you can track that from any other many other trials as well you can see a decay rate and that our reduction in our blended event rate is even lower than expected in that regard so we have again we have to also be cautious of course it's a famous line is you know a good way to lower your risk is to be a placebo patient in a cardiovascular outcome trial so it's you know it's always something you have to be aware of but even taking all that into consideration we look at the ranges of event rates and placebo across the whole spectrum of these trials you know we are in our blended rate looking very encouraging across all these trials so that that gives us I think the reason why we decided to go with the interim is for that reason I mean ideally you want to go all the way to the end and maximize the results but in this situation it's about a year difference and we think that year difference is critical if we feel encouraged by it if necessary we'll go the extra year if we don't stop to the interim but the chance to get on the market a year early and a competitive environment and with this type of data that we're seeing we came to this this conclusion that it's the best thing for for the drug and for the And for where we are, we want to go with developing the entire spectrum of benefit. We want to get ahead of other competitive LDL drugs. There's good reasons to do it, but we were hesitant because we didn't in any way want to jeopardize the final results. And we feel we're not going to do that, either by the powering or by the expected relative risk reduction. We feel that this is a relatively conservative, you know, smart decision to make. And if we can stop at the interim, which we feel encouraged about, all we do is basically have to match what we saw in Broadway to do that. If not, we go to the end, and we'll have still a very good drug to launch as well. So that's kind of our thinking about the whole process. But a lot of it went into it. I'm a very conservative decision maker by nature. And I wanted to make sure we don't in any way jeopardize the trial. Again, Prevail is designed for success. We don't want the trial to fail the drug. It's always been our main principle. Because of all the history of other studies in this class, we're focusing on HDL raising and not focusing on what was the right type of study for an LDL-ary therapy. And we feel we've done that with Prevail, and we want to see it complete, and we feel this is the right decision going forward.

Dennis Deng, Analyst — Jefferies

So you said something really interesting, which is that, you know, you're trying to match it with Broadway, right? And Broadway showed 21% at one year. So when you're thinking about powering for the interim, like, I guess, can you comment a little bit on, like, how much power you have? And, you know, I know that's not disclosed yet. Maybe we'll get it later this year.

Michael Davidson, CEO

But just curious, what approach are you taking to that? are you assuming like a similar 20% you know like a risk reduction to hit on the interim or we say we're well powered and said two things we are well powered and we also said that if we do hit the 21% for both 4.3 point again the 20% for four point in Broadway that will be sufficient to get a p-value to stop the trial that I think that's as far as we want to go on disclosure because there's a there's always a range of you know it's it the the p-value is determined by the number of events and the relative risk reduction and so we we there's a range there where it could be and we want to we want to be careful so we actually you know lock that time in that you know we the power could change modestly so we feel right now we have really good power well projecting at that interim analysis stopping at the end of end of this year with the results in the first quarter of next year but at the same time like what do you view as a clinically meaningful uh mace for reduction right because like you know if it were to show 15 16 70 percent right that's still better than Fourier and like Odyssey and some of those studies so like if it does end up being that scenario could the trial also stop because it could stop yes good stuff I mean it's it's it's it's more likely to stop if it's in that closer to 20% range but but it still has a chance to stop it's all depending on on the number of events the actual number of events at the end of the day but there but that's a scenario where you know if you don't hit the p-values that that have been designated which are designated based on the regulatory approvals then then we could go longer and have more more power more events that get us to those those relative risk reductions that are still you know quite impressive considering you know these studies are like I said the range of benefit is range from 9 to 19 percent in all the different trials, and ezetimibe, which is 9 percent, is now widely, widely used. I mean, so it's not about the relative risk reduction that matters. It's about the LDL lowering with its overall profile that matters for clinicians.

Dennis Deng, Analyst — Jefferies

Yeah, I was going to ask, because, like, you know, when you speak with investors, there is some sort of expectation that you know the risk reduction would be closer towards the 20% range but like I'm curious you know the feedback that you get from cardiologists I'm sure you're very well connected you talk to all the leading cardiologists like what is their feedback like does it really matter if it's 15% versus 20% in terms of how excited or enthusiastic they would use you know your product it doesn't matter there are some that matters yes but not majority you know we've already done it's roughly of all the cardio maybe 10% it

Michael Davidson, CEO

matters for those tend to be the ivory tower types that don't really write prescriptions anyway I mean so it's it's it's not not to not to to be derogatory about the ivory tower they're all my friends but the idea is that when when you know the drug works and it lowers the thing that I know this is getting into the weeds a little bit but it's actually the amount of reduction per milligram or millimole of LDL lowering and you can adjust that as well and that's why the reveal study is very important because the reveal study showed that the 11 milligram per deciliter drop in LDL was a 9% benefit so people said 9% that's not very impressive but that 11 milligrams if you look at how that correlated, that would be more like a 25% relative risk reduction, the amount of aldeolaurin that was achieved. So that's really what's the important parameter, and we're starting to recognize, as people dive into these studies, they realize that's a more and more important parameter. When you adjust for how much aldeolaurin you had in the trial, that, and that, how that relates to the relative risk reduction, that's a much more important number to look at. It's not what the study overall, because you have drop-in, drop-outs. You have lost the – if you look at on treatment, on the drug, getting great LDL lowering, you have a much different number than the overall study results. And so that's why it's so important for us. One of our most important goals for the company is to maintain a high quality of Prevail. We're out there. We have full-time people going to all the sites. We've had many, many meetings at the site level to encourage investigators to maintain compliance in the trial. That's what we can do. That's our most value add to Prevail is to really work hard to make sure that every patient that's in the trial stays in the trial and ideally stays on drug throughout the treatment That's the best we can do. So, and the more we can do that, the better the results are going to be.

Dennis Deng, Analyst — Jefferies

Yeah, and, you know, even though the trial might be longer in terms of the full top line, the fact that you guys have a very, very clean safety should minimize the amount of dropouts over time, which, you know, because MACE benefit gets better over time, but also that's offset by dropouts.

Michael Davidson, CEO

Like, like, like, like, like, like, like, like, like, like Clary Outcomes had a pretty high dropout rate. and that was a little bit of a skewed population because with stat intolerant patients and that was it still worked but you know that was the amount of aldeolaurine they were hoping for wasn't quite there overall but that's why what's great about the centropib is because people that are on the drug we don't know of course who's on drug and placebo but we're seeing a low event rate We also think that, sorry, a low dropout rate, which we think is also, again, a good indicator that the drug is being well-tolerated for patients.

Dennis Deng, Analyst — Jefferies

And can you also comment on just the magnitude of drop-ins in terms of like GLP-1s and PCSK-9s?

Michael Davidson, CEO

Those are very low. They're low single digits for all those things. GLP-1, SGLT-2s, and PCSK-9s, and azetamide. If you look at all those drop-ins, and they're all quite low compared to the baseline treatment. Remember, we allowed p-ciscanidins at the beginning, so there was a few percent. There's just one or two percent more during the study.

Dennis Deng, Analyst — Jefferies

Okay. So, you know, it seems like based off of your own analysis of just, you know, the best CBOT trials over the last 10, 15 years to try to figure out if the lower event rate is really driven by obocetrapib or placebo it seems like based off of your analysis you seem fairly confident that it's not placebo overperforming or performing better than expected right so it's mostly we're let's say cautiously optimistic it's all driven by a obocetrapib benefit so again because we look for all these other causes we look for change of care you know drop in dropouts and we just not

Michael Davidson, CEO

seeing those would be any substantive amounts i mean remember talking about events that are you know three to five percent per hundred and if you lose one or two percent for drop in or drop out that that that numbers don't make that much difference yeah okay so the interim at the end of the year is going to be on mace four but how important is mace three well it's base three is important because we want that to also be positive for regulatory purposes especially in Europe where it becomes important even the FDA has made a comment that it's a review issue if you hit mace 4 but you don't hit mace 3 now this has not happened before so people don't there's there's no really historical thing to look at just to say that so but but I think it's it's still important to have mace for now what we have said though is that if you look at the event right so we track all the different forms of the events you know we've asked and but what we see the greatest decline in the years is that it is in the three-point mace events non-fatal MI stroke and and CHD death is where we're seeing the greatest decline in the blended event rates so it gives us again that gives us more confidence that the the three-point mace rate would be it also stuck you know efficacy would stop the trial okay but the interim is based off of mace four and three both have to hit the p-value yes okay okay you guys will probably host an investor day or commercial day later in the year so so I guess what should we expect in terms of incremental disclosure at that event well I think I guess the the biggest things we want to continue to show is we'll have even more data on on the event rates will be no six months late later on the the numbers that we've been talking about you know post you know post our second year announced and it will be you know roughly close to that three-year mark overall on the meeting follow-up and so you want to highlight for the investors who are looking at the interim and of course the final trial we want to show really multiple ways to look at it and and one is our LDL lowering non HDL apob lowering what what what without taking the event rates what what will be the expected risk reduction for the amount of LDL lowering that we get with ovacetrapib because compared to like 20 other trials that have been done and then again I think people feel optimistic about you know what Broadway results would translate into a prevail similar LDL lowering benefit into an outcome benefit secondly is reveal itself with the Merck study showing that that amount of LDL lowering actually outperformed on relative risk reduction you'd expect and we have evidence from that upper tertile where that's even you know very well you can see the it's all in the public domain that in that upper tertile is simply significant in its own right for mace reduction with a CT inhibitor does not lower LDL as much as as obacetrapib and then and then of course we'll go into even more detail potentially on on the event rates that we're seeing and why we feel that the Broadway is a really good de-risker of the results of a prevail and like I said we've done you know 15 other CVOTs out there to look at their matching of the event rates and we feel good about that as well even taking the Broadway was an outlier for some reason which was very highly unlikely to be the case we have also a lot of other evidence from these other trials that we can pull from to give us again encouraging view that the interim will be able to stop the trial at the interim analysis or at least complete the trial with a very successful study based on what we're seeing. So that's the kind of the framework we want to try to highlight for investors on that. They also have a lot of things that have happened in the commercial side of things and the market itself. You know, the market is getting much better and we're seeing obviously entrants in the market that are going to be competitive to us and we want to explain you know why obacentropia will do very well against this these other competitors in a rapidly growing market again for LDLC lowering then we'll talk about more about their Alzheimer's data presenting four new studies at the AIC meeting coming up in July and highlight again you know how impressive the Broadway biomarker data is and how that's helped us design our next study which will be starting relatively soon So one of the major reasons why I'm so excited about Amsterdam is not even just in ASCBD.

Dennis Deng, Analyst — Jefferies

I think what's super interesting is just the combinability of Obacetrapib, given the strong safety profile, and it's a convenient once daily pill, with many other sort of mechanisms as well. And I feel like strategics would obviously be very intrigued about that sort of profile. When you look at AstraZeneca, one of their strategies is to combine their oral PCSK9 with some of these other drugs. And I think they did start a study with statins. And even Merck, their oral PCSK9, I think they just started a phase one combination, not a fixed-dose combination trial, but with their LPLA oral. Yes. So I guess, you know, as you think about, you know, New Amsterdam for the next 3, 5, 10 years, like, would you explore all of these different combination opportunities? And, like, how would you prioritize?

Michael Davidson, CEO

Yeah, we are looking at all those combination ideas, and, you know, more to come on that. We believe that it is a pipeline and a pill, and there are other assets out there that would combine very well with ovocetrapib. And so we feel this is a really important pipeline build for the company. And so we feel with a successful launch at a pipeline, you know, will be evaluations that are far higher than they are now, you know, build shareholder value. And that comes with a, you know, with building a pipeline, and we are doing that.

Dennis Deng, Analyst — Jefferies

We haven't disclosed anything yet, but, you know, more to come. yeah and maybe that's gated by FDA approval right because getting like a fixed dose combo approved I think you only just need like bioequivalent study to it right we're setting the status for all those things yeah for all those things okay in the last minute or two maybe just comment on you know your cash position and just how well positioned you are to interrogate all of these opportunities as it stands today we're roughly 700 million in cash so we feel we're in a really good cash position and we have enough cash on hand to to

Michael Davidson, CEO

launch the drug and also potentially do some some pipeline build as well so we were planning on on doing that and so like I said we're we feel really good about where we are in our our company and we're building out the right we also want to highlight at the R&D day or investor day how the high caliber of people we've recruited to work on Obacetrapib I think people are very impressed by the caliber of people that have come to New Amsterdam just for the purpose of this of the value of Obacetrapib that they believe will will happen with patients perfect all right well I think that's all the time

Dennis Deng, Analyst — Jefferies

that we have today but thank you so much Michael thank you thank you Dennis