Hi, good morning. Welcome to the Jefferies Healthcare Conference. My name is Dennis Ding, biotech analyst here at Jefferies. I have the wonderful pleasure of having Michael Davidson, CEO of NewAmsterdam Pharma here with us. Welcome. Thank you. Before I go into the fireside, would love to give you the opportunity to just make some opening comments around NewAmsterdam. Just some of the incredible progress that you guys have made over the last several years. Sure. Thanks everyone. Thanks for joining this morning. Of course, we feel it's been a really great year of progress for us at NewAmsterdam. We filed in Europe for approval and we announced just a few weeks ago that based on what we're seeing in PREVAIL and tracking BROADWAY 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, where we really feel encouraged by a reduction in all endpoints across the board, in our second year, and then tracking even beyond the second year. We feel we're in a good sp ot to have an interim analysis that would maybe stop the trial a year before otherwise completing. We want to make sure we don't in any way jeopardize the results of the overall trial. We've done a lot of digging into when do you see the best results, and it's roughly year three to four. We're right in that point because then you have to worry about study maintenance and retention and drop in, drop out. We feel we're in a really good spot whether the interim is successful, and we are optimistic about that, or we need to go the full four-plus years to get the ultimate number of events that we want to make sure we power the study down to a 15% for the primary endpoint if necessary, which we know has been the benchmark for all the other LDL trials. If you look at all the other LDL trials over the last decade, it's ranged from 9% to 19%. 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 obicetrapib in our differentiation in the marketplace. We feel we're in a good spot and we're moving forward with RUBENS and REMBRANDT, our other important trials for labeling. In general, we're very excited about where we are. 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 obicetrapib is doing in patients that are at risk for Alzheimer's. 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. 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. We feel we're in the right spot with the right drug, to make a big difference for that devastating disease. Our data's, 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. It sounds to me like if I take a step back, it's really more than just about LDL-C, right? You guys have shown an Lp(a) benefit, some benefit in diabetes. You guys are starting an Alzheimer's trial to try to tease out some of these benefits. I guess biologically, what is really driving that level of LDL plus sort of benefits? Do you have a hypothesis about that? Sure. First and foremost about obicetrapib that I think is not really appreciated as much as it should, is how well-tolerated and no difference in the side effect profile than placebo in our phase III trials. That really resonates very well with patients and clinicians. That's important differentiator number one, because listen, 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 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. It sets us 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. It lowers the risk of diabetes, lowers Lp(a), it lowers the risk of Alzheimer's disease based on our BROADWAY biomarker data. It lowers the small particles, which statins don't really address in residual risk patients with cardiometabolic disease. 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 the either the drug to add to statins, or as often the case, people want to prefer a different drug than a statin. We feel very optimistic about how this drug's going to go when it starts getting utilized after launch. Yeah. You guys are obviously running PREVAIL, CVOT, almost a 10,000-patient trial. We just crossed the two-year mark for all these patients. Maybe comment a little bit about the event rates that you have seen on a blinded basis, and how does that track relative to your internal expectations? Also touch a little bit about the new statistical protocol that you guys implemented. Right. When you start a trial, you use a certain predicted event rate from other trials that you can look at. 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. When we looked at PREVAIL getting started, we felt this was going to be the right kind of base to judge our outcomes on. That's where we started from. That's one range. If you look at 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. We've done that, of course. 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 core investigators and coordinators. You could not ask for a better mini de-risking study for PREVAIL than BROADWAY. When we saw that the first-year event rates in BROADWAY track the first-year event rates in PREVAIL very closely, in 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 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, if assuming the placebo arms are going to be the same. Again, there's no reason to believe they would not be. We look at year two and three now follow-up, and you expect a little bit of decay in the placebo arm over time. Again, you can track that from many other trials as well. You can see a decay rate, our reduction in our blended event rate is even lower than expected in that regard. We have to also be cautious, of course. There's a famous line is, "A good way to lower your risk is to be a placebo patient in a cardiovascular outcome trial." It's always something you have to be aware of. Even taking all that into consideration, we look at the ranges of event rates in placebo across the whole spectrum of these trials. We are, in our blended rate, looking very encouraging across all these trials. That gives us, I think the reason why we decided to go with the interim is for that reason. Ideally, you want to go all the way to the end and maximize the results. In this situation, it's about a year difference, and we think that year difference is critical. We feel encouraged by it. If necessary, we'll go the extra year if we don't stop through the interim. The chance to get on the market a year early in a competitive environment with this type of data that we're seeing, we came to this conclusion. It's the best thing for the drug and for where we want to go with developing the entire spectrum of benefit. We want to get ahead of other competitive LDL drugs, and there's good reasons to do it, but we were hesitant because we didn't in any way want to jeopardize the final results. 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, smart decision to make. If we can stop at the interim, which we feel encouraged about, all we do basically have to match what we saw with BROADWAY to do that. If not, we go to the end, and we'll have a still a very good drug to launch as well. That's kind of our thinking about the whole process. 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. 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-lowering therapy. 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. You said something really interesting, which is that you're trying to match it with BROADWAY, right? BROADWAY showed 21% at one year. When you're thinking about powering for the interim, I guess, can you comment a little bit on how much power you have? I know that's not disclosed yet, and maybe we'll get it later this year, but just curious, what approach are you taking to that? Are you assuming a similar 20% risk reduction to hit on the interim, or could it be a little bit lower? We say we're well-powered, and we said two things. We are well-powered, we also said that if we do hit the 21% for both 4-point and 3-point, again, the 20% for 4-point in BROADWAY, that will be sufficient to get a P value to stop the trial. I think that's as far as we want to go on disclosure, because there's always a range. The P value is determined by the number of events and the relative risk reduction. There's a range there where it could be, and we want to be careful until we actually lock that time in, that the powering could change modestly. We feel right now we have really good power, what we're projecting at that interim analysis, stopping at the end of this year with the results in the first quarter of next year. At the same time, what do you view as a clinically meaningful MACE for reduction, right? If it were to show 15%, 16%, 17%, right, that's still better than FOURIER and ODYSSEY and some of those studies. If it does end up being that scenario, could the trial also stop? It could stop, yes. Okay. It could stop. It's more likely to stop if it's in that closer to 20% range. It still has a chance to stop. It's all depending on the number of events, the actual number of events at the end of the day. That's a scenario where, if you don't hit the P values that have been designated, which are designated based on the regulatory approvals, then we could go longer and have more power, more events, that get us to those relative risk reductions that are still quite impressive, considering these studies are, like I said, the range of benefit is a range from 9 to 19% in all the different trials. Ezetimibe, which is 9%, is now widely used. It's not about the relative risk reduction that matters. It's about the LDL lowering with its overall profile that matters for clinicians. Yeah, I was going to ask because when you speak with investors, there is some sort of expectation that the risk reduction would be closer towards the 20% range. I'm curious, the feedback that you get from cardiologists, I'm sure you're very well-connected you talked to a ll the leading cardiologists. What is their feedback? Does it really matter if it's 15% versus 20% in terms of how excited or enthusiastic they would use your product? It doesn't matter. There are some that matter, yes, but not the majority. It's roughly, of all the cardiology, maybe 10% it matters for, and those tend to be the ivory tower types that don't really write prescriptions anyway. Not to be derogatory about the ivory tower, they're all my friends. The idea is that 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. You can adjust that as well. 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. People said, "9%, that's not very impressive." That 11 milligrams, if you look at how that correlated, that would be more like a 25% relative risk reduction, the amount of LDL lowering that was achieved. That's really what's the important parameter, and we're starting to. As people dive into these studies, they realize that's a more and more important parameter. When you adjust for how much LDL lowering you had in the trial, and 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. If you look at on treatment, on the drug, getting great LDL lowering, you have a much different number than the overall study results. That's why it's so important for us. One of our most important goals for the company is to maintain a high quality in 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 period. That's the best we can do, and the more we can do that, the better the results are going to be. Yeah. Even though the trial might be longer in terms of the full top line, the fact that you guys have a very clean safety should minimize the amount of dropouts over time, which, because MACE benefit gets better over time, but also that's offset by dropouts. Right. Like CLEAR Outcomes had a pretty high dropout rate. That was a little bit of a skewed population because it was statin-tolerant patients. It still worked, but the amount of LDL lowering they were hoping for wasn't quite there overall. That's why what's great about obicetrapib is because people that are on the drug, we don't know, of course, who's on drug or placebo, but we're seeing a low event rate. Sorry, a low dropout rate, which we think is also, again, a good indicator that the drug is being well-tolerated from patients. Okay. Can you also comment on just the magnitude of drop-ins in terms of GLP-1s and PCSK9s. Those are very low. They're low single digits for all those things. GLP-1, SGLT2s, and PCSK9s, and ezetimibe. You look at all those drop-ins, and they're all quite low compared to the baseline treatment. Remember, we allowed PCSK9s at the beginning, so there was a few percent. It was just a one or two% more during the study. Okay. It seems like based off of your own analysis of just the best CVOT trials over the last 10, 15 years to try to figure out if the lower event rate is really driven by obicetrapib or placebo, it seems like based off of your analysis, you seem fairly confident that it's not placebo over-performing or performing better than expected. Right? It's mostly obicetrapib. Yeah. We're, let's say, cautiously optimistic it's all driven by o bicetrapib benefit. We look for all these other causes. We look for change of care, drop-in, dropouts, and we're just not seeing those to be any substantive amounts. Remember, talking about events that are 3%-5% per 100, and if you lose 1% or 2% for drop-in or drop-out, that numbers don't make that much difference. Yeah. Okay. The interim at the end of the year is going to be on MACE-4, but how important is MACE-3? Well, MACE-3 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. There's no really historical thing to look at to say that. I think it's still important to have MACE-4. What we have said, though, is that if you look at the event rates, we track all the different forms of the events, Revasc. Where we see the greatest decline in the years is in the three-point MACE events. Non-fatal MI, stroke, and CHD death is where we're seeing the greatest decline in the blended event rates. Again, that gives us more confidence that the three-point MACE rate would be, also efficacy would stop the trial. Okay. The interim is based off of MACE-4. Three. Three. Both would hit. Both have to hit the P value, yes. Okay. Understood. You guys will probably host an investor day later in the year. I guess, what should we expect in terms of incremental disclosure at that event? I guess the biggest things we want to continue to show is we'll have even more data on the event rates. We'll be six months later on the numbers that we've been talking about, post our second year announce, and we'll be roughly close to that three-year mark overall on the median follow-up. We 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. One is our LDL lowering, non-HDL ApoB lowering. Without taking the event rates, what will be the expected risk reduction for the amount of LDL lowering that we get with obicetrapib, just compared with like 20 other trials that have been done. Then again, I think people feel optimistic about 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. We have evidence from that upper tertile where that's even. Very well, yo u can see that's all in the public domain, that in that upper tertile is simply significant in its own right for MACE reduction. With a CETP inhibitor does not lower LDL as much as obicetrapib. Then, of course, we'll go into even more detail potentially 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 PREVAIL. Like I said, we've done 15 other CVOTs out there to look at their matching of the event rates, and we feel good about that as well. Even if 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, an encouraging view that we'll be ab le 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. That's the kind of the framework we want to try to highlight for investors on that. Also, we're going to have a lot of things have happened in the commercial side of things, in the market itself. The market is getting much better. We're seeing, obviously, entrants in the market that are going to be competitive to us, and we want to explain why obicetrapib will do very well against these other competitors in a rapidly growing market again for LDL-C lowering. We'll talk more about their Alzheimer's data, presenting four new studies at the AAIC meeting coming up in July, and highlight again how impressive the BROADWAY biomarker data is and how that's helped us design our next study, which will be starting relatively soon. One of the major reasons why I'm so excited about NewAmsterdam is not even just in ASCVD, right? I think what's super interesting is just the combinability of obicetrapib, given the strong safety profile, and it's a convenient once-daily pill, right, with many other sort of mechanisms as well. Right? 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. Even Merck, their oral PCSK9, I think they just started a phase I combination, not a fixed-dose combination trial, but with their Lp(a) oral. Right? Yes. I guess, as you think about NewAmsterdam over the next three, five, 10 years, would you explore all of these different combination opportunities, how would you prioritize them? Yeah, we are looking at all those combination ideas, and more to come on that. We believe that it is a pipeline in a pill, and there are other assets out there that would combine very well with obicetrapib. We feel this is a really important pipeline build for the company. We feel with a successful launch and a pipeline, we'll be evaluations that are far higher than they are now, build shareholder value, and that comes with building a pipeline, and we are doing that. We haven't disclosed anything yet, but more to come. Yeah. Maybe that's gated by FDA approval. Right. Because getting a fixed-dose combo approved is, I think you only just need a bioequivalence study to a pprove product, right? Yeah. We're setting the stage for all those things. Yeah. For all those things. Okay. In the last minute or two, maybe just comment on your cash position, and just how well-positioned you are to interrogate all of these opportunities as it stands today. Right. We're roughly $700 million in cash, we feel we're in a really good cash position, we have enough cash on hand to launch the drug and also potentially do some pipeline build as well. We're planning on doing that. Like I said, we feel really good about where we are and our company. 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 obicetrapib. I think people will be very impressed by the caliber of people that have come to NewAmsterdam just for the purpose of the value of obicetrapib that they believe will happen with patients. Perfect. All right. Well, I think that's all the time that we have today. Thank you so much, Michael. It's great to see you. Thanks, Dennis. Dennis. Thank you. Thank you, Dennis. Bye now.