All right, great. Thanks everyone for joining. Happy to kick off day two of the healthcare conference, and it's a pleasure to be here with the NewAmsterdam team. We have CEO Michael Davidson and CFO Ian Somaiya, and you know, a lot of exciting things going on in the lipid space, a lot of things going on at NewAmsterdam. Maybe Michael, you know, just can kind of level set with kind of where things stand with PREVAIL, kind of anything to take away from this past weekend at AHA, and then we can dive into some more details.
Great. Thank you for inviting us. We just came from the American Heart. We were there over the weekend, and on Saturday, the Freselius trial was presented, and it was great to see when these trials, when they first show the outcome, everyone starts applauding because, you know, we do not always get these types of positive trials. It was actually a moving experience because what was most important about Freselius is that, you know, when FOURIER, which was the previous Repatha trial, reported out, it actually worked, and everyone thought it was a good trial, but it had a 15% relative risk reduction, even though it had a very powerful LDL-lowering benefit, and there was no mortality benefit. This was kind of the monkey on their back of our lipid world guidelines and so forth.
When Freselius read out a 25% four-point MACE, 19%, sorry, 25% three-point MACE, 19% three-point MACE, and a mortality benefit, everyone got really excited. That cloud over the LDL world on top of statins, now for the first time, you see a mortality benefit adding to a statin. Lower is better is back, and I think this study is going to change guidelines, and it's going to change guidelines in a very important way, which is that it's going to markedly broaden the population whose LDL should be below 55, because that's what the evidence tells us, maybe even below, maybe at least 40, based on the evidence, because the mean LDL at the end was 45 milligrams per deciliter to show this benefit. This is a much broader population.
These patients did not have a heart attack or stroke yet, but they did have evidence of atherosclerotic disease, either a stent, you know, high coronary calcium score, or very high-risk diabetes, more than 10 years of diabetes, or taking insulin. It was still a high-risk population, but not nearly as high risk as FOURIER. FOURIER had about a 5% placebo event rate every year. This had about a 3.7% annual event. Still have events, but less so than FOURIER. The read-through for PREVAIL is very helpful to us because they went longer. That is how they got the benefit. They went 4.6 years, and that is how PREVAIL was designed, to go longer. There are events that they are imputing for their power, or what we have roughly decided will be for PREVAIL as well.
Those are the key learnings, that if you go long enough and you have the adequate number of events, you get a very good result. We are doing, obviously, dissecting that trial, you know, very well. It also was on the CTTC line, so that the amount of LDL lowering correlated with the benefit. They got a really strong benefit on myocardial infarction. That was their best benefit, you know, 30-35% reduction in MI, which was really profound. We, you know, we believe this is a very important study for the field, and it is also a very important study to validate that what we, how we design PREVAIL, you know, should also optimize for success when we read that trial out.
Yeah, yeah, makes sense. It was really interesting data. You know, I know some of the labels are kind of evolving to allow kind of less restrictions around exactly in sort of like what patient population to use. It seems like these data should obviously only really kind of help, just as you like think about how this treatment landscape will evolve, and you mentioned guidelines will change. Is this idea of like primary prevention versus secondary prevention kind of blurring, where there's it's just kind of the whole continuum just start as early as you can and just go as long as you can? Is that kind of where you see this going over time?
Yes, I do. I think, you know, they always say, what's the difference between a person the day before their heart attack and the day after their heart attack? It's not that much difference. We want to try to treat disease a lot earlier. That part is probably going to take some more time to get into guidelines completely, but this is a big start. Right now, I think what we're going to really, the primary prevention world is still very important. In fact, I'm a big advocate for the earlier in life you start, the better. That when you had a, if you want to treat somebody for 30 years, it's better to be 20-50 than 50-80. That's kind of how I explain it to patients.
When you think about that, that's still going to be, you know, more of an optional kind of desire among certain doctors to certain patients. What we're going to see now is anybody who has atherosclerotic disease, regardless of the severity, the LDL should be below 55, or high risk, like have diabetes below 55. That doubles the market, basically. Of course, you know, we believe we have no better drug to add to a statin to achieve the goals that are now going to be much more aggressively needed to manage what evidence tells us to do about reducing atherosclerotic risk.
Yep, yep, makes sense. Yeah, really interesting. Obviously the other big data there was Merck's oral PCSK9. Just curious your guys' kind of take on those data and, you know, implications for you or just the lipid space broadly.
Sure. It's really, you know, great to see the push towards orals. That's, again, that's been our focus, and oral is much more well accepted by patients. This particular oral, though, is kind of in between. It's not an injection, but it's also, it's kind of like Rybelsus. You know, Rybelsus is an oral GLP-1 that's been around for a number of years, and it's not very popular because you got to take it after eight hours of fasting, and you can't take any other drugs with it. It is not without its limitations. With that said, they were able to have really high adherence during the trial. They were able to keep people, 97% or greater were on that regimen, which is, so this is the maximal efficacy that you would see. And they got 56% at 24 weeks and 47% at the end of the trial.
That is exactly an expectation based on the phase two data. We believe our FDC will get us 50% LDL lowering, much easier to take, you know, no food effect. We have always said all along that we look at our drug and what it provides. It is the plus benefits that really drive utilization, the ease of use, for sure, the safety, the tolerability, but also the LPL-A lowering, the diabetes benefit, the small particle reduction. What we heard loud and clear from all the KOLs at the meeting was they are really excited about the Alzheimer's benefit. We are going to continue to develop that science behind that. We hope to have an announcement early next year on our plans for how we are going to develop obicetrapib further for Alzheimer's disease. That is something that I think really differentiates us. We are a very differentiated product.
Based on all our market research, you know, this should be the product that we know that this will be the product that most doctors will go to on top of statins to get to the patient's goal.
Yep, yep, makes sense. And, you know, kind of on that, obviously you guys in your lipid trial in BROADWAY showed a really interesting 21% MACE benefit. To your point about this plus dynamic, it went well beyond just what you would expect for cholesterol. We did not see any MACE data from Merck. I guess we will wait to see maybe their full publication to get the full details. But I guess, what do you think the implications of that are, the fact that Merck did not share any MACE data? And is that just like another validation data point that, you know, what you saw on BROADWAY is like really unique here?
Unfortunately, we don't see the data. I did hear from a colleague who was involved with the study that they didn't see anything. I think that's probably why they didn't present it. Merck will probably need to show it in the New England Journal paper, which is coming, which I think will get more insights into what the MACE data was. They also, in the JAMA paper that followed the FH trial, the data they didn't show was that there was like 7% diarrhea versus 2% on placebo, and some more nausea and vomiting versus placebo. I think the paper itself could be, you know, more enlightening about, you know, what the trial with that drug shows. Again, we're very happy they're going to be in the market.
One of the best things that we can have is a Merck in helping us get the messaging out about LDL lowers better. We just think we have a better drug, and we can highlight that, you know, with our own efforts, including, you know, all our publications, which we'll have available, and including, hopefully, with really stellar outcome data when we launch the drug.
Yep, yep, makes sense. Yeah, I would love to kind of dive into some of those dynamics with PREVAIL and kind of obicetrapib's, you know, broader profile. Maybe just to level set, it'd be good to get a sense of kind of like the latest on timelines for PREVAIL, kind of how you're thinking of sequencing filing with that, et cetera.
Yeah, I mean, the timelines, I can speak to both the clinical as well as give you a sense for how we're thinking about the regulatory timelines. From a clinical standpoint, the next big update for us internally will be when we hit the two-year mark following the completion of enrollment of PREVAIL. Just as a reminder, we completed enrollment back in April of 2024. Once we're at that time point, we can give you a little bit additional sort of clarity on what we expect the timeline to be overall for PREVAIL. In terms of regulatory, the strategy hasn't changed. We have a very unique opportunity, and that is to have outcomes data available at the time of launch, which no other company or no other product has had, and potentially to have that data set as part of the label.
One of the conversations we're looking forward to having is with the FDA, and this will be some point next year, where we gauge what their willingness is or what they would want ideally from a timing of filing, and how late or what point during the regulatory review process they would accept the outcomes data. That's going to inform our decision in terms of timing of that data set and overall regulatory timelines in the U.S. In Europe, our partner Menarini did file, and the filing was accepted. That's something we announced several months ago. We're on track to get approval in Europe some point in the second half of next year. Shortly thereafter, we expect Menarini to launch.
Great, great, all makes sense. Yeah, obviously really interesting dynamic of having these outcomes data at launch, and maybe just kind of like diving into, you know, some of the dynamics underlying that early MACE benefit and, you know, what they may imply for PREVAIL. I think at your guys' R&D day, you laid out a really interesting set of data kind of supporting small particles, LPL-A, et cetera, kind of driving this additive benefit. Maybe it'd be great just to kind of quickly kind of walk through some of the key highlights of those other aspects and, you know, what gives you confidence that that outsized MACE benefit is, you know, real, I think it said.
It's a well-known fact that in the first year, you get roughly, you know, half your benefit because you don't get any benefit for at least six months. It takes time for the plaques to stabilize. You know, we had what would be expected from LDL lowering alone, we would have been in that, you know, roughly 9-10% event reduction. We got 21%. You have to say, what else was going on to lead to that benefit? What we do, we looked at different correlations on treatment baseline of these certain parameters like small particles and LPL-A and even HDL. We find that the, you know, the higher the LPL-A, the greater the risk, the greater the benefit of obicetrapib. We found the higher the particles, the greater the risk, the greater the benefit.
Then same thing for HDL. The higher the HDL was achieved, you know, the greater the benefit. When you look at all those other parameters, you know, that gave us, you know, some confidence that when you have these benefits that are very highly correlated with these changes that obicetrapib provide, you can then speculate. We'll know more with PREVAIL, but you can speculate these added LDL plus benefits are ultimately being ultimately achieving the benefits on MACE reduction. That's kind of one other example is the REVEAL trial with Merck. With the anacetrapib, the LDL lowering was that was a huge study for us because it showed that a CETP inhibitor by lowering LDL results in a very significant MACE benefit. When we put it on the line compared to other therapies, the benefit was about 50% greater than expected.
We feel that these other benefits that also lowers LPL-A and raises HDL and lowers small form, not to the same degree as obicetrapib, but we think that that contributed to that oversized benefit in that trial. Yeah, we're optimistic and we can, you know, we are, as Ian said, we're tracking events and we feel good about the events. We feel good about the event rates that we're seeing based on what we expect the placebo rate to be. That means that we believe that PREVAIL is performing well, not just on metrics of quality, but also what we hope to achieve at the end with at least matching that 21% relative risk reduction.
Yeah, and I think the REVEAL trial has always been like a really interesting sort of data point to us in terms of the PREVAIL-like subgroup. It was a 15% kind of plus MACE benefit and your guys' drug is, as you mentioned, more potent. Really interesting data point. I think, you know, beyond sort of, you know, all that data that you've shown, which is really compelling, I think some investors are looking to Pella Carson's data next year as sort of the first true clinical test of the LPL-A kind of hypothesis. Yeah, curious kind of one, your guys' expectation for those data and two, how important you think those data are for thinking about PREVAIL.
You know, I think we heard right from one of the main leaders of that trial that it is still, it's supposed to read out in the first six months of next year. That's good. I think, you know, a lot of investors are putting a tremendous amount of weight on that study for us. I think that's fine, but I do think there are reasons why even if it doesn't work, it's still very important that LPL-A lowering gets in, the other trials read out as well to give us more kind of confidence about what the right trial design should be. Because the study, I think, in my view, is a little underpowered. What I worry about the most, because before I started at NewAmsterdam Pharma, I was involved in inflammation in heart disease, IL-6.
Every time you inject with an ASO, you get a CRP spike. I just do not know what that means clinically. It may not mean anything, but it could be something that could negate some of the benefits of LPL-A lowering. That is one thing I worry about. It may not mean a thing, like I said. We will have to see what happens. At the end of the day, if it does work, that is great. We validate LPL-A lowering as a benefit. It could work something in between where the benefits are modest, but the lower you got your LPL-A, the better, which would be great for us too. You know, maybe it does not work.
I think if it doesn't work, there'll be some reasons for that, you know, as far as the powering or the loss of follow-up or things like that. It, but at the end of the day, if it does work, that's great because it validates LPL-A lowering. That's a big part of our benefit. If it doesn't work, then we would theoretically be the first LPL-A lowering drug on the market. Not exactly because we're an LDL lowering drug, but we would be the first LPL-A lowering, pretty much most potent LPL-A lowering therapy available for a lot of that unmet need. Like I said in my lipid clinic today, that's the most common referral that I get is high LPL-A. People want to know what to do. I think that it'll be a, we'll be fine either way, is what I'm trying to say.
We will be looking forward to that data and then seeing how we apply that to our modeling. Because remember, the drug does a lot of other things beyond LPL-A lowering. And we already have the 21% benefit in BROADWAY as well as the REVEAL data with anacetrapib showing an outside benefit on MACE benefit reduction.
Yeah, yeah, that makes sense. I guess your view on the trial maybe being underpowered, is that just because it seems like it's been delayed and, you know, or is it based on like the design? Like I'm just curious, like if you think it's more or less likely to kind of work or is it.
I think it's going to work.
Yeah, just a matter of how well.
Right, right. It only has under 1,000 events though, which is a little bit on the light side. But I think we're going to see an LPL-A therapy work. That I'm very confident about.
Yeah, yeah, makes sense. Okay, great. Yeah, I mean, you mentioned it, but beyond just cholesterol, there's small particles. You know, it's interesting. It seems like some of the literature suggests that like particle count might even be a better sort of predictor of MACE than LDL-C even. Like how is like the field's understanding of that dynamic evolving and the importance of particle number, but especially like small particles?
Yeah, I think, I think again, it's widely done, but it's compared to other, it's not, it is widely done, but it's not widely done. I mean, a lot of doctors do it. Most don't. I think at the end of the day, if PREVAIL does read out positive and we show the particle reduction correlates the best with outcomes and getting those particles, that's what obicetrapib does tremendously well. It brings down the small particles. Basically, if you ever get a particle number, it would put everybody in the green. It's just a magical drug about getting everybody into the right range for all these different parameters. You know, that'll become more widely tested then once the evidence shows the benefit of that too. I see that as a future.
You know, once people have a drug that can really make all those particles, small particles go away, it'll become even more important to test for it to make sure you have the right drug for those patients.
Yeah, yeah, makes sense. Awesome. You know, there's so much data kind of supporting PREVAIL. There's, you know, BROADWAY, all the literature kind of around all these other dynamics. You kind of mentioned it sounds like event rates are tracking as you expected. How much of like a line of sight can you have on like how compliance is tracking, some of the other sort of trial execution dynamics and how those are looking?
We check that all the time. We have really added a lot of people to go around all the sites and deal with any sites that have patients that have dropped out and bring them back in. We are doing a lot of metrics comparing all the other trials. Compared to all the other trials that we are looking at, recent trials, we are doing better than any trial that we could find on quality metrics.
Yeah, I mean, it is sort of the biggest focus for the company. It is our most important study that's outstanding. As Michael and I do our roadshow with investors at conferences, there's a larger team that visits every major site around the world. One of the benefits we have is being able to share with them the completed phase three data, so the data from BROADWAY, BROOKLYN, and TANDEM. There's no greater motivator for a clinician to see the benefit that their patients could derive from a treatment. It's the benefit that goes above and beyond LDL lowering. It's also the safety profile. As you think about reasons why patients tend to discontinue trials or might, where compliance might play a role, it is typically driven by that.
For us to be able to share with them the efficacy and safety results across, you know, several thousand patients with a safety profile that's comparable to placebo, I think that that's what's helping drive some of the metrics that Michael mentioned.
Yeah, yeah, makes total sense. Great. I guess, you know, thinking commercially, obviously lipid market's huge. The PCSK9s are starting to do, you know, really well now. You guys at your R&D day kind of put out an $8 billion sort of opportunity for this drug. Maybe just kind of like walk through kind of what underlies sort of those assumptions and just kind of how you're thinking about this evolving landscape generally.
Yeah, so it was $8 billion with a really large plus next to it. We have to be very comfortable in the $8 billion for us to add the plus. There are a lot of factors that give us that confidence. I think one you mentioned and one I think that's quite apparent is that this is a large market. There are 30 million individuals in this country that are diagnosed with hypercholesterolemia who are on treatment, but not at goal. We have two product forms, OB and OB plus ezetimibe as a fixed-dose combination that can get the vast majority of patients to goal. If you look at the Tandem data for the combo, depending on what your risk-based goal is, we're able to either get 70% or 80% of those patients to goal.
We've talked at length about the characteristics of the drug that go beyond LDL. When you start to put patients, associate patients with those characteristics, it's 14-15 million individuals in this country that have a combination of elevated LPL-A as well as elevated LDL. There are 30 million patients with diabetes with elevated LDL. APOE4 is a similar number. There are just many more reasons for a physician to choose OB across this sort of risk spectrum. When you think about the market and how it's evolved over the past seven years, I think we all point to the pricing, the pricing coming down for the injectable PCSK9s. We also need to focus on what happened after that. It's the availability or the access that that lower price triggered. Today we have 90-95% of covered lives who have access to PCSK9s.
Most do not need prior authorizations. If they do, they are electronic. The navigation through the U.S. payer process is becoming a lot easier. We have seen treatment goals that are now risk-based and go down all the way to 55. We have seen FDA label changes that no longer, from a MACE standpoint, restrict the label of the drug to the components of MACE where there was a statistically significant benefit. It is across that MACE spectrum. The same thing from an LDL perspective. It is really any patient that has elevated LDL. The last pillar of this, the last sort of potential catalyst of this, is the one we discussed earlier, which is the VESALIUS study, which could advocate for earlier treatment in addition to more aggressive treatment. This ultimately gives us a lot of confidence in achieving that number. It is just not us.
When you look at companies that are developing PCSK9s, the oral PCSK9s, they've each advocated $5 billion plus in sales. It's not at the detriment for the injectables. I don't think I've seen Amgen or Novartis suggest that they expect share loss or sales erosion because of the availability of injectables or availability of orals. We're looking at a market that once was $100 billion if you inflation adjusted. That's the opportunity that's available to all of us. That's why we need multiple large companies to go to physicians and have the focus once again be on lipids.
Yeah, yeah, makes sense. A lot of tailwinds and just, again, as highlighted by this past week and a lot of like focus and attention and all these non-statin options and, you know, all the dynamics we talked about. It makes total sense. Maybe just in the last couple of minutes, you know, on Alzheimer's, you've generated some really interesting data on, you know, obviously relevant Alzheimer's biology. You mentioned next year there might be kind of a more formal update on kind of the path forward there. What are you guys like thinking about? Like is there a path to pursuing a true sort of like Alzheimer's indication, you think?
I think one thing, obviously, that we learned that, you know, when you have elevated p-tau 217, and especially if you're APOE4, you already have Alzheimer's, stage one Alzheimer's disease. This is a treatment. And we found, you know, a really good biomarker, p-tau 217, went down in patients that had this Alzheimer's stage one improved over 12 months compared to placebo. We know there's high-risk groups that in our study we found these. If you're E3, E4, which is your heterozygotes, you're over 70, and you have an elevated p-tau, you progress very rapidly. If you're E4, E4, over 60, elevated p-tau, you progress very rapidly to cognitive impairment. We think this population, they're now cognitively normal, but they have very rapid progression to maybe have cognitive impairment. Why not intervene then when you can make a difference? And obicetrapib already showed that in BROADWAY.
We think this is the right population to target for a phase, a next phase trial, whether it's 2B or 3A or accelerated approval. We're meeting with the FDA about this type of population. We'll see what they say. We're committed to doing another prospective trial. I would say we're getting tremendous interest from our KOL community, from the Alzheimer's community, from the APOE4 Alliance, the patients that have APOE4, and strategics on this, what we've discovered. We're going to build upon it. We'll get more information out to the community, I'm hoping early next year. We also are thinking about ways how to develop it as a separate therapy than the LDL benefit.
Yeah, okay. That's really interesting. Yeah, maybe, you know, we're bumping up on time, but just real quick, obviously there's a ton of strategic interest in the lipid space, cardiometabolic kind of broadly recently. Just like curious what you can kind of say there in terms of like how you guys are thinking about the path forward for NewAmsterdam, obicetrapib, etc., and kind of, you know.
We feel we're in a great place. We do have a lot of interest, but we also have a lot of, thanks to Ian and his team, we have a lot of cash. We have a fantastic commercial team. We have a great drug. You know, we're going to move forward and build value. We'll see where it takes us. Our plan is to launch this drug ourselves to create the greatest value for the company.
Makes sense. Great. Thanks both for being here. And thanks everyone for joining.
Thank you.
Thank you.