NewAmsterdam Pharma Company N.V. (NAMS) Earnings Call Transcript & Summary

Good morning, everybody. Welcome to day 3 of our 37th Annual Healthcare Conference. My name is Jim Fehrenbach. I'm the COO of the Equities business here. We have had record attendance, record attendance on day 1 and record attendance on day 2. And for the 37th Annual, that actually is saying something. I would like to thank you for your support and partnership with this event. Without further ado, it's my pleasure to introduce you to Michael Davidson, the CEO of NewAmsterdam Pharma; and Yas Rahimi, who is a Senior Analyst and Managing Director. And because there's no other analyst, I'm here, our favorite at Piper Sandler. So thank you so much.

Thank you so much, Jim. Michael, so wonderful to have you. And what an incredible 2025 in terms of the execution of the study. And 2026 is another very big year for the company. So lots to discuss. I think maybe the first place is 2026, the year for PREVAIL CVOT to read out in the back half of 2026. Maybe help us understand how much visibility do you guys get in terms of event rate and how is the study progressing? And what confidence do we have that it's going to be on track for the back half of the year?

Right. Well, good morning, and thanks, Yas, for inviting us. We're excited to be here. It has been a very exciting year for NewAmsterdam, 2025, a year of execution, a year of data release and getting our BROADWAY published in The New England Journal of Medicine England Journal of Medicine and BROOKLYN and JAMA and then, of course, the Journal of American College of Cardiology, the JACC paper is going into more detail about the events in BROADWAY and how they separated and statistical power, less than 0.003 for a MACE benefit of 21%. So that's the key thing about the events that we have to track is we had a very -- we have very good data on other studies that have similar populations. So you can estimate events and FOURIER being the most probably relevant. It was a CHD population and treated for 2.5 years. You had the 2 semaglutide trials, SOUL and SELECT, also CHD patients, not exactly the same patient populations. So you can get a good estimate of patient event rates in these high-risk cardiovascular disease populations. And so we had projected those event rates into our study going in and then you predict a certain relative risk reduction, we said it 20%. And so that is what we track. So we see a blended rate of events. We know that the 2.5-year mark is the minimum follow-up. And so what we're really telling everyone is that the 2 reasons to stop would be hit the 2.5-year mark and we've hit the required event rates. And so we're keeping an eye on that. I would say if it does not read out by the end of '26 is all because the event rates are lower than expected, which is going to be, we believe, a very good sign because we do have excellent kind of benchmarks to know what the event rate should be. But that -- we're going to come back to the -- all our stakeholders, KOLs and update around mid of '26. We've had a 2.5 year -- 2-year follow-up for every patient so we can get a really good handle on what all the adjudicated event rates are. I think that's the right time to come back and kind of get more clarity. Once you have that, you can get a pretty much a straight line about when you're going to hit your events.

Okay. So expectation would be mid to give an update. And based on that, either with -- the scenarios would be yes, it's on track and you could fine-tune potentially the timing. I guess help us understand if it does have to be -- the events are tracking low -- lower, that's also not a bad thing, right? So maybe help us explain...

Right. Yes, that means that the assumptions that went into the event rates were off, which is a possibility. But the thing is we have many studies to predict that. We have also AI and you can almost match exactly patient populations. So we have really good tools to identify the event rates these days. And so if we are slower than expected, I think we believe that would be a good sign that what we saw in BROADWAY is translating into an even better relative risk reduction. But we -- again, there's always a little bit of -- I think it's a blinded trial. So you're going to have to kind of consider that. But right now, what we really feel good about is the quality of the trial. The things that we measure drop in, dropouts, off drug, those that have withdrawn from the study. And when we put our benchmarks against any other trial that's been done to date, we're exceeding all those quality benchmarks. So we feel we have a really good study, very motivated investigators. The investigators when they saw the BROADWAY trial said, "Wow, this drug is amazing. We got to keep all the patients." Those are the things that help these long trials to keep patients on drug. So from that perspective, we think we're really working hard to maintain patients staying on the drug and completing the trial.

That's wonderful. And I've already made the commitment whenever obicetrapib becomes commercially available, I will be on it, even though I probably don't have any elevated risk. But just in prevention for all of the above as I will be aging because it's an incredible product. One of the questions we still get now is, I think you guys have done a great job kind of helping us understand the differentiation between MACE-4 versus MACE-3. Is that something to still -- is there some thoughts as we go into that mid disclosure to also give an update if there's a reason to move away from MACE-4 to MACE-3? Does it even matter?

It doesn't. We've committed to MACE-4, which happens to be the established what's called the CTTC 4-point MACE. When everyone publishes they're on the line, what they predominantly publish is the cholesterol trial treatment center line, which is called the CTTC line. That's made of the 4-point MACE, which is the CHD death, coronary artery disease death, nonfatal MI, ischemic stroke and coronary revasc. That's the 4-point MACE. However, everyone does acknowledge that 3-point MACE is the harder MACE, we call it. And you want to see that also being positive as well. And so we're powering the study for both 4-point and a 3-point MACE benefit.

Okay. Perfect. Maybe next we could transition is regulatory filing. August 18, you guys announced that the EMA accepted obicetrapib LDL-C-based monotherapy plus the fixed-dose combo with ezetimibe. So I guess maybe give us an overview where are you in the process right now in Europe? And maybe also what is your partner, Menarini doing in terms of getting commercially ready?

Right. So we have, as you said, filed. We're getting -- already getting a significant amount of regulatory interactions. The typical process is going through -- it's going well. Menarini is the filer based on our agreement with Menarini. They -- what thing about Menarini is that their footprint across Europe is #1. I mean they have 6,000 reps, which is a huge sales force. They have the standard medical science liaisons and the medical affairs. And so they're gearing up for launch. This is a really big product for them. They tend to be more generic type drugs, but they have branded drugs as well. So they have a lot of interactions with physicians on a regular basis, which I think is perfect for us. And of course, we're excited because we have very good economics on royalties and milestones. And so for us, we see helping them with our commercial team, integrating with their team quite a bit on how we're going to successfully launch obicetrapib. So again, they'll launch before PREVAIL, of course. And then for us, they get a period of time where they can establish a price.

Okay. And how do you think -- I think a lot of investors have been a little worried about the price discrepancies between the U.S. and Europe with MFN. Obviously, cardiovascular drugs are not priced at orphan pricing. So have they given any color how they're thinking about pricing and as you guys are thinking about pricing here in the U.S.?

They're doing a lot of work on different scenario planning on pricing. And so we're working with them. We cannot influence the pricing other than we can have discussions and it will be their decision ultimately what the price. But we know that we have a drug that provides greater value of LDL lowering, Lp(a) lowering, diabetes prevention, now Alzheimer's benefit. So we feel that all that will take into consideration when they do the pricing. And so we're working with them. And we feel that whatever pricing it is, we can work with that in the U.S. as well because it is a separate company. I think that's -- we don't exactly know how that plays out. But we do think that makes a difference. And then, of course, with list price versus what actual prices end up being is often can be done in a discrete way where you're not really locked into a price that they're using in Europe on the discounting side of things.

Okay. And in the U.S., maybe you guys also are very actively planning to file the NDA in the first half of 2026. Can you give us an idea of where you are and how much of that process has been completed? What is left to do?

So we are moving forward with some of the preliminary filing requirements that the FDA needs. And we will meet with them, again, in the first half of this year to get an understanding about when we want to file the LDL NDA and then when -- for the PREVAIL data to be inserted into the file. So we've discussed that with the FDA. Like I said, one of the things that we feel is very important, although when we surveyed physicians, 90%, the outcome study is not critical for the decision to prescribe obicetrapib, about 10% it is. And so we want to make sure that when we launch, we have maximized the label. And so we believe that having a launch that has the outcome study either in the label or soon after that with an updated label is going to be important. We also have the RUBENS study, which is going to finish at the end of this year -- sorry, the end of '26 that we'd like to get in the label as well, which is the diabetes trial. It will give us a broader patient population to talk about with clinicians. And then the Alzheimer's data, we also would like to have that soon around launch, too, because what we're hearing from our KOLs in particular is that, that is such an important differentiator even more so now with the EVOKE-01 and EVOKE-02 studies not working. So we want to line up everything when we launch to have the whole label and/or information about the drug in the public domain to maximize launch success because you get one chance to launch and having all that at launch, we believe, is going to do what we need to make sure that everyone knows that obicetrapib can provide greater value to patients beyond just LDL-C lowering.

And another study that you guys are also conducting is the VINCENT study, which is the combo with a PCSK9, and that's on track to read out in 2026. Maybe help us conceptualize that study and the importance from those results, right? Obviously, investors understand -- want to understand the combination ability of the [indiscernible] agents.

I think the key thing is we have a lot -- this is a small study. It was really designed to talk about the combo with a PCSK9 because that's -- those orals are coming. So we wanted to be thinking about what a combo product would look like as a prototype. And so that was really the purpose of the study. As we got more into the BROADWAY data, we realized that the data was so compelling already that we had a 50 to 150 range for Lp(a), which had a 50% Lp(a) reduction, which is really a very important patient population because we know that when the injectables come out and they show a benefit, it's going to be relegated to the above 150 and those that have heart disease already. So for the majority of patients, by far, it's going to be -- we're going to have Lp(a) levels below 150 and they may not yet have heart disease where obicetrapib becomes the ideal therapy. And so we think VINCENT will help, again, clarify how we position ourselves with -- compared to the PCSK9 inhibitors for that patient population.

That's very helpful. And team, I think one of the questions we always get is sort of a vision on how obicetrapib is very unique, right? It has multi-phototrophic effects that cause many lipid reductions as well as an Alzheimer's benefit as well as a glycemic benefit. So how do you think it's going to be used in practice? You still practice. Maybe is it once a month, right, at a very heavy...

3 times -- 4 times a month, yes.

4 times a month, wow. I don't know how you point out. But help us understand where are we in terms of current management of dyslipidemia? And how do you think obicetrapib will be used in the real world?

Right. So thanks. I think the patient care part is still my passion, and I actually see patients 4 full days a month, which is a busy clinic. And it is a great opportunity to get insights into what patients are thinking and how they go about their journey to go on to a lipid therapy. I would say care has evolved over the last generations where taking a medication was so widely accepted and you didn't get much resistance. Now the new generation is much more -- they want to know why they were taking it, how to avoid taking it and why do I need to take this particular drug versus another. And so that is where I believe having that insights as a clinician is why obicetrapib is going to be so successful because when you think about the patient journey, they know they have high LDL. They know they have a high risk of heart disease or they already have heart disease. They are motivated to do something about it, but not that motivated. They'd rather try anything else, but taking medication for many patients. But when you have high Lp(a) or you have diabetes or you have Alzheimer's risk with APOE e4, those patients are very motivated, very motivated. And when you have a drug that can address those 3 things, you get not just willingness to take it, but they want to take it. And so that makes a big difference. And that's why I'm very, very convinced that obicetrapib, when we do launch the drug will be extremely well received because of the patient advocacy on their own part to be on a drug like obicetrapib. And I know it's -- I guess I just have high confidence that I know -- the patients that I know, they're all going to want to take obicetrapib versus any other LDL drug, and they'd like me to also, if I can, reduce their stat dose if at all possible, while they're on the obicetrapib. So it's all about that journey and the patients wanting to deal with these very personal things for them. The Lp(a) have a very bad family history of heart disease. In diabetes, of course, they worry about all the other comorbidities. And for APOE e4, nothing is more motivating than knowing that they don't start something soon. They're destined to get Alzheimer's dementia. So to me, it's going to be a rocket for obicetrapib for those reasons.

And where are we in terms of measuring Lp(a) in the clinic? Has it become a standardized test? Are patients understanding Lp(a) is a risk factor and managing it?

It's getting much better, I would say, even -- I've been doing it for my entire career. But if you look at the last couple of years, it's becoming more and more evident. We also have like by leading referral to the clinic now is high Lp(a). I think 1/3 of all my new patients are coming in for high Lp(a). So it's becoming more known. And of course, when HORIZON hopefully reads out positive, then the therapy is available, will have even much more widely done testing. And then I think obicetrapib could theoretically be the first oral Lp(a) therapy that's maybe not labeled that way, but it would have certainly the knowledge that it can affect Lp(a) levels beneficially.

And do you think that we have a good understanding of what level of Lp(a) reduction is needed? Like do we have a good understanding of what is the target goal?

That's a very, very difficult question. We're going to learn that from the HORIZON trial as well as others yet to come. There's many multiple trials coming. But the typical 100 nanomoles per liter decrease in Lp(a) should be about 15% relative risk reduction. That's kind of the benchmark that the epidemiology suggests. Now whether it's a linear thing is -- would be great, but also might be a threshold thing. I think that at least what I believe is that an Lp(a) is kind of like smoking, and that is that if you have high Lp(a), your risk is elevated. If it's above 50 or 75 nanomoles. Your risk is elevated. So you want to bring it below the 50 to 75 level. If it gets really high, that could be more risk, but it's -- usually, it's more of a factor that gets enhanced when you have other issues like diabetes or inflammation like CRP, that's when Lp(a) becomes much more of a significant factor in causing premature heart disease. Again, obicetrapib being what it is, we think it mitigates the risk not just on the LDL lowering, Lp(a) lowering, but also by the metabolic syndrome features that it improves. We think it could really have an outsized benefit on not just lowering Lp(a), but also reducing risk in those patients.

No, very helpful. One of the questions we get, obviously, HORIZON was on schedule to read out in 2025. It got pushed into 2026. I know John is not here, but he's, I think, the steering committee of the study. Do you -- I guess, we're trying to figure out, could we get HORIZON before PREVAIL? Or could it come after TBD? Do we have any...

Well I think PREVAIL is going to -- well, we heard that HORIZON is going to read out the first half of this year. So it will before PREVAIL. But yes, I think it's -- again, they're tracking events just like we're tracking events, lower than expected is probably most likely a good thing. I do think when I look back at their projected event rates from their design paper, they put in 4.6% annual event rate based on their inclusion criteria. They use urgent re assets very close to our 5% rate per year that we think is the right kind of benchmark. So they probably had predicted a little bit too low because the LDL is only 60 milligrams per deciliter. In other words, the event rates are probably lower than that because of the LDL 60. I think they weren't expecting an LDL of 60 in the trial, which can mitigate the high Lp(a) rate. So I think it's a good sign the event rates are lower. I think they can also like I said, you can look at what the expected event rate should be. But that means readout for them is going to be the, I think, second half of -- first half of '26, yes.

Do you think that you guys did a really nice job this summer when you had your R&D Day to take the BROADWAY data and put into context of what drove that 21% MACE reduction. And I think it was alluded to like 5% of that was a contribution from Lp(a). I guess I'm trying to understand like, let's say, fast forward HORIZON comes out, whatever we get, is that an opportunity to go back to those analysis and see if the contribution is different? And what kind of analysis could you do at that time to help us understand whether it is a 5%...

Right, right, right. We believe we can. That will be -- like we said, that 100 nanomoles per liter is based on observational epidemiology. Now we'll have a true intervention trial that can model it even better. And so we'll see that will help us. But I do think what we feel about BROADWAY data is, yes, we do -- we can model Lp(a). We can also model all particles. We can also model HDL, if you want. I mean so you can look at other things that obicetrapib does, but the bottom line is you got the 21%. And so we feel that's the key thing is we already have the evidence of benefit in a relatively large trial over 1 year. And so we think Lp(a) is a very important factor, but it's not the only factor with obicetrapib that could explain the benefit in that -- in the BROADWAY trial.

And then maybe one last question. One of the things that I think always gets underappreciated about obicetrapib is its safety product profile and its ability to be combined, right? Because these patients are on multiple various agents. It would be great if you could just put it into context as a practicing cardiologist, the importance of a very clean, safe drug and then also a product profile with no CDIs and combination ability.

I cannot emphasize more. But again, being on the clinical side, the patient scrutiny on safety is just -- it's just unbelievable. They go to AI now or Google and get all kinds of information about the drug. They'll question why you pick this drug over another drug for the safety purposes and so forth, all the time, almost is universal. And so having a drug with obicetrapib with a great profile, is going to make a big difference. Again, you mentioned the combo thing, and that's something we're exploring, of course, with -- obviously with ezetimibe already. But thinking about combinations with obicetrapib, it's a very good drug to combine. And we feel that, that's going to be one of the elements about obicetrapib that we feel that will be enhanced as time goes on. We're looking at all kinds of life cycle management options that we have for obicetrapib in the future.

Wonderful. Well, Michael, it's a pleasure having you, and it's been really an incredible journey covering your company and working with you guys. Every time I talk to all of you, I learn a lot more. And obviously, you're an incredible physician as you would -- on top of everything you do, you practice in Chicago 4 times a month, tells you how passionate you are about the field. So let's give a big applause to Michael.