NewAmsterdam Pharma Company N.V. ($NAMS)

Bank of America Healthcare Conference in extremely toasty Las Vegas. Ending up our final talk of the day is I'm very pleased to have join us the team from NewAmsterdam. So this is Ian Somaiya and BJ Jones, Chief Commercial Officer. Gentlemen, thank you so much for joining us.

Pleasure.

Yes. Thanks for the invite.

Maybe just to start at a high level for those maybe not as familiar with the NewAmsterdam story. Can you give us a brief overview of the company and obicetrapib?

Sure. Look, it's been an exciting couple of years. Obviously, we've shared a lot of data with you from our Phase III studies for both of our lead programs, obicetrapib as well as the combination with ezetimibe. And really, the goal is to help redefine how patients with elevated LDL are being treated today. The data from the Phase III studies has been quite consistent with the monotherapy showing somewhere between a 35% and 40% reduction in LDL. The combination that would benefit that's in the 50% range. And the benefit goes beyond LDL. So that's when I said the opportunities to redefine the care of patients is looking at the LDL plus characteristics of the drug. So it's the roughly 50% reduction in Lp(a). It's the improvements that are driven by the HDL raising profile of the drug, which include the reduction in the rate of new on-set diabetes, the improvement in kidney function that we recently reported at the ACC as well as the early Alzheimer's signal, which we're going to be further exploring in a short order in a Phase IIb study. So that gives you a sense for kind of what we've shared over the past 2 years. More recently, and specifically last week, we provided an update on our outcome study where based on an evaluation of the blinded data, what we're continuing to see from now up through the 2-year mark is a continued decrease in the overall event rate, which is obviously quite encouraging. Although the data remains blinded, the comparisons we can make are to our BROADWAY study, which was nearly identical in design and was conducted at the same time, the first 2.5 years of BROADWAY, the same 2.5 years of PREVAIL. And given the overlapping patient populations, it makes for a very unique basis for comparison. So the fact that the 1-year data of PREVAIL on a blinded basis look comparable or in line with what we saw in BROADWAY and now observing the 2-year mark where the trends are -- continue to be quite encouraging, what we decided to do and we announced this last week was introduce an interim analysis, which will be triggered by the end of this year and the results shared in the first quarter of next year, where we feel good about the potential for that trial, for the interim to lead to the trial concluding. But if we're wrong and the trial needs to continue, then we're looking at an extension that goes into the end of next year. So overall, we think we have 2 opportunities to deliver on what we expect to be a positive PREVAIL outcome and that ultimately unlocking the -- what we expect to be a blockbuster opportunity for the drug.

Lot to pick apart there. But maybe let's just start with, is there one output that's truly differentiating between ApoB, Lp(a), LDL particles? Or is it just the overall breadth of what you can lower there?

Do you want to speak to that from a commercialization standpoint?

Sure, I'm happy to. The first thing we need to do, and we've done effectively is just make sure is can we actually address what is the primary like metric in some sense, right? And that's what's the efficacy associated with LDL. And we feel very confident in that regard, Ian just walked through that data for you. So we can say that we are consistent and kind of best-in-class in terms of efficacy around LDL. We can also say that we're best-in-class as it relates to safety and tolerability. We're an oral, obviously, we're in a space in which we're not SNAC technology. We don't have to worry about like eating and issues of that sort. So it's a very different profile than what's either currently on market or coming to market. But the relative benefit that we also see across Lp(a) and diabetes and small particles. And as Ian also mentioned, the hope and what we see kind of initial in terms of Alzheimer's and ApoE4 folks. I wouldn't say it's any one particular incremental benefit. It's the host of those benefits because what we're doing essentially is like reducing what is the overall risk. And so again, with all the primary research we've done with over 1,000 doctors over years now, and basically shown RTPP versus others currently on market or coming. Others will do well. It's a massive market and there's tremendous unmet need, but consistently, it shows that OB, OBEZ will do better than those competitors.

You opened up a great question. How many patients don't currently achieve their LDL-C goals? To what extent is this going to be structural versus the pharmacological? And then when you think about how can an asset like obicetrapib both capture and grow share?

Well, I'd say -- yes, is that when we look at essentially kind of what's happening in the marketplace today, sadly, frankly, a tremendous number of patients are actually just not meeting goal. And they start on statins, and they do well, but not well enough. And so what we found is that even current data basically says there are about 30 million of those folks who are actually not achieving what is their base goal and the target. And now that target is shifting, going to be more difficult to get to, if you will, because of the guidelines, the evolution of guidelines, which is very good for clinicians and for patients to get people actually where they need to be. And so again, we're talking about tens of millions of folks who are kind of in that sweet spot of where we would be used in addition to the statin. And I would say that, again, it's -- there's -- you asked the question around is it structural in some sense. It's just a means of people actually, whether they be specialists, but especially in primary care is that today, there's this apathy, not only on the clinician side, but the patient side as well in terms of if I just put somebody on a statin is good enough. right? Like I've done my job. And the hope is that in the very near term, we start to see a more aggressive nature in terms of prescribing and really looking to achieve the goals that are necessary to get to the outcomes we're looking for to reduce this overall tremendous burden in CV.

And the most important data set that we've seen to drive home that point is Amgen study VESALIUS, where in this patient population, the benefit that you can provide by effectively managing LDL in terms of reducing overall risk became quite clear. So there was a 19% improvement in their MACE-4 number, 25% when it came to MACE-3, and those are the hard endpoints. And for the first time with that drug, we saw a mortality benefit. So they addressed one of their biggest criticisms from their secondary prevention trial. So there's obviously the guideline changes that BJ spoke to, but there's clear clinical evidence. And this is the way Europe has been treating patients forever. So it's the opportunity for the U.S. to catch up. And that 30 million patient number, we don't know what -- where that number goes. We could easily be looking at an opportunity that's twice as large as what we had only a couple of months ago. And that's why really every company, every drug has the opportunity to benefit. And as long as we focus on driving that point home, manage your LDL, get the patients to goal, all options available to them will get utilized.

Maybe we could drill down a little bit deeper into this, Ian. Obviously, you have the expanded use of the parenteral PCSK9s in first-line setting, but now the orals as well. Is that a risk at all to obi?

Look, I learn a lot from BJ. And obviously, those are -- these are all commercial [indiscernible] questions. So I want to make sure that he has an opportunity to give his answer.

No, absolutely. And we actually don't see this as a risk in some sense at all. Frankly, as we've said, the market is just so large, it's a tremendous unmet need is that it's a good thing for doctors to actually have options and patients have options as well. And so what we see in the near term is tremendous increase in terms of overall utilization of branded meds in this space. And even ezetimibe, right, is growing at 20% year-on-year. And in the branded space, driven primarily by Repatha is growing at 40% plus. And so we expect that to continue. We look forward to what is the Merck launch in the near term oral PCSK9. They're going to continue to fuel, right, and promote branded but also unbranded, right, to get to patients to activate, right. And that's all positive. And frankly, honestly, it's wind in our sails because when we enter the marketplace, the market will be much bigger and doctors and patients' behavior will be changing as well, where they're looking now to address this in a more aggressive way. We come to the marketplace with actually a better opportunity that can not only address LDL, but also the incremental benefits we talked about. So we look forward to that.

So in order to demonstrate the superiority, can you maybe give us a sense of BROOKLYN, BROADWAY, TANDEM, incremental insights that you provided at ACC just recently. I mean, what stands out in terms of efficacy and differentiation? And how do the data position obi relative to these other approaches?

So just from a clinical perspective, if you look at data, whether it's the drugs that are on the market today or the drugs that are in development, the benefit is primarily limited to reduction of LDL, which is obviously very important. But the risk that these patients experience goes well beyond that. So as you look at the other populations where risk remains, it's the Lp(a) aspect of it. And obviously, at some point this year, we'll get data from HORIZON, and there are other trials that will follow. And we'll have an answer to the question, how much risk is there with Lp(a). And when you look at the available options today and the ones in development, we have a pretty dramatic effect on that risk factor. As you think about the LDL particles, CETP is central to the production of small particles. And what we've seen in our data set is complete elimination of those small particles. So as we focus on residual risk, with a patient that's on a statin or combination of a statin or other drugs, this is one aspect, one key aspect of it, which differentiates us from other molecules. And the same is true for diabetes. Diabetes is a risk factor, and that's something that we -- not only us in terms of obicetrapib in our Phase III data, but really the CETP class has consistently shown roughly a 15% reduction in the rate of new on-set diabetes and related endpoints. So this is yet another point of differentiation. When you look at statins, the higher the dose of statins, the greater the risk of diabetes. And if you're on the highest dose of statins, your risk increases by roughly 35%. So there is an opportunity for us to be combined with a statin. Potentially bring the dose down of that statin and still get the patient to goal. So if we look at the combination data, this is the combination of ezetimibe and the TANDEM study results, we're able to get vast majority of patients to goal, even the new goal, the revised goal of 55 milligrams per deciliter. So we think this is an ideal product and the timing couldn't be better. And we spoke to the guideline changes. But when you look at the labels, the labels have all been harmonized now. If you have a successful outcome study, what you inherit is a label for treatment of all patients with elevated LDL. Your MACE benefit is no longer limited to the individual components of MACE where you hit stat sig, you get the full benefit and the label claim for that. So it's the harmonization of labels, it's the treatment guidelines. It's the resetting of the price many years ago, which brought -- which has opened up payer access and the benefit of having multiple companies saying the same thing, which is get patients LDL under control.

So with that in mind, then why wait for PREVAIL before filing? Again, if LDL-C is recognized as a validated surrogate for CV risk, how necessary is kind of that stand-alone outcomes?

Yes. So we still operate within IRA. So that's the big consideration for all of us as we contemplate launches in the U.S. And based on the market research BJ and his team have done, what's quite clear is that if we deliver on positive outcomes data, and it's either sort of a yes or no, right? As long as we have the data, we get the broad label and we get the broad payer access. So that's what's limiting or informing the timing of the filing and approval in the U.S.

Last one from me. Obviously, a few days ago at your earnings, you provided an early update on PREVAIL. What are the key implications here as you look towards the first quarter '27 readout?

Yes. So the update we provided calls for an interim analysis of the results of the interim becoming known to us in the first quarter of next year. And again, if the DSMB recommends that the trial continue, we'll be -- we'll get to the requisite target event rate by the end of next year. So the implications to the investment community and to us as a company is we just increased the probability of success. We feel very good about the trends that we're seeing. We're encouraged by the observed MACE event rate, all the individual events as well as the composite, and we believe they're tracking well for us to be able to potentially stop the study at the interim time point. And if we're wrong or if the DSMB exercises discretion, which they fully have and recommends that we continue the trial because they're encouraged by some other signal that they're seeing in the trial and they want that data to mature, then we'll continue the trial into the end of the year. But if we continue at the end of the year, there'll be many more events that will support potentially achieving statistical significance. And as a result, the risk of success increases. So I think we've taken at this point, every step we potentially can to derisk the outcome. And as Michael Davidson, our CEO likes to say, ensure that the trial is designed and executed in a manner which allows the drug to succeed.

Ian, BJ, thank you so much for joining us, and appreciate you coming by.

Yes. And thanks for everyone sticking around until the end.

Thank you. Thanks, everyone.