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

Good morning, everyone. Welcome to this session of the 22nd Annual Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of this mid-cap biotech analysts here, and we're very pleased to have NewAmsterdam Pharma represented by CFO, Ian Somaiya with us. Before we jump in, let me just read a quick disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative.

Right. So with that, Ian, maybe we can start for some of the folks that are less familiar with a brief introduction to NewAmsterdam, how the company was formed and how the management team came together.

Sure. Well, before we do that, let me just thank you for the kind invitation to present at this conference. Morgan Stanley is a special place for me. It was nearly 25 years ago that I was first promoted to a senior analyst -- research analyst here. So I've had the opportunity to host many companies at this conference, and it's always a bit of deja vu but with a special meaning when I am at this conference. So those that are unfamiliar with NewAmsterdam, we are a company that's focused on cardiometabolic disease. It's an area of, obviously, quite a bit of interest from the investment community, but also from the industry, the pharma industry as a whole and clinicians because there are many new medicine tools available to treating these patients. We are developing a cholesteryl ester transfer protein inhibitor or CETP. It's a class of drugs that's been evaluated in the past, but our intent is different. We're not looking to raise HDL, which these drugs are well known to do. Our goal is to reduce LDL and that's a marker that's been well established and correlates beautifully with reducing what matters most, which is cardiovascular risk and cardiovascular events in these patients. We are in Phase III trials, multiple Phase III trials. In fact, we've released data from -- at this point, 6 clinical trials, 5 Phase I/IIs and our first Phase III study a little while ago. And I'm sure we'll go into the details of those. Cardiovascular disease is a multifactorial disease. There's just not one thing that ultimately impacts the patient's quality of life and life expectancy. And we believe we have a drug that could benefit patients across the spectrum.

Okay. Great. And like you said, the company is focused on lipid lowering and cardiovascular disease. So obviously, tens of millions of patients in these indications. So can you help us understand where you see the unmet need for these patients in addition to statins, there are oral therapies, injectables. So where is the opportunity for your lead program?

Yes. So with cardiovascular disease, it still remains the #1 unfortunately killer in the Western world. And you're right, it is tens of millions of patients there. In fact, there are 30 million patients in the U.S. alone that based on their risk-adjusted LDL goals are well above those goals despite the availability of statins for obviously quite a bit of time and many other therapies that are on the market today. And on top of that, there are approximately 10 million Americans who have been diagnosed with increased or hyperlipidemia, which are not on any therapy. So the market opportunity is quite significant. And despite the availability and effectiveness of statins, there remains an acute need. Now what I would say in terms of how we fit in and where we fit in, if you look at the marketplace today, the drug that is used most often in combination with the statins is ezetimibe. This is a generic drug. Generic drug that's growing at 20% plus every year. And what's remarkable about this drug is the preference for ezetimibe is safety. This is a safe drug. Doctors are very comfortable with it. Patients are comfortable with it. The efficacy is quite modest. What we've seen across clinical trials is 15% to 20% LDL lowering. So when you think about the market, I mentioned the 30 million patients that are above their risk base goals, vast majority of those patients are 20% or more above their goals. So ezetimibe is not getting these patients to goals. But it is a preferred agent for safety. And as we'll go into a bit of our data set, I think what we should do is lead with safety because this is a patient population that's asymptomatic, right? If you have elevated cholesterol, you don't feel it. What we're trying to do, what physicians are trying to do is reduce LDL to prevent cardiovascular events.

That make sense. And you touched on it, but we do hear this refrain of lower is better when it comes to LDL. So how does that play into the unmet need? And are there any changes in the regulatory environment in the recent past that you'd highlight in the space?

It is an important point. For a better part of a decade, it wasn't lower is better. We had gotten away -- the AHA had gotten away from treatment guidelines, advocating risk-based goals, LDL goals. So what we've seen more recently is the ACC, American College of Cardiology mirror the goals that have been quite prominent in Europe for a while, which is depending on your risk for cardiovascular event, your family history, whether you've had events in the past, there are different thresholds, different levels of LDL, which are set for you as goals. And that change from the ACC has really driven what we've seen is pretty remarkable market growth in terms of statins growing at low to mid-single digit annually from a prescription standpoint. And as I mentioned, ezetimibe growing in the 20% and the branded drugs growing at a much higher rate.

That makes sense. All right. So one more before we dive into the clinical programs. You mentioned the CETP inhibitor class. There is a bit of a history there. I think we've seen 4 late-stage CETP inhibitors fail historically. So can you just remind us of some of the history there and why maybe it's not fully precedent for your program.

Yes. So one of the things that attracted me to NewAmsterdam, and we are in a sense of a unique company because we think we have a great drug and the consistency of the data supports that. But we also have a team that's uniquely qualified to conduct these studies -- design the studies and conduct these studies. So it's the learnings from the CETP class that have informed our program. The nuances in our trials, which has led to the benefit and the consistency of benefit across different patient populations and different geographies. So as you go through the four CETP inhibitors that have been evaluated in the past. Let's start with the first, which is Pfizer's torcetrapib. This is a drug that was designed as all of them were, the prior 4 CETP inhibitors, to evaluate the benefit of raising HDL. So the thesis was that if you increase HDL by 1 percentage point, that would translate to a 3% improvement in cardiovascular or reduction in cardiovascular risk. So what we learned across these programs was HDL raising has no benefit from a cardiovascular event standpoint. But what we also learned specifically for torcetrapib was the drug had an off-target effect. It raised aldosterone, which meant that it increased blood pressure in patients. And ultimately, that led to an increase in cardiovascular events in their outcome study. So an unfortunate setback for the class, but one that was primarily driven by the unique safety profile of that molecule. The next drug in the class was developed by Roche, dalcetrapib. And this is a drug that had no effect on LDL. So neutral effect on LDL, but did raise HDL by 50-plus percent. So really the first opportunity for us to learn what is safe drug. But one, what an HDL effect could do in the clinic in terms of events. And once again, what we learned was there was no benefit from a cardiovascular event standpoint. There were 2 other drugs that were developed. Lilly was the next one, evacetrapib. And evacetrofib had an effect on HDL as well as LDL. So it did lower LDL for -- by 15% to 20% based on what are more stringent assays. So beta quantification is an asset that we can rely upon. It's an assay that we use in our studies because the FDA asked us to. So learning from Lilly's clinical trial, and this is, again, one other trial that unfortunately failed in its outcome study. The lesson there was not as much on HDL or LDL. There's more on study duration. So it takes upwards of 2 years for the Kaplan-Meier curves to separate in an outcome study. And unfortunately, Lilly stopped the study at the 2-year mark. And this is an important lesson not only for us, but for the next company that developed a CETP inhibitor, and this is Merck. Merck's anacetrapib conducted the study for a better part of 6 years and we saw a clear separation of those curves and a benefit that equated to 9%, 9% reduction in MACE. Now this product could easily have been in the market today were it not for another unique feature of that molecule. The drug had a half-life of a few weeks, but what they got in the outcome study was there was accumulation of the drug in fat. And the accumulation led to the drug still be available or found in patients for a matter of years. So again, in a post Vioxx world, which Merck was living in, the decision was made to not pursue clinical development. But the lessons were quite clear to us. If you run a study that's long enough and Merck did take cues from Lilly and powered the study for LDL production, not simply for HDL. So if you power a study for LDL reduction, which we have and you conduct the study long enough, and in our case, our minimum duration of follow-up is 2.5 years. So on median, we're looking at 3.5 to 4-year follow-up. That's the longest minimum follow-up of any study that's been done today. And if we do that and we have a baseline LDL that's high, we can -- CETP drug specifically our drug, obicetrapib, we believe can translate LDL reduction to a MACE benefit. That's profound, and that's relevant to a practitioner.

Okay. Great. And last one in the history lesson. I think obi did belong to Amgen at one point. Why did they part with it? Maybe you answered the question with the history there.

Yes. So I mean it's always complicated. And obviously, I wasn't there for the history. I wasn't there for the formation in NewAmsterdam or the licensing of the asset. But let's take a step back. John Kastelein, our CSO, was an adviser and a consultant to many pharma companies. And that's the -- again, the beauty of the scientific leadership of the company, John and Michael. They are KOLs. They've been involved in every LDL study that's been conducted by the pharma industry. There are a lot of lessons that have been learned by them. But going back to John and the licensing of obicetrapib, it was -- this drug was licensed from Mitsubishi Tanabe. Mitsubishi had developed the drug, conducted a Phase I study. And what John saw was a clear LDL effect, a reduction of upwards of 40%. And so he, along with the four beyond the seed investor, the founder of the company or predecessor company called Dezima. Dezima was acquired by Amgen. And unfortunately, and I think we've all have a sense for the history of the PCSK9 and Repatha and its development and commercialization, licensing or the acquisition of Dezima was right around the same time as Repatha was being launched. And Amgen as an analyst that covered Amgen at the time, was quite stringent in terms of the R&D dollars that they put behind on a percentage of revenue basis behind this pipeline. So with four cardiovascular assets at the company and the setbacks by -- that we're seeing with other CETP inhibitors, obicetrapib was #4 in the rank order. So this is the wonderful thing about our industry. There are these rare occasions where drugs become available and in the right hands with the right design, you do get sort of the alignment of the stars, and you can have not only a product that's clinically successful, but one we believe can get FDA approval or regulatory approval and help millions of patients. So it was just simply that a rare opportunity. And John, once again, but this time with Michael Davidson, our CEO, along with Forbion reacquired obicetrapib back from Amgen for an equity stake in the company. So no further rights are available to Amgen or Mitsubishi. They were equity investors. They are no longer. So it's a drug that's unencumbered. And I would say, so are we as a company.

Okay. Great. And we've been talking about LDL, but obicetrapib does more than just lower LDL. So can you speak to its effects on other disease markers like Lp(a) and others? How might that be important for patients and physicians from a high level before we dig into the data.

Yes. So as I mentioned, this is a space or a patient population that has many factors that impact ultimately outcomes and risk of events. So LDL is obviously the most established marker that we have. There's dozens of studies and many mechanisms by which LDL reduction has translated to MACE benefit. So as we think about the overall impact of the drug, to your point, it goes beyond LDL reduction. The drug also reduces Lp(a). So what we've seen in our Phase II studies is an Lp(a) reduction from anywhere between 40% and 50%. And as part of our Phase III data release, although we haven't shared the Lp(a) reduction in the BROOKLYN Phase III trial, we did say that the results were in line with the Phase II studies. Beyond LDL, what we also need to look at is what do currently available therapies do? Or how do they benefit patients? And what could our role be or obicetrapib's role be. So when you look at statins, they do a beautiful job of reducing LDL. The vast majority of the LDL that's reduced by statins is large molecules, large LDL molecules. What obicetrapib does beautifully is it completely eliminates small particles and small particles are more atherogenic and represent the residual risk that's present in these patients who are being treated on statins. On top of that, to your point, with Lp(a), Lp(a) is a target of quite a bit of interest. There are many outcome studies that are being conducted today. And the first of which we'll read out in some point in 2025. This is the Novartis Ionis pelacarsen study. And we'll learn what the impact is of reducing Lp(a). Is there a linear relationship, which is what we know to be true for LDL? Or is there a threshold effect? Is there a certain level of Lp(a) that you need to reduce or achieve for there to be a benefit? What's wonderful about obicetrapib and its effect is that represents an incremental benefit, the incremental feature of the drug, LDL reduction in and of itself has been shown clearly to result in MACE benefit. And the other aspect of the drug that are quite unique, and I'll speak to the class here more than obicetrapib because we'll learn of this from our own trials. But CETP inhibitors and the four that we have -- that have been developed before, have consistently shown an ability to reduce the onset of new onset of diabetes. So if you think about statins, significant benefit from an LDL reduction. But if you're on a high dose of statin, what a recent Lancet paper would suggest is there's a 36% increase in the new onset of diabetes, so risk of diabetes. And the CETP class has been shown not only to negate that effect, but further reduce it by 15%. So as we look at our drug in every way, it's twice as potent or twice as effective as the prior CETP inhibitors. The prior CETP numbers have shown a benefit of an LDL reduction of 15% to 20%. We have consistently shown a benefit of somewhere between 36% and 40%. If the prior CETP inhibitors have shown an LP reduction of 20%, ours has been more than that. So we expect these features to continue to be quite prominent. And let's not forget safety. The CETP class, if you ignore the off-target effect of torcetrapib and maybe we can spend a minute or 2 focusing on Merck's program anacetrapib. They ran a 30,000 patient Phase III study, followed these patients for 6 years. And what we've learned was the safety profile of that drug and overall, the 3 out of the 4 is quite clean. And when we look at our own data, what we've consistently shown in our Phase II studies is a safety profile that's comparable to placebo, a true placebo.

Yes. That's a great overview. Maybe just jumping over to your clinical trial design. You have, like you said, a couple of Phase III trials going on. You also have an outcome study plan. So can you walk us through the design of the Phase III and outcome study program and why it's being run the way it is.

Yes, of course. So we have 2 LDL studies, LDL focused studies, BROOKLYN and BROADWAY. BROOKLYN read out a short while ago, and BROADWAY is on schedule for the fourth quarter with one caveat, we don't want to release data in the second -- during the holidays, so the last 2 weeks of December. So you should expect the data either before that period of time or after and after would take us into the early part of January. The other studies, TANDEM is a registration-enabling study for our fixed-dose combination. And we have a fixed-dose combination of obicetrapib and ezetimibe is the most often prescribed add-on to statins. And the other registration-enabling study is PREVAIL. And the PREVAIL is the outcome study where we've enrolled in excess of 9,500 patients, and that data is expected in the latter part of 2026, really towards the end of 2026 or beginning of 2027.

Okay. Got it. And with that in mind, can you talk a little bit about your filing strategy, assuming you succeed in all these trials. Would you plan to file for approval after the lipid study is finished, would it come after PREVAIL reads out? How are you thinking about timing it?

So it's -- the time lines do defer depending on geographies. So Europe, we're partnered with Menarini in Europe. And Menarini will be responsible for the commercial launch in Europe. But we will be submitting the application to the EMA. And the plan is to submit that application following the conclusion of the LDL study. So BROOKLYN, BROADWAY and TANDEM, so that should occur at some point in the second half of 2025. And that will be the basis for approval in Europe. Launch is slightly different in Europe. There are -- most countries provide window that's upwards of the year from launch to pricing. One country is unique France. So France, we want to make sure that we have the outcomes data available to negotiate a price. So the launch in that country will be delayed for that reason. In the U.S., we want to really take advantage of the proximity and when I say proximity, the time lines for PREVAIL relative to our LDL studies. Michael and John had the foresight to start the outcome study at the same time as the LDL-lowering trials. And that gives us a very unique opportunity to have the outcomes data available at the time of launch. So what that implies is we're going to hold on to the filing for a short period of time and file the application. So during the regulatory review period, the PDUFA period, the outcomes data is in the public domain. So this doesn't mean that our initial label will have outcomes in it, but payers will be able to confirm that CETP inhibition, obicetrapib specifically and the LDL reduction that we're able -- that we've been able to show does translate to an outcomes benefit. And we believe based on our payer ad boards, this will translate to payer access, a more widespread payer access.

Okay. Great. And like you mentioned, you did recently report out data from the Phase III BROOKLYN trial in HeFH patients. So can you recap what the data looked like, were the reactions in the data the same or somewhat differentiated between investors and KOLs and where do you see the disconnect there?

Sure. So I mean, first and foremost, we are thrilled, and this is just not me being a company representative. I think we've all had the opportunity in our careers to look at different programs. And there's a moment where you know you have a drug and we have a drug. We have a drug that not only can get FDA approval, again, assuming there's always a caveat in life that the remainder of the studies are successful. But a drug that has the potential to benefit millions of patients. So to recap BROOKLYN, I mean, I would say the one word I would use is consistency. This is our sixth clinical trial data set that we've shared with you. And the data has been remarkably consistent irrespective of where the trials are conducted, whether they're conducted in Japan or the U.S., irrespective of the patient population. And one could argue that both BROOKLYN represented are toughest test in terms of heterozygous FH patients, which only have one functional [ LDL ] and which are heavily pretreated. So these are patients that were a vast majority of them were on high-intensity statin. Half of them were on ezetimibe and 14% were on PCSK9. So if you think about where PCSK9 is more widely available, which is in the U.S. and where our trial is conducted with many or most of our patients, PCSK9 patients in the U.S. So despite the challenge of this patient population we once again reported was a 36.3% reduction in LDL at week 12, which improved to 41.5% at week 52. And that week 52 data matters most because when you plot the CTT regression line, so when you translate the LDL to MACE benefit, it's the week 52 time point that's utilized. So as we think about in future studies, BROADWAY, we expect results to be quite similar in terms of the LDL reduction. And from a PREVAIL outcome study standpoint, whether you look at 36% LDL reduction or 41.5%, it should allow us to exceed the current benchmark that's been set by the high efficacy PCSK9 inhibitors, which are all injectables today, and that is a 15% MACE benefit.

Okay. Great. And just going again beyond LDL lowering, it did seem like there was a lower rate of new onset diabetes, worsening of glycemic control. Just remind us the significance of that, and maybe you can also tie in some of those other biomarkers, Lp(a), non-HDL. They're not LDL and ApoB.

Yes. I can -- we'll obviously have more data to share with you. We're targeting an upcoming cardiovascular conference in November. Once the abstracts are accepted or the abstract is accepted, we can confirm the presentation time and the venue. But we do plan to share more data and some of the data that you mentioned on Lp(a), on ApoB as well as on non-HDL. So let's start with the special, the adverse events of special interest, which included diabetes and it's a bunch of different ways of looking at that data set. But that is -- that data set is quite consistent with what we've seen with the CETP class in the past. And what we can say today is the safety profile looks to be comparable to placebo, right? You don't have design studies for statins on a safety standpoint. So we're very pleased with the early readout. We know one point -- one additional point I would make is, when you look at the number of dropouts, the percentage dropouts in the 2 arms, placebo versus OB, the OB arm had half the number of dropouts. So we are seeing patients that are staying on therapy. And when you look at the waterfall plot, which is the most honest way of representing the clinical data set where you get to see individual lines, which represent a patient and the degree of benefit experience from an LDL standpoint, that was quite exciting to us because you can compare that to the most recently studied PCSK9 in this patient population, which is inclisiran and the 2 waterfall charts are superimposable. And the goal of our program has always been to deliver a high-efficacy oral LDL-lowering therapy and the benchmark is statins. And we think we're achieving that goal. But where statins and -- sorry, PCSK9 sort of leave off, which is limiting their benefit to LDL. We're seeing the other factors also play out. So Lp(a), back at -- in April, we hosted an R&D event. And we shared with you a waterfall plot of our Lp(a), that was seen across our Phase II studies. So that's a data set that would like to be able to share with you at AHA. And what we know to be true today is as potent as our drug is on LDL, it's even more so when we think about Lp(a).

Got it. And you did mention that we're going to have BROADWAY data in Q4. So I think that's an ASCVD population primarily. Can you remind us -- what do you think are the read-throughs or read-acrosses from BROOKLYN to BROADWAY? What would be the expectation should result be similar?

Yes. No, I think, again, I would go back to the word I used before, which is consistency. There's been a consistency to our data set, and that's what you should expect from Broadway. There are reasons to believe the data could be better. There are reasons to believe the data could be less robust. But what we know to be true across our clinical program, and again, 6 clinical trials. There's a narrow band. Somewhere between 36% and 40% is what we've seeing. And there's really no reason to have expectations that are any different for BROADWAY. And I would say, more importantly, there's no need. That 36% to 40% translates quite well to a robust outcomes benefit in our PREVAIL study. In fact, our LDL reduction would need to go down to somewhere in the mid-20% range for us to show a 15% MACE benefit, which is what the PCSK9s have shown. So there's always lower is better, as you said earlier, Judah, and we agree with that. But what we know to be true across our program is that we're getting vast majority of the patients to go.

Got it. And I'm sure you hear this all the time, but there are some oral PCSK9s in biopharma pipeline. So how do you think about competition from those molecules? Is LP(a) maybe a differentiating factor or anything else we should think about when we're thinking about these programs head to head?

Competition is great. It's not only welcome, it's needed. We really need the pharma industry to once again invest in this space. So if you go back to the '90s and now I'm dating myself because that's when I took on the role as an analyst and to the early part of 2000s, you had multiple pharma companies with thousands of sales reps calling primary care physicians, calling cardiologists, urging their patients to go on a lipid-lowering therapy. What that translated to was a category from a revenue standpoint that was $50 billion plus. And obviously, all the statins are generic today and ezetimibe is also a generic drug. And despite the fact the needs haven't changed. So what pharma companies and I think the 2 you're referring to is Merck and AstraZeneca, both of them were involved or leaders in this space. So if they were to come back and they clearly seem energized with the 2 molecules that they're developing. We have the opportunity to really transition this market, which is generic to branded once again. And then the question really is which drug do we think physicians and patients would prefer. And to your point, when you look at PCSK9s, whether it's an injectable or an oral, they are simply an LDL-lowering therapy. Our drug does more. So it reduces Lp(a) and we'll know what -- how that translates to an outcome standpoint when Novartis reads out the HORIZON study data next year. As we think about the risk of new-onset diabetes, the risk that remains with statin therapy with the small LDL particles. Our drug is able to offset those risks and improve upon them, whereas PCSK9s are not. In fact, when you look at the LP(a) benefit of PCSK9, it's about 20%. And so our drug more than doubles that benefit. So as we look at the 2 oral competitors you mentioned, let's start with Merck, theirs is a true peptide. The efficacy is quite outstanding. They've shown upwards of a 55% reduction in LDL. As long as the patient remains compliant and compliance entails taking the drug on a fast state. So 8 hours fasting, not eating for 30 minutes afterwards. I think that's possible to do in a clinical trial. But when we're talking about an elderly patient population, with lots of other comorbidities, I mean, again, I'm not that old. And I would find it challenging to wake up and not like at least get a cup of tea or coffee before taking anything. So even slight changes or deviations from what's needed leads to a pretty dramatic effect. So that efficacy goes down from 55% to 20%. So we'll see how the drug performs in the clinic. But we're excited to have Merck as a partner to build out this category once again. And AstraZeneca has shared with us their Phase I/II data. We saw data from 2 doses, 30 milligrams and 60. Theirs is a true small molecule, so there is no food effect. And what they showed was an LDL reduction of 30% at the low dose and 38% at the high dose. So really no different from what we have reported. And as we've already discussed at length, theirs is a PCSK9, where the benefit is truly just limited to LDL reduction. And I don't want to understate the importance of LDL. And obviously, that's what we're all targeting today. But these patients need more.

Okay. Thank you. I think we will leave it there. We appreciate the time today.

All right. Thanks, Judah. Really appreciate you being here. And thank you again for being in the room and those that are listening.

Thank you.