All right, good morning, and thank you for joining Guggenheim's 2026 Emerging Outlook Biotech Summit. I'm Debjit, one of the therapeutic analysts, and my privilege to welcome our first presenting company, New Amsterdam Pharma. Joining us is Ian Somaiya, company CFO. Good morning, Ian.
Good morning, Debjit, and, thanks for the invite. This conference gets better every year, so we're hoping to continue to get the invitations on a recurring basis.
Thank you for the shout-out. Although a lot of people would say, "We don't wanna see you every year from now on, because we would rather have you bought out." So you could play it both ways. Anyway, start with PREVAIL.
Yeah.
You know, there's an update expected mid-year.
Mm-hmm.
What should we expect in terms of the readout timelines, and if there is a push-out, why, why should there be a push-out?
Yeah. So look, it's exciting, the observation which we shared with you back in January. So if you go back to the start of these two studies, there's clear intent with BROADWAY. BROADWAY was designed to be a mini PREVAIL, so a mini outcome study, and the update we provided in January was that on a blinded basis, the event rate in PREVAIL at 12 months was tracking in line with BROADWAY.
And why is this encouraging? Because we observed a 21% MACE benefit in the BROADWAY study. The other reason is, these are two studies which are nearly identical in design. So as you think about looking for a like making it... trying to make a like-to-like comparison, it's an ideal comparison to make.
Two studies that are similar in design, conducted at the same time, and at the very same sites. So we're obviously encouraged by what we've observed to date, and, Debjit, you're correct, that we have committed to providing an update in terms of the overall timelines for the study. And this is gonna be based on continued adjudication of events out to at least two years, which will give us a better sense for what the actual timeline for the study would be.
Do you think the standard of care has evolved to the point that, something meaningful could change between year one and year two follow-up?
Yeah, so we don't think it has. So as you can imagine, we not only compared our blinded PREVAIL results to what we saw in BROADWAY, we're also able to make comparisons to other contemporary studies. So again, all that just points to... gives us confidence that we're headed in the right direction.
If you could just remind us, in terms of powering, I believe the study was originally powered to show a 17% delta?
So, Debjit, we have actually never commented on the power- the powering of the study. So the, this, a ll those factors we'll be happily able to share with you when we publish our design paper.
Timelines, when should we expect that? Because that would help us model it out as well.
Right. In terms of the design paper?
Yep.
Yeah. So, we would ideally like to be able to share that with you at some point this year.
Got it, and in, you know, of the things that you monitor in the study-
Mm-hmm
... compliance, how is that tracking?
Yeah, so that's again been a focus for us. With an outcome study, every patient matters, right? And that's true of really every trial that you conduct, but even more so with the outcome study. So with the completion of the vast majority of the LDL studies, which we did back in 2024, there was an enhanced focus on PREVAIL in terms of making sure that there were appropriate number of site visits, both from our CRO as well as from NewAmsterdam, an ability to share the results from the LDL studies to motivate patients to continue to stay on treatment.
The challenges of an outcome study is they're very long in duration, and you can experience clinical trial fatigue, patients do. And the benefit of having BROADWAY, the data from BROADWAY, BROOKLYN and TANDEM, you know, we can't overstate. It's typically when you have a patient that chooses to or wants to leave a study, it's because of an adverse event. And when you look at our results from all the completed LDL studies, what you'll note is adverse events occurred at a lower number than on drug versus placebo.
So again, we'll never be able to claim that our drug is safer than placebo, but as we're engaging with clinical sites and engaging with patients, there's nothing more powerful than to be able to deliver that message that if you're experiencing an adverse event that's causing you concern, that may prompt you to leave a study, it's highly unlikely to be related to the drug, and if you stay in the study, we can help you figure that out.
So, the I mean, there are obviously giants within the field, both within the company and externally participating in the PREVAIL study.
Yeah.
What have you heard from them with respect to what obicetrapib needs to show to be started ahead of non-statins?
Yeah. So I think we've shared a lot, a lot of that with you already. We have the benefit of having Michael Davidson, our CEO, and John Kastelein, our CSO, two renowned KOLs that have been involved in every cardiology study over the past two, three decades. And you can look at the scientific advisory board and those that are involved in the clinical trials.
They are, you know, pre-eminent cardiologists, lipidologists. So their opinion matters a lot, but so does the opinion of what will ultimately be the prescribers of obicetrapib. So we, you know, we've done a significant amount of market research in the cardiology community, as well as the primary care physician community. And what's quite clear is, there are many aspects of the drug's profile that resonate.
First off and foremost is the ability to get patients to go. So if you look at the data that we've shared with you, whether you look at obicetrapib alone or, more importantly, the fixed-dose combination with ezetimibe, we're able to get 70%-80% of patients to their risk-based goal.
That's really critical. And we're able to do that with a format that's very convenient. It's a 10-mg pill that you take orally once a day, and I've already mentioned to you the safety profile, which, again, is important because we're talking about a disease state which is asymptomatic. So really, you want something that's very, very easy for a patient to comply to. On top of that, from a clinician perspective, it's predictability.
You wanna have a drug that, that's reproducible from a benefit standpoint, and that's what our data continues to support. Then we go beyond the LDL aspect of the therapy. Lp(a) was shown benefits of being able to reduce Lp(a) by upwards of 50% in a target 50 to 150 patient population. We're the first drug to be able to virtually eliminate small particles, and that's another differentiating aspect of the drug, and we've been able to show a reduction in the rate of incidence of diabetes.
On top of that, one of the more recent data sets we've been able to share is the potential role for obicetrapib when it comes to prevention or treatment of Alzheimer's disease. So there are many reasons why a clinician would choose obicetrapib.
We find it very difficult to come up with a reason why they wouldn't. But there, there's the beauty of participating in a market which is not limited by patient numbers. There are at least 30 million patients who are not at their risk-based goals in the U.S. today, despite being not only diagnosed with hyperlipidemia but also being on treatment. So the opportunity is available really to all incumbents and all newly marketed drugs.
Let's touch upon the small LDL particle elimination.
Sure.
That contributed about 6% to the overall benefit in the BROADWAY study. How confident are you that number is real, and that's gonna get replicated in the PREVAIL study?
Yeah. So just going back to the analysis, and this is the BROADWAY study. The goal of the study was to demonstrate the reduction in LDL in an ASCVD patient population. But because of the size of the study, and obviously, ultimately, the benefit we saw, it led to many questions.
And one of the questions was: How were we able to demonstrate a 21% risk reduction when what would have been anticipated by looking at LDL alone is 9%? So, we shared the analysis where we felt that there was likely equal contribution from Lp(a) and LDL particles, so roughly 5%-6% for each. And that's something that we'll need to validate through our own ongoing studies.
Unfortunately, there's not a historical data set, or a CTT regression like there is one for LDL-C, for which we can point to, which says that X% reduction in LDL particles equates to Y% reduction in MACE. One data set that we can reference is Merck's anacetrapib, which showed a 9% MACE benefit in their outcome study, when what would have been predicted by LDL-C alone would have been 6%. So there we saw a 50% greater benefit in MACE, and likely there was contributions from both of those factors, Lp(a) and LDL particles.
You've got three ongoing studies, VINCENT, RUBENS, and REMBRANDT.
Yeah.
Which of these should sort of address the small particle?
Which of these? I would say the one you didn't mention, which is PREVAIL will give us the best answer in terms of the small particles. But again, I would. It's less about contribution. It's less focus on the overall benefit, and that's already quite profound.
The opportunity, and I think that you're, you know, going about this the right way, is to further differentiate the drug because there are many drugs, and I would say all drugs today that are approved or in development for the treatment of hyperlipidemia are singularly focused on LDL. We are one of the first to have many of the additional benefits. So as we think about a world where other aspects of the drug are going to be targeted, Lp(a) is a great example.
There are many drugs in development targeting Lp(a), which will solve for that need, especially need in patients that have the highest Lp(a) levels, so that we now look at particles. There is no other drug that does what obicetrapib does in terms of LDL particles, which is based on our clinical data, reducing LDL LDL particles by anywhere between 80%-100%.
There's still a little bit of skepticism on the class of drugs or CETP inhibitors in general.
Okay.
Given the luminaries within the company and outside who are participating, clearly there has been decades of learning, which is learnings which have gone into the design of the PREVAIL study. Maybe talk about why PREVAIL was designed to succeed, given that we don't have your, design paper yet. Sort of, distinguish between the benefits that obicetrapib brings to the table versus the prior four CETPs never had.
Yeah. I first and foremost, it's. You know, we are fortunate to have leadership that's been at the forefront in this space. Not only just at the forefront in terms of being cardiologists, lipidologists that have knowledge of these drugs, they were involved in many of the trials. So they had a seat at the table. They knew exactly what was going on in these studies.
And the benefit to us and comes in terms of PREVAIL is a trial that is designed not to fail the drug, and well, that's what Michael will say over and over again. And I think we feel pretty good that we've been able to achieve that. And now the focus is obviously on the execution of the study.
But really, you know, going back to your question, if you look at the four prior CETP inhibitors, it was a failed thesis. The focus was on raising HDL. And the idea was that if you raise HDL in a patient population whose LDL is well controlled, you could further improve that outcome in these patients in terms of reducing MACE events.
What we learned, unfortunately, was that that really was a failed hypothesis. But equally important, and what really supported New Amsterdam and where we are today, was the Merck anacetrapib study, which showed that reduction in LDL, even if it's modest, did, in that trial, translate to a MACE benefit. And, you know, we are the beneficiaries of that knowledge.
So as you think about the trial design, and then I go back to the premise, which is designing a study that does not fail the drug, we have enrolled patients that have high LDL. Our baseline LDL in the PREVAIL study is over 100, 102, 103. And what matters is the absolute reduction in LDL.
That's what translates to MACE outcomes. So the math is roughly 38.7 points of reduction in LDL equates to about a 22% MACE benefit. So having a high baseline matters a lot. Not the percent reduction, but having a high baseline LDL. Second is, again, based on observations of our studies, recognizing that there are certain patients that are just not going to benefit from an LDL lowering therapy.
So we excluded patients that had heart failure or were hospitalized for heart failure. So there are many aspects of the nuances in the trial design that we believe set us up ultimately for success.
So, as we have sort of over the last two years, talked to people, tried to overcome the, you know, hesitation on CETP inhibitors, now you have an oral PCSK9, causing more confusion as to what the commercial landscape is going to evolve or how it's going to evolve.
Mm-hmm.
So maybe talk about the recent oral PCSK9 data, and that, on that same context, the fixed-dose combo with ezetimibe, how that plays into the equation.
Yeah. So I guess I wouldn't view it as adding confusion. I think it was further confirmation that PCSK9s are exquisite at doing one thing, which is reducing LDL. The data we saw from the Merck study was quite consistent with what we have observed with the injectable PCSK9s. So as you think about the future landscape of hyperlipidemia, and I go back to the point that I made earlier, which is, there's no shortage of patients. The opportunity is for us, as a field, to once again bring to the forefront the care of patients with that are at risk because of their elevated LDL.
So if we all focus on ensuring that patients are not only diagnosed and then are provided appropriate treatment, commercially, we'll all succeed, and that's what our market research also demonstrates. In terms of the competitive landscape, we are one-on-one.
We're the only company with a CETP inhibitor that's in development. We are very close, as you all know, with the, sorry, the acceptance of the EMA filing last summer. So we expect approval in Europe this year, and we'll provide regulatory timelines for the U.S. in the middle of this year as well. But as you think about the commercial landscape, it's being able to speak to the benefits of obicetrapib that go beyond LDL-C.
So if we can focus on LDL-C plus , and it's really an opportunity to go back to patients and physicians and deliver a message that they should expect more from their treatment for hyperlipidemia, because most of these patients have risk factors that go beyond LDL-C.
So if you just look at patient numbers, looking at the diabetes patient population, there are 30 million Americans that have diabetes and also a risk for hyperlipidemia. And this is a patient population that's ideally suited for us because we're able to demonstrate a reduction and nuance of diabetes in our BROADWAY study, which is, again, only a 12-month trial.
When we look at Lp(a), there are roughly 10 million-20 million Americans that have both of those risk factors. Alzheimer's, the numbers grow even more. Those are the decision points for physicians and aspects of the drug, which are going to resonate, we think, commercially.
You brought up Lp(a), that's another sort of a added benefit here.
Yeah.
Obey had a very profound benefit in a subgroup of patients on the higher end of the Lp(a) spectrum, right? So what percentage of that is actually reflected in the PREVAIL study?
Mm-hmm.
Is Lp(a) still dominating discussion here, or has the field moved on, given the other sort of benefits?
Yeah. So, so let me speak to the trial enrollment. We didn't enrich for Lp(a). So when you look at our trial, the patient population that we have enrolled is in line with what's expected or what's seen in the general population. So half of our patients are going to have Lp(a) below 50. So those patients, based on our understanding today, have no risk or low risk because of their Lp(a) levels. Forty percent of patients are going to be somewhere between 50 and 150, which is what we believe is our sweet spot, and the remaining 10% are going to be above 150, and these are the patients that the injectable Lp(a) targeting agents have enrolled in their studies.
Got it. So, let's go back to the risk reduction seen in the BROADWAY study. There's still debate about, is that real, given that coronary revascs was a pretty big contributor?
Yeah.
Then we saw the Amgen data at AM, AHA-
Right.
kind of went that same direction.
Mm-hmm.
Thoughts around those?
Yeah, so again, I wouldn't call it a debate.
Mm.
I would call it a clear observation, an observation others have also made, which is nearly half of the events in our one-year BROADWAY study were revascularization. Obviously, we looked very closely at the data and the reasons for the revasc, and what was quite clear to us is if these patients had not received revascularization, they would have likely had an event, whether it's an MI or a stroke.
So the point you made is absolutely correct. So if there is a debate, we can literally squash that debate with the VESALIUS-CV data, right? What VESALIUS-CV taught us was that, at roughly the six-month mark, very similar to our BROADWAY study, there was a separation, and that was a separation of the curves driven by revascularization.
And because VESALIUS-CV had both a three-point and a four-point MACE, and the difference being in the three-point MACE, exclusion of revasc, that three-point MACE separated at the one-year time point. So, if BROADWAY was a longer study, a longer duration study, we believe we would've observed a similar trend. But, if you look specifically at the BROADWAY results and the individual event rates, not only do, did we see a separation in terms of fewer revascularizations on drug, we also saw fewer patients, fewer mortality as well as fewer MIs on treatment.
Got it. So this brings us to the filing and commercial aspects of it.
Mm-hmm.
Can New Amsterdam launch in this setting?
Yeah
versus your obvious competitors?
Yeah. Look, I, I'm smiling because, you know, we're, we're all excited to launch. This is truly a once-in-a-lifetime opportunity to have a drug like this, which has the opportunity to treat, not millions, potentially tens of millions of patients, and by the time the drug is generic, potentially hundreds of millions of patients.
So, when you look at our commercial organization, that, where we have leadership in place, this is a team that's, in essence, been there, done that, and they've done it in a similar dynamic. So, the most recent example being, Biohaven, our commercial head, and many of the team members launch, Nurtec.
Again, a large market opportunity, and a launch into competitive space with a drug which is quite similar in terms of the efficacy profile and likely had some advantages from a safety perspective. So the differences there were modest, but the results, you know, we can't argue with. They're they were able to take lion's share of the market and outcompete larger, you know, better entrenched competitors.
So as we think about now the landscape of hyperlipidemia with a highly differentiated drug, with a market segment that's multiples larger than migraine is, and the team that's in place today and the team that we'll hire in the future, or assemble in the future, we're not only confident that we can successfully launch this drug, we're excited to do it.
Got it. With respect to the U.S. filing timelines, obviously, your- the oral PCSK9 has, the Commissioner's National Priority Review Voucher-
Right
... et cetera.
Right.
How does that play into your strategy or timelines, with respect to the filing?
Yeah. So our filing is really predicated on what we believe to be an essential to a successful launch, which is to have outcomes data in the public domain at the time of launch. We also want to be able to confirm that LDL-C reduction through inhibition of CETP does also lead to an outcomes benefit. So that's what's gonna predicate timelines in the U.S. It doesn't in Europe, because pricing in Europe has another 12-month clock associated with it. So that's why the filing in Europe occurred earlier than in the US.
In terms of Merck's launch in the U.S. this year, and that was entirely expected, whether through the means that they were able to or through the purchase of, of a priority review voucher, we fully expected Merck to, to launch in the U.S. first. And if you look at their non-branded, you know, sort of advertising or non, non-branded efforts, it's really on making sure that hyperlipidemia and the treatment of these patients is at, is at the forefront.
The message that they're delivering is going to be: oral option is a better option for patients. That's the same thing, that we'll be able to say, but that's really where the comparisons end. When we launch, we can speak to every other aspect of the drug, which they won't be able to.
So we do view this as an ideal situation, where yet another large pharmaceutical company is going out to primary care physicians and cardiologists and making sure that their patients' LDL-Cs are being monitored and treated.
In the last just sort of few seconds, what would you guys be looking for in the HORIZON, the Lp(a) study that helps, you know, conviction on the PREVAIL?
Yeah. What we can learn has changed because of the delayed timelines for the release of the HORIZON data. We've already reported on our MACE benefit in BROADWAY. So as we think about the readout of HORIZON and what we can learn from that, it's really attribution or contribution. What was the contribution of Lp(a) in our BROADWAY study?
And as a result, what could the contribution of Lp(a) be in our PREVAIL study? I mean, that's what we hope to learn. This is an important study for the field. There's been a focus on Lp(a) for many years, so it's an exciting outcome for the community and for patients at large. But this is the first of several studies to target Lp(a), which will read out.
And so we'll... You know, we're obviously positive inclined, and if you ask John and Michael for their opinion in terms of you know, whether they expect HORIZON to be positive, they would say yes. But the read-through to us is now less because we've already reported on a observed MACE benefit in our BROADWAY trial.
Unfortunately, we have run the clock.
All right.
Thank you very much, Ian, and good luck.
All right. Thank you, Debjit.