Thank you, guys, for being here. Super excited to have NewAmsterdam management. Ian, so good to see you. And I think it's our first time doing a Farsight together, so I'm super excited.
It is. I'm excited to be in Florida while there's a, well, I guess there was supposed to be a snowstorm in New York, so I found that one.
I heard. There's people here that canceled their flights and stayed, so.
Yeah, that's my plan too.
Is that right?
Yes, that's kind of the plan.
Our director of research is here. He planned an amazing evening, and he's the performer, so I'm sure everybody's in attendance.
That's right.
Well, listen. I'll let you kick things off. Important launch coming up for you guys in the cholesterol space. A few hours ago, Merck management was here, and their head of commercial was here. They were really talking up their conviction with their sort of PCSK9 program. So perhaps just remind us, what are the timelines? What are you guys thinking? And we will build it up from here.
Yeah, no, absolutely. So last year, we presented quite a bit of our phase III clinical data, specifically looking at LDL reduction. So we had three positive phase III studies that read out two for our monotherapy drug, obicetrapib, and one for the fixed-dose combination with ezetimibe. And that was the basis for the regulatory filing in Europe this year, which was accepted. So we're on track for approval in Europe next year, and our partner, Menarini, would launch shortly thereafter. As you think about overall timelines and focus for investors, it's been really singularly on the PREVAIL study. And we continue to, obviously, follow the blinded events in that trial. And the plan is to provide an update on overall timelines, not only for PREVAIL, but also for the U.S. regulatory filing.
So PREVAIL's needed for the U.S. regulatory filing?
No, we find ourselves in what I would consider to be an enviable position. Because we started our outcome studies at the same time as our LDL studies, the opportunity we have is to have the outcome study data read out at the time of commercial launch versus every other lipid-lowering therapy. And including what we would expect for the oral PCSK9s, their outcomes data is to lag the launch by several years. So that's a fairly unique position that we find ourselves in and an opportunity to leverage that data set at the time of commercialization.
And Ian, where's your head at in terms of launch? Are you prepared to launch solo, or do you want to have a partner in the U.S.? Because sometimes companies are designed only for sale and not to actually execute it through.
Yeah, so.
And you've covered many like that, so.
No, absolutely. I think it really depends on the capabilities of the organization, and what we have in our company is not only a company that clearly knows how to execute clinical trials. We've done that. We have two scientists at the forefront in the lipid space and the cardiovascular space, which have designed studies to really enable the drug to succeed, and we've shown that with the phase III study readouts. What's maybe less known is the commercial organization, and this is an organization that, obviously, we've not put in front of investors because it just really wasn't the right time, but it does make sense to put the commercial organization in front of you next year, and starting with our Chief Commercial Officer, BJ Jones. So many will be familiar with his work and his team's work at Biohaven in the launch of Nurtec.
This is an individual and a team that successfully launched into a market where there were many me-too therapies and in a space that was a combination of specialty and primary care. When you think about the comparisons and think about obicetrapib in the space of lipid-lowering therapies, we have a highly distinct drug. That really affords us a unique opportunity in terms of being the first drug in the CETP class with the differences in terms of the advantages that go beyond the LDL reduction and a sales organization that has previously been able to successfully launch a mass market drug.
Right. So realistic launch time frame for U.S. is what? PREVAIL dependent?
It is PREVAIL dependent because what we want to do is maximize the opportunity during the period of the IRA. That informs a lot of the thinking for us and for really every company in this industry now. PREVAIL, having PREVAIL allows us to get the broadest possible payer access. As you think about labeling, the labeling is now fairly uniform, whether you look at it on the lipid side where drugs are approved now for patients with elevated cholesterol, so irrespective of patients that have had an event in the past or not. The same thing goes for MACE. It is really leveraging the data from a payer perspective to garner adoption and access.
Got it. How's the clinician feedback from AHA recently, your data versus Merck data as well?
Yeah, so I would really reference the better part of this year, not just simply AHA, because we've had our phase III data released, not only published, but also presented throughout 2024, 2025. And we've had the opportunity to engage with over 1,200 clinicians on a global basis to really ask the question, how does our product profile compare to not only the PCSK9 class, but compare to what's available today for patients? And it's quite clear that we are in a class of one with the CETP inhibitor.
Merck says that too, by the way.
Well, I think you should ask Amgen and AZ that same question. And I'm sure you'll get a very similar answer. I think there should be shared excitement about participating in the lipid-lowering field because the market is massive and the market has a clear unmet need. So when you think about the patient numbers, we're talking about 30 million patients in the U.S. who are not only diagnosed with hypercholesterolemia but also are far removed from achieving their goal. And that's the market that sort of at the headline we're all trying to go after. But then as you think about the future and the benefits, the unique aspects of obicetrapib going beyond LDL, we have the opportunity to address patients whose Lp (a) is elevated. Those patients that are on either diabetic or pre-diabetic or on a high dose of statins, which increases the rate of new-onset diabetes.
Because what we know to be true with the class, so this is not a unique aspect of OB, but what we've seen with the CETP class is a reduction in the rate of new-onset diabetes by roughly 15%. When you look at the other salient features of the drug and why we think would be an ideal combination agent for statins, is statins do a wonderful job of reducing LDL, but it's largely large particles. So what's left from a residual risk standpoint are smaller particles. And when you look at our data, we're able to reduce the vast majority of the small particles that remain. So again, think about ideal combinations in this treatment paradigm. And the latest data we shared with all of you is on Alzheimer's.
So, really intriguing signals from a sub-study of the BROADWAY ASCVD trial where we showed an improvement not only in p-tau217, a marker that's increasingly being validated, but a whole host of biomarkers that have been correlated with improvement in Alzheimer's function. So, Alzheimer's is going to be, or patients that are ApoE4 carriers are also going to be candidates for this treatment in the future.
Got it. Excellent. So one of the points Merck's making is they want to maximize access.
Sure.
And we've seen Amgen net price now down to low 200s. So let's just call that about $2,600 a year or so, $2,700 a year. Presumably, Merck has that price point in mind and may even come in slightly lower than that on a net basis. Is that consistent with how you guys have modeled it through for launch?
Yeah, so it's not as much about price. It's really about, I think, as Merck's appropriately said, access. And what we want to make sure is we have the broadest possible access at launch. So if that entails pricing within the existing framework, I think that's a good assumption to have.
Meaning same list, but on net is where you make access happen?
I think that's the current pricing paradigm in the U.S. is that, right, high list, lower net price, and the discounting structure that really motivates the decision.
But the net numbers I threw at you, those are not very novel to you. You're well aware that those are the numbers and Merck is playing around those. Okay, got it.
Sure. Yeah.
Okay, makes sense. Now, in that backdrop, what does PREVAIL outcomes trial need to show in terms of a signal? And I ask because we've seen PCSK9s max out at about 0.75 or so, which is a pretty real signal. But is the bounds between 0.75 and, I don't know, 0.94, which was the anacetrapib signal, is that the bookends?
So you're referencing 0.75. That's in a different patient population. So if you look at the FOURIER trial, which is in secondary prevention, the benefit there was 15%. So the hazard ratio is 0.85.
Correct.
In the Vesalius study data, which was presented at the AHA conference, again, these are patients that you can't say they were primary hypercholesterolemia or primary prevention patients, sorry. These are patients that had likely revascularization as part of the entry criteria. So it's a hybrid patient population, but then really trending more towards less advanced or less severe. So in that patient population, you're correct. We did see a 25% risk reduction when it came to three-point MACE and a 20% when it came to four-point MACE. So going back to your question.
Which one is yours, by the way? Three?
Four-point MACE.
It's a four-point MACE.
It's a four-point MACE.
Okay. Which bias is it to be a little lesser?
Right.
Theoretically. Okay.
Right, but going back to your question, it's most important that we demonstrate clinical success, so we have stat sig in our outcome study. The numbers matter less, because ultimately, when you think about a physician and determining what medicine to give their patient, prescribe their patient, it's really based on several factors. It's how far removed are they from their LDL goals.
Right.
So we have two product forms. One, the monotherapy drug, which helps patients achieve anywhere between 35%-40% reduction in LDL. The combo, which is shown somewhere between 50%-55%, so similar to the PCSK9s. And then beyond that, what are the other risk factors their patient is susceptible to? So if you have a patient that has elevated Lp (a), that has preponderance of LDL particles, small LDL particles, is at risk for diabetes or has diabetes, is an ApoE4 carrier, those are patient populations which number anywhere between 20-60 million patients. And in those patient populations, when you look at our data, there's a consistency of benefit. So irrespective of what the other risk factors these patients have, what concomitant medications they're on, including other lipid-lowering therapies, we've been able to demonstrate a fairly consistent benefit.
And on top of that, in a patient population which is truly asymptomatic, and the goal is to make sure that they remain asymptomatic, you look at our adverse event profile. It's really nothing of note. We have a really well-tolerated regimen where a vast majority of the adverse events occurred at a lower rate on drug than they did with the true placebo.
Fantastic. So what would the launch timing look like for your cholesterol-lowering drug versus Merck PCSK9?
So I believe, and you can correct me, but Merck's commented recently that they plan to file for approval.
They haven't filed yet.
They haven't filed yet, but they plan to file for approval at some point in the first half or early next year. Right? I'm not entirely sure geographically which geography they've committed to. But as I mentioned, in Europe, we're already on file.
Correct.
So we know we're going to be on the market before.
Yeah. What would your U.S. be?
So as I mentioned to you, the U.S. is really dependent on the timing.
So, 2027, though, something in 2027.
It's going to depend on the timing of PREVAIL.
Right. Would you be surprised if Merck ends up filing with a voucher?
No, not at all. I mean, I think it makes sense for them to pursue that.
Okay.
Again, they're in a bit of a race with the other PCSK9s in the field. We are one-on-one. We're the only drug in the CETP class.
Sure.
So it's not the same sort of pressure incentive that they have.
Among new orals for cholesterol-lowering, how do you see share play out versus Merck on an NBRx basis? Based on your market research, is it 50%-50%? Is it 80%-20%? 30%-70%? Because you'll be a little less.
Yeah, so the commercial team has done an assessment of the overall opportunity for OB and utilizing the phase II profile of Merck's oral PCSK9. And what we clearly showed is the PCSK9 , as a class, is going to be highly successful and Merck, as with their individual drug. What our data also supported was that we're going to be more successful than them. And it's because of the.
More successful.
It's because of the additional features, the other aspects of the drug.
Okay.
So when I think of some of the numbers that AstraZeneca and Merck have shared, they've alluded to a market opportunity that's $5 billion or higher. And we believe that's true. I think we think the PCSK9 drugs individually and as a class will be that successful. We just have an opportunity to do better than that.
Makes sense. So one cholesterol-lowering drug, which is not in the Merck or the NewAmsterdam conversation, in my opinion, is Lilly's Triple G. There's some patient anecdotes tracking at close to 50% LDL reduction with that molecule. And considering all the amount of interest in sort of obesity side to begin with, how does that factor into how you guys think about the commercial landscape?
Yeah, so again, when we think about the overall size of the pie, the size of the market, it is quite large, and there's not going to be one size fits all in terms of one solution for every patient.
Sure. Or are those different markets?
They can be. Because if you're looking at a GLP-1, you're looking at.
30-something-year-old.
Exactly. You're looking at a patient with metabolic syndrome. You can also factor in if you're a patient that is obese and going on any one of these therapies, what is the persistence of that patient?
Could it be as simple as, in many cases, yours and Merck's launch is more Medicare population and those are non-Medicare populations? Is that too simplistic?
It is. A large segment of the population we'll go after is commercial lives.
Okay.
Yeah.
Okay. Sorry, I meant age-wise, not necessarily Medicare-wise.
That's right.
60+ versus below 60.
Yes. Unless everyone follows.
Guidelines. I should be doing that too, then.
You're absolutely right about the guidelines, and we should talk about the impact Vesalius is going to have on that. Because we are getting to a point where the Vesalius data really drove home the point that if you can get a patient on drug earlier. So again, asking the question, what is the difference in a patient that's either had a heart attack or not, whose LDL is elevated? There isn't really a difference. So it makes the most sense to get these patients on drug, modulate a risk factor such as LDL as early as you can, and if Michael were here, I mean, he's a big proponent of treating early, he'd rather treat a patient from 30 to 50 and stop as opposed to start at 50 and try to modulate a lifetime's worth of risk.
Makes sense. My last question. And this is a question I used to be very confused about when I first started looking at NewAmsterdam. So you guys have LDL reduction north of 40% for a CETP inhibitor. I remember going back to my old notes with Schoenebaum, and I found this Merck disclosure on anacetrapib showing low 30s LDL reduction as well. And then I saw the footnote, which was the beta-quant method of measuring versus an alternative.
Versus the direct method, yeah.
Correct. So remind me then, which one are you guys using for all the presentation? And is your method consistent with how everybody else reports their LDL lowering as well?
Yeah. So you're right to pick up on that variability. And I think the data you referenced, I don't know if it was for Merck's anacetrapib or.
It was the old Merck slide. I do remember that one.
So the issue with the measurements, the direct method, there was a high degree of variability as patients' LDLs were low. So at lower LDL levels, there was a high degree of variability. And the market as a whole, the field as a whole has shifted to using beta-quant. And that's the methodology we're using. But we have also shown methods which calculate for LDL. So whether it's Martin/Hopkins or Friedewald's.
So all the Merck data we just saw, was that on beta-quant or no?
I believe the Merck data was in beta-quant. The AstraZeneca phase II data release was actually using the direct method. So they did something a little bit different.
I see.
Yeah.
Okay. Excellent. Last question. Alzheimer's opportunity, do you need additional trials? And what would the launch timelines for that look like?
It's a good question. We're clearly excited about the signal we've seen in Alzheimer's. This is something, Ben, that Michael has contemplated for, I would say, a better part of a decade.
EVOKE is irrelevant to how you guys think about it.
EVOKE is irrelevant because we haven't seen impact on plasma biomarkers such as p-tau217 with the GLP-1s. And we clearly saw that in our BROADWAY study. So as we think about the path forward, it begins with engaging with the FDA, which we're planning to do relatively soon. What we've committed to is conducting a phase II-B trial, which will once again look at p-tau217 as a biomarker. So that's the primary endpoint. We'll also look at other biomarkers, which you're all too familiar with. What we also want to do is evaluate as a secondary endpoint, cognition. And in a subgroup of patients, and again, this is all based on feedback from the FDA, we could potentially also have a subgroup of patients where we measure PET scans.
To try to really drive home the point that there is a correlation between p-tau by the biomarker and endpoints that what we would consider to be more standardized in the field.
Excellent. Last point. I feel like one of the limitations for the PCSK9s have been, since they don't lower CRP, I think that might have been the reason why they never got to the 0.5, 0.6 hazard ratios, which were initially thrown around or contemplated. Do you know the CRP data for your molecule? And is it any more than what a PCSK9 produces?
No. We have a neutral effect on CRP.
Nothing on CRP. Okay.
Yeah.
So the bounds for an outcome's benefit are between that, somewhere between 0.7 and 0.9, depending on the trial design, etc. So realistically, around 0.8 would be the.
I think we have a good starting point with BROADWAY, the data where we showed a 21% benefit in terms of the MACE endpoint at one year. I think the role that you could assign to whether it's CRP or other factors, in our case, the other factors would be Lp (a). We'll be able to better sort of define or quantify once the HORIZON study reads out in the first half of next year. And the other factors, the other prominent factor would be LDL particles. So there's no good data set to try to quantify the impact of LDL particles and the influence that would have on sort of MACE outcomes. But that would be the other facet of the drug.
Outstanding. Well, good luck into the launch. Thank you again for joining us.
Thank you, Umar. Really appreciate this.
Fantastic.