NewAmsterdam Pharma Company Stifel 2026 Healthcare Conference

Sure. Yeah, thank you. Thanks, everyone, for coming. Just got back from American Heart in my hometown of Chicago, and it was obviously the two big studies was HORIZON and ZEUS.

A lot of very important learnings. ZEUS, of course, that was my drug, Corvidia, sold to Novo, ziltivekimab. I still think that a lot more to be learned from that trial, but it ended up being a very sick population. I think more to come. I do not think the inflammation story is over by any means. Even IL-6, I think there might more come out of that as time comes on. But I think what is a learning there is that we have learned this already in the LDL field, that when you go too sick in a population, it is too late, and you cannot have a benefit.

It was designed in some ways for that because we know that statins do not help this population because they already have heart failure, kidney disease, and we thought inflammation would be a driving effect that we could mitigate with IL-6. I think we will learn more, but I think there was too many patients were already too late.

I hope that more comes out of that. ARTEMIS is ongoing, less sick population, which might see a benefit. That is ZEUS, and I think it factors into the overall pessimism of CVOTs that we are now facing in the field, which is, that is the life we lead in trying to develop new therapies, but we are not giving up, of course, and remaining optimistic about the whole anti-inflammatory approach to reducing residual risk. HORIZON is, I think, another important learning, and it has a lot of read-through to us, but I do not think how people think about it the way I think about it as a clinician.

Up until HORIZON, because I see a lot of patients in my University of Chicago clinic that have high Lp(a), and what we have been telling them for a few years now is, "If we get your LDL low and your CRP, your inflammation marker, low, the risk is substantially lower.

You have high Lp(a), let us get your LDL down below 50. Let us get your CRP as low as we can. That is usually weight loss because visceral fat is the most inflammatory contribution there. If we do those two things, we can make a big difference on your events. HORIZON confirms that decision because overall, there was very low risk if you had a high Lp(a) and you also had a low LDL and a low CRP. In fact, the numbers are pretty astounding, actually. If you had a high LDL above 100 in HORIZON versus a low LDL below 100, the risk was something like 10%-18%, more than 50% increased risk for having a high LDL versus a low LDL or lowish LDL. That is the PREVAIL study. The PREVAIL study is a high LDL over 100 is our median.

Median is over 100, and we have high Lp(a) in a subset of patients, but it is not a high Lp(a) trial. I think one of the takeaways that we have heard from investors is, "Oh, now that Lp(a) is dead, the PREVAIL trial, that added benefit in PREVAIL is no longer going to happen." Any differentiation that obicetrapib had from other LDL drugs is also diminished because the Lp(a) lowering benefit is no longer part of that overall benefit that obicetrapib delivers to patients.

When you look at HORIZON in those contexts of the subgroups, you see that in that upper LDL population, which is like PREVAIL, you saw not only much higher risk, but also a 0.83 hazard ratio for pelacarsen, which suggests that there might be some benefit when LDL is high for lowering Lp(a), and that's what the PREVAIL study population is all about. I wouldn't write off that there might be something extra about Lp(a) lowering that obicetrapib provides that could contribute to the PREVAIL benefit. I think obviously, there's a lot more to that. Obicetrapib raises HDL 150%. It lowers the risk of diabetes. It lowers all the small particles by 90%. Of course, the Alzheimer's benefit. We have many differentiating features.

In addition to the fact it's a small little pill that you don't need to worry about food effects and no side effects more than placebo. In combination with ezetimibe, we're in that 50% plus range, which is comparable to any other PCSK9 inhibitor for that matter. We think HORIZON does, in fact, give us more optimism about obicetrapib having an extra benefit in PREVAIL.

The other thing, of course, it provides is that new- If there is no benefit for Lp(a) lowering for secondary prevention, we think primary prevention is another. That came up quite a bit in the discussion, that primary prevention for Lp(a) lowering is where the risk is really the most obvious.

What's interesting to me about HORIZON is the average age was 59 in that trial. These are patients post-MI that had high Lp(a). In a typical CVOT of the same type of patients, the average age is over 65. These are younger patients having an event, which suggests that for Lp(a), the biggest issue, you get more premature disease. It leads to earlier heart disease. Primary prevention really should be the focus.

And we have other studies ongoing that will look at primary prevention, but obicetrapib could become the main primary prevention-type drug for these patients because, again, talking to patients, they don't want a statin, which raises Lp(a). They'd rather have a drug like obicetrapib that lowers LDL and lowers Lp(a), if they have high Lp(a). So we think it really helps differentiate us even more so than any other lipid drug going into the market. And I think the main point is that differentiation, we believe, is still there for Lp(a) benefits. We think PREVAIL, HORIZON does give us, I think, insights about that PREVAIL higher LDL, higher Lp(a) group could have an added benefit.

And the last point I want to make is that because all these other Lp(a) drugs have gone away, and ZEUS has really diminished the inflammatory kind of drugs out there, we become the next big drug out there for cardiovascular, assuming PREVAIL works. And so that's going to create a lot more, I think, excitement for our drug, once it's approved.