Okay, great. I think we're at time, I'll kick it off. Hey, everybody. I'm Roanna Ruiz, one of the Senior Biotech Analysts here at Leerink Partners. Just wanna welcome everybody to our global healthcare conference, it's my pleasure to introduce NewAmsterdam Pharma. I've got the CEO, Michael Davidson, with me here, also the CFO, Ian Somaiya. Thanks so much for joining us.
Thanks for having us. Yeah.
Good morning.
Yeah. Good to see you guys. Maybe to kick it off, I'll start with a bigger picture question for any investors that are new or revisiting the story. Could you guys just help frame, you know, what are some of the main updates that have happened recently and, you know, what are you most excited to look forward to for your lead asset, obicetrapib?
Sure. Well, thanks everyone for coming. We're having a big year, 2026. You know, obviously we had tremendous progress, you know, over the last year or two. We finished our phase III trials, BROOKLYN, BROADWAY, and TANDEM, really demonstrating the differentiated profile for obicetrapib as a potent oral, well-tolerated LDL-lowering drug. In combination with ezetimibe, we get LDL lowering in that 50% range, which is comparable to the injectable therapies. What I think it was important about our trial progress and differentiation is that the drug, again, well-tolerated oral, we filed in Europe for approval, so that'll be happening this year. I think one of the key kind of moments for us was the BROADWAY data showing...
It's a mini outcome study, 2,500 patients at one year, you know, showed a 21%, you know, MACE benefit. We had, you know, again, the foresight or whatever you wanna say, courage to start our outcome study as early as we could in phase III , and that's PREVAIL. We designed PREVAIL to maximize for success, you know, with 9,500 patients, high baseline LDL over 100, enriching it to those that we know benefit the most from LDL lowering plus what we think the unique benefits of CETP inhibition are with obicetrapib, the small particles, the Lp(a), the diabetes benefit. We maximize our outcome study to match the benefits we've seen in the past and for all LDL trials, especially for a CETP inhibitor.
That PREVAIL trial will be announced early this year that it's matching our blended benefit, blended event rate we saw in BROADWAY at one year, that gives us, again, confidence that that 21% relative risk reduction is consistent with what we saw in the BROADWAY study. We have other readouts this year. The RUBENS study is specifically a diabetes trial, where we know the drug has the greatest efficacy, and we wanna use that data to expand our label, because right now it's for diabetes with heart disease or all heart disease. Now we have the diabetic patients, two-thirds do not have heart disease yet, so that's a $20 million increase in patient population that would be in our labeled indication.
We have the VINCENT trial looking at Lp lowering in combination with a PCSK9 inhibitor. Again, a big year for us. The two and a half-year mark, which is the minimum follow-up for PREVAIL, ends this year around November or so. We, that's when the study can complete, but we also it's event driven, so We'll have to see how the events line up. Right now we're on track, you know, for in the, in the next, you know, in this timeframe to get, have the study completed.
Yep. I hear you.
Michael gave an update on the clinical trials. I'm most excited about the prospect of us getting approval in Europe.
Mm-hmm
... and being a commercial company. We've shared with you previously our expectations for the potential for this drug being $8 billion or higher. As you think about the role or the contribution from outside the U.S., it's gonna be likely in the 40%-50% range with significant portion of that coming from Europe. That is an opportunity that we're excited to see Menarini take full advantage of, potentially launching at the end of this year, starting in Germany and the U.K. Just take this opportunity to remind everyone this is a highly lucrative agreement for us.
As you think about the economics on this drug, and when the deal was signed, after phase II data, we'll collect royalties in the low double-digit all the way up to mid-20% range. Given the sales thresholds that lead to those higher tiers, we fully expect to be able to get to the 20%+ range in the future. We're still owed roughly EUR 800 million in milestones. That's driven by a contingent on approval in Europe, country by country launches for the monotherapy, fixed-dose combination, and as well as future sales milestones.
Yep.
Yeah.
Sounds good. Yeah. Since things are getting real for PREVAIL, the outcome study, I'll dive in there first. One question that I get often from investors is just, so you powered this for 4-point MACE. you do have optionality or you're also thinking about disclosing information about 3-point MACE. How should we think about how does the results and how does it read to commercial implications, clinical implications? Like, how would you guide investors on those two?
Well, there. The data shows that when you have 4-point MACE, 3-point MACE is also very close in the relative risk reduction. You have less, you know, you have less 3-point MACE than 4-point MACE, obviously, 'cause you don't have coronary revasc. That's the difference. I think it's important, especially outside the U.S., that the 3-point MACE is also positive, 'cause it's for regulators there, they like to see that, a 3-point MACE in particular. The FDA has actually harmonized their approach to these outcome studies where in the past you had to hit each individual component to be on the label, and they decided to match the cardio renal division where every component, whatever is in your component, you get in your label.
You know, for example, Repatha didn't show coronary heart disease death reduction. It was actually a hazard ratio slightly above 1. They initially got their label, they couldn't mention cardiovascular death, coronary heart disease death in their label. Now the FDA has taken that requirement away, so they got that added to their label, coronary heart disease, even though it was not individually significant. That's a really a bonus for us 'cause we were hoping this would be their approach. Now with our in the FDA mind, whatever we have on our 4-point MACE, as long as we're positive overall, the composite's positive, we can include all four of those components in the that's why we included ischemic stroke also.
Again, for the previous Merck trial, they didn't have ischemic stroke, had a slightly better hazard ratio. For us in BROADWAY, you know, we didn't see ischemic stroke yet, but we know from many other trials that the first year is always very challenging for ischemic stroke. Over time, it becomes one of the bigger contributors to the composite benefit. We have that now in our 4-point MACE. The bottom line is you wanna ideally have both 4-point and 3-point MACE to be positive. You have more power with 4-point MACE obviously, but you still wanna have sufficient power for 3-point MACE ideally to complete the trial.
Okay. I noticed you're talking about revasc possibly driving a little bit more of the benefit. How are you thinking about that? Does that matter? Is that depending on which all the different components contributing to the overall MACE at different levels or hypothetically, how are you thinking about that?
Well, I mean, that's the thing. In the FDA's mind and of course, clinicians' minds, it's just really what the composite tells you, so the % reduction in the composite. You know, you can speak to individual components in promotion, which is always, you know, kind of a helpful thing. If you have that data, you could talk to that in your promotional presentations to physicians and so forth. It'd be nice to see every component in the right direction at least. For the bottom line is for approval and just acceptance, it's really the composite overall that makes the biggest difference.
Yep. I hear you. Interesting. Just zooming out a little bit, thinking about obicetrapib , it not only does LDL-C reduction, it also has benefits in Lp(a) and other biomarkers of CV risk. How do you think about physicians, you know, absorbing that messaging, assuming everything goes well with the PREVAIL outcome study and all the benefits of obicetrapib ? Like, where would it be prescribed?
There's actually a really good opportunity for us for exactly where the drug works the best, and that is the 50-150 range. It lowers Lp(a) roughly 50%. That, that population represents... Of the high Lp(a) population, that's 80% or more of the Lp(a) elevated population. That provides an opportunity for us to be the kinda like the go-to Lp(a) lowering therapy, quote, 'cause it won't be indicated for that, but it would be for the LDL lowering in those patients that also have high Lp(a). It's a really good. 'Cause you wanna lower LDL anyway. All Lp(a) low. All the patients should have an LDL as low as possible. That's the key.
You wanna have a drug that can lower LDL and lower Lp(a) for those 150 to 150 patients. The injectables will be, like, relegated to those that have above 150 and already pre-existing heart disease. Again, the people that don't yet have heart disease or preclinical heart disease, this become the go-to drug even for those above 150 potentially. You have the specialty pricing of the injectable. It's gonna be premium priced 'cause that's the highest risk population. We'd be a lot less expensive, probably greater access. Also the injections and especially for this type of injection, it's not completely innocuous it is because of this...
I do feel here that there's like any ASO, there are more skin site reactions. It's also monthly dosing. I think we're gonna be in a really good position no matter what happens with Horizon, whether it's positive or negative to be the majority go-to drug for those that have high Lp(a).
Yeah. You sort of preempted my next question. I was gonna ask you more about HORIZON.
Yeah.
I'll dig in a little bit more. Just to double-click on that.
Yeah.
Thinking about the HORIZON trial from Novartis and their Lp(a) lowering agent, what are the possible read-through scenarios to NewAmsterdam Pharma and obicetrapib ? What would be a win for you guys, and how are you thinking about the data implications for obicetrapib ?
Right. Right. I think the, I think the key is that we think it's a win-win no matter what happens with Horizon because we already have our established our 21% kind of signal of benefit from BROADWAY that we're tracking now in PREVAIL. We feel, you know, we're gonna have outcome benefits with our drug. In that sense, we feel that we don't necessarily have to rely on a positive Horizon as a read-through to us. That's important. I think, if it's a positive, of course, it's a read-through for Lp(a) lowering and the benefit of Lp(a) lowering. That's an, I think, an easy one. I think there's many different kind of caveats to that. You know, one is that it's modestly positive.
It's only positive when you get below a certain threshold, like 50 as an example, where the risk starts to come down to normal as opposed to. Maybe if you lowered it, because they have a lot of really high Lp patients in that trial. You can see people that could go from 500 down to 100, you know, maybe not benefiting. We'll learn that from the Horizon trial. It may dilute some of the benefit. If that's the case, then they were set up for a, you know, even greater success because we'll be the first Lp lowering drug on the market that.
'cause of this therapy either doesn't get approvable regulatory path or the benefit 'cause its benefit is modest or it does get approval, but people realize it's gonna be, again, relegated to that very high-risk niche population.
Mm-hmm.
That, in that sense, we feel it's a win-win either way for us when it comes to Lp lower. I think a totally negative trial is still okay because I think people still realize how important Lp is as a risk factor, and I think others are following, like OCEAN(a) and Lilly and all the orals and so forth. I think that a totally negative trial, depending how negative it is still could be a positive read-through for us.
Mm-hmm. Interesting. Okay. That's great. Thinking commercially for a sec, I know Merck has their oral PCSK9 moving forward and could potentially launch ahead of obicetrapib in the U.S. How are you thinking about the market evolving with potentially two new orals on the market available for physicians? Like, how are you framing it for investors?
Yeah. I can speak at a high level, and maybe you can speak to it in from a clinical practitioner standpoint. We're excited for Merck to launch in the US. We fully expected them to launch ahead of us here. Similarly, we'll be in the market in Europe before they will. The focus for them is going to be on orals, high potency orals. That's where the similarities really end between the two drugs, ours and theirs. The goal has to be to get patients to goal.
When you look at our data, especially the fixed-dose combination data, the fact that we're able to get 70%, 80% of patients to their risk-based goals, I think bodes well for clinicians and the choice they'll have to make between these two therapies. What benefits us is all the plus characteristics of the drug. You spoke about the Lp, obviously, that's a hallmark feature of obicetrapib and the mechanism. It's the benefit we saw in terms of the rate of nuance of diabetes, which has also been reported by every other CETP drug that's been developed. It's the virtual elimination of small particles, a topic that doesn't get enough attention.
As we look at our data, that could be driving a significant portion of the benefit. We shared that with you as part of the mediation analysis, and one of the read-throughs from Horizon very simply could be, well, maybe Lp is not as causative, and we need to attribute more so to the particle side. And I'm sure we'll get into the conversation on Alzheimer's, but that's yet another unique aspect of our drug. We're rooting for Merck. We're rooting for really all the players that will enter this market because there are 30 million+ patients today, and the opportunity with the treatment guidelines potentially getting updated this year is for that number to double. Plenty of patients out there, we're not competing for sure, and that shouldn't be the mindset.
It's let's get patients to their LDL goals and let's drive other aspects of the drugs profiles, let those drive treatment choice.
Yep.
I say that as far as the oral, I mean, I think the oral Wegovy launch success, you know, speaks to an oral versus injectable, you know, quite well. We're seeing a big increase. Obviously, we're doing well, you know, oral Wegovy versus injectable Wegovy.
Yeah.
It does speak to the oral, even the peptide type of... Of course, that's weight loss. It's different than, I think, LDL lowering is gonna be a little bit more of a motivational challenge, you know, for taking the drug after fasting and then not taking any other drugs for 30 minutes thereafter. I think it's gonna have a nice benefit. It shows how oral benefits, but also it's not quite exactly the same scenario. I think Merck will do well. Remember, we're launching with outcome studies in hand, so they don't... They have the PCSK9 that they can reference, which is 15% based on the Repatha label.
What they haven't announced yet is, which I think is insightful, is they haven't announced their own MACE data from phase III , which has always been done. They haven't announced. I think it's because it didn't show a benefit, which is kind of interesting. They also have not announced their anti-drug antibody levels, which they'll have to disclose for sure in their label. That's what Repatha has disclosed that. Again, that's something that I think is something that we'll have to see how ultimately the label looks. Of course, we have Repatha, you know, counter deal tailing it. You know, we have now outcome benefit, we have, you know, not just FOURIER, but now VESALIUS-CV.
Why is no MACE data for them, and we better go with what's already proven. We're gonna have all that proven when we launch the drug with our own, with PREVAIL.
Yep.
They can't, you can't counter detail that with the evidence.
Good point.
... that we're gonna have.
Yep.
Yes.
I hear you. Wanted to think just in terms of future market opportunity and help frame it. You alluded to the RUBENS trial earlier.
Yes.
I think this is a really interesting, maybe somewhat under radar study going on for obicetrapib, but actually could be really meaningful. Can you just explain, so looking at these diabetes patients with metabolic disease, how could this expand the eligible patient population for obicetrapib?
Well, you have.
It's often patients restriction from payers because what's in the label, you know, what's the indicated population? That opens up that, you know, that access to the diabetic patient with not yet have heart disease. That's one thing. Also we think this is a unique opportunity to, you know, position the benefits of obicetrapib in the diabetic patient in particular. We know from BROADWAY that this is where the drug works the best. We know that it also reduces the onset or worsening of diabetes. We think. We can't speak to it promotionally because it's a subset of a big study.
Once we have it in a officially in a study, you can speak to it more promotionally as well as with publications, because it's not just a subset of a study that you've already done, but a full pre, you know, prospective trial in the diabetic population. That's a very powerful kind of enhancement to what you can say to message wise. We know the diabetic subgroup from BROADWAY. We know it did really well and all the other things. We can't talk to physicians separately unless we have our own trial. That's the way it works.
Yeah.
BROADWAY does that. I mean, sorry, RUBENS does that for us.
Mm-hmm. Thinking about RUBENS, I mean, what are you hoping to see if all goes well with that study? What would be, like, exciting going forward for obicetrapib?
I think again, it's, we wanna. Remember it has the FDC in there also.
Mm-hmm.
It has the fixed-dose combination and monotherapy versus placebo. We wanna show obviously good LDL efficacy, good tolerability, improvement of glycemic indices, which are again, we can talk about separately because it's a diabetes patient population. Again, this is where the small particles are the most at risk for the population. We see that as another key benefit of obicetrapib in the diabetic patient population. REMBRANDT, just keep in mind, REMBRANDT is our imaging study with the fixed-dose combination. That also is gonna complete enrollment this year, and that read out 18 months later. That has a lot of diabetic patients in the study too.
We see the diabetic patient showing obviously benefits from PREVAIL, even in the subgroup, its own RUBENS study, promotional benefit of that and efficacy and safety and all the other unique benefits. REMBRANDT as well. PREVAIL outcome benefit. I mentioned that. Even REMBRANDT showing plaque reduction in this very high risk progressive group, puts together a whole package of benefits for obicetrapib and the FDC that we think is gonna really make that, which is roughly. You look at diabetes and pre-diabetes, it's 80% of patients on lipid therapy today. What's important is statins don't have that benefit. If anything, it makes things worse. We see this as a real differentiator that we wanna continue to build upon with our RUBENS study, and then others to follow that have the diabetic, large diabetic subgroups.
Yep. Got it. I'm glad you mentioned Rembrandt because I was thinking about this being a really unique trial looking at imaging data. How are you thinking that the imaging data could influence prescriber mindsets?
Yeah
... seeing the plaque reduction themselves, assuming everything works out, how could that drive more prescribing potentially?
Because I think plaque reduction, if you One cardiologist goes where you have that what's called oculostenotic reflex. You see a lesion, you wanna open and dilate it. You wanna shrink it. Cardiologists love seeing plaques get smaller. You know, that's what we're trained to do. That's what REMBRANDT hopefully will show is that, you know, plaque reduction. The field is moving rapidly to a CT angio, you know, plaque analysis. We have, you know, multiple companies looking at a non-calcified plaque as a way to track disease. We're gonna see that become more and more widely available and what will be one of the first, if not the first study to show a plaque reduction with a drug, a non-calcified plaque volume.
That's REMBRANDT. Again, there are others that are looking at this as an endpoint. I think we might well be the first to show that benefit. I think we look at the Halson study, which is a Repatha imaging study. It's not in the label, but they're able to promote about it. According to what we've seen, and I've heard directly from the Amgen folks, is that study, which showed plaque reduction using intravascular ultrasound, which is a very invasive technique, was one of the best ways to promote Repatha benefit. That, since that study came out, they're able to talk about it with physicians. They can't talk about it in combination with FOURIER.
It was kind of strange how the FDA thinks about these things. Even talking about that study alone, they got tremendous increase.
Hmm.
... in Repatha sales because of that study. Again, it's a, for cardiologists in particular, it's a very exciting endpoint that they like to see for a drug.
Yeah.
One can imagine from a patient standpoint, that visual is obviously, you know, quite, quite comforting. As RUBENS is label enabling, REMBRANDT is, has a commercial bent to it in terms of driving potential uptake. Those are two of the more, I mean, as you described it, under the radar, but very important studies for us.
Yep. Got it, got it. I wanted to have some questions also on the Alzheimer's initiative.
Yeah. Sure.
... as well for obicetrapib. This is also super interesting. Can you talk about some of the goals for the phase II-B ?
Right
... planning? What trial design features are you thinking about? To just sort of maximize the messaging and capturing the profile of...
Right. Right.
... obicetrapib.
Again, we started the company over five years ago. Alzheimer's was always part of our initial development plan, cause we had some funding put aside for Alzheimer's. The thing is APOE4 is a lipid gene. You know, in fact, of all the genes associated with Alzheimer's, almost all of them are lipid related. This kind of gives you the first signal that, you know, something going on with lipid metabolism, especially in APOE4 related population. You have the Mendelian randomization data showing benefit. We have preclinical studies showing a benefit. We had a proof of concept study in people with MCI showing stabilization of the biomarkers in cognition over six months.
Now we have our pre-specified analysis from BROADWAY in a very large patient cohort, you know, 700 patients, showing now for the first time, this wasn't available before, but this p-tau217, if you follow the literature, is exploding in publication showing how good this biomarker is, as good as. The PET's gonna go away and p-tau217 is gonna be plasma, you know, in the blood, replacing PET as measurements of amyloid in the brain. We showed a significant reduction in p-tau217, especially in APOE4 homozygotes. With AI, looking at our data, we can identify, you know, populations where we see the greatest increase in p-tau217 in the placebo arm, where we have the greatest benefit with obicetrapib.
What's important to point out is, and we'll talk more about this later, but in anyone who has a p-tau increase, either they're because of APOE4 or their age, obicetrapib blunts that increase or decreases it. It's kind of like any of the groups that have a progressive rise in amyloid, obicetrapib is blunting that increase or decreasing it. With that, we can design a study. We wanna look at the three four fours and the three fours, even three threes. These are APOE I'm talking about. That we can then identify the populations that would be best suited to go into a true phase III quote, outcome study with obicetrapib on preventing cognitive impairment. Because the future of this treatment is prevention. And is.
What's learned about Alzheimer's, it's not Alzheimer's equals dementia. It's not the right way to define it. Alzheimer's is a biological process that starts 20 years before you get cognitive impairment. In that 20-year window where there's increased amyloid but not yet cognitive impairment, we think obicetrapib could delay or prevent that onset of cognitive impairment. That's what we're trying to show with our next trial. Again, getting ready for the true outcome study. I think also we understand, you know, people's hesitancy about believing in Alzheimer's treatments because of all the past failures, but we really think we have something important here to develop, and we're not gonna be spending that much money at all until after PREVAIL.
That's the time, how the timing works. Still it's an important area for us to develop. We already know from market research, the day we already have and have published in a leading journal that increased obicetrapib use by 30% from market research. We think this, just having this benefit alone, again, we'll confirm it and enhance it and get it into, you know, more and more... 'Cause I think the biggest feedback we've had from KOLs and from strategics is this data's just too good to be true. You have to confirm it. We are gonna confirm it, and then that's what's our new trial called SPINOZA is going to do.
Yeah. The, the goal is really that simple. Replicate the results we saw in the BROADWAY sub-study.
Yep.
Instead of in an ASCVD population, now in a preclinical at-risk for Alzheimer's patient population.
Yep. Yep. Got it. I know, Michael, you're alluding a little bit to some, the blunting effect or the reducing with obicetrapib. Can you elaborate on that a little bit more and why it's?
P-tau goes up over time, and then the thing is, unfortunately, there it goes up gradually, and then you hit a period of time where there's like a rapid exponential increase. Again, we're only talking about one year of that 20 years, okay? With BROADWAY. You're talking about do what we'd expect to see in a preclinical population over one year, the benefits are there overall, but it's even more so when you look at APOE4, the placebo arm goes up quite significantly, and obicetrapib blunts it completely.
In the E4, which is the most, obviously, it's a small population, it's 2% of the population, we saw a 21% decrease in amyloid p-tau217, which is comparable to the lecanemab or, you know, the donanemab, the anti-amyloid drugs, what they saw overall. We, they also saw that in the APOE4 homozygous, there was no benefit. I mean, so this is. We have the APOE4 homozygotes, like the Chris Hemsworth's of the world, if you know, if you follow him, he's all upset about his APOE4 homozygote. He's trying to do what he can to prevent that. That's 7 million people.
Yeah.
You think about the need there alone is quite substantial. They're, and they're highly motivated. That's where we saw a benefit already. Again, a small sample size. Again, we wanna confirm it with this bigger study.
Yeah. Great. Very exciting stuff. I could keep going, but I think we're at time.
Okay.
I just wanna thank you, Michael and Ian.
Thank you, Roanna. Thank you
for joining us.
Thanks for coming.
Really great discussion.
Thank you.
Thank you, Roanna.
Thank you.