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

My name is [ Matt Hartzell. ] I am from Goldman Sachs. Pleasure to be here with Dr. Michael Davidson, CEO of NewAmsterdam Pharma. So thank you for coming in.

Thanks, Matt. Yes.

So let's just start off. It's an important year for the company, several important readouts. But before we get to that, can you just give us an overview of obicetrapib and kind of how differentiated the other CETP inhibitors that have been pursued by [indiscernible] stores.

Sure. So obicetrapib is a much more potent CETP inhibitor. It's only 10 milligrams. And it lowers LDL in that 40%-plus range, raised HDL 150%. And so the other benefits that this drug has are very differentiated from any other LDL lowering drugs. So it's not just an LDL lowering drug. It also lowers Lp(a), lowers the risk of diabetes, which is -- mitigates the statin-related issues there because statins raise Lp(a), raise the risk of diabetes, and it also reduces the small particles by 90%, total particles by 50%. So it's got this very unique profile. Now the other CETP inhibitors in the past, it has a very long -- I been -- was involved with it myself as a researcher, I'm a cardiologist, lipidologist and they're all -- we're focusing on HDL raising, and there was a rush to do that because the science said the association was any 1% increase in HDL reduced risk by 3%. So everyone was saying, let's get HDL up and then they rushed to drugs out the market. And unfortunately, they all were discontinued for different reasons. Trocetrapib being an off-target toxicity, which none of the other ones had. They've all been very safe since then. And then they all had very low LDL lowering efficacy because they were focused on the HDL raising. And so they designed the studies for focusing on HDL. But the most important finding for us was the was the Merck one with anacetrapib, they actually did -- they actually powered the study, 30,000 patients, and they went long enough to see an LDL lowering benefit translate in the cardiovascular outcomes. So that -- for us, that was the Eureka moment. It was all about LDL lowering. And the genomics also supported that. And so when we had obicetrapib -- we got that back from Amgen and so now when you saw this data from REVEAL, the outcome study with anacetrapib for Merck and all the genomic data, it shows all about LDL-lowering -- we have, now had a much more potent LDL lowering drug that we could then take forward into into the Phase II and now Phase III trial. So it's an evolution of thinking about how to target this very important protein and how to make it effective in reducing cardiovascular risk.

Great. Thanks. And we'll go back to some of the biomarkers in a bit. But a number of important readouts for the company this year and then subsequently into '25 and '26. So can you talk about kind of the top priorities for the company this year heading into the BROOKLYN and BROADWAY studies.

Sure. Well, I think the -- from the trial perspective, we've really executed on all cylinders. I mean we're a small company, but yet, we enrolled all our trials. Either on schedule or ahead of schedule. And we also were able to start our outcome study PREVAIL at the same time as our LDL trials. And we fully enrolled that in April of this year, 9,500 patients. But our 2 pivotal LDL trials finished enrollment, and now we're getting to the end of the studies readout, that BROOKLYN has already finished. We'll have the cleaning up the data, be ready to present that in the third quarter. And then BROADWAY is almost soon to complete, and we'll have that data towards the end of this year. They're both pivotal LDL lowering trials one, BROOKLYN be first 350 patients, 2:1 randomization. All the patients have familial hypercholesterolemia, so the baseline LDL is quite high. And then BROADWAY is mostly atherosclerotic cardiovascular disease patients that will read out towards the end of this year and that will be the larger of the 2 trials. So we're really on track for all our Phase III readouts for LDL lowering, and then the outcome study will follow the roughly the end of '26.

And then you touched on kind of the biomarkers and the mechanism of action for OBI here. What are your expectations for -- can you help us set the stage for the expectations for both the BROOKLYN and the BROADWAY readouts in terms of biomarkers, what you expect to see based on the compelling Phase II data that you had demonstrated so far.

Right. So in the lipid world, we have what people focus on what's called the atherogenic burden, what causes heart disease, it's LDL, the non-HDL might be a little bit better than LDL, they have ApoB and we have LDL particles. We all people debate which one is the best. And we focus on LDL primarily, clinically. It's the easiest to evaluate. But we're going to look at all those parameters. Again, in Phase II, we were in that 43% for LDL, non-HDL around 40%, ApoB, close to 30%, LDL particle 50%, small particles 90%. So we're across the board on all the different after genic lipoproteins, we do very well for all of them. And so -- but we can debate which one is better in predicting events. They're all good. And so we plan to show that data ultimately for the trial. Our first readout will be the LDL, which is the primary endpoint when we announced the data initially. But we also have very exciting data on Lp(a). I talked about that already, and diabetes prevention benefit that we may be able to see even that in our Phase III trials because it's 1 year, usually -- it might take a little bit longer to see the diabetes benefit really come to fruition because you're preventing diabetes with these drugs as well. It's been shown for all the CETP inhibitors.

And then on Lp(a), it's obviously become more of an interesting target and people are more focused on it from a biomarker perspective. Can you talk a little bit about what you've seen there in the Phase II studies and kind of how that -- what kind of role that plays with OBI. I don't believe other CETP inhibitors have not seen that.

Well, all the CETP inhibitors actually did lower Lp(a) except for dalcetrapib, again, less potent, but anacetrapib and we lowered it by about 20%. So about double. We're double. We're in that as low as 40% in 1 trial, up to 57% in another. So we're in that range of Lp(a) lowering but we're not seeking an indication for that. That will be the injectable therapies, iron AI and ASO approaches. They're going after much higher levels of Lp(a), which is, in my lipid clinic, which I still see patients, it's a very important unmet medical need for those very high Lp(a) patients who still have high risk despite being on statins. But for us, the way we look at it is it's a differentiating feature for patients that have high Lp(a) that don't meet the threshold of where an injectable drug would be necessary. Assuming their -- the outcome datas are positive for all the injectables, which will happen over the next few years. But we would be for the patients that have the mild to moderate Lp(a) lowering -- net need for Lp(a) lowering, which is the majority of patients that have high Lp(a). And based on the data we know so far, it's a lower is better issue. So even having a mild elevation increases risk. And so we -- we believe, again, this will be a differentiator that we could provide to clinicians that they could utilize obicetrapib and then if they have really high alkaline, then they go to the injectable drugs. And that would be where the indication would be for those therapies.

And then can you touch on the safety profile? And you haven't seen any issues with blood pressure in that blinded data, which is great. What else should folks be paying attention to from a safety perspective.

Well, this is a long list of lipid drug issues, liver enzymes, muscle enzymes, kidney function, blood pressure and those are the things you look at the most as far as safety of diabetes, again, we think we'll have the other direction, but all the other lipid drugs, especially statins have this diabetes increased risk signal. So those were all adverse events of special interest for us. And so we'll have that data when we fully -- when we release all the data in the upcoming meetings, medical meetings and publications.

That's great. And then as you think about the kind of registrational path here, I know you have the 2 LDL-lowering studies coming up this year. You'll get your outcome study. You said I think late 2026. Can you talk to me -- kind of talk to us about the registrational path here, how you're thinking about filing for timing, assuming you do have positive LDL studies and then where the outcomes piece plays in?

So we want to launch with outcome data in hand. And so we will be able to meet with the regulators, the FDA. Europe is a little bit different path because they can file. We have already the green light to file based on LDL and then the pricing would happen a year later in different countries. So the outcome data would be available at the time of pricing. For U.S., we want to have outcome data in hand at launch. And so we can look at our event rates and PREVAIL and pretty accurately estimate when that study will finish. So we will file -- the PDUFA period is 12 months. So assuming when we believe PREVAIL finish, we could file the LDL indication. So it would read out during the PDUFA period. That's how we're thinking about it right now.

Okay. And then can you talk about commercially assuming a positive BROOKLYN, BROADWAY and the PREVAIL study, can you -- you're in a unique position, your KOL and the -- in the cardiology space and epidemiology space, but you're also -- happen to be the CEO of this company. So I think you're in a unique position relative to other companies to kind of understand the commercial opportunity? And can you talk about how you might use this in your clinic and how your peers may use this product?

Right. I think the biggest issue for treatment is inertia. And treatment inertia where physicians have, at this point, limited options. They have 2 oral atonastat, ezetimibe and bempedoic acid. Lower LDL in the 15% to 20% range. One is generic and it actually is growing well. It's 20% annual growth. So it's easy to use. It's a generic pill. You just to add on is safe, well tolerated. So it's growing bempedoic acid, also efficacy, generally well tolerated, but does have some side effects, it's branded and has that hurdle of getting the payer authorization and so forth. Then you have injectables, which are very effective, generally well tolerated, but expensive and injections. And so what physicians need and this is, again, speaking from my own clinical experience, if we can just give you 1 little pill to take that's well tolerated and we even have to get no headaches, no side effects. Everyone gets the goal which is what our data shows. And if you remember -- we're also doing a fixed dose combination with ezetimibe. And roughly in our studies, 50% are on ezetimibe already in BROOKLYN and BROADWAY, it's 20% prevail, 25%. So we're talking about if we can just have the monotherapy or the FTC combination, that's all they need to do. In fact, our data would suggest, based on our modeling, that almost everybody with those 2 options get the goal and you're done. And so there's very few drugs like that in [ Prague ], even the diabetes drugs, you're thinking, okay, I got a little bit more A1C lowering. And than I'm at another third drug or fourth drug to get the A1Cs below 7. In our situation, just 1 simple well-tolerated oral therapy, and you're done. I think it has to be very appealing to the primary care doctors out there, and we're doing all the work, hopefully, ahead of time to maximize access. So we can get them great access at the time of the launch. And part of that is having the outcome data in hand at the time of launch.

And then is there anything you can learn from kind of prior precedent launches in PCSK9 or bempedoic acid you mentioned?

Well, yes, I think key is, again, outcome data in hand is important for the payers. And then, of course, pricing it where you get the maximum amount of access, which doesn't mean -- unfortunately, it doesn't necessarily mean lower price, but a price where the payers can get their rebates so they can give broad access without too many prior authorization requirements and then, of course, the overall profile of the drug. At the end of the day, it comes from patient demand, clinical demand to get the payers to move. And so we believe with this type of profile, the efficacy on LDL, but all the other benefits, the demand itself, we believe, that can be created, we'll get payers to get on board as well. That's our focus. So we have enough lead time. We hired this BJ Jones, who ran the Commercial -- Chief Commercial Officer at Biohaven. He's brought many of his former teammates on to help us lead this commercial effort, but we want to prepare the market well for what we believe is a very exciting [Audio Gap] we can make in the market ahead of time.

And can you remind us how big the market opportunity I think this could be?

Well, if you look at -- I mean the 1 analogy I like to talk about is historical is ezetimibe when it was 15% [ add the stands ] with a $4 billion market, and it had another $2 billion of Vytorin. Again, easy to use, safe, well tolerated, modest efficacy. So -- that was a market that was, I think a good benchmark for us. We actually believe the market could be even bigger because then the goal was [ 70% ] and maybe not even a hard [ 70%. ] Now the goal is [ 55% ] or less. So the unmet need is actually greater. And so again, with a simple-to-use oral, efficacious, well-tolerated drug, getting almost everybody below 55 with 1 add-on treatment, we think the market could even be larger than what they saw with ezetimibe.

That's great. And you mentioned ezetimibe, you're running a fixed-dose combination study with ezetimibe. Can you talk a little bit about that study, kind of who you're rolling into that study and how you see that expanding the opportunity here or enhancing the opportunity...

That's the TANDEM trial. It's a pretty standard 4-arm study where you get placebo and then you have each drug individually, then the fixed-dose combination, and you want to start to show added efficacy of the combo versus each of the components versus placebo. And so that next [ Gazette ] did that, and I think is -- that's probably the more successful the 2 options because it does have the greater efficacy, we want to try to fulfill that same kind of regulatory path, but we have something special about the 2 drugs that we've enhancing the science behind because CETP inhibition actually improves, remove of colesterol through the intestines called TIC, transintestinal cholesterol eflux and Ezetimibe is an inhibitor of intestinal cholesterol absorption. So it kind of like opens up the faucet and then also opens up the drain. So you turn on the faucet more powerfully, open up the drain to get a lot more flushing out of cholesterol. We believe that, that has not just LDL-lowering synergy, which we showed in our Phase II trials, but also, we believe that could have an impact on aplosclerosis, and we also now launched an imaging study with CT angiography as the biomarker of noncalcified plaque volume, which is a growing target of many imaging modalities to look at plaque. And I believe as a cardiologist, lipidologist, that's the future. We're going to look at plaque now. And before people have events, determine that we've turned off the plaque progression. And so I think with those tools and we apply them effectively, no 1 should get to the point where they get heart disease. It would be -- and we want to treat it before it actually becomes a clinical event. And these plaque analysis are very helpful. Even if people that already have events, we can then treat them until we know we've turned off the plaque progression with these type of modalities. So if we're using that -- this new technology to enhance the change in that parameter in the what's called the REMBRANDT trial, which will read out slightly after PREVAIL actually.

That's great. So the totality of the data coming out over the next couple of years is going to be really, really quite a watch. Can you talk about kind of the rest of the portfolio, the strategy here? I know you guys raised some money earlier this year and kind of what you're thinking in terms of what else you'd like to do with OBI or other strategy around the portfolio?

Well, it is in some ways a pipeline in a pill because we have the mono, we have the fixed-dose combination. We also have an exciting this proof-of-concept Alzheimer's trial, this, even the Alzheimer's Disease Discovery Foundation, wrote a full report on CETP inhibition on Alzheimer's disease because there's a lot of scientific rationale for it. What we decided to do was to -- with this proof of concept study showing we do modify cholesterol metabolism [ in the brand of ] people that have APOE4, which is alipogene, and it's the most prominent gene for developing Alzheimer's because they -- our theory is they can't transport cholesterol out effectively. We showed that we did get cholesterol out of the brain with our proof-of-concept study. We're now in BROADWAY, which is a 12-month study, 2,500 patients. We will have a large subset with APOE4 and we're going to look at tau and amyloid biomarkers. If we see a positive signal then, we could -- we may decide to move forward with a separate Alzheimer's program. But that would be -- that's an upside very large upside opportunity that will -- again, we're not banking on that, it's not part of our main investment thesis right now. But if we do show that, it would be a very big upside for the company.

That's great. And then I've got 1 more for me and then open it up to folks if anyone else has any other questions. But so I think there have been some recent kind of FDA label expansions or extensions for marketed products for like we saw this with bempedoic acid. How do you think about that as a potential tailwind for the space and kind of what does that imply the FDA's thinking around this space.

Actually, there's a couple of tailwinds. One is that the FDA, I think, recognizing that payers were using labeling to restrict access so they had -- first had this label where you can use the drug on top of max [indiscernible] statins in certain high-risk groups, ASCVD or FH atherosclerotic cardiovascular disease or familial hypercholesterolemia because the LDLC are still too high. And they didn't define what exactly too high means. And they also required statin background therapy. So now the new label does -- takes away the statin background or the ASCVD FH requirement. So they're basically giving the indication across the board for anybody that needs LDL lowering, including primary prevention, secondary prevention. And so those are -- those then should no longer effect. They're no longer -- payers can't use that, the label to restrict here. So that helps. And then secondly, the guidelines have shifted back to targets again. There was a period of time where goals were taken away, that was 2013. It was a very unfortunate period of time where there was no data showing that on top of statins, there was benefit. Now there's substantial data showing there is benefit. And so the guidelines have now moved back to goals again. And now the goal shifted even lower to 55. So those 2 tailwinds are going to help us even more so when we hopefully have a great drug available for launch.

Any questions from anyone else in attendance.

Probably like a quick questions regarding -- people are kind of wondering the correlations between the lowering down like LDLC around like 30% to 40% compared with the percentage of the MACE reduction. The MACE event rates that will happen. So I think what we see like in the past history that if you see around like 20% of the lowing down of LDLC might trigger is around more than 10% of the MACE and we are kind of trying to forecast that we have around 30% to 40% of the LDLC lowing and it could be like higher than 25% of the base. So what is the forecast that for your -- in your forecast about [ insulins too ] -- and we're also seeing the discrepancy around in -- like PCSK9 and body -- like previous trials, the correlation seems a little bit off of the line compared to statins in the future? And how you kind of explain why PCSK9 was not reflecting the same on the [ front ]? And how does that compare to our own trial.

Right. So yes, there is a well-established relationship between absolute LDL lowering and event reduction, but it's also time based. You have to take the time to get there because the first year or two, the benefits are very modest. And so for the PCSK9 inhibitors, the issue there was that they had -- yes, they had a profound LDL lowering of 40 to 50 milligrams per deciliter. However, they only went 2.3 years median and then they had over 10,000 patients that had only 9 months of exposure in that trial, which dilute out the overall benefit. If you just did an analysis where you take anyone who's been on the drug for only a year, a minimum of a year, the relative risk reduction went from 15% to 20%. So when you model the LDL lowering efficacy by time, it's right on the line for PCSK9 inhibitors for what you saw with statins. So time is the other factor that never -- everyone has to adjust for time and as, so is in absolute LDL lowering is really the key, not percent LDL lowering. And so what we've done in our trial to maximize both is we have a much higher baseline LDL, I think we -- we came out with our baseline LDL at the -- our R&D Day a few weeks ago, are based on LDL is around 100 milligrams per deciliter. The outcome studies that were done with REVEAL in [indiscernible] the baseline was 61 milligrams per deciliter. If you went to the higher tertile, the baseline LDL was a little over 70%, it was a 17% relative risk reduction. So baseline makes a big difference and in that trial in particular. So we went on to maximize both the baseline being higher, the absolute magnitude of LDL lowering in the time horizon. And so I put that [ to an after a ] minimum follow-up in there. So our modeling, and we showed this, we're over 20% relative risk reduction with our modeling for our drug. However, you've got to account for drop-in, dropouts, which is always more challenging as trials go on because you've got the people go on other drugs, as other drugs available. So you have to adjust for that. But so far, we feel really good about the drop in dropout rates in all our trials, so far so good, and we hope to continue that. And I think part of the reason for that is that we started the trials, people are already on maximal drugs, what they already can take. And so we want to make sure that the standard of care was well achieved, that we were able to get the patients that were at the higher baseline LDL into the trial. And then already on maximal therapy, that helps prevent the drop-ins and the dropout.

Just following up on that, do you expect to see many PCSK9 drop-ins.

We might see some, but most of the patients are in Eastern Europe, China, about 2,000 of the 9,500 are in the U.S. But in these other countries, the access to the PCSK9 are just not there right now. So again, we're seeing very little drop-ins right now. And so now we got another roughly 2 years to go. So we hope to hold steady with that.

Anything else from anyone else in the audience?

Thank you. So when you took a look at the blinded data for blood pressure, what exactly did you have access to? Did you look at the average, median, the range, did you have assess of outliers what was the highest elevation seen.

All that, yes, all of the above, yes. We looked at mean median, those who had to go on other blood pressure medicines who had their -- her dose of medication changed. We saw, again, mean and median, no effect at all on blood pressure. We saw very, very little changes in blood pressure medicine during the trial. So that's what we're seeing blinded in a blinded way.

And what's the highest elevation in blood pressure you saw in a blinded manner, of course.

Yes, Okay. I can't tell you what that is because that happens in every trial. We see sometimes people go off their meds and they come in. We have not. But we're seeing, again, nothing surprisingly. Well, like I said, I've done a lot of trial. I've never -- we see blood pressure completely flat in the trial overall. And this is 2:1 randomization in the studies.

Anyone else? With that, thank you, Michael. I appreciate it. A pleasure to have you here and look forward to the studies reading out later this year.

Yes. Thank you. Thank you, Matt. Thank you.