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

Great. Well, welcome to our next session. I am very pleased to have -- my name is Asad Haider, I'm the U.S. pharma analyst here at Goldman Sachs. And I'm very pleased to have the management team of NewAmsterdam with us, Michael, thank you for being with us. Welcome

Thank you, Asad. Great to be here.

So let's -- I know we're just a little bit over time. So let's dive right into it, Michael. Maybe just start by laying out the overall market opportunity that New Amsterdam is addressing. And why is now a good time for a new mechanism in LDL, lowering class? Like why is now a good time to be looking at that?

So I think a lot of things have transpired over the past roughly 15 years in the lipid world. In 2013, the guidelines shifted away from goals to just using statins and high-intensity statins. And then came a number of studies that were showing that the more you lower LDL on top of statins, the better. So the guidelines first got revised in 2018 and then again in 2022 to recommend a 55 LDL target for high-risk patients. And ever since then, and there's even more follow-up guidelines that are now in process. So the market itself has moved more towards a lower is better, again, approach. And we're back now, if you look at the unmet need and the number to treat, we're back to where we were in the statin early days, statin only days was to get LDL below 100 and we had a lot of people that went on statins and it was very successful. We saw a decline in heart disease. Unfortunately, since 2013, that decline, not only did not stop, but it started going up again. So in hindsight, may have been -- it was all evidence based, we didn't have the data. Now we have the data. So getting LDL below 55 is the new kind of target. And ever since then, we've seen the market grow dramatically. Branded drugs like Repatha, growing 40%, even generic ezetimibe growing 20%. And so we believe that an oral, well-tolerated drug like obicetrapib alone or with ezetimibe lower LDL from 35% to 50% is all patients need to get the majority of people to goal now, and that's just the LDL aspect. The other exciting thing is about obicetrapib, of course, is it an LDL plus drug, it has other things that help reduce risk beyond just the LDL-lowering benefit.

I guess I remember, Michael, some fairly high-profile failures in the CETP class. I mean I remember torcetrapib happened, and I believe that was subsequently followed by about 3 others at least. So just given these failures, just maybe explain to us why it's different this time.

It's really important to know the history. I'm a cardiologist, lipidologist, been involved in the field from the very beginning, the first one to patent CETP inhibition back in the 90s. So for me, it's something I know very well and been involved with. And so it's important to know why the other 4 failed and why our drug is different. That's been the thesis behind the company from the very earliest, but we're about 5 years old now as a company. We've got obicetrapib back from Amgen. And so the key is that the first one, torcetrapib was off-target toxicity, raised blood pressure, but that was really the tip of the iceberg. It raised aldosterone and steroidogenesis, had this very prominent off-target effect and had a increased mortality in Phase III. The other 3 since then have been very safe, actually. But the difference here is that they all were studied for their HDL raising properties. They designed the studies accordingly and they were designed, the first one dalcetrapib was just a weak CETP inhibitor, did not lower LDL at all, again very safe and had other attributes about HDL raising that we have actually are developing for obicetrapib like the diabetes protection, but no MACE benefit and it would not lower LDL at all. And then Lilly designed a study for HDL raising, but the LDL-lowering benefit was, again, modest and they only had a 2-year follow-up period, which is way too short for an LDL-lowering benefit to be achieved. And so then came Merck and Merck to its credit, and we wouldn't be here without the Merck REVEAL trial, because they decided they're going to look at HDL raising, that's the prominent benefit. But just in case, we're also going to power the study and go long enough to look at LDL lowering. And so they set it up though with a HDL raising focus, the baseline LDL was only 60%, which is very low. And they lowered LDL by 11 -- 17%, 11 milligrams per deciliter. They got a benefit that was statistically significant based on LDL lowering. In fact, in the upper tertile, which is the 10,000 patients, LDLs in the 70s and higher, they had a 17% relative risk reduction. So if they were to just did the study in that upper tertile, they would have shown the benefit, they may have well launched the drug. But the other issue with that drug was that it had -- it had absorption in fat tissue, they would not stop accumulating and Merck decided not to file. So then knowing all this, John Kastelein and I, the co-founders, knowing the drug, knowing the failures, knowing why they failed, knowing a drug now that has much more effective CETP inhibition, better at lowering LDL, better raising HDL, better lowering LP(a), better potentially reducing diabetes. And now, of course, we've been working on this for several years, the Alzheimer's benefit because HLD raising in Alzheimer's, a very exciting science behind it, which I can get into if you want. But it's something that we've always thought is an important element about this class, that -- especially obicetrapib. So it's very potent 10 milligrams and very -- knocks down CETP by 97%. And knowing all the background and why they fail, we designed a drug -- a trial program focusing on LDL, they now put the drug in the right position to be successful for approval for baseline LDL lowering.

I want to maybe just stay with a little bit of a big picture question and then I want to drill into some of your own programs here. It's encouraging to see that after some period of dormancy, there does seem to be a little bit of a renaissance in cardiovascular sort of trials and new things getting tested. Obviously, you've got you guys, but then you've also got Merck and AstraZeneca, but there pretty -- with their oral PCSK9 programs and then you've got the LP(a) plus that -- that Novartis and Amgen are going after. So maybe in the context of that broader landscape, talk about your positioning with -- in that backdrop? Where do you see the differentiation?

Yes. So -- the thing is I think we have a really good convincing place to be for the vast majority of patients, because it lowers LDL 35% to 50%, so the -- in combination with the ezetimibe, the combo -- a very small little combo pill. Also -- first of all, our drug is exceptionally well tolerated and adverse events comparable to placebo. So we have a really well-tolerated medication that you can take and not worry about side effects for the -- so that makes it very appealing to primary care, where most of these drugs are likely to be prescribed. But what the drug does provide, though, is that when you think about where the drug fits in for other reasons, the LP(a) lowering of 40% to 50% falls exactly in the [indiscernible] they're not going to qualify for an injectable -- so the LP(a) is skewed about 50% have high LP(a) in the high-risk population, only 10% have LP(a) levels that are being earmarked for the injectable drug. So the 40% of patients that have high LP(a) but don't qualify for the -- the injectable, that's where obicetrapib works the best. And so for all those other patients, a majority of patients have high LP(a), they're going to go to obicetrapib, as they don't qualify for the injectables if they have primary prevention, they won't qualify for the injectables either. So the majority of patients with high LP(a) would be well suited with obicetrapib as your first-line approach in combination with LDL lowering. And then the PCSK9 inhibitors, they are, again, great drugs, they're projected to be in that $4 billion to $5 billion range. But the Merck one, which is the first is an oral peptide. So it's like RYBELSUS. It's challenging in that it requires taking it after 8 hours of fasting, not within 30 minutes of any other pill, which for a heart disease patient, the challenging dosing regimen, they are on all these other drugs. We don't like -- I don't like to prescribe RYBELSUS that often for that very reason. You've got to watch all the other drugs that they're taking and so forth. And it lowers LDL, roughly that Merck announced today, their Phase III data that -- it didn't give us the results, but assume it's 50%, which is what the injectables are, it's still not any different from our combo with ezetimibe. We have 50% but doesn't have the plus part. It doesn't have the LP(a) lowering as well as ours. It doesn't have the diabetes benefit. Now you have these Alzheimer's -- exciting Alzheimer's benefit. That's going to be -- for patients, they're going to want to take our drug for those reasons. It's not because when you have a patient in your office, trying to convince them to take a drug, they want those other benefits that, in some ways, are much more motivating, preventing diabetes, lowering LP(a), preventing Alzheimer's disease. Those all become very strong rationale for a patient to take a drug like this.

So that's a perfect segue into my next set of questions, which is really around your own programs and maybe sort of drilling into those a little bit further. You have data from 3 Phase III trials, BROOKLYN, BROADWAY and TANDEM. I guess -- I love the name, by the way. What would the -- I guess, maybe the takeaways from each one, what were the primary endpoints? And importantly, what have you discussed with the FDA regarding requirements for approval?

Right. So the first one, BROOKLYN was a similar hypercholesterolemia trial those have very high LDLs. They're all -- everyone's -- in all trials are on background high-intensity statins predominantly. And any other drugs that could take ezetimibe, even PCSK9 inhibitors, that lowered LDL in that 36% to 41% range compared to placebo. And then the next one BROADWAY was a much larger -- mostly a heart disease population, lowered LDL in that again, 33% to 36% LDL lowering and TANDEM, very similar on LDL lowering, but also had the 50% in combination with ezetimibe. So those are all kind of high-risk patient populations. Those are the. So for LDL lowering NDA, we meet all the criteria. We have 1,500 patient years of safety, we meet the LDL thresholds, we are -- of course safe and well tolerated. The FDA made us do a dedicated blood pressure trial, which is completely normal, which is very safe. So we have all the elements of the filing for LDL in place. However, the FDA has been clear from the very beginning, they want to see the outcome study during the review period. And so we are timing that so that during the review period, the -- during the PDUFA period, the outcome study reads out, which is not to the end of '26. By the time you've kind of do all the paperwork, you're probably a little bit in early '27. So we're in that filing period where that outcome study can be provided to the FDA during the PDUFA period for review. And then we follow that with the MACE indication later.

And I guess on the MACE indication, maybe just discuss the exploratory MACE endpoint. How does that compare with standard of care? And how should we think about that reading through to prevail?

Yes. So BROADWAY saw a 21% MACE benefit, which was a 4-point MACE of CHD death, nonfatal MI, revascularization, total revascularization and stroke. And so that's a pretty standard 4-point MACE and we are going to -- we're going to announce this on R&D Day, what we're officially going to do, but you can see that will carry over to PREVAIL. And what's great about BROADWAY, it's many very similar patient populations. Obviously, the same dose of drug, the same background medications and PREVAIL actually, when we look at it even closer, it's even more of the type of patients that respond better to obicetrapib based on our analyses. So we feel that probably really derisked PREVAIL quite a bit. And so we're going to talk more about that at our R&D Day on Wednesday that this is a really strong confidence builder that PREVAIL will read out appropriately. And we're right on track on time -- time lines and also on our all our quality metrics look great. I mean drop in, drop out concomitant med drop-ins all look really good on PREVAIL.

I guess one question that I have is what might drive a patient to receive monotherapy versus combination with ezetimibe. I mean what are you more going to be more focused on commercially.

It's something we're doing a lot of work on. And I think there will be doctors that will want to take the -- provide the combo predominantly. And we're also developing our own identity for the combo pill. It has its own identity because it does show synergy, not just additivity and we're doing an imaging study called REMBRANDT, where we're looking at noncalcified plaque volume over 18 months versus placebo versus the combo tablet and that study will read out about the same time as the PREVAIL study. So we have -- and we'll launch with both the outcome study PREVAIL and the REMBRANDT trial in promotion. So we have -- so that -- so the combo pill, I think depends on what audience you're talking to is going to probably be the dominant of the 2. I mean so -- but it's still the monotherapy, some people just like monotherapy, don't like combo pills. And this situation, it's an exceptionally good combination because they work very well together and they augment each other when it comes to efficacy and maybe -- and we have good data, again, we'll share that at R&D Day where the antiatherosclerotic effect is actually also augmented with both drugs together.

And I guess, regarding the safety profile, do you have enough data to be validating for such a large indication?

Yes, yes. 1,500 patients. Yes.

And what are the tail risks that could emerge in a larger population?

We're through our eighth DSMB meeting. I mean we're well -- we only have roughly 18 months to go. We're well over -- we're probably approaching the 10,000 -- 20,000 patient mark now of years of safety and DSMB has been very quick meeting, all I can say, it's a very rapid, you're fine move on type of analysis, yes. We've been through eighth DSMBs so far, yes.

Wow. So -- let's maybe pivot to -- any questions from the audience? I can take a pause there. Maybe, Michael, we can pivot to the financial position and just maybe talk to us about the current financial position and the runway and what that gets you in terms of launches and further trial readouts?

So over $800 million in cash. We reported that. So we're in a very, very strong position as a biotech company. We have put in place a exceptionally good launch team, BJ Jones, who launched Nurtec. A lot of his former colleagues are now with us. And we have MSLs deployed in the field who are very experienced. So we're developing the prelaunch commercial messaging and so forth to the medical community. So we're gearing up, and we have enough capital now to take us all the way through to launch. I mean, so we feel we're well financed, and we have -- again, BJ will share more of this on Wednesday, but we -- he's extremely bullish on our market research, where we are as a company with this drug.

And I guess from a commercial perspective, where are you in building out the infrastructure to build out larger broad patient population?

We're going to do this in a structured way. And again, we want to -- we're waiting for the -- just to know when the regulatory filings are going to think of. But we have the team in place when we gear up, it will be based on knowing more and more about the timing of the launch exactly.

And in Europe, I guess, you have a partner, do you anticipate -- maybe talk through sort of how that came about? And then do you anticipate a BD partnership in the U.S. as well?

We have a very good partner in Europe, Menarini, they came at a really important time for the company. They gave us a large upfront payment that helped us catalyze our SPAC PIPE, which was, of course, out of favor at the time, we had -- I think we had the best one of the entire 3 or 4 years that went really well. And I think that helped us bring in the cash balance sheet that we needed to get all the way through Phase III. Plus we have really good economics with that. we haven't disclosed it, but we feel good about the economics of royalties and milestones from our European partner, and they're well known in the cardiovascular space. And then for Europe, after Japan and China, we have full rights. They've already done all their work. They're also ready to be filed in those geographies as well. We're holding on to those for a potential larger partnership. But we -- we'll explore all options for that. But I only say that we feel really good about our go-alone plan. We feel we have the right team. We have enough cash. And these partnerships they have pluses and minuses, and we want to just make sure we're doing all the right things for the shareholders to get the most value. Right now, we see ourselves as being very, very low valuation, and we want to build value and the more we can hold on to everything, the more value we can create with execution of all aspects of the company. And so that's where we -- our focus is on that go-alone approach, knowing that there's a lot of companies out there that have big gaps in their pipeline where a drug like this could be a very attractive target.

You're not ruling it out?

Not ruling it out, no.

Got it. We've gotten this fine. We haven't touched on the external operating environment as well at all. So I feel like a compelled to ask you how are you thinking about the things like MFN, drug pricing policy dynamics that are currently being discussed. It's been a big theme through this whole conference. So how might that play out specifically with your European partner?

Yes, that's an interesting question because we -- the answer is we don't -- no one knows for sure how that's going to play out, but in our situation, it may be to our advantage, not to have the rights in Europe ourselves, it's a third party. We don't have control over pricing there. So we can't provide most favored nation status, and we don't have the right -- we're not selling it in that area. So for us, there might be an advantage. Again, it's too soon to tell what that might mean, but we feel that we'll have to wait and see basically on that issue.

Okay. Let's maybe just talk about the catalyst path from here. You've got the R&D day this Wednesday that you touched on briefly through this conversation. Maybe just give us a little bit more high level on what we should be expecting on that day from you guys? And then beyond that, what are the next events that investors should be keeping there eye on?

We've had a lot of data presented in our -- we got published in Journal of Medicine, Lancet. We had a high level -- we have more data to present from BROADWAY in particular, on the MACE benefit, trying to get -- again showing the relationship between the MACE benefit and what may have led to that unexpected upside benefit. Now that translates into the PREVAIL study. So that will be a big focus of our R&D discussion. I already alluded to the -- some of the other key data that we have on atherosclerosis and regression in preclinical models, how that derisks the REMBRANDT study. BJ, is ready to go out with, again, more and more information about why he's so bullish on our opportunity here with over and then we will present a little bit more color on the Alzheimer's Day, although we are limited by what we can say with the outcome -- with that data being presented in July 30 at the AIC.

What can you say about it?

What we want to say is, first of all, we're very excited about it. I believe it's a game changer. The AIC put a post out today saying they're excited about it. They're very excited about it. And so we feel -- where we want to focus more on is what this could mean for patients that have risk for Alzheimer's. And how big APOE4 subgroup is 25% of the population. A lot of them have ASCVD and high LDL. And so in many sense, again, it becomes another reason why to pick obicentravib over anything else to have this type of data. And then, of course, we'll follow up once we have the presentation on what our next steps might be for this very important unmet medical need.

And I guess beyond the R&D Day, what else is coming up?

July 30 is the presentation at the AIC/

I mean even broadly for the company, not just for Alzheimer's.

Yes, we have a filing in Europe in the second half of this year. We have a VINCENT study, which is looking at the LP(a) combination of obicetrapib with PCSK9 more to kind of set the stage for a potential combination of the 2. We have, again, our completion of PREVAIL at the end of '26 and then the filing time lines on that for the company. So a lot in next 18 months, yes.

Question from the audience, Nick?

We haven't decided officially yet, but -- but we are going to go meet with the FDA. We also have PREVAIL. PREVAIL is a much larger trial. We can -- but I think without saying too much, the data is going to really speak strongly about where obicetrapib can potentially play a role in the prevention of Alzheimer's disease.

We just have a couple of minutes left. Michael, what else have we not talked about that you'd like to take this opportunity to talk about?

I think that getting back to one of your questions about the landscape, the LP(a) and the oral PCSK9s and GLP-1s and so forth. What think people don't appreciate about obicetrapib, is not just its great clinical features and well-tolerated, safe, is that we can combine with a lot of other drugs. I mean with the IRA out there now, we become a very attractive combo. It's a very tiny little size of a baby aspirin. So that -- that would be another added value that we have to work with collaborations with partners and so forth. And then I think the other.

I'm sorry, are you suggesting you could combine with the oral PCSK9?

And/or GLP-1

And potentially the GLP-1.

So we're looking at all that. That's how we're looking at the drug look at combinations with other drugs that we think could be very attractive commercially as well. It's a pipeline and a pill story about obicetrapib. And so then -- and the other thing I think is just a very important message. Again, I'm speaking as a clinician who sees patients that the LDL-lowering part is great and it's effective, but when a patient wants to take a drug, they want some other compelling reasons to do it and obicetrapib really addresses that. Those other compelling reasons. Everyone's if -- they have a LP(a), they know they have, there's nothing they can do about it from a lifestyle perspective and statins make it worse actually; diabetes, statins make it worse; Alzheimer's, statins don't help. We know that from a study. So you think about what obicetrapib can do either alone or in combination with statins, it addresses all the liabilities or limitations of statins in a very effective way. So it becomes really your go-to therapy more than anything else out there for treating patients.

Fascinating. Fascinating story. Thank you very much. Michael. I appreciate you being here with us. And with that, we can probably wrap up. Thanks.

Thank you very much.

Thank you.