Great. Welcome, everybody, to the Leerink Global Healthcare Conference. My name's Roanna Ruiz, and I'm one of the senior biotech analysts here. It's my pleasure to introduce NewAmsterdam. Here with me today, I have Michael Davidson, the CEO, and also Matt Philippe, the member of IR. Thanks for joining us today.
Thanks, Roanna. Good morning.
Good morning. I'll probably kick it off with some bigger picture questions first, and then we'll sort of drill down to more detailed questions. For any investors new to the story, could you just talk about NewAmsterdam's strategic focus, highlight some of the key clinical advancements that have happened for your lead product, obicetrapib, and how are you thinking about that reinforcing its differentiation in the cardiovascular space?
Sure. Good morning, everybody. It's great to be here. Just to give the big picture, we're developing obicetrapib, a CETP inhibitor. The great thing about the target itself, and a lot has evolved over the past several years, is it's a very potent LDL-lowering drug, but also has other important attributes like lowering Lp(a) and reducing the risk of diabetes. Of course, this very profound effect on lowering the small particles, all these things are associated with increased cardiovascular disease risk. When you think about a drug that can lower LDL and can also modify these other important risk factors, you get really excited. I'm a clinician. I see patients still four days a month at the University of Chicago.
I can tell you these are the type of attributes you want to see in a drug to further reduce risk beyond the traditional LDL-lowering therapies, particularly statins. Statins are great. I don't think I'd be alive today without them with my family history. They do have issues that make them somewhat challenging for many patients. The side effect profile, for example, is generally well tolerated, but they have a lot of side effects for certain patients. Statins raise Lp(a), which is another important biomarker. We can get into more detail about that. They raise the risk of diabetes. Obicetrapib, as a companion to statins, can really make those risk factors significantly mitigated or improved. I think most importantly for me is the fact that in phase III, we showed this drug was very well tolerated.
It's a single little pill every day, very well tolerated. That is what influences most decision-making by clinicians. They want something very well tolerated, safe, that they just give a pill and they're done. What we've shown in our phase III data with obicetrapib and then obicetrapib as a fixed dose combination with ezetimibe, that's all you need to do to treat LDL today. You can basically have the statin as a mainstay and then add obicetrapib, obicetrapib with ezetimibe, and 90%+ of patients have their lipids where they want them to be, and no other therapies are required. We're excited about that. Our phase III data came out last year. Exciting year for us. We had three major phase III readouts all demonstrating robust LDL efficacy, safety, tolerability.
I think what got the community and us most excited was that we already saw a reduction in MACE, major adverse cardiac events, in our phase III data, especially our Broadway trial, which is our largest trial designed to show that type of benefit. We saw the benefit there, 0.79 hazard ratio, 21% relative risk reduction. Pulling these two studies together, the Brooklyn and the Broadway, and you look at the three-point MACE that's been used in the other previous trials, you saw a 0.68 hazard ratio, 32% relative risk reduction, which did reach statistical significance of less than 0.05. We are very, very encouraged by the benefits of this drug. We have our ongoing PREVAIL trial, which is our pivotal outcome study, which was enrolled a year ago, pretty much in April, and it's tracking very well on events that we were expecting.
We are seeing, based on blinded data, extremely safe, well-tolerated drug, very low dropouts. We hope to get that study finished at the end of 2026 and have that available for when we launch the drug around the same time.
Great. That's a good overview. Talking a little bit about PREVAIL, your outcome study, and looking ahead, can you talk about some of the catalysts that you think might be interesting for investors to follow and some of your regulatory versus commercial versus clinical priorities going into 2025 and beyond?
Sure. We didn't make the ACC deadline, unfortunately, but we will be there kind of meeting with our colleagues and KOLs and so forth. We do have two meetings in May where a lot of data will be presented. One is EAS, European Atherosclerosis Society. That's in Scotland in the early part of May. The National Lipid Association, which is in Miami at the end of May. We have the ESC meeting in Europe in the end of August. Over those three meetings, we will be releasing all our phase III data. We also have submitted all our major studies for publication, Brooklyn, Broadway, Tandem, all have been submitted to major journals. We'll see how that plays out over the next few weeks to months. All the data will be out there in the public domain.
I think when people see the data finally in print or in presentation, you can get into the fine details that we're hoping to show about the drug again, about the safety, efficacy, the other attributes, the Lp(a), the diabetes, the small particles. All those things are, again, I think, very relevant to why doctors, when they hear about our profile, get very excited about the drug. That is the catalyst. We do plan to file in Europe this year. We are meeting with the FDA sometime this year also to discuss the filing for the U.S. All that is going to happen in this year. I think quite a bit of catalysts. We do have one small trial called Vincent, where we are looking at Lp(a) lowering obicetrapib, but then adding on a CETP inhibitor as a prototype to a potential combination of those two therapies.
That's a small study that we want to build a pipeline of drugs too, because this drug is extremely well adepted to combine with other drugs. If you look at where the IRA is heading and where you think about cardiometabolic drugs, combinations of drugs make a lot of sense. This is an excellent drug to combine with many other drugs, and one of them being a PCSK9 oral, for example. You could have a profile that would be even better than we have as a monotherapy. That, I think, is going to be something we're looking into from a life cycle development perspective. That's the catalyst on the clinical side of things. Commercially, we are continuing to build out the company. We already have the core commercial team led by BJ
Jones, Chief Commercial Officer, who led the launch of Nurtec very successfully for Biohaven. That led to the major acquisition by Pfizer with really good launch trajectory. A lot of the same people involved in that launch are now with NewAmsterdam Pharma, and they're building out the team. We have MSLs in the field. We plan to hire even more this year. This is building out all the capabilities that we need to get ready for a launch in 2027. That's our plans right now for this year.
Got it. Okay. Sounds great. You were talking a bit about PREVAIL and the top-line data coming later in 2026. Maybe could you remind us a bit about your strategy in terms of in the U.S. regulatory filing, the timing of that with possible PREVAIL top line, et cetera?
Right. Again, learning from experience, and we want to be able to launch with outcome data in the public domain, or at least soon after launch, where you can have confirmation that the great data we saw in phase III translates into MACE benefit in a larger outcome study. With that said, we want to try to take advantage of the one-year PDUFA period so that when we file and we can track the events, we can try to time the launch right around when the PREVAIL trial will read out. We have heard from all our stakeholders, the KOLs, the payers, that they do not need to have it in the label per se. We would just have the information in the public domain, and that would be sufficient to get broad access, which is our key, having broad access for the drug.
Our feedback from the payers so far has been extremely positive about this drug. They see this as a real differentiated therapy from anything else. They like the concept of a small oral pill that can be widely used and well tolerated. That is, I think, we feel confident that having this plan in place will lead to a successful launch ultimately. It does require a little bit of flexibility about when exactly to do that, because no matter what, we're going to be within a few months of launch. We're going to have to try to kind of understand the best timing for that. Europe will go first. Europe will go first in October figuring the launch, I'm sorry, in the summer. We figure that the approval would be in the second half of 2026.
Got it. Are there any sort of historical examples of these CV outcomes trials accelerating prescribing and even whether or not it is in the label or not in the label that we could point to as an analog for obicetrapib?
I think the best analog, of course, is the statin. It goes back to 1994, which I remember well, because when the 4S trial came out, simvastatin and Zocor was doing well. Once the outcome study came out, the sales of simvastatin skyrocketed. Lipitor came out a year later without outcome data and was able to leverage that and got out in a very strong way anyway. I think historically, there have not been outcome data at launch. Even the PCSK9, I think what really changed the trajectory there was not so much the outcome study, which was important, but the fact that they were able to get broader access with better guideline support. I think at the end of the day, it is not just outcomes, because we think based on our research, the vast majority of doctors, including myself, will treat based on LDL lowering.
They don't need to see outcome data. Nevertheless, we do have, we knew, are some out there that want to see outcome data for every single MOA. We have more work showing that our MOA is just like any other LDL drug with improved clearance of LDL. I think that type of information is very helpful to get some of the skeptics on board. We ultimately believe that this type of profile, again, especially the safety and tolerability, is going to win the day with clinicians knowing that they can get very safe, robust LDL lowering in a single little pill.
Yep. Got it. It's not just about LDL as well. Obicetrapib has benefits on Lp(a) and other markers of CV risk. Maybe could you walk us through some of your enthusiasm around those benefits and how could that also help expand the addressable population for obicetrapib down the road?
Sure. Lp(a) is a very important genetic risk marker. In fact, in my lipid clinic today, seeing patients just four days a month, the most common referral now, and often self-referral, is high Lp(a). It's getting more and more well known, because these patients have family histories. They know they have heart disease risk, and their LDL levels may not necessarily be elevated. They kind of wonder what to do. Right now, we give patients statins to get the LDL down, knowing that statins actually raise Lp(a) modestly. The LDL lowering going down seems to mitigate the risk of elevated Lp(a). The therapies on the horizon, which is the Horizon trial, using ASO and then RNAi as the follow, are very exciting.
They are going to address only the top decile of patients, the ones that have Lp(a) levels that are 150, 175, even 200 nmol per liter. That will be a great, hopefully, risk modifier for those patients. For the majority of patients with high Lp(a), those that have Lp(a) levels that are, say, 50-150, they will not be available to those patients. That opens up that opportunity, because everyone will start knowing their Lp(a), because there is nothing you can do about it from a lifestyle perspective. You cannot lower it. It is pretty much elevated. It stays elevated. Family histories are usually bad, so you are very motivated. You want to figure out what to do in that 50-150 range. We feel we have that right option for patients. If you think about it, they have to have heart disease also.
That would mean it's even fewer patients than would qualify, because these are going to be injectables. I feel because they designed the trials the way they did to get high risk, potentially high benefit, they're going to be priced like a form, they're going to be priced in that specialty pricing of $15,000. You talk about cost also involved. You want to go with something that's oral, less expensive. We see this as a huge upside opportunity for us with obicetrapib. The delay in Horizon actually maybe works to our favor in that if it's working, which I believe is the case, and there's less events than expected, this therapy will be available after obicetrapib launches.
For all that pent-up demand of Lp(a) lowering, we'd be the first potential therapy in the market before the ASO Novartis drug, and people will start using obicetrapib. I do think it's even to the point where obicetrapib might be the go-to first-line therapy, and then you add an injectable if you need it to go forward. There are a lot of potential ways to use it effectively, especially for primary care doctors who want to—they don't want to be involved with specialty drugs. They don't want injections. An oral therapy could be quite impressive. Based on the benefits, we've seen 50%. We've seen 35%. We're in that range.
We think 35%-40% median reduction of Lp(a) is where we think is the right median benefit, which is probably the best way to look at it, because there's such a very different skew for Lp(a). If you look at the population, most people are normal, and then some have mild, and then it goes like this as far as percent of population. There's a lot of between 50 and 150, a lot below 50. At least half people are below 50. You see how this drug could fit in for that sweet spot of 50-150 overall, which is a lot of patients still. We believe that it could be the right drug. Based on our BROADWAY data showing the surprisingly better results than expected, we think that Lp(a) lowering might be part of that benefit.
If you look at the REVEAL trial with anacetrapib, you look at the upper tertile of Lp(a), they also had greater benefits. We think there is some evidence that the Lp(a) lowering with CETP inhibition can translate to greater than expected event reduction.
Yep.
I mean, I'd like to also add for the core product of the LDL lowering therapy, I think the Lp(a) benefit is just another product differentiator for us that allows physicians to say, if you are someone who has LDL, well, if you have high Lp(a), what drug is the physician going to grab next? It'll be obicetrapib. If they have prediabetes or diabetes, what would they grab next? It's obicetrapib. We're trying to change the definition of what is efficacy for LDL-C lowering. It's no longer just lower your LDL, because there are so many other attributes of statins and other compounds that you're trying to offset and drive adoption. We finally think, given the safety profile of the drug, this is the first choice where physicians can just say, okay, I don't have to think about what a patient has or doesn't have.
I just grab obicetrapib because I know it will work for the patient, versus some other compounds that are out there. You have to say, well, do I have to worry about diabetes? If they have diabetes, why would I grab something else? We're trying to make this decision easier for physicians. I think Lp(a) is one of those aspects that's extremely popular, because remember, the LDL-C market is much larger than the Lp(a) market. Being able to target that market with a very significant differentiator will hopefully drive commercial success.
Yep. I hear you. Talking about physician decision-making and having different options, we have been getting a bunch of questions from investors, just how do you think about the cardiovascular landscape evolving with possibly oral PCSK9s being on the market? You also have your fixed-dose combo strategy with obicetrapib as well. How does that layer into the treatment paradigm, and where do you think things will shake out in prescribing?
Right. I think the oral PCSK9s, again, speak to the fact that you have two major companies that are basically stating $5 billion each in sales for one of those, each of those oral PCSK9s, which is great, because that kind of validates what we've been saying about the market, about the unmet medical need. It is really nice to see people investing large capital into better oral therapies for lowering LDL. I think, though, when you believe what Matt said about the patient selection, the oral PCSK9 by Merck is a peptide.
It is like Rybelsus, I think. And Rybelsus is used quite a bit. It is an oral GLP-1. The challenge with Rybelsus is that you have to take it with fasting for eight hours and then no other drug within 30 minutes. It is usually in the morning. It has its challenges. It is not that it is not used.
The Merck oral PCSK9 will be similar. It will be relegated to that kind of morning dosing without any other pills in the same time frame. Most of these people are on a lot of other pills. It does create its own challenges. We will see what their phase III data looks like when they release it, because there is a very prominent food effect. It is 50%+ without eating, with that paradigm of dosing. If you take it with food, it goes down to 20%. It is a very, very significant food effect issue that makes it difficult. We think that will be a factor. More importantly, it gets down to the other attributes that obicetrapib has on Lp(a) and diabetes benefit, small particle reduction.
That, in the end, I think, is going to be what gets clinicians to decide to use obicetrapib over and above an oral PCSK9. Again, we're going to have outcome data right around launch. That does not become a hurdle for people going to the oral PCSK9 rather than obicetrapib. We see it as a great thing for having these other large players in the market, because at the end of the day, we want clinicians to get excited about more and more LDL lowering to achieve clinical benefits. That is what we think these other products will do for us. The AstraZeneca one will have data at ACC. Again, we're expecting similar data with what they showed us in phase 1b, that 35% LDL lowering.
They're trying to, as you can tell, they're trying to look at a combination with statins where they get in that 70% LDL lowering range. We actually have very similar data from our phase two trial with a combination with statins. We're in that same LDL lowering range as well. We are thinking about that as also a lifecycle extension. That's about three or four years away from us. We will be well established on the market. Again, having outcome data ahead of time, we feel that'll be something that will be another strong advocacy of getting LDL lowering down. We feel we'll be in a good position, very well to compete with that with our profile.
Yep.
I think it's important to also realize from a payer perspective and also a physician perspective, we are a completely different mechanism of action. Right now, the physician and everything else that's in development is a PCSK9. The question will be, a physician has a choice. Do I take a CETP or do I use a PCSK9? If they decide to use a PCSK9, then it'll be, do I use an oral? Do I use AstraZeneca? Do I use Merck? Do I use an injectable? We feel like we're earlier in that decision process where, as I said earlier, if the physician comes and a patient says, I have high Lp(a), they'll choose obicetrapib. If they're prediabetes or have diabetes, they'll choose obicetrapib. If they have a large number of small particles, they'll choose obicetrapib.
There's a lot of reasons to choose obicetrapib. It's really difficult to find a reason to choose a PCSK9 first. I think that's the decision we want to be in. It's easy for a physician just to choose obicetrapib, and then they can see how the patient responds and decide what's best next.
Yep. Got it. Got it. You kind of answered this a little bit, but I did want to drill down. You mentioned you have a new head of commercial, very strong track record. What's he doing to lay the groundwork for possibly launching obicetrapib and just layering it in there? We do get questions from investors as well. How are you thinking about going alone versus possible partnership? How do those different pieces fit together?
Like I said, BJ and his team have done this before. I think we did make that decision to bring him on over a year ago to get ready for launch. Right now, it's all about getting in that pre-launch phase, getting interactions and communication with the key opinion leaders and getting them to understand our drug and the class history and why we're different. That's a big part of building enthusiasm, meeting with payers, doing market research. Hopefully, we can come out with this in more details later. We're getting tremendous support with our market research is giving us extremely high confidence that this launch will be successful. That's always good to see. BJ has a lot of experience with this. This drug does really well when you present that profile to clinicians, high prescribing doctors, and so forth.
That's the work that we're doing right now is getting to understand. Now we have the data and doing the market research with the profile of the drug that came out of phase III. It's being very well received by the medical community, this type of information. We are preparing to launch ourselves. We have $800+ million in the bank. That'll get us through launch. It is a great place to be as a company to have those resources to do that. We're also open to how best to deploy that capital with a partnership. Again, Matt, Europe is taking care of. That'll be generating royalties for us very soon. We have options in Japan and China.
I think one of the things that we're proud of is that we're able to enable both of those big geographies as a small company to be in play as well. They're ready to be filed just like Europe is. We have the capability of using those geographies to bring in more funding to support the U.S. launch if necessary. Right now, we're not thinking about that. We do have a very growing team in place to get ready for us, which creates value for the company, because even a partner or an acquisition will want to see a lot of work done on the commercial side before they would make a decision. I think everyone who would come in and see us would see how well we are preparing for the launch of this drug. We are planning to launch our alone because we need to.
That's the way the world works in biotech. That's how we focus on for the company. I believe the greatest value for us will be to show a successful launch. That's how we create the greatest value for the company. Because this drug meets all the criteria for a very successful launch. I think one thing that I keep emphasizing, because I know it's true, is that doctors choose drugs 90% based on side effects and tolerability, 90%. 10% is the other stuff. As long as the drug is well tolerated and safe, they ride it like water for somebody who needs it. Especially true today. I mean, most of my time in the clinic is spent trying to explain side effects, no matter what the side effect is. It's even more true today than it's ever been.
This drug, I believe, will be, I think, one of the best launches in the cardiovascular area in many years. Ezetimibe was a good example. Ezetimibe, an LDL lowering of 15%, no outcome data, very little pill, safe, well tolerated, launched as a rocket with $5 billion in sales, $6 billion if you add in the Vytorin part of it. It is a good kind of metric benchmark to look at where we could be with obicetrapib. Now the market's even more amenable for an add-on to statins than it was back in 2001 when ezetimibe was launched.
Yep. I hear you. We have a couple of minutes left. I wanted to open it up if anyone in the audience has any questions. Okay. I can ask one in the meantime. This is a unique one I've gotten from an investor before. How are you thinking about GLP-1 agonists starting to show CV risk reduction results in certain patients? How is that going to impact the treatment paradigm going forward?
We have a lot of GLP-1 patients in our trials. We're going to show this more definitively. We see the drug works as well, if not better, on top of GLP-1. GLP-1s are here to stay, and they're going to be a growing part of the reduction of cardiovascular risk overall. They're not effective LDL lowering drugs. You might see some modest benefit in certain trials. Overall, they don't lower LDL. If you look at the data, 90% of patients started on a GLP-1 are not taking a GLP-1 at the end of the year. It's a very high dropout rate for multiple reasons. Either they lost their weight, and now they want to stop, or they can't tolerate the drug, and they want to stop. These are not long-term therapies for the majority of patients.
We believe that with our drug, which actually works the best in that cardiometabolic patient, it's a very great companion drug to GLP-1. In fact, we believe the future, one of the greatest potential combo pills would be a GLP-1 oral with obicetrapib. That would be a fantastic combination. We're thinking about how to go about doing that, because that would be something that would take care of almost everything that relates to cardiovascular risk. You can see the impact that would have on heart disease reduction to have that type of combination of benefits. We see that as, again, more of a down-the-road strategy for us. We see the GLP-1-obicetrapib combination as being something really, really important for getting cardiovascular risk where we want it to be for patients, which still the leading cause of death is heart disease.
Yep. Got it. I know you alluded to Europe a little bit earlier too. Just wanted to squeeze a question in thinking about upcoming filing in Europe and possible metrics to watch for your partner, Menarini, in that area.
Menarini has a really good footprint in Europe. If you look at the rankings of cardiovascular drugs, they're at the top of their interactions. They've done a great job with previous cardiovascular launches. They're fully engaged. We have worked hard to have a unified communication to education program, the same trade name, the same way to get education across the world synced up together with Menarini. That's important. We see them as a great partner, as they're also a great partner to many other big companies too. We like the relationship. I think their projections of sales, of course, is based on their experience. We're looking forward to that happening. They have a situation where they launch, let's say, Germany as the prime example. Then they have a price that's set.
A year later, the government comes in and says, "The price is fine," or, "It's too high." You have to adjust according to what the government tells you. During that one year, then PREVAIL reads out also. This is just a different system. It also works well to this strategy of launching and then having the outcome data read out within the year after that.
Yep. I hear you. Great. I want to give everybody a few minutes to get to their next sessions. Thanks again, Michael and Matt.
Thank you.
It's been great having you.