Hi, everyone. Thanks for coming. My name is Matt Phipps, Biotechnology and Austere William Blair. I'm glad to announce, happy to announce the next company at our Growth Stock Conference. It's NewAmsterdam Pharma. We have Michael Davidson, one of the CEO and co-founders. It's a company that's had a lot of success over the past, you know, really a couple of years, but really demonstrating some great clinical data with their novel LDL-lowering therapy and has a couple more big readouts to come over the next year plus. Good time to meet with the company and hear the story as they get closer to that commercial stage. Michael, we'll start with the presentation and we'll do a couple of questions as well.
Thanks, man. Thanks, everyone. My clinic, by the way, is just right around the corner at the University of Chicago. I see patients four days a month, a Lipidologist, Cardiologist. This is my... So I'm excited about where we are and where we're going to be in the next few months on some of our key catalysts. To kind of set the stage, I'll go through quickly some of our key information and then open up for discussion. This is a good time to be developing a new Lipid Therapy because in 2013, the guidelines kind of shifted back to no longer having goals. It was at the time when Evidence-based medicine was the focus. We didn't have trials to show that lowering LDL beyond Statin therapy was effective.
Since then, which is roughly 12 years ago, we've had a lot of new data about the benefits of lowering LDL even lower. Now, 55 LDL as a target is back for those high-risk patients. What that means now is that we have a lot of people that are well above that target that need additional LDL-lowering therapy despite being on optimal Statin dosing. It's 30 million plus people. Obicetrapib is the drug that can get the majority of those patients to goal with monotherapy or in combination with Ezetimibe. It achieves LDL lowering of 35%-over 50% reduction. We already have great benefits in our first larger Phase 3 trial showing reductions of Cardiovascular events of 21%.
We have very, very well-tolerated and safe and effective LDL-lowering therapies that can get patients to goal and already established Cardiovascular benefits that will hopefully be confirmed with our ongoing larger Cardiovascular outcome trial called PREVAIL. We were well-funded. We had financing in December of last year. We raised almost $500 million. Now we have over $800 million in cash to get us to where we need to be, which is to launch this drug over the next few years. One thing I want to point out that people ask me about is the market, is it well-served? Is there a need for new therapies? The guidelines changing to more aggressive targets has certainly impacted utilization uptake. We are seeing a very robust market now. Branded drugs are growing 40% plus. Even generic Ezetimibe is growing over 20% per year.
The market, which was relatively flat up until recently, is now growing very robustly, which puts us again at a good time to launch a new and effective and very well-tolerated LDL-lowering therapy. This is the issue. The guidelines say less than 55, and that means only about 25% of patients are even at that goal. Even if you look at 55, sorry, 10%, only 10% are at that goal based on the latest surveys, which are consistent across all the different evaluations of targets to therapy. Here's my sad analysis of the guidelines. I do not want to say it is all due to this, but when you look at when the guidelines were changed in 2013 and goals were taken away, we saw this really significant uptick in Cardiovascular death.
LDL levels basically stayed flat that were going down, and now they're starting to come back. We saw this really significant increase in Cardiovascular death once those guideline goals were taken away. This is where Obicetrapib fits in. If you look at existing therapies to add to Statins, we have Ezetimibe generic, modestly effective, Nexletol, an oral that's branded and basically the same efficacy as generic Ezetimibe, fairly well tolerated, but it does have some side effects, but very difficult to get covered by insurance because for most patients, this is not going to be enough to get them to their target goals. We have the injectable drugs, PCSK9 inhibitors, which are very effective and well tolerated, but they do require injections and injection training. I, for example, I have a full-time nurse that helps me with this resource at my lipid clinic.
Again, I'm seeing patients four days a month. I'm the leading prescriber of PCSK9 inhibitors in the entire city of Chicago. It really requires that type of support and resources to get most patients on treatment. Consequently, for the primary care doctors where most of these drugs should be written, they're not writing these more effective and well-tolerated injectable drugs. We have Obicetrapib, which is our drug, very effective, lowering LDL of around 35-40%. In combination with Ezetimibe as a single combined tablet, we get that LDL-lowering efficacy equivalent to the injectable drugs and therefore can be a very nice add-on to Statins that get most patients to their targets. There are some other oral PCSK9 inhibitors that are coming in the next few years. Again, speaking to the benefit of a systematic large market.
However, when we do our market research, we outperform these other drugs quite significantly due to the fact that we have additional benefits, which I'm going to get into, that really make this drug very well received by academic leaders and also by the key opinion leaders in the lipid community. Here's our efficacy. I guess I'd mentioned 35-40% as monotherapy, roughly 50% in combination with Ezetimibe. And this benefit sustained over the full year of phase 3, which was gratifying to see. This study recently, BROOKLYN and then BROADWAY, BROADWAY was recently published in the New England Journal of Medicine in May, highlighting the benefits of this drug over the one-year period of time. Here's the achievement of goal in these two trials showing that with Obicetrapib and Obicetrapib with Ezetimibe, you're basically done. You have Statins, and you have these two agents.
For the 90% plus patients, you're getting them to goal, which they need to get for LDL-lowering control. Even more so with the tandem or combination with Ezetimibe, we see this 90% plus getting to target with that combination approach. What was exciting about our data and led to our financing was the demonstration of a MACE benefit, a major adverse cardiac event reduction of 21% just at 12 months, which is much more than expected for this amount of LDL lowering on that short period of time. We combined BROOKLYN and BROADWAY together in two phase 3 trials, it's even better. We have two studies showing a benefit on MACE benefit in only 12 months of treatment. Here is the Kaplan-Meier curve, which always is the true kind of way to show this data.
At day 200, the lines separate, which is exactly what you'd expect for an LDL-lowering therapy. It takes time for the plaques to stabilize and then separate with effective LDL-lowering treatment. The reason why the drug worked better than expected, we're going to present more of that information at our R&D day next Wednesday in New York. Expected about a 9% reduction based on LDL lowering alone. What our drug provides, in addition to LDL lowering, is Lp(a) lowering, which is another very important atherogenic lipoprotein. It reduces small particles, and it reduces the risk of diabetes, which gives us that LDL plus phenomenon. Here's the small particle reduction. Small particles are measured in the blood. The way I explain it to patients, you have a bucket of sand or a bucket of pebbles.
If you have a lot of small particles, you have a bucket of sand. The amount of cholesterol per volume is the same, but the amount of particles are much greater. We knock out the small particles by 90%, which are much more associated with Cardiovascular events. The small dense LDL cholesterol goes down by 30-45% with Ezetimibe. Here is our data on particles. This is if you're ever going to a lipid specialist, and if you ever get these tests measured, you'll see that we get everyone to those really ideal levels of both total LDL particles and small particles with Obicetrapib, and even more so with the combination with Ezetimibe. Lp(a), we just presented this data last week at the National Lipid Association meeting. Lp(a) lowering of around 40-50%, especially in the target population that have 50-150 nanomoles per liter.
This is an exciting new target. There's many therapies on the horizon to lower Lp(a). It's kind of one of the last unmet lipid-related factors that we can now address with therapy. Those other therapies are injectables. Their RNAi or ASO approaches can lower Lp(a) much more effectively, 90% plus, but they're injections. They're going to only be limited to the very highest levels of Lp(a), only about 10% of patients. With our profile, where we fit in, we can address the other vast majority of patients that have high Lp(a) that won't qualify for these injectable therapies. Here's what we try to describe the benefits of Obicetrapib. It's a rainbow of other benefits beyond just LDL lowering. It raises HDL by 150%. It lowers Lp(a). It lowers small dense LDL particles. It lowers the risk of diabetes.
All these factors together contribute to a much greater than expected Cardiovascular benefit in our BROADWAY trial published in the New England Journal of Medicine just a month ago. The drug safety is really one of the unmet kind of value that we provide to patients. Again, speaking as a clinician, I would say patients today do not want to accept any side effects at all for a drug. This is what Obicetrapib has shown in its clinical studies. No side effects different from placebo, no increase in liver enzymes, no increase in muscle enzymes, decreasing risk of diabetes, decreasing risk of renal endpoints. It is an extremely safe drug based on our phase 3 data. Here is where we are. We have had multiple read-outs, as Matt mentioned. We had a very successful execution of all our studies.
Broadway and Brooklyn in tandem being our phase 3 lipid trials. Our Cardiovascular outcome trial is fully enrolled over a year ago, and that will read out towards the end of 2026. We also are working on Alzheimer's disease. It's an exciting area because of HDL raising. It's something that I've been very interested in, especially for APOE4 gene patients. That's a lipid gene. It's 25% of the population, but more than two-thirds of Alzheimer's patients carry E4. That issue is because APOE4s cannot remove cholesterol from the brain effectively. That's the Bain hypothesis, that HDL raising could interface with the blood-brain barrier and remove that excess cholesterol, resulting in an improvement in progression of TAL and amyloid and thereby prevent Alzheimer's disease in that high-risk genetic subgroup. We have data coming from Broadway looking at that with biomarkers, PTAL and amyloid and so forth.
That'll be reported this year in the near term. We also have an imaging trial with our combination product, Obicetrapib with Ezetimibe on plaque reduction called REMBRANDT. That study is also enrolling well. I'll have that read out about the same time as our MACE trial at the end of 2026. The last point I want to make is PREVAIL is doing well, our big outcome study. What we want to present next week in New York is, again, more and more confidence that BROADWAY is a mini PREVAIL, same patient population, showing this benefit. PREVAIL is a much larger trial, longer trial, but very similar patient populations, which therefore gives us more and more confidence it will translate into a very significant Cardiovascular benefit in this study. As I mentioned, it's been a year of execution and now data release.
We have many catalysts this year coming, and we look forward to getting that information out to the investor and medical community over the next few months. Thank you, and looking forward to your questions.
Yeah, thanks, Michael. You obviously showed us a good amount of data here today, but you've also had a lot of data at a recent conference at the National Lipid Association. I thought there were a couple of interesting things in there. On this Lp(a) benefit, it almost looked like there's an absolute level of Lp(a) benefit kind of regardless of baseline. Therefore, the kind of relative benefit is best in the moderate patient population. Is that how you're viewing it? Is that really what's informing why you want to focus on this kind of moderate and the elevated Lp(a) patients?
Yeah, I mean, yes, you're absolutely right.
The same thing is true for the PCSK9 inhibitors. They work best in this kind of moderate range. Again, we do not know the mechanism by which it lowers Lp(a). It is not exactly clear. We do think it is production. It serves like you hit a certain magnitude of absolute benefit that is kind of fixed, like you said, which should translate to an additional MACE benefit. I think more importantly, what our data is showing is that, as I said before, it fits very well into the whole Lp(a) treatment paradigm because the Injectables will be pretty much to the extreme. It will be specially priced injections, all that kind of stuff. Great drugs. We are looking forward to them.
On the other hand, for those majority of patients who still need Lp(a) lowering, it's going to be the right sweet spot for Obicetrapib to maximize risk reduction in those patients. It should, one of the things about Lp(a) is that if you never had your Lp(a), but it's a very strong familial genetic factor. When they know, because you can't do anything about it from a lifestyle perspective. Statins, actually, if anything, make it go up. You can't lower Lp(a) with existing therapies. There's a lot of urgency to treat, and people are more motivated to treat.
One of the things about the Lp(a) therapy that, again, is not appreciated is that when someone is trying to convince a patient to take a drug, which is harder today than ever, knowing that they have high Lp(a) and having a drug that affects it is going to make a big difference for Obicetrapib once we launch the drug. Yeah, the other benefit you touched on, but also some data out in LA was this new onset diabetes benefit looking across all the trials and true of the class more broadly. I guess as a clinician, as a treating clinician, how important do you think that benefit is on new onset diabetes in this patient population? Again, I think any I have patients come in with the package insert saying, "It increases the risk of diabetes.
I don't want to take this drug." I said, "We try to go through the Risk-benefit with them." It is still overall beneficial because your heart disease rates go down by X. But I don't want diabetes. I don't care what the LDL levels changes are. I think having a drug like this takes that off the table. You can lower LDL and also reduce the risk of diabetes, therefore, with the medicine. That is a huge difference for patients and clinicians. Clinicians can, I think, have a much better sense of Risk-benefit, but patients don't want any risk.
Yeah. Okay. You showed the Kaplan-Meier curve of the events from BROADWAY, but obviously have looked a little bit more in the publication on kind of some breakdown of those events.
Some investors did have questions on just the number of revascularizations, which I think is not surprising given the time course of the trial, but maybe just talk to us about seeing those revascularization events early. Also, just how did you characterize or what was the criteria? Was it urgent requiring hospitalization, those kinds of things?
I think we're doing a lot of work on this exact issue because things have changed a lot in the treatment world on Cardiovascular disease. You no longer, when I finished my fellowship in cardiology, one of my good friends moved down to Florida.
He said, "Mike, in Florida, the indication for an angiogram and a stent is stop at a red light." No longer is that the case because you have to go through a whole lot of prior authorization, and you have to show that you have stenosis and symptoms. Even revas now, elective revas for somebody who somehow got a stress test and does not have any symptoms is no longer happening. You have to prove that there are things going on. The total revas, and now a lot of studies are moving to that total revas composite endpoint. The TIMI group is using total revas basically as the endpoint. In our study, we looked at urgent and then elective. They had identical hazard ratios, 0.6, almost exactly the same hazard ratio for urgent and total.
We think total today reflects a better and with medicine getting better, people being able to do more testing and imaging and recognition, that becomes the predominant event. You do not want to wait till someone has a heart attack or stroke or dying. Seeing that event reduction so robustly, 60.68 or 63 was the hazard ratio combined. That is, I think, a really important part. The other events did go in the right direction. CHD death and non-fatal MI all turned in the right direction. Stroke did not. Stroke was small numbers. We are going to continue to probably look at stroke in the Prevail endpoint because it is an important endpoint that you need to continue to show and benefit for overall composite benefit.
That leads me right to my next question. You guys have discussed this three-point versus four-point MACE in the Prevail.
I know you can look at all the blinded event rates. Maybe we get some more on this in the R&D day. When you look at that stroke, though, I know there's been trouble on, okay, are you adjudicating? Is this an ischemic stroke versus a hemorrhagic stroke?
It was total stroke. When you look at ischemic stroke, it's similar. I mean, it's not that much difference. There weren't that many, very few hemorrhagic stroke. What's good to know is the FDA has changed their requirements on the composite. It used to have to hit every single one of them selectively to get in the label of the four. They changed it now that you just have to hit the composite and get all four in the label. We think having stroke in the label is an important factor.
It is not going to be a big, the events are going to be driven more by revas and CHD death and MI than stroke. We will talk about it next week more, but we plan to probably continue to have stroke in the composite endpoint for that reason.
Yeah, great.
Because again, if we show benefits with Alzheimer's, which we hope to show, and you have dementia from vascular dementia, which is stroke, and now with Alzheimer's, we could get a lot into the brain benefits of Obicetrapib for both stroke and for Alzheimer's, assuming we have Alzheimer's data that is supportive of that.
As we are watching the landscape here with obviously the oral PCSK9s you mentioned, I mean, how much more important does that make your fixed-dose combination with Ezetimibe, just being able to really push the LDL lowering with a single pill?
No, it is important.
I think it's going to be, I mean, it's up to me. If I was a clinician, based on my data, I'd be one of the high-target doctors that we'd go after commercially. It looks like the combo will be more attractive than the mono for that reason because it's a very, again, very tiny little pill, very well tolerated, more efficacy. The lower, the better. I do think the combo will become the dominant option for clinicians. It competes very well with injectable therapies.
You touched on how Nexletol has problems getting coverage from insurance payers. I know the injectable PCSK9s had a lot of issues, particularly out of the gate with that as well.
As you guys are planning your commercial strategy, how do you avoid all the prior authorization and at least minimize and be able to work through that to make sure you have access, which is clearly necessary for?
Yeah, we have plans for that. We're not going to talk about that yet, but we have some good plans in place to how to get to it all's based on patient demand. And so with patient demand, and again, we're going to have factors that really make a difference, like Lp(a) diabetes benefit, the great tolerability. The more we can get demand up on the drug for both patients and clinicians, the better coverage we're going to get. We think the profile of the drug will make a difference. The problem with Nexletol is it has a hard time figuring out where it fits into the treatment paradigm.
It's alone, it's better than as a top of the Statins. But alone, if you're talking about a Statin-tolerant patient, the Repatha's of the world are a lot more effective. Doctors just say, "I need usually need an LDL lowering more than 20%." It has a hard place knowing where it fits in. Therefore, the demand is just not there to get payers to even think about making it more widely available and less copay issue, which is the biggest issue. It's just too expensive for most patients.
Maybe lastly, Michael, as a treating physician, as more options become available to you, what do you think is going to help differentiate? What do you think is going to be segmenting patients based on whatever else they might comorbidities they have or, again, that moderate Lp(a)? What kind of things do you think will help?
I think we're going to highlight the Cardiometabolic patient because that's where the drug works the best. That's where CETP activity is the greatest. So the overweight patient, low HDL, high triglycerides, prediabetes or diabetes. It happens to be 80% of the patients. And then the Lp(a) represents the other 20%. So basically, it's everybody. When you think about if you have the physically fit, low Lp(a) patient who has pure high LDL, it's still a good drug. But our target is the much larger numbers that fit those criteria, really. It ends up Obicetrapib becomes the go-to for almost everybody that needs these extra benefits. The LDL plus story resonates very well.
Great. With that, we do have a breakout in Burnham A, if you all can join us. We can talk a little bit more about this.
Michael, I appreciate the time today and walking us through the story. Obviously, there are some exciting months and quarters ahead for you.
I encourage everybody to tune in next Wednesday for R&D Day.
Yes, if you can. It is going to be a lot more of what I talked about, plus some new exciting stuff too. Okay. Great. Thank you. Thank you.
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