To the Jefferies Healthcare Conference, Day One. My name is [Dennis Stein], Biotech Analyst here at Jefferies. I have the great pleasure of having NewAmsterdam Pharma here with us CFO, Ian Somaiya here. [Nice way] to see you, Ian and welcome. Thank you, Dennis. Really appreciate being here. It's an exciting time for the company, and I know we have a lot of great questions we're going to get through today. Yeah. Talk about, like, I guess, where the company is right now and just some of the updates that you guys have had over the last couple of months at these various different cardiology conferences. You know, what's the major takeaway from all the data? Yeah, so let's go back to last year. I mean, last year we had three of our phase III trials read out all positive. What it gave us was quite a bit of confidence in being able to get regulatory approval, and ultimately having confidence that we'll have a drug that'll be on the market soon, that could benefit a lot of patients. This year, to your point, the presentations have really been geared to differentiate obicetrapib and its many aspects of its profile, compared to drugs that are on the market today as well as those that are in development. The two conferences that we presented over the past month or so have further highlighted the benefits in terms of the Lp(a) reduction that we've seen, as well as the benefit to patients who potentially are at risk for diabetes in terms of reducing HbA1c and reducing the overall risk for some of those patients advancing to diabetes. That's a theme that's going to continue for the remainder of this year. We have two additional conferences that we're targeting, and additional analysis that will further differentiate OB from other drugs that are in development today. Good, y eah. I think overall it's about developing the product profile, right? We all know that it has good LDL reduction and that's great, b ut then what about diabetes, Lp(a), plaques, and things like that? Like all that stuff should contribute to the overall filing, I'm assuming, the commercial competitiveness once approved. That's right. The opportunity for us is to really redefine the treatment of ASCVD as we see it today, from one that's purely focused on reduction of LDL to really looking at every other risk factor that these patients continue to face. It starts with LDL, but it's also Lp(a), as you mentioned. It's also the residual risk that these patients experience, who are on a combination of LDL-lowering drugs. As we think about statins, whether it be in a backbone of statins and ezetimibe, or bempedoic acid or PCSK9s, one of the areas of risk that's quite prominent is the remnant cholesterol or the small LDL particles. Beyond that, as we mentioned already, the other aspects of the cardiometabolic risk that these patients face, namely from a diabetes standpoint. Okay. Maybe if we can take a step back, because I do kind of have some detailed questions around small particle LDL, et c., h ow do you see the market, right? You mentioned ASCVD, but then you also have this Lp(a) benefit. Talk about that. Yeah, so that's one of the areas of focus for R&D Day next week, amongst others. It's helped describe the types of patients who are candidates for our treatment. The starting point is obviously one we're all too familiar with. There are 70 million patients in the U.S. alone with elevated LDL that are under the care of a treating physician, and on some semblance of treatment. As we think about the classic Venn diagram, where you look at the ASCVD patient population and what are the risk factors they experience? Y es, LDL is quite prominent. When you start to look at Lp(a), which affects millions of patients, same thing with diabetes, same thing with patients who have some semblance of kidney dysfunction, all those concentric circles really give you a sense for how prominent this drug could be across those patient populations. The starting point is patient populations that number in the millions, if not tens of millions. As you think about building out your model and obviously the fairly detailed analysis you've done, as well as others, what we want to be able to do is to really provide you comfort, if not confidence, that irrespective of how you sort of slice up the market, the opportunity for obicetrapib and the fixed dose combination with ezetimibe is quite vast. You also talked about, obviously when you think about the future positioning of obicetrapib, there's the Lp(a) aspect of it as well. You mentioned that the 50-150 nanomole per liter, what is it? L ike 80% of the population, that's not addressable by these injectables like Pelacarsen, et c. That's an area where obicetrapib could potentially be used as well. Can you talk a little bit more about that, and how big that pool is and what proportion of those Lp(a) patients also have high LDL? Yeah. No, look, it's an important question because these are patients at significant risk today. What we have seen across our phase III studies is an average of 45% reduction in Lp(a), specifically in the patient population that you mentioned, which is within the 50-150. These are patients that wouldn't qualify for the Lp(a) targeted agents. When you look at the enrollment criteria for the siRNAs or drugs that are specifically targeting Lp(a), what we find is an addressable market that's roughly 10%-13% in size. The question then is, all the other patients who are still at risk because of their elevated Lp(a), what will they receive? I think we've started to answer that question with the analysis we've done across our phase III completed studies. We have one more study that we're conducting today, which is a VINCENT study. It's a phase II trial evaluating the combination of obicetrapib, in combination with the PCSK9, specifically Amgen Repatha. That study data is expected later this year. We would be able to further define what the role of OB will be. The next step is engaging with regulatory agencies. In Europe, what we have seen is an agency that's willing to include Lp(a) as part of the clinical trial section. You can look at the data tables for a drug like inclisiran, in which you'll find measurements in terms of the benefit on LDL, non-HDL, ApoB, and Lp(a). That's not true in the U.S. That's again, the basis for a conversation with the FDA i n terms of whether there will be changes once the Lp(a) targeted agents do demonstrate an outcomes benefit against that target, or whether additional clinical trials will be required from us. That will help us ultimately address the vast majority of patients, the roughly 40% of patients that remain at risk, but would be under the cutoff that are currently utilized in the phase III studies, the outcome studies. Okay. Y ou mentioned VINCENT, right? That's the Lp(a) study on the Repatha. Can you talk a little bit about what you're trying to achieve there, and what would be a good outcome? Should we expect some sort of synergy in terms of Lp(a) between obicetrapib and Repatha? Yeah. We know quite a bit about how those two drugs behave together from our phase III trials. We obviously allowed for enrollment of patients who are on a background of a PCSK9, and obviously in combination with statins and so on. We have some knowledge already in terms of how the two drugs behave. It is quite consistent across the board in terms of, irrespective of what the background therapy is, OB reliably reduces LDL. What we do not know is how the two drugs behave in terms of the reduction in Lp(a). That is something that we will learn through the VINCENT study. This is the first study that we have conducted, where we have included patients with high baseline or elevated baseline Lp(a) levels, as well as LDL levels. We will have a good sense for what the benefit is on both those lipid markers. Our expectation is to see additivity. If we have a drug that simply combines the LDL reduction and Lp(a) reduction of its components, we're going to have a drug or a combination that has the potential to garner quite a bit of use. Really, the question then is, how do we engage with regulatory agencies to potentially get either labeling or inclusion in our label? Don't you have the PCSK9 plus obicetrapib Lp(a) data from BROADWAY? Like, what have you seen there? Yeah, so we have that data, but as you know, in the BROADWAY study, the patients in BROADWAY were not required to have Lp(a). We did not enroll for that specific risk factor. The VINCENT study really gives us that opportunity to look at both those risk factors and enroll patients with the highest possible risk, because of those markers. Obviously, we have had certain patients that had both elevated LDL as well as Lp(a). That data is something that we will share over time. I think the best way to answer that question is to complete the VINCENT study. Obviously, the wait is not that long, because we do expect that data to become available at some point later this year. Yeah, ok ay. If we take a step back and think about the ASCVD market in the next 10, 15, 20 years, like I'm talking about a very long-term view, right? Like, what do you think the market would look like? Would people still be focused on monotherapy drugs and add-on therapies? Would they start investing in combination approaches or fixed- dose approaches? H ow does Lp(a) play into that? I think that's a very important big picture question that people may need to start considering. Yeah, I think we've already started to see movement in terms of gaining some sort of direction in how these patients are going to be treated in the future. It' s one of the reasons why we believe this is an ideal time to launch into the space, especially with a drug that's truly differentiated. As we think about the payer perspective on LDL lowering, there's a high degree of comfort, if not confidence, that they are able to manage access to patients. Access is broadly available because we've gone through a reset in terms of the pricing in the U.S. We've also seen the FDA amend labels for lipid-lowering therapies, to include potential treatment for primary hyperlipidemia, primary prevention, as well as broaden the scope of the labels for MACE, no longer limiting it to components that are positive from a statistical significance standpoint, but really looking at the breadth of the MACE claim. That provides a good backdrop for what we're already starting to see today, which is statins growing at low to mid- single digits, generic drugs, such as ezetimibe growing north of 20% and branded drugs growing closer to 40%. It's one of the reasons why PCSK9s have finally realized their potential in terms of being a blockbuster category. We expect this to continue, so t he opportunity is really for all participants. It takes us back to 10, 20 years ago, when you had an industry, half a dozen or so companies calling into cardiologists, primary care physicians, endocrinologists, focusing on LDL as a risk factor and making available to them, making known to them the treatment options that were there. If you fast forward to 10-15 years from now, our goal is to redefine what care is and have a therapy that addresses multiple factors that implicate risk. It is no longer looking at LDL alone, but looking at the residual risk if a patient is effectively or on a treatment of a high-dose statin, and potentially on a combination with an ezetimibe, bempedoic acid, or PCSK9. That risk is LDL particles, first and foremost, because no other drug reduces particles, in our case, virtually eliminates small particles. Lp(a), where PCSK9s have shown an ability to reduce Lp(a) by 20%-25%, we've been able to show across our phase III studies, a 45% reduction in Lp(a). There are other benefits as well that could drive usage. When you look at all these populations, these subpopulations, they're all in the millions, if not tens of millions. O verall, when you think about this space, we're looking at a category, a treatment area where you have a portfolio of options available to patients. Most of those patients are going to be treated in combination. When it comes to treatment choice, irrespective of what the background is of that patient in terms of other risk factors, what their baseline LDL is, what concomitant medications they might be on, obicetrapib to us remains an ideal option. Right. I think our view is that when you look at, over the next 10 years, the market is not just going to be people with high LDL, right? It's going to be sliced up into multiple pieces. What's interesting about obicetrapib is it has a benefit on diabetes. It could address the patients with diabetes, with LDL, with Lp(a), HDL. Maybe we could talk a little bit about that. Just overall, it does seem like obicetrapib does have a place in all these different kind of segments, right? Yeah. No, Dennis, I couldn't agree with you more. As we've continued to engage with physicians, and we did that most recently following our phase III data, so w e engaged with several hundred physicians. As BJ Jones, our Head of Commercial would say, we did the mother of all demand studies to really get their perspective on a global basis, how they view OB and how they would potentially use it. It is not a U.S.-centric view. It is not a view that's limited to specialists. We really wanted to get a breadth of perspective. That is something we'll be able to share at the R&D Day next week. In addition to that, we also engage with payers because they're also another important constituent that's going to play a prominent role in terms of how these drugs are utilized in the future. The profile resonates. It's difficult to identify a patient population where OB would not be an option for these patients, and for most, a preferred option. I think that's a good starting point. As our CEO, Michael Davidson likes to say, safety is tantamount. We're talking about a patient population that's asymptomatic, that has the risk of a future event. A treatment option has to be convenient. We believe we provide that with a low-dose once-a-day pill, as well as safe. That to us, gives us the greatest confidence that we could become a preferred therapy in this patient population. Good. T he R&D Day, what should we expect there? The goal is to answer your questions, right? First and foremost, yours, Dennis and everyone else in the room. The two questions that we get asked most frequently are, one, really looking at the BROADWAY data. The MACE benefit that we observed, which obviously was quite startling and a surprise to us, what we had predicted was a 9% MACE benefit, given it's a one-year study and based on the magnitude of the LDL reduction that we have reported. What we saw instead was a 21% MACE benefit at year one. The question that we get asked most frequently and the one we want to answer is, what led to the benefit above and beyond what LDL would have predicted? The incremental 12%. The areas that we're going to focus on are Lp(a), as well as looking at small LDL particles and another category, just we're going to describe as other. What we want to do is for you to walk away from that analysis with the same level of confidence we do in PreVeil ultimately reading out positive, and that benefit and the differentiated product profile translating to commercial success. The other question is really focused on commercial. It is the translation of the clinical data to the commercial setting. BJ will spend a lot of time sharing with you feedback that we've received from providers and payers, but also sharing with you his perspective on what the opportunity is for OB globally. Can you talk a little bit more about small particle LDL? It does not seem to be something that is widely understood by investors. Yet obicetrapib seems to have a very profound effect on small particle LDL, relative to many of the other drugs in the lipid-lowering space. Can you talk a little bit more about that, why that is important and perhaps also the read-through overall to PreVeil, your CVOT? Yeah. The reason why it's not top of mind for clinicians, and I would say more primary care than lipidologists or specialists, specialists do screen for LDL. When you start your study, you get your overall lipid profile read out, then you have a sense for how many large particles you have, how many small particles you have. A year later, you go through that test again. You have a sense for, well, how do we define residual risk for that patient? You're right, it's not true more broadly as you think about the primary care setting. The reason is, there hasn't been a treatment like ours to impact or reduce that particular risk. When you look at statins, they predominantly reduce large particles. That's true across the board for the other treatments that are available, PCSK9s uniformly reduce LDL. If a patient experiences a 50% reduction with the PCSK9s, it's going to be a 50% reduction in the large particles and small particles, b ecause of the mechanism of CETP, what we see is principally a reduction of small particles. That's the residual risk that a patient experiences, who's on a statin-based backbone. It's really an opportunity for us to bring that to light in the physician community. The good thing here is the tests are readily available. Any patient that gets screened for their lipid panel specifically, and especially for Lp(a), they'll also see their particle numbers. It's not something that we need to create in terms of a diagnostic. That's something that's available. What we need to make sure that clinicians are aware of is, finally, there's a treatment option that can mitigate that risk. Testing for LDL particle size, is that standardized? You find it to be quite common among specialists. It is something that the primary care prescriber base will need to become aware of. I would really re-emphasize my point, Dennis, which is unless you have a treatment that mitigates that risk, there is really no point discussing it. It will be the first treatment that does exactly that. Okay. There's also this discussion around whether in NewAmsterdam, for PreVeil, whether you would choose MACE- 4 versus MACE- 3. Talk a little bit about that sort of discussion, and the pushes and pulls on that. Maybe also kind of loop in what you saw in BROADWAY, and the New England Journal of Medicine publication and the breakdown in terms of the MACE components, and how that would ultimately impact your decision to choose one versus the other. Yeah. It is important to remind everyone that whatever decision we make, whether it is MACE- 4 or MACE- 3, it is not designed to increase the probability of success. We are confident irrespective of which endpoint we choose. We are also confident in the overall timelines for the study. That is an important, obviously factor for investors. Either direction, we are confident in our ability to report positive data for PreVeil. The question and sort of the answer is really more nuanced. It is, what do we want on the label? If we were to remove a component, let us use the example of stroke, then stroke would no longer be in the label. The question is, what is the commercial implication of not having stroke in the label? When you think about the backdrop of lipid-lowering therapies and their ability to drive a stroke benefit, we've seen that quite consistently with the PCSK9s. We do think it's a matter of time. In a one-year study, and this is also true for the PCSK9s and their LDL trials, they did not show a stroke benefit. In their outcome studies, which followed patients for a couple of years, they did. That would be our expectation as well. It's really a question with a regulatory lens, as well as a commercial lens, not specifically focused on increasing the probability of success or decreasing the risk associated with a positive outcome. Would that label not reflect the secondary endpoints on stroke? If you had MACE- 4 as a secondary, would that not be in the label? Yeah, i t's a great question for BJ Jones next week. I'm going to preempt that, I'm sure he's listening to this webcast. It's a question of, how would a commercial organization be able to utilize their primary endpoint and the label claims associated with that versus something that shows up in the secondary? There are limitations in what we can say and how we can interact with providers. Okay. I think in the last couple of minutes, let's talk a little bit about the other big question in the room, which is, how translatable is the BROADWAY data to the PreVeil data, right? If you're showing 21% benefit at one year in BROADWAY, and the company's messaging is that BROADWAY is a mini PreVeil, right? Patients are the same. Why should we not expect similar 20% benefit at year one, which would only, I guess, widen until you get to two and a half years, which is your minimum duration of follow-up? Right. W e did fine-tune our messaging related to PreVeil after the BROADWAY data became available, and really getting away from 15% plus benefit to 20% plus benefit. The BROADWAY data did give us a lot of confidence. That is something we've shared with you. In terms of continuing to extrapolate the 21% out to year three and a half, four years, yes, the benefits of obicetrapib over time should further enhance the overall or further reduce the risk of outcomes in the trial. There are also other factors that we need to consider. One of the simplest factors is the challenges of maintaining patients in a trial out to three and a half, four years. There are always going to be sort of counterbalancing, countervailing factors that play a role. Ultimately, if we're able to report on a 20%-21% MACE benefit, it'd be far better than what we have seen with approved agents, including the high-efficacy PCSK9s, where we have a 15% MACE benefit. The goal is to have a positive study. The p- values have to support that positive outcome, and ultimately for that to support the regulatory approval as well as pricing. Beyond that, we're doing everything we can from a trial execution standpoint to really take advantage of and realize the benefits of OB, and the benefits that go above and beyond LDL alone. Great. I think we have one more minute left. Can you just remind us of your balance sheet and the runway? Yeah. Last year, we were able to execute on two financings raising upwards of $700 million. As you look at our balance sheet as of the end of the first quarter, we're roughly at $810 million. That gives us an ability to not only complete all of our clinical trials. We spoke about the outcome study obviously at length. There is also the Rembrandt study that is looking at, it is an imaging study. It answers the question in terms of, what is the benefit we can provide to patients with the visual? That could be quite powerful from a marketing standpoint as well, as well as other trials that we could potentially contemplate. In addition, it allows us to broaden our CMC base, so having redundancy for our API as well as fill and finish, and to ensure that we have an appropriate amount of inventory to support the global launch. Last, and probably most important to this audience is, we have funding today to launch the drug independently in the U.S. Okay, and t hat would be around 2027. Our plan is to launch the drug in the U.S., with outcomes data in the public domain. Okay, p erfect. Thank you so much, Ian for chatting with us. Really excited about the company and the outlook. [Thank you].