Hi, good afternoon. Welcome to the 2024 Jefferies Healthcare Conference in New York. My name is Dennis Ding, biotech research analyst here at Jefferies, and I have the wonderful pleasure to have NewAmsterdam Pharma and Chief Financial Officer, Ian Somaiya, here with us for this fireside. Ian, maybe we can just kick things off with the overall kind of vision of the company. You know, I, you know, I don't think everybody's fully aware or familiar with the story, so why don't you just kind of kick us off there? Yep, and, Dennis, let me just begin by saying thank you for the kind invitation, and thank you all in the audience and online for for not only being interested in NewAmsterdam, but also, I think what we've increasingly found is, share our enthusiasm for the opportunity that we have. So just to answer your question, we are a company that's focused on the cardiometabolic space. Our lead asset, obicetrapib, is a CETP inhibitor that's in multiple phase III studies, and we'll spend quite a bit of time on that, I'm sure, in this Q&A session. The reason why we're excited about obicetrapib is the consistency of the data we've seen across multiple phase II studies and the drug's ability to lower LDL by upwards of 40%, and the benefit it provides beyond that. So we do view obicetrapib as LDL plus, and again, we'll, I'm sure we'll discuss that in greater detail. The opportunity we believe is quite clear. There are well over 30 million Americans with elevated LDL despite the availability of effective treatments and despite, you know, being diagnosed with the condition. So we do think there's a significant opportunity for any and all LDL or lipid-lowering therapies. Got it. And eventually, as you guys make your way through clinical development, and, you know, you guys are in a very unique and interesting position where you guys have 3 or I think 4 now major Phase III studies going on. So talk a little bit about, you know, those studies and some of the clinical catalysts coming up. Yeah. Let me begin by thanking our clinical operations team. Having been in your seat for a better part of two decades, it is the exception, not the rule, for companies of our size, and we are still fairly small, to conduct as many trials as we are conducting across the globe and to remain on schedule. That's really one of the you know the key characteristics of this company. It's just not only running on schedule, but also designing studies that ultimately will highlight the benefits of obicetrapib. As we look at our phase II program, we've had five phase II studies, which have fairly consistently shown a 40% reduction in LDL-C. Importantly, I would say even more importantly, we've been able to share with you safety data across the phase I/II program, which represents in excess of 800 patients, where the safety profile has shown a tolerability profile that's comparable to a true placebo. So that's really the goal of our program as we think about the upcoming phase III data release, to replicate those results. You guys will be reporting two sets of Phase III data in the second half. Mm-hmm. FH is coming in Q3. The bigger ASCVD Phase III is coming in Q4. Both will report LDL reduction. Can you comment on how... You know, what's the relationship or correlation on LDL reduction in FH, and is there a read-through to the ASCVD? Sure. So both of those studies have a 12-week primary endpoint in terms of LDL reduction, but we will be following these patients out to 52 weeks, and we'll report data for both of those time points in our initial press release. Obviously, we'll also make comments as it relates to safety at that time. So as we look at the heterozygous FH patient population, in the BROOKLYN study, it's a smaller study. It's a study in a patient population that's highly motivated. These are patients that have either had an event or had family members that have experienced events or died at an early age. So as we track the clinical trial execution of our study, what we're finding is very low rate of dropouts, very low rate of drop-ins, and compliance in terms of patients adhering to study drug. What that ultimately gives us is confidence in our ability to show a 40% reduction in LDL. And one other point I would make is, when we look at CETP inhibitors that have been developed in the past, anacetrapib, which is the Merck CETP inhibitor, had its best efficacy in the heterozygous FH patient population. So there is potential for our trial, the BROOKLYN study, to demonstrate the benefit above and beyond what we've seen in our phase II program, which is primarily limited to the ASCVD patient population. Remind us, what did Merck show in the FH study? Roughly a 40 or 41% reduction in LDL, versus roughly 20% coming off in the ASCVD patient population. Why, why was there such a large delta between the two? I think, look, a part of it is, CETP inhibition has, is... CETP is more highly correlated or highly expressed in these patients, so inhibition is going to show outsized results. I think the way we tend to think about this is, the benefit that we demonstrate in our Phase II, Phase III studies, whether it's BROOKLYN or BROADWAY, whatever the highest benefit is, in those trials, is what we'll be able to show on the label and what we'll be able to reference to clinicians. So, can you talk about, because since the FH readout is coming earlier, what is the top-line disclosure strategy that the company has going into Q3? Yeah, so we want to be consistent when sharing results across the two studies that you referenced, BROOKLYN and BROADWAY. So at the time of the press release, what you should expect from us is LDL reduction at week 12, which once again, is the primary endpoint. We also want to disclose at the time, week 52 LDL reduction, so you can see there's consistency in the benefit we're providing. We also want to be able to provide some insight into the safety. Don't expect an adverse event table, because the goal is to ultimately present the data and have a concurrent publication at a scientific symposia. As we think about the BROOKLYN data set, the conference we're targeting is one in the fourth quarter, so the conference we want to ideally present at is the AHA. As we think about BROADWAY and the data released later this year, in terms of press release, we want to target the ACC next year. Got it. That's very helpful. You made an interesting comment because the primary endpoint is indeed 12 weeks, but you guys will also be reporting 52-week data. Mm-hmm. How do you think the efficacy on LDL reduction evolved from 12 weeks to 52 weeks? And to take that one step further, why is that so important, given that you guys are also running a large CVOT? Yeah. So when you look at the lipid-lowering space, and this is data across different programs, mechanisms, what we find is high level of predictability going from phase II to phase III. So we don't expect our program to be any different. What I would also remind everyone is we've not conducted 1 or 2 phase II studies, we've conducted 5, and there's been a high degree of reproducibility in those results, and that's exactly what we assume as we move to a phase III study. A good reference point for our trial is another high-efficacy drug, the PCSK9, Amgen's Repatha, where we saw a consistent benefit from week 12 to week 52, and that's what we expect out of our study. And maybe another factor that we should always think about when looking at longer-term benefit is, what is the patient compliance in the trial? What is the impact of lack of compliance or dropouts or drop-in? And as we track those aspects of our trial, we're quite confident in the outcome because of how well these trials have been conducted. We're seeing very low rate of dropouts. We're seeing very low rate of drop-ins. And as we're able to measure patient adherence or compliance, we're also quite confident that that's not going to play a role in our studies. Right. So if you guys do report, let's say, 40% LDL reduction at 12 weeks, you would expect that to kind of generally stay consistent throughout the 52 weeks, and your reasoning is that because the safety profile is very good, compliance is very good, it's once-daily oral, et cetera. Is that fair? Exactly. And we're talking about a patient population with established disease. Especially true for BROOKLYN, but also quite true for the BROADWAY study, where we have a secondary ASCVD patient population with a mix of heterozygous FH as well. So one of the, you know, bigger Phase III studies that you guys are running is the cardiovascular outcomes trial, PREVAIL. You guys just completed enrolling just a month or two ago. Talk a little bit about that and what you're hoping to see, eventually when that data reads out. Yeah. So I think with PREVAIL, you're right, we completed enrollment. We announced that at the end of April. In fact, we over-enrolled. Our target was 9,000 patients. We enrolled slightly above 9,500 patients, so that puts us on track for data release towards the end of 2026, 'cause the trial has a minimum 2.5-year follow-up, which is the longest follow-up across cardiovascular studies, longest minimum follow-up. The median will be approaching 3.5-4 years. In terms of our expectation, and this is one of the things that we highlighted at our more recent R&D event, if we're able to reproduce the Phase II data, in terms of LDL reduction of 40%, whether you look at LDL or non-HDL or ApoB, we think we can improve on the highest efficacy drugs that are available today, which are the injectable PCSK9 inhibitors. When you look at Amgen's Repatha or Sanofi and Regeneron's Praluent, they both showed a 15% MACE benefit, and we think we have an opportunity to improve on that just based on the tracking of the factors that I mentioned, without really factoring in incremental contribution of the other aspects of our drug, whether we think about Lp(a), which we've shown an ability to decrease by 47%-57%, or the fact that our drug preferentially reduces small LDL particles. Got it. You know, when you guys were designing PREVAIL- Mm-hmm. you know, talk about some of the risk enhancer, those elements and, you know, other ways that you guys thought about in, you know, I guess, improving or increasing the probability of success. Yeah. So this, this is, you know, we are a unique company because we're led by two prominent KOLs, Michael Davidson and, John Kastelein, who have not only had a front-row seat at the table in terms of viewing, but they've been either an advisor or a clinical trial participant in really every study that's been conducted in this space. And there are many learnings from those studies, and the first and foremost is the benefit in terms of translating LDL reduction to MACE is highly correlated with the absolute reduction in LDL. So one of the design elements of the study is to enroll patients where the baseline LDL is high. In our PREVAIL outcome study, the baseline is 103, and that's well above what's been recorded or reported with other outcome studies. A good example of this would be Amgen's Repatha or Sanofi's Regeneron's Praluent, which were somewhere in the low 90s. So that's first and foremost. We also wanted to add risk enhancers to the trial such as patients who have diabetes. We also took note of results from the PCSK9s, which showed that patients with high triglyceride, low HDL also tended to do poorly. So these are all aspects of the study, and there was a population of patients that we wanted to exclude from the study. These are heart failure patients who have been hospitalized over the prior five years, because those are patients that are unlikely to benefit from a lipid-lowering therapy. So I appreciate that the CVOT, I think your guidance is that'll read out at the... or late 2026. Mm-hmm. Can you talk about what are some of your assumptions in terms of—because it is an event-driven trial. Right. So can you talk about how many events are you expecting? What is, sort of your expected event rate, and things like that? Yeah, so you're right, it is an event-driven trial. There is a minimum follow-up component to it, so that's the first trigger. The second trigger is a requisite event rate. And in terms of some of the other questions you asked, I don't. And I apologize in advance, I'm not gonna be able to provide that level of detail. But what I can say is, over the course of the next 12 months, we'll have a better idea of what the event rate is. The first year, there's a high degree of variability. There's a lot of noise in terms of the overall events in a trial. So over the next 12 months, we'll have a better sense for what the event rate is and what we're tracking towards. If necessary, one of the levers that we have is an ability to extend the study to get to the requisite events. At this point, we obviously don't believe that's necessary, but that's something we can consider as we continue to follow these patients and have a true sense for what the event rate is and ultimately what we want before disclosing the data or unblinding the data. Right. And, you know, for any event-driven study, you know, there's gonna be an assumption made on what that event rate is, and if you kind of look at Amgen's Repatha, the events actually accrued much, much faster than you anticipated. Mm-hmm. So I guess that's kind of where the 2.5 years minimum follow-up kind of kicks in, so that, you know, you can ensure that there's enough follow-up so that you could get a separation of the curve on MACE. Yeah. Right. Well, I think the way to think about the Repatha study is it's a lesson in what's the best way to drive events. One is to enroll a larger number of patients. As I mentioned, we're enrolling slightly north of 9,500. They approached 30,000. They were in a footrace with Sanofi-Regeneron to unblind their outcomes data and obviously disclose it in the public domain. In hindsight, what we learned from that study is that if they excluded patients who were followed for fewer than 12 months, which is approximately 9,000 patients, then the MACE benefit achieved with Repatha would have been 20% versus what they reported as 15%. So we do think this is a better way to drive event rates, and it's a lever, something that we'll be able to control as we continue to execute the trial. Is there an interim analysis built into the stats plan? There, there is not. The FDA would not allow for it, and, I think, this is, again, based on the history in this space where premature looks at the data have led to unfortunate decisions. You know, one can easily imagine if Lilly were to have conducted their trial for another year or two, they would've been, evacetrapib would've been the first potential CETP inhibitor on the market. Got it. So, if we kind of pivot over to the competitive landscape, right? There are many drugs in the LDL-lowering space that are in development, and one of the topics that come up in many of our discussions is around oral PCSK9. Yeah. So talk about your views on those drugs, one from Merck, one from AstraZeneca. We just had some interesting- Yeah ... data from AstraZeneca, one or two weeks ago. So talk about that and how NewAmsterdam would fit in. Yeah. And we couldn't be more excited to see the level of enthusiasm and excitement that Merck and AstraZeneca have conveyed as it relates to their oral PCSK9s. What this market has been missing is a presence from major pharma. And if you go back to the heydays of the statins, you had half a dozen companies, you know, making calls to clinicians, encouraging patients to be diagnosed, to be treated, and ultimately, that led to tens of billions of dollars in revenues for that class of drugs. And that's what we're missing today. So we are excited to see not only continued voice and share voice from Amgen, Novartis, but to see these new entrants. As you think about the drugs themselves, the similarities are limited to the oral delivery. They're all once-a-day orals. But beyond that, the differences are quite meaningful as it relates to obicetrapib. So our drug reduces LDL by roughly 40%. It also reduces Lp(a) by anywhere between 47% and 57%. That's based on our Phase II data. What we've also seen for the CETP class is a diabetes benefit, a delay or reduction in the incidence of onset of diabetes. When you think about the patients that we're going to be treating, vast majority of them who are on high-intensity statin, which is associated with a 36% increase in the rate of incidence of diabetes, this is a key feature, a key aspect of our drug that I think will be well received by by patients. So looking at the the oral PCSK9 data, Merck has shown fairly significant LDL reduction, somewhere between 50%-60% in their phase I study out to 14 days. But the drug also has a prominent food effect. It requires a patient to be in a fasted state for 8 hours. Once they administer their oral PCSK9, they need to, again, be in a fasted state for 30 minutes. If the patient is not compliant, the efficacy is cut in half. So as we think about the patient population, a person that's in their sixties or early seventies with other comorbidities, this is a patient population that's going to be taking a lot of other treatments. We believe in the real-world setting, this is going to be challenging. In a clinical trial setting, I think you know we all expect Merck to execute a trial and to produce solid results, but in real-world setting, this could be quite different. And now, looking at AstraZeneca, we saw their phase I data earlier this week, and what we saw was with the PCSK9 the monotherapy data. And so monotherapy, looking at week 4 compared to baseline, what we saw was a 30% reduction with a 30-mg dose, and roughly a 34% reduction with the higher dose. So, on average, what the company demonstrated was a 30% reduction across those two arms. So this is obviously much lower than what we have seen. And with all PCSK9s, the benefit is limited to LDL, versus our therapy, where we're seeing a more prominent effect on other risk factors, such as Lp(a), such as small particle size, and the diabetes benefit. Right. I think, you know, to kind of circle back on what we discussed before, just around compliance- Yeah. In cardiovascular, this is large primary care market. Compliance is generally around 50%. If you make it harder to take the drug, people are not gonna be compliant. Mm-hmm. Especially over, like, a longer-term CVOT that Merck is doing, you know, how do you think about compliance over three years? Yeah. 4 years, right? Yeah. So I think that's a great point, Dennis. We are talking about a patient population with an asymptomatic disease state. So to request someone or require someone to change their lifestyle, change how they eat, what they have for breakfast, when they have breakfast, and also, you know, when they take their concomitant medications, it's a significant enough change. What we do think, over time, especially in an outcome study, it's going to have an impact. Right. And then for AstraZeneca, their 30% LDL reduction is a little bit weaker than what you guys have at 40% plus. Mm-hmm. No food effect, that's good, but overall, the efficacy is probably a little bit lower than what you would expect. Yeah. And despite the more modest benefit or the efficacy that AstraZeneca reported, what, what AstraZeneca has suggested is that this translates to a $5 billion revenue opportunity. So we're very excited about both of those numbers, and maybe a little bit of onus on for you to make some adjustments to your estimates. So, if we kind of take a step back and look at the cash balance, you guys, you know, remind us how much cash you have- Yeah ... your runway. I mean, you got some pretty big catalysts coming up- Right ... over the next few years. Yep. So as of the end of the first quarter, we're at $481 million in cash. We have cash to get through all the four Phase II study, Phase III studies, three that we discussed, one that we didn't. So we have cash well into 2027, and it's an exciting position to be in, so we can really focus on the execution of our clinical trials, generating the clinical data, and ultimately translating that to commercial success. Last question for me is your commercial strategy? Yeah. Right? I mean, if you guys have your phase III data at the end of this year, you know, why not file for approval and launch in late 2025? And maybe talk a little bit about Europe and your partnership with Menarini. Yeah. So we are in a unique place in terms of timing. We have the potential to be the first company to have not only the LDL data, but also the outcomes data at the time of launch. And we believe that's going to be quite critical to really capturing the market. One of the challenges of CV has always been drugs get off to a slow start. Partly, it and largely, I think it's driven by the inferior product profiles of the drug in the fast in the past, but it also... We also need to be aware in the U.S., payers restrict access. And one of the ways we can circumvent that is to have outcomes data available at launch. And from a timing standpoint, it represents roughly a 6-month delay in our filing. We also live in a world with IRA, so we do want to maximize the period of time that we have with our product, and getting off to a fast start is critical. So then you guys would, I think, the goal is to get approved in, let's call it early 2027 or first half 2027. By then, you would already have the CV outcomes data, hopefully, and that would help drive some of the commercial uptake, at least initially. Yeah. Yep. So based on our conversations with payers, they want to see the outcomes data in the public domain. They do not need it to be part of the initial label for the product. So the first half approval and launch supports that. Okay, very good. Well, I think that's all the time that we have. Thanks so much, Ian, for hanging out with me today. All right. Thanks, Dennis, and thank you, everyone.