Praxis, who's gonna run through a presentation. Megan?
Thank you. Thank you. Hi, good afternoon. I'm Megan Sniecinski, the Chief Operating Officer at Praxis. Building on a remarkable 2025, we've continued executing across our portfolio in our journey to become a commercial company, and we're gaining momentum across all of our four late-stage assets. These are our forward-looking statements. Everything we do at Praxis comes back to one thing: accelerating the delivery of life-altering therapies for patients suffering from CNS disorders, many of whom have been waiting for decades.
Looking at our near-term horizon, what's ahead for us this year sets us up well to deliver on this mission. I wanna use our time today to share more about what's happening across each of our programs, what we're excited about, and what lies ahead for the company. Our broad pipeline has several near-term catalysts, and we're heads down executing to deliver on them.
Our Ulixa NDA and essential tremor is under review with a PDUFA date late January 2027. Ahead of that, we have our NDA for relutrigine under priority review with a PDUFA date in late September. At our earnings call last week, we also announced that recruitment was complete for our EMERALD study in broader DEEs, with top-line results reading out in the fourth quarter of this year. Looking to vormatrigine, we have our POWER1 phase III study readout this quarter, and we'll be initiating the POWER3 monotherapy study, a milestone this community has been waiting for, using all of the existing exciting features of the vormatrigine profile to deliver on what patients need. Later in the year, we'll complete the POWER2 phase III study.
Enrollment's progressing well. We're on track to finalize it later this year and report early next year. Looking at elsunersen, we recently reported results from our EMBRAVE Part A study. EMBRAVE3 is now enrolling and expected to complete in 2027, serving as the registrational trial for our NDA filing. We're building towards four first and best-in-class CNS therapies over the next two years, representing more than $20 billion in peak sales potential. Our cash position of $1.4 billion at the end of March positions us well with a runway into 2028, putting us beyond the launch of relutrigine and Ulixa and giving us the resources we need to continue executing and creating value for patients. Let me start with ulixacaltamide and essential tremor, a disease that's been completely neglected for decades and where we're about to change everything.
Essential Tremor is one of the most common movement disorders affecting 7 million Americans, and yet there has never been a single FDA-approved therapy specifically for this disease. ET patients struggle to write their name, to eat with a spoon, have a hard time even pouring a glass of water to drink. These are not minor inconveniences. These are devastating daily losses.
We estimate approximately 2 million patients are seeking treatment and seeking a therapy that can meaningfully improve their daily function. This represents about a $10 billion in peak sales opportunity in the U.S. alone. Our Essential3 program was comprised of two phase III studies, a placebo-controlled parallel group design, and then a randomized withdrawal study design, with a very unique design feature that allowed study allocation and treatment allocation to be fully blinded between participants, study staff, and investigators.
At AAN last month, the Essential3 program was awarded the Abstract of Distinction in Movement Disorders, a very meaningful recognition for a study at the most important neurology congress in the U.S. During the plenary presentation, we showed the baseline disability of the trial participants, which mirrors what's seen in clinical practice. What stands out is that over 90% of participants reported worsening in the last three months. This speaks to the progressive aspect of the disease. In the data on the chart you see here, you can see the extent of significant disability across everyday activities that these patients experience. Essential tremor impacts all aspects of functioning. With the unmet needs so high, we are thrilled Essential3 is the first successful phase III program for a drug in essential tremor.
Both phase III studies were positive, with clinically significant and statistically significant results across both primary and secondary endpoints. On safety and tolerability, we saw no drug-related SAEs, and the treatment-emergent AEs were mild, occurred early during titration, and resolved. What physicians tell us is that they feel very comfortable managing these side effects in the context of proactive patient counseling.
At AAN last month, we also shared further data supporting the rapid, deep, and consistent drug effect we observed across activities of daily living and other outcome measures. Patient-reported and clinician-assessed outcomes all move in the same direction, it's this kind of consistency that really builds physicians' confidence. When we look at the extent of response in our combined analyses, we see remarkable gains in functioning. These results were statistically significant at all responder thresholds, this real robust data represents true functional gains for patients.
To have nearly half of the patients regaining four points is remarkable, and that's why we're seeing strong interest and engagement from the medical community. Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of Essential Tremor and ulixacaltamide. We surveyed over 2,000 physicians in the U.S. who collectively manage over 40,000 ET patients, and the results were beyond encouraging. They validated Ulixa's profile across efficacy, the breadth of benefits, as well as the tolerability profile. It's clear Ulixa addresses a need physicians have felt for decades. The pent-up demand is real and reinforces the $10 billion peak sales I mentioned earlier, and also demonstrates the real need for a drug like Ulixa in the market.
We also surveyed almost 1,300 patients. The activities they told us were impacted most are exactly the activities where Essential3 showed benefit. It's truly exciting to be at a place where there is such alignment between the physicians, the patients, and the results of our program. We're full steam ahead on our commercialization and build. We have our leadership in place, and the field force hiring is on track for completion well ahead of the launch, where we want to have the field teams in place and trained well in advance of our PDUFA date. We continue to expand and build the commercial infrastructure across all commercial areas.
We've also successfully established a distribution network to ensure drug availability at launch in sufficient levels. We continue to engage with the healthcare professionals, including launching the ESSENTIAL to me disease state awareness campaign last month at AAN. Now turning to vormatrigine, our common epilepsy program. Vormatrigine is the most potent and selective sodium channel modulator ever developed in epilepsy. With over 3 million patients affected by this disease, we see a third, over a third, are changing their medications each year. Nearly two-thirds have to be on two or more anti-seizure medications. The patients are simply cycling through treatment options that don't work well enough. They deserve better. This represents the differentiation vormatrigine can bring to patients. It goes well beyond just the efficacy. It's once-daily dosing, no food requirements, fast-acting, no titration, and minimal DDI risk.
These are the features that physicians and patients have been asking for. We know physicians need more good drugs for their patients, and vormatrigine represents that real differentiation, and we're positioning it for broad foundational use in the treatment paradigm. At AAN in December, we presented the full data from our RADIANT study, where vormatrigine demonstrated best-in-disease potential in focal onset seizures. vormatrigine has fast-acting efficacy without the need for titration, and the effect continues to increase with more treatment time. Additionally, we saw that vormatrigine improved efficacy on top of other common anti-seizure medications that patients were taking. As I mentioned earlier, there are three key milestones in the near future for this program.
The first is the readout of POWER1 study this quarter. POWER3 is set to generate data in the context of monotherapy treatment, which the majority of the market really needs. Enrollment is progressing well in our second phase III study, POWER2. We're on track to finalize that this year and read out early next. In our DEE programs, we have two complementary assets that together have the potential to address real need in epileptic encephalopathies. relutrigine stands to become the first approved therapy specifically for SCN2A and SCN8A DEEs, severe childhood epilepsies where seizures can begin in the first weeks of life and where nothing works for these children. Our clinical profile is ideal. It's once daily, no titration is needed. A pediatric-friendly formulation that can be given orally. It's designed for families caring for severely ill pediatric patients.
The EMBOLD study was stopped early at interim, where we delivered overwhelming efficacy, and we saw relutrigine treatment leading to a clinically meaningful and statistically significant change in seizure frequency and associated developmental endpoints like disruptive behavior, alertness, and communication. Beyond these impressive results, the effect of relutrigine was rapid, durable, and continued to deepen with time. The strong efficacy results and a favorable safety profile really underscore relutrigine's best-in-class potential.
Looking at DEEs broadly, you simply cannot have seizure activity without participation of the sodium channels. Across all DEEs, regardless of the underlying genetic etiology, hyperactive sodium channels are in the pathway, and relutrigine addresses that common mechanism. The current U.S. DEE market is over 200,000 patients, approximately 20 times the initial 2A and 8A population. If EMERALD is positive, this becomes one of the largest rare disease commercial opportunities we know of.
We shared last week that recruitment of EMERALD is complete in record time, and it's clear caregivers, patients, and investigators share our view of the potential of relutrigine. Our top-line readout for EMERALD will be the fourth quarter of this year. We build the foundation with the potential launch of 2A and 8A, and the results of EMERALD later this year, if positive, will significantly expand the commercial potential for relutrigine by severalfold.
Let's talk about elsunersen, the first ASO in our platform. We recently presented exciting results from our Part A study, and we're thrilled with the impressive seizure reduction, as well as disease-modifying components that we saw. The overall data from the EMBRAVE program and open label ex-extension, as well as our emergency access program, really set up the potential for this to be a transformational drug in DEEs.
In conclusion, we are off to a great start with momentum across all of our clinical profiles programs. We're on track for our commercial launches in both relutrigine and Ulixa. When we're backed by a strong balance sheet and a broad IP portfolio across our programs, we continue to be focused on our execution and delivering innovative therapies for CNS. Thank you.
Of our annual healthcare conference in toasty Las Vegas. I'm very pleased to have join us the team from Ligand, Todd Davis, CEO, Tavo Espinoza, and Lauren Hay. Thank you so much for joining us.
Yeah.
Todd, maybe just to start broadly for those who are newer to the story, can you give us a brief overview of Ligand and its royalty model?
Sure. Yeah. I think today we have a royalty portfolio about over 100 assets, about 30 commercial. About 12 of those are really driving our growth right now. Things like FILSPARI, OHTUVAYRE. KYPROLIS is hanging in there. It's been there a long time. It's a pretty broad and diversified set of cash flows generating a little over $200 million a year in cash flows. We recently announced a proposed merger or acquisition with XOMA, which would just about double that portfolio at another seven commercial assets, 14 late-stage assets. It's aggregating fairly quickly. That'll take us closer to about $300 million in cash flow. The profile of the company is we have less than 50 employees.
To investors, I think we are a royalty aggregator, they would call us. We use several different techniques to do that. We use royalty monetizations, project finance, and what we call special situations. Either create or acquire the royalties over time. We have an investment pace of about $200 million a year. Our average investment size is kind of in the $20 million-$60 million range. We're trying to build a diversified portfolio, so it's the portfolio math and the our risk assessment that assesses the kind of the size that we're willing to do in any given situation.
We have gone up to 100 on certain very low-risk assets, and of course, some is much larger. We view diversification not by deal or by company, but by the number of assets. That's how we're building the company out. For companies, they really think of us as a capital provider or co-funder of clinical studies. We do focus on late-stage clinical. Majority of royalty capital is commercial stage. That's what we're looking for, are assets with very high unmet clinical need and with teams that can manage them because we like to be passive investors.
Just opening up this to the entire group, but what is it about that $20 million-$60 million range that's ideal? And then kind of secondary to that, when you think about your competitors, is it other aggregators, or is it the primary markets? Is it, is it private equity?
Yeah, I'll kick this off and then let Lauren weigh in. I think that the 20 - 60 is really driven by portfolio math. We're trying to create a diversified portfolio. As the value of our portfolio grows, we can go up. You know, there are a couple other kind of royalty funders out there, and they're quite large. Being smaller in size and focus differentiates us within the market. We're really providing capital mostly to kind of late-stage private, up to mid-cap companies, and that deal size fits very well for that, so it's differentiating.
I think a good analogy would be the $100 that I took to the blackjack table last night. I, you know, I didn't want to put it all on one bet, so I divided it by $5 at a time. We just, you know, want to diversify so that you know, you don't use up your whole bankroll. Our bankroll, $1 billion on the balance sheet entering this year, mostly cash, and we have access to a, you know, revolving credit facility. I think a lot of that also informs our limits on what we'll deploy.
I don't think I can top that.
Did you make money?
You don't play blackjack? I always double down on 12.
I'm impressed you could find a $5 table.
Circus Circus.
One of the more common questions we've received from investors is what's the best way to value the company? I think what's unusual about your organization versus a typical sort of biotech is that, you know, you have this regenerative property, that the proceeds that you make from your investments can fund the next round.
Yeah, I think most of our investors are generalists, and we're trying to build a company. The company is the product, and the market is investors. That is a good fit for generalist investors that want exposure to biotech, and they should value us the way they value a lot of their other investments, which is as a multiple of profits. I think we're probably around 15-ish or so, but we're growing at over 20%, so I think that's a pretty good deal. I'm not a portfolio manager, so they have to reach their own conclusions on that. You know, the other key thing is perpetuity value. You know, we have both a very good team that can execute on this. I think we've demonstrated that over the last three years as we've built that out.
Also the portfolio. You know, we're mostly valued on our commercial assets. You know, that's the tip of the iceberg. There's a lot of iceberg under the water in the company, so I think it's quite robust. The market we're addressing, there's lots of other alternatives for the companies that we deal with because they usually have alternatives. There's high demand for the capital that we're providing.
I'll just add, we do put out five-year guidance every December at our Analyst Day to give investors a little bit of a sense of, to your point, how to value the future growth of Ligand. To give it a little bit more granularity on that, you know, our existing commercial portfolio, we expect will grow at around 20% year over year for the next five years. Above that, we have about 5% that we call our farm team. Those are assets that we already own that are pre-approval, and they're pretty heavily risk-adjusted. That contributes another 5% to annual growth. Beyond that, we estimate around 3% annual growth for a new deal flow.
When we get to December of this year, we'll have updated guidance. Importantly, within that 5% farm team, we had two major catalysts this year. The first was the approval of FILSPARI and FSGS, where we have a 9% royalty. That was pretty heavily risk-adjusted in that farm team section. Then Palvella generated positive phase III data in QTORIN rapamycin and MLM. That, you know, farm team contribution, some of that will move down into the commercial section with FSGS. Then, you know, as we go back to risk-adjust that Palvella segment, that'll grow as well. It's a nice kind of, you know, predictable compounding growth story that we're generating.
Yeah. Maybe, Lauren, again, the team has pointed to Ligand's investment team as a key asset and a key source of differentiation. You know, what is it about the team that makes it unique? What is it about this group that allows you to have that conviction and that trajectory moving forward? 'Cause those are some healthy growth projections.
Yeah, you know, certainly you can weigh in here too, but we've really assembled a pretty diverse team. That's been intentional. When you're underwriting pre-approval investments, you need a lot of different areas of expertise around the table. Because we're a publicly traded entity, we have a lot of flexibility in terms of the transaction structures that we can deploy to really kind of customize our investment structure to our counterparty. You know, we have five deal leads.
We've recently just hired two of those five, we expect our investment pace to accelerate from here. We have people from private credit backgrounds. You know, Todd came from a commercial royalty investment background and growth equity. Michael Vigilante came from growth equity. We have kind of people from across the cap stack around the table, as well as deep scientific and medical expertise and commercial expertise. We're really able to kind of, you know, diligence any type of deal that comes into us and structure around it appropriately. Feel free to add to that.
I think that was well said.
Tavo, maybe one for you. When you think about something Todd said earlier about, you know, the overall structure of the company and the scalability of it, when you're looking at your margin growth, you know, where can that take us given these, again, very healthy growth outlooks, but the fact that, you know, overall there's not much needed to run the business?
Yeah, I mean, that's part of the beauty of the model, right? We are growing the top line, in particular the royalty receipts line at, you know, mid 20% compound annual growth rate. In fact, to be more specific, we came out in December at Investor Day and told investors that we expect to grow that line at a 23% compound annual growth rate over the next five years. That all sits on a base of about $45 million in operating expenses that are growing at the rate of inflation. We did double down a bit this year in 2026 to build up the team just given the opportunity set that's out there. Corporate profit margins are in the 80% plus here and growing from this base. It's quite powerful compounding operating leverage.
Excellent. Maybe one more on overall strategy, but when you evaluate potential opportunities, what tends to factor most in your decision-making process? Is it the probability of approval, commercial peak sales, time to royalty inflection? I mean, what's driving those decisions?
Yeah. The product criteria really are strong evidence of safety and efficacy addressing a very high unmet clinical need. When you're doing royalty investing, there are some subtleties about it in that you're really investing in the product. If the company's acquired, that's not an exit for you're in the product. You're in it even if it changes hands. When you're investing on the development stage, there's no label yet. Your forecasts are really estimates with some error bars around them without a label. You really wanna be solving big clinical problems, which reduces your commercial risk. We really kind of focus on that. Those are the main kind of asset criteria.
One of the things that differentiates royalty investing is that we're able to do all of our diligence, typically under CDA with our counterparties. We're getting access to FDA correspondence, you know, clinical trial information that's not necessarily out in the public domain, CMC information. We put a lot of time and effort into underwriting each of our investments with access to information that isn't available to, say, a public equity investor.
Got it. Maybe just one briefly on the XOMA acquisition. There are over 120 assets that are being added to your portfolio, you know, both commercial and late stage, but how are you thinking about prioritization across such a large portfolio? Obviously, there's a huge boost to the overall core assets, you know, any thought that you might need to spin out some, sell some off, bring on more people?
Well, I'll let Lauren weigh in on this as well, but we've really been setting up over the last couple years to absorb a significant number of assets. The reason that our OpEx and profitability is very favorable is because there's a lot of infrastructure in the industry, there's a lot of good teams in the industry, and there's a lot of good assets. We partner all of that. We try to avoid absorbing a lot of infrastructure.
What we're really absorbing in most of our acquisitions or in investments are passive contractual rights. Now we're constantly reworking the portfolio, reprioritizing. We'll follow on with our investments. I think we've invested in every round at Palvella on the equity side since we did the royalty investment. We support our companies because we believe in the asset and the team and the royalty value. You want the equity rounds to go well. We coexist with equity. We're within the kind of the ecosystem. That takes a lot of portfolio management, which is Lauren's main charge.
Yeah. The XOMA team has done a great job of assembling a really compelling royalty portfolio over the years that we think is a kind of a really important and critical point of inflection that has really nice synergy with the Ligand model to focus on more kinda mid to late-stage clinical investments. You know, we're kinda focused right now on three commercial drivers. They have 14 late-stage programs. Importantly, one of the major areas of focus for us after the close is gonna be looking to identify situations where we can leverage the Ligand balance sheet to accelerate the development of those assets.
We've already done that once, with the recent, closing of a elafibranor investment, and that's gonna be an area of focus for us, is to look where we have assets that we have a lot of conviction in and where we can deploy, capital and then potentially leverage external capital to try and accelerate the path to market for some of those products.
Got it. Maybe just a final couple of questions on the commercial portfolio right now. Great growth drivers in terms of FILSPARI and OHTUVAYRE, but I guess in terms of the confidence and the durability, especially, you know, given there is some quarter-to-quarter variation, I think you saw some in first quarter of this year. You know, what gives you sort of conviction moving forward and how do you manage that sort of maybe lumpiness in some of these assets?
The main lumpiness in our business comes from either product seasonality, which varies product to product. You know, in for example, at the beginning of the year, there's copay resets and some prescription areas go down a little bit. I think the key thing for us is just to manage expectations. Those are very durable assets. One of the beauties of the pharmaceutical industry is we're granted legal monopolies in the form of patents.
They're quite durable if they provide a lot of clinical value, which is what we spend a lot of time analyzing. That's one. Then we have milestones in a lot of our agreements. Those can be chunky. We just try to predict those the best we can. Overall, that, you know, the royalties, you know, with the underlying IP focused on high clinical value, I think is one of the most durable business models.
Maybe a final one. You know, there's been a lot of discussion, I think between you and investors on the current commercial growth drivers. You know, when you think about some of the considerable optionality that you have, are there some underappreciated late-stage assets you've really got your eye on that could be, you know, an overlooked driver?
Yeah. Lauren, why don't you take that?
Sure. We're really excited about Palvella's QTORIN rapamycin. We earn a tiered 8%- 9.8% royalty on that program. They have positive phase III data in microcystic lymphatic malformations, which is a rare dermatological condition with no FDA-approved treatments. They're gonna be starting a phase III in cutaneous venous malformations later on this year. Collectively, management estimates that across those two indications, they're looking at a $1 billion-$3 billion opportunity. The team is really executing extremely well. Great MLM data, that phase III study that surpassed even their kinda high case expectations. There was a recent announcement from our partner, Orchestra BioMed, yesterday. We have two device investments with them on the AVIM pacemaker-enabled technology and then on the Virtue Sirolimus AngioInfusion Balloon .
They've announced that they expect recruitment to complete in the AVIM pivotal study at the end of Q3. One final phase III asset is lasofoxifene. It's a SERM that is now being developed by LeonaBio. They expect enrollment to complete in the phase III program by the end of the year. We'll have data probably in the second half of next year. Management estimates that'll be a $1 billion product, and we have a tiered 6%-10% royalty on that, so around an $80 million annual royalty to us. You know, just across those three late-stage programs, we're looking at really, really material royalty revenue potentially coming out of that farm team segment.
Perfect. Well, I think that's it for time. Todd, Lauren, and Tavo, thank you so much for joining us.
Thanks for having us.
Thanks for having us. Thank you.