Thank you all. Our next presentation is from HLS Therapeutics, so please give a warm welcome to Craig Millian.
Great. Thanks, Shubs. Appreciate the invitation to speak this afternoon. Craig Millian, I'm the CEO of HLS Therapeutics. Been with the company since May of 2023. Got some colleagues in the room with me, Brian Walsh, who's our Chief Commercial Officer, and John Hanna, our CFO. If we get any tough questions, I'll send it to them. I will make some forward-looking statements. HLS Therapeutics is a North American specialty pharmaceutical company. We are a Canadian-based company. We have operations and generate revenues in the U.S. and Canada. We are focused in two therapeutic areas, neuropsychiatry and cardiovascular. You can see what our revenues and EBITDA were in 2025. That's in U.S. dollars. We're listed on the TSX. Market cap, roughly CAD 140 million. We don't do organic research and development. We acquire our assets through partnering or in-licensing or purchase.
We really focus on both Canada and the U.S. We are a relatively young company. We are actually celebrating our 10-year anniversary just this month, so happy birthday to us. We have a diversified growing portfolio. You can see most of the products that we commercialize are in Canada, with the exception of Clozaril, which is in both the U.S. and Canada. We consider ourselves to have very strong organizational capabilities in cardiovascular and neuropsych in Canada and think we're an attractive partner and have had some success in terms of generating partnerships with some really great companies, originator companies. I'll drill down into several of these assets in future slides. In terms of why we think this is an interesting time to be thinking about HLS, really three reasons.
The first, I would say, is over the past couple of years, we've had an intense focus on improving the efficiency and productivity and profitability, frankly, of our operations and really strengthening our financials. Certainly improving our cost structure, but also really strengthening our balance sheet to give us more flexibility. This year, we are launching or have launched in the last few weeks a very exciting medicine called Nilemdo into the cardiovascular market. We'll talk more about that, but we have great expectations for that asset. We think we're set up extremely well to move from a focus really on efficiency and profitability and getting our operations in order now to really a focus on accelerating growth in the years to come, and we think we have the right portfolio and the right team in place to do that.
Really starting with that first statement around strengthening our operations and financials. I won't get into detail in terms of what we did just for the sake of time, but these are essentially the results. On the left, you can see this is a chart of adjusted EBITDA net of royalties. This is really EBITDA generated by our promoted product portfolio. This is a trailing 12 months ending each quarter. You can see over the last two years, we've seen a consistent improvement in terms of the profitability of our product portfolio. This is really a combination of both growing top line but also removing excess cost. On the other side of the slide, you can see over the last three years, we've also made tremendous progress in strengthening our balance sheet and de-levering.
When I joined the company, we were at about $80 million of net debt, and we've cut that by half. We're under $40 million now, which with a much lower leverage ratio, gives us far more flexibility in order to do different things with our capital than we were able to do when I first joined the company. If you combine the growth in adjusted EBITDA with the de-levering and the considerable decrease in interest expense, we're generating more cash than ever, and you can see last year, we increased our cash from operations by 114%. If we switch gears a little bit, that's a little bit of the overview of the work we've done really to improve our operations and generate a stronger financially-oriented organization. Really on a go-forward basis, what's going to drive performance is going to be this product portfolio.
This visual is a little bit of the vision of how we see the company evolving in the next few years. Clozaril is our drug for treatment-resistant schizophrenia. It's been around for 30 years and continues to deliver consistent revenue, profit, and cash. Has done so for many years, and we expect it to continue to, and it serves as a really strong foundation for our company. Layering on top of that, Vascepa product in cardiovascular that we launched in 2020, which continues to grow, and we consider it to be a growth asset for us and one that's become more and more profitable for us. We'll talk about the two newest assets, Nilemdo and NEXLIZET, are products that we brought in last year from Esperion, in-licensed in Canada. Nilemdo just launched a few weeks ago. NEXLIZET we expect to launch first part of 2027.
We think that we're going to see significant growth from these assets, likely, we believe, doubling potentially the size of the organization over the next few years. Just double-clicking on some of these medicines, I'll go relatively quickly through some of the older ones. For those of you who are familiar with the company, you know Clozaril r emains the only approved clozapine. The generic is the only approved treatment for treatment-resistant schizophrenia. There's been a lot of new developments in the field of schizophrenia, but none of these medicines really have the efficacy or are garnering the indication for this very difficult-to-treat patient population. They remain undertreated, only one in four, so there actually is still headroom, despite the fact that clozapine's been around a long time, we still think there's room to grow. We compete in Canada and in the U.S. in a generic market.
Despite the fact that clozapine has been a generic market for about 20 years or even longer, our branded Clozaril still enjoys roughly a 50% market share in the Canadian market. We generate something on the order of the mid-30s in terms of millions each year in terms of revenue, with about a 75% operating margin. This really creates a very strong financial foundation to allow us to leverage those resources to do other things like BD. But the question is, how do you maintain 50% market share over time on a branded drug in a generic market? It really comes down to in Canada, somewhat of a competitive moat that we've been able to build around Clozaril through our services and our technologies, which we think are quite differentiated. In Canada, there is a mandatory patient registry.
Any patient starting clozapine has to be enrolled into one of the manufacturer, either the brand or the generic registry, and these are quite different. They're quite bespoke. Ours is called CSAN. We integrate within our CSAN registry state-of-the-art technology, in this case, CSAN Pronto, which we make available to our accounts free of charge. The key barrier to treatment of treatment-resistant schizophrenia with clozapine is the need for frequent white blood cell count monitoring. In the first year alone, a patient needs to be subjected to 39 needle sticks to test for their white blood cell counts, which you can imagine this vulnerable population is quite cumbersome. CSAN Pronto is a point-of-care finger stick device that can be done right in the physician's office.
Results are achieved within a few minutes, as opposed to having to send a patient to a lab for a venous blood draw, again, almost 40 times in the first year alone. This is a real value add that is quite patient-centric. Moving along to talk a little bit about our cardiovascular portfolio, which we believe HLS is building really a premier cardiovascular medicines portfolio within Canada, and we think we are on our way to becoming a leading Canadian cardiovascular company. These are quite remarkable medicines. Vascepa, which is the product we've in-licensed from Amarin in Canada, launched back in 2020. Nilemdo, again, launched just in March, and NEXLIZET we expect to launch early next year. There's a number of commonalities across this portfolio. First of all, these are not competitive products.
Vascepa operates very differently than Nilemdo and NEXLIZET, so these are very much complementary and in some cases even synergistic medicines. They are first and only in class, so they're quite unique. This is an all-oral portfolio, very well-tolerated. Each of these medicines comes with evidence from large cardiovascular outcomes trials, which is quite unique in that many medicines launch just with biomarker data, and it takes them many years to generate outcomes data. The reason we have that outcomes data is because these medicines have all been on the market for many years in the U.S. and Europe. We benefit from that experience, that real-world experience, that very great clarity around the safety profile of these medicines. No surprises, and obviously all of them have had tremendous commercial success. Gives us great confidence when we bring them into the Canadian market.
Again, because they've been on the market for a number of years, they're already well-known and integrated into global treatment guidelines, which gives us a head start. In the case of, for example, Nilemdo, bempedoic acid, the generic name, is very well-known among cardiologists and other specialists within the Canadian market because they go to the meetings in Europe and the U.S., and again, these medicines are in the guidelines. Importantly, with Vascepa, our cardiovascular sales and medical organization was a one-product field-based organization. Now we're able to now leverage that organization with three medicines. Obviously amortizing the cost of our field organization and our other capabilities across multiple assets allows us to become that much more efficient. These products have a high degree of overlap in terms of the go-to-market model, the call point, et cetera.
Even from a messaging perspective, they work in an orthogonal fashion. They're all under the umbrella of optimizing cardiovascular risk for patients at risk, but they do it in different ways through different mechanisms, so highly complementary. Starting with Vascepa, this is data from REDUCE-IT. This is a product that is indicated for patients who present with elevated triglycerides and other risk factors. Either they've had a cardiovascular event or diabetes and other risk factors, so a high-risk patient population. What's interesting about Vascepa is that it was studied in patients who were already on optimal doses of statin. So statins treat LDL cholesterol, which is the primary risk factor that doctors are trying to manage in an at-risk patient. You think of LDL blood pressure, those are the things you manage. That takes out already, reduces risk of an event to a very large degree.
To be able to produce another 25% reduction in cardiovascular events on a patient who's already being optimally managed for their LDL cholesterol is quite remarkable. Of note is actually cardiovascular death was reduced by 20%. In and of itself, this was part of a composite endpoint, but this in and of itself was statistically significant and highly clinically significant, because I think the ultimate goal of any medicine is to reduce death. This is data that's really second to none and has been the engine that has driven the performance of Vascepa in the U.S. and other markets, but certainly in Canada as well. Launched in 2020, and you can see even in 2025, continuing to generate very robust double-digit growth in demand as measured by prescriptions and prescription units, and we continue to see that into 2026.
Of note, for the first time in 2025, Vascepa actually made money for HLS. We've been investing in this asset for many years. For the first time in 2025, we actually saw a positive contribution towards adjusted EBITDA that now has expanded. It's a growth asset that's growing profitably, and we continue to see margin expansion in the years to come. Importantly, this has a patent expiration or an IP that runs out through the late 2030s. We think we have a very long runway to continue to enjoy the growth of this asset.
Beyond Vascepa, which we've had since 2020, we brought in these two medicines from Esperion, Nilemdo, also known as bempedoic acid, and NEXLIZET, which is bempedoic acid in a fixed combination with a drug called ezetimibe, which is a product, an oral non-statin that's been on the market for many years, that's commonly used. Nilemdo is oral. It's a non-statin. It's been studied in a large outcomes trial where it showed strong outcomes data, lowers LDL cholesterol, can be used with other therapies. I guess the special sauce here as it relates to Nilemdo is that it works on a pathway that's similar to statins in terms of mechanistically, but it works further upstream, and you don't see the side effects that are most problematic with statin use, which is kind of muscle aches and pains, myalgias. These are really more than nuisance side effects.
These are often side effects that limit the utility of statins, often lead to patients dropping off treatment or not being able to tolerate up to higher doses of optimal statin. There's a real unique place for Nilemdo. Nilemdo was approved late last year. We launched it in March. We just kicked off with our sales force in April. NEXLIZET is under review with Health Canada. We're in the process of submitting some additional data they requested, and we expect that to be approved and launched in the early part of 2027. Just a quick comment on why LDL-C matters. You can see here an artery getting full of plaque, which is generated by these LDL particles, among other atherogenic particles. What we find is LDL is probably the most studied and validated biomarker in all of cardiovascular medicine.
Incontrovertibly, elevated LDL is associated with increased cardiovascular risk, and every millimole per liter drop is associated with significant reductions in cardiovascular events. The guidelines continually are evolving to suggest lower and lower is better and better, especially for patients at greatest risk. Surprisingly, most high-risk patients don't get to goal. You would think that in a market that's been around for quite some time, and you think about statins have been around for decades, there's still quite a gap in terms of the number of patients getting to their treatment goals and really minimizing their cardiovascular risk. This is where these new products fit in.
Nilemdo has a broad set of indications, and if we think about the NILEMDO or the NEXLIZET patient, again, NILEMDO being bempedoic acid, NEXLIZET being a combination of bempedoic acid and ezetimibe, you start with in Canada, again, we've licensed these products in Canada, about 5-6 million at-risk Canadians who either have cardiovascular disease or at increased cardiovascular risk. 3 million of those are on statin, w e're not going after all of those. We're going after a very well-defined subset of those patients. Either those who are on a statin and/or ezetimibe who are unable to get to their LDL goal, or an equally large, maybe even larger group of patients who can't tolerate statins or can't titrate up to a dose of statin that is optimal because of side effects.
Again, as I mentioned earlier, you don't see those muscle side effects with bempedoic acid that many experience on statins. Conservatively, we estimate that to be 500,000 patients. I can say there are other sources I could cite that would say something even greater than that, but I think we're trying to be conservative in our assumptions, and that's still a rather large population with clear benefit of these medicines, potentially. This really lays out where we see Nilemdo and NEXLIZET fitting in terms of the treatment paradigm. Just about all patients who need LDL lowering are going to be started on a statin. Again, many are not going to get to their goal on a statin alone, and many are going to drop off of a statin, either because of perceived or real muscle-related side effects or other side effects.
At that point, the clinician has a decision to make in terms of whether to just give up or the patient, to add something, to switch them to something else. Often, first line, they'll add the drug ezetimibe, and then oftentimes again, they won't get to goal even on a statin and ezetimibe, and then they have to try to get an approval to get put on very potent drugs, injectables called PCSK9s. Very difficult to get access and reimbursement for these medicines in Canada. Their market share of the overall LDL-C lowering market, I think, is less than 1% in Canada. Highly restricted utilization. Again, these patients are at an impasse.
This is where Nilemdo and NEXLIZET fit in, really fill in that gap, when a patient can't get the goal, either because they can't tolerate the statin or they simply can't achieve that goal on statin or statin and ezetimibe alone. You can see the pricing fits in very neatly. Certainly more expensive than generics on a daily basis. This is our list price, f ar less expensive on a daily basis than PCSK9. We think it's a very compelling value proposition when you look at the unmet need, marry it with very strong clinical data, and a very clearly defined patient population at a price that's quite reasonable. Bringing these drugs to market, we did some market research with 70 specialists, 50 cardiologists, 20 endocrinologists. We're very pleased to see that extremely high level of pre-launch awareness of bempedoic acid.
Again, because these products have been commercialized in the U.S. and European markets, almost everybody is familiar with them. They've been integrated into global treatment guidelines. They've been published, presented, and in fact, there's been, I think, great anticipation of when a company might bring these medicines to patients in need in Canada. High level of awareness, high level of interest in prescribing, and of course, as we know, these specialists are treating patients who are not at goal. Over 50%, they report, are not adequately controlled. The opportunity's there, the awareness is there, the interest in prescribing is there. The first order of business to getting out of the gate quickly is ensuring that we get access and reimbursement, starting with the private payer side.
Literally, the drug's only been in the channel for a few weeks, and we've already got agreements with Canada Life and Sun Life, really the two largest private payers in Canada, to make bempedoic acid or Nilemdo available without restrictions with no prior auth. These will be available full stop, by the end of April for prescribing and will be fully reimbursed. We're making great progress with the remaining private payers as well. We expect very strong private access really by the second half of this year across the board. Of course, we'll be engaging with PCPA to ensure great public access as well, which we expect in the early part of 2027. The third point I just want to cover briefly is around why we're confident that we're set up to accelerate our business beyond 2026.
As we've said, proof of concept, I think we're seeing signs of getting out of the gate quickly with Nilemdo, certainly on the private payer side. As mentioned, we're optimistic that the value proposition will hold on the public side as well, and we'll get broad public access starting early next year. We're very confident we'll also have NEXLIZET, the fixed combination of bempedoic acid and ezetimibe, which we think is a very compelling product, very significant LDL reduction, and obviously the opportunity to reduce pill burden with a single pill replacing two medicines. We expect that to be approved and launched in the first half of next year.
I won't go into detail here, but of course, we continue to be active on the BD front as well in terms of bringing in additional assets, either to complement the therapeutic areas we're already in or potentially new adjacent specialty areas. This is our guidance for 2026. Some modest growth on the top line. We're just getting Nilemdo off the ground this year. We expect that to pick up considerably in 2027. Adjusted EBITDA, we've had a very strong run over the last couple of years, as I showed you earlier, where we've stripped out a lot of excess cost. This is the time now to reinvest a little bit and ensure that we get a strong launch and optimize the launch of Nilemdo.
We're putting a little bit of money back into the launch, and for that reason, we expect our adjusted EBITDA to be relatively flat. A lot of that spend will be front-loaded. As I said earlier, we're not expanding our footprint because of the complementary nature of these medicines. We have a sales force, a medical team, and a footprint that is stable, not growing. It's more than adequate to support all three medicines. There'll be a one-time investment in launch, and then we expect to see margin expansion quite rapidly in the future years. These are some of the catalysts that we're excited about over the next 12 months. Again, I'll just highlight that all of these medicines have very long patent runways. In the case of Vascepa to 2039, the final patent in Nilemdo, NEXLIZET's patent estate runs out to 2040.
Lots of time to continue to enjoy the growth and profitability of these medicines. I added this as more of an illustrative example. It's not formal guidance in terms of what we think peak sales will be, for the main reason that I think until we finalize our negotiations on the public side, it would be difficult to really commit to a number or a range. We put in what we felt were quite conservative assumptions around things like gross-to-net and patient compliance and persistence, and even market penetration of this 500,000 target audience. We come out to a range of $50 million-$100 million in revenue. At that level, again, that would essentially double the size of our company. Again, we might do much better than that. Maybe not. There's other variables at play here.
We think based on our assumptions, at least for people that are trying to get a sense of scale, this is a good starting point. I'm not going to get into detail on BD, but we feel like we've got capacity within both of our business units in Canada to continue to add on. Of course, the more products we bring in, we continue to increase the efficiency and profitability by leveraging kind of those operating capabilities. We also feel like, again, now with our balance sheet in much better shape, we've got much greater flexibility from a capital allocation perspective to be even more ambitious in terms of pursuing additional BD. Just to close out in terms of why we're excited about where we're at as a company.
We certainly have faced some challenges over the past couple of years, but we're very confident we're on the other side of much of it. We're a much healthier, stronger financial company, much stronger balance sheet, trimmed down middle section of the P&L, got our cost in order. We're launching a very important and very exciting medicine, Nilemdo, and all signs are pointing in the right direction that the launch is off to a good start, early days, but so far so good. Then a number of additional catalysts over the next 6-12 months that we think will just accelerate performance even further. We think at the levels we're trading at, we think this is a very attractive set of opportunities in front of us. That's all I had, and at this point, if there's any questions, be happy to take them. Thanks.
We have a couple of minutes for questions, if there are any, for Craig and HLS. Oops, there's one back there.
Thank you. Great presentation. For Nilemdo, you're kind of moving from a specialty schizophrenia space where treatment-resistant schizophrenia is usually treated by psychiatrists into a primary care physician market. How are you guys planning to do that promo shift to the physicians and to be able to grow the product?
Yeah. Just to be clear, I didn't talk a lot about the structure of our organization, but we actually have two separate business units. We have a really bespoke model within psychiatry specific to Clozaril, which includes our patient services, field nurse educators, salespeople, and other type of things exquisitely suited to that book of business that we can continue to expand in psychiatry. A separate organization that calls on cardiologists, endocrinologists, other specialists, and actually high-prescribing primary care physicians who treat a lot of cardiac. Those who are the top decile lipid statin writers, for example, would fall within that. We have a separate sales force as well as a dedicated cardiovascular medical liaison team. They're the ones who have been calling on Vascepa. We'll add the products to their bag. Thanks for the question.
Maybe time for one more, if there is one. Great. Thank you, HLS.