All right, everyone. Presenting next, we have HLS Therapeutics. Please welcome to the stage Craig Millian, CEO of HLS.
Thanks, Scotty. I want to thank the entire team at Bloom Burton for the invitation to present today, tell the HLS story. Here today, I've got John Hanna, our CFO, with us as well in the back of the room. Note that the comments today will be forward-looking in nature. Some of future results will differ from what we present. HLS is a company that's based out of Canada. We have operations and sell products in Canada and the U.S. We are entirely focused on commercial stage assets. We don't have internal R&D. We grow inorganically through business development. We're currently focused in two therapeutic areas, cardiovascular and psychiatric disease. We have two key assets. One is Clozaril, which is the leading medicine for treatment-resistant schizophrenia. We sell Clozaril in both Canada and the U.S.
Our other key product is Vascepa, which we have the marketing rights to in Canada. Amarin is the owner of that product in the rest of the world. In 2023, we generated revenue of $ 63 million, with more than $ 21 million in adjusted EBITDA. We think we're just getting started on our path to growth, which we'll talk a little bit about. Before we kind of dive into the story, we had a lot of change over the last year. I joined the company last May, so I guess it'll be almost a year. Feels like a year in dog years. It's been terrific. We brought on a new head of commercial last summer. John moved into the CFO role in January. We also had significant changes to the board, a new board chair, John Welborn, last summer.
We scaled back the size of our board from 10 to eight, and about half of our board turned over. A lot of change in leadership in a small period of time. Really, a key part of my agenda, more than anything, has been to focus on operational execution. A big part of that has been kind of adapting our go-to-market strategy for Vascepa, which is our growth asset in cardiovascular. We're starting to see some progress there. We'll talk more about that. But importantly, it's really the combination of a balanced product portfolio along with improved operational effectiveness that we believe has us positioned for organic growth and margin expansion in the years to come. Again, we'll talk more about that. We'll spend a little time talking about each of our key assets, starting with Clozaril, which is really a foundational product.
It can be a life-changing medicine for patients with treatment-resistant schizophrenia, which is really a devastating condition. Just a little bit of background on treatment-resistant schizophrenia and Clozaril. I'll use the acronym TRS in lieu of saying treatment-resistant schizophrenia too much. It really describes those diagnosed with schizophrenia and who don't respond to first or second-line treatments. TRS afflicts 1/3 of all patients with schizophrenia. That's about 135,000 Canadians and about 1.1 million Americans. Large prevalence. Clozaril is the branded version of clozapine. Clozapine is the only approved treatment for TRS patients and has demonstrated a response rate as high as 60% in a very difficult-to-treat population. It's a life-changing medicine, and it's such an effective treatment for TRS patients that's actually on the list of World Health Organization essential medicines. It's considered the last line of defense for TRS patients.
So we acquired the rights for branded Clozaril in both Canada and the U.S. And we actually face generic competition in both markets and have for many years. But we've built and maintained a leading share in Canada. And we'll talk a little bit about how we've been able to do that. And this is really kind of the key, which is what we call CSAN, which is our patient support network and associated technology platform. And this has enabled us to maintain a leading market share in Canada despite over a decade of generic competition. So Clozaril is a very effective treatment, but it does come with a potentially significant side effect, which is the lowering of white blood cell counts. And so anybody on clozapine needs to be part of a registry and tracked very closely. And it requires very intensive monitoring of white blood cell counts.
Actually, when you start on clozapine, you need to get your white blood cells checked weekly. As you can imagine, it's rather cumbersome. Think about a patient with treatment-resistant schizophrenia that needs to go to a lab to get a venous blood draw on a weekly basis. Imagine this is quite a barrier to treatment. One of the solutions that we've come up with is called CSAN Pronto, which is actually a point-of-care technology which allows for a simple blood draw from a fingerstick right in the office. So very, very patient-friendly. This is something that has really helped differentiate Clozaril in the Canadian market. We offer this technology. It's synchronized with our CSAN patient support services to help ensure that patients are compliant with their testing as well as staying on treatment.
So just as a point of proof, we actually commissioned a study to see how patients on our CSAN platform compared against patients who are on a leading generic platform. And we actually showed a 32% higher retention rate after 18 months for patients on branded Clozaril on our CSAN platform versus those on the leading generic. And we presented that data last year at a pharmacy conference in Atlanta. And we've also confirmed this with market research as well, that this truly is the preferred platform in Canada. So we think our CSAN team we have a dedicated team that's extremely patient-centric, works closely with physician offices in combination with this technology has really been a key differentiator for us and has allowed us to maintain very, very high market share. As borne out in this slide, Clozaril has been a very consistent performer for HLS.
We acquired the rights to the product eight years ago. We've seen an increase in patients on Clozaril every year over the past eight years. And that's translated into consistent revenue, Adjusted EBITDA, as well as cash flows, as you can see on this slide. And in 2024, actually, our goal is to drive incremental growth of 1%-2% for Clozaril while continuing to maintain very favorable operating margins. So with that, I'll switch gears to kind of our other key asset, which is Vascepa. And this is a medicine that is very effective at reducing the risk of cardiovascular events in certain high-risk patient populations. And there's sometimes a perception that cardiovascular disease has been solved for with the advent of highly effective agents like statins and other drugs that typically focus on LDL lowering.
You can see on the left, in terms of as we kind of conceptualize the patient population, that we would consider candidates for Vascepa, it's about 3 million Canadians that either have established cardiovascular disease or diabetes with other risk factors. And again, despite these improvements in treatment, in particular, really agents highly effective at lowering LDL, there's still significant residual risk. In fact, studies have shown that statins reduce the risk of major cardiovascular events by 15%-44%. So that's a great start, but that certainly leaves room for improvement. And certainly, as we learn more about the pathophysiology of cardiovascular disease, we know LDL is a key risk factor, but there's other factors at play. And Vascepa is quite unique in that regard in terms of operating on a different mechanistically than certainly statins or other classes of drugs that are focused primarily on LDL.
Really, the value proposition for Vascepa is driven by a very compelling set of clinical data. This is the REDUCE-IT trial. It's a large global trial. It was over 8,000 statin-treated patients. And this is a really important distinction. These are patients who were already being optimally managed on, in many cases, high-dose statins, and their LDL was at goal. And despite a very well-managed patient population, we were able to see rather dramatic reductions in cardiovascular events in the Vascepa arm. This was over five years. And you can see kind of the composite endpoint. There was a 25% reduction in major adverse cardiovascular events. Each of the secondary endpoints were also statistically significant, so reduction in MI, stroke. And here's an important distinction with really, I'd say, almost any other drug on the market.
I'm not familiar with any other cardiovascular product that actually successfully reduced cardiovascular death. It has a p-value specifically around that endpoint. Certainly, as part of a composite, we've seen that. But as far as a p-value around reducing cardiovascular death, which is a very important goal of treatment, as you can imagine, you're treating a patient. The most important thing you're trying to do is avoid death. So that's very compelling. And really, in terms of kind of the proof point in terms of supporting this clinical profile is a study called EVAPORATE, which actually showed a very significant reduction in kind of the worst form of arterial plaque. So mechanistically, there's kind of an understanding about how this is impacting the underlying physiology to drive those really dramatic improvements in cardiovascular event reduction.
So in terms of our assessment of the size of the market, there's about 800,000 Canadians that we feel kind of fit or within the label for Vascepa and also have access to reimbursement. We estimate this translates into a potential market as large as CAD 1 billion. Even assuming a relatively modest penetration of 10% gets you to a potential sales of CAD 100 million or more. That's kind of been the goal that we've put forward. We're confident that we've got the right factors in place to achieve this target. We've had a number of recent successes, including in February, we just signed a product listing agreement with British Columbia. Now, with the addition of British Columbia, over 95% of patients on private plans are covered for Vascepa. We estimate over 85% of patients on public plans are covered for Vascepa.
We've got very strong support from most of the major international medical societies recommending Vascepa as part of the standard of care. And importantly, we have a belief that we have a very long runway for this product. Data exclusivity ends at the end of 2027, but we have a very robust patent estate that extends through 2039. The last patent extends into 2039. And obviously, that provides us with a great opportunity to drive a lot of value and do a lot of good for patients as well. So I want to just touch upon some of the I talked earlier about the focus that we've had on kind of operational execution and how we can put the right conditions in place to optimize Vascepa. So to this point, we've made a sizable investment. We're near five with Vascepa.
We've not yet made a positive contribution to our corporate Adjusted EBITDA. So we're currently losing money on Vascepa with the belief that we're making an investment to really optimize growth in the near term. And then obviously, the goal would be to turn that into profitable growth. And as I mentioned, we have a very long runway to do that. But our goal that we've put forward is, by the end of this year, to make Vascepa profitable going into 2025. And so that will have all of 2025 to have two profitable products with Clozaril and Vascepa. And we believe we put conditions in place to achieve that. One important step that we took as far as our go-to-market model, we have a specialty sales force to support Vascepa. We call on cardiologists and endocrinologists on the HLS side.
We have a partnership with Pfizer who calls on primary care physicians. One of the things that I did when I joined relatively early on was identify opportunities to amend our partnership agreement with Pfizer to make it far more cost-effective for us. We're saving on the order of about $2 million-$3 million of expense that now we can repurpose or go straight to the bottom line. Importantly, we didn't really sacrifice effectiveness because it's a much more targeted strategy with a more, I would say, focused call point in primary care. We think we've kind of threaded the needle of both increasing the effectiveness of our call plan in primary care, but also saving quite a bit of money on that.
The other focus, in addition to refining the go-to-market model, was improving our access and reimbursement, which we have made some strides there. I mentioned we got the listing in British Columbia, which was important to us. We've also seen some improvements in Ontario, where patients were waiting as long as two-three months from the time the drug was prescribed till the time it was actually approved by the authorities in Ontario, which was unacceptable, obviously not the right thing to do for patients and obviously not helping us. And so that's gone from an average of about 55 business days in Ontario down to less than five. That was from last summer to now. So we think that's certainly a tailwind and should help us in terms of sales growth this year.
In terms of how the product has performed, this chart shows prescriptions from launch all the way till now. You can see it's, even though we're in year five, the demand growth is still quite remarkable. We had the misfortune of launching this product in March 2020 right at the same time as everything shut down due to COVID. So we have a belief that the trajectory out of the gate is not reflective of really what the potential of this product is. You can see even in year five, rather significant growth in demand. In fact, we've seen in 2023 versus 2022, an increase of 86% in total prescriptions. And that translates into about 70% growth in unit demand when we convert that into 30-day bottles. Importantly, we're seeing growth in both new prescribers as well as what we call consistent prescribers.
We define a consistent prescriber as somebody who has written Vascepa for out of the last five weeks. We're getting kind of breadth in terms of continuing to get new prescribers, but also importantly, depth in terms of product adoption. Just to spend a couple of minutes on our financials, and I'll close it out for Q&A. Since inception, really, HLS has generated solid Adjusted EBITDA and stable cash from operations. You can see the recent full-year results reflect kind of the growing impact and momentum from Vascepa in Canada, which you can see on the chart on the right. Those are actuals through 2023 with our projections for 2024 for Vascepa. The stability of Clozaril, as well as we have a royalty portfolio, has enabled us to generate an Adjusted EBITDA margin of 33% in 2023.
And that's, again, all while investing quite significantly in Vascepa, continuing to drive the growth of that important product. And we're a cash-generating business. We generated $15.8 million in 2023. So our belief is this is a very balanced portfolio with a very steady and consistent cash flow-generating asset in Clozaril, which has successfully maintained a leading market share in a highly competitive generic market for over a decade. So we continue to enjoy the stability and cash flows from Clozaril. And that helps us fund our key growth asset, which is Vascepa, which, again, we believe has very significant sales potential and is close to turning the corner on profitability. This is just some guidance that I recently shared on our year-end earnings call for 2024.
2024 is a very interesting year in that, historically, we've enjoyed a very high amount of royalty revenue that's made up a significant part of not just our revenue, but our Adjusted EBITDA because, obviously, that goes straight to the bottom line. Our largest royalty revenue product ended in Q4 of last year. And so last year, we guided to the fact that we were going to see a dramatic decline in royalty revenue starting in 2024. But the good news is that we're able to really offset that revenue and EBITDA decline with the growth in our product portfolio, which really is the focus of the organization. Our goal, ultimately, is to bring in assets, leverage our organizational capabilities, our commercial capabilities to grow those assets.
Starting in 2024, we're going to really start to see that become front and center with really significant growth projected for our portfolio of about 15%-19% for Vascepa and Clozaril. You can see the proportion of adjusted EBITDA driven from our product portfolio will go from about half to about 80%. Overall, we're looking to see just some modest growth in the total revenue for HLS this year, again, with the growth in our product portfolio. So 2024, again, with the drop-off in royalties and the continued growth in Vascepa and with the goal of actually Vascepa turning profitable by the end of the year, sets us up very well as we go into 2025. These are some of the key considerations of why we're so excited about where the company's heading.
We'll have a profitable product in Vascepa to join Clozaril that now extends potentially into the late 2030s. Second, we've scaled our sales and marketing investment for Vascepa to such a degree that, as we grow sales of Vascepa, we really don't need to add additional OpEx. We're really scaled for a product that could be $50 million, $75 million, $100 million, even though right now we're more in the $18 million-$20 million range. So obviously, our margins will continue to improve each year as our sales grow. Third, our royalty portfolio, although declining from 2023 to 2024 quite significantly, will begin to grow back in subsequent years because we do have a royalty interest in a relatively recently launched product called Xenpozyme, which we expect will grow in the years to come.
Then our expectation is that, as we start to show improved operating results from our core product portfolio and strengthen our financials further, and hopefully, that's reflected in the valuation of the company, we'll be in a position then to bring in additional assets because we do feel we have very strong commercial capabilities in Canada as well as certain organizational capabilities in the U.S. as well. But our primary focus in 2024 will be to execute the business plan specifically with Vascepa and Clozaril. This is our balance sheet. At the end of 2023, our cash balance was $22 million. We've progressively deleveraged the business since inception in 2015. Important point, at that time, HLS borrowed $185 million, which has been paid down to $88.5 million or $66.5 million on a net debt basis.
In terms of capital allocation and return of capital to shareholders, we do currently have a share buyback in place. We believe that, at the current stock prices, that's an efficient approach to return capital to shareholders. In closing, we think we have a strong team in place. This is a year of execution. We have a belief that we'll exit 2024 with a growth portfolio and one that's increasingly profitable as well and sets us up well for the future. I think we've got just a couple of minutes to take questions, Scotty. Thank you.