Good afternoon, everyone. Thank you so much for joining us. Excuse me. Really pleased to have Brad Campbell, President and CEO of Amicus. Brad, to start here, can you give us a snapshot of your business today and your strategy on commercial execution in the second half of the year?
Sure, yeah. Thanks, Sylvie, and thanks to Goldman Sachs for having us here. It's a great conference, great schedule, so appreciate that. Yeah, so as a reminder, Amicus, we are a global biopharmaceutical company focused on delivering therapies for people living with rare diseases. We have two core products, both commercial. First, of course, is Galafold. Galafold is a small molecule chaperone for patients living with Fabry disease who have amenable mutations. That's a business that continues to grow quite well. We saw a great first quarter. In fact, we raised our guidance from 11%-16% growth year-on-year to 13%-17% growth, and that's a product now that's in its seventh or eighth year of commercialization. So great to see that continued growth trajectory. I'm sure we'll talk more about drivers there.
That really, I think, sort of represents the core value of Amicus today. The exciting piece, of course, now is the addition of Pombiliti and Opfolda. We sometimes shorten that to PomOp, so it's a little bit easier to say. PomOp, for us this year, we've given guidance for the first time. It'll do $62 million-$67 million in global sales, and that contributes overall to Amicus with a 25%-30% top line growth. So we think really a core business in Galafold, you're now adding a great new launch product in Pombiliti/Opfolda. Both of those products, we think, have $1 billion of peak sales opportunity, and again, I'm sure we'll talk about kind of drivers and confidence in that launch. And then all of that is kind of underpinned by a strong financial profile.
We will deliver non-GAAP profitability for a full year for the first time this year. And so, as you said, really this year is all about commercial execution, continue to strengthen the financial profile, and delivering value for shareholders.
You've guided to achieving a full year of non-GAAP profitability in 2024. Can you describe what is baked into that guidance and your expectations on the operating expense side over the course of the year?
Sure, yeah. So again, fundamental, of course, is top-line growth, and as I mentioned, 25%-30% year-on-year growth from the combined portfolio. So last year we did just shy of $400 million, $399 million, and so that translates to a, you know, $500 million-$520 million in top-line revenue for the year-end with the two combined products. You combine that with our expense guidance, which is about $345 million-$365 million in global non-GAAP expense, and about 30% of that, to give you a flavor, is R&D OpEx. We're still investing in registry commitments for both products. We're still investing in pediatric studies for Pompe, which we think could lead to label expansion over time.
We're still investing in bringing the second WuXi facility online, and so all of that kind of contributes to investments that we think in the long term will create value again for shareholders and for the programs. But when you combine those two, you can see, you know, full year non-GAAP OpEx. Another way to think of that is that we've kind of now gotten to scale with the Galafold business alone, about $400 million, which will do, you know, more than that this year, is where the whole global business turns profitable, and now you're adding the Pombiliti/Opfolda piece, you know, taking out cost of goods, of course. And that's how you can really see leverage on the overall P&L.
You've really been, at this point, a commercial stage company, with limited pipeline. Maybe speak to us about how you'll bring in a future growth lever via R&D.
Sure. Yeah, so I would say there's two sort of phases of that. The first is where we are right now, which is, you know, we will continue to execute on Galafold and grow that business. We will continue to execute on the launch of Pombiliti/Opfolda. We have lots of new products, or sorry, countries to bring on board there. And so, you know, if we simply execute on those, I think we're well undervalued today, and I think there's lots of opportunity to drive shareholder value. I do think, though, that we've built a very capable, global commercial infrastructure and a very capable late-stage development infrastructure, and I do think those, we still have some leverage we could get out of those.
And so one of the things we've talked about is if we can find the right thing at the right price in the next kind of 12-18 months, you could see doing something that would accelerate the revenue growth and continue that profitability track. And so I don't think we have to do that, but if there's an opportunity to leverage what we've built in the next couple of years, I think we could do that. You've seen examples of that being productive ways to create shareholder value. In the next kind of three-five years, though, when we start to generate our own free cash flow and have our own resources, then I think we can also build into a pipeline. We do have some early-stage programs still that I think have some traction that could be very interesting.
And then, of course, you could always look at, you know, bringing in an earlier stage asset, but that would be when we can kind of fund that development through our own operating profits and cash flow.
What do you think, with regard to the full story, is underappreciated by the Street, and, and what are you most excited about over the next year?
Yeah, I think there are a few things. So first of all, I think Galafold alone should be a $12 or so-ish dollar valuation from a share price perspective. I think in some ways people have really focused on the launch, which I get and makes sense, but I think it distracts a little bit from what is just the value of our core business. So there's not a lot of downside, you know, which I think for many biotechs, you've got binary events, which can challenge that thesis.
The other thing I think that clearly has weighed on the stock, and I'm sure we'll talk more about it, is BIOSECURE, and now that we've gotten much more clarity around the transition period that Congress is allowing for, hopefully, that takes that away and allows us to kind of clearly perform past that. For sure, there's an element around the launch and what's going on there. And I think the most important question that investors need to ask themselves is, you know, is there an issue with the product? The answer is no. We've got great data. We're having great experience with physicians putting patients on Pombiliti Opfolda. You know, is there an issue with Amicus and our capabilities?
I think we've demonstrated with Galafold, we have very strong commercial capabilities, and we're doing that here. And so then you say, "Well, then what is it?" I think it's really just a matter of timing, and we'll talk a lot more about why that is. What I'm most excited about, frankly, from an Amicus perspective is, if you look at the feedback we're getting from physicians, if you look at the data we've generated, if you look at the feedback we're getting from patients, we're seeing over and over again this really positive response to switching on to Pombiliti Opfolda. And again, it's the only product that's demonstrated an ability to improve the outcomes of patients after switching from standard of care.
I have very high conviction that this is a 50%+ market share product at peak, and this market is growing to more than $2 billion. So to me, it's just a really underappreciated opportunity to grow on top of what is already, I think, a really healthy, growing business in Galafold.
Let's start on the PomOp launch.
Sure.
How is the launch that's currently underway in the U.S. and U.K. and Germany progressing? I think you've mentioned, as you just did, about $1 billion in peak sales opportunity. Could you speak to the assumptions baked into this guidance and when you expect to get to the peak sales number?
Sure. Yeah. So part of it is, if you just take a step back and look at the overall market, it's a $1.3 billion market today. We're a small contributor to that, but we will be a bigger one over time. And I think most, you know, physicians, you know, analysts, et c., would think that that's probably a two billion-ish market by the end of this decade. That, by the way, is assuming a conservative rate of growth. It's growing at a faster clip like, you know, today in the last few years. But, but if you just kind of assume it's gonna slow down a little bit, you get to two billion by the end of the decade. And that's, that's, I think, driven by two things. They're driven, number one, by just increasing diagnostics.
Part of it, we've talked about this, and this is really a big deal in Fabry as well. Low-cost genetic screening just helps facilitate faster diagnosis of patients. The other thing is, you see this over and over and over again, when you have another player enter into a space or another therapy offered, you oftentimes see an increased growth in the market. So I think those two things. And then if you just look at the ERT markets broadly, Gaucher, Fabry, you know, MPSs, et cetera, you just see this long-term healthy growth until something gets displaced, and then we don't see anything on the horizon that's gonna displace that. So I think the market is just robust and growing, which is really good. And then you look at our therapy and how it can, it can play within that.
We can talk about specific kind of regional dynamics, but fundamentally, what we, what we point to is the UK as a great comparable to look at sort of where this product can go in the short term and maybe medium term. It was made available through the EAMS program, which is the Early Access to Medicines Scheme, a little over 2.5 years ago, almost three years ago. And that was effectively, the physicians could prescribe it freely, just as if it was a launch product. So in our mind, that's kinda really the start of the launch. And in two years, in the presence of both Nexviazyme, which was available through the same program, and of course, Lumizyme, the legacy product, we've now passed a little over one-third market share in that market.
So our ambition is within every market we launch in, we can get to 30%-35% within three years. I think from there, you can easily see your way to continuing to become standard of care, and we can talk about how that happens, and get your way to 50%+ market share. But we know within three years, we're already at 30% or one-third, actually, in the UK. If you look at the other launches so far, Germany, U.S., and now Spain, which is pretty recent, we're on track right now to exit this year between 10%-15%, which puts you in each of those markets, which puts you on that 30%-35% sort of pathway.
I feel like all the things that we wanna see in the early, you know, months of launch are on track, and we see great line of sight to getting to that, you know, 50%, which would translate to $1 billion.
Are there any other dynamics that are playing out with regard to, you know, use of the competitor drug, and how recently they may have gotten on that drug with regard to understanding.
Yes
T hen the time before you, you would switch over?
Yeah, and I think, and I've talked about this. I like—I feel like that piece is... That's how you come to have conviction of this is gonna be the, you know, the 30%, and it caps out there versus this is gonna be standard of care, i.e., more than 50% of prescriptions. And by that, I mean, what we're hearing from physicians and what we anticipated, and I think is playing out now, is physicians are saying they need about 12-18 months of experience with a product before they're willing to switch. I think you've re-shared in some of your reports, we've heard from a number of sell side and other sources that, that physicians sort of want to see what happens over that period of time before they switch.
Therefore, in the United States, where Nexviazyme has been approved for, like, 2.5 years, you have just a big chunk of patients that are in that middle segment. So, so they've been on drug, on Nexviazyme for less than 18 months. What we are clearly seeing, and we've seen this with great, you know, data now, we're clearly seeing the decliners who've been on for, you know, potentially 18 months or more, switching over to Pombiliti Opfolda, and I think that's the segment that we're getting, you know, very demonstrably in the U.S. and in other markets. The way we win is through continued improvement when patients switch from either product to our product, and then you can challenge a patient to say, and by the way, that's, we're the only product in our label that says that improvement is possible.
Literally, that's the FDA-approved promotional materials say, "Improvement is possible," because that's what our phase III data demonstrated. So when you can convince a physician that actually you shouldn't wait eight, you know, twelve to eighteen months because that patient may end up having a declining event in how they can walk or, how they breathe, that you may never recover from, so why not improve them now and change the trajectory of their disease? That, to me, is the difference between, like, "Yeah, we'll get the decliners outside the U.S., we'll get naive patients," et cetera, et cetera, but that and actually truly being the winning therapy. And that, that takes time, and that's kind of the, the, the course we're on, and I'm, you know, we're seeing things that give us confidence that we're gonna be able to do that.
How do you think about the U.S. versus ex-U.S. split?
So the other side of the coin, I'll start with kind of the market share dynamic. So right now in the U.S., Nexviazyme has the majority market share, because they launched a lot sooner, and so we're getting a higher percentage, much higher. We're getting, like, 70%+ of our switch patients are coming from Nexviazyme, and the balance from Lumizyme. I think that'll continue to play out just because that's the way the market has evolved. Outside of the U.S., it's the flip. So the majority market share is still Lumizyme, and so we're getting a majority of switch patients from the Lumizyme pool, and again, I think that will continue.
We are also getting a healthy uptake in the naive patient population as well outside the U.S., so that's really exciting and so I think we'll continue to pull from kind of all three segments. If you look at revenue distribution, because we came into the year with more European patients in clinical trial and expanded access, and because we launched a little bit sooner in those markets, we'll get a higher revenue this year from Europe. That being said, because of the price differential and because of the market size, if you look at kind of steady state, if you look at Sanofi's numbers, 40%+ of their revenue is coming from the U.S.
So I think we will evolve to that, in our portfolio as well, and I think this year even, we'll have more new commercial patients coming from the U.S. because it's a bigger country, but the revenue will catch up, you know, as we, as we go.
How is the frontline market playing out in terms of the various players right now?
What you mean frontline, meaning?
Meaning, if a patient were naive and being put on drugs.
Ah.
For the first time.
Yeah.
What proportion are coming onto your drug versus.
Yep
The others?
So in the United States, as a reminder, our label is for experienced patients, and so we cannot promote to first-line therapy, nor will we do that. Eventually, every patient can be a switch patient, right? And in the U.S., there's probably 400 or 500 treated patients. There's probably, you know, 40 or 50 new patients that come on every year. So the vast majority of the revenue opportunity globally is switching patients, and again, if even in the U.S., if they start on another product, eventually they can be eligible to switch, and our job is to encourage that switch sooner. Outside the United States, interestingly, we're hearing for the first time that actually in some of our earlier launch markets, that we're the dominant treatment of choice in naive patients. And I'm not surprised.
If you look at the data, we don't have the label in the U.S., but you look at the data, we've shown very impressive impact on naive patients, and the Europeans included that in the label. So right now, I think you're seeing strong uptake in the markets where we have an ability to market against those patients. In the long term, as you continue to demonstrate the value of the product, I think that should only increase the preference. But again, even if they were to start on another therapy because of our switch data is so strong, and it's again, we're the only manufacturer that's shown in a controlled study that we can improve patients switching from standard of care, I think that you have a preferential share of switch patients over time as well.
Could you speak to the path to get naive patients included in the U.S. label?
I think there's, you know, two obvious choices. One would be to do kind of a head-to-head study against, you know, naives. You could do all three products. You could just do Nexviazyme and, and our product. That's an expensive study. It takes a long time. You know, we've seen six-minute walk has variable outcomes, so I'd say that's a highly unlikely choice, although you might, over time, have enough conviction in the data that it's worth. I mean, that would be a, you know, home run outcome. But the other piece that I think is probably a more likely outcome is what, you know, Sanofi demonstrated in the Fabry case, is they used registry data to expand...
move from an accelerated approval for the original Fabryzyme approval to full approval, and they were able to use registry data to do that. So I think there is a precedent in the LSD world with regulators to use registry data. We, as I said, there will be naive patients in it because we- outside the U.S., we have them on label, and we have a growing pool of those patients. So in, you know, three-ish years, I think you could think about using that data to support a label expansion.
Can you speak to the reimbursement dynamic in the U.S.? I think you've spoken to a lag that was playing out with regard to referral forms, to time to infusion.
Yeah.
How long does it take for that to be shortened?
Yeah, and I will say, you know, that was the biggest disconnect for us between expectations and guidance. And we had said, "Look, we need enough time to understand how those trends play out," and so we needed data and time to be able to confidently give guidance. And it, it's unfortunate, but we understand it much better now, and now we've worked through that process. That was probably about $15 million of the difference between expectations and our eventual guidance. The rest is probably pricing mix. And the real issue as we look back on it was less here after prescription to infusion or reimbursement, and that's really a U.S. phenomenon. Outside the U.S., it's immediate. It was really getting the clinical trial physicians to write the prescription to start the process.
It seems kind of, I guess, you know, obvious that they would want to do that and get moving on that process. But if you think about it from a physician's perspective, number one, they already have access to the drug, so the urgency to, like, I really want to switch my patient, well, they're already on PomOp, so they don't need to switch. The second piece is, for the end of the study, they do have to come back in. They actually have to do two infusions in the clinic, so it's a pain in the butt for the doc, it's a pain in the butt for the patient. Again, there's no urgency 'cause they're already on the drug they want to be on. So it just took a lot longer for us to get those first prescriptions written.
Now, we've worked through that whole process, and that's behind us. If you look to the question you have, which is now the metric, the relevant metric for, for new patients, is the time from prescription to, to infusion. We started off with a target of about 90 days, you know, some a little bit longer, some a little bit shorter. As of our Q1 call, which was in April, that's down to 70 days. We also shared that a couple of our patients, the more recent patients, actually gone through in about 40 days, and that's our target, is from a steady state perspective, is 30-45 days. So we have data that says we're moving in that direction. Our goal is kind of by the end of the year to be in that range.
We saw that with Galafold, and we're in that same range with Galafold, so it's, you know, we clearly can demonstrate that, and I think that's something that we'll track as we go through the year, is kinda making sure we continue to narrow that process. The good news is, what you really don't wanna see is formulary rejections, patients being denied, and we're not seeing that at all. It's just a matter of sort of getting through the system.
Can you speak to the Myozyme switch dynamics? Have they all mostly gone to Nexviazyme, or are you seeing some switch over to your drug?
Yeah. So we are still seeing Myozyme switchers to us, and it's proportional based on the market. So in the U.S., it's the minority. We, 70%+ of our switch patients have come from Nexviazyme, the balance from Myozyme. In Europe, where it's kind of flipped from a market share perspective, it's the opposite, the majority coming from Myozyme and the smaller minority coming from Nexviazyme. But, you know, that matters a lot to us 'cause you wanna make sure you can take share from both products. I think from a physician perspective, really all they care about is, like, how are they doing? So they don't ask themselves what drug are they on. I think they ask themselves, how are they doing, and have I had enough time to evaluate that performance?
So to me, yes, you wanna make sure you can take market share from both, and now that we've, I think, clearly demonstrated that, I think really what we wanna focus on, as I said before, is that let's shorten the time to come to the decision that they need to switch to PomOp.
You touched on the BIOSECURE Act. Maybe help us understand the plan here.
Yeah.
And if you, you know, look to opening another second WuXi
Yep
Plant about the move elsewhere with regard to manufacturing.
Yeah. So if you look at our current plan, there's a couple of things that we've done to mitigate against risk. First is moving to WuXi, Dundalk, so still a WuXi facility. And by the way, they invested in that facility, and they've been, you know, very high quality, great partners, and again, they invested in a second site of manufacture, which is great. That's online, and that product should come into the supply chain sometime next year or early 2026, and that's what we had planned for. So that's all on track, which is great. We've also taken a near-term supply strategy of always having 18-24 months of inventory throughout the supply chain, so everything from, you know, from drug product to drug substance to finished goods.
But what we did, and this was really a lesson from COVID, is we started moving product out of China. So 65% of our product is in finished goods outside of China, either in a distribution site in Europe or in markets, so the U.S., U.K., et cetera. So we have, you know, a significant portion of our supply that's finished goods that's sitting in our distribution centers, which is great, so we own that product. In the medium term, and this is where the BIOSECURE Act was so confusing for people, you know, when the first bill was proposed. And I get it.
You know, we were very confident this wouldn't be the case, but when the bill was first proposed, one interpretation is that you would sort of stop cold turkey, and any patient who was on—any government patient, I should say, who was on a product manufactured by a named company in China, would no longer have access to that medicine. Now, we were confident at the time that, in the end, Congress would wake up and say, "Oh, gosh, this is like millions of voters who would be taken off of, like, life-saving medicines. They're not gonna do that." But clearly, we need time for, for some of us manufacturers and BIO as well. We give a shout-out to, to the CEO of BIO, who you guys all know well, John Crowley, who was really instrumental in making sure that Congress did understand the importance of that new language.
Now what you see is this transition period of out to 2032, so eight years, to transition away from WuXi to to another supplier. And so we've already talked about our second-generation manufacturing process, which is our attempt to bring down cost of goods, and effectively, we have - we will now, you know, look to put that in the hands of another supplier. And the good news is, we've already identified three who not only have the capabilities but also have the capacity and the physical plants to be able to do that. WuXi, I think, will always be a partner of ours and a manufacturing partner of ours. Obviously, with the BIOSECURE Act, we wouldn't use their supply to go into the United States, but you've got Asia Pacific, rest of world, Europe, et cetera, where, you know, I think they could be a long-term partner.
They've been super high quality and really great part of the development of the product, so I think they'll be a long part of the story, but we have plenty of diversification away from them in the context of BIOSECURE.
Under BIOSECURE, you could be a U.S.-domiciled company and still partner for the ex-U.S. supply?
Yeah, exactly.
Okay.
The technicalities of that contract are—or that contract, the bill, are that no government contract can occur for a product that's manufactured in by a named company in China. So effectively, Medicare, Medicaid, NIH, anything government, the Defense Department, VA, et cetera, would be restricted. I think the practical reality is that probably most American companies are gonna have a supply source for all of their patients in the United States, but technically, it's limited to government contracts.
Got it.
I will say the knock-on, I think the knock-on effect of BIOSECURE is actually a positive one, which is kind of reframing the narrative of the American biotech and pharma manufacturing industry broadly, and, you know, focusing on what should be a competitive advantage for the United States, which is not just, you know, developing, but also manufacturing medicines for the world. And we used to do that, I think, and we used to be leaders in that, and you've seen an erosion of that capability over time. If you could see like a CHIPS Act kind of thing for biotech, it would be great for our whole industry and great for the United States as well. So I'm hopeful that that's kind of the second issue of this initiative.
But in the meantime, you know, we're very comfortable with the strategy and I think investors will now sort of you know, realize this isn't kind of a black swan event. In fact, there's clear ways to... You know, you have the transition period, you have our strategy. So hopefully, investors now can kind of put this aside and focus on the business.
Returning over to Galafold, help us understand what's baked into the assumptions around your guidance there?
Yeah. So there, too, we think this is a billion-dollar product opportunity at peak. There are a few big assumptions there. The first is that this is a, you know, $2.1 billion market today. We think it grows to a $3 billion market again by the end of the decade. How does that happen? Well, in the Fabry case, what's been, I think, remarkable, it's even a larger disease than Pompe disease, and you've seen, therefore, even a faster diagnosis rate there. As an example, when we launched eight years ago, there were 10,000 diagnosed patients, 5,000 treated, 5,000 diagnosed, untreated. At that time, it was about a $1 billion market. Within seven or eight years, it's doubled to a little over $2 billion market.
We've fueled some of that growth because Galafold's an oral product, I think, that has some, you know, positives. So now there are 11,000 treated patients, but there's another 6,000 diagnosed, untreated patients. So if even if you don't find a single other patient and you just penetrate into that population, that gets you well past $3 billion from Galafold, but then you ask yourself: Well, you know, what are the dynamics around Galafold? First is, we're eligible for a third to a half of those patients. Those are the amenable patients based on our estimates. So right now, we're sitting at a little over 60% share of treated amenable patients, so there's still a significant chunk of just switching patients that we have to go.
But we're also getting a ton of growth from the diagnosed, untreated or newly diagnosed patients, and that's where, you know, I think the market will grow and our product will grow with that because we're now standard of care in, you know, the switch market. We're getting to 80% or 90% market shares of Germany and U.K. and other more mature markets. So for me, you know, the market already exists today to get to that $1 billion. As long as we just continue to execute the way we have, I think there's a clear path there. And I think that's the people say, "Well, how long does that take?" I mean, I think that's still a relatively kind of steady growth process. We're growing at, you know, high teens rates today.
Again, if you kind of assume that continues roughly in the, you know, low teens over time, you could sort of see how you would get to that $1 billion.
How are you thinking about emerging competitors that are using different modalities, such as the substrate reduction therapy through gene therapy?
Yeah. So, I think there are three main classes of technologies that are out there today. First is substrate reduction therapy, as you... Well, maybe first is ERT. So we have seen the new launch of the Chiesi Protalix ERT. And what we had seen previously in the Fabry, what we had seen previously, so there is so JCR has a product in Japan that's an ERT. There's a Korean company that sells a biosimilar ERT in Asia as well. And effectively, those products kinda compete with other ERTs. Some of the best growth kind of six to nine months for Galafold, launching their product. So I think the ERTs for us will each other for patients. Great for patients to have choice, and so we, you know, we wish them business.
The second one is the substrate reduction therapies, and you've had two developers of those over time. One of them has failed to meet its primary endpoint, and is, you know, sort of in a, you know, trying to sort of see if there's an outcome there that could be positive. Another one has taken a lot longer than it was anticipated. And so I have high skepticism that an SRT is ever gonna work in the Fabry space. The other piece of that is, even if it does, you know, if you, the reality is, even though it says substrate reduction, as you know, you're turning off the production of substrate, you're not actually reducing existing substrate. So if you're talking to a patient with an amenable mutation, whereas Galafold does turn over existing substrate.
If you're talking to a patient with an amenable mutation, they're already on a safe, effective drug to a new mechanism that's unknown, that, you know. So I just think there's limited likelihood and limited impact from the launch of that product. I do I really like the idea of a gene therapy or a, or a gene editing or a non-viral delivered genetic payload for the non-amenable patients in Fabry. We have our own program that we're, you know, keeping warm. We're investing, like, less than $5 million in it. As I mentioned earlier, like, you know, once we get enough of our own resources, I'd love to be able to kind of bring that program forward in, like, two years or so. But there are a lot of issues with gene therapy today that still need to be solved.
I know you guys have covered this, too. We still don't know the best way to deliver them, and, you know, we've tried a whole host of different ways to do that, and none of them seem to work as well as we want. In particular, they don't seem to lead to long-term expression and durable outcomes. Dosing is a challenge. We've seen a lot of safety issues, and again, I think that's because of the protein that we're expressing isn't optimized for a gene therapy mechanism. I think we've done some interesting things in protein engineering that might have solved that. Manufacturing leads to much higher prices than I think the current system is willing to, to sort of, you know, deal with.
I think you have to get, you know, a $1 million or less price point, and I'd love to be able to redose these things so that it fits better within kind of the current payment landscape. So I think all those things are kind of putting a challenge on it. But I do—I love the idea, if we could solve some of those things, find a better way to deliver it, you know, therapeutic option for non-amenable patients, that would be, that would be