Okay, great. Welcome, everyone, to the Leerink Global Healthcare Conference. My name is Roanna Ruiz. I'm a senior biotech analyst here at Lyrink, and it's my pleasure to introduce members of the Xeris team, John Shannon, CEO, and Steve Pieper, CFO. Thanks for joining us.
Thanks for having us.
Yeah.
Yeah, so plan for today, I'll start with bigger picture questions, and then we'll drill down to more detailed questions over time. Maybe to kick it off, and just for investors that are new or revisiting the Xeris story, could you just recap your key focus areas and key differentiators going into 2025, particularly across your commercial portfolio and late-stage pipeline?
Okay. Thanks, Roanna. For those that don't know, Xeris, we're a fast-growing biopharmaceutical company. What's unique about us is we have three commercial assets. We have Recorlev for endogenous Cushing's. We have Gvoke, which is for diabetics, a rescue med ready to use. It's basically an EpiPen for diabetics. We have an ultra-rare product, Keveyis, for periodic paralysis, or PPP. All three of those are growing, fast-growing. We just guided to over 30% growth for this year. We also have a pipeline with our organically developed XP-8121. XP-8121 is phase three ready. We're getting ready to move into phase three with that. It's a once-weekly subcutaneous for hypothyroidism, which is a very large market and a great opportunity for us to build another asset. What we showed in the end of last year is that we went adjusted EBITDA positive.
We are now in a unique position and a different company where we can truly fuel our priorities of growth, both of our commercial assets as well as our pipeline. We have kind of turned that corner, and 2025 is a transformational year for us to really start driving even more growth for shareholders.
Yep. Thinking about next year and your strong performance, how are you going to balance commercial execution, pipeline advancement, and financial discipline going forward?
Yeah, we said that when I came in as CEO back in August, financial discipline is key. There is the guy keeping track of it, Steve, for us to really invest in the assets that can drive the most value short-term and long-term. Those key assets are continuing to drive our revenue growth and driving it. We did 24% growth last year. Driving it above 30% this year is our main objective. Making those investments to do that, at the same time, that is generating enough income and cash that allows us to really start our future, which is 8121, and start fueling that. Finding that balance, we continue to do that. We see that this year as a great opportunity for us to continue that because we said once we go positive, we are staying positive, and we will this year.
Yep, got it. You talked about key products, especially in the commercial front. Can you just walk us through your expectations into 2025 for Gvoke, Recorlev, and Keveyis?
Yeah. All right, I'll start with Recorlev, and maybe I'll make Steve do some of these too. With Recorlev, the way we like to describe Recorlev, it's the right product at the right time. The amount of excitement that's going on in the marketplace as it relates to hypercortisolemia and the impact it's having on identifying very stubborn diseases like diabetes or even stubborn hypertension has really created a situation where more and more clinicians are testing and diagnosing people with hypercortisolemia and Cushing's syndrome. Like I said, there's a lot of momentum in the marketplace in that space, and we have the right product. I mean, we think we have the best product. If you want to normalize cortisol levels and you want to get after the underlying cause of synthesis of cortisol, we have the ideal product to do that with Recorlev.
We're in a unique market dynamic where we can take advantage of what's going on in terms of tailwinds and really drive a lot of growth here. We saw this coming early last year, and by, I don't know, by August, we had doubled or added 50% to our sales force and our patient services group. As we saw this phenomenon happening in the marketplace, we added resources, and those resources were able to pay off very quickly at the back half of last year. We started seeing some really accelerated growth for Recorlev at the back half of last year, and we see that continuing into 2025 with the dynamics that are going on in the marketplace. Again, right product, right time with probably the best product out there for normalizing cortisol.
Yep.
I'll go to Gvoke. Maybe I'll cover Gvoke. Gvoke is our kind of early on, it was our key product designed with one of our technologies, XeriSol technology, and it's been a steady grower for us for now five years. That marketplace is very unique. There are 15 million people either on insulin or a sulfonylurea that should have a rescue med just in case, just in case they go low. That's a very dangerous situation. If you go low in those situations and you don't have a rescue med on hand, bad things happen. You end up in the hospital or even potentially death. The guidelines have all been updated the last couple of years, and that basically said anybody on insulin or sulfonylurea should be protected in those situations and have a ready-to-use glucagon. We're helping to drive that.
Right now, there's only about a million of those 15 million people I talked about actually have a product in hand. It's really changing medical practice from a standard of care to a standard of practice in terms of getting clinicians to actually comply with the guidelines. Our sales teams are out there doing that. There's a lot of opportunity. We continue to grow that product fairly steadily. We see that now that marketplace is kind of matured where the old standard kit, chemistry kit, is pretty much gone. There's just a little bit of share left there. It's really bringing new people into the market and getting them protected just in case. We continue to drive that growth, and we'll always drive the market growth, and then on top of that, we kind of capture a little bit of share.
We tend to grow better, a little stronger than the market in that situation, and we'll continue to invest in it. We have a long runway on Gvoke. It's got patent protection till 2036. We continue to just grind at continuing to grow that business. And then Keveyis, maybe I'll let Steve talk. Take a break.
Keveyis, as John mentioned, is for an ultra-rare population, PPP population. That product has faced generic competition since early 2023 and has remained really resilient. The reason why is because of all the support we give that patient community. We see that that revenue stream, what that translates into from a revenue stream, has kind of remained relatively steady. We see that continuing into 2025, that maybe what we've seen in the last couple of quarters kind of reached a new level, and we expect a nice steady contribution from Keveyis moving forward, so.
Sounds good. Great. Good overview. Maybe I'll stick with Recorlev for a bit here. How are you thinking about its overall safety and efficacy profile as it continues to differentiate itself versus generics and possibly other branded products like Korlym? What are you hearing from prescribers today on that front?
Yeah. Like I said, I think it's the right product at the right time. There's a lot of talk about how do we manage hypercortisolemia. Once it's identified, then one of the key things is you want to get it down. Unique about Recorlev is its mechanism of action, where we block the synthesis of cortisol in three different places. That's why I say it's the right product. It's kind of the perfect little mechanism of action to bring down cortisol levels and normalize them. Korlym blocks it at the tissue level and at the receptors, so the cortisol is still running around. If the clinicians want to normalize cortisol at the source, then obviously Recorlev is a better choice. The other player in there is Recordati.
There are also blocks of synthesis, but it's very hard end at the hand. It's kind of almost like a sledgehammer at the end. I like to think we're just right in that respect. Obviously, I'm a little biased, but in terms of that case, there's a number of side effects that go on with hitting it too hard. You want to find that right balance, and I think that's where Recorlev fits in very nicely from a mechanism of action standpoint.
Yep, got it. Thinking about the recent revenue acceleration for Recorlev and just possible market expansion in the Cushing's space, what are you thinking there, and how could that flow into the next couple of years' growth for Recorlev?
Yeah, I think we're very much in the early innings of where this market growth can go and come from. As clinicians are looking at the various stubborn forms of diabetes or cardiovascular and other areas, they're checking in and looking at cortisol levels. It's incredible what they're finding is the number of people that are 1.8 times or 1.7 times above normal. In those scenarios, like, that's what we need to go and start addressing. There's been good data in that respect that's not generated by us, but others that would say that that's the right approach. I see that continuing for some time now.
Got it. Great. Switching gears to your other commercial product, Gvoke, I did want to ask a couple of questions. Maybe start with competition landscape for Gvoke. Are you adapting any of your commercial strategies going forward, or can you talk about the strengths of your approach so far in driving steady growth for Gvoke?
Yeah, I mean, we've always been focused on one thing, and that is getting the people that are not protected, protected. The 14 million patients out there that today do not have a ready-to-use glucagon, they need to get one. That's our story. That's our message. Our sales force has been focused on that, and they're hyper-focused on it right now on helping the clinicians, the clinician office, become more compliant with the guidelines. That's a really important aspect of being able to so that it becomes more standard of practice every day that if you're on insulin, you should have this. If you're on a sulfonylurea, you should have this. How do you make the systems and everything work in the office so that that just automatically happens? That's what they're focused on. We're not focused on the competition.
We're not focused on market share. The opportunity is in all those people that are not protected. That's always been our focus, but we continue to really be more diligent in there. I would like to see the competition spending more time doing the same thing. I think they're starting to make some investments in this area, which would be great because that's really important that we get these patients protected.
Yep, I hear you. I guess as this is one of your more long-standing commercial products, are you seeing any shifts in the payer dynamic or patient adherence trends? Can you just remind us, is there any seasonality to the Gvoke trends that we should watch out for?
There's always payer shifts. Every year, you're battling with the payers to try to maintain and make sure patients have access to your meds. There are games that go on every year with the PBMs and others. You will see those shifts. They normally normalize out by end of first quarter, within a few months, because there are so many patients out there, and there is still such great access to these products that you may shift from one contract to another. You see a little bit of movement early on in the first half of the year, like every year. In terms of seasonality, the seasonality for this product really is back to school time, and you always see a big pop of the entire market in late July, early August, and it is usually over by mid-September.
You see that big pop, and then it normalizes for the fourth quarter and into first quarter.
Yep, got it. Then third product, wanted to talk about Keveyis. It is reporting continued steady revenues, which is impressive given some generics on the market. Could you just elaborate a bit on the retention strategies that you have been using? You talked about high-touch patient services as well. How could that keep sustaining Keveyis revenues, and how are you thinking about it going forward in the next couple of years?
Yeah, I think we're the ones relative to the generic competition going out there and finding new patients, right? That has been part of our strategy is we go out and find these patients. That's not done at a prescriber level. That's done by us. We identify those patients, so that's been a core part of our strategy. What you mentioned is supporting those patients once they're on therapy. I think the patients see that. They understand that difference. I think there's always dynamics with pricing and reimbursement, but as long as we can continue to identify new and retain existing patients, this product should hold pretty steady.
Yep, got it. Great. I'll shift gears a little bit to the pipeline now. One of the interesting future programs that I'm watching for is XP-8121. That's your once-weekly subcutaneous levothyroxine for hypothyroidism. Maybe just to frame things, what are some of the catalysts coming up this year for that program, and how do you see this product fitting into the hypothyroidism market?
The catalyst is really we're just in the planning mode and working out with the agency exactly what it's going to take to get this product on the market, make sure that we can hit the real unmet medical need in this space, which I'll talk about in a minute, and get to registration at some point. As you know, there's been no real innovation in this space for decades, and it's probably the biggest drug class out there, thyroid replacement. We're in this unique situation where we're and there's no clinical data. All the products are all old products based on DESI and bioequivalents. We're generating data around TSH and T4 and things like that, as well as demonstrating a real clinical improvement in these patients.
What's unique about this is there's a real unmet medical need in the people that cannot, the oral bioavailability just doesn't allow them to get the product in their system, to get the drug in their system. These people are constantly changing, moving, trying to get their levels right, and it just doesn't work, bioavailability. People with celiac disease or people on proton pump inhibitors can't really regulate these and get normal thyroid levels. This is a real opportunity for us to meet a pretty significant marketplace where 20% of the patients out there, there's 20 million people on thyroid meds, and 20% of them just can't get normal levels based on oral bioavailability. Now you have a once-weekly sub-Q that will allow them to be able to achieve what they're trying to achieve.
What was really interesting is when you talk to clinicians, is this is a real hassle. These patients are a real challenge for them because they're constantly trying to change meds, titrate all over the place in terms of how can I stabilize these patients on an oral therapy, and they can't. There is a real opportunity there. We have the work that we're doing this year, and I get it all the time, why is it taking so long, is because it's challenging, and we got to work through this for the first time. We're generating clinical data for the first time. We're working with the agency. They're working very carefully with us. We're working in a narrow therapeutic window area in terms of drug, and we're working on a drug-device combo in a once-weekly subcutaneous form. A lot of kind of pieces to that.
We're doing it in a planful way. We've been doing it and working through the process with the agency in a stepwise fashion because the last thing I want to do is go into a phase three trial with not the go-to-market type product. I want to be able to go into it, do it in a way that we can cover a large range of doses in a therapeutic window that will be able to go right into phase three and then into commercial. I don't want to have to do some bridging studies later and things like that. We're really taking a very planful approach to this and make sure we get it exactly right and make sure we have the right kind of label when we come out of there that we can really kind of really make an impact in this marketplace.
Yep, I hear you. Talking about the FDA interactions so far, what's the FDA's perspective been like on this program, and how do you plan to address some of the FDA's feedback on things like dosing equivalents, etc., going forward?
I think the dosing equivalents question is asked and answered pretty clearly, especially with what we saw. What we did in phase one, then we did a pretty significant study with using PK population modeling, and then we confirmed all that in phase two. We hit the exact same dosing. I think we know the dose and all that. That's really not the issue. The issue is how do you hit in a way that you can differentiate in a way in the marketplace, specifically with this population of patients that just can't be treated, not treated very well at all with daily orals. That's really the focus there. How do you deliver it in this wide range of doses in a device so that patients can easily do this at home?
That's really the work, and that's where we're having most of the dialogue with the agency.
Got it.
I would just add to that that the expectation is that we would provide a more fulsome update about the program mid-year timeframe. In terms of catalysts, what are we looking for? What does phase three look like? What is the market opportunity for this product? A more fulsome update mid-year.
Yeah. You preempted my next question. I was going to ask you possible considerations, I'll put it, for phase three in terms of design, etc. What are you thinking about in terms of structure? I know it's early days, but if you can share some ideas.
I get that question all the time, and we are thinking about everything and anything. We look at this as this has got blockbuster potential. This could be a very big asset. We want to do it right. We literally want to approach this so that we can truly position this product to meet what is a very significant unmet medical need in the marketplace. I do not want to get into exactly how we are going to do that, but when we do talk to everybody by mid-year or so, we will be able to lay that out.
Yep, got it. Okay, we'll stay tuned.
Yeah.
More of a big picture question. Just wanted to check in about the recent appointment of a new CMO, and how will this potentially help shape clinical strategy for you going forward, particularly for 8121 and some of the earlier Xeris Biopharma programs?
Yeah. Obviously, Xeris is really turning to a different point in our life cycle here and bringing in Anh Tuan. Anh Tuan was with us years ago when we were developing Gvoke. He left for a while to do some other biotech stuff and move around. He's got an unbelievable background, and it was great timing with the amount of work we want to do in the clinical space and the regulatory space with not only XP-8121, but also with Recorlev. There was a real great opportunity to bring him back and bring him in as CMO. Yeah, he's digging deep already. It is exciting to be able to bring someone back, bring someone who knows the company, knows the culture, knows what we're trying to do, and is bought in and able to do that.
It's just another sign of the work we have to do and the investments we want to make to really drive the growth of this company.
Sounds good. How do you think about your balance sheet's capabilities supporting the pipeline investments and possible BD going forward into 2025?
I'll let Steve talk.
Yeah, so there's a lot there. One, what I said last week is I think Xeris has never been financially stronger. We have a strong balance sheet, plenty of cash. We guided to 30% revenue growth, over 30% revenue growth at the midpoint, gross margin profile in excess of 80% and growing, and we're really being disciplined about our expenses. Particularly in 2025, that gives us a lot of flexibility to invest for growth as our top line continues to perform. It gives us confidence that from a balance sheet perspective, we've got a lot of flexibility, a lot of optionality, I guess.
As it relates to business development, I think when John took the role in August, we said, "Look, we're always looking at business development opportunities, but going to continue to be a little bit more disciplined about what we go after because we have such great opportunities with our own assets to drive value." That is really the first priority for us out of the gate.
Yep, I hear you. I noticed you used to guide more on cash, and now you're guiding more on adjusted EBITDA going forward. Could you talk a little bit about that change, what motivated it, and some of your excitement behind that?
Yeah, yeah. Having been at the company for eight years now, right, the company has been kind of a cash burn story to this point. When are you guys going to turn the corner? I think we're turning the corner in 2025. We felt like now is the right time to focus investors more on the strength of the P&L. One, we have plenty of cash. I talked about the revenue growth at the midpoint of our guidance, strong margin profile, and really being disciplined about our expenses. We felt like adjusted EBITDA was the right metric for the company at this point in its kind of evolution.
Got it. Okay, makes sense. Thinking forward as well, I wanted to ask a little bit about the XeriJect technology platform overall. Are there any milestones that we should watch out for in 2025? What are your latest thoughts on large pharma partnerships and licensing opportunities?
Yeah, we continue to do work with our XeriJect platform as well as our Xeris Biopharma platform. Both of them are great platforms for really advancing drugs in the space of if you want to get to a high-volume subcutaneous injection, we can do that with both XeriJect and even with Xeris Biopharma. We continue to have these partnerships. What I guided everybody towards was what you saw the last couple of years is what you'll see this year in terms of revenue, other revenue, or our partner revenue. We're still doing work for that. We're still bringing on new partners. We're just not talking about it as much. The partners are happy about that because a lot of times they do not want everybody knowing what's going on there. Our primary reason is it's out of our control.
What they're doing, the work we're doing, we generally get a specs or a target product profile. We develop that. We'll prepare that for them. If they decide to take it into clinic or go anywhere, that's up to them, right? We continue that business. It's still a very good business for us. If it's something meaningful and it's coming out, you'll hear about it. Otherwise, just kind of think about it as steady kind of revenue in that space and what we've seen in the past couple of years. We'll continue to do what we do for those partners, probably just a little more quietly.
Yep, I hear you. I know a few minutes left. Just want to pause, see if anybody in the audience has any questions. Otherwise, I'll keep rolling. Okay. Maybe bigger picture, Xeris Biopharma, Xeriject. How are you thinking of exploiting those technologies going forward in the next, let's zoom out like three to five years? I know you're not making too many comments about partnerships, but what else are you thinking about in the background?
Yeah, so I mean, start with XP-8121. It's a product of Xeris Biopharma. It's organically developed in-house with our Xeris Biopharma technology. I see it as twofold. One is we continue to develop other assets for us down the road with Xeris Biopharma or Xeriject for Xeris. If they fit into that metabolic space or endocrinology, great, because that's where our footprint is. That's why another reason why I'm so excited about 8121 is because it fits right into where we're going with Gvoke and Recorlev so we can commercialize ourselves. An exciting opportunity for us. I see that same thing with Xeris Biopharma and Xeriject. Down the road, we can continue to invest in it. At the same time, we can actually make a significant difference with other people's assets in those technologies, which is what we're doing. It is our future.
It allows us to do everything we want to do going forward organically rather than have to go out and out-license or use business development to continue to fuel future shareholder growth.
Got it. Last question before we close out. Is there anything you think investors are not appreciating right now across your story? You've got a lot going on. There's a lot to look forward to this year. What should we be thinking about going forward?
Yeah, I think one, I do think that Xeris is a really unique investment opportunity. One, we have three commercial products that are growing very quickly and picking up steam, actually going into 2025 and with a pipeline and a platform technology that underpins it all. Super unique and turning a corner financially this year sets us up really well. I think there's still room to grow from a shareholder perspective in terms of driving that value. I think there's a lot to like about the story.
Great.
Yeah, a lot of opportunity short-term for shareholders as well as long-term. I really wanted people to see us in both those lights.
Yep, makes sense. We will stay tuned for more updates. Thanks again, John and Steve, for coming out with us here. Good to have you.
Thank you.
Thanks for having us.
All right.