Ironwood Pharmaceuticals, Inc. (IRWD) Earnings Call Transcript & Summary

Good afternoon, everyone, and welcome again to the Piper Sandler Healthcare Conference -- sorry, 36th Annual Piper Sandler Healthcare Conference. We're delighted to have Ironwood with us. We have Tom McCourt, CEO. We have Greg Martini. What's your title? Is it VP of...

Finance, Investor Relations.

Finance, Investor Relations. Okay, I wanted to make sure I got that right. Thanks, Greg, thanks, Tom, for joining us.

And yes, lots to talk about. So we'll just -- we'll dive right in. I actually wanted to start with a question about the capital structure, given the debt levels following the Vectiv acquisition and also bearing in mind that you guided down on EBITDA earlier this year, so maybe we'll get the unpleasantness out of the way first. Just talk to net leverage ratios and also what kind of net leverage ratios you hope to have once apraglutide launches?

Greg, do you want to take that?

Yes, so I think it's important to think back to the time when we did the VectivBio acquisition mid-last year in 2023. At that point in time, we had about $800 million of debt. At the end of September of this year, we had about $600 million of debt. So over the last 5 quarters, we've paid down $200 million of debt. So we've made meaningful progress in terms of debt paydown. As we think about moving forward, we continue to focus on paying down debt timely based on the cash flows we're generating from LINZESS. And we really focus on 2026 to be able to accelerate that debt paydown with the launch of apraglutide, where we expect to be able to generate significant operating leverage in the P&L to bringing the second product to market.

Okay. And so once you -- do you have a target that you're willing to point to once the product launches in terms of net leverage target?

Yes. We haven't necessarily guided to a specific target. We are focusing on getting that net leverage ratio down from the level we're at currently and doing so as quickly as possible.

Okay. So let's start with LINZESS. And I have a whole bunch of questions on apraglutide, but I wanted to talk about LINZESS because it's been a bit of a bumpy road admittedly. So just first, I'll start just looking ahead and the impact or potential impact of IRA-related Medicare Part D pricing negotiations to the extent LINZESS is included on the next list of drugs to be the subject of negotiations. I think that will be published on February 1. So I guess the question is how are you thinking about impact?

Yes, I think, first of all, when I take a step back as far as where we are and how healthy is the brand really, right? And what we are seeing is just tremendous growth in demand, as you know. To have a drug that's generating 5 million prescriptions a year and you're growing at 10% to 12%, I mean -- and this is year 12, you just don't see brands like this as far as the trajectory and the momentum and the dominance in the market. It's over 50% market share and it continues to grow. And that's really -- that's all driven by the investment in the brand, one of which is payer access. It's the most significant thing we invest in, which really enables it to dominate the market. And over time, we've got to look at making the brand more profitable. So I think I don't see the growth of the brand slowing down between now and LOE. So I think that looks very promising. We did get surprised a bit with some of the legislative changes and the impact of the Medicaid this year that we had to adjust our guidance. And we do see some headwinds with regard to next year with regard to the IRA. But the tricky part here is when you look at how the Medicare redesign is working, how much of our business will be in catastrophic. And that's -- we're working very closely with our partner, AbbVie, to model that. So I think next year, I don't think we're really going to know where we're at until we get through the first quarter to really start seeing what's happening. But certainly, we're looking at a strong performance year with regard to demand. We're going to really focus on profitability of the brand as opposed to net sales because we are going to see some impact on net sales. And to Greg's point earlier, to me, this is now a focus on EBITDA. Next year, it's got to be focused on EBITDA. We have to maximize where we are financially, particularly when you look at the debt load that we have.

Yes. No, that's helpful. And totally get that the volumes are there, when you look at overall volume growth, new-to-brand Rx growth continues to be strong. But there are the payer headwinds that you cited. So here's a big-picture question. Are you and AbbVie fundamentally rethinking your contracting strategy as sort of a way to manage the gross to net and get to stable sales -- net sales for LINZESS going forward?

Yes, no question. And each major contract, we really scrutinize with regard to how badly do we need this. And I think, as you know, one of the things that we're, in the past, very fortunate is we had not just preferred but exclusive payer access, which we really don't need anymore, right? I mean, with a market -- a brand that's this dominant in the market, we don't need the exclusive piece of that contracting strategy. And we're looking really hard at loosening that up, let other players come in because of the dominance of the market. So we're really looking at that. And like I said, the other trade-off then becomes how much more investment do you really need to have in promotion, particularly DTC, with a market -- a brand that's this well-known in the level of treatment satisfaction that we see, we see that growing. But I think we have to really take a healthy look at how much exclusivity do we really need in our contracts.

Yes. No, that makes sense. I guess the follow-up to that is does that -- to the extent that you are rethinking your contracting and changing the landscape, does that impact '25? Or is that more of a '26 impact?

Yes, I think it's like -- well, most of the contracts are set right now. So it's -- we're not going to really affect '25. I think really, we're looking at '26, '27, '28, where I think we can be -- we can really pull back some of the rebating that we've been doing with regard to exclusivity.

So this sounds like sort of a part of a broader strategy to manage the asset as it moves to the end of its commercial life. And so I guess, you did allude to this, so maybe just expand upon it, but how are you and AbbVie thinking about just underlying spend, promotion? I hate to say the word autopilot with a brand like this because it doesn't promote itself. But that being said, you are sensitive to commercial margins. So can you talk about the different things that you and your partner are looking to do to try to maximize those margins?

Yes, I mean, there's obviously three levers here, right? I mean, we talked about contracting. We have a sizable DTC spend, which is largely in media buy, which you can turn on and turn off fairly efficiently and then, of course, personal promotion, right? And we've continued to throttle back on personal promotion and we haven't seen any impact on demand growth. So I think we're going to be looking at all three of those as far as we move forward. I think the other piece that we have gotten alignment with AbbVie on is the OTC play. And David, you and I have talked about this a little bit. There's clearly a path here for an OTC move or the over-the-counter move with a brand that's this large in a market that's this sizable that we're working with the FDA to figure -- we'll be working with the FDA to figure out what that path is forward. But clearly, the path has been defined previously with MiraLAX as far as what would it take to take this over-the-counter in a large market with really relatively few players, which we do think is another revenue stream that nobody has really quantified yet. And I think we'll be working with AbbVie towards that as well.

Okay. Do you have -- and you're going to guide when you guide, but I mean, you do provide commercial margin target. Is that -- how much, I guess, change on the commercial margin front can you affect in '25? Or is the -- I guess, where I'm going with this is how much is the -- has the cake been baked, so to speak?

Yes, I think we're still -- we haven't finalized the brand plan yet. We're actually in the final throes of that right now. In fact, I'm going down to meet with AbbVie tomorrow on this. But I think we all see the opportunity here to certainly further harvest the brand that we'll certainly be focusing on.

Okay. So let's turn to apraglutide, which I know we all want to talk about. Let's start with a high-level question. And just frame the addressable market here in short bowel syndrome with intestinal failure just in terms of the size of the population, the mix between stoma and colon-in-continuity patients. I think that would be a good refresher.

Sure. So the previous estimates based on survey was somewhere between 8,000 and 12,000 patients. Now recently, there has been an ICD-10 code that's been made available, which has really validated that. So for the first time for billing codes, there's actually a billing code for both short bowel syndrome patients with stoma or colon-in-continuity. And it's validated the size of the market. And it's about split, 50-50. Now the other piece of that is very few of these patients have actually been treated with a GLP-2. So there's a very sizable market out in front of us.

Yes. And that sort of gets me to my next question regarding GATTEX being the only GLP-2 available. What is your understanding of the patient footprint for that product? Or maybe asking it a bit differently because there's been some churn with the population that's been on it, how many patients do you think over the years have been on that product, been exposed to that product?

Well, we have probably 2/3 of patients have not been treated with the GLP-2 of the group. But at any one time, there's roughly, based on the sales, probably 1,500 patients that are actively treated on GATTEX. But there's a lot of churn in that, right? So we know 50% of these patients discontinue within 12 months. So when I look at the available population, the largest portion are the treatment-naive patients. And largely, that's a group that the docs don't really see the benefit for the challenge with GATTEX. Because GATTEX is a daily injection. It's got some tolerability issues. And it's hard to justify daily injection when, let's say, a patient is on 3 to 5 days of parenteral support as opposed to 5 or 7. So there's a number of patients that just they won't go to GATTEX with. Where we're seeing in market research, a once-a-week drug that's extremely well-tolerated is far more attractive for these patients. So we could clearly see us broadening that part of the market. And I think the other -- the second target audience is really these patients who were on GATTEX and discontinued, which is a pretty sizable population. And you think about what we really need to get to, let's say, $1 billion in net sales, there's a couple of thousand patients. So the patients are clearly there. The doctors clearly, in market research, are saying this is a far more appealing treatment option. And I think the other one that we really need to pay attention to is overall patient adherence. When you think about how valuable one patient is and keep -- once you've got patients on, how do you keep them on? So that's kind of how we're thinking about the available population beyond GATTEX.

So can you talk about the NDA for apraglutide and just your progress towards the filing?

Yes, so we've got agreement with the FDA to do a rolling submission. And we'll be initiating that in the next couple of weeks. So the preclinical package is ready to go. The clinical package is ready to go. We may have to make some tweaks to that. And then the last, the CMC package, which you recall, we made some adjustments in the syringe that makes it easier for the patient to use, which we had to do some additional human factor studies on, which will be the last piece. So we think right now, we're on track to have the entire NDA submitted by the end of the first quarter.

All right. And I know glepaglutide got a standard 10-month review. Is that your expectation here that you'll have a standard 10-month review?

I mean, that's what we're planning for. However, this drug did get fast-tracked because of the favorable profile going into the Phase III trial. And we won't know that until after we file whether we go. But we're anticipating an early '26 launch.

Okay. Let's look at the body of data for apraglutide. And I know much has been made of the CIC subgroup and the fact that you didn't hit statistical significance on that, the key secondary endpoint. But I guess the question here is how do you think that will translate into commercial impact on the product, if at all? Or maybe I'll put the question differently, do you envision significant usage of apraglutide in CIC patients?

Well, let's take a step back. I think, first, this is the most robust study ever done. So there's three times as many patients treated with active drug in this study than any other study. The primary endpoint was both the stoma and CIC population together. It was positive. Precedent that FDA has previously is if that's positive, you get the entire population. And when you break that up in the sub-analysis, it's clear that the CIC population clearly contributed to that overall endpoint. So we are anticipating a broader -- a full indication across both populations. That being said...

In other words, broad...

Broad, both stoma and CIC. Because when you look at the secondary analysis of patients, not just a volume reduction, but days off therapy, we had over 40% of patients had 1 day off. We had 1/3 of the population had 2 days off and 25% of the population had 3 days off of parenteral support, which is really significant. And those data were just presented at the American College of Gastroenterology meeting. And it got -- it created quite a stir because nobody has ever seen this before. So I think we're going in with a very strong argument for supporting an indication for both populations.

Or maybe, I guess, I'll ask it differently, I mean, do you -- I mean, I think GATTEX, if I'm not mistaken, they're indicated for short bowel syndrome. It's not -- there isn't a delineation between stoma and CIC. So is that your expectation here?

And I think what happens to glep will also provide -- I mean, the reality is the one endpoint we had, which was an endpoint nobody had ever measured before, right, so this was a carve-out of just the CIC population, the primary endpoint was 24 weeks. This is a 48-week endpoint. And we clearly saw a reduction in parenteral support, but the placebo rate was a bit higher than we expected. But we clearly saw a separation. So I think we have a very strong argument that both will. But to be clear, the indication is actually for short bowel syndrome with intestinal failure for all patient populations.

Now my understanding is the glepaglutide trial was run somewhat differently. I mean, you -- I mean, the way that Vectiv designed the trial is they had this weaning protocol and that was sort of with the goal of, I think, replicating a real-world design. Is that something that you think almost stacked the deck in favor of a high placebo response? Because these are patients -- the CIC patients naturally get better, right? So is that what you think was happening here?

We're all speculating at this point. But I think that's likely. And I think the reality is when patients are being actively managed by a physician, constantly encouraging them to wean off parenteral support, they're going to wean off parenteral support. And again, the study was clearly underpowered to be able to hit that state. But clearly, the benefit was observed from treatment.

Yes. Let's talk about the competitive landscape. I mentioned Zealand's glepaglutide. But there's GATTEX, there could be a generic of GATTEX. So that's certainly something to think about. But we have the PDUFA for glepaglutide in the very near future. So there's that. I guess, with that in mind, how do you think about the opportunity for apraglutide?

Yes, I think we've always anticipated there'd be three players in the market. It's really unclear whether we see a generic. There's no evidence that anything is in development. There's been a file made, but certainly, nobody seems to be moving on it. And this is not really a market where generics -- there's so much other support you've got to provide these patients with regard to a REMS program and the hub services that generics generally don't do, right? So that remains to be seen. And like I said, I certainly don't see it over the next few years because there's just nobody is developing one. So that leaves the three branded products basically. And I think when I look at the clinical profiles, because that's what's going to, I think, win the day, when you look at the efficacy and tolerability profile of apra, it clearly stands out when you've got adverse events comparable to placebo, which is very different than you see in the other two products, and you have a really simple once-a-week injection.

Yes. And one question, it's just a bit of an elephant in the room kind of question, but Zealand does not have an intention to commercialize glepaglutide on its own and they are looking for a commercial partner. So that's a bit of a wildcard. But you certainly have commercial infrastructure and you're building the appropriate commercial infrastructure to support apraglutide. So maybe talk about the infrastructure that you're building in, particularly all the support services that have to go with it in the context of this highly specialist-driven rare disease market.

Yes, I think it might be helpful to kind of break that up into a couple of pieces. First of all, what is it going to take to succeed in this market? And that's something, obviously, we're really focused on right now. And a lot of it is market preparation. The strength that we have is we have a very experienced, skilled sales force in those offices today, who are already -- will be starting to do disease awareness. So we're going to be identifying patients that need for a year before we get the launch. And that starts now, right? And so we certainly see the sales force being a huge competitive advantage, having access to physicians' office. And we all know how difficult it is to get into physicians' offices these days. But we are in the GI offices. We would probably fold in some additional targets in some of the large academic centers. So we think the sales force is certainly adequate to support adding this into the bag. I think the second piece is, and one of the things we hear from physicians all the time, is what are you going to do to help me manage my patient? And this comes down to a top-notch patient support hub, where you're holding the patient through the entire process. And we brought in a team to help us put that together. We've been working on it now for 9 months to really put together a state-of-the-art hub services that really helps the patients not only get through the payer access and administration but also encouraging them and informing them how to more effectively manage their disease. So this would be a high-touch hub service. But when you look at how valuable each one of these patients is, it's clearly justifiable. So I think that's probably the biggest single factor that we have to get right to succeed in this marketplace. And we're hearing it from docs, we're hearing it from caregivers and we're hearing it from patients.

Yes. And that sort of leads me to my next question, which is reimbursement and building a hub that helps the practice navigate all the reimbursement challenges here. I guess my question as it relates to reimbursement is you've got GATTEX. We don't know if there will be a generic, but it's there, it's a possibility. How are you thinking about access in this market where you might be one of three GLP-2s?

Yes, I think, again, one is where do we price it, right? And I think right now, we want to make this as easy as possible for the patient to get the drug. So our going-in position is we price probably at parity to GATTEX, even though we have a better clinical profile, that makes sense. But we also need to be -- we'll be working with payers saying, "How do I minimize the barriers?" So do we rethink the pricing strategy? If I can get broader access, we'll definitely look at that, right? But we have some work to do there. I think the other piece is most of the payers certainly reimburse for GATTEX, but it requires prior authorization. And that's the piece that doctors just don't care to do. So you've got to help them with that, right? And that's a big part of what the hub service will do to gain access because just about everybody pays. If you have somebody that's on 5 to 7 days of parenteral support 8 to 10 hours a day and you can give them a couple of days off, I mean, it's pretty justifiable that these patients are entitled to that or deserve that. So if we've got -- if it requires some additional administrative support, we're going to provide that to make sure that they have access.

I've heard that Takeda has kind of pulled back their support of GATTEX. When Shire were on the asset, I mean, that was a big priority. And then Takeda, of course, bought Shire. And now with the product sort of later in its commercial life, my understanding is that the commercial support is just not quite what it once was. What are you hearing about that?

We're hearing the same thing from docs. I think what Shire and GATTEX did for these patients was a huge step forward. And I really compliment them for the work they did. And hey, it's nice to have a playbook, right, to say what's working and what's not working and what do we need to do better. And I think that's the piece that we really want to make sure we get right.

Okay. So maybe in the minute we have left, I wanted to pick your brain on your appetite for business development and in-licensing to bolster the pipeline. I know we talked about debt levels and getting debt down. But that being said, what is your appetite? Are you looking at different kinds of assets? What are your latest -- what's your latest thinking?

Greg, do you want to take that?

Yes. So we're always looking at different opportunities to add to the portfolio. I think right now, our primary focus is on getting apraglutide to market as quickly as possible, making sure we're investing to ensure a successful launch. I think on the other side of that launch, likely in 2026, we would look to continue to add to the portfolio at that point in time to continue to add to the growth trajectory of the company moving forward.

You did have some early data in graft-versus-host disease for apraglutide. And Vectiv, before pre-acquisition, they had talked about other potential uses for the product. So how are you thinking about different potential avenues of development for the asset?

Yes. So the GVHD, or graft-versus-host, we read out an interim readout of the data at day 91 earlier this year. It was really encouraging data. However, we do want to see longer-term data to be able to make a call in terms of the viability of continuing development in that program. I think we're also focusing on other lifecycle management opportunities, specifically within SBS, things such as a pediatrics opportunity down the road that we think there's a lot of additional opportunity to continue to drive value for apraglutide overall.

Yes, I think the other piece, too, David, and you and I have talked about this, if I was running the program, I probably would have went into Phase III with two doses. And they made their best guess on what they thought the best clinical profile would be. And clearly, the drug works, clearly, extremely well-tolerated. So the benefit/risk ratio looks great. The question is has the efficacy been maximized and optimized? And I don't think we know the answer to that. And that would probably be another thing that one of the studies that I would really like to understand is have we really tapped out on the efficacy? And would a higher dose be a preferred option to the dose that we'll go to market with?