I guess we can get started. Thanks so much, everyone, for joining us. It's day two of the London Healthcare Conference. Appreciate you all for coming bright and early. So my name is Amy Li. I am a biotech analyst at Jefferies, and I have the pleasure of hosting Sravan Emany, the CFO of Ironwood, and then Greg Martini, the VP of Strategic Finance and IR at Ironwood. So let's get started. So starting with Linzess. So you know you've given updated guidance in Q2. Do you feel like the modified guidance has effectively reset expectations going forward?
Yeah. First of all, thank you, Amy, for inviting us to the conference. We're excited to be here. I will say that at the end of the second quarter, we just, as a reminder for everybody, we provided updated guidance for full year 2024 of net trade sales of $900-$950 million, Adjusted EBITDA of greater than $75 million, and in the third quarter, we reiterated guidance, feel confident based on the trends we're seeing, specifically the amount of Medicaid utilization we're seeing as a percent of our book of business, that those trends have stabilized, and we feel that that will be there for guidance for the full year of 2024.
Excellent. Can you just walk us through some of the shifts in gross to net and payer dynamics that you're seeing in the beginning of the year? What gives you confidence that that's stabilized?
Yeah. So as a reminder for everybody, I think over the course of 2023, at the start of 2024, we adjusted for some movements in 2023 receipts. We saw an increase in Medicaid utilization in 2023, and we've accounted for that in our 2024 guidance, and I think that's the biggest driver for us, as the pricing in Medicaid is very different than the pricing in our commercial or Medicare books of business.
Okay. Fair to say that you think gross to net will be stable from Q4 versus this prior quarter?
Yes.
Excellent.
For 2024, yes.
Excellent. Excellent. And then moving forward, how should we think about Linzess growth? And can you kind of go over the moving parts there?
Sure. First of all, we'll give 2025 guidance in 2025. It's a little early for us to do that, but what I will say is, as always, we think about it as a mix of price and volume. Demand growth for Linzess has been linear since launch. It's actually quite amazing to see the brand continue to grow double digits this year in 2024 in terms of demand. From a price perspective, I think that's the biggest headwind always for us is at this point in time, at this point in our life cycle, is government and where government pay is, and we'll provide those updates in the early part of next year for 2025.
Right. I know you're not talking about specifics, but directionally, given you have this Medicare, the Part D redesign headwind, do you think net-net Linzess will come out as a winner, a loser, or net neutral post that?
Yeah. So what I will say is this. I think at the end of the third quarter, we did say that Part D was going to be a headwind for us. How much it will be a headwind, we'll give that clarity, I think, in the first quarter or 2025 when we give full year guidance. But I mean, at this point, for us, I think that that's all I can really say.
Okay. Okay. Can you go over kind of the moving parts with Part D? Because I've gotten a lot of questions too, like, hey, you guys, is your annual WAC around $6,500. By itself, it shouldn't eat into the catastrophic coverage phase, right? So is that a mix of kind of more heavy rebating? Do you expect to kind of eat into that catastrophic coverage threshold just directionally so we can get a good idea?
Sure, so I think the first thing to, I think, recognize would be that the redesign and the ability to tap into the catastrophic tiers versus the initial tiers are tied as much to all the prescriptions and the prescription therapies that a patient may consume, not just Linzess, and so that's hard to, at this point, to estimate, and it's really complex to understand where a patient may fall with respect to their utilization of Part D and prescription therapies, and so that's why I think at this point it's too early for us to give guidance on that point.
Okay. Makes sense. Makes sense. So you've alluded to a couple levers that you can pull to improve gross to net going forward. Can you walk us through what you're considering internally?
I think we've got a couple levers to improve our brand profitability.
Right.
And so I think we're constantly focused on maximizing the cash flows we produce from Linzess. It's one of our core tenets from a strategic perspective. And I think looking at our brand and the amount of investment we put behind it and the amount of spend that we have on it, it's something we're coordinating with AbbVie constantly on. But the goal here for us is to, whether it's DTC spend, whether it's field spend, whether it's overall marketing spend, whether it's, and the payer mix is part of that. It's just one component in terms of how we negotiate access with payers. That's all part of our, we view that all as part of spend to drive profitability and brand. It's squeezing balloon one end or the other.
Okay. Perfect. And is that a conversation that you've already started with AbbVie? I know.
It's a constant conversation.
Okay. Okay. Because we did see a slight improvement in commercial margins, whether it be a real signal or kind of just fluctuations. Because I think, is there a seasonality component to?
There is.
Okay.
There is. So the fourth quarter will be the most profitable quarter in the year. And it's always been that way as patients tend to work through their deductible over the course of their year, and they tend to have larger prescription fills in the fourth quarter. And then in the first quarter, that kind of goes down again.
That makes sense.
Yeah.
Perfect. And how long does it take for these discussions with AbbVie if you were to think about how you want to spend media? And how do you think about it in Linzess's life cycle as well, right? Because I do understand there is a component of marketing to kind of maintain your market share. But as you get closer and closer to LOE, is there any levers that you can pull to kind of cut that spend? And one, and number two, how long does that take to kind of kick in post your discussions with AbbVie? And then three, what part of that commercial spend are you kind of looking at?
So, I'll answer the first two. One, yes, there is opportunity to do that. We have regular conversations with AbbVie, just so everyone is aware. As a reminder, we jointly run the brand 50/50 as a collaboration, and we split the brand profits 50/50. And so AbbVie, we have quarterly meetings, regular conversations about the state of the brand and where we're going from a commercial perspective and from a development perspective and the amount of investment we put behind it. With respect to the second piece of how quickly, some of these things are longer lead times. When you buy ad time, that goes well in advance of when you actually air their commercials or put that spend in because you're going externally. So some of that has a multi-quarter lag before they can actually be modified. Other things could be more immediate.
Perfect. You've also talked about contracting strategy with payers. How are those discussions going? Is there a lag time for that? And how are you kind of thinking around your strategy for discussing Linzess with payers?
Yeah. So again, I think that happens in the back half of 2020 of any sort of calendar year as we head into next year. Most of the conversations we've had have been positive and in line with our initial expectations heading into this year. I think we are entering, as we enter the latter stages of life cycle. I think we are having more productive conversations on access with payers given our size and scale.
Okay. Makes sense, and then longer term, what's your expectation on how the pricing negotiation will go for Linzess under the IRA?
Yeah. So the next 15 drugs that are going to be identified as part of the IRA, I think, haven't been announced yet. I think we're waiting to see whether we are included. We don't know or don't anticipate at this point, but we don't know. But we're planning in any eventuality and any outcome. We're ready for it.
Okay. Perfect. And you've alluded to this a little. You're still seeing continued volume growth, right? I think it was mid to high single digits quarter over quarter and then kind of low teens year over year. Do you still expect that going forward? And can you kind of talk about some of the dynamics that you're seeing with competitors coming online and kind of the existing market share?
Yeah. So I think, again, this will be where we're going to enter our 13th year on market with the drug. So it's pretty amazing to see that the demand growth and the volume growth of the drug continue to grow at this pace. I think it goes to, one, the size of the patient population and the unmet need is really significant for treating patients with IBS-C. And we've only treated five million patients out of the 45 million plus patients that exist. I think the second thing is we're also seeing that the barriers to prescription have come down a little bit as patients present themselves. They've already tried OTC, and I think docs, instead of prescribing OTC out of the gate, recognize that patients have probably tried OTC first before coming to see them.
And then the third thing is, given our market share and given our position in the market as the leader for the treatment of IBS-C, I think we get a disproportionate benefit of that market growth as a whole in terms of prescription therapies. I think as a whole, we've seen the prescription therapy market grow over the last several years as that kind of barrier or that cycle between a patient presenting themselves and being put on therapy has shortened.
Excellent. Super helpful. Well, moving on to apraglutide, which is what we're internally more bullish about long term. So you've had.
I'm glad to hear that, buddy.
You've had data out from a couple quarters now. It looks like you're doing medical educations. You've been at conferences. What's been the feedback on apraglutide post your phase three data? What are you hearing from physicians? Are they saying that they would change their prescribing habits? And I know one of the big debates is how much CIC patients will get on drug versus stoma. What's been the physician feedback on that aspect?
Yeah. First of all, the feedback has been exceptionally positive from the physician communities that we've interacted with. I would say that the biggest driver of that is we re-ran the largest ever trial in a clinical setting with the largest number of patients. It's a very heterogeneous patient population. And then we've shown benefit across all patient subtypes. And we've shown, I think, from a relative to placebo, I think we've shown great benefits in overall, sorry, reductions in volumes. And then I think we've shown best-in-class safety and tolerability data. So I think as an overall profile with our once-weekly therapy that providers and physicians are really excited about having Apraglutide in their toolkit for these patients.
Perfect. You've said that you expect to complete filing first quarter of next year with a potential launch in early 2026, right?
Yes.
Should our base case be kind of standard approval, or is there a potential for priority review?
The way I would guide you is your base case probably should be standard approval, but there is a potential for priority review as well. We'll know when we have those interactions with the FDA.
Perfect. Great. So I think you talked about safety. Have you seen any signs that apraglutide could have longer durability? And can you kind of remind us what the real-world data looks like for Gattex and where there's room for improvement?
Sure. So Gattex, again, the first therapy that was a GLP-2, it's on market today, sold by Takeda. They have treated about 2,000 patients overall. And I think there's a high discontinuation rate that exists for Gattex. And some of those reasons tend to be duration of therapy, the amount of times per week that a patient has to treat themselves, lack of benefit or perceived benefit. And then I think some of it is just some of the safety and tolerability things we've seen. What I would say about our drug is I think the overall profile of our drug of being a once-weekly therapy, safety profile that is near placebo. And then I think the overall benefit it provides patients across all subtypes, and we've shown that again in the large trial in this space.
I think we feel confident in our ability that patient, as an overall, with that entire profile, will receive benefit over a long term.
Okay. Okay. And just as a reminder, apraglutide is once weekly. Gattex is currently a once-daily injection. So you presented some updated safety in your open label extension to us. It looks really encouraging. You have 95% patients continuing on therapy. I think what we found particularly interesting is the rate of injection site reaction is low, and it looks balanced with placebo. You've seen some competitor data where the injection site reaction almost doesn't seem balanced, right? So can you kind of go over the dynamics outside of just it being a once-weekly injection versus once daily or even twice weekly? Is there anything about the formulation that could kind of explain the phenomenon of that you're not seeing an increase in ISRs over placebo?
Yeah. Look, I think it's just, I think we're excited by the data. I think we're pleased that the safety and tolerability is better than what we've seen from our competitors. We do think that there is something in the formulation and there's something about apraglutide that is in the way we ran our trial that reduced those ISRs. But I mean, I think it's part of the overall profile that we're excited about in terms of giving providers an opportunity here to help these patients.
Right. Makes sense. So you mentioned this kind of transiently on your earnings call. We're seeing low, balanced rates of GI hepatobiliary neoplasm. I know the data is early. I know it's very small N, but we do know that this is on Gattex's warnings and precautions. It is potentially a GLP-2 mediated phenomenon. Could you actually argue for any labeling differences for apraglutide based on this data versus Gattex?
I think it's early to say.
Okay. Okay. Makes sense, and then you also presented some really interesting subgroup data, ACG. I think one thing that we had internally to be looking at is the baseline PS, how that impacts it, because you can have almost like an enhanced benefit if you had a higher or lower baseline PS. Can you kind of walk us through some of the major findings, what subgroups of interest should we and what are physicians paying attention to, and what actually surprised you about the data?
Yeah, so I think one of the important things to acknowledge within the SBS population is that it's a very heterogeneous population overall, and so one of the benefits of having the largest phase three study is that we were able to do a very detailed subgroup analysis across several different baseline characteristics, and the benefit of the data we presented at ACG really showed that there was a consistent treatment effect across all of those demographics, and so I think for us, that was really encouraging, and I think physicians also view this as very encouraging that apraglutide is applicable and can be effective for the broad patient population based on that heterogeneity.
Perfect. I know the size of the SBS-IF market has been kind of a constant question that we've been getting from investors. It's been difficult to size it up because Gattex, like you've said before, there hasn't been a big incentive to adopt Gattex. And even so, you're still seeing around $600 million a year from the U.S. alone. ICD-10 codes were put in late last year. Can you kind of, and it sounds like you guys have been tracking it pretty closely. Can you give us an update on how those prevalence rates are tracking? Is there a sign that the market could be better than we expect?
Yeah. So I think one of the things that we've always said about this market is that there is a significant high unmet need, which is something we, as a pharma company worker, always focused on. And that's what excited us about the opportunity of acquiring VectivBio and acquiring apraglutide. And we said, I think when we acquired the company, that we thought the patient population was 8,000-10,000 patients in the United States. And I think the ICD-10 codes have essentially proven that out for us. And we've kind of seen, I think they've supported that data or that estimate. And then more specifically, I think we also know where these patients are located, which is as we gear up for a launch, that's important to know where these patients are.
Perfect. And what percentage of those 8,000-10,000 patients do you think is addressable by GLP-2?
Yeah. I think 8,000-10,000 is sort of the.
The addressable market.
Yeah.
Okay. Excellent. That's super helpful. And what activities are you doing ahead of launch to kind of educate and prime the market? I know we've talked about, given there hasn't been a very effective therapy, there needs to be a disease education effort. So can you kind of go over what you're doing here and then maybe even the geographic footprint of these patients?
Sure. So first, I'd say that, again, I think having a disease state that's only 20%, even in a rare disease, it's only 20% penetrated at max today, I think says the unmet need is pretty significant, and so raising awareness is our first goal here about the disease and the disease state and helping these patients not only just manage their disease, but eventually thrive in their life and just having freedom to do the things that they want to do outside and away from parenteral nutrition. As a reminder, these are patients that tend to have had a major event, had a resection of some component of their GI tract, and they are dependent on parenteral nutrition to survive.
The goal of one of these GLP-2s is to increase or regenerate absorption capacity within the small bowels and be able to allow patients to wean off or just reduce their amount of parenteral nutrition or parenteral support. That reduction creates freedom for these patients and allows them to live their lives away from being tied up to IVs for significant portions of their week. That's the goal of all this, and raising awareness of the disease state, raising awareness that it can be treated, raising awareness that the possibility of that treatment can create this sort of freedom for them is something we can do in advance of launch without specifically talking about apraglutide. I think if you were at ACG, you would see our booth and see that we've started that process.
Perfect. And just stepping back, can you help us segment the market? So 8,000-10,000 addressable by GLP-2. How many of these patients are currently on Gattex? How many of them have been on Gattex previously? And then I think the bigger question for us is, what could that launch trajectory look like? Can you kind of convert those Gattex refractory patients almost immediately? Could you see kind of that bullets?
Yeah. So I think overall, the 8,000-10,000 estimate that we had talked about is patients in the U.S. that are dependent on parenteral support. I think our estimate is at any given point in time, there's about 1,500 patients on Gattex based on what their sales are for a fiscal year. So there is a pretty significant portion of the market still untreated. A portion of that market has been on Gattex and has since discontinued. And as we look at going to market, we look at first, how do we really get that first new patient? So a patient that is GLP-2 naive, looking at the overall profile of apraglutide with the demonstrated efficacy, once-weekly dosing, and the tolerability profile that we've shared, we think that apraglutide would be the first choice for these physicians and for these patients as they consider taking a GLP-2.
So we really look at that as the first opportunity as we go to market. I think then there's a natural opportunity to also be able to attract some of the refractory patients from Gattex that have discontinued for many of the reasons Sravan pointed to earlier. If they've discontinued for tolerability reasons, again, the profile of apraglutide is very much suited to be able to attract some of those patients to retry a GLP-2. And then over time, we would consider the ability to switch patients as probably a longer time duration to see those conversions. But we do think that will be a likely opportunity over time.
Okay. Perfect. So if you were to position apraglutide, would it be naive? Would it be most refractory? Would it be kind of switch? Where do you think that low-hanging fruit population for you guys is?
Yeah. So we think the largest bolus of patients is really those GLP-2 naive patients. And to Sravan's point, it's really educating the market of physicians and the broad demographic of these patients who are many times really dispersed across the country, really finding these patients, making sure that their providers understand the need and understand the options. And really the disease awareness and education that we're really focused on now, along with these ICD-10 codes, helps us be more targeted to try to attract and educate those patients and their physicians.
Perfect. I think what's really unique about your launch is that you have an existing GI salesforce, right? And you talked about how you don't need to hire new people. You're already getting a lot of the similar touch points. So can you go over when do you expect this launch to be and the creative and kind of the SG&A considerations as well?
Yeah. So I would say that, first of all, as a reminder to everyone here, Ironwood has about 90 sales reps that are Ironwood employees. They detail Linzess, and they call on the top prescribing gastroenterologists across the United States. From our perspective, that will be the largest sales force ever arrayed against this disease state. We've said that before and believe that we can have enough coverage of where these patients are located. I think the thing about this patient population is, while many of them are treated at high academic centers, they live everywhere and they're in the community. And the incremental and marginal patient is pretty valuable to our perspective. From an accretion standpoint, year one, just given the fact that we already have the sales force, we already have the reach, and then much of the spend is already incurred now.
Okay. Perfect. If you think about early discussions with payers, Gattex is still a pretty expensive drug. How are you thinking about pricing? And kind of what's been the early feedback from payers?
So it's early. So it's been positive. And we'll report back when we have something to say. But I think the most important thing is rational.
Okay. Perfect. Finally, I think we have time for one more question. Since you're the CFO, I'd love to kind of get your sense of what do you expect free cash flow to be going forward for Ironwood? And you've also kind of, just to go over the capital structure, what flexibility have you had? Can you kind of go over the intent of the recent change in the revolver terms?
Sure. I'll start with the last piece. Just as in the third quarter, we announced we amended and extended our credit facility, moved the maturity almost out to Linzess LOE in December 2028. The second thing we did was, and that puts us on the other side of the apraglutide launch, which we thought was helpful. The second thing we did was added an extra bank, $50 million of additional capacity, and amended some of the key terms and conditions. With respect to the first part of your question.
Free cash flow.
Free cash flow. Look, we think we're already positive from a free cash flow perspective. We produce a fair amount, and we're using that to pay down the debt to acquire VectivBio.
Perfect. I think that is time. Thank you so much, everyone. Thank you so much, Sravan and Greg, for coming.
All right. Thank you again, Amy.