Good afternoon. Welcome to the Citizens Life Science Conference. Happy to be joined next by Ironwood Pharmaceuticals. Ironwood is a company focused on GI diseases and has been commercializing successfully LINZESS for about the last decade. Exciting new pipeline product in apraglutide for the treatment of short bowel syndrome. We will talk about that as well. We are joined this morning by Tom McCourt, company CEO, and Greg Martini, CFO. Tom, Greg, really appreciate you being here. You reported earnings this morning.
Yeah.
Always fun.
Yeah, go ahead.
I'd say maybe just give you the opportunity, Tom, to give a quick intro and then we'll jump into.
First of all, Jason, thanks for having us and thanks, a big thanks to Citizens to let us participate. As you know, it's been a very, very active few months for us as an organization. As you mentioned, we reported earnings earlier this morning. LINZESS, which you had mentioned, has continued to do extremely well as far as growth demand. High single digits in its 12th year. It's just really been a remarkable molecule over time. We reiterated our guidance for the year. We're on track to either meet or exceed the guidance. We also raised our EBITDA target from $85 million to $105 million. We also disclosed earlier, a few weeks ago, that our partner, AbbVie, has changed some of their accounting mechanisms by which they account for reserves for rebates, which is going to create some seasonality in how it affects the net sales.
The first impact that Greg will explain in greater detail was this first quarter. We also believe that it will change over time. We are very confident if demand continues to hold up, that we will certainly land the EBITDA and certainly land the net sales goal. As far as apraglutide, which we believe will be the best in class, GLP-2, initially for short bowel syndrome, the largest clinical trial ever run in this disease entity. We had very strong efficacy data, as you know, but particularly good safety and tolerability data, which is a bit of a challenge sometimes with Gattex, where we saw basically placebo-like adverse event reporting with a once-a-week injection. We are very bullish on that. We were a little surprised and somewhat disappointed that the FDA has asked us to do a confirmative trial. We talk a bit more specifically about that.
Right now, we're working with the FDA to get that up and running as fast as we can. We think it's largely going to be a smaller study that we could probably do faster. I think there's no question the market opportunity is there. This is going to be the best in class GLP-2, and we just want to get it to patients as quickly as we can. The last piece that we did announce a couple of weeks ago also is with some of the pricing pressures that we've had on LINZESS combined with the delay with the apraglutide as far as the additional trial, we're certainly evaluating other strategic options, alternatives for us as an organization. We've been very busy over the last couple of weeks since we announced it.
The good news is we're getting a lot of inbound interest, lots of different opportunities and structures that we'll be working through, but we'll certainly keep everybody posted as we move forward because the real intent here is how do we create more shareholder value, which obviously we are not satisfied with the stock performance where it is. I think there's a real opportunity to turn that around.
Great. Thanks, Tom. Maybe we'll start with LINZESS and the demand growth. You said it's incredible how consistently the product has grown year over year, quarter over quarter almost. What is it today that is still driving demand growth for the product?
Yeah, I think it's three things still. One, there's still a lot of patients out there suffering, tens of millions. As good as the drug has done, we've treated like five to six million patients, which is incredible. But there's tens of millions out there that are still suffering. This is a best in class clinical profile. I think the treatment satisfaction that we see both from patients and physicians is best in class. You combine that with very broad payer access. We invest heavily into payer access. It's easy to prescribe. I think this is still how do we drive demand and continue to catapult it? I think we do see a play towards the end of LOE to take it over the counter. There's no question we've been in conversations with the FDA already about what it's going to take.
There's a clear path forward that could create a longer tail because it's a very big market. I had the opportunity to do that both with Prilosec and Nexium, which were highly successful drugs, as you know, over the counter, as well as prescription drug. Those are very crowded markets. This is as big as far as prevalence of patients, but there's only a couple of different players. This drug could really thrive in that environment.
Every year, you and your partner, AbbVie, think about not just the growth opportunity, but also the investment that you're putting behind the product. Can you talk about those most recent conversations and just how much are you investing in that growth at the tail end of the branded life cycle?
This is something, as you know, we've evolved over time. This was largely early on, literally, this was solely about personal promotion. Then we moved into consumer advertising, et cetera. We've evolved the marketing mix quite a bit. We've continued to kind of ratchet down the personal promotion because once you get such a strong position in the market, I mean, we have 50% market share. How much personal promotion do you really need? We launched with 1.4 million calls. Now we're down to like almost 200,000 calls. The growth of the brand hasn't slowed down. It's actually accelerated. It's really primarily we're still going to be present in the offices. That's largely AbbVie that will be doing that. We'll continue to look at the investment in the consumer advertising because the benefit of consumer advertising isn't just new patients.
It's also reminding the millions of patients that have taken it to go refill their prescriptions when they have symptoms again. It is a very, very profitable marketing tool. We have continued to reduce the investment, the increase of profitability of the brand. Everything we have done to tweak it has not slowed down the growth. I think we have great confidence that it will continue to grow as we continue to maximize the profitability of the brand.
Great. You mentioned the changes that AbbVie made to revenue recognition. Can you just walk us through those details? I think the important thing you said was seasonality, right? You expect there to be there was an impact in Q1, but there's not going to be an impact overall to the full year. Can you just walk us through those dynamics and what changed?
Yeah, absolutely. I think, Jason, you hit the two key points in terms of our confidence in the full year. In the first quarter, we saw 8% prescription demand growth. That's in line with our expectations of high single digits for the full year. We reiterated our full year expectation of $800 million-$850 million for net sales, even with the lower net sales in the first quarter. Our confidence in this is really driven by the fact that this change is focused on really gross to net rebate estimates being tied to units dispensed in the quarter, which is more closely linked to the actual channels that those units are now being sold through. In the first quarter, we always have a seasonal dynamic where we have lower volumes in the first quarter that are sold to wholesalers.
In the first quarter, historically, units dispensed have exceeded units sold to wholesalers. That's ultimately what's resulting in a larger rebate now in the first quarter relative to gross sales. Q1 is being impacted because you have more units being dispensed. In subsequent quarters, you'll see gross sales and units dispensed be more aligned in terms of that seasonality. We really have historical data to really provide confidence that we are on track for the full year and that this is really more of a pronounced impact in Q1.
Got it. Another part of the net price discussion has been the Medicare Part D rebuild. Can you just walk us through the background there, how you think it has impacted LINZESS and what your confidence is now that you understand those dynamics moving forward through 2025?
Yeah, absolutely. Again, just going back to our guidance and our expectations for the year, our range of $800 million-$850 million took into account several assumptions associated with the Part D redesign being the first year with this impact. We feel like we've conservatively covered the range of outcomes of what could play out with the Part D redesign for LINZESS. I'd say the key for us ultimately will be these new manufacturer rebates in the initial and catastrophic coverage tiers. Ultimately, as we get further into the year, we'll see what portion of the LINZESS Medicare volumes are going through each of the initial and catastrophic phases. We, again, feel very confident our guidance range accounts for the various scenarios of what those volumes could look like. We'll continue to have better visibility into the potential impact as the year progresses.
Fantastic. Tom, you mentioned OTC. You made some progress over the last couple of years with the FDA and the label for LINZESS itself, giving the FDA some more comfort around, I guess I'd describe as theoretical safety questions. Where do you think the, what is your strategy, let me ask it that way, to get the product approved in an OTC format?
Yeah, so the issue that FDA had, there was a theoretical concern that kids have more GCC receptors than adults, so higher density, and therefore will be more sensitive to LINZESS. There was also a preclinical study in neonatal mice where we saw some dehydration in the rats which we ended up with this box warning for all kids under the age of 18. Since we've, one, we've disproved the hypothesis because it isn't true that they have a higher density. Two, the neonatal mice was never a validated model. Then we ran clinical trials as part of a post-marketing requirement to make sure that we knew how it would behave in kids. What we saw is very good efficacy in kids with very good tolerability.
The first group was kids from 6 to 17, which then got added to our label, the only drug ever approved for pediatric constipation. We then have just finished a trial with a cohort of 2-year-olds to 6-year-olds. That looks very good as far as tolerability. There is clearly a path forward to eliminate the box, which then creates an opportunity for us to take it over the counter because we obviously want to take it over the counter with as clean a label. By the way, I lived this with Prilosec. I do not know if you remember 100 years ago, Prilosec launched with a box warning. For carcinoid tumors, we were able to work with the FDA to remove that box. Of course, it became one of the biggest OTC brands ever.
Right, right. I guess positively, you have very good visibility into loss of exclusivity. You can plan for that. Can you just speak, I guess there's a couple of questions here. One, what's the investment in the brand going to be as we approach LOE, but also as we get past this year when we have more certainty around the Medicare Part D rebuild, how much more visibility and certainty will you have about net price between now and the end of brand life?
Yeah, I think it's going to, the net price is going to get increasingly more predictable, right? I think we see this as kind of the, probably the transition year where I think we're going to go back to seeing net sales growth over the next three or four years. Part of that is how we're contracting and how much broader access do we really need considering how strong the brand is in the marketplace. We'll certainly be really critically assessing that. We're moving towards a harvest mode for the brand where we can increase certainly more profitability while the brand continues to thrive. I think that's kind of the path forward. One, I think we're going to see an increase in net sales over time. I think you'll see greater profitability of the brand as we head into LOE.
At some point, we'll have to figure out when do we bring the OTC into the market.
Got it. Okay. Would love to switch over to apraglutide. You said potentially best in class GLP-2. We agree, not just the administration profile, but also the clinical data look fantastic. Can you just, this is an asset that you acquired, I guess it's getting on two years ago now. Can you just walk us through what attracted you to the product in the first place and how you view the product profile in the marketplace?
Yeah, I think for me, it all starts with the unmet medical need, right? And when we looked at this market, I mean, I think clearly Gattex was an advancement in care, but it's a daily injection. It's not well tolerated. Over half these patients discontinue within the first 12 to 18 months because they either can't take the injection every day or they just can't tolerate the drug. There was clearly a benefit to the patient if they could keep on the drug. What we saw in apraglutide was, one, it was clearly a more potent agent. It was clearly a much, much longer acting agent. It could be a once a week.
We felt, one, if the patients, if it worked and the patients could tolerate it better with a once a week injection, I can hang on to those patients for a longer period of time. That was exciting. That is what really got us going. I think what we have learned over time, which is new, and we just shared some of this data with the FDA recently, is the longer these patients are on, the better they get. We announced that of the 110 patients that were in the treatment arm, we had almost 27 patients that were completely off parenteral support. These patients went from five to seven days, eight to 10 hours a day of parenteral support to nothing.
We're seeing that continuing to grow in the extension trial, which the FDA strongly encouraged us to include in the NDA package because nobody's ever seen this before. I think you combine the unmet medical need with the clinical profile, but also the ability to keep patients on drug so they can really realize the full benefit of therapy over time is really an incredible clinical profile to bring to market and bring to patients.
I think it's important to remember that you highlighted some of the limitations of Gattex, but it's still a very successful drug. I mean, its peak sales are around $700 million.
In the U.S., yeah.
Yeah.
It's growing.
Yeah.
It's continuing to grow in spite of the fact that they have trouble keeping patients on. I think about every patient that we get will probably be more valuable because we can hang on to them longer.
Right. So when you acquired the asset, the phase III start trial was already ongoing. You read out the results from that trial last year. Trial met primary endpoint, multiple secondary endpoints. Can you just walk us through the kind of key takeaways from the phase III trial?
Yeah, certainly the fact that there's two anatomies of patients, those that have a stoma and those that have some remnant colon. In our primary endpoint, we showed that both contributed to the positive endpoint. That was a lengthy conversation with the FDA because we had a third secondary endpoint where we just looked at CIC rather than 24 weeks, 48, where we saw separation, but it wasn't statistically significant. It raised some questions about does a drug really work in CIC. There's no question the drug works in these people that have remnant colon that I think we were able to get good alignment with the FDA on. I think that piece was really the telling piece. The piece that evolved was post phase III, we started looking at the kinetics and dynamics, and the drug exposure was lower than we expected.
We did not understand why. Was it a bioavailability issue? Was it an administration issue? We did a rather extensive root cause analysis. What we found was that the way the drug was being administered, the full 5 milligrams was not actually administered. It was less than 5 milligrams, but the reality is the drug still worked. It was extremely well tolerated, and it was a consistent dose, right? We felt very good about going and having a conversation with the FDA about it to make sure we are clear on the path forward. All of our advisors were fully supportive. We were a bit surprised when the FDA came back and said, "Yeah, we agree that the trial was successful.
The profile looks good, but this dose thing, we'd like you to run another confirmatory trial just to make sure we know you're in control of the dose. Since then, we've also significantly improved the delivery device that we would test anyways. Now we really need to get this confirmatory study up and running. We'll be talking to the FDA in the coming weeks, but this is going to, like I said, it'll be a much smaller trial for probably to the primary endpoint, which will be a 24-week endpoint. Hopefully, we can get it up and running quickly. I think the good news here is all the study centers are still in the extension trial. We don't have to activate study centers. We can just go right into the study centers and start recruiting patients.
I think that's the one thing we learned a lot about is how to find these patients and then how to get them into the trial as quickly as we can.
One point you mentioned was that you weren't delivering the full dose. Is there a potential then if you delivered the full dose that you would see better efficacy? At the same time, I'll ask the question, is there any safety concern by delivering the full dose?
First of all, the answer is yes, and I don't know yet. We have to obviously match the dose from the first trial, which we'll do. The one question is, do you add another dose, right? To really say, how good could the drug really be, which is a question we should definitely answer at some point. I think right now, we really want to focus on, let's satisfy the FDA with regard to the least effective dose that's extremely well tolerated. I mean, we have no evidence that the tolerability changes from what we've seen so far. I think we're fairly confident that we could probably push the dose, maybe have a better clinical response. I think that's obviously work to do as far as our life cycle is concerned.
Got it. Just back to that FDA dialogue right now, you mentioned maybe a smaller trial, hopefully faster to results. What are the other components of trial design that you still think need to be agreed with FDA?
I think it's pretty straightforward because we have a validated endpoint, accepted endpoint as far as a primary endpoint. We definitely want to have both patient populations, stoma and remnant colon patients in the trial. The primary endpoint has been at 24 weeks. I think those are the key components. I don't think there's going to be much change beyond that. The only other thing that we would consider, depending on what we end up doing with our strategic options, is do I add another dose and to really push to see how good the drug could be.
Just a few minutes left. Maybe we could just talk about the strategic alternatives process. I'm guessing there's not a ton more you can say, but just how are you thinking about the different options that you have? I guess, do you have a sense of what you're willing to consider versus scenarios that you're less in favor of?
Maybe I'll just say a couple of things and I'll hand it over to Greg because obviously he's closer to it. He's really largely running the process. I think being in a situation where you have two great assets and we've got some debt that we got to manage, right? I think these are two very attractive assets. I think we're getting some inbound interest. Maybe Greg can kind of share more about kind of the range of things we're seeing.
Yeah, absolutely. I think the acknowledgment that we have at this very moment is where we're trading from a market cap standpoint. As Tom mentioned, we have two valuable assets in LINZESS and apraglutide, each individually likely more valuable than where we're trading today as an enterprise. Really the concern is ultimately the funding and the balance sheet associated with our current portfolio. As we look at all these options, we're really looking to realize more of the potential of each individual asset, whether that's through addressing our balance sheet or potentially monetizing either one or both of the assets that we have in our portfolio.
Got it. I guess just when you think about where you're sitting today with the EBITDA guidance that you have out there, what's your comfort level about managing that debt in the near term or near to midterm?
Yeah, absolutely. I think OpEx and cash flow management is definitely a key focus of mine. We took some steps to restructure the organization earlier this year with the intent of driving cash flows and making sure that we were going to be in a position to continue to repay debt and meet our debt obligations. That continues to be a focus. I have a very high degree of confidence that we will be able to continue to maintain our debt covenant compliance, that we'll continue to drive cash flows. With the recent increase in adjusted EBITDA guidance, it provides additional comfort with our ability to do that.
One of the things as part of that process is you've pulled back on the commercial investment for apraglutide as well as your field force for LINZESS. One of the things that's always been core to Ironwood is that expertise and physician relationship network within the GI community. How are you planning to maintain that as you run through this confirmatory study and then get ready potentially to launch a product again when that study is done?
Yeah, I think we saw this as really a pivot year for us. As I mentioned, we had been throttling back on the selling effort both within the GI community as well as the primary care community. Looking at what we really needed to do to be successful for apraglutide was really a different selling model with far fewer reps in the large academic and large GI practices. It was kind of where the future was going to go. We were going to have to retool that and really build out a hub service group for patient support. That was really kind of the focus point. I think certainly we still have a very strong medical affairs group that knows all the key GI players. We have certainly a great heritage there that I think when it's time to retool, we'll be able to retool quickly.
Fantastic. Tom, Greg, really appreciate you being with us this afternoon. Looking forward to staying up to date on the progress.
Thanks.