Ladies and gentlemen, good morning. My name is Abby, and I will be your conference Operator today. At this time, I would like to welcome everyone to the Ironwood Pharmaceuticals Fourth Quarter and Full Year 2021 Investor Update conference call. Today's conference is being recorded, and all lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one once again. I would like to introduce Matt Roache, the Director of Investor Relations. Mr. Roache, you may begin your conference. Thank you, Abby. Good morning, and thanks for joining us for our fourth quarter, full year 2021 investor update. Our press release crossed the wire this morning. You can find it on our website. Today's call and accompanying slides include forward-looking statements. Such statements involve risks and uncertainties that may cause actual results to differ materially. A discussion of these statements and risk factors is available on the current safe harbor statement slide, as well as under the heading Risk Factors in our quarterly report on Form 10-Q for the quarter ended September 30, 2021 and in our future SEC filings. All forward-looking statements speak as of the date of this presentation. We undertake no obligation to update such statements. Also included are non-GAAP financial measures, which should be considered only as a supplement to, not a substitute for or superior to, GAAP measures. Please, if applicable, please refer to the tables at the end of our press release for reconciliation of these measures to the most directly comparable GAAP measures. During today's call, Tom McCourt, our CEO, will begin with an overview and provide an update on the commercial performance of LINZESS. Mike Shetzline, our Chief Medical Officer, will provide updates on our pipeline. Sravan Emany, our Chief Financial Officer, will review our financial results and guidance. Today's webcast includes slides. For those of you dialing in, please go to the Events section of our website to access the accompanying slides separately. With that, I will turn the call over to Tom. Thanks, Matt. Morning, everyone, and thanks for joining us today. When I became CEO last year, I was energized about the commitment to developing innovative solutions in the area of high unmet need in GI. In 2021, we made significant progress against this important mission. I am proud of the Ironwood team, who even through the ongoing pandemic, was resilient in their commitment to advancing the treatment of GI diseases and redefining standard of care for patients. Thanks to their hard work and dedication, we closed out the year with a lot to be proud of. We started 2021 with a clear roadmap which included three strategic priorities. One, maximizing LINZESS. Two, strengthening our innovative GI pipeline. And three, delivering sustained profits and generate cash flow. By the end of 2021, I'm excited to report that we made tremendous headway across all three of these key pillars. Let's begin on slide six with a quick overview of some of our highlights and achievements in 2021. First, LINZESS has been an extraordinarily resilient market-leading brand that continued to deliver strong demand growth and profitability. In 2021, I'm proud to share that LINZESS achieved blockbuster status, exceeding $1 billion in U.S. net sales, representing 8% growth year-over-year. Prescription demand grew a robust 12% year-over-year, and commercial margins were 74%. The continued impressive LINZESS performance is no small feat, and I want to acknowledge the dedication of our team who made this achievement of $1 billion in sales a reality. In addition, we previously announced that the FDA approved a revised label for LINZESS, modifying the prior boxed warning, which included all children under 18 years of age, to the warning of a risk of serious dehydration and contraindication against use in children less than 2 years of age. This label change is a significant accomplishment for the team as we continue to advance the pediatric program. As a reminder, LINZESS is not currently approved for use in patients under 18 years of age. Next, we strengthened our pipeline by entering into a collaboration and license option agreement with COUR Pharmaceuticals to develop and commercialize CNP-104, which, if successful, has the potential to be the first approved disease-modifying therapy for primary biliary cholangitis. In addition, we advanced IW-3300, our wholly owned asset for the treatment of visceral pain conditions, and our linaclotide pediatric development program in IBS-C and functional constipation. Mike will elaborate on these exciting pipeline updates in a few moments. Finally, we ended the year with $528 million in GAAP net income, which includes a $338 million non-recurring income tax benefit related to the release of valuation allowance in the second quarter of 2021. Adjusted EBITDA of $234 million and $620 million in cash and cash equivalents, a significant increase from the end of 2020. We initiated our board-authorized share buyback program with $27 million of shares repurchased as of the end of 2021. Another important highlight in 2021 was the addition of several experienced leaders, including Andrew Davis, our Chief Business Officer, John Minardo, our Chief Legal Officer, and most recently, Sravan Emany, our Chief Financial Officer. We're thrilled that Andrew, John, and Sravan have joined the team, and I'm honored to be at the helm of a very talented group of leaders. Uniquely capable of advancing our mission and ushering in a new era in growth and innovation at Ironwood as we look to continue to grow the company and our pipeline to address areas of GI diseases. Now let's turn our attention to LINZESS. Starting on slide 7. Ironwood has had tremendous success with LINZESS from its inception to its recent achievement of blockbuster status. It continues to serve as the backbone of the company. As I mentioned a few moments ago, LINZESS prescription demand increased 12% year-over-year in 2021, resulting in U.S. net sales of over $1 billion. LINZESS ended the year with approximately 44% total prescription share, a new record high for the brand. As you can see in slide 8, new to brand prescription growth increased a robust 15% year-over-year, which outpaced the market. In addition, 90-day prescription growth has continued to increase over time, making up approximately 20% of the business as of the end of 2021. Turning to slide 9. It's not every day that a brand achieves blockbuster status, and it doesn't happen by accident. First, LINZESS has demonstrated an improvement in constipation plus overall abdominal symptoms, which is important in the treatment for adults with IBS-C, who are often frustrated by bloating, pain, and discomfort. Additionally, the strong brand awareness has helped LINZESS become the number one prescribed branded treatment for adults with IBS-C and chronic constipation by gastroenterologists and primary care physicians. This robust momentum and market leadership position has enabled us to refine our overall marketing mix and investment over time while we continue to deliver strong demand growth and expand brand margins. We expect to continue to grow LINZESS through patient activation, refined professional promotion, our class-leading payer access, and by pursuing future lifecycle management opportunities. Looking ahead, we're confident in our strategy and in the future, and we will continue to focus on delivering value to our patients and shareholders. We believe the investments we're making in the brand and in our pipeline will position our company for long-term growth. Since joining the company in 2009, I've seen firsthand the outstanding capabilities of the Ironwood team in advancing our development and commercialization strategies, as well as our unsurpassed level of commitment to making a positive difference for millions of patients affected by GI diseases. I'm very honored to lead this organization full of talented people, and I look forward to continuing to build upon Ironwood's success as we plan for 2022 and beyond. I'll now turn the call over to Mike to discuss our pipeline and clinical development efforts. Mike? Thanks, Tom. We're thrilled that we have expanded our pipeline as we seek to bring new, potentially first-in-class therapies to patients suffering from GI diseases and disorders that we think we can impact in a clinically meaningful way. I'll start with the linaclotide pediatric program on slide 11. Functional constipation affects an estimated 4 million-6 million 6-17-year-olds in the U.S., and there are currently no FDA-approved prescription pediatric therapies for functional constipation. We believe that this is a significant opportunity to potentially expand the clinical utility of LINZESS to this large patient population. We're excited to continue to advance this program, and we expect the functional constipation study in 6-17-year-olds to read out in the second half of this year. Next is an update on IW-3300. I'm pleased to share that our clinical study is officially underway. IW-3300 is a guanylate cyclase-C agonist and a wholly owned asset for the potential treatment of visceral pain conditions such as interstitial cystitis, bladder pain syndrome, and endometriosis. Interstitial cystitis and bladder pain syndrome affect an estimated 4 million-12 million Americans, according to the Interstitial Cystitis Association. These diseases have a limited number of treatment options available and significantly impact patient quality of life. The scientific evidence to date supports the opportunity for IW-3300, acting in the colon to provide a pain benefit to other visceral organs through a mechanism known as crosstalk. Crosstalk is a biological phenomenon where sensations of injury originating in one abdominal or visceral organ can result in altered sensation in a nearby organ because of overlapping nerve pathways. We're particularly excited about the launch of this phase I study, as it will be the foundation to clinically test the crosstalk hypothesis in humans for the first time later this year. Next, CNP-104. We're tapping into external partners as we identify opportunities to meaningfully advance novel GI treatments for patients where we can leverage our GI expertise and resources to help drive success. We're thrilled to collaborate with COUR on CNP-104 for primary biliary cholangitis, which is a prime example of our strategic approach to enhancing our pipeline. PBC is a slowly progressive and debilitating rare autoimmune disease of the liver that affects an estimated 133,000 people in the U.S. Currently, there's no approved therapy that addresses the underlying pathology or root cause of bile duct destruction in PBC. The loss of bile ducts is fundamental to this disease and leads to decreased bile secretion and the retention of toxic substances in the liver, resulting in continuous hepatic damage which can ultimately require liver transplant. Since signing the agreement with COUR, CNP-104 has been granted Fast Track designation by the U.S. FDA, underscoring the significant unmet medical need of patients with PBC. We're also pleased to share that COUR has initiated the clinical study of CNP-104, which will look at safety, tolerability, pharmacodynamics, and efficacy, with the readout currently expected in 2023. We recently participated in a virtual symposium of leading experts in gastroenterology and hepatology to discuss the impact of PBC and existing gaps in care and treatment. During this forum, many leading gastroenterologists and hepatologists who treat PBC highlighted the importance of stopping the progression of liver bile duct destruction that is foundational to this disease. You can see why we're really excited about this clinical program. We believe CNP-104 has the potential to shift the treatment paradigm in PBC and could be the first truly disease-modifying therapy for this condition if successful, and potentially a real game changer for patients suffering with PBC. This collaboration with COUR allows us to expand our pipeline, leverage our deep relationships within the GI community, and advance innovation via differentiated opportunities. We believe COUR's expertise in immune programming and Ironwood's development and commercial strength, as well as reach in the GI disease area, will help advance this exciting program. This is how we plan to focus our business development efforts going forward. On assets that are highly differentiated, target clear unmet medical needs, have an established mechanism of action, and provide clear decision points. We're seeking to identify more assets like this as we further build out our pipeline. I'll now turn it over to Sravan to review our financial performance. Thanks, Mike, and good morning, everyone. I'm excited to be part of such a team, great team here at Ironwood, and a great culture. As the new CFO, it is fantastic to report such great numbers and see how much Ironwood has strengthened its financial position over the past few years. I would like to provide a few updates this morning. First, I will highlight our fourth quarter and full year 2021 performance. Then I will discuss our capital allocation strategy. Finally, I'll review our 2022 guidance. Please refer to our press release for our detailed financial information. I'll start on slide 13 with LINZESS. U.S. net sales for $279 million in the fourth quarter of 2021, a slight increase over the fourth quarter of 2020. As a reminder, we saw fewer inventory channel fluctuations in 2021, which resulted in favorable net sales growth in the first half of the year, but resulted in a dampening of net sales growth in the second half. Going forward, we expect quarterly inventory channel levels similar to 2021. For full year 2021, U.S. LINZESS net sales were $1,006 million, an 8% increase compared to full year 2020. Growth was mostly driven by robust prescription demand. Turning to LINZESS brand profitability. Commercial margin in the fourth quarter of 2021 was 76%. For full year 2021, commercial margins were 74% versus 72% for full year 2020. Moving to Ironwood revenues. In the fourth quarter, Ironwood revenues were $117 million. For full year 2021, Ironwood revenues were $414 million, with U.S. LINZESS collaboration revenues of $400 million. Ironwood U.S. LINZESS collaboration revenues increased 9% compared to full year 2020. GAAP net income was $41 million in the fourth quarter of 2021 and $528 million for the full year, which includes a non-recurring income tax benefit of $338 million, which was recorded in the second quarter relating to the release of our valuation allowance against the majority of our deferred tax assets. Adjusted EBITDA was $57 million in the fourth quarter of 2021, which includes $19.5 million in expenses associated with the COUR option agreement. Adjusted EBITDA was $234 million for full year 2021. Moving to cash and capital allocation priorities on slide 14. We are in the unique position of being a profitable biotech company that is delivering meaningful cash flow. In the fourth quarter, we generated $65 million in cash flow from operations and $262 million for the full year 2021, and ended the year with $620 million in cash and cash equivalents, up from $363 million at the end of 2020. We continue to execute our board-authorized share purchase program of up to $150 million that runs through the end of this year. As previously mentioned and announced at the JPMorgan Healthcare Conference in January, we repurchased $27 million of shares of our common stock as of December 31, and we repurchased an additional $51 million of shares through February 15, 2022. We believe we are positioning our company for future success by maximizing LINZESS growth and actively pursuing innovative, highly differentiated GI assets to bolster our portfolio. We continue to take a balanced and disciplined approach to capital deployment and remain focused on identifying and investing in opportunities that we believe will create value for our patients and shareholders over the long term. Next, I'll review our 2022 guidance on slide 15. As we previously stated in January, we expect LINZESS net sales growth in the low single digits. We again anticipate continued double-digit prescription demand growth. Over time, we have continued to refine our investment in the brand to support demand growth, improve brand margins, and ultimately maximize Ironwood cash flow. In 2022, we made an investment to maintain broad payer access, which we anticipate will result in high single-digit price erosion this year. We expect to manage price erosion to be more modest in 2023. Next, we expect total Ironwood revenue of $420 million-$430 million. Lastly, we expect adjusted EBITDA of greater than $250 million. As you can see, we are pleased with the progress we made in 2021. Successfully driving LINZESS growth, leading it to blockbuster status, adding CNP-104, a potential game-changing asset to our pipeline, advancing IW-3300, a linaclotide pediatric program, and initiating our share repurchase program. With this momentum carrying us forward, coupled with our current balance sheet and skilled management team, we have confidence in our ability to pursue new GI assets that potentially will help us make a difference for patients and help grow our position as a leading GI healthcare company in the United States. We are excited about the work ahead of us, and we'll continue to keep you posted on our progress. Operator, you may now open up the line for questions. Thank you. At this time, I would like to remind everyone in order to ask a question, please press star then the number one on your telephone keypad, and we will pause for just a moment to compile the Q&A roster. We will take our first question from Boris Peaker with Cowen. Good morning. Question on IW-3300. Can you discuss what you need to see in the data update later this year to invest further in this drug? Are there any kind of reference data sets or reference drugs that we should be considering when we're looking at this data? Well, good morning, Boris. This is Sravan. I'll hand it over to Mike to answer that question. Yeah, sure. For 2022, we're actually, again, excited to kick off the program. The clinical program, as we said, started in quarter one 2022. It's a significant undertaking because it's a very well-established medical need. To your point, through 2022, we're gonna complete, you know, the phase I program, so we'll have data available from a safety and tolerability perspective. We do plan to kick off what we call the phase II or proof of concept study later this year. That design of that study is actually being worked on as we speak today. It's also found that in other analogs, you know, there are a couple of products approved for bladder pain syndrome. They don't work well from the information we get from externals, but that's just a clinical opinion. That's one of the reasons why we think the medical need is quite significant. Using those analogs, we're sort of designing the program. Of course, we'll run it by the FDA to get their feedback as well. It really is looking at the symptomatic improvement of patients suffering from visceral hypersensitivity from bladder pain syndrome. Got it. My last question is, obviously, the valuation of biotech has come down quite significantly. You guys seem to be actively buying back your own shares. I'm just curious if with this new re-evaluated environment, are you being more aggressive in M&A? Is that an objective, or are you happy with the pipeline you have right now and more focused on just returning cash to shareholders via buyback? Yeah. Thanks, Boris. Look, I think from where we stand today, again, I think we've said it a few times now that we're gonna be pretty disciplined with our capital allocation strategy, whether that's deploying capital for future acquisitions or for repurchasing our own shares. I think part of that comes down to when we find an opportunity that makes sense for us and that we think creates value, we'll actively pursue it. Part of it is finding those opportunities, but we're open to whatever makes sense in the best interest of shareholders. Yeah. Boris, this is Tom. You know, the couple of our thoughts, too. I think the thing that's been really kind of remarkable to me is, you know, the resilience of LINZESS and our ability to continue to refine the marketing mix and the investment to really drive, you know, bigger numbers to the bottom line, which is gonna set us up for the future. I think CNP-104 is a classic example of a real area of significant high unmet need and a potential game changer, you know, for the treatment. It's assets like that that we would be excited to be able to bring on board and get through proof of concept, to determine whether we continue to invest in the future. You know, you know, we're very excited about where we are right now. I think about, you know, where we were three years ago, and I think the team has just done a really strong job in kind of getting us on the right track. Great. Thank you very much for taking my questions. We will take our next question from Eric Joseph with JP Morgan. Hey, good morning, guys. Thanks for taking the questions. Just picking up on the pediatric opportunity. Any color that you might be willing to share in terms of the type of uptake you'd be expecting, within that, around, you know, 5 million patients or children with functional constipation? Well, good morning, Eric, and thanks for your question. I'll hand it to Tom and Mike. I mean, what I can share with you know, is really kind of what we've learned in market research in this space. The reality is there's really not many good options for kids. As Mike mentioned earlier, there's nothing actually currently approved for pediatric constipation or IBS. I think there's a couple of sizable pieces to this market here. One is the adolescent population, which is probably the most visible high-need population that I think we can access very quickly. A lot of these patients are treated both by gastroenterologists as well as primary care physicians. You know, they're actively seeking care. I think the one difference in this population is, you know, when these kids are suffering, they're actively engaging physicians for help. I think to have a drug that's actually approved and can not only improve, you know, constipation symptoms but also improve abdominal symptoms is a huge step forward for this population. Mike, maybe you can comment further, you know, with regard to kind of your clinical view of the need and the opportunity. Yeah. I think similarly, the key is that constipation in general is a significant, you know, medical morbidity for patients. Primarily actually in one of the populations we're studying and studied all the way down later years to 6- 7-year-olds. From a functional constipation perspective, from an IBS-C perspective or IBS with constipation perspective, you know, they're fairly prevalent conditions in pediatric populations. As Tom mentioned, as you know, they sort of rotate through laxatives. They don't have real good alternatives, and nothing's currently approved. That's why we're real excited to see the data at the end of this year in the 6- 17-year-old populations 'cause moving forward with improving, you know, symptoms of bowel frequency, in patients with functional constipation could provide a real good therapy for patients, in this patient population. Yeah. One other closing thought on this, Eric, and I mentioned, you know, there's always been this question as far as drug safety, you know, in the younger population. Due to the hard work of Mike and his team, they've really kind of resolved many of those concerns, both with regard to the basic science, as far as what was, you know, hypothesized when we launched the drug. More importantly, what we're seeing in the clinical data that this drug does look like it's effective and well-tolerated. You know, we're gonna continue to work with the FDA to make sure that, you know, it's going, you know, it's going in the right direction. We do see this as a very sizable commercial opportunity. Yeah. I think with the Oh, go ahead, Eric. Better. Sure. Oh, I thought I was just trying to, Mike, to get a little more help sort of framing expectations for the readout in the second half, which is, you know, the total study size. You know, what might be, what the trial is powered to show in terms of improvements in SBM and really whether that data set if positive would be used for the purposes of label expansion. The current study, which is a 6-17-year-old study, looking at improving bowel function obviously in 6-17-year-olds with diagnosed functional constipation. At that level, and as with other constipation disorders, that's really founded in an improvement in bowel function. Bowel movement frequency, spontaneous bowel movement measurements. They're sort of the endpoints in what we're looking for to see an improvement in bowel movement function in those patients. And that's hopefully will give us a path to an indication for functional constipation. Clearly, we've got to see the data at the end of the year. We'll have discussions with the agency actually earlier this year to prepare for that. And it'll obviously be data-driven and discussion with the agency, endeavor to move that forward. Okay. Great. Final question, if I could. Strong commercial margin for LINZESS that you did in the fourth quarter. How should we be thinking about the trend in 2022? You talked earlier about sort of additional spend for the franchise. Any diminishment of that commercial margin we should be anticipating? Yeah. First of all, let me just take a step back, Eric, and just say, look, we're really proud of where LINZESS is from a profile perspective in terms of having a brand that's thriving and being able to produce double-digit prescription demand growth year-over-year, 10 years into its life cycle. At the same time, we've been pretty prudent in terms of what goes into our commercial spend to maintain that. As Tom had mentioned, and I think we talked about a little earlier, we've made some choices as to where to make those investments in either payer access, marketing, et cetera to manage and drive that prescription demand growth. 'Cause we think that's the ultimate driver of overall profitability and ultimate driver of overall cash flows for the company. Specifically to your question, what I would say is, look, I think like every other CFO, I'd be wanting if I didn't mention that we're in an inflationary environment, right? Like the broader economy, we're exposed to inflationary pressures within our business, whether that's labor and the like. We continue to monitor that. But I think from where we stand today, from a commercial margin perspective, we think we're gonna hold steady about where we're at for 2022 and continue to drive profitability through cost containment. Thanks, Sravan. Just one other comment as I think about this is, you know, we talked about the momentum that this brand has in the market, which, you know, has allowed us to really tune up the marketing mix. You know, as you know, we have dramatically pulled back on personal promotion, which is, you know, one of the biggest ticket items with regard to expense, and we haven't seen the demand growth waver, which says a lot for the, you know, the effectiveness of this drug in the marketplace, and ongoing growth. Obviously, you know, we continue to look at promotional response. We look at investment both on the consumer and professional side. Of course, the payer mix is also critically important, which has continued to enable, you know, patients to easily access the drug. Okay. Excellent. Thanks, guys, for taking the question. No problem. We'll take our next question from Tim Chang with Northland Securities. Thanks. Hey, Tom, you know, just given the revaluation in a lot of pharma biotech names, you know, have you guys considered looking at other existing approved products to complement LINZESS, just given the fact that you already have a commercial infrastructure in place? Tim, this is Sravan. Look, I'll start by saying that, you know, we don't comment on business development activities as the standard course. What I will say is, look, we are open from a strategic direction perspective to whatever creates the most amount of value for the company, and we will evaluate any and all opportunities that we think can drive that for us. It's a broad answer to your question. I appreciate that. You know, we're not gonna get specific about where and what we're looking at. Yeah. I think just in addition, I mean, I agree. I think this is, you know, the environment's changing, which could create nice opportunities for us. You know, the team is looking at a lot of different things right now, Tim. I think we have a number of opportunities in front of us that we're critically evaluating and working closely with our board to make sure that, you know, we're making very sound decisions, you know, for, you know, you as an investor. Okay, great. Let me just follow up. Just on, I know you guys have provided 2022 guidance, which I think is, which is solid. You know, do you guys expect R&D expenses to ramp up this year, or it's more of a flat type of year for R&D? Just as a reminder, taking a step back. Last year in 2021, with respect to R&D expenses, you know, first of all, one, Tim, we don't give guidance on R&D expenses. I think it's the first point. We just talk about EBITDA. What I would say is our 2021 R&D expense included about $19.5 million associated with the COUR license option agreement, and we don't expect those costs to recur in 2022. At the same time, you know, we've got some interesting things that we're looking to get readouts on this year, specifically pediatrics and, you know, the progress we're making on IW-3300 and CNP-104 itself. Yeah, I'd just say that, you know, we don't have those recurring costs. We don't provide guidance on that. Okay, great. Thanks. We will take our next question from Jacob Hughes with Wells Fargo. Morning, Jacob. Hey, good morning. It's Nick on. Hey, it's Nick on for Jacob. Thanks for taking this. Hi, Nick. Just one from us. Is there any update you can share on the LINZESS OTC pathway and maybe what progress you expect into this year? Well, thanks for the question. At this time, we don't have an update on the OTC pathway. We'll provide an update when we have one. Yeah. I would just comment. I think that's spot on, Sravan. You know, we're still working through that obviously with our partner to, you know, look at, you know, feasibility and the timing of that. So, you know, right now we're primarily focused on moving the pediatric program forward and resolving any outstanding questions that the FDA may have on drug safety before we can even really move forward with the OTC assessment. Got it. Thank you. Ladies and gentlemen, that concludes our question-and-answer session, and this also concludes today's conference call. We do appreciate your participation, and you may now disconnect.