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spk03: Good morning. My name is Rob and I will be your conference operator today. At this time, I would like to welcome everyone to the Ironwood Pharmaceuticals third quarter 2021 investor update call. 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 session, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star 1. Thank you. Matt Roach, Director of Investor Relations, you may begin your conference.
spk02: Thank you, Rob. Good morning, and thanks for joining us for our third quarter 2021 investor update. Our press release crossed the wire this morning and can be found 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 State Harbor Statement slide, as well as under the heading Risk Factors in our quarterly report on Form 10-Q for the quarter ended June 30th, 2021, and in our future S&T filings. All forward-looking statements speak as of the date of this presentation, and we undertake no obligation to update such statements. Also included are non-GAAP financial measures, which should be considered only as a supplement to, and not a substitute for, or superior to, GAAP measures. To the extent applicable, please refer to the tables at the end of our press release for reconciliations of these measures to the most directly comparable GAAP measures. During today's call, Tom LaCour, our CEO, will provide an update on progress towards our strategic priorities and commercial performance of Lydess. Mike Schetzlein, our Chief Medical Officer, will provide an update on our pipeline, including the option agreement with Core Pharmaceuticals that we announced this morning. And Jason Riggard, our Chief Operating Officer, will wrap up the review of our financial results and guidance. We will be referring to slides via the webcast. For those of you dialing in, please go to the events section of our website to access the slides. With that, I will turn the call over to Tom.
spk05: Thanks, Matt. Good morning, everyone, and thanks for joining us today. We closed another strong quarter in 2021, driven once again by double-digit Linza's prescription demand growth year over year. This morning, we announced that we've expanded our pipeline by entering into an option agreement with Core Pharmaceuticals, which we'll review in more detail in a few minutes. We're coming out of a terrific American College of Gastroenterology meeting where we presented new findings from a survey on the impact of abdominal symptoms on adult patients with irritable bowel syndrome with constipation. In addition, we gave an oral presentation and presented four other posters, one of which received ACG's Presidential Poster Award. I couldn't be more proud of the team's execution and the work we're doing to advance treatment in GI diseases and redefine standard of care for GI patients. Let's start with a few overview of our strategic imperatives, as well as our strategic priorities. Our strategy starts with maximizing LINDSES. Since launch in 2012, LINDSES continues to experience accelerated demand and widespread acceptance among healthcare practitioners as a leading prescription treatment for adults with IBSC and chronic constipation. In the third quarter, Linza's total prescription demand grew 12% versus the prior year quarter, and new-to-brand prescription growth continued to outpace the market. Next, we are looking to build an innovative portfolio, both through the development of internal assets and through bringing external therapies that target serious organic GI diseases. Mike will be providing an update on our pipeline. Finally, we're committed to delivering sustainable profits and cash flow, We had another impressive quarter on the bottom line and ended this third quarter with $574 million in cash and cash equivalents on the balance sheet. We're taking a thoughtful and disciplined approach to capital allocation in an effort to maximize return to our shareholders as we continue to explore growth opportunities with the same high bar we've always had. Now, I will turn it over to Mike to discuss our pipeline. Mike?
spk02: Thanks, Tom. And good morning, everyone. We're advancing our pipeline through the development of IW3300, our wholly-owned asset for the potential treatment of visceral pain conditions, such as interstitial cystitis, bladder pain syndrome, and endometriosis. We're on track with the IND application to the FDA this year and the start of the clinical program in the first quarter of 2022. In addition to IW3300, we're excited to announce that we entered into an option agreement with CORE to acquire an exclusive license developed and commercialized in the U.S., CNP-104, which we believe, if successful, may have the potential to transform the treatment of primary biliary cholangitis, otherwise known as TPC, a rare autoimmune disease targeting a liver that affects an estimated 133,000 people in the U.S., Coor's novel approach uses a biodegradable nanoparticle encapsulating PDCE2, which is the autoantigen believed to be responsible for the autoimmune pathology of primary biliary colon injury. CORE's proprietary platform combines PBC-E2, the state-of-the-art pharmaceutical nanoparticles that tolerates the immune system and potentially eliminate the immune cell biofuel destruction present in PBC. CORE's platform has shown proof of technology in clinical and preclinical settings, further demonstrating the opportunity for the platform to treat PBC. Currently, there is no therapy that addresses the root cause of the autoimmune destruction of the bile ducts in PBC, which can result in profound fatigue and pruritus, as well as other symptoms, and not uncommonly can lead to irreversible damage and scarring of the liver, ultimately requiring liver transplant. We believe CNP-104 has the potential to shift the treatment paradigm in PBC with the opportunity to be the first disease-modifying therapy for PBC. Collaborating with CORE allows us to move our strategy forward through expansion of our pipeline, leveraging our deep relationship with gastroenterologists, and advancing innovation via differentiated opportunities like CMP104. We believe CORE's expertise in immune reprogramming and Ironwood's development and commercial strength, as well as our reach in the GI disease area, presents an opportunity to help introduce a potentially new, game-changing therapy to patients in significant need of new treatment options. We're thrilled to be collaborating with CORE, which expects to begin a clinical trial for CNP-104 this year. Jason will provide more detail on the agreement later on the call. Ellen Ford will continue to share new updates as our pipeline development progresses. Now back to Tom to discuss the commercial performance of Linzess.
spk05: Thanks, Mike. Linzess continues to deliver a remarkably strong performance in the third quarter, powered by both new patients and refill volume. further reinforcing its position as the number one prescribed medicine in the U.S. for the treatment of adults with IBSD and chronic constipation. As I mentioned earlier, LINZUS' prescription demand grew 12% year-over-year, resulting in U.S. net sales of $253 million. This strong performance reaffirms our confidence that LINZUS has the potential to exceed $1 billion in U.S. net sales in the near future. We believe that the impressive demand growth we're seeing with Linzess continues to be the result of strong execution of our commercial strategy and fueled by a few sustainable drivers. First, our clinical focus on constipation plus overall abdominal symptoms is a key differentiator for Linzess relative to the needs of adult IBSC patients who often are burdened by bloating, pain, and discomfort. Second, we believe our consumer promotional efforts are encouraging more potential patients to seek information, as evidenced by the increased visits to Linzess.com and the growing new patient starts. Telemedicine also continues to help make physician care easily accessible for IBSC and chronic constipation patients. Third, our professional promotion efforts focused on gastroenterologists and high prescribing primary care physicians are nearing pre-COVID levels and are having a positive impact on our overall selling effort. Finally, our class-leading payer access continues to be paramount to the success of the brand. Linzus recently became preferred brand across all commercial formularies for yet another major payer in the U.S., and we expect Linzus will continue to maintain class-leading unrestricted access in 2022. We continue to advance a number of lifecycle management opportunities with the goal of increasing the clinical utility of Lnsys. As we mentioned in August, I am very pleased that the FDA approved our proposed modification to the Lnsys label based on clinical data generated in pediatric studies. The updated label modifies the box warning for the risk of serious dehydration and contraindication against the use of children in those less than two years of age. The box warning and contraindication previously applied to all children less than 18 years of age and less than 6 years of age, respectively. As a reminder, LINDSES is not currently approved for use in patients under 18 years of age. The warning on the LINDSES label at launch was primarily applied due to preclinical findings, and there was an absence of any clinical data in the pediatric population at that time. Since that time, we've been generating clinical data in pediatrics to better characterize the potential benefit-risk profile when accrutied in this population. This important label update reflects the clinical and safety data that has been generated to date in children 2 to 18 years of age. As soon as all the ongoing planned pediatric studies with Lenacritide are completed, we plan to engage the FDA on potential additional label updates to reflect all the pediatric clinical and safety data that will be generated. Looking ahead, we're focused on delivering value to our patients and shareholders. We're confident in the strategy and the opportunities that we see ahead to improve lives of millions of patients suffering from GI diseases. We believe the growth investments we're making positions our company for long-term success. GI symptoms and GI disorders can be severe and debilitated, often ranked near the top of the list for reasons why patients seek medical care. In most cases, these disorders have limited or no treatment options, creating urgency around the need for new and innovative treatment options. To address this problem, we have built a strong, experienced team that is focused on pursuing innovative assets in GI with significant medical need and strong scientific rationale. This is what drives us every day at Ironwood, and I would like to thank all the employees, patients, caregivers, and advocates in the GI community for their shared dedication to supporting our efforts in this underserved market. I'll now turn the call over to Jason to review our financial performance. Jason?
spk06: Thanks, Tom, and good morning, everyone. I have a few updates to provide today. First, I'll walk through our Q3 financial performance, then touch on our capital allocation strategy, and provide more specifics on our agreement with CORE. And finally, I'll review our 2021 guidance. Please refer to our press release for our detailed financial information. Moving to Lindsay S., U.S. net trade sales grew 5% compared to the third quarter of 2020, given by robust prescription demand growth, partially offset by net price and inventory channel fluctuations. For the balance of 2021, we expect that the impressive non-vest prescription demand growth will sustain and we'll continue to expect mid-single-digit price erosion. Regarding the channel, we've seen fewer inventory channel fluctuations to date in 2021, resulted in favorable net sales growth in the first half of the year and is resulting in a dampening of net sales growth in the second half of the year, as was the case in the third quarter, and is expected to continue through the fourth quarter. Through the third quarter, net sales growth is up 11% year-to-date, and we continue to expect to meet our net sales growth guidance of between 6% and 8% for the full year. Turning to Linzess brand profitability, Commercial margin in the third quarter was 74% versus 78% in the third quarter of 2020. I'd like to point out that the lower commercial margin versus the same period last year was primarily the result of an increase in selling expense in the third quarter of 2021 versus the third quarter of 2020 when we did not execute as many in-person details due to COVID-19 restrictions. As you may recall, by selling expenses related to virtual call details, We continue to seek to expand margins over time due to growing Linzess net sales and disciplined investment behind the brand. In the third quarter of 2021, Ironwood revenues were $104 million, driven by $100 million in Linzess-US collaboration revenues, which were flat year over year due to net sales growth being offset by higher selling expense versus last year, as I just mentioned. Now to Ironwood's profitability. We delivered gap net income of $56 million was $65 million. Moving to cash and capital allocation priorities, in the third quarter, we generated $75 million in cash flow from operations, and ended the quarter with $574 million in cash and cash equivalents, up from $363 million at the end of 2020. As a growth company, we're focused on identifying and investing in opportunities that create We are positioning our company for future success, which includes continued investment pipeline theft and expanding our innovative pipeline of assets, such as the agreement announced this morning with CORE. And as we previously disclosed in the second quarter of 2021, we have received authorization from our board to buy back up to $150 million of our outstanding shares of common stock through December 2022. Before moving to our financial guidance, I'd like to provide more detail on the option agreement with CORE. Under the terms of the agreement, we will make an upfront non-referrable payment of $6 million to CORE and additional payments of $4 million upon commencement of CORE's clinical study for CMP104, $2 million upon receipt of FDA Fast-Track designation for CMP104, and approximately $7.5 million to perform the study. We expect approximately $10 million in 2023. After we review the data from CORE's study, if we exercise the option, we will pay CORE $35 million in exchange for an exclusive license to develop and commercialize CMP-104 in the U.S. for the treatment of PVC. Additionally, we will pay royalties to CORE in the high single digits to low double digits percentage of the aggregated annual net sales in the U.S. on products containing CMP-104, and CORE will be eligible to receive commercial milestone payments term of the agreement. We're excited to be collaborating with CORE to potentially help transform the treatment of PBC. C&P 104 fits squarely within the framework and guiding principles of our business development strategy. Going forward, we're looking at bringing assets similar to C&P 104 that are highly differentiated, target clear unmet medical needs, and have clear decision points. And we continue to see these types of opportunities in the market. Turning to our 2021 financial guidance, in addition to invest U.S. net sales growth between 6% to 8%, we continue to expect total Ireland revenue of $390 to $410 million and adjusted EBITDA of greater than $210 million. We believe in continued financial performance, strong balance sheet, and disciplined approach to capital allocation positions as well to continue to invest in our business and pursue additional opportunities in the GI space.
spk05: I'll now turn the call back over to Tom for closing remarks before Q&A. Thanks, Jason, and thanks, everyone, for joining our call this morning. I'm extremely proud of our financial performance this quarter and of our team's continued dedication to our vision of becoming the country's leading GI healthcare company. We look forward to updating you on our progress and on our 2022 outlook at the upcoming JP Morgan Healthcare Conference in early January. Operator, you may now open up the lines for questions.
spk03: At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. And your first question comes from the line of Eric Joseph from JP Morgan. Your line is open.
spk00: Hi, good morning. This is Hannah on for Eric. Thanks for taking the question. So just first with regard to the core deal, just wondering how the mechanism and clinical potential of CMP 104 contrasts with the other assets being developed for PBC. And can you speak to some of the properties of the candidate with respect to administration and dosing?
spk05: Sure. I'll have Mike Schetzlein, our head of medical, take that question.
spk02: Yeah, thanks for the question. So as you're probably aware, current therapies directed at PBC are primarily derivatives of bile acids, things like Erso and things like Ocolivin. What we're trying to achieve with the poor acid is actually very much a disease-modifying effect. because the platform actually is directed towards tolerizing the immune system. So what PBC is, it's an autoimmune disease, and the antigen responsible for the pathology of that disease that we believe today is the PDCE2 antigen. What the core asset does is it takes that antigen, encapsulates it in nanoparticles, those nanoparticles get directed primarily to the liver and spleen, In those organs, the immune system, when they see the antigen, the PDCE2, they recognize it and polarize to it so they become anergic or less responsive, or sometimes not responsive, and would not then continue the autoimmune destruction of the bile duct cells. That's the pathology of PBC. So in principle, the core acid targets the root cause of PBC, the autoimmune destruction of the bile duct cells. Current therapies try to manage disease by mimicking what bile acids do. Does that answer your question?
spk00: Yes. And can you speak a little bit just to the properties of the molecule, how it's administered, and how you ? Yes, certainly.
spk02: Yes. So currently, the dosing for the first in human study will be IV dosing given two doses one week apart. And the evidence so far to date in clinical and preclinical models suggests that that could be sufficient to adequately tolerize patients to the PBCD2 antigen.
spk05: So from a commercial opportunity, as we look at this, obviously this is a highly symptomatic disease. It's quite serious, and it could be quite debilitating in the long term. And to have a drug like this that could be a disease-modifying agent obviously could be a huge breakthrough. And you can imagine the value that could be created for patients. So I think the way we've structured the deal and certainly the clinical development pathway you know, really gives us a clear line of sight to a decision point, you know, whether we move on or not. But we're very excited about the opportunity. We're very excited about the science. And I think we're, you know, we're looking forward to working with CORE, you know, in moving this asset forward.
spk00: Great. And just looking on cc.gov, it looks like the primary study has a 120-day primary study period before the follow-up period. Just wondering, when you expect to see data and have that data in hand and how soon, after receiving that data, you have to make the option decision.
spk02: Yes, so good question. So as you know, this is the first in human study. So it is a 120-day study that we're proposing. We actually, as you mentioned, core to our strategy is understanding GI diseases and disorders, which we have a good understanding of the mechanism of action, the pathology, and the ability to interpret the data to understand the clinical value. And this approach in PBC delivers all that. That's what I'm very excited about the opportunity. So we're working currently with CORE. We're going to have opportunities to check on study progress and also look at some of the objective endpoints within the study, like the biochemistries involved in the liver pathology, things like the alkaline phosphopase, which is a recognized marker for not only disease progression, but also improvement in PBC, and also the immune-modifying aspects of the platform or of the CORE asset. where we can actually look at the response to the T cells in patients with PDC to understand their reactivity to the PDCE2 antigen. We can actually see that improve, hopefully, that's obviously the goal of the therapy, during treatment. And so we'll need to sort of get that data through the study. There are obviously labs that will be drawn through the study. And we do hope that integrating all that clinical data will give us clear decision-making for the exercise of the option.
spk00: Great. Thanks for taking the question.
spk02: Thank you.
spk03: Your next question comes from the line of David Lebowitz from Morgan Stanley. Your line is open.
spk04: When you look at the asset MP-104, I guess, could you tell us a little bit more about the indication? How is it currently managed? How is it actually, how impactful it is on these individuals' day-to-day lives? Mike, do you want to take this?
spk02: Sure. So PBC is a very chronic and debilitating disease. It not uncommonly progresses to a degree of liver dysfunction and bile duct destruction that can ultimately lead to the need for liver transplant. So it's a very serious medical condition. On the way to that, patients suffer very clinically detrimental fatigue and pruritus. the itching can be quite debilitating. And the parent therapies are urso, that I call it the acid, it's called urso, and then for urso failures, or people intolerant, they can take Ocaliva. So those parent therapies are bile acid derivatives. So they help increase the liver bile flow. So note that when we talk about what's happening in the liver to patients with PVC, they get bile duct destruction, they get fibrosis, and that impedes the flow of liver through the liver, through the bile ducts, and out into the digestive system. And that impedance of the bioflow is one of the things that drives some of the symptoms. But again, it's more managing that through bioflow. Those therapies do not treat the underlying cause of the disease, which is that immune destruction of the bile duct cells. And that's what CMT-104 is targeted to do. By taking the PDC-E2 antigen, its goal is to re-educate the immune system for how the body responds the back antigen, whereas in the PPC patient, it would destroy the bile ducts. By re-educating the T cells, therapy has the potential to eliminate that destruction or reverse that destruction and provide a better immune profile, meaning that bile duct destruction could potentially cease and patients should have a very clear disease-modifying and much better course and may even obviate the disease course if it works out completely. you know, reprogram the T cells.
spk04: If you had to look at the landscape right now on other drugs in development for PBC, how do you see this therapy as compared to them in terms of the promise?
spk02: Yeah, so along the same lines, many of the therapies that are even being considered, like fibrinates and such, still focus on that a bile acid mechanism or their bile acid mimics. So they still try to approach the PVC patient from just enhancing bile flow to the liver. So really that competitive landscape is pretty much consumed by age assets that improve liver flow, but don't really get to the underlying mechanism of the T cell destruction.
spk05: Yeah, and I think as we've talked to a number of the hepatology experts, I mean, this identification of the antigen and the specificity of the target, you know, they're very excited about this as being really the first disease-modifying agent that we've been able to have and certainly could be a real breakthrough for patient treatment. So, you know, I think we're very excited about the opportunity for this to be a game-changer and really position it all alone, you know, in this space.
spk04: And last question, as far as path forward, what would we expect on, I guess, the path to market as far as what trials are needed and the timings?
spk05: Mike, as far as the trials, are they required to get the drug approved? Yeah, sure.
spk02: So clearly, this is the initial study, as we proposed. And we're going to really need that data set to understand the benefit-risk occurring to that clinical data with the platform I demonstrated to be this will be new data in that patient population, but we'll absolutely need to see the data from this initial study to really inform when the next subsequent studies would be designed, and also obviously have an engagement with the agency. But this is sort of an orphan and rare type of disease, which means usually we can have options that could be more expeditious to market. But, again, it is premature today to sort of get too granular on that without any data in patients.
spk05: Yeah, I think, David, that's one of the things that's also attractive to us is, you know, with the potential designation, you know, by the FDA for accelerated, you know, review as a priority, you know, the time to market looks also could quite be, depending on the clinical outcome of this study, you know, could really, you know, be attractive.
spk03: is part of the reason why we see a significant value here um as we move forward got it thank you for taking my question again if you'd like to ask a question please press star then the number one on your telephone keypad your next question comes from the line of tim chang from northland capital your line is open hi thanks um
spk01: I'm just looking at the core website, and I guess their target for data would be the first quarter of 2023. And I just wanted to sort of go back. Is there orphan drug status already with this CNP-104? Mike?
spk02: Yeah, I think they have orphan drug status. I haven't confirmed that, but I think that's the case.
spk01: And... I was also looking at the clinical trials website, and it looks like the inclusion criteria for this Phase IIa study, I guess, is it treatment failures, patients that have failed on, I guess, standard of care. Is that right?
spk02: Yeah, it's in patients who have failed either ERSO or intolerant ERSO and or Ocaliga. And Ocaliga is currently available for people who can't tolerate or fail ERSO. And again, they're the bile acid derivatives that I mentioned earlier.
spk01: What is the failure rate with current meds? Is it pretty high?
spk02: Yeah, it's a range, so it's up to potentially 40%, but I think it's important to understand that even with patients on Urso or Ogiliva, this mechanism is very much synergistic in terms of if this first asset proves successful and we can polarize the immune system, then clearly that benefit applies to people even on ERSO or even on Oblivion. Now, we'll start to do studies to demonstrate that. Don't get me wrong. But I'm really trying to distinguish the fact that this immune-modifying profile is distinct and unique from what patients get when they take ERSO or Oblivion.
spk05: I think, Tim, the piece of this is it could be this disease-modifying agent that obviously and initially we'll probably look at in those failures. You think about how debilitating and problematic PBC is. It is certainly an opportunity for these two treatments, as Mike mentioned, to work together. And over time, it would probably be pulled up into earlier therapy. So if it can indeed be a disease-modifying agent.
spk01: Right. Okay. And I guess on the BD front, I mean, obviously you're looking for additional assets to bring in on the pipeline side. I think you had mentioned celiac disease previously. Is that still an area of interest?
spk05: Yeah, it is. We've talked about certainly, you know, pancreatitis. We've talked about celiac disease, which is an area of interest. You know, there's a lot of activity in these spaces that look attractive in addition to, you know, this opportunity in PBC.
spk01: Okay, great. Thanks. Thanks, Tim.
spk03: And there are no further questions at this time. This concludes today's conference call. Thank you for your participation. You may now disconnect.
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