Ardelyx, Inc. (ARDX) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Ardelyx Corporate Update and IBS-C Key Opinion Leader discussion. During this event, we will refer to the press release issued earlier today, which is available on the Investors section of the company's website at ardelyx.com. During today's discussion, we will be making forward-looking statements that are subject to risks and uncertainties. Our actual results may differ materially from those described. We encourage you to review the risk factors on our most recent quarterly report on Form 10-Q that was filed on October 31, 2023, and can be found on our website at ardelyx.com. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. Our President and CEO, Mike Raab, will begin the first portion of today's event with opening remarks, followed by Susan Rodriguez, Chief Commercial Officer, who will provide an update on the performance of IBSRELA in 2023, as well as our plans and expectations for the product in 2024 and beyond. Justin Renz, Chief Financial and Operations Officer, will conclude the formal remarks by reviewing the financial implications of today's announcements. During the second portion of our event, our Chief Medical Officer, Dr. Laura Williams, will conduct a Q&A with our guest key opinion leader, Dr. Philip Schoenfeld, the Chief Emeritus of Gastroenterology at the John D. Dingell VA Medical Center in Detroit. Dr. Williams and Dr. Schoenfeld will discuss the IBS-C patient population, the dynamics currently at play within the IBS-C market and the impact of IBSRELA, Ardelyx' FDA-approved treatment for IBS-C on the treatment landscape. At the conclusion of the event, we will accept questions from attendees in the room. For those listening along on the webcast, please submit your questions through the Q&A function of the webcast portal. With that, let me pass the call to Mike.

Thank you, Caitlin, and good afternoon. Thank you, everyone, for joining us here in San Francisco and online. In March of 2022, we launched our first commercial product, IBSRELA for the treatment of IBS-C. IBSRELA is a first-in-class product that was discovered and developed in our labs here in Fremont by Ardelyx. It has a strong clinical profile, and we knew that it could benefit patients who are suffering from the debilitating symptoms of IBS-C. With that launch, Ardelyx delivered on its mission of discovering, developing and commercializing first-in-class novel mechanism therapies that address significant unmet medical needs. Over the past 21 months, we have demonstrated that when there is a clear need in an established market and when a novel drug such as IBSRELA enters the market with the right commercial approach, that a significant impact can be made. Now, nearly 2 years later, we find ourselves in a position that we anticipated disrupting the IBS-C market and bringing meaningful benefits to patients who need another option. Our consistent quarter-over-quarter growth clearly demonstrates the potential for IBSRELA and reflects the success of Ardelyx' innovative commercial approach. Several factors have contributed to that success. First and foremost, IBSRELA is a remarkable medicine. It has a differentiated mechanism of action and a strong clinical profile that is translated to the real world. Initial positive experiences with IBSRELA have encouraged health care practitioners to expand their consideration of prescribing IBSRELA to their other IBS-C patients. Second, we launched IBSRELA with an innovative commercial approach. Susan and the team have demonstrated that when you think differently about launching innovative products in established markets, you can find success. We launched IBSRELA focused on a large subset of patients not well managed by existing IBS-C therapies, and we targeted only those high-writing health care practitioners who see these patients every day. Third, we focus on supporting patients at every step and have made significant investments on access and affordability. Today, we stand with nearly $100 million in sales since launch, and we can confidently say that IBSRELA is addressing an unmet need amongst patients who are now finding relief from their IBS-C symptoms. Our optimism has grown since launch, and I'm excited to have the opportunity today to share our future expectations for IBSRELA. Before I hand it to Susan, I will take a moment to comment on XPHOZAH, our first-in-class phosphate absorption inhibitor that was approved late last year. We're extremely pleased with the initial performance of XPHOZAH. These early days are validating that the demand and interest demonstrated by our research are real. That early demand in combination with XPHOZAH' strong clinical profile, novel mechanism of action and the Ardelyx' commercial approach, gives us confidence that we have yet another significant opportunity with XPHOZAH, an opportunity which we will discuss in more detail during our fourth quarter earnings call. I will now pass the call over to Susan. Susan?

Thank you, Mike. I am so pleased to be here today. As Mike alluded to, it has been an incredible 24 months. This time 2 years ago, we were preparing to launch IBSRELA, building our commercial team, finalizing our positioning and marketing strategy and executing on our access strategy. Since that time, we have seen consistent quarter-over-quarter growth with IBSRELA becoming increasingly established as an important option for patients in the IBS-C treatment armamentarium. Our preliminary Q4 results that we announced this morning, reflecting approximately 26% growth over the third quarter continues to demonstrate persistent growth in new prescriptions, refill prescriptions and new writers, as well as continuous expanded use across our growing wider base, all key indicators of growing foundational demand. There are some very important learnings from 2023 that predict continued strong growth momentum in 2024. First, IBSRELA, with its novel mechanism of action, has established an important role in the IBS-C treatment armamentarium, addressing an important clinical unmet need for patients whose symptoms persist despite treatment with existing prescription therapies. Second, the IBS-C market is highly responsive to IBSRELA's profile and our promotional efforts. Our experience in 2023 demonstrated that engagement with our sales team yields adoption and high-frequency engagement with either our team in the field or with messaging from our omnichannel communications yields expanded use. Third, patient experience with IBSRELA has been favorable. And as a result, physicians are persistently expanding their view of patients who could benefit from treatment with IBSRELA. And fourth, positive experiences with access and affordability further supports expanded use. As we look ahead, the growth potential for IBSRELA is significant. At launch, we stated that we believed we could achieve mid- to high-single-digit peak share with estimated sales at that time of $500 million. HCP interest in adopting and expanding their use of IBSRELA, combined with the responsiveness we are seeing to our go-to-market approach and promotional activities indicates even greater potential for IBSRELA. 21 months of on-market experience has provided us with a clear view of the long-term growth potential. We believe it is realistic to expect that with our approach, IBSRELA can grow to achieve approximately 10% share of the $5 million annual IBS-C prescription market. With achievement of this market position, we expect that IBSRELA has the potential to generate more than $1 billion in annual sales before patent expiration. Continued investment in this market will be key to realizing the full potential for IBSRELA. To accomplish this, beginning this quarter, we will increase our sales team to 124, expand our promotional programs and omnichannel digital capabilities, increased sample availability and expand the office and patient support provided by our ArdelyxAssist patient services program. Physician adoption, recognition of patients in need, positive treatment experiences and favorable access are the fundamentals driving our IBSRELA growth, all driven by our proven best-in-class commercial team. The combined strength of these forces predicts continued persistent share gains as we bring the benefits of IBSRELA to more and more patients in need. With that, I will hand it to Justin.

Thank you, Susan. Earlier today, we issued a press release providing important updates into our commercial performance in 2023 and future expectations for IBSRELA. I wanted to briefly walk through that information, as well as our cash and investments position as of December 31, 2023. Please note that these are preliminary unaudited financials. We will share our final audit financial results when we report our fourth quarter and full year 2023 earnings in late February. We believe that having the most recent information that we can share available aid today's discussion. Our fourth quarter 2023 U.S. net product sales revenue for IBSRELA were approximately $28 million, reflecting an approximately 26% growth over Q3. On an annual basis, U.S. net product sales revenue for IBSRELA were approximately $80 million in 2023, exceeding the guidance range we provided in late October of approximately $76 million to $78 million. In addition, we also had approximately $2.5 million in U.S. net product sales for XPHOZAH in the fourth quarter, bringing total U.S. net product sales revenue to approximately $82.5 million for the full year 2023. We expect IBSRELA's strong performance to continue. And as Susan said, we now believe that IBSRELA can achieve approximately a 10% share and could generate greater than $1 billion in annual net product sales revenue at peak. Our path to achieving that, we expect 2024 full year U.S. net product sales for IBSRELA to be between $140 million and $150 million. Growth will be driven by continued expansion of the patient population and the additional commercial team members and marketing investment that Susan outlined. To support this increased investment in IBSRELA, we anticipate that we will incur incremental operating expenses over the course of 2024, averaging approximately $20 million more per quarter than our fourth quarter 2023 run rate. Finally, as of December 31, 2023, we have an unaudited cash and investments position of approximately $184 million, not including a $3 million milestone payment we received last week from Fosun, our partner in China in recognition of our XPHOZAH U.S. approval that we achieved back in October. We currently have 232 million shares outstanding as we have made no sales under our ATM program in the fourth quarter of 2023. We feel confident that our cash and investments position will support our planned investment in IBSRELA, our commercial support for XPHOZAH and some initial investments in early-stage R&D programs. Our focus in 2024 will be to grow the top line, maintain a strong balance sheet and deliver shareholder value. Thank you. And with that, I'll hand it back to Caitlin.

Thanks, Justin. We'll now transition to the second portion of our program, the Q&A session moderated by Ardelyx' Chief Medical Officer, Dr. Laura Williams. Dr. Williams will be joined by Dr. Phil Schoenfeld, the Chief Emeritus of Gastroenterology Section at the John D. Dingell VA Medical Center in Detroit, Michigan. Dr. Schoenfeld received his bachelor's degree, medical degree and a Master of Science degree in medical education at the University of Pennsylvania. He completed his gastroenterology fellowship at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr. Schoenfeld went on to serve in the U.S. Navy Medical Corps for more than a decade, retiring at the rank of Commander. After his service, Dr. Schoenfeld joined the University of Michigan School of Medicine as Professor of Medicine and practiced in the specialized functional bowel disorder group. Throughout his career, he has held a number of leadership roles for the American Gastroenterological Association, including Chair of the Education Committee, governing board member and Chair of the Clinical Practice section of the AGA Council. As a thought leader in the field of GI, Dr. Schoenfeld has shared his expertise with a number of organizations and is a paid adviser for Ardelyx. Dr. Schoenfeld has published more than 250 original research studies, editorials, book chapters, commentaries and abstracts. His original research studies have been published in the New England Journal of Medicine, British Medical Journal, Gastroenterology, Journal of National Cancer Institute, American Journal of Gastroenterology Pediatrics and the Annals of emergency medicine. He has been involved in the development of evidence-based guidelines and its co-authored the American College of Gastroenterology guidelines on irritable bowel syndrome and chronic constipation among others. Dr. Schoenfeld is currently Editor of Evidence-Based GI in ACG publication. Previously, he served as an Associate Director of Gastroenterology in the American Journal of Gastroenterology. He has been on the editorial boards of numerous GI journals. He has given more than 150 lectures at national and international gastroenterology and internal medicine meetings, as well as gastroenterology and internal medicine grand rounds at academic medical centers. I am pleased to have Dr. Schoenfeld join us today to share his perspective, and I'll hand it to Dr. Williams.

Thanks, Caitlin, and thanks again to Dr. Schoenfeld for joining us today. What an amazing body of work. Before we dive in, an opening question for you, we've gotten your bio, but can you please tell us a bit more about your vast experience in the IBS-C space?

Well, thanks very much for inviting me today, Dr. Williams. And listening to that bio, just made me think, gosh, I'm old. I've been doing this for a long time. So I would just highlight that I've spent the majority of my career as a GI motility specialist, focusing on the management of patients with irritable bowel syndrome and similar GI motility disorders, as well as focusing my research on that. And fortunately, I've then been able to lecture, not just at GI-focused medical education meetings, but also at this stage in my career frequently with primary care physicians at what are called Primate Conferences. So, I think although my most recent career journey has had me practicing at Veterans Affairs Medical Centers that I do have a very broad understanding, both at the primary care level, as well as the GI practitioner level of what they're experiencing through giving those lectures and interacting with those folks.

Absolutely. And that's why we're so excited to have you here with us today. So with that, let's get started. I've tried to group our discussion around 3 general topics. First, focusing on IBS-C and the need for different therapies, and then evaluating the experience to date with IBSRELA. And then finally, we should end on discussing the evolution of the treatment paradigm for IBS-C, particularly in the setting of new therapies like IBSRELA. So with that, as you know, the pathophysiology of IBS-C is multifactorial, and the burden of patients can be great. So from your experience as both a physician and thought leader in this space, can you speak to us a little bit about the need for additional therapies with different mechanisms of action for patients with IBS-C?

Sure. And although I recognize that the audience is quite sophisticated, I do want to just establish a baseline, remembering that irritable bowel syndrome has no single underlying pathophysiology and that it's a disorder characterized by constipation with abdominal discomfort and bloating or crampy pain. And we believe that there are multiple different insighting pathophysiologic defects. It could be changes in the bacteria that live in the gut. It could be defects in the way different receptors work in the intestine. It could be defects in the way the brain communicates with the intestine to control the way the smooth muscle and the colon squeezes. So, based on that, there's also no single therapy that's going to work in everybody. And for the vast majority of my career, we were quite limited in our treatment options and still are, to a large extent. Remember, the FDA has only approved essentially 2 classes of medications for the treatment of IBS-C, Amitiza, which is a chloride channel agent working on chloride channels in the intestine and linaclotide, or Linzess, and plecanatide or Trulance, which are guanylate cyclase-C agonist, again, working on receptors in the intestine. But other than that, we don't have any treatments that have truly met the high bar for demonstrating efficacy set by the FDA until now the addition of IBSRELA.

Great. Great. So what would you say are some of the challenges in treating patients with IBS-C?

Well, again, because it is a multifactorial disorder, one of the big challenges is that, no single medicine works in everybody. And thus, we want to have medicines with different mechanisms of action to utilize to see what's going to work in patients. Because when you look at the whole spectrum of studies in irritable bowel syndrome, you rarely find that more than 40% to maybe 50% -- close to 50% of patients are responders based on stringent endpoints for therapeutic success. So I know going in when I treat patients that I may have to work through a few different medicines before I find a combination that's going to be successful in that patient. And that's troublesome when there are very few options.

Yes. No, that's a very good lead into the next question, which is what is the typical treatment journey for patients with IBS-C? And what impact does this condition have on patients?

Well, let me answer the second part of this question first, that although irritable bowel syndrome with constipation is not a life-threatening disorder in the way, say, diabetes can be or inflammatory bowel disease like Crohn's or ulcerative colitis. I've spent my whole career taking care of these patients. And frankly, a lot of them are just miserable. They find that their day-to-day life is disrupted by their symptoms. And although some of my medical colleagues may be a little bit dismissive that, "Oh, you're not going to die from this. It's not a big deal." My experience is much more that these patients really suffer and really benefit when they get treated effectively. Now, having said that, as far as the patient journey goes, for many years, the approach was to use over-the-counter therapies. Osmotic laxatives, like MiraLAX to help them pass stool, adding some fiber supplements to their diet, like Metamucil or Psyllium or to try to modify their diet to eliminate foods that might trigger their symptoms and maybe also trying some probiotics. Although the bottom line is, when all of those things have been studied in rigorous randomized controlled trials with the possible exception of fiber supplements, they haven't shown benefit to treat the overall symptoms of IBS, meaning not just to maybe get your bowels to move more frequently, but to actually treat the underlying abdominal discomfort and bloating and cramping, which can be so debilitating for these patients. So generally, the patient journey is, they see a few different physicians and try multiple over-the-counter therapies until, hopefully, they find a provider who takes them seriously and tries to treat them a little more aggressively.

Great. Great. So here's a 3-part question. I'll start with this. Among the patients with IBS-C that are treated by a physician, approximately what percent would you say are treated with a prescription medication?

So it's tough for me to give a great answer to that question. I would say at the level of a gastroenterologist, the vast majority of these patients now are getting treated with a prescription medication, assuming that they've already tried over-the-counter therapies. And by the time a patient gets to a GI doc, they've tried over-the-counter therapies like MiraLAX or Metamucil. At the primary care level, I think it can vary quite a bit. But I would say, based on my experience, lecturing multiple times per year at primary care conferences, at primate conferences that there has been a huge expansion in awareness of treatment for irritable bowel syndrome among primary care providers. All of you are in marketing and investment in sales, and the number is better than I. But certainly, there has been a big growth among primary care providers about willingness to write prescription therapies for irritable bowel syndrome in the last 10 years.

Yes. And among those patients who are on prescription-based medicines, what would you say is the percent of folks who actually have residual symptoms despite being on those medications?

Well, just to kind of get down to the brass tacks of it, the things that our FDA approved are Amitiza, which is a chloride channel agent that works on these channels in the intestine. That's been available for more than 15 years. The problem with it based on my clinical experience, and really, if you also look back at the RCT data is that, it's not a very potent agent for abdominal discomfort and as you increase the dose, you tend to see nausea developing your patients. So although it's now gone generic, really GI docs at least don't use that. So bottom line is, what we use or guanylate cyclase-C agonist agents, linaclotide or Linzess, or plecanatide or Trulance. The problem is that, that tends to provide adequate relief in only about 50% of patients, which compared to when I started my career, 30-plus years ago, gosh, if I got 50% success in IBS-C patients, I'd be ecstatic. But now I think there's growing awareness that we can still do even better.

Right, right. So what would you recommend or what do you recommend for those patients who have persistent symptoms despite being on these prescription medications?

Sure. The answer to that is partly based on what their predominant symptom is, whether it's bloating, whether it's feeling a lot of abdominal discomfort and cramping, whether it's very severe constipation symptoms. But generally speaking, your go-to as a GI doc, is to use the guanylate cyclase-C agonist such as Linzess or Trulance. And again, that's because by the time a patient gets to me, they've almost certainly tried some combination of osmotic laxatives and diet modification and using some of the different peppermint oil extracts that sometimes can be helpful for abdominal spasm.

Right. So, again, how important do you think it is then to have therapies with different mechanisms of action? I think there are other examples in other disease spaces, but just wondering what your thoughts are on that.

Well, I think there are 2 parts to my answer to this. The first part is that, as a provider, and I think among patients, our expectations have grown. And here's an analogy I'll use. Again, going back 30 years, pretty much all I had to treat inflammatory bowel disease, meaning Crohn's disease or ulcerative colitis was going to be using prednisone or steroids, maybe a 5-ASA product like Asacol or surgery. And any improvement in symptoms was going to be beneficial, was going to be, "Hey, we at least, you're not pooping out blood 5 times a day with hit success." But gosh, now in the last 30 years, there has been such an explosion about all the different points in the inflammatory cascade that we can target with treatments so that our expectations for improvement we expect to see in Crohn's disease or ulcerative colitis is much higher. Same kind of idea here. We've gone from having Zelnorm as a prescription agent to having guanylate cyclase-C agents like Linzess, now adding on IBSRELA and thus, our expectation for how much better we can make patients feel begins to get higher, too. 30 years ago, all I could do is give him an osmotic laxative and say, "Hey, I hope you poop more often even though you still have a lot of bloating and cramping. So expectations are higher. Now, having said that, and again, just kind of getting down to the brass tacks of it, that if somebody fails on, say, Trulance or plecanatide, because that's the preferred guanylate cyclase-C agent at my own institution. I am not going to switch them to Linzess to another treatment with the same mechanism of action. I'm going to switch to something that works differently because I know IBS is a multi-factorial disorder. I want to use something with a different mechanism of action. So to that extent, having these different options becomes much, much more important.

Yes, absolutely. I like that whole analogy in terms of inflammatory bowel disease. It's almost -- it's very similar to just primary care. You wouldn't take somebody who has high blood pressure on a diuretic and give them another diuretic. So I like that.

Yes. And going back to, gosh, the 1960, diuretics were all we had for high blood pressure. And then over time, we've identified multiple other targets to reduce blood pressure. So, again, yes, you're not going to start another diuretic if one diuretic failed to do the job in high blood pressure.

Absolutely. Well, that sort of concludes that first bucket of questions in terms of just IBS-C and the need for additional therapies with different mechanisms of action. And I think it's fair to summarize your responses as there is definitely still an unmet need and using drugs with different mechanisms of action is, obviously, approach that you've taken in that we've seen in a number of different therapeutic areas. So with that, let's move to the second group of questions, which is really around your experience with IBSRELA to date. Just looking in terms of both clinical outcomes, as well as access to the drug. So we spoke earlier about the typical patient treatment journey for patients with IBS-C. How would you say IBSRELA fits in that treatment journey?

For me, it's really very straightforward. If a patient that I see with irritable bowel syndrome with constipation has tried guanylate cyclase-C agonists like Linzess or Trulance, and they haven't gotten an adequate response. And again, that to me means about 40% to 50% of patients will experience at least about a 50% improvement in the frequency and severity of their symptoms. That if they don't get a good response, then the next thing I choose to use is IBSRELA because it's a different mechanism of action. And that's actually pretty consistent with the hoops I need to jump through in order to get access. Pretty much it's a diagnosis of IBS-C and the patient failed to guanylate cyclase-C agonist at my Veterans Affairs Medical Center.

Right. Right. Well, I think you've answered the next question, which was approximately what proportion of patients would you consider to be good candidates for IBSRELA and why? And so, maybe the why piece, I think you've touched on that also, but I don't know if you have any additional comments...

I think the bottom line there is just -- and this is my anecdotal clinical experience. It's not necessarily something that's been studied in a prospective randomized controlled trials is that, a lot of my patients who failed a guanylate cyclase agonist, get treated with a sodium hydrogen exchange 3 pump inhibitor, meaning tenapanor or IBSRELA, and they do get a good response to that. And that works for them where what they had been tried on previously didn't work. And there are nuances here. I do want to emphasize that. Depending on the patient, if they have severe pain that might be a centrally mediated pain syndrome, meaning things like fibromyalgia or post-traumatic stress disorder, I may look to use different types of agents that work in the central nervous system. So I don't want to make it seem like it's truly a cookbook. There is a lot of art to the practice of medicine here. But having said that, there are also just some quick bottom lines about what we're going to go through next. Certainly, that's what I teach when I work with my GI fellows.

Right, right. No, that's great. I mean, the art of medicine piece is also an important piece. And so, when you're -- when new innovative products come to market, it can be challenging. And so, I'm just curious, what sort of methods or strategies that you use when you're explaining to patients or introducing a new innovative product to patients and why they might benefit from it?

Well, I think one very important thing is to address safety whenever you're dealing with the new medication, and it just can't be emphasized enough. Medicines like IBSRELA don't get absorbed. You can't measure them in the blood stream. These are agents that work on receptors that line the intestine and don't get absorbed. And the corollary there is, if it's not getting absorbed into the bloodstream and circulated, then you're not going to see an increase in adverse events or side effects compared to when you use a placebo. That's not to say a patient never gets the medicine and says to get a headache, but that happens if you give them a sugar pill, too sometimes. The only thing that I actually try to educate my patients about is, you may get a little bit of diarrhea when you first start this medicine. Well, but that's to be expected because that's the therapeutic response to using the medicine. And usually, any loose watery stools are pretty mild and occur in the first week. And I just try to preview that to the patient. Having said that, yes, it's important for them to know you're trying something that works in a different way if they've already failed a few different medicines previously.

Right. Absolutely. So then, what are you seeing in terms of treatment response to IBSRELA in your patients, as well as any anecdotal color you're able to share from your patient experience?

Sure. I think it's fair to say that my clinical experience is that, I tend to see about a 50% responder rate among patients who have already failed guanylate cyclase-C agents. That's my clinical experience, not necessarily something demonstrated in a prospective trial. But again, if patients who have failed back try IBSRELA and they come back to me 2 months later and say, I'm seeing a really significant reduction in how often I feel bloated and crampy, and I'm passing stool much more frequently, than having a 50% response rate in this type of disorder is really quite good, especially considering this is difficult to treat if somebody has already failed a few different medicines.

Right. Absolutely. So what are you hearing also from other gastroenterologists who have started to use IBSRELA from their vantage point in terms of clinical experience?

Sure. A lot of my experience is with other GI physicians who specialize in motility disorders. These are the docs that take care of the really severe IBS patients at Cleveland or the Mayo Clinic or at Stanford, and they found very similar experiences. Having said that, I think among the broader GI community, they haven't tried it yet, or maybe they've only tried it a couple of times. And I think that reflects the potential for further growth because the average GI dock takes a little while before they pick up and start using newer medications. And it's really only been out and available for about 18 months. So it will be interesting to see where we are in another year or 2 down the road as hopefully, first general GI docs and then growing out in primary care too begin to use the medicine.

Right, right. And I know at your institution, there are prerequisites to prescribing IBSRELA. But once the patient has met those prerequisites, what would you say has been your experience in terms of access to IBSRELA?

I'm the GI motility specialist in my institution. So, if they have a diagnosis of IBS with constipation and they failed to guanylate cyclase-C agonist, that's essentially it. And for my colleagues that are GI motility specialists, that's usually all they face as far as prior auths go. As always, with physicians, we complain about the paperwork and what has to be done to overcome prior auths. But there are things that you can do to overcome those obstacles. I'm sure we'll talk about that in a minute.

Right. Absolutely. So that brings us really to the third bucket of questions that we've sort of put together here. And it's around the introduction of IBSRELA and how it's influenced the overall treatment paradigm for IBS-C. There has been an evolution, obviously, of the treatment paradigm as each new innovative therapy comes to market. And so, a few questions, just a couple, I think, in that group. First, how has -- how would you say the introduction of IBSRELA changed the approach to treating IBS-C?

I think that for GI motility specialist, we're aware that we have something else to offer to patients because there are a lot of patients with IBS with constipation who don't get adequate relief with currently available products. So there is a big population of people that can benefit from this. And I think that's really the bottom line message.

Okay. Great. And then how would you say IBSRELA has advanced the care for patients with IBS-C?

Well, I think, again, if I go all the way back 30 years, my hope with patients was if I give them an osmotic laxative like MiraLAX, I could just get them to poop a little bit more frequently. And then with the introduction of Zelnorm and then ultimately, then when we move to guanylate cyclase-C agonist, we were like, okay, we can really do something to take care of the bloating and the cramping, our threshold for what success began to rise. And I think that's the case here now. I might have somebody on a combination of a couple of agents where they're mildly better, but compared to the kind of success I'd like to achieve in my patients, to help them live their lives happily every day, I know that I can still try to do better in terms of managing them and working with them.

And has that changed the sort of the dynamic, the patient physician conversations that you have with your patients now because you have something else to solve?

Sure. I mean, joking with my GI colleagues in the past, a patient with irritable bowel syndrome with constipation, all we'd want to ask them is, how often you're moving your bowels? Because if the patient said, "Okay, now instead of only moving my bowels twice a week, I move them 4 times a week." We'd say, great, you're doing a lot better and head out the door because we didn't want to stop to ask them any other questions about how they were doing because we knew we couldn't take care of the other stuff. Now, a good GI motility specialist is going to ask them a little bit more. How often are you feeling bloated? How often are you feeling crampy? How often is your day disrupted by your symptoms because we have higher expectations about what we can do for those patients.