Great. Good afternoon, everyone. My name is Jessica Fye. I'm a Senior Biotech Analyst at JP Morgan, and we're continuing the 42nd Annual Healthcare Conference today with Crinetics. I'm joined by the company's CEO, Scott Struthers. He's gonna give a presentation on the business, and then we're gonna go into Q&A after that. If you wanna ask a question in the room, raise your hand and someone will bring you a microphone, or alternatively, you can send questions through the portal up to this iPad over here. So with that, let me turn it over to Scott.
Thanks, Jess. Good afternoon, everybody. Thanks for having me. Thanks for coming. Thanks to those of you who've supported us through the years. I'll refer you to our forward-looking statements, of course, which I'm sure you've all read carefully. Since the last time I was here a year ago, we're a very different company. The strategy we've been following since the beginning of the company hasn't changed, but it's beginning to bear real fruit. By the end of this decade, Crinetics will be the premier, fully integrated endocrine company, and it's happening now. Patients around the world will be able to get our products in clinical development, candidates in discovery will be making their way into late-stage development, and revenue from sales will begin to self-sustain the growth of this business. 2023 was a hugely successful year for us. We advanced the pipeline dramatically with paltusotine.
We're poised for patient data from our second molecule, 4894. Our balance sheet is strong, and we leveled up on several different dimensions. But 2024 and 2025 are gonna be transformative to us as we complete phase III in acromegaly, submit our first NDA, make paltusotine broadly available to acromegaly patients around the world, and keep the rest of the pipeline moving, including investing in new discovery programs. But how have we been able to do this, and why do we think we can keep on doing it? Well, our way remains unchanged since the beginning of the company. We have deep roots in endocrinology. Myself and Alan and many others in the company have spent our entire careers studying endocrinology or working on drug discovery and development in endocrinology.
It's a wonderful branch of science and medicine, and we have also an unwavering personal commitment to the patients we've met and are hoping to help, and help transform their lives through the science that we work on every day. We built a world-class in-house R&D capability, and it's bringing together the combined skills and experience to craft some very finely crafted molecules designed to harness endocrinology to make a difference in human health. And by following that way, excuse me, we've built a remarkably deep pipeline. All of these have been internally discovered. All of them we own the rights to, and I think this is fairly exciting for us on many different levels. The lead program is approaching registration, and we anticipate a PDUFA date in 2025.
The second candidate is in phase II, with key patient data coming soon, and there's multiple programs in discovery, some almost on the verge of coming into development, targeting important diseases that can affect many millions of patients. We're just getting started. Paltusotine is leading the way. It's our lead program for acromegaly and carcinoid syndrome. It exemplifies our commitment to personally, purposely crafted medicines that I think you'll see in some of the data, can really have a transformative effect on patients' daily lives. We've built a world-class development capability to bring us to this point, and that capability is now in place to let us take the next drug, and the next drug, and the drug after that into global development, and we use many of the same sites and centers for all of those.
So I wanna talk a moment about paltusotine as an example of how we approach things, and you'll see it applied throughout the rest of the program. So when we thought about this, starting this program, it was very much designed with the needs of the patient in mind. The current standard of care for people living with carcinoid syndrome or acromegaly involves monthly deep subQ or depot injections that, that are given intramuscularly, most of the time requiring time out of your day to visit a healthcare professional. And for many, they wear off towards the end of the month, meaning you need to go get these injections every two weeks or every three weeks. And just imagine that, what this does in terms of trying to manage your life in addition to managing your disease and just normal everyday things.
But also imagine what it would be like if you can get rid of all that and just take a pill every morning, one that can control your disease throughout the month, that provides durable and stable control, and I think this could have a real impact on people's lives. And our goal with paltusotine is to help patients focus on living that life and not focus on managing their disease.... Now, in September, we reported what I believe to be some of the best phase III data in acromegaly, certainly that I've ever seen. We hit the primary endpoint with a very high responder rate and a very low placebo rate. All secondary endpoints were met, including ones measuring the effects of paltusotine on patient well-being in an Acromegaly Symptom Diary, which has not been done in previous medications in this indication.
It continues to be safe and well tolerated as it has throughout its clinical development. And I think this study showcases our commitment to running high-quality global trials, and you see it in things like a 4% placebo rate. You know, a lot of us, especially in the investor community, take for granted running clinical trials, and we expect certain outcomes. It's hard, and you've got to follow every little thing going on around the world to make sure that you get this type of data, and we built a team that can do that and does it repeatedly. Now, beyond acromegaly, we're also developing paltusotine for carcinoid syndrome using the same model and know-how that we've already established in acromegaly. Carcinoid syndrome affects 30,000 patients in the U.S., and it's caused by some of the subsets of neuroendocrine tumors.
Patients to treat these are also taking some of the same depot injections that have the same impacts on acromegaly. It's the same medication. Our treatment goals with carcinoid syndrome are to reduce the urgency and frequency of excess bowel movements, to reduce the flushing that can be quite debilitating, but also to reduce the potentially severe complications such as carcinoid heart disease. Again, as with acromegaly, let people focus on life, not managing their disease with these monthly injections. You know, I know we like to look at statistical data, and I have some of that for you, but to me, looking at the effect on an individual patient really helped bring that to light.
And this is just one of the subjects in the study, and if you look at our data release from last December, you can see a couple other examples. But here's somebody with no prior therapy. In the reddish-brown bars is the number of bowel movements, and you see the... Sorry, in the brownish bars is bowel movements, and in the red bars are flushes. And you see in the flushing that this person had up to nine, eight, seven a day, and bowel movements four or five times a day. Now, put yourself in the place of this. This is. You know, you wouldn't be able to work your way through this day's meetings. And then the day after they started taking paltusotine, the flushing went to zero, and it stayed at zero throughout the treatment period.
And on bowel movements, it went down to normal, which is one to three per day. So this is the type of thing that a somatostatin analog can do for a patient with carcinoid syndrome. And of course, as you look at the population, we show the statistics here on the left, number of excess bowel movements, so this is more than three per day. On the right, frequency of flushing, and this, you know, any flushing is abnormal, and both were reduced by 65%. In addition to this, we've shown benefits on the severity of flushing, the urgency of bowel movements, and we're measuring a variety of other dimensions of how this impacts patients' lives. So this is the initial data set. It was roughly 23 patients. 36 patients have now been enrolled. That data we'll report out later this, later this quarter, early next quarter.
I think we said the first half. That'll be a more full data set. In addition to building a world-class R&D organization, as you've seen, we're also trying to build a business. Together, acromegaly and carcinoid syndrome represent a significant market opportunity where we intend to be the dominant player. Acromegaly alone represents a $800 million U.S. opportunity, and for carcinoid syndrome, it's already a $1 billion-dollar market. But surprisingly, there are many patients not yet on somatostatin analogs. And presumably, since we know it works, you know, the existing drugs still work for carcinoid syndrome, it's got to be something around burden of care or access to care that's keeping them from that. We see that as a growth opportunity.
And we're working hard to understand the details of the patient journey in both these populations, and particularly in carcinoid syndrome, so we understand what we need to do in our phase III program, which I anticipate starting later this year, to fully bring out the potential benefits and uses to optimize the label we get in carcinoid syndrome. Over the past year, actually year plus, we've also been aggressively building out our commercial capabilities and understandings in these specific markets. We've been working with the pituitary centers, I mean, Alan and I, for decades, but, as a company now for the life of the company, as well as the top KOLs. But many of these also overlap at the sites with the top KOLs and centers for neuroendocrine tumors.
But we're also digging a little deeper into exactly who are the people at these institutions that are writing the scripts that patients are filling, so that we make sure we have a detailed plan when we're ready for launch. Also, not surprisingly, as we begin to learn about the market and test different messaging, we're finding that the data from PATHFNDR-1 is really resonating with this community and generating a great deal of excitement, both in the acromegaly prescribers and in the carcinoid syndrome prescribers. Beyond the HCPs, we're really starting to work on understanding the payer perspective. It's super important in getting to new drugs, getting new drugs out to patients who need them. So our Chief Commercial Officer has hired a VP of Market Access. She's building out her team.
We've talked to more than half the top payers already and beginning to understand what are their concerns. And we know that they appreciate some of the benefits, both to the patient and to the economics of the healthcare system, that an oral pharmacy benefit could provide. We've also done work on some of the more logistical aspects, like getting our third-party logistics underway, and we're finalizing specialty pharmacy agreements to make sure we can provide full service options to the patients and the physicians to get the drug to them as easily as possible. And finally, you know, this is also about transforming the company into one that is ready for commercial at all levels, including from an IT and a compliance, and you shouldn't underestimate the lift that's required. But we're on it.
Leading the way with paltusotine, behind it, we've built a very strong R&D capability that we're now deploying to help increasingly more patients with each new candidate entering development. The one right after paltusotine is 4894, which is an ACTH antagonist. The lead indication there is congenital adrenal hyperplasia, which affects about 27,000 patients in the U.S. Now, in patients with congenital adrenal hyperplasia, they can't make cortisol, and they make too much adrenal androgens, exemplified by the A4 on the bottom left. But it's not just about normalizing those adrenal androgens. In women, we wanna help restore normal menstrual cycles. In men, they have these testicular adrenal rest tumors, which both cause pain and impair fertility. And so in both men and women, we hope to improve fertility.
We also hope to prevent the consequences of androgen excess in the pediatric population, which can be long-lasting, including atypical genitalia, precocious puberty, short stature, and hirsutism. What we find is right now, the prescribers are a bit stuck 'cause the only tool they have is glucocorticoids, and, you know, these are the same glucocorticoids you use for, you know, inflammation, for example. They end up giving high levels of glucocorticoids to try and suppress these adrenal androgens, which causes a whole set of other problems associated with too much glucocorticoids, like weight gain or hypertension or bone disease. So one of the other treatment goals is to enable physiologic dosing of glucocorticoids, physiologic replacement. To deal with this, to address this, we employ the tools of endocrinology. The hypothalamic-pituitary-adrenal axis is one of the great stories in endocrinology.
The pituitary controls the secretion of ACTH by the... Sorry, the hypothalamus controls the secretion of ACTH by the pituitary. There's a couple of different factors that do that: corticotropin-releasing factor and arginine vasopressin. ACTH is then acting at the adrenal, where it stimulates the production normally of cortisol, but in these patients, just A4. And there's a couple different ways that ACTH is regulated, and so now we're starting to see the effect of CRF antagonists in CAH and the ability to start to suppress A4. And we're targeting this ACTH receptor because there's no other way to stimulate the adrenal with ACTH than through that receptor. So we think that's a lower level, more complete possible blockade.
That is now in a phase II study that is targeting, as I said, the ACTH receptor, to try and achieve maximal A4 suppression, with data coming out, preliminary data coming out now in the second quarter. And the way to think about it is like shown on this diagram. So first, many patients on glucocorticoids come in with very elevated, A4 levels, and we've seen now in some of the trial populations in phase III, levels of 600, 700, over 1,000, depending on the study population. When normal is really 200-300, 200 or below, and actually quite a bit lower than that for many different types of populations. And to get there, they're on multiples of what they should take for glucocorticoids, and that's shown in that upper gray box on the right.
Now, what we've seen with the ACTH antagonist is the ability to suppress this part of the way, which is fabulous. And so when you add a CRF antagonist, you can eliminate the CRF-dependent part of the A 4 secretion, and then as you lower A4 , you can adjust down glucocorticoids and get some patients down into normal glucocorticoids, normal A 4 levels. But an ACTH receptor antagonist blocks all the signaling, or can block all the signaling to the adrenal, so we expect that to not only be able to achieve the CRF-dependent levels of suppression, but also all the other activity of ACTH that's going at the adrenal. So we expect that to be able to have lower levels of A4 suppression, which should enable better achievement of physiologic, glucocorticoid replacement. But we're not stopping at 4894.
We're also developing multiple preclinical programs, and the next two on deck are shown here. On the left are antagonists of the parathyroid hormone receptor, or PTH, and this is for hyperparathyroidism, or too much parathyroid. You've probably aware of some of the work being done on hypo for too little. Well, this is the opposite, too much. So, but we can induce hyperparathyroidism in a rat by giving them a pump infusing excess PTH, and you see here the vehicle group with excess PTH causes a severe hypercalcemia. And then if you give back the PTH antagonist, we bring them back to normal levels of calcium. This is the same type of thing one would do in a hyperparathyroid patient. We're now at the final candidates. Several molecules are in toxicology studies and should enter IND-enabling work this year.
The one slightly behind that is a TSH antagonist for Graves' disease. Graves' disease affects 1%-2% of the population. Many of those patients go on to get Graves' ophthalmopathy, or more recently referred to as thyroid eye disease, probably 'cause it's a lot easier to say than ophthalmopathy. But we can induce this model in a mouse. It's caused in people by an antibody which activates the TSH receptor. So we take those same antibodies, give it to a mouse, thyroid hormone levels go up, and with those TSH antagonists, we can bring them back to normal. Now, this isn't quite at the candidate selection stage, but we've got a lot of really good molecules, and we're just trying to solve the last little pharmaceutical problems to make them a real drug.
And like every program in here, we're making, you know, thousands of molecules to make sure we get the one that is good enough to go into millions of people. 'Cause you don't skip on discovery, 'cause you're gonna live with that molecule for the next 20 years, first in development and then in, in commercial. This stuff is really hard to do. You're optimizing 20, 30 different dimensions with difficult chemistry and difficult assays, and you need a lot of different experts. But this is what we're, we're really been working at our entire careers and the entire life of the company, is crafting small molecule drugs at peptide hormone receptors. And there's a lot of different peptides out there. They touch every part of every cell in the body. But continuing this story in the coming years will lead to tremendous growth and value creation.
2024 sets the stage by submitting our first NDA in addition and advancing additional indications and candidates. But 2025 will be a real inflection point as we come up on our first PDUFA date and, FDA willing, our first launch. Going into the second half of the decade, we expect multiple additional launches, a continuous stream of clinical milestones. As sales of paltusotine grows, we'll become self-sustaining, and we'll continue to invest in our discovery and development efforts because there's lots of patients out there that can benefit from intervening in these peptide hormone and other endocrine systems. Endocrinology has the ability to impact almost all aspects of human health, and we're just getting started. So thank you for your attention, and I believe we're gonna have the rest of the management team come up for some Q&A. Happy to take your questions.
I have with me to my left, Jim Hassard, our Chief Commercial Officer, Alan Krasner, our Chief Endocrinologist, and Marc Wilson, our Chief Financial Officer.
Great. Thanks for the presentation. So we saw really robust data from the PATHFNDR-1 study, and now that we're on the cusp of PATHFNDR-2 data, can you just recap the differences between the two trials and talk about the extent to which PATHFNDR-1 could support high likelihood of success for PATHFNDR-2?
Alan?
Sure. PATHFNDR-1 and PATHFNDR-2 represent a package of data, which address pretty much the broad spectrum of acromegaly patients that we'd like to cover in our NDA. PATHFNDR-1 were the well-controlled patients already on the injection treatments, who switched from paltusotine versus placebo, and that's some of the data Scott showed you in the presentation that turned out very well with very strong response rates on drug, very low response rates on placebo. That's the maintenance population. PATHFNDR-2 is about the treatment population, that is, patients with acromegaly who are not controlled and not controlled biochemically and not treated currently.
So that would include patients who are truly naive to medical therapy, patients who need medical therapy but have not been treated, for four months prior to entering into the study, or patients who are controlled on medical therapy, sort of like in PATHFNDR-1, but who are willing to wash out of that, those injections during a screening period. What these patients all have in common is when they are randomized to receive either treatment, or placebo, they all start out with a high IGF-1. This is the registrational biochemical endpoint, and paltusotine would be expected to lower IGF-1 in a way that is superior to placebo. So in terms of read-through, you know, I think PATHFNDR-1 data were very, very clear that paltusotine effectively lowers IGF-1, and based on that, I would expect read-through to PATHFNDR-2.
The goal for PATHFNDR-2 is much the same as it was in PATHFNDR-1, to show an increased rate of IGF-1 normalization at the end of treatment compared to placebo.
Maybe we can spend a minute on the commercial potential for paltusotine, specifically thinking about acromegaly. Is it possible to walk through a framework about how to think about that peak sales potential?
Jim?
Sure. Thanks, Jess. So I think the numbers that Scott shared are the numbers that we look at, and that is: What's the market? What's the price? And then, obviously, what's the market share? In terms of the market overall, we do look at about 11,000 patients within the acromegaly space. There are about 2/3 of those 11,000 are on a somatostatin analog, an injectable, currently. There are about 30% of the patients that are actually on a monotherapy dopamine agonist, and so we look at the opportunity across both the somatostatin analogs and across the dopamine agonists as well. In terms of price, we're looking at right now about a $70,000 list price per year for each acromegaly patient.
And again, we really feel that, you know, comparatively, we've got a better opportunity to manage the gross to net within that price point, so we're thinking about, you know, a much closer net price to that $70,000 mark. I think the big question for us is share, obviously, and so, in terms of that framework, how will we influence share? It's a relatively small market in terms of the endocrinologists that are in the space. 80% of the prescriptions are written by about 200 endocrinologists at 40 pituitary centers, and the additional maintenance of those patients is conducted by an additional 800 endocrinologists. So a total of about 1,000 targets for us to influence market share on that front.
You mentioned having better gross to nets, you think, than the injectables. Where are the gross to nets for the injectable?
Yeah, so the gross to nets currently for both Somatuline and for Sandostatin are in the range of 30%-40%, and that's a function of essentially the buy and bill market and, you know, discounts, rebates, and the constant maintenance of the average selling price within that space. So we really do feel that we've got, as an oral in the specialty pharmacy space, in the rare space, we've got a better opportunity to manage that gross to net.
Assuming PATHFNDR-2 is successful, what are some reasons why 100% of the patients on injectable therapy would not eventually adopt paltusotine?
So a hun-
I asked the same question, Jess.
100% market share. I was just gonna say, Jess, you've been speaking to Scott, my boss. So I think—you know, first of all, you know, successful PATHFNDR-2 will give us the broadest possible label in combination with PATHFNDR-1 , so we'll have the opportunity to look at both switch and treatment of acromegaly patients. When we think about the successful PATHFNDR-1 , as viewed by key opinion leaders in this space, we've had a number of advisory boards post PATHFNDR-1 , and they view this as not just successful, but really exceeding expectations. So it has added a great deal of confidence. You know, that 83% response rate has given physicians a great deal of confidence that they can switch from their injectables to the oral.
So that has helped out a great, a great deal. But I do think that the number one thing that we've got to be aware of is just habit. It's physician habit in terms of prescribing, and a lot of that is going to be mobilizing patients to really talk to their physicians about their experience on injectables, tolerability issues that they may be having, efficacy issues that they may be having, certainly pain, the pain of injections, and really get those patients to speak to their physicians again, to break that habit.
That's an interesting point about mobilizing patients, since the physicians don't feel the pain of the shots. What are your kind of techniques or tactics you're gonna use to do that?
Yeah, so I think you'll see this year we're going to start a disease state education campaign with physicians, first of all, just to. There is a lot of published data in this space on, again, the experience of patients with it, with standard of care. We'll start on that front with physicians, and closer to launch, we'll run the same type of campaign with patients. We've already been testing this, and almost, you know, universally, patients do experience these breakthrough symptoms or an issue of tolerability and certainly the pain of injection. But these are stoic patients.
You know, they. It's taken a long time for them to get diagnosed with acromegaly, and they've known this therapy of injectable SRLs now for some time, but universally, they will tell you if they had an oral option, they would take that oral option. So it's really getting that dialogue between patient and physician mobilized and enacted, especially as we head into launch.
But in addition to just that messaging and communications, we're putting in place a patient and physician services hub, so that we can help those physicians manage the prior auth, for example, help the patients deal with their insurance companies, you know, have somebody to talk to if they need help getting this all worked out. Because I think we all experience this in the room, and certainly my friends that are prescribers feel a lot of frustration with actually making the system work for you to actually get the medicines you need. And with our, our patient and physician services hub, we can help them with that in a compliant way.
I think you talked about kind of the potential number of target prescribers. So how are you thinking about building a sales force in the U.S. for acromegaly, and what about outside the U.S.? Do you wanna go it independently, or would you partner?
Yes, so within the United States, we're looking, first of all, medical affairs, we're building out over the course of 2024. As we enter 2025, closer to launch, we've already mapped out where the, you know, the territories are, and what the coverage is. We're looking in the range of maybe 30 sales reps to cover that target list across the 40 pituitary treatment centers. With outside of the U.S., we have a partnership with SKK in Japan. We're looking at partnerships in China, South America, and also in Europe as well.
Just to be clear, we're not needing those partnerships. Maybe in China, and PATHFNDR-2 does have enough patients to support a Chinese submission. But the alternative is we go into those regions ourselves. But one way or another, these drugs need to get to patients around the world. We just need to figure out the right economic way of doing that.
Me switching to carcinoid. That initial data you provided looked pretty clean and consistent, so what is it that you want to see in the final data from that phase II study?
Alan, maybe you want to comment.
Well, right. We are running a phase II study in patients with carcinoid syndrome, primarily to explore the relationship between paltusotine dose and response. Response in carcinoid syndrome is defined as reductions in the frequencies and intensities of the key symptoms, which are diarrhea and flushing. Really, I think the interim data that we did disclose already are pretty compelling, and I suspect that when we complete the dataset with 36 enrolled patients treated for the eight-week core part of the study, it will confirm the kinds of conclusions we're already beginning to arrive at based on this interim data.
That is, paltusotine really looks like an SRL in terms of its ability to relieve patients, both of the diarrhea and flushing, in a very rapid and sort of consistent way. So this will be the final dataset that we will take to the FDA with us, as we have an end of phase II meeting and talk about phase III planning.
So speaking of phase III planning, what is your initial thinking on, you know, the potential design or designs that you're kind of mulling over for a phase III trial? And what specifically, what decisions around that will the phase II data inform?
Yeah, yeah. The phase II data will be incredibly valuable to help us look at dose response, as I mentioned before, but also to explore and test using data a variety of potential endpoints that we would want to use either primarily or and secondarily in our phase III trial. I mean, at a high level, I would predict that we're heading toward a placebo-controlled trial. At least the most recent regulatory approval precedent in carcinoid syndrome was a three-month parallel group, placebo-controlled trial. And I suspect, based on our understanding of what the regulators might expect for approval, that's kind of where we're headed.
We are very much interested in capturing the full benefit of paltusotine in these patients, in this patient population, and that would include controlling both the diarrhea and flushing associated with this syndrome. So we will be testing various approaches to showing that quantitatively and in a statistically rigorous way, so that we can propose the right endpoints for the FDA at our end of phase II meeting.
Can you talk about why you would or wouldn't think about expanding into broader NETs beyond carcinoid?
Well, a couple different things. So neuroendocrine tumors affects about 170,000 patients in the U.S., and a subset of those have carcinoid syndrome, where somatostatin analogues have been remarkably efficacious. And as you saw in this patient example, you can see effects, like, that day. So it makes for a very facile study. On the flip side, as you start looking at progression-free survival in broader NETs, for a while, somatostatin analogues were the only game in town, and they would slow progression to an extent in neuroendocrine tumors. But those trials are very large, very long, 'cause median progression in those patients is many years.
And over the last few years, we've seen the advancement of radiotherapies, which provide a significant new option for people with neuroendocrine tumors, and I think you all know how exciting the radiotherapy space has become. I think as anti-tumor agents, naked somatostatin are less and less relevant, but we're committed to these patients, and we have some very clever ideas, I think, in discovery about how we might make non-radioactive options to have real anti-tumor effects. There's lots of different things going on in the discovery kitchen, and I think that's the better approach than committing a lot of capital to a large, long study to have an incremental effect on these patients. And part of this comes into fiscal responsibility, which I know is a big topic for all of us the last couple of years.
You know, we're, we're very sound financially, but we have a lot of different things to invest in, and an incremental benefit for paltusotine probably doesn't outweigh fully exploring thyroid disease or the obesity programs that are on the horizon. So we gotta be thoughtful about where we invest our dollars.
Where should we think about pricing for paltusotine evolving, if at all, if the label does expand from acromegaly into carcinoid?
Jess, probably what we'll look at is actually linear pricing between acromegaly and carcinoid syndrome as well, and it'll then just depend on the dose. So I know that we're looking at, you know, a price comparison of, say, the 40 mg to the standard of care right now, maybe in acromegaly, and maybe it'll look at, you know, a multiple of that as we get into carcinoid syndrome.
I think the other thing to realize is we're starting to develop a package out of phase III in acromegaly, you know, that really is unique in talking about direct benefits to patient symptoms and consistency. And similarly, we're thinking about how to do that in carcinoid syndrome. And I think, as Jim mentioned, that the whole burden of care of these injections on the healthcare system and the cost associated with it leave a lot of room for us to create a lot of value with this oral pharmacy benefit. So it's a little early to talk about price per se, but I think we're in a good place.
Okay. Looks like we're about out of time, so we'll stop there. Thank you.
Thank you, and thank you, everybody.