Hey there. Great. Good afternoon, everyone. My name is Jessica Fye. I'm a biotech analyst at JP Morgan. We are delighted to be continuing the conference today with Crinetics. We're gonna have a Q&A session in this room after the presentation. If you wanna ask a question, you can raise your hand. Someone will bring you a microphone, or you can submit them electronically via the portal. With that, let me turn it over to Crinetics CEO, Scott Struthers for the presentation.
Thank you, Jess. Thank you, everybody, for coming. It's really good to see people in 3D, although I miss seeing your kids and your dogs and some of the fun things we've had over the pandemic, this is better. I'd like to tell you about Crinetics today. We're building a deep endocrine franchise and a company that can support it time and again from product to product, from discovery and soon into commercialization, being led by our phase III program, which will read out this year. There's a lot more behind that. I'm gonna illustrate with that pipeline what we're trying to do. My forward-looking statements. If you look at the company today, I think we've proven to those of you who know us that we've built a very strong GPCR drug discovery platform. We've built global endocrinology clinical trial capabilities.
We've got these phase III readouts for the first of the program coming later this year. We built a pipeline now with three product candidates with proof of concept. I'd really like you to also think about Crinetics tomorrow. Tomorrow, meaning a few years from now, we'll also be shifting into more and more prevalent indications, and we'll be getting proof of concept in those. We should have global approvals in multiple products and indications. We'll have fully integrated commercial capabilities and multiple programs in late development. We're building a sustainable company that's gonna innovate again and again in the endocrine franchise, and there's nobody else doing that. There's a lot of companies with good products in endocrinology, but nobody else going time and again to the same groups.
A little bit about how we approached it is, endocrinology allows you a fairly unique strategy for value creation. You know, we understand a lot of the biology here around endocrinology. It's not some brand-new gene that we just figured out last year. We pair that with the unmet needs and then craft high-quality drug candidates against it. We've been comparing it lately to a very fine crafted watch. You know, we're trying to design it carefully, make it perform flawlessly and look good too. This is then translated into reality because we have very predictive, translatable, highly conserved animal models. Healthy volunteer studies can predict efficacy in patients. Endocrinology invented the field of biomarkers. We measure things in the blood all the time, and in fact, it's registrational endpoints for many of our programs.
I get this secret sauce question all the time. The secret sauce is the people in our discovery group. You know, we employ. There's a lot of cool new tools coming out in GPCRs and in endocrinology, and we use a lot of them, but that's not the differentiator. The differentiator is a focused team operating on strategically designed portfolios with all the pieces playing together. You know, our teams have been playing together for more than a decade, and some of us in previous companies played together for 20+ years. It's also culture of hunting drugs, and so bringing that culture together to go solve the problems, to find the best candidates, take them into development and take them to the market.
That differentiation, speed, and probability of success is all gonna be from the teams using a lot of cool new tools and some things that we have just for ourselves. Endocrinology is actually, even though it's somewhat of an old field, it's a wide-open field. GPCRs is the largest gene family in the human genome, many times the number of gene products than, say, kinases, for example. These class that we're working on typically recognize peptide hormones, which makes them particularly difficult to target. It's high-probability biology and high-probability value opportunities as well. I list some of those indications that we're currently addressing on the right. A few that we see in the future, but there's a lot more that goes beyond just what you see here. That's illustrated with our pipeline today.
Acromegaly with paltusotine is deep in its phase III program. We've finished enrollment on the first of the two and guiding to finish the program by the end of the year. Two more programs just starting phase II, and then a discovery pipeline where we're starting to branch into more and more prevalent indications like PTH antagonist for hyperparathyroidism. We've got a very novel approach to polycystic kidney disease, which has some pretty high unmet need and also TSH antagonists. TSH may not mean much to you, but it's for treating Graves' disease, of which Graves' ophthalmopathy is a pretty good subset of those patients. I think we all see the tirzepa commercials on TV or saw the buyout, so we know that there's a decent market there.
This is going after the underlying cause of the disease, not just the eye, but the root cause, which is activation of the TSH receptor. There hasn't been a new Graves' drug for true Graves' disease since, like, 1945. And then our shtick that, one of the thing we've been really quite good at in discovery is figuring out how to make quality small molecule drugs against peptide hormone receptors in endocrinology. The most exciting thing for a lot of people lately in peptides and endocrinology are these incretins and some of the other targets for diabetes and obesity. If that's what we do the best, how can I not go into that space? Super competitive. I probably won't be talking too much about what we're doing, but very excited to get started.
All of this also shows you what I was talking about as a franchise. All of these programs are going back to the same investigators, the same prescribers. We're part of the endocrine community, not just a sponsor or somebody selling one or two products into it. There's more. I like to make sure that discovery can go in the directions that the science takes us. These small molecule ligands at peptide hormone receptors can also be used for drug targeting, solve a lot of the problems around biologic targeting for radiopharmaceuticals, for example. That's a bit of a different venture than what we do at Crinetics. We spun off Radionetics last year with help from 5AM and Frazier, and we're building that company.
The first of the INDs should be going in in the next few months. A second one later this year, a third one early next year, and a number of targets behind that. I won't spend any time on that, but I just wanted to use this to illustrate there's more to us than even just the endocrinology. We still own a pretty big position here, even though we will get diluted as time goes on. Let me talk a little bit about paltusotine, which is a first-in-class small molecule for acromegaly and carcinoid syndrome. It's more than that for us. It's the vehicle we're using to build our capabilities, both development and commercial. For those who know acromegaly, it's caused by a benign tumor of the pituitary gland that secretes too much growth hormone.
That growth hormone acts at the liver to secrete too much IGF-1 or insulin-like growth factor. It has a range of problems associated with that. Oh, what I should have said is that somatostatin receptor ligands prevent the secretion of growth hormone and help mitigate the disease. Somatostatin also inhibits other cells, including the ones that give rise to neuroendocrine tumors in the gut or the pancreas. Somatostatin receptor ligands are also used for neuroendocrine tumors, particularly those that cause carcinoid syndrome, where the tumor starts secreting serotonin or VIP or some other factors that cause severe diarrhea and flushing. It's very debilitating. Somatostatin analogs work very well there. There's a couple somatostatin analogs on the market. We have a very established biology here. We have a very established market.
It's $2.7 billion in sales with Sandostatin being, last I checked, I think it was number five or six drug at Novartis, and of course, Somatuline, number one drug at Ipsen. The market's there, but it's may even be bigger than I think the current market, current sales are. We tried to, you know, for those of you who follow us, we've started talking a little bit more about the market opportunity throughout the deck to give you some handles. In acromegaly, there's about 11,000 patients that should be addressable in the U.S. About 10,000 of those are on endocrine therapy, and you start multiplying by that by WAC, and you can see the type of market that we're talking about.
neuroendocrine tumors is a much larger population, a good 19%-30% of those get what's called carcinoid syndrome that I mentioned. That's about 3 x the addressable market as acromegaly. Right now, only about a third of those patients are being treated as we dig deeper and deeper into the script databases. We got a question we're trying to ask, which is why? It's not just about switching people and taking this market opportunity, but it's also, can we grow it by reducing the burden of care? These are not insubstantial commercial opportunities. The current treatments have a variety of challenges. Yeah, a big needle in an intramuscular injection is a problem, right? It, it is not like an immunization or something. It's more than that.
You have return of symptoms towards the end of the monthly depot cycle. You sometimes have an exacerbation of side effects at the beginning of the cycle. There's efficacy and tolerability limitations, but generally, it is associated with a very high burden of care. If we can lower that burden of care, can we improve or can we grow that market? That's what we did in laying the foundations for paltusotine when we first designed the molecule and as we designed the development program around it. Obviously, our goal is to reduce the burden on the patients, and we've engineered a number of factors into that, and we'll engineer the company to provide other factors, you know, like patient support services to help the patients. We've also made it easy for physicians to adapt.
It's a very well-behaved drug. It's simple dosing. We'll be providing HCP support services. Even if you go into the healthcare system, we're adding value there. Part of what we're also doing is preparing the company to be ready here by looking at the commercial function and the associated functions like medical affairs and quality and all that, and growing that out in time to really be ready for that launch, which is coming down the road. We're not waiting till the last minute. We're resourcing it now. It's not that. Apologies to Jim, who you'll meet in a minute, who is our Chief Commercial Officer. It's a big lift, but it's not a gigantic lift. It's, you know, the 80% of the new scripts are written by 200 endocrinologists at about 35 centers in the U.S. That's a very focused group.
The people who then maintain patients, about 80% of those scripts are written by 1,000 endocrinologists out in the community. Well, 800 in the community and 200 at the centers. It's a very defined commercial target opportunity. What we've shown, and I'm not gonna spend a lot of time on data today. It's against my grain as a scientist. I usually like to show you data slide after data slide. I'll show a little bit on each program, and this is some recent analysis of our open label extension study in acromegaly, where patients in the phase II program remain on paltusotine, quite a few of them getting out to two years now, and this continues to go on.
What you see is very stable control of hormone levels, which is the registrational endpoint for these patients. Also a very high enthusiasm for the drug, with almost 90% of the patients participating and staying in this trial, despite the pandemic and all the other things that are going on in the world these days. That is now deep into a global phase II program with over 100 sites around the world. These sites we'll use for the next trial in carcinoid syndrome, many of them, or at least the same centers, sometimes the same investigators. For Cushing's disease, congenital adrenal hyperplasia, time and again, we'll be going back to the same people who we know well now. This is just the example of how we're doing it. We have two phase III studies going.
We've completed enrollment on PATHFNDR-1. That reads out in the third quarter. Enrollment is continuing on PATHFNDR-2, but it's a shorter study, so we're predicting that's gonna finish in the fourth quarter. I might mention that for almost all of these things that I mention in data, there's hyperlinks in our slide deck, so you can go back to some pretty rich content on our webpage if you wanna dive a little deeper. I just told you that carcinoid syndrome is also a very important opportunity and even larger than acromegaly. We've started a study to begin to explore in patients with carcinoid syndrome. We're not really trying to prove a biological point because we know this target is right and we know the drug gets to that target.
We are trying to test the dosing and pharmacokinetics in the patient population. In acromegaly, we're using 40 mg and 60 mg, but based on history with the injectables, we think we may need a higher dose in carcinoid syndrome. We're doing 40, 80, and an option to go up to 120. Once we figure that out, which we hope to report out later this year, then we'll switch into the phase III program for carcinoid syndrome, so that after we get, you know, the launch going for acromegaly and get that whole organization going, the next thing comes into the commercial pipeline. We're expanding this franchise with additional product candidates that are now starting to mature and get into patient studies.
We reported out last year some very exciting first in human healthy volunteer studies, which prove the pharmacology and show the value of these biomarkers for making sure you've got the right drugs, the right dosing, or at least dose ranges. I'll just illustrate a little bit on these opportunities. I'm only talking about the indications we're doing today. There may be additional indications for both of these molecules. For 4894, this is an ACTH antagonist, is the only way in which the adrenal is stimulated by the pituitary. ACTH is a 100-year-old hormone. Harvey Cushing identified his first patient in 1910. There's 60-something thousand papers about ACTH in PubMed, there's no other ACTH antagonist in the clinic. I don't even know if there's any in preclinical.
That's Cushing's disease, which is tumors just like acromegaly that make too much ACTH, treated by the exact same pituitary docs. Sometimes it's cured by surgery, it leaves a population of about 5,000. It's a fairly difficult patient population for the pituitary docs. A little smaller than acromegaly, very substantial market, the current drugs in there are priced higher than the acromegaly drugs. Look at CAH. This is a disease where you lose the ability to make cortisol, so you lose negative feedback in the pituitary, you start making way too much ACTH, which causes a range of problems.
There's probably 17,000 patients there in that population, and there's no other approved therapy, so it's a little harder to figure out what the, you know, the potential uptake would be for that. Again, not an insignificant market opportunity. What we've shown in our healthy volunteer studies is that we can affect this system, be well-tolerated, and at 60 mg or 80 mg once a day, reduce urinary cortisol down to 70%-75%. Urinary cortisol in Cushing's patients is the registrational endpoint. So we've shown this drug does what it's supposed to do. There's a bunch of other information on this trial available in various posters and talks that we have up on the website. This shows part of the power of being able to de-risk a compound early in development in healthy volunteers.
We're starting now a study in ACTH-dependent Cushing's syndrome. This is being done at the top investigator at the NIH. It's a dose escalation study trying to figure out exactly what the doses are we'll need for the Cushing's population. You may notice that we're going 80, 120, 160, whereas in the healthy volunteers, we stopped at 80. A lot of the reason we stopped at 80 is because these healthy volunteers were starting to lose too much adrenal function, and it really wasn't ethical to keep going higher. In Cushing's patients, we can go higher if we need to. This is an open label study. We'll be looking at each patient, looking at PK, looking at hormone responses, and setting up the data to let us jump into registrational studies afterwards. This is probably a 24 event.
In parallel, we're doing something similar for CAH. Just on the Cushing's. That's already been through the FDA. It's starting at the NIH. We're just waiting for an IRB approval to get going on the study. The CAH program, you know, each indication needs its own IND. Here we filed the IND for CAH later or earlier this week. In another month, we should have clearance, which will allow us to start program, again, open label, exploring a range of doses, looking at endocrine biomarkers, to make sure we understand the dosing, tee up for subsequent studies in 2024 with the data readout in 2024. 2023 is about data in paltusotine, acromegaly, and carcinoid syndrome. 2024, we start seeing data here.
The next opportunity that I wanted to talk about is 777, which is a somatostatin receptor five agonist that suppresses insulin secretion. This is for kids who are born with genetic defects where they just make too much insulin. If you make too much insulin, you cause hypoglycemia. It's profoundly damaging disease. About half the kids end up with developmental disorders because of repeated episodes of hypoglycemia. On the right, I have a utilization of healthcare example from a little girl. Each of those symbols is a healthcare access point. The top rows are diagnosis, where she was diagnosed with CHI and hypoglycemia and a bunch of seizures. The middle row is about hospital utilization. Look at all those ER visits. This is despite being on standard of care.
It just gives you a sense of how brutal this disease is. There's a significant population of these patients in the U.S. This isn't an ultra-rare. I mean, it's pretty rare, right? Probably 1,500 kids in the U.S. that could benefit from this. There's another class that doesn't have this monogenic hyperinsulinism, but it has a syndrome. They have a syndrome that is one of the components is hyperinsulinism, and that's probably another 1,700 patients. This is a fairly rare indication, but you start adding up the burden of care, and it's a pretty decent market.
Again, in healthy volunteers, we showed that we could stop insulin secretion in a model where we create a constitutive secretion by giving a sulfonylurea, which knocks out the activity of the KATP channel, which is the most commonly mutated gene in the kids. This is a pharmacologic model in healthy volunteers that very adequately reconstructs the genetic defect. We show 90% suppression of insulin. In order for this to be safe, when you give that sulfonylurea, you're essentially giving them sulfonylurea poisoning. In order for that to be safe, you hook them up to an automated glucose infusion system. This is called a glucose clamp. If you know, don't treat them, they need a lot of glucose being pumped in. If you treat them with seven seven seven, they don't need any more glucose.
There's a lot of little kids who are still hooked up to glucose pumps or get glucose feedings through a G-tube multiple times in the day. If I can get rid of some of those G-tubes, that's pretty awesome. We're not done there. Our GPCR discovery group is continuing to work on new targets, new ideas. You know, I mentioned the radiotherapy. One of the things we've started doing is shifting from these rare disorders into the more prevalent disorders. It's almost as much work to discover a drug for a rare disease as a something that will help millions of people. As we've grown the company, we think we can start addressing it. As we think about the company in the next few years, as we continue to grow, we'll be ready to handle some of these.
I won't get into all those details, but I did want to just wrap up some of the market opportunity because I think sometimes we get pigeonholed as an acromegaly company, which is not a bad market. You know, if you start thinking about the totality of what we're addressing, we're starting to address some pretty large populations and large market opportunities. On the left is total addressable market just with our things in the clinical pipeline, just in the indications that we're looking at, and it starts to add up to a $9 billion U.S. opportunity. I'm almost embarrassed talking about the right-hand side because these numbers are so amazingly huge. When you start talking about hyperparathyroidism or polycystic kidney or Graves, which is like 1% of the population, 2% of the population, mostly women, by the way.
Of course, I think we all know that the market projections for the obesity field, diabetes, obesity combined, and all the other things that does, it just kind of goes off the charts. We're not going to take all that market. I'm not that crazy, but we're going to take some segments of it, and I think we can make some really good drugs addressing these populations. With that, I'd just like to kind of highlight what's coming up next. 2023 is a big year for us. I've kind of said that every JP Morgan, Jess has invited me to. You know, 2023, we have the two phase III readouts. We have the carcinoid syndrome data. Some of these new products, new candidates I'm talking about should mature this year, and we'll start IND-enabling work in those.
As we go into 2024, we'll be doing the NDA submission. That's a big lift. We're building the organization to do that. We'll start getting the phase II data out of Cushing's adrenal hyperplasia, congenital adrenal hyperplasia, and hopefully some of those new drug candidates from the discovery efforts are starting to get in the clinic and maybe even generating some early proof of concept in healthy volunteers. We are in a pretty strong cash position at the moment. I know it's been terrible markets for many. We've been very fortunate. Thank you to all of you who have supported us. We have money to the end of 2024, which gets us past a lot of these data points that are coming up.
I think we also start to reach a level of flexibility in our financing strategies as we get through phase III and other things that makes a little less dependent on the equity capital markets. With that, I'd just like to thank everybody, I guess we're gonna open it up to questions and bring some of the rest of the team up so that. You know, I can't handle all the questions anymore. I used to know everything that was going on, I'd like to introduce Marc Wilson, our Chief Financial Officer, Dana Pizzuti, our Chief Development Officer, and Jim Hassard, our Chief Commercial Officer. Thank you. You guys. Okay.
Great. As a reminder, if you wanna ask a question, just raise your hand, or you can submit them electronically. Scott, I'm sorry to start on acromegaly.
It's an obvious area to ask us about.
Can you walk through what results would represent a win in your mind for each of the phase III acromegaly trials?
The primary win is beating placebo. That's, I could say, a low bar. But it's also not just about the responder rates, which are the primary endpoints. It's about IGF levels. What you care about in patients is not whether they meet some arbitrary threshold on IGF of 1x the upper limit of normal, which defines, you know, a responder in our case. But if we show that IGF levels are the same on paltusotine as they were on the patients in the run-up, where they were on standard of care, and that's in PATHFNDR-1, that's great. What hesitancy would you have of switching a patient then to a much less burdensome therapy, if you can show the same efficacy with a more less burden?
In PATHFNDR-2, these are patients who are not on current SRLs. They've been off for some reason, never had it, or have washed out. They'll all be uncontrolled acromegaly patients. We expect the vast majority of them to have improvements in their IGF levels, and some proportion will hit the responder threshold of one. There you also get a feeling for the real population out there, where almost everybody benefits from an SRL. If they don't quite get low enough, you add something else on top of it. I didn't give you a single number, you know, X%, but I think you get the gist of what makes this a good drug.
These studies are reading out in sequence, right? If we get positive results from PATHFNDR-1, how's that gonna make you feel about the odds of success in the next study?
I'm actually, I'm not. Maybe I shouldn't say this. I'm not that worried about the biological outcomes here. It's about study designs that we've committed to. It's about recruitment. It's about making sure the data integrity is good. By finishing PATHFNDR-1, we've shown we can do all that, right? We've shown we can recruit that study. We re-finished it last fall. I think it helps with PATHFNDR-2. There's still some risk left in PATHFNDR-2. It's a population many of whom we haven't looked at before. There's not much biological risk there. There's a lot of execution risks, so.
Can you talk about some of the reasons we could expect stronger data from paltusotine in phase III than we saw from MYCAPSSA?
Sure. For those of you who don't know, MYCAPSSA is a twice-a-day reformulation of a generic octreotide that gets about a half a % bioavailability. What we've seen in the studies there is that on average, patients who switch from standard of care to that drug have an increase of about 20% in their IGF levels. Goal of switching somebody, you're trying to reduce IGF levels. You're not trying to increase them. That provides a pretty big burden. We've shown in our phase II that switching keeps IGF levels the same. I actually don't spend too much time thinking about that. I think more we're thinking about how do we message to patients and docs so that switching is easy, so that they're aware of our drug.
That those people who are used to using Sandostatin or Somatuline for a long period of time are comfortable switching. That's the competition to us.
I know you said this was it a medium lift, not a huge lift or something?
I shouldn't say.
Can you talk a little bit more about how you're thinking about building the sales infrastructure for acromegaly and beyond the U.S., do you expect to launch independently in Europe, for example, or would you partner there?
Yes. My part of that is to hire Jim and let him answer the question please.
Thanks, Jess. In terms of sales force, what we have already started to do was, we've hired on commercial operations, which you saw the marketplace by the numbers. We've now gone through the claims analysis and I think have a much better understanding of what acromegaly looks like, what carcinoid syndrome looks like, not only here in the U.S., but also ex-U.S. Next is to really build out market access, because we do recognize that's one of the lessons learned, I think for us from the MYCAPSSA launch, is to make sure that we've got a very strong relationship and value proposition in front of the payers, but also in front of providers and in patients. When we think about the sales force, you saw the numbers.
I mean, 200 physicians who are initiating, about 1,000 doctors who are in total that are maintaining. We're thinking, you know, maybe a sales force of September 20 sales reps. We think that we can be very cost effective about launching into acromegaly. The other thing that we're doing is we know that carcinoid syndrome is coming along the road not too long. As we develop the infrastructure for commercial, we're keeping one foot in acromegaly and rare disease and one foot in oncology, which we know is probably gonna be in-office dispensing and probably a little bit different world. We wanna be ready for that and flexible for that. On the ex-U.S. side, we have already partnered with SKK in Japan, and we are, you know, again, taking a very cost-effective look at launching paltusotine ex-U.S..
We are definitely gonna launch with Crinetics team in the U.S.. Ex-U.S., we're really looking at, again, are there partners out there that can do it more cost effectively than we can and provide more value to the marketplace and to Crinetics.
Yeah. Maybe I'll just add also who really understand their geographies. It's a big lift to launch a drug in the U.S. for a small company launching their first drug. Don't wanna go too broadly, but yet there's patients out there around the world where we're doing our studies who should be getting access. That was Japan. China's not too far away. We need to think about China, and we're doing some of these studies there. Europe, of course, and Western Europe. Europe is not one country, obviously. It's a complex mix. I think we could use some help there. As you think down to the future, like in CHI, there's very narrow prescriber base. I don't think we need any help in, say, Europe with CHI or maybe Cushing's or maybe CAH.
I think we need to be flexible in our partnering to get paltusotine to the people who need it as soon as we can, but also keep optionality so that as we grow and build this global franchise, maybe we have the opportunity to be a more global company down the road as we grow into it.
Maybe switching to carcinoid and NET, I don't have the slide right in front of me, I think you were talking about a opportunity in carcinoid that was sort of on par or maybe even bigger than what the injectables are selling in NET already. Can you unpack that just a little bit more, how this kind of subset population could be bigger than the injectable sales are today?
You wanna talk about that, Jim?
Sure. Again, the numbers by the numbers, it, we see about 33,000 carcinoid syndrome patients diagnosed within the U.S. space. We estimate that again, about 11,000 of those patients are on a somatostatin analog at any point in time. You know, this is actually a question that we're diving into. You know, why is only a third of those patients when it's a symptomatic oncology, almost a supportive care type of opportunity, why are there only that many patients treated? I think some of it is just adherence. Believe it or not, you know, patient adherence within the oncology space, which is a little surprising, but it is one of the things that we're uncovering. I think the other piece is, I do think that there's also an efficacy opportunity here as well.
We know that there are many of these carcinoid syndrome patients that are being treated more frequently than monthly with the somatostatin injection. In some cases, every two weeks, every three weeks. Physicians are having to employ just a number of different strategies in order to treat more severe patients with carcinoid syndrome. It's perhaps an efficacy opportunity for us with a once daily, again, oral opportunity for for carcinoid.
Can you talk about what kind of data we should expect to see from the phase II you're running in carcinoid syndrome?
Yeah. I'll start with what you shouldn't expect to see. This isn't a big powered study to prove some proof of concept. This is an open label exploratory study to make sure we have the right doses, because we're going up into doses we've only really explored in healthy volunteers. We think from the way the injectables are used, that you really do need higher doses in carcinoid syndrome than you do in acromegaly, and that's why people double up the frequency to multiple times a month instead of once a month. We wanna explore that. We wanna make sure that we're getting the exposures we know should be saturating receptors throughout the body. Make sure we get our entry inclusion/exclusion criteria right.
It's basically setting up to be ready to launch a registrational program as soon as we get enough patients in to make us comfortable about our choices on dose and these other aspects. I gotta say, it's also always nice to get a little experience in that indication. And those investigators in the U.S., it's a slightly different set than the acromegaly investigators. ex-U.S., sometimes it's the same investigators. You know, gaining a little experience is also helpful.
What are you gonna be looking for clinically? What's kind of the meaningful signal to you?
We'll see, I'll call it almost anecdotal efficacy. We're looking for an increase in symptoms as they wash out from their existing drug, and then a resolution of those when they go back on paltusotine. It's not a powered study to detect that. We really wanna see, make sure we got the right PK, right patient entry criteria. It's not so much a go, no-go as. You know, unless we see something really unexpected about absorption, right? Which, remember, these patients have very severe diarrhea, so their gut transit times can be much faster. Now, paltusotine is absorbed very rapidly, so I think it's okay, but that may contribute to dose selection issues. We know about PK/PD in acromegaly. There's not a lot of reason to believe there's a difference in PK/PD if you can get as much in as you need.
Maybe last one just on CHI. I think the IND didn't get cleared late last year, and I think there was gonna be some period of time. You might have heard from the FDA a little more detail. What's the latest?
Our DNA whisperer.
Yeah, right. Yeah, as far as the, you know, clinical hold, I mean, we need to really sort of understand the big picture because we did the phase I outside the U.S., right? In adults. We had, you know, very, you know, good response, no safety issues at all. What we did with the FDA is give them, you know, a full IND package, you know, sort of wanted to go right into kids, right? I think that it was quite a large, you know, set of documents, including a, you know, tox reports and things like that. As it came up to the deadline, they still had some more questions about that, you know, sort of preclinical data. They sent us the details of what the questions were.
We also had several other studies ongoing at the same time. You know, based on our assessment, we'll just need to pull all those things together. We have a lot of confidence we'll be able to sort of get them to lift the hold. It'll take a couple months to get all these additional pieces and to directly answer the questions that they had on what we had submitted. It shouldn't take too long.
I think we're out of time, so thank you.
Thank you. Thank you, everybody, for coming.