Great. good afternoon, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th Annual Healthcare conference. For our next session, we're very excited to have a hybrid presentation and fireside with Crinetics, and it's my pleasure to introduce Tobin Schilke, the Chief Financial Officer, and Alan Krasner, the Chief Endocrinologist. Tobin and Alan, thank you so much for joining me.
Thank you, Tyler. It's great to be here at the used to be just the Cowen, but now it's the TD Cowen Conference. I've been coming for almost a decade now, and it's always a pleasure, and you're a terrific analyst, Tyler, and I really appreciated working with you the last year I've been at Crinetics.
Thanks very much.
We're gonna be making forward-looking statements. Please read them as you do your diligence about this investment opportunity. Crinetics was founded in 2008 by three great entrepreneurs, and they have this crazy mission in 2008 to be the world's leading endocrine company. Here we are last year launching our first drug, and it's been an amazing journey. I've been only part of that, but the breadth and scale of diseases and the ambition that this company can treat is really remarkable. Our first drug was approved for acromegaly. That same medicine will be, and Alan will talk in greater detail, being in advanced clinical trials right now for carcinoid syndrome.
We have our second drug, all developed in-house for CAH for both adults and pediatrics and also for Cushing's disease. We have our third drug that started in the clinic, last year for NETs, our first sort of quasi-oncology opportunity, and a really diverse and interesting pipeline rooted in endocrine science, that we are excited to introduce in the years to come. Like we said, it's a really experienced team of drug hunters in the GPCR space, have brought one drug already successfully to the marketplace, another one in advanced clinical studies. Like I said, nine clinical programs and a really deep, scientific-driven, conversation that we've had. Again, like we said, a lot of clinical trials, a lot of execution, a lot of catalysts that Alan will talk about down the road.
We launched our first drug last year, and that is quite a journey, having done it a few times at various companies. All the things that are required from being a R&D house to being an R&D commercial company, and that vision to becoming a self-sustaining company, is there. Building those capabilities was a core focus of management in 2025. I believe we've demonstrated that by selling and being able to deliver PALSONIFY to patients, delivering $5.4 million in revenue and over 200 start forms. Again, that goes on to ensure patients. Like we said, 2025, a breakout year, that fully integrated pharmaceutical company.
We did raise some additional capital at the beginning of this year, and we're well funded into 2030 with all of our ambitious agenda. Again, we feel that PALSONIFY, our first program that was approved, should be the standard of care for acromegaly, and we feel like we are on the right trajectory at this point in time for where we planned for the vision of this product commercially. Again, we were really pleased to show additional phase II data from cohort 4 of our phase II trial in CAH for atumelnant. It's a very exciting study, and we've announced that our first patient's been enrolled in the adult and the pediatric phase IIIs program as well. We also announced just last week the design of our Cushing's disease program for atumelnant as well.
We initiated first patients into our 9682 program as well. Again, kind of zooming in a little bit to our launch of PALSONIFY or paltusotine, over 200 enrollments, strong demand from patients. Of those 200, there were about 22 that were all the U.S. patients that were in our open-label extension program enrolled and were part of those enrollment forms. We had a really good breadth and depth of prescribers for acromegaly, over 125 unique prescribers, and they were nicely split between the academic centers or the pituitary treatment centers, PTCs, and the community setting. We feel that that's a very healthy mix at this phase of the launch between academics and pituitary treatment centers.
The last thing is we priced the product, and we announced that price and the value proposition of what the product delivers and can deliver versus how the payer's receptivity is promising. While it's early days, there's some really good promising starts to what we're seeing, and that's what we tried to identify here basically is that, you know, over 50% of the patients who are getting quickly reimbursed through these medical exemption forms, and the others are going through a Quick Start process, which we hope to bring them on to reimbursed medicine in the next average 60 days or so. For the prior authorizations that have been granted so far, 12 months, about a year is the average duration or about for most of these. That's really good.
That's translated into over $5 million of product revenue in our first quarter. With that, I'm gonna turn it over to my friend and esteemed guest once he fixes his microphone. Alan, we enjoy these conferences very much and working together.
Thanks very much, Toby.
No problem, Alan.
Toby.
It's all good. Take your time.
There we go.
There we go.
Thanks so much.
I'll pass the baton.
Thanks. Well, thank you. Thank you, Toby. Thanks for your attention. This is the Crinetics pipeline. The theme of Crinetics pipeline is novel small molecules generally designed to interact with GPCRs in therapeutic ways, oftentimes targeting not known therapeutic endocrine receptors. We are, in some of these cases, targeting some of these receptors for the first time in therapeutic medicine. The prototype example there is atumelnant, which is an ACTH receptor antagonist. We've known about the ACTH receptor since the 1930s, or at least the ACTH itself and the receptor subsequently, this is the first time an antagonist has been tested in humans. We will review some of that data, I'm sure, during our discussion. paltusotine is the first, as Toby mentioned, approved molecule, approved last September.
It is also it illustrates another theme at Crinetics pipeline, that is simplifying the treatment of patients with complex and sometimes esoteric endocrine diseases. Paltusotine is a once-a-day oral agent, which is in some patients so far and hopefully more later, replacing decades of traditional therapy, which is primarily consisted of once-a-month, very painful and sometimes disfiguring injections that require healthcare provider administration. You can see overnight, the way this disease can be treated and by whom it can be treated, is being, I believe, revolutionized by paltusotine. Atumelnant will simplify the treatment of two other very complex and esoteric diseases, congenital adrenal hyperplasia and Cushing's disease. We also have a very rich preclinical pipeline, particularly in endocrinology, including a TSH receptor antagonist and a PTH receptor antagonist.
None of these have been targeted in humans before. We hope to have clinical candidates as early as next year for those. paltusotine is also being studied, as Toby mentioned, for a completely different indication, and that is for the treatment of carcinoid syndrome. 20% of patients with neuroendocrine tumors have the carcinoid syndrome, which comprises diarrhea and flushing, which can be a very disabling syndrome for patients. We have phase II data which we've already announced, which shows great promise that paltusotine itself, orally delivered once a day, can make a big difference and again, supplant those monthly painful injections of octreotide or lanreotide. This has entered phase 3. Phase 3 is enrolling for carcinoid syndrome. atumelnant is also entering either phase III in adults or phase 2/3 for pediatric CAH patients.
Phase 2/3 for adult Cushing's patients, as we recently announced too. You can see it's a very robust and active pipeline, both in clinic and in the preclinical setting. We're also interested in endocrine oncology at Crinetics. Just as paltusotine itself might be a treatment for a paraneoplastic syndrome that results from neuroendocrine tumors, we are also, we've also invented in-house a novel molecule which hopefully can help be an antitumor agent for those same kind of neuroendocrine tumors or related tumors. This is CRN09682. This is similar to an antibody payload, toxic payload conjugate molecule.
Only in our case, consistent with our theme, this is a small molecule that was invented from scratch, specifically targeting the endocrine receptor SST2, conjugated to a payload for a cytotoxic reduction of neuroendocrine tumors or related tumors. This is in first-in-human phase I dose escalation as we speak. Very robust pipeline for a company our size, as Toby mentioned, all these things came from in-house discovery work. We've also been doing in-house development of the clinical candidates and continue to internalize many of those development functions. Once again, we are commercializing our first product. Let me just wrap up with upcoming milestones for paltusotine. Those with the star are this year. We are continuing to execute commercially on PALSONIFY in the U.S., paltusotine.
We have just received a positive recommendation from the CHMP for European approval, hopefully in May. Atumelnant, the ACTH receptor antagonist, we've talked about initiating the trial in Cushing's or ACTH-dependent Cushing's syndrome first half of this year. We expect to have additional data from an ongoing open-label extension study from our congenital adrenal hyperplasia patients. Getting back to Cushing's, we also have an ongoing single center study at the NIH, which is still generating data, and we hope to update the Cushing's disease data with atumelnant as early as mid this mid part of this year at the Endocrine Society. 9682 , the SST2 targeted anti-tumor compound, which is in first-in-human study. The name of that study is the BRAVESST2 study. It's in the dose escalation phase.
Hopefully, someday we'll advance into a dose cohort expansion phase as well. The early-stage compounds, which are also very exciting, that I mentioned. Thank you very much for your attention. We look forward to the question and answer period.
Wonderful. Thank you very much for the presentation, Alan and Toby. We will start with, naturally, with the PALSONIFY launch. A strong, early launch, as you noted. What can you say about, well, we're in March now, right? We have January and February under our belt. What can you say about what we've seen year to date and what we should expect from that launch over the course of the year?
I think in general our messages are really resonating. The team has been really engaged, and like I said earlier, you know, when we think about 2025, we ended the year with really strong momentum, and we hope to carry that momentum into 2026. I do wanna be careful on sort of our discussion about interim quarter results here, we're not gonna be talking about how we're doing inter-quarter, but we feel very confident on the progress we're making right now with PALSONIFY and introducing it to the marketplace.
As we think about, the 200 patient enrollment or start forms and that number building over time, can you tell us kind of so far what you're seeing in terms of the time between a start form or enrollment form and going on drug and also the Quick Start program, what's that process look like in terms of conversion to paid drug as well?
Yeah, that's a great question. Maybe we take it in turn. We'll, our hub and our specialty pharmacy receive an enrollment form. We look at it to make sure it's generally in the right direction, and at that point in time, if we do so, we say we've received an enrollment form. We can't just say we've got 200 enrollment forms because someone faxed in a little piece of paper. It has to be generally complete. At that point in time, the specialty pharmacy then tries to take it to a payer at that point in time, we wait for about a week or so to get feedback from that payer. If we're not hearing anything, we get them on the Quick Start program.
I'm diving into this a little bit to sort of put that 50/50 metric in context. What we talked about is that 50% of the people have that medical exception form and have reimbursement at that first node of decision, basically. The rest of those folks get a bottle of PALSONIFY, which is a month's supply, under the Quick Start program administered through our CrinetiCARE Hub. At that point in time, our team works with the practice and the payer to sort of get the right paperwork done that will make the payer want to reimburse PALSONIFY. Our goal and industry benchmark is typically a couple of months to kind of adjudicate those Quick Start forms through. They'll have a month's supply.
We'll be working hand in glove with the office and with the payer. What we've seen generally in those sort of navigating those first batch of is feedback from the payer isn't, "Gosh, we're not ready to reimburse PALSONIFY." It's, "This form needs... Do we need more information on this piece of form, this and that." It's more about completing and being as accurate as possible and providing them the correct literature for them to take a decision versus step edits or other things along that prior auth pathway. That's the journey so far, and it's been quite encouraging.
When do you expect full coverage to come online?
Well, I think what we guided is to have like three-quarters of lives covered within nine months of launch. That's sort of what our benchmark is. I don't know if it's efficient to get every single person covered or try to, you know, over time as we build and scale, kind of get beyond that because there's a law of diminishing returns, if you could imagine. Like we've had some really quick wins early on that were surprising to us, honestly. The decision earlier this year by CVS Caremark, which is, you know, a global fact, to be on formulary. We think we're all on the right trend. We typically see a little bit more...
There's some seasonality about formulary decisions that happen sort of late spring, early summer, but we feel like we're all on the right trend there.
To what extent do you expect step edits?
We expect maybe there'll be a few, but primarily this will just be prior authorization. We don't expect major step edits.
That's great.
If any.
The gross to net, what's the latest on the gross to net that should be expected?
Yeah. It's premature to guide on a specific percentage, but I do wanna be a little bit clear here, and I'll tell you why. You know, we priced PALSONIFY for a year of therapy in the U.S. for $290,000, and we announced that at launch. What we know, and we're just experiencing the marketplace, we're one quarter in. From claims data for other acromegaly products, it's about 10% of patients are Medicaid patients, 30% are Medicare, and about 60% are commercial pay. That sort of informs. We don't plan to discount to the commercial pay side of things, they'll just be low single digits for that section. For the government, they're typically a 20%-ish discount for Medicare, Medicaid patients.
There will be a mix of those patients that are treated or prescribed and dispensed in a 340B hospital. The key variables right now, Tyler, to kind of land that plane on giving guidance are that better time to give us better sense of the mix. Is that 60/40 split the right, and what is sort of the 340B mix? I think it's premature to guide on right now.
Okay. As you mentioned, you all received a positive CHMP opinion. Potential European approval could come by the end of the first half, and it should come. What are your expectations for the launch there? Do you guys plan to go it alone, or are you still thinking about adding a partner to help you launch Ex-US?
I think as we... You know, taking a step back in Crinetics and the overall strategy to be, you know, the closed cycle, fully integrated pharmaceutical company, it's important for us to keep the asset whole. I think it preserves a lot of optionality in a world of uncertainty, in the US perspective with sort of a changing landscape on most-favored-nation and understanding that. An approval in Europe is really important for us. Now we have the opportunity, you know, provided we get a, you know, an approval, to have conversations on a country-by-country basis in a pragmatic and thoughtful way. Also, in that same point in time, the development of MFN will be going on parallel, and we'll make pragmatic and measured places and decisions to take in Europe. We feel we're best positioned to launch this.
This, again, is an orphan indication, so it doesn't need a incredibly large lift, and we'll do this country by country where it makes sense in Europe.
Again, PALSONIFY obviously is a oral pill that's as effective as the standard care SRLs, with potentially even some improvement when you look at the switch date on symptoms. Obviously, what's nice about it is you're not getting harpooned, you know.
Yes
... In the glute with a thick, viscous solution.
There's the YouTube videos about that, Tyler, too.
It's horrible.
It's horrible.
It's horrible.
... What patients have to put up with.
Especially with children.
Yeah.
I expect as long as you guys execute, you should take the majority of the market. I know that's not your formal guidance, but.
Well, I think we've said we would. It's a matter of when, not if. I think we would say we aspire to be the standard of care for acromegaly. I agree. We'll go with you on that one, Tyler.
I like to hear it.
Yeah.
Just to recap on the market, it's SRLs globally is roughly $2.5 billion, and $800 million-$900 million of that is acromegaly. Is that a fair kind of rough assumption to use?
It is directionally correct. It's tricky to split, sort of the. Because there's a long list of other indications that SRLs are used off for spontaneously. It's a little bit tricky split, but it's directionally correct.
Can you give us a sense of how much of that is in the U.S. versus Europe or Ex-U.S.?
I would say it's two-thirds US.
Okay.
Yeah.
Great.
Just there's a difference in pricing.
It'll come down to your execution, your ability to convert the market and the patients, and obviously, it should also expand with your pricing as well.
Yeah.
Okay. carcinoid syndrome phase three was recently initiated with paltusotine.
I mean, before we go on, sorry, I think one more thing. I think there are opportunities to improve the TAM of acromegaly, in the U.S. and globally, to be honest with you. One, you talked about, you touched on the lever pricing. I think the other. We've published data that 80% of patients who are on an SRL discontinue or switch within five years, and they're discontinuing and switching not because their acromegaly is cured. It's, it's a, it's a difficult condition to treat. These conditions, as you pointed out, are painful and hard to deal with. If you can keep patients on therapy longer or get those who have stopped taking therapy or to improve diagnosis rates, you can measurably have a larger market and be more beneficial to patients.
That really is our mission of acromegaly. Sorry.
Yep.
... To before.
No, that's a good point. Definitely multiple areas of expansion.
Yeah. Thank you.
Okay. And carcinoid syndrome for paltusotine since the phase three was recently initiated, really the other half of the market, which is very meaningful as well. Maybe you could just talk a little bit about that trial, when we could get data, and what would be considered a success with that trial?
We're not projecting how long it takes to recruit any of these major trials in rare diseases. Our goal is always to beat historical precedence across the board, including for carcinoid syndrome. It's the things are going well. It's enrolling, and I do expect to have data in a reasonable timeframe. I think it's particularly exciting to use paltusotine in this condition because we talk about acromegaly not being served well because these depot injections of octreotide really don't last a whole month. That situation is even further magnified in carcinoid syndrome.
If you can imagine having paraneoplastic diarrhea and flushing that breaks through periodically, this happens a lot to the point in these patients where they have to use short-acting subcutaneous boluses of octreotide on top of their monthly injections of long-acting octreotide in order to really control their symptoms. If you just take an efficiently absorbed oral agent once a day, I suspect you'd have better control of symptoms than you can see with these injections. Really, that's what we need to show is that we have greater numbers of patients who have reductions in their flushing and diarrhea frequency relative to placebo. These are placebo-controlled trials.
What levels, what reductions do you hope to achieve in the trial?
Well, in the case of carcinoid syndrome, the primary endpoint is flushing episodes frequency, and we have to show a greater decline from baseline of flushing relative to placebo. There's a key secondary endpoint, though, which is the frequency of bowel movements to reflect the severity of diarrhea. Both parts of this study, both endpoints are powered. Independently, we should be able to show significant differences from placebo. Together, we have the complete indication for carcinoid syndrome.
We've read out phase II data on this too and measured similar endpoints.
Right. Very similar, and that data, looks very promising, and phase III should succeed.
Indeed. Let's move to atumelnant. Plenty of people out there think atumelnant could be significantly larger than PALSONIFY, which is, as we just discussed, is a reasonably large indication as well, or indications, should I say. Maybe you could briefly describe why you think atumelnant is differentiated as a molecule from Crenessity. You may not be first to market, but you potentially have an advantage with your novel design for the phase III trial. Maybe you could describe that a bit and how you could have potentially a better registrational data set as you think about getting to market and promoting to patients.
Right. Our goal in our phase III atumelnant trial for CAH is the therapeutic goal of CAH, which is twofold. Firstly, to correct hyperandrogenemia. Many of these patients have unacceptably high adrenal androgen concentrations causing a whole host of clinical problems. In addition to that, we also want these patients to be able to lower their high glucocorticoid doses into the low physiologic replacement range. Our primary endpoint in phase III for CAH is actually a composite endpoint, both goals of therapy, normalizing androgen and correcting glucocorticoid doses into the replacement range. This is quite distinct from what was studied by crinecerfont.
What they showed in phase III was a, what I would call a pure steroid-sparing effect, where they showed they were able to allow patients to have some degree of reduction in their glucocorticoid dose, although not always to the low physiologic range. They were not able to simultaneously show meaningful reductions in androgens. Crinecerfont gets part of the way there. You have to kinda choose either glucocorticoid dose reduction or androgen reduction, but with that mechanism of action, you really can't have both, it appears. The case of atumelnant, we have to do phase III, but I'm optimistic based on what we see in phase 2 that both goals of therapy can be achieved, and we hope to have a approved label someday which clearly demonstrates that as the primary endpoint.
You guys, earlier this year reported a great cohort for data suggesting that you guys are well on your way to achieving that goal in a phase III, and no liver tox, which was encouraging to see given the case previously that some people were concerned about. I see a star up there for potential 26 milestone on the slide for longer duration of data from the OLE portion. How can that complement what you've already shown?
Our core phase II study, the data that we've shown, including this cohort four you're mentioning, that was a three-month treatment experience for small numbers of patients with CAH. All those patients, or a large number of those patients rolled over into a long-term open-label extension study where all patients are receiving atumelnant plus required doses of glucocorticoid. This is a longer period of time where doctors will have to reduce those glucocorticoid doses into the target replacement range and follow long-term trends with the adrenal androgens. We had one patient that we were able to highlight last time where we showed this progressive reduction in adrenal androgen once he even went past month three.
That's consistent with observations in the core trials where we could physically see adrenal gland volumes being reduced even in a three-month period, which is unprecedented kind of data. My theory is that with continued treatment, we would see even further reduction in adrenal size as well as lower androgen levels, and just it will make the ability to lower glucocorticoid doses into the replacement range even easier.
We are approaching time here, but I wanna get at least a couple more questions in. Maybe we'll try to be brief. Atumelnant in Cushing's, another star up there, right? Additional data from the ongoing Phase 1b/2a.
Right.
... Again, its potential, but what might we be able to receive in terms of additional data this year?
At the NIH, we are testing a variety of doses now of atumelnant in active Cushing's patients. We saw already that the 80 mg dose pretty much normalized all of those patients' urine free cortisol within a 10-day treatment period in that study, and we're looking at other doses that we hope to be able to report later in the year. This is helping inform our phase II , phase III trial design as well.
Okay. On the ACTH program, 9682, starting to dose patients there, obviously a very novel approach. Could we get early response data later this year, or when do you plan to update us in terms of clinical data from that program?
We are dose escalating now. We have sequential dose cohorts at higher doses based on PK and safety data at each cohort. This is going along well, and there's a lot of interest in this study from patients and physicians. This would be largely data dependent and driven. If we have a critical mass of information from this dose escalation phase, especially if it's the kind of data that we would use to potentially go into the dose expansion cohorts, I feel like that might be an opportunity for sharing. Exactly when that would occur, I can't. It would be dependent on data.
A final question. You have some really exciting preclinical programs. Could we see any new INDs on those programs at some point this year?
Yes, I think you could. I think progress is being made across the board, in particular the TSH receptor antagonist and the PTH receptor antagonist. I hope we're in clinic next year with those. We shall see.