Crinetics Pharmaceuticals, Inc. Q3 FY2025 earnings call

Launch Progress of PALSONIFY

• Launch is going well with initial patients switching from other therapies and some newly diagnosed starting on PALSONIFY. 95% of filled prescriptions are from switch patients early in the launch, but some treatment-naive patients are also enrolling.
• Field teams have called on over 95% of highest priority prescriber targets, with positive reception from community and academic physicians. Symptom control and efficacy-first messaging are resonating.
• Payer engagement has been favorable with quick prior authorizations and some approvals for up to 12-month supplies.

Pipeline Updates

• For carcinoid syndrome, Phase 3 study of paltusotine is ongoing, with interest in tumor progression-free survival. CRN09682's BRAVESST2 Phase 1/2 basket study is underway.
• In CAH, Atumelnant showed promising results in Phase 2, with a fourth cohort added to evaluate morning dosing and glucocorticoid reduction. Phase 3 CALM-CAH trial and Phase 2/3 BALANCE-CAH study for pediatric patients are ongoing.
• Delays in some pipeline candidates: Lead TSH candidate for Graves' disease delayed due to IND-enabling tox study weaknesses, and SST3 agonist program for ADPKD delayed for follow-ups.

No specific detailed financial performance breakdown by product segment as described in the transcript. The focus is on the launch and pipeline progress rather than traditional segment financials.

Guidance

• Maintains net cash used in operations guidance for 2025 at $340 million to $370 million.
• Existing cash and investments are expected to fund operations into 2029, providing runway for U.S. commercialization of PALSONIFY and pipeline advancement.
• Anticipates key data readouts in the near term, including from CAH trials, carcinoid study, and BRAVESST2 study, with further milestones expected in the coming 18-24 months.

Risks

• Uncertainties in clinical trial timelines for pipeline candidates, such as delays in IND-enabling studies for certain candidates.
• Risks associated with forward-looking statements, including potential material differences between actual results and stated or implied forward-looking statements due to business uncertainties.

Q: I just want to ask a little bit maybe about some of the data that you showed at NANETS last week. I'm very interested to see the PFS data in the NET patients with paltusotine that is. Can you tell us what the evidence is for somatostatin receptor ligands in this setting? Will you ever want to conduct survival studies with paltusotine alone?

A: Thanks, Catherine. Somatostatin receptor ligands are known to be slowing of the growth of neuroendocrine tumors, and that was proven in the CLARINET study with lanreotide. Mechanistically, we expect the same thing out of paltusotine, which is why we're monitoring this in the open-label extensions of the carcinoid Phase 2 and then soon the carcinoid Phase 3, but maybe, Alan, do you want to comment a little bit more on that to clarify what we see and what we're hoping to see.

Q: You mentioned that the sales force has called on greater than 95% of top priority prescribers. Can you just remind us, one, how many prescribers that specifically includes? Two, the concentration of the immediately addressable, call it, 10,000 acromegaly patients that are at those top priority prescriber centers? Three, can you speak directly -- as you speak directly with these centers, what was the initial perception from those docs on PALSONIFY? How many of them have converted to actual prescribers or are actively working to make it part of their practice in the long term?

A: Yes. Thanks, Cory. Maybe before I hand it to Isabel to answer in a little more detail, just a reminder that we're deeply part of the pituitary community and the endocrinology community more broadly. It's great that our field force has been out there talking now at that level, but they've been out there with warm introductions from those of us who know these people for these prescribers for a long time. I'm really glad to see the response from the community, which has been quite favorable by all comments from all across our field force and directly that I've been hearing from them. We're still working our way through some of the administrative aspects of the pituitary centers, but I think that's well underway. Maybe you want to answer in more detail, Isabel, some of the more specifics that Cory was asking about.

Q: Congrats to a great start, and thank you for sharing all the color. Maybe one question for the commercially related. I appreciate if you could kind of tell us about how you're thinking about providing free drug while getting reimbursement and how do you make those decisions? Then very excited to look forward to the CAH open-label data early 2026. Help us understand sort of in early 2026, whether you would be able to get to all 10 patients and what you hope to show in that data set?

A: Yes. Let me take the second part first, and then Isabel, maybe you can take the first part about -- on the acromegaly side of things. Look, in addition to Cohort 4, patients have been rolling on to the open-label extension. That one has a relatively infrequent sampling, and so the first sampling there is 13 weeks. By the time we get to the early part of the year, we'll then have data from the Cohort 4 patients, plus a handful of patients who've gotten to 13 weeks from Cohorts 1 to 3 in the open-label extension. Now it's still a relatively small sample size, but we'll start to give a sense of what -- how this is behaving in a real -- more real-world setting where physicians can both reduce glucocorticoids and see what's happening with adrenal androgens. Isabel, sorry, I wanted to take care of that part. Maybe you want to talk about the question she had on acromegaly.

Q: Again on all the progress. I guess maybe just feeding off the question in terms of where you're initially seeing demand in the community versus the centers of excellence. I'm just curious to the extent that you get a sense that this is -- there's awareness within the acromegaly community, who I know has a very active patient group and how much is sort of coming from the ground up versus prescription written by clinicians who as they see their patients are sort of recommending a switch or offering that choice to patients?

A: Yes. Thanks, Doug. I think it's still very early days, so it's very anecdotal, but we're hearing both, right? We're hearing physicians who talk to patients and tell them about something they hadn't heard of and are ending up switching to PALSONIFY. We're hearing about patients going in asking their doc for PALSONIFY. That's kind of cool, actually. I think it's a mix of both, but it's too early to start putting any sort of numbers to that.

Q: Congrats on the results so far. Based on your launch experience with PALSONIFY so far, what has been going well for you? Where can you see improvements? It would be great if you can talk about it in context of like commercial, Medicare and Medicaid segments. I don't know if it's too early because I assume most of these patients are coming from commercial.

A: Yes. I mean, broadly, I'm super pleased with the way the team is out there performing and the response to the community. Any improvements are really incremental, but maybe you want to comment on some of your favorite pieces, Isabel?

Q: Has the timing of benefit verification for the Quick Start program met your expectations? When do you expect to have clear visibility into the breadth and depth of prescribing trends?

A: Well, I think the prescribing trends will update you further in the -- as we finish out the quarter, and we'll see and gain experience with that over time. Isabel, maybe you want to talk about the Quick Start program.

Q: Congrats on the progress so far in this launch. My question is you reported that 95% of filled prescriptions today are from switch patients, which we've talked about a little bit now. What's the plan to reach additional treatment-naive patients? Which do you expect will be the largest drivers of long-term growth?

A: Yes. I think if you look at the -- what we've said in the past, there's roughly 500 patients a year coming on to medical therapy. It's kind of a trickle of those new patients. The fact that we're starting to pick those up, I think, goes very much to the profile of the drug, like this one patient that's already controlled 3 weeks in. I mean that's awesome. I think the bigger challenge then is, as we talked about this phase -- 3-phase strategy is getting to those patients who, for whatever reason, are not on medical therapy, but should be. There's roughly 4,500 treatment naive. Some of these are patients who probably are not at the level of control that they should be, and so we're digging into that. I think like many rare disease therapies, once you start getting the word out there that there's a new therapy that's not the burden that you have with the depots that we'll start to get people back. Those are the ones -- those first ones in Phase 1 are just the tip of the iceberg because the next part are these patients who've discontinued therapy and/or have been lost to follow-up and bringing those back in is another very significant group. Then, of course, the big aim is to really start to improve awareness and find better ways of getting people to suspect acromegaly so that you can do an IGF-1 test and diagnose it. there's 17,000 people out there that the best we can tell that have yet to be diagnosed, but they're getting damaged to their joints, their heart every day. We'll be launching a variety of different efforts to do that more specifically next year. I think even these awareness things that we're doing like Alan's interviews with Tony, I think that's going to start helping sooner rather than later.

Q: In the opening remarks, you mentioned aiming to position PALSONIFY as a first-line therapy. We're curious to know how you expect to do that with generics currently on the market?

A: Well, that's an easy one. I mean, if you look at the label, it's indicated for the treatment of acromegaly in-patients who have not had adequate response to surgery or for whose surgery isn't indicated or appropriate. The biggest reason why you want to go on to PALSONIFY in that situation for the new patients is like that one I mentioned, they're controlled in 3 weeks. We got great data from PATHFNDR-2 showing 2 to 4 weeks to get people controlled, whereas in the depots, your first dose adjustment isn't for 3 months. You don't even know if that first dose works after 3 months, and then you go to the second dose, so you wait until 6 months. Then you may need the highest dose until you're 9 months out before you know whether it works. That's not the right medicine, so PALSONIFY is really the best option for somebody newly diagnosed. I don't see an argument that whether it's generic or not matters.

Q: Congrats on the progress. Scott, you kind of discussed the 3 phases of PALSONIFY 's launch. I was hoping you could talk a little bit about the timing of the sequence and how you think about moving from one phase to the next, if there's benchmarks you want to hit in each one or if it's going to be more of a continuum.

A: Yes. I don't mean to imply it's a sequence, but it's a sequence of enhanced efforts. I really want the group out there in the field focusing on those patients in the first phase and getting the word out so that we have broad prescriber base. I think you're seeing that already with the response of the community. Then, in addition, because it will take some time to work our way through all those Phase 1 patients. Before we're done with that, then we also would start getting more active in finding ways to bring patients back to care. That may be -- that may take a variety of different forms. It's really just about how we layer on our efforts rather than go from one phase to the next, if that makes sense.

Q: I wanted to follow-up on one of the earlier questions. What should we be most focused on when we take a look at the Cohort 4 data for Atumelnant? What are you going to be watching for similarly in that Phase 2 OLE data? I guess, stepping back, how much of a read is Cohort 4 or these initial OLE patients going to give us into the potential steroid reductions that we could expect in Phase 3?

A: Yes. Well, a couple of things. One, I'll just put some caveats. It's still relatively small numbers of patients. It allows the chance for physicians to begin to do steroid reductions in the actual treatment period of 12 weeks, that's pretty fast, right? I think that, together with the open-label extension data where there's a little more time. Generally, I think it will give the directionality, but I wouldn't start doing power calculations or things based on it. That makes sense. I think there's been a lot of interest in this Cohort 4 data, and it's interesting, but again, it's relatively small numbers.

Q: On the naive patients, are you guys seeing different dynamics here from payers? Or is it similar to the switch patients?

A: Similar dynamics. We had some reimbursed claims and some that we are processing through the Quick Start, so similar in both cases.

Q: How does the traction you're getting at this early Phase 1n the PALSONIFY launch compared to the market research you've done in terms of willingness to prescribe or any other factors you consider important?

A: Thanks, Joe. I think we have not had any real pushback from prescribers about use of PALSONIFY, as was mentioned earlier by Isabel, who shouldn't get PALSONIFY. I think it's just the normal -- we're observing the things that are basically in line with our expectations. We're building momentum and working through a little bit of inertia in the system, but the patients are starting to come in. As they come in, I think they'll be best served with PALSONIFY. There's really not much pushback.

Q: Just 2 quick ones. On PALSONIFY, could you elaborate on just how many patients in the open label are now transitioning to commercial supply and the time lines there? Just curious if we would see all of that contribution in Q4 or later in 2026. Then on the pipeline, any updates on the progress for the GLP programs? I think there was previous talk of candidate selection in '25, so just curious on progress there.

A: Yes. Just on the open-label extension patients, all 22 are in various stages of enrollment. They've all enrolled for commercial supplies, but they have to wait until their final follow-up visit as part of the open-label extension so that we can finish all the monitoring as part of that. I think most of those are through -- are completed by the end of the year, but I don't know the exact numbers at this point. Then the GLP-1s, obviously and other obesity things we're working on, obviously, a very interesting space, especially today. I think we're going to stop talking as much about our early-stage programs now that we're really concentrated on the launch and our late-stage clinical development. I think it's just more appropriate that we -- when we're in the clinic, we'll let you guys know, but we're thinking hard about it, working hard on it, and you're going to see a lot of new things come out of the Discovery Group and not just soon, but for years to come.