Charles Moore: Hey, guys, this is Charlie on for Brian. Thanks for taking our question. So, just wanted to switch gears a little bit towards the PTH asset or assets. Just kind of wanted to ask what, from the presentation earlier this year at the Bones and Teeth Gordon Research Conference, really gave you confidence in the profile of the molecules you’re developing. And if maybe you could kind of walk us through what excites you about it, as well as if this is kind of the profile that you’re looking for from the other assets that you’re selecting from. Thank you.
Scott Struthers: Got it. How about, Alan, I’ll talk about the preclinical, and you can talk about why we’re excited about it clinically. But very much, this is like many of our programs, where the endocrinology in animal model species is almost identical to the endocrinology in humans. And we know that it’s very robust way in rats, for example, to induce hyperparathyroidism by infusing excess of parathyroid hormone. And we can watch calcium go up. And then we can introduce one of our antagonists and watch calcium normalize. We can also take normal rats and give them PTH antagonist and see their PTH levels rise. So this type of pharmacodynamic response in a model system is very much the same type of thing we would do in a healthy volunteer, and it goes up and down our pipeline.
And it’s a reason why, from a business perspective, endocrinology is just such a great field because you do so much derisking so early on, whether it’s in animal models which closely mimic humans, or it’s early healthy volunteers or early patient studies where you’re measuring biomarkers that are completely objective and well defined. But maybe, Alan, you can comment on the clinical need and why we’re excited about a PTH antagonist for these different patient populations.
Alan Krasner: Yes, sure. This is a novel mechanism of action for — that could potentially help a great number of patients who have parathyroid hormone excess for any number of reasons. And by the way, also parathyroid hormone-related protein excess. So beginning with hyperparathyroidism, this is a fairly common endocrine disease, primary hyperparathyroidism, in which the — one of the parathyroid glands in the neck typically overgrows and causes unregulated excess secretion of parathyroid hormone. That results, as Scott mentioned, in hypercalcemia, high calcium levels in the blood. But it’s really a multi-organ systemic disease that also damages the bone and the kidneys in particular. And the hypercalcemia itself can cause sometimes very serious symptoms.
Now, fortunately for patients with primary hyperparathyroidism, there are very, very effective surgical options available, and many of these patients are cured surgically. However, there is a very important subset of patients who don’t get cured by surgery, sometimes because more than one gland actually enlarges in some patients. And there is really a great number of patients who could benefit from having a medical option to control hyperparathyroidism when surgery has not worked. The other thing I would point out is even with patients who potentially could have surgery, it turns out. A lot of them don’t have surgery for any number of reasons, including the fact that they may not be surgical candidates. And so, therefore, I see a lot of potential for a medical option in this area.
That’s just one potential. That’s probably the most straightforward indication. But there’s also something called hypercalcemia malignancy, which is caused by parathyroid hormone-related protein, which also binds to the PTH receptor. Those patients could also use a new option. There are treatments available, but they all have limitations, and these patients can be quite ill. And I think it’s an exciting prospect also potentially for the future for a PTH antagonist. And then there’s more, but we don’t have time to talk about more.
Charles Moore: Great. Thank you very much.
Operator: Your next question comes from David Lebowitz from Citi. Your line is already open.
David Lebowitz: Thank you for taking my question. With respect to the data being presented for CAH, how should we benchmark it versus what we’ve seen from other therapies? And what should we expect? And conversely, what should we not expect?
Scott Struthers: Alan, maybe you want to reiterate that.
Alan Krasner: Yes, I mean, I think, again, we’re expecting directional information in the biomarker responses. Again, as we discussed, it’s more than just what’s the percentage reduction in the biomarkers. It’s also about how many patients actually get into — get normal levels of biomarkers. And then there’s all the clinical features of the disease we want to carefully assess when we look at our data. So again, it’s — this — our Phase 2 interim data will not be a statistical exercise, but I’m hoping we’ll get good directional guidance in terms of what doses may or may not be effective and what doses we and designs we may want to contemplate for future development beyond Phase 2.
David Lebowitz: Thanks for taking my question.
Operator: Your next question comes from Dennis Ding of Jefferies. Your line is already open.
Dennis Ding: Hi. Thanks for taking our questions, and congratulations on all the progress. If I can ask on CAH, maybe just talk about how you’re thinking about having to go to the high 160-milligram dose, as it was an optional cohort. And just wondering if that cohort has started enrolling or not, or do you even plan to. Thank you very much.
Scott Struthers: Alan, do you want to talk about how we think about cohorts and dose selection?
Alan Krasner: Yes. So this is a sequential dose cohort study, and the first cohort of patients with CAH receive an 80 milligram, once-per-day dose of Atumelnant. This is based on the Phase 1 healthy volunteer data showing that, that dose looked like it should be effective. After we complete the first cohort of dosing, all the data from that cohort is reviewed by a safety review committee, and that committee then recommends the dose for the next cohort. That dose, that next cohort could be a higher or a lower dose. We will certainly share that information at the Endocrine Society meeting as part of the scientific presentation. And I think it’s fair to assume we’d have patients from the first cohort, as well as some of the second cohort as well.
Operator: There are no further questions at this time. I would hand over the call to Scott Struthers, Founder and Chief Executive Officer, for closing comments. Please go ahead.
Scott Struthers: Thank you, everybody, for being with us today. And we look forward to seeing many of you in Boston in the beginning of June and throughout the year as more and more interesting things start coming out from the pipeline. Thanks again for your time. Good night.
Operator: Ladies and gentlemen, this concludes today’s conference call. Thank you for your participation, and you may now disconnect.
