Geoff Meacham: Hey, guys. Thanks for the question. Another one on 133. When you think about the Phase III program, I just wanted to know what sort of informs the next indications you’re going to go after? Is it unmet need? Is it the potential for differentiation on 133 and the timing of that, do you think that you’d want to have the Phase II data in hand? Or is this something that you could roll out sort of that risk? Thank you.
Robert Bradway: Yes. Thanks for the question, Geoff, really appreciate it. As you know, obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30 massively costly. So a huge burden to the global third-party payers and societies. The obesity-related disease list is quite long and expanding from cardiovascular disease and heart failure, type 2 diabetes, obstructive sleep apnea, NASH and AFLD kidney disease. These are chronic conditions that really demand medicines that can deliver durable and chronic weight loss. And so we think we have a really strong offering for these obesity-related diseases rising in our Phase II program, as you know. And obesity has a strong genetic component and we locked on to gipper [ph] inhibition based on genetic insights.
So the opportunity space is quite large. You asked the question what indications and perhaps even in what sequence. And when we have all the requisite data, we’ll remark in due course. But we intend all indications where this dual mechanism can improve public health. And we are actively planning and on track for an expansive Phase III program.
Jay Bradner: And in terms of – Dave, you want to add the regulatory piece?
David Reese: Yes, I think — Geoff, this is Dave Reese. I would just add that we’re planning a very expansive Phase III program. So you can expect to see multiple indications move forward in parallel. And as Jay indicated, as we start to see data, we will begin launching those trials, and we’ll discuss them. And then in addition, as you’re aware, regulatory authorities around the world require a certain body of safety data before Phase III launches. And so of course, we will be compliant with that. But our goal is to launch Phase III as quickly as possible once we have the requisite data set and regulatory approval.
Justin Claeys: Great. All right. Julian, we’ll go to the next question, please.
Operator: Thank you, Geoff. Our next question comes from David Risinger from Leerink Partners. Please go ahead. Your line is open.
David Risinger: Yes. Thanks very much. So I have another question on AMG 133, please. Could you add some more color on your expectations for the impact on blood pressure and lipids in Phase II, specifically whether you anticipate tirzepatide-like efficacy on those metrics? Thanks very much.
Robert Bradway: Yes. Thanks, David. I mean we’re making all these measurements, and I’m not going to try to forecast the outcome of that pharmacology at this time. As you’ve seen in our Phase I program, the medicines very well tolerated, delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it’s too early to try to answer your question, and we’ll have all that data at the end of the first part of Phase II towards the end of this calendar year.
Jay Bradner: And the best extrapolation that you can have is from the preclinical data that were just published, I urge you to take a look at that.
Justin Claeys: Okay. Julian, we’ll go to next question, please.
Operator: Thank you, David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.
Q – Unidentified Analyst: It’s Ege [ph] on for Michael. Thanks for taking our question. A quick one on [indiscernible] Can you talk about your plan of data disclosure this year and your current thinking on the potential registration path? How do you think about the positioning of this agent relative to some of the other emerging agents based on different mechanisms such as ADC or AR degradors in prostate cancer? Thank you.
Robert Bradway: Yes. Thanks for this outstanding question, Michael. And Zalaritamag [ph] is a very interesting and exciting molecule for those on the call. This is a steep on CD3 bispecific. We have been studying this in advance castrate-resistant prostate cancer. We have expanded a cohort in the Phase I monotherapy. We’re opening to reduce monitoring as well as – as you invoke the existing and novel androgen receptor modulators integrators, we’re exploring combinations with novel agents in that domain as well. The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We’re looking at the feasibility of reduced monitoring. We have a great experience with these T-cell engaging bispecifics as well as the plausibility of outpatient therapy.
The approach to the regulatory path will present in due course. There’ll be no surprises there. The path to bring medicines to patients with castrate-resistant prostate cancer alone and ultimately, in combination is well worn, thankfully, and we know how to deliver there. You asked about differentiation in other medicines. These are often apples to oranges comparisons. We have looked at that, of course, and we really like the offering of Zalaritamag. The patients treated on our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines such as radio ligand therapies.. And the response rates we’re seeing are really clinically meaningful to patients. And that gives us great encouragement to develop the medicine more ambitiously in the next few years.
Murdo Gordon: Jay, in terms of the data sharing, do you want to share…
David Reese: For data availability – as Jay mentioned, we’re nearly complete in terms of dose expansion enrollment. So as those data roll forward over the course of the year, we’ll provide guidance as to when we might have the next look at that data. But that’s probably the next meaningful set of data we’ll get a look at either later this year or early into next year.
Justin Claeys: Julianne, next question, please.
Operator: Thank you, Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.
Tim Anderson: Thank you very much. So Eli Lilly today made a couple of sets of comments about this topic of GIP agonism versus antagonism and they also weighed in on the data you published yesterday. And I’m wondering, in as much as you heard that or read those comments, is there any context to add or anything that’s factually incorrect or anything to refute because they covered quite a few points, and they continue to express their view, which is agonism is the best way not antagonism?
Jay Bradner: Tim, this is Jay. I open it up to anyone else who wants to contribute to this. I don’t believe that – yes, that engaging in the dialogue around this is as much to the narrative. Rather, I’d say that the argument for GIP receptor antagonism comes from just the highest level of scientific data, the human experience across populations with 1 million patients studied, among those who have variations in the genes associated with this pathway where that variation is directionally inhibitory, the BMI is lower. And so we’re hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.
Justin Claeys: Okay. Julianne, next question, please.
Operator: Thank you, Tim. Our next question comes from Robyn Karnauskas from Truist Securities. Please go ahead. Your line is open.
Q – Unidentified Analyst: Hi. Thanks so much for taking the question. This is Nicole on for Robin. So on Daxdilimab, targeting ILT7 business, can you talk about your level of confidence in this target in light of the competitive landscape? And would you expect to see near term from safety and efficacy?
Robert Bradway: Sure. Jay and Dave?
Jay Bradner: Yes. Well, it’s very early days with this medicine. There is strong preclinical support from the published literature and our own preclinical work. It’s nicely for patients, a very competitive landscape, but this is the earliest phases of clinical investigation. And so we’re going to approach this with total aquapoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.
David Reese: Yes. I would say the target, as you mentioned, is one that helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here. And at this point, I think it’s all efforts towards generating the clinical data.
