Kerry Holford: Hi, I’m going to take a different topic here. Looking Lp(a) your new product, you now said that you’re taking into Phase 3. Can you confirm whether you published the Phase 2 data, haven’t found any. So if I’m correct, when we might see that published? And can you confirm what dose and frequency of administration you’re looking at for that Phase 3 study? And I guess that you appear to be positioned third in that race, would be interested to hear how you expect your drug to be differentiated versus the competitor as already in Phase 3? Thank you.
Dave Ricks: Thanks, Kerry. So a good multipart question, but on Lp(a), happy to talk about lepodisiran. So Dan, do you want to comment on this?
Dan Skovronsky: Yes. Thanks, Kerry, for the good questions here. You’re right, we haven’t yet published a Phase 2 data. But I think we just recently were able to publish the Phase 1 data. That was really exciting and well received. I think one of the things that people noted in our Phase 1 data was a very long durability of action in the very deep reduction in Lp(a) levels following a single dose of lepodisiran. We now have, of course, a Phase 2 data in hand and use that design and to begin the Phase 3 trial. I think we haven’t quite disclosed dose or frequency yet, but I’m sure that will happen in time. You asked about differentiation. I think there’s probably a couple of different potentials for differentiation here versus a shorter-acting ASO into siRNA that are both in Phase 3 studies.
Maybe first is the depth of clearance of Lp(a), we don’t know how much you have to reduce Lp(a) to lead to benefits in cardiovascular outcomes and whether there’s a threshold effect or a floor to this. So the depth of clearance is one. The second, as you asked about, could be frequency of administration or durability of action, those two being closely linked. And the third, of course, is the population that’s being studied to I noted we’re studying secondary as well as primary prevention here. So I think we have a good package with multiple opportunities for differentiation and eager to test the Lp(a) hypothesis here in this Phase 3 study.
Joe Fletcher: Thanks, for the question, Kerry. Paul, next question.
Operator: The next question will be from Steve Scala from TD Cowen. Steve, your line is live.
Steve Scala: Thank you very much. Given that based on all available metrics, the SURPASS-CVOT interim likely already has passed, can you confirm that the only way the trial would have stopped is if there were either a survival benefit or futility and not simply non-inferiority? And anything you can say regarding your confidence in eventually hitting superiority based on what you know so far? Thank you.
Joe Fletcher: Thanks, Steve. Dan, do you want to take the question on SURPASS-CVOT?
Dan Skovronsky: Sure. Thanks, Steve. As you know, we do our best not to comment on interim analysis, although many of our different trials kind of corporate interim analysis. But when we do talk about the risks, unintentional unblinding of results, for that reason, we prefer not to do that. You’re right that the primary analysis of the study and the design is around noninferiority versus what we are ready to know to be a very good drug that reduces cardiovascular risk, and that’s Trulicity. So it’s designed as a noninferiority trial. Of course, when the final data come, we would be delighted to see even superiority. You asked about our confidence. Confidence continues to increase for this readout. In fact, as disclosed in the prepared remarks today, we got additional data here even from the OSA study that should make us feel more confident, not just the benefit of sleep apnea, which itself could lead to cardiovascular benefits, but actually the weight loss.
And I think there are some concerns about weight loss of different populations and different trials and males, females, et cetera. So some of that was discharged here. So remain excited and look forward to getting that data when the study is complete.
Joe Fletcher: Thanks, Dan. Paul, next question?
Operator: The next question will be from Evan Seigerman from BMO Capital Markets. Evan, your line is live.
Evan Seigerman: Hi. Thank you so much for taking my question. I wanted to touch on donanemab with the AdCom approaching. Can you discuss how your – if your confidence has changed in the asset? And maybe any specific points that you will hope will be addressed during this discussion with these outside experts. Thank you so much.
Dave Ricks: Thanks, Evan. Anne, you want to discuss with on the AdCom?
Anne White: Yes. Thanks so much for the question. And we are incredibly confident in donanemab potential and the fact that it offers very meaningful benefits to people with early symptomatic Alzheimer’s disease and just the overall approvability of the package. We do look forward to seeing there’s questions. We haven’t received those yet. I think that what we’ll anticipate really is discussions around the safety and efficacy of donanemab and those – the safety and efficacy profile remain very consistent with what we published and presented. So nothing new there. We do expect there’s a couple of unique aspects to our trial that we anticipate they’ll want to discuss. One is around limited duration dosing. We think this is an incredibly important feature of donanemab, the chance to stop dosing when you’ve cleared the plaques and donanemab clears them robustly and rapidly.
So, we think that allows for this limited duration dosing approach. So we really do look forward to getting into that data and having the advisors see that and respond to it. Another unique aspect is assessing tau at baseline. This is important for the field that we understand the prognostic factor of tau, and that was able to be earned. But what we saw in the trial was all patients benefited regardless of tau level with those early in the disease doing even better. It’s one of the reasons that we remain so enthusiastic about TRAILBLAZER 3. And while Dan didn’t mention that in his remarks, I think he remain even more enthusiastic about the opportunity to intervene earlier based on what we saw in that early population, the people with low tau and those that had no tau with such strong biomarker results.
I think you probably remember the data that patients in the earliest part of our study had a 60% slowing. And we believe that could be even stronger as you get into the earlier patients that are preclinical. But maybe just one remark. In the meantime, though, this is not time loss. We’ll continue to make sure the health care system is ready. We’re going to make sure that we launch into an even stronger market with potential approval. So we’re making the most of this time and look forward to the AdCom, [ph] as Dan said, in mid-2024, answering any questions that they have.
Joe Fletcher: Thank you, Anne. Paul, next question?
Operator: The next question will be from David Risinger from Leerink Partners. David, your line is live.
