Roanna Ruiz: Got it. Thanks.
Robert Blum: Thank you, Roanna.
Operator: Thank you. Our next question will come from Salim Syed from Mizuho. Your line is open.
Robert Blum: Hello Salim.
Salim Syed: Hi, Robert. Good afternoon, everybody. And I’d like to all extend my welcome and congrats to Sung. Its good to reconnect, Sung. I guess on 586, if I can, I know you’re not – maybe this is for Fady, providing any details exactly on the Phase 2 design. But is there anything in particular Fady from the Phase 1 trial that you learned that how this compound could potentially differentiate from the MyoKardia 224 compound and the read across there into how a trial could differentiate from their current Phase 2 study?
Fady Malik: It’s a challenging one to answer, Salim, because we don’t really know very much about 224 and we haven’t told you very much about 586. I guess I’ll just say, and maybe I can ask Stuart to expand a little bit, but our goal is to make dosing of 586 simpler than aficamten, and we think it has some unique properties that may enable that as we have looked and seen in Phase 1. Stuart, do you want to maybe elaborate a little bit?
Stuart Kupfer: I think the only thing I’ll really add is that CK-586 was designed to target what we consider more vulnerable population. These patients have had many comorbidities, perhaps more risk of some decreases in ejection fraction, for example. And we think CK-586 properties that would make these patients more manageable and less prone to that or other risks. And so again, those details will be more forthcoming.
Salim Syed: Okay. Got it. Thank you very much.
Robert Blum: Thank you.
Operator: Thank you. And our next question will come from Jeff Hung from Morgan Stanley. Your line is open.
Jeff Hung: Thank you, Robert and team. Hi, Robert and team. Thanks for taking my question and congratulations on your new role. Congratulations Sung on your new role. For CEDAR, what are the expectations for the dose range that’s likely to be sufficient for most pediatric and adolescent patients if they end up being a similar dose range as the patients from SEQUOIA, would you expect a higher rate of ejection fraction excursion because of the differences related to age?
Robert Blum: Stuart, do you want to take that one?
Stuart Kupfer: Sure. Thanks for the question, Jeff. So as we mentioned, the doses in adolescent patients are exactly the same as the doses that we’re studying in adults between 5 and 20 milligrams. And again, what’s important is that the dose selection is individualized based on achievement of target gradient and maintain — maintenance of a normal ejection fraction. In terms of younger children, the key question will be really what is the safe starting dose. And the plan will be to as I mentioned, evaluate doing interim analysis, evaluate 20 patients, adolescent patients, pharmacokinetics and safety and determine for younger children, what is a safe starting dose. And that’s the basic strategy. And so with that in mind and individualized dose selection, we don’t — we anticipate that the benefit-risk ratio in children will be just as good as we’re serving an adult.
Jeff Hung: Great. Thank you.
Robert Blum: Thank you.
Operator: Thank you. Our next question will come from Mayank Mamtani from B. Riley Securities. Your line is now open.
Mayank Mamtani: Good afternoon, team. Thanks for taking our questions. Also pleased to see Sung join the team. Just maybe on the next Monday’s, ESC Heart Failure Congress data, just could you please clarify if you could get the patient level safety analysis relative to maybe what we saw at the top line. And also obviously curious to see how much of the dose titration and the responder rate of patients staying at higher efficacious doses is helpful to having that peak VO2 number that is — seems to be on the higher side and not connected to the baseline characteristics that we had initially thought. If you could clarify that, that would be great?
Fady Malik: Yes. Hi Mike. I mean I think most of your questions will be addressing those presentations. Remember the 3 of them, 1 will speak a lot about dosing and safety. And so we’ll show the characteristics of patients at the various doses and how safety is related to that. With regards to peak VO2, can’t really comment. I’m not sure that there is a dose specific analysis. But you got to remember these patients were not randomized to dose, they were randomized to a dosing strategy, and they achieved a dose based on their individual response to the drug. And so in that way, we, in a lot of ways, consider them just all part of the same dosing strategy.
Mayank Mamtani: Got it. Thanks for the input
Operator: Thank you. Our next question will come from Jason Butler from Citizens JMP. Your line is open.
Jason Butler: Hi. Thanks for taking the question, and congrats on all the progress. Just wondering if you could give us an update on regulatory progress for China and what next steps are there?
Robert Blum: Hi Jason, I’ll take that one. In light of that, we’re making very good progress, but we aren’t in a position yet to be specific until such time as we JI XING our partner are aligned on setting those expectations. So I do hope that we’ll be able to say something with the next earnings call.
Jason Butler: Okay. Great. Thank you
Operator: Thank you. Our next question will come from Jason Zemansky from BofA. Your line is now open.
Robert Blum: Hello Jason.
Cameron Bozdog: This is Cameron Bozdog on for Jason. So you’ve discussed the potential of a novel rat and is based on a risk algorithm. I mean, could you kind of elaborate a little bit on what this could look like? Have you received any feedback from regulators on this point? And then if you could maybe touch on your base case assumptions currently for number of echoes likely to be required in both titration and then in the maintenance setting as well? Thank you.
Robert Blum: Sure. It’s premature to speak to the second part of your question, the number of echoes is a function of conversations that we’re still going to be having with FDA. But I think there’s no scenario by which we expect a similar REMS. I think in light of the fact that the dosing strategy employed in SEQUOIA-HCM and continuing in FOREST-HCM is itself differentiated. And therefore, that ties to the risk mitigation strategy. It’s, I think, going to be clear that there will be a different kind of REMS program. And with that, we expect to have conversations with FDA about what that could look like in a concrete way as will be informed by how we might approach risk mitigation in an NDA submission. And there are different ways to approach risk mitigation, as you know.
Some of that can be handled by labeling. Some of that can be handled in an informational REMS. Some of that may require [ITASU] REMS. And the current cardiac myosin inhibitor is the subject of an ITASU. And our objective is to understand how FDA thinks about risk in light of not just the EF excursions as seems to be the focus of Wall Street, but also as pertains to ADME properties, drug-drug interaction properties, pharmacokinetic properties that speak to half-life and shape of the curve with regard to pharmacodynamics, all these things factor into how one approaches risk mitigation. And I do think we’re going to be in a position as is our base case to have a differentiated profile for risk mitigation. I think that’s the best I can do today, but we do hope to have more to say down the road.
Cameron Bozdog: Thank you.
Robert Blum: Thank you.
Operator: Thank you. Our next question comes from Carter Gould from Barclays. Your line is open.
Carter Gould: Hi, Robert. Team, good afternoon. Thanks for taking the question. I’m going to ask you a bit of an unfair one in that the AHA and ACC HCM guideline has dropped this afternoon. But I’m going to go out on a limb and say that you probably had a good sense of what was going to be in there. So I guess at a high level, is there anything in there that’s surprising? And maybe just at the risk of provoking Diane and the operator, when you think of — I guess, for Andrew, when you think then about the importance of guidelines down the road, conveying that differentiation between mavacamten and aficamten. How important is that based on all the prior kind of case study work you’ve done? Thank you.
