Onaiza Cadoret: Yes, sure, Robert. We’re very excited with the data that we’re seeing. The week 85 data was very encouraging. We saw a duration of effect sustained TTR suppression for TTR and then obviously, halting disease progression and seeing improvement in a substantial number of patients in both mNIS+7 and Norfolk Quality of Life. So we’ve got a really great efficacy data package. We have from all of the research we’ve done, the more preferred administration profile with self-administration at home, allows patients to be empowered in taking control of their disease and taking the medication wherever they are with them, not relying on going into the HCP’s office. The efficacy combined with this self-administration profile gives us a really strong way to end the marketplace.
As I’ve said before, this is a market where we still have 40,000 patients and less than 20% of those patients have been either identified, diagnosed and treated for polyneuropathy, including mixed phenotype. So our ability to get to where these patients are identify them and get to the offices outside of the centers of excellence where they’re presenting is going to be really important. And those are some of the strategies we’re working on with AstraZeneca. And then as to your question on whether we will be first in many global markets, yes. That is the goal. We are planning to file in different markets outside of the U.S. in the second half of the year, particularly in Europe. But as you know, we’re also looking at expanding into markets such as Eastern Europe, Russia, China, Japan.
And again, these are places where AstraZeneca’s global scale will bring the ability to really penetrate and get these patients in care where there is needed.
Brett Monia : And as you know, Robert, we’re very pleased that AstraZeneca also enthusiastically license Latin America rights for eplontersen for, of course, all indications, neuropathy as well as cardiomyopathy. It demonstrates the their enthusiasm for eplontersen, our partnership and enthusiasm for the data that has been generated to date.
Operator: The next question comes from Kostas Biliouris with BMO.
Kostas Biliouris: One on pelacarsen follow-on molecule that you recently announced. Can you discuss the potential technologies that you could leverage there to improve the efficacy and the dosing frequency of the first-generation molecule? And approximately how many years did you expect this follow-on molecule to enter the clinic after — to enter the market, sorry, after pelacarsen?
Brett Monia : Sure, Kostas. Thanks. Very excited that Novartis came to us with a proposal to work on with them a follow-on strategy, follow-on program for pelacarsen. Let me just say right from the outset that pelacarsen — the pelacarsen Phase 3 program is going well, very well on track, and is on track for data readout and potential filing in 2025. The fact that Novartis came to us really demonstrates their enthusiasm, their added enthusiasm for this — there’s opportunity for Lp(a) cardiovascular disease. They expect to be a semi-approval for pelacarsen the first on the market and to have a substantial global reach. And the follow-on form is to extend that reach the purpose is to reach more and more patients with the follow-on program.
Novartis recognizes our expanded and vast capabilities in RNA-targeted therapeutics. And we’re bringing our full arsenal to the table, and they appreciate that — that’s why they partnered with us on this. That includes all the great work that our research organization has been doing over the last few years in expanding our medicinal chemistry capabilities, including NspA backbone that we have talked a lot about in the past and other chemistries as well as our rapidly emerging capabilities in RNAi technology and combinations of both. We can utilize chemistries that we utilize in ASO technology as well as for RNAi platforms. It’s tough to beat the efficacy that pelacarsen has demonstrated in Phase 2 Kostas. I mean, with 98%, 99% of patients with CBD due to high Lp(a).
