Yale Jen: Thanks On and Brett.
Operator: The next question will come from Paul Matteis with Stifel. Please go ahead.
Q – Unidentified Analyst: Hi, this is James [ph] on for Paul. Just one on Olezarsen, quickly. I guess as we get ready for the FCS launch I guess how are you thinking about pricing just given that the higher trade opportunity may be coming behind it and assuming there will be different price points there. And I guess, just as you’ve kind of put some of this commercial infrastructure in place for the FCS launch, how much I guess leverage either from like a sales force or spend perspective do you anticipate getting from this FCS infrastructure as you think about launching the higher trigs opportunity? Thanks so much
Onaiza Cadoret: Sure. So we’ve done some extensive work with payers to understand kind of this dual indication that we’re going after in prevalent and rare disease does that actually really make a shift in your pricing strategy? Do — we know that once we have the more prevalent indication, the pricing will obviously be in line with good kind of cardiovascular premium priced products. We see really no indication in terms of, thinking about this differently as a result of the two indications, if they were to single indications in different molecules. We priced the rare disease along rare disease, pricing corridors and the broader indication along the quarters of a good cardiovascular premium price benchmark as well. So, you should think about it that way.
I would say, that the SCS account sales team, we’ll be calling on obviously, a much smaller portion than the total universe of physicians you would call on for SHTG. It will be more focused on the lipidologists, but extend out a bit beyond that as well for where we believe the FCS patient population is we’re doing a lot of work from our integrated data analysis, and qualifying where those physicians are that actually have FCS patients. And then, as we get into the broader indication, those sales teams will obviously stay on board and we will extend the size of the sales team for the broader SHTG market, to incorporate some of the other physician specialties that we believe will be very important for the uptake of that product.
Q – Unidentified Analyst: Excellent. Thank you.
Operator: The next question will come from Allison Bratzel with Piper Sandler. Please go ahead.
Q – Allison Bratzel: Hi. Thanks for taking the question. So first, I guess I just wanted to ask on the anti-tau update last week for BIIB080. I know Biogen is responsible for development of the asset. But I’d still be curious just to get your thoughts on how that approach could fit into the Alzheimer’s treatment paradigm, be it in combo or monotherapy or what have you. I’m then hoping, you could also just describe how that data maybe influences your confidence in the wholly owned neurology assets. And then on a second front, just on the complement Factor B program looking at that interim Phase 2 data being presented at ASN in a couple of days. Is there any update just on your view of the IgA nephropathy market and potential opportunity in IgAN just given the context of an evolving competitive landscape there? Thank you.
Brett Monia: Thank you, Allison. The Phase 2 study evaluating tau in patients with Alzheimer’s disease is underway and enrolling. And it’s a very — it’s really quite an extensive study with more than 700 patients to be treated for well over a year, with the primary endpoint really being efficacy improvement in cognition. And the purpose of that Phase 2 study, is to really make a decision to set up and support a path forward to go to Phase 3 development for a pivotal study. And in this study, we are exploring different dose levels as well as different dose regimens including, twice a year dosing and that’s based on the data that you’re referring to which is the Phase 1/2 study that is now published in JAMA Neurology and was presented at CTAD last week and is incredibly supportive of that Phase 2 study and the Tau program overall.
We and our partner Biogen could not be more thrilled with the data that was generated from the long-term extension of the Phase 1/2 study in patients with Alzheimer’s disease. tau is considered by exploring essentially all the efforts in the field as being the most important target for Alzheimer’s disease based on the neurofibrillary tangles that appeared just before cognition impairment occurs. It’s downstream of beta amyloid, which can be present long before cognition deficits occur. But it’s a difficult-to-drug target because what matters most is intracellular tau that closes the neurofibrillary tangles from neurodegenerative. What we have shown for the first time is not only can we substantially lower our all forms of tau in CSF, we can actually reverse tau pathology in the long-term extension data in patients by PET imaging.
But now we also have from the long-term extension data actually signs, trends that patients are actually improving in cognition. So we couldn’t be more thrilled about the data. And this has built on our confidence from the CLIA Phase 2 study that’s underway that I referred to earlier. As far as combination monotherapy that kind of thing that’s – this is the start of a development program for a drug that’s leading the way to target tau. The Phase 2 study is intended to assess the benefits of tau on cognition as a monotherapy. That does not preclude future studies looking at different combinations as this field evolves, whether it be with the beta amyloid treatment in combination with the tau-driven and so on. That will require further development and – but it can make sense.
We can see how those two mechanisms can actually complement each other and maybe even synergize with each other. So all that is on the table. But right now Biogen and Ionis are focused on the Phase 2 study to bring that forward as quickly as possible. And as far as confidence in neuro, this is just another piece of data, evidence, validation of our leading neurology platform. I would start with SPINRAZA and QALSODY, two approved breakthrough treatments for neurodegenerative diseases using the same platform as tau, using the same platform as our Angelman’s program, using the same platform as all of our 12 drugs that are currently in clinical development for all kinds of different neurodegenerative neurodevelopmental disorders. And as Richard highlighted in his earlier remarks, we expect to start a prion program wholly owned program by the end of this year and three more next year that are wholly-owned, neurology programs for diseases that have a high unmet medical need for both rare and large indications.
