Arrowhead Research Corporation 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thank you. Thanks for having us.

Yeah. Thanks, Prakhar. We did report out our SHASTA-3 and SHASTA-4 clinical study results at the European Society of Cardiology. The physician feedback has been incredibly positive. This is actually good timing. We conducted market research here in New York just last week with physicians getting their sense of the data. Similarly, this week, we are conducting market research in Los Angeles. So we have received lots of physician feedback. I would say it circles generally around three key areas: efficacy, safety, and dosing. From an efficacy perspective, the attributes they tend to focus on the most was the potency around the TG reduction, so up to 81% triglyceride reduction. The reduction in acute pancreatitis, so 78% reduction in acute pancreatitis, which was statistically significant across the pooled analysis.

Then importantly, they talk about more than 90% of subjects in the treatment arm getting below 500 milligrams per deciliter, which is a guideline-directed threshold for acute pancreatitis risk. So those are kind of the three data points that they tend to focus on as it relates to efficacy. From a safety perspective, they tend to circle on a number of differentiating aspects. In particular, the fact that with plozasiran in those studies, we saw no meaningful increases in liver enzymes, no statistically significant difference in hepatic fat fraction, no thrombocytopenia, reduction in platelets, and no hypersensitivity reactions, which they view as differentiating within the class. So those have been some compelling messages that we have heard back from physicians through this research.

Then lastly, the every three-month dosing does present some unique opportunities for patient benefit as far as only four injections a year and the potential for improved adherence over time as well.

Yeah. I think we can talk about what we saw or didn't see in SHASTA-3, SHASTA-4, and we didn't see an increase in hepatic fat fraction. Olezarsen did. I think it still remains to be seen how that will play out over time. The open label extension data was presented out to 24 months, and there was still elevated hepatic fat in the open label extension. We'll see how that plays out from an olezarsen perspective, but we can at least confidently say from a SHASTA-3, SHASTA-4 in our MRI-PDFF sub study, we did not see a statistically significant difference in hepatic fat fraction. There is some potential analog here as well around the difference between ASOs and siRNAs as it relates to hepatic fat fraction.

You may recall from the previous vupanorsen data related to ANGPTL3, that being an ASO, there was an increase in hepatic fat fraction that led to the discontinuation of that therapy. We similarly have an siRNA targeting ANGPTL3 zodasiran, and to date, we haven't seen an increase in hepatic fat fraction. It's possible this is attributed to the mode of action between ASOs and siRNAs. I think it still remains uncertain at this point, but the one thing we can say confidently is coming out of SHASTA-3, SHASTA-4 in that sub study- Right which was powered for safety, there was no difference.

When you say does it come up a lot, meaning does it come up in relation to olezarsen resulting in switches to plozasiran?

Yeah. Because we don't have hypersensitivity.

Right. Yeah. We see about 10% of prescriptions presently are olezarsen switches.

Okay. The vast majority are APOC3 treatment naive, and that's our focus.