Bruce Cozadd: Annabel, Rob loves it when you say what gets him excited about our pipeline. So, on zani, we’re in a really fortunate position of having had a couple of data readouts even since we signed the initial transaction that give us confidence, but I’ll let Rob jump in on specific answers to your questions.
Rob Iannone: Yes. Thanks for the question. Thanks, Bruce. You have it, you have it right, I described the very strong data from the single arm Phase 2 trial that’s front-line zanidatamab in combination with standard of care. And that was meant to provide data in support of the ongoing pivotal program. And I think the results give us a lot of reassurance about what we can expect in that Phase 3 pivotal program and confidence that it’s likely to be the standard of care. So, you’re thinking about that in the right way. In terms of where else to go with this, if you look at all the data published now, BTC, gastric, breast cancer data, other data from the Phase 1 trial, it’s very clear that this is highly-active anti-HER2 therapy and just about any tumor type that is overexpressing HER2.
In fact, we see activity in patients progressed on other anti-HER2 therapies, which is very important, as you think about where to position this next, different lines of therapy. And so, we’re actively looking at different opportunities beyond our current strategy. As you know, we’re planning a fast-to-market strategy with BTC and then our next pivotal trial in gastric, but looking at other opportunities.
Operator: Thank you. Our next question comes from David Amsellem with Piper Sandler. Your line is open.
David Amsellem: Hey, thanks. So, I wanted to switch gears to one of your pipeline products. This is the orexin agonist 441. So, in the study, if I’m not mistaken, you’re dosing it at night time. And I’m just trying to get a better sense as to the rationale here given that this is ostensibly a wakefulness or alertness drug. And do you think that there is something there that could set you apart from the other vaccines that are in development, be it the Takeda ones or the one from Alcami’s or potentially others? Thank you.
Rob Iannone: Yes…
Bruce Cozadd: Rob, you want to jump in on that?
Rob Iannone: Yes, happy to, Bruce. I’ll answer the second part first, which is we looked at this molecule carefully before we did the deal preclinical data, emerging clinical data, and we do have a lot of confidence around it being differentiated potentially to other products that are in development. In terms of our approach to the study design, you asked specifically about dosing healthy volunteers at night, this is really a way for us to quickly in healthy volunteers establish the proof-of-concept around wake promotion. So, in healthy volunteers, when they are sleep deprived, you can then measure alerting effects in that population that would be harder to measure during the daytime in otherwise healthy population. So, as we do that comprising single dose study, evaluating increasingly higher doses, we then have an opportunity to interrogate the relative wake-promoting effects across those doses, which then sets us up for the necessary downstream study.
So, clearly, then we need multiple dose safety and that will help to select the dose for the study that we just posted on clinicaltrials.gov, and then ultimately together help us to select the dose for the first patient studies.
Operator: Thank you. Our next question comes from Gary Nachman with BMO. Your line is open.
Gary Nachman: Thanks. So, my question is on Rylaze, which has been growing pretty nicely. So, how much will the Monday/Wednesday/Friday dosing help further uptake of that product? And then, what’s the cadence for expanding Rylaze geographically, including the EU and Japan? And how much will those ex-U.S. markets ultimately contribute? And then, with the CRL for the IV, how important is that ultimately to the franchise? So, would there be a long-term impact if you don’t move forward with it? I know, there won’t be an impact in the near term, but what about the long term? Thank you.
