I’m not sure that’s always easily picked up, certainly this morning. But we are — it’s our last LOE. And I would strongly encourage some reflection on that because we are — as we exit ’23 on track for a BOI in ’25, that’s a major moment for us to be launching and with the last LOE behind us. That’s why we’re excited about what we’ve communicated even if it takes a little bit of reflection. Okay. Next question?
Operator: Next question is Mark Purcell from Morgan Stanley. Mark?
Mark Purcell: I have just two. Firstly, in terms of Dupixent, could you help us understand how to gauge the potential probative success here in COPD? I guess if we look back at other IL-5s, but not with Dupixent and eosinophilic enriched populations against the triple combination therapy. We’re seeing roughly 17% to 18% exacerbation benefit. And that, I guess, is maybe on the cusp of if clinical meaningfulness. So, it would be great to get your viewpoints on your thoughts and expectations ahead of the data readout on the top line later in the first half of this year? And then secondly, Paul, you provided us with some of the key drugs to keep a progress support on back in December ’19. As you sort of think about these sort of 3 to 5 new products with €2 billion to €5 billion of peak sales potentially each launching over the second half of this decade, could you sort of help us by identifying which you feel we should focus on?
A drug like the OX40-ligand, for example, Phase 2b data and in Q3, would that be one of them? Just to try and get some additional color there would be great. Thank you.
Paul Hudson: Okay. Mark, thank you. So, John Reed, Dupixent COPD?
John Reed: Well, listen, we’re very excited about our COPD programs. We’re the only company in the industry that has two assets in Phase 3 development for COPD, which is a huge healthcare burden, as you know, some estimates are the third leading cause of death, a huge burden on healthcare systems and no new mechanisms have been approved for over 50 years. So to have two opportunities with Dupixent and itepekimab in advanced Phase 3 studies is really exciting for us. The dynamic around exacerbation rates has been affected by the pandemic and the overall rates are lower. We have monitored that in the unblinded total population and believe that our studies are adequately powered to show the statistically significant differences based on the effect sizes that we’ve assumed.
And so, we remain confident in the studies going forward. I think also the lung function part of the equation too is something that’s often overlooked in addition to exacerbations. But the lung function improvements that we’ve seen with both of these molecules have just been really rock solid, unequivocal. So, that’s an important variable to also mention when you think about what our prospects are for doing something meaningful for patients with COPD.
Paul Hudson: Thanks, John. So, we know there’s no advanced therapies, I think inhaled therapy is what we referred to in triple, and we know we passed a high hurdle on the interim. And so, we know we have high expectations, but we’re also turning the cards over here. So — and this is exactly what we should be doing in the Company. Maybe just to flow on from that in terms of your other question, let’s stay in COPD for a moment. Itepekimab, IL-33, that’s around the corner. In an ideal world, we’ll have two advanced therapies in COPD that would be — well, incredible, frankly. Amlitelimab, I think you’ve mentioned yourself that’s starting to get very exciting. We’re doing some very clever work around there, getting some really interesting data now that we’re getting first patients in, in our nanobodies, IL-13/TSLP, for example, TNF IL-6, I think we have 3 already in the clinic.
