Gregory Renza: Great. Thank you very much for taking question. And congrats on the quarter and the progress so far. David and team, just maybe a question and a request for your renewed thoughts on really the path to profitability. Just curious as you have prioritized certainly the pipeline programs doubling down on the commercial portfolio, how you think about the investments that you’re committing to and just that ramp there as it relates to looking at these early programs that you believe have a high probability or a better probability of success as it pertains to looking at profitability? Thanks so much.
David Epstein: Yes. So, I’ll start and then Todd will follow up. I mean, the short answer is in the JPMorgan meeting, healthcare conference meeting and in this call, we’re highlighting three global or near globally owned assets, each of which can be a blockbuster. And just to put that into context for you, non-small cell lung cancer for B6A is a market that’s, call it, 6 times the size in terms of epi than the first line PADCEV bladder cancer market. So, we’re talking about really tremendous opportunities for our company. So, the way I think about these things is our first priority is to invest adequately in terms of having the breadth of pivotal trials necessary to capture those huge upsides. Obviously, we’re very thoughtful about how we spend our cash, balance sheet is strong.
And when we do get the profitability, I would suspect it’s not going to be eking out minor profits but would be profits that really matter, they would become substantial. Anything you’d want to add, Todd?
Todd Simpson: Maybe just one thing. Thanks, Greg, for the question. If you — this is first all a question that we’ve gotten for a long time, and it’s a good question, it’s one we steer out. I think our strategy continues to be investing in our portfolio and our platforms to bring more meaningful drugs to patients in need. And I think if you just look at last year’s print, we — our revenues were up about 25% for the quarter and the year. When you look at the €˜23 guide, even excluding Cohort K, we’re up about 15%, and this brings our total revenues to $2.25 billion just about. So I think that’s an illustration of how successful we think the strategy has been. With that in mind, we’ve got an amazingly broad and deep pipeline to continue investing in.
You heard a little bit on the call today about programs like B6A and DV and B7H4. These are drugs that address meaningful solid tumor populations and their assets that for all intents and purposes are wholly owned by Seagen. So, we think those are the types of assets that make a lot of sense for us to invest in and invest in heavily to really continue to drive the growth and the success that we’ve had today.
David Epstein: I think just to add to that in another way, I think what Todd just told you was we could get profitable pretty soon if we wanted to, but we would be cutting off our future, which is much more exciting than where we are today.
Todd Simpson: Agree.
Operator: Our next question comes from Michael Schmidt from Guggenheim Securities.
Yige Guo: This is Yige on for Michael. Thanks for taking our questions. One question on PADCEV. You previously reported medium treatment duration of 11 cycles for PADCEV KEYTRUDA combo in Cohort K. Is that a good modeling assumption for PADCEV duration in first-line cis-ineligible patients in clinical practice post approval, as we are nearing the PDUFA date in April? And how could this number still change with longer follow-up as there were still roughly one-third of the patients still on treatment by the last data cutoff? Thank you.
David Epstein: Yes. So, we are very excited about this upcoming FDA decision with the April PDUFA date. I’m going to ask Chip to try to give you a little bit of thinking about how long we think patients might be on therapy. One thing I would say to you is that they will be on therapy longer in the front-line setting than in the second-line setting in part because these patients are generally healthier, in part because the dose density is probably a little bit less, and all told patients should do better when this drug is combined with KEYTRUDA, given the synergies that we see between vedotin and anti-PD1. Chip, any more thinking you’d want to add?
Chip Romp: Yes. Sure, David. I think it’s just important to note we don’t have a label yet. So certain details on this could change. But our general thinking with regard to the clinical trial experience we have is that we would expect to see a longer duration than what we do in second line. The duration in frontline, we think is going to be somewhere closer to 7 months. As David mentioned, it’s a little bit less of a dose dense regimen on a monthly basis, and the patients are also generally speaking, a little bit fitter. So, we think that’s kind of what we’re looking towards.
Operator: Our next question comes from Andy Hsieh from William Blair.
Andy Hsieh: David, congrats. Great to hear from you. So, I am just curious about the biology and underlying clinical characteristics of first-line cisplatin-ineligible patients versus, let’s say, second or third line as you enroll in the EV-301 or the initial accelerated approval? I’m just curious, is it beyond the realm of possibility to receive a broad label as the FDA review the PADCEV in front-line UC?
David Epstein: So, I’m going to put this one to Roger. Let me just say — you gave me a nice opening there, complement. Let me just say that I’m really happy to be at Seagen. I’m about three months in right now, I’m even more bullish on the future of this company, and you heard some of that in the call. We have strong in-line growth, B6A is shaping up to be a transformative asset, leading position in bladder cancer. And although we haven’t been asked yet, we have a discovery team that’s getting ready to file this year IND with the campto payload. So, this company is really on the move. Now for your specific question, Roger, what do you think?
Roger Dansey: Hey Andy, thanks. It’s an interesting question. I think our view is essentially, we get — we hope we get what we ask for. As David said, the review is going well. The population is well defined as cis-ineligible based on characteristics of things like renal dysfunction and hearing loss. And we have, right behind it, EV-302, which we’ve signaled we may — will have top line data sometime in this year, towards the end of the year perhaps. So I think although it would be fantastic, I think it would be very unlikely. My personal view is if we’re successful, the likely outcome is the label will reflect the population we studied, which is cis-ineligible patients.
Operator: Our next question comes from Joe Catanzaro from Piper Sandler.
Joe Catanzaro: Hey guys. Thanks for taking my question. And congrats on the progress. So Roger, you just mentioned EV-302. With enrollment now complete, I was wondering if you had any visibility into the extent of avelumab maintenance usage in the control arm and how you think about how that may impact the potential performance of the control arm in that study.
David Epstein: Roger?
Roger Dansey: Yes, Sure. Thanks, Joe, for the question. So just to give you a little bit of history, if you recall, avelumab went through its approval process as we were rolling out EV-302. And it is obviously part of the care of patients with frontline disease, provided they have either a response — complete response, partial response or have disease control, meaningful disease control. And so the population that actually gets avelumab relatively restricted compared to the population that we’re looking at on EV-302. Nonetheless, they will be used. I can’t share with you what that level will be. It is a global trial. So, EV-302 has been conducted around the world. And if physicians on the control arm consider that avelumab should be used, well then that likely will happen.
So I can say there is avelumab use, I just can’t give you any more detail as to how much. With regard to the outcome, I mean, obviously, the trial itself will demonstrate in the end what the value in terms of things like overall survival and progression-free survival is with PADCEV and KEYTRUDA. I would remind you, we have done — although there are single-arm experiments, we have done two experiments through the form of Cohort A and Cohort K in a population of cis-ineligible patients that are generally perhaps not as well as an older than cisplatin-eligible patients. And the survival curves they’ve generated from there give us optimism and confidence that if we repeat that type of outcome in the context of a broad global trial, which includes all of these different populations and a degree of avelumab use, I mean, again, we have — we’re optimistic.
We’re excited about the combination. Until the trial reads out, I can’t tell you what the results will be. But I think we have a good shot of the positive outcome.
Operator: Our next question comes from Andrew Berens from SVB Securities.
