Seagen Inc (SGEN) 2019 Q4 法說會逐字稿

Ladies and gentlemen, thank you for your patience in holding, and welcome to the Seattle Genetics Fourth Quarter and Full Year 2019 Financial Results Conference Call. Today's call is being recorded.

It is now my pleasure to turn the call over to Ms. Peggy Pinkston, Vice President, Investor Relations. Ma'am, please begin.

Thank you, operator, and good afternoon, everyone. I'd like to welcome all of you to Seattle Genetics Fourth Quarter and Full Year 2019 Conference Call. With me today are Clay Siegall, President and Chief Executive Officer; Robin Taylor, Chief Commercial Officer; Todd Simpson, Chief Financial Officer; and Roger Dansey, Chief Medical Officer.

Accompanying today's conference call are supporting slides, which are available on our website in the Investors section, Events and Presentations page. Following our prepared remarks, we'll open the line for questions. (Operator Instructions)

Today's conference call will include forward-looking statements regarding future or anticipated events and results, including the company's 2020 financial outlook, anticipated product sales, revenues, costs and expenses; and timing to achieve potential clinical and regulatory milestones, including data readouts, regulatory submissions and approvals.

Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty in forecasting sales, revenues and expenses and the uncertainty associated with pharmaceutical development and regulatory approval process. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the company's periodic reports filed with the Securities and Exchange Commission, including the company's annual report on Form 10-K for the year ended December 31, 2019.

Now I'll turn the call over to Clay.

Thanks, Peg, and good afternoon, everyone. Seattle Genetics has entered a new decade as a multiproduct oncology company. In December, we expanded our commercial portfolio with FDA approval of PADCEV for metastatic urothelial cancer. PADCEV for metastatic breast cancer is on the horizon in 2020 as a potential third-drug approval.

And ADCETRIS remains an important brand globally that has been used in the treatment of more than 60,000 lymphoma patients worldwide.

Beyond these 3 products is a robust pipeline of novel programs that we believe have the potential to help more than -- more people with cancer.

2019 was a banner year, and our progress has positively impacted future potential of Seattle Genetics.

Turning to 2020. Our revenues from product sales will be more diverse as we add PADCEV and, if approved, tucatinib to a strong ADCETRIS pace. PADCEV was approved in late December, roughly 3 months ahead of its PDUFA date. Joint sales team with our partner, Astellas, is actively engaged with oncologists in both the academic and community settings. We're very pleased by the positive reception to this important drug and by the number of accounts and increasing number of vials ordered in the first full month of sales. We are early in the launch phase of PADCEV and have not -- and have decided not to give sales guidance until we gain more experience in the marketplace.

In parallel with our PADCEV launch activities, we are investing in a broad clinical development program with a focus in urothelial cancer.

Today, we are announcing the recent completion of enrollment of our randomized Phase III trial called EV-301. This trial is intended to confirm the accelerated approval of PADCEV and support global applications for approval.

Importantly, we have initiated a Phase III trial in first-line metastatic disease, which is key to our global development strategy. This trial is being conducted under a collaboration between Seattle Genetics, Astellas and Merck, with each party providing significant funding. In addition to these registrational trials, we are evaluating PADCEV in earlier-stage bladder cancer and believe there's also potential in other Nectin-4 expressing solid tumors.

Next is tucatinib, which is in line to become the third drug in our commercial portfolio. This program has advanced significantly in just the past couple of months based on outstanding data from the HER2CLIMB pivotal trial in metastatic HER2-positive breast cancer, including patients with brain metastases. Full results from the trial were featured in an oral presentation at the San Antonio Breast Cancer Symposium in December and simultaneously published in the New England Journal of Medicine.

HER2CLIMB, which supported FDA breakthrough therapy designation, positions tucatinib as the potential best-in-class HER2 tyrosine kinase inhibitor. Based on HER2CLIMB results in December, we completed submission of the NDA, which is being reviewed under the FDA's real-time oncology review program. Another significant regulatory accomplishment with tucatinib was the January submission and recent EMA validation of the MAA in Europe.

We're also participating in Project Orbis, an FDA-sponsored program that provides a framework for current submission and review of oncology drugs among the United States, Canada, Switzerland, Singapore and Australia. We have now submitted tucatinib in each of these countries, positioning the drug for global approvals beginning later this year.

Our goal is to bring tucatinib to patients in need around the world. With that in mind, we're in the process of expanding our European capabilities.

Through our teams in the Netherlands, Switzerland and the United States, we're prosecuting our MAA submission, and we're adding leadership in key countries.

As with PADCEV, we are conducting a broad global development program with tucatinib. Roger will provide additional details on the clinical development activities, and Todd will speak to the investment we are making in these important programs.

Moving on now to ADCETRIS. We're pleased to report record 2019 revenues in the U.S. and Canada of $628 million, up 32% over 2018. This follows a 55% growth rate in 2018 driven by adoption in frontline Hodgkin lymphoma and peripheral T-cell lymphomas.

Taken together with sales of ADCETRIS by Takeda in its territory, global sales in 2019 exceeded $1 billion, underscoring its importance to physicians and patients around the world. We expect 2020 ADCETRIS net sales in the U.S. and Canada to be in the range of $675 million to $700 million. While this reflects more modest growth, we believe that our ongoing and planned clinical trials with ADCETRIS will provide opportunities for additional expansion of the brand. We also expect to report 5-year progression-free survival results late this year from the ECHELON-1 trial in frontline Hodgkin lymphoma. This is an important milestone for lymphoma patients and could further establish the positive long-term benefit of ADCETRIS+ AVD.

Our clinical-stage pipeline is robust and we're conducting trials across a spectrum of both hematologic malignancies and solid tumors. Most advanced of these programs is tisotumab vedotin or TV, which we are developing in collaboration with Genmab.

Our initial focus is in recurrent or metastatic cervical cancer. We expect to report top-line data from a potentially pivotal Phase II trial in the first half of 2020. We are also evaluating TV in other solid tumors, including ovarian and head and neck cancer with activities underway to optimize dose and schedule.

In 2018, we initiated trials with several novel agents. We intend to continue our investment in innovative new product candidates, including ADCs and other targeted therapies, with 4 INDs planned in 2020 and another 4 in 2021. These early-stage programs are based on efficient clinical trial design that are intended to inform clear rapid development decisions.

We are also pleased with the progress of ADC collaborative programs, namely the U.S. and recent EU approval of Roche's Polivy, and the ongoing priority review by FDA and recent MAA validation of GSK belantamab mafodotin. Both of these ADCs employ Seattle Genetics' proprietary technology. There are more than 10 ADCs using our technology in clinical development by us and our collaboration partners.

Lastly, in the fourth quarter of 2019, we completed a license agreement with BeiGene, our first collaboration with a company in China, an increasingly important market for anti-cancer therapies. This included an upfront payment of $20 million, and we are eligible for progress-dependent milestones. This program recently entered a Phase I clinical trial.

I'm proud of our exceptional progress in 2019. We're diversifying our commercial portfolio and revenue drivers, addressing meaningful unmet medical needs and investing across our portfolio to fuel future growth. We are well positioned to continue transforming Seattle Genetics into an important biotechnology company focused on helping cancer patients around the world.

At this point, I'll turn the call over to Robin to discuss our commercial activities. Then Todd will comment on our financial results and 2020 guidance. After that, Roger will discuss our clinical development activities. Robin?

Thanks, Clay. I'm excited to provide an update on our commercial activities. ADCETRIS net sales in the U.S. and Canada were $166 million in the fourth quarter, an increase of 26% compared to the same quarter in 2018. Total year sales were $628 million, an increase of 32% over 2018. Growth was driven by our frontline indications in Hodgkin lymphoma and PTCL.

4-year follow-up data from the ECHELON-1 trial that were presented at ASH complement the value proposition that ADCETRIS offers patients. Aimed clinical benefit of A+ AVD over ABVD enables meaningful discussions with physicians who have been slow to adopt the A+ AVD regimen. We also look forward to the 5-year data later this year.

For 2020, we are focused on continuing to promote ADCETRIS under its broad label that now includes 6 indications. We're describing the clear and durable advantage of A+ AVD in the frontline setting for patients with Stage III and IV Hodgkin lymphoma.

In frontline PTCL, A+ CHP is the standard of care for patients with ALCL. And we are working hard to drive use in additional CD30-expressing subtypes while engaging with pathology labs to improve the reporting of CD30. Through these efforts, we intend to continue growing the ADCETRIS franchise.

Now I'd like to transition to PADCEV, which was approved late in 2019. Seattle Genetics and Astellas sales forces are active in the field. Reaction from physicians is very positive, and the number of accounts that have ordered PADCEV from both academic and community sites has exceeded our expectations in January, our first full month of launch. We estimate that there are approximately 3,200 accounts in the United States that treat metastatic bladder cancer patients and may order PADCEV. In the short period of time that we've been in the market, our representatives have already called on 1,500 of these accounts.

We're also pleased with the rapid inclusion of PADCEV in the NCCN treatment guidelines. There's significant unmet need in metastatic urothelial cancer, post-platinum chemotherapy and PD-1 or PD-L1 therapy. The team is focused on driving awareness and understanding about this important new treatment option. I look forward to updating you on our progress throughout the year.

Moving on to tucatinib. The commercial team is excited by the clinical data from HER2CLIMB and the positive reaction to our presentation at the San Antonio Breast Cancer Symposium in December. Our sales leadership team is in place, and we are hiring the U.S. sales force. We're attracting top sales talents with significant oncology experience. Metastatic HER2-positive patients, especially those with brain metastases, needs new treatment options, and our team eagerly awaits the approval.

In summary, the growing commercial team at Seattle Genetics is well positioned for a transformative year as we bring meaningful products to patients in areas of unmet need.

Now I'll turn over the call to Todd.

Great. Thanks, Robin, and thanks, everyone, for joining us on the call this afternoon. Today, I'll summarize our financial results for the fourth quarter and full year in 2019, and then I'll provide our financial outlook for 2020.

Total revenues were $290 million in the fourth quarter of 2019 and $917 million for the full year. This included ADCETRIS net sales of $166 million in the fourth quarter and $628 million for the year. PADCEV was launched during the holiday period at the end of the year and therefore only provided a modest contribution to sales.

Royalty revenues in the fourth quarter of 2019 increased to $72 million compared to $25 million in the fourth quarter of 2018. This included a onetime $40 million milestone from Takeda that was triggered by annual sale of ADCETRIS, exceeding $400 million in its territory in 2019.

For the full year in 2019, royalty revenues were $138 million compared to $83 million a year ago. This growth reflects a sales milestone, higher sales by Takeda in 2019 and the royalty rate on sales above $400 million increasing to mid-20%. Royalties from Roche on Polivy also contributed to 2019 results.

Collaboration revenues were $51 million in the fourth quarter of 2019 and $150 million for the full year. These revenues included $55 million in milestones from Takeda related to international approvals of ADCETRIS in frontline Hodgkin lymphoma, FDA approval of Roche's Polivy and the initiation of GSK's Phase III trial with their ADC utilizing our technology. Additionally, we recognized $20 million in upfront payments from BeiGene upon entering into a product licensing agreement in the fourth quarter.

R&D expenses were $201 million in the fourth quarter of 2019 and $719 million for the year. Growth over 2018 reflected higher investment across our late-stage pipeline, most notably for PADCEV and tucatinib, which included the pivotal trials that led to the PADCEV approval and the tucatinib submissions.

SG&A expenses were $115 million in the fourth quarter of 2019 and $374 million for the full year. These are both increases over 2018 and reflect commercialization efforts related to the ADCETRIS frontline indications and preparations for the launches of PADCEV and tucatinib.

We ended 2019 with $868 million in cash and investments. In addition, we held approximately $163 million in Immunomedics common stock. These shares are mark-to-market, which resulted in a noncash gain that contributed to investment income of $64 million for the fourth quarter and that led us to reporting net income, as you saw in our press release this afternoon.

Regarding our financial outlook for 2020. I'll begin with revenue guidance. There are 3 main components. First, we expect ADCETRIS net sales in the U.S. and Canada to be in the range of $675 million to $700 million. At this time, we're not providing PADCEV guidance. Second, we expect royalty revenues to be in the range of $105 million to $115 million based primarily on anticipated sales growth of ADCETRIS by Takeda. And third, we expect revenues from collaboration and license agreements to be in the range of $30 million to $50 million.

Turning now to expenses. We expect R&D expenses to be in the range of $860 million to $950 million. This primarily reflects planned investment in PADCEV and tucatinib, including several registrational trials as well as investment across our earlier-stage portfolio.

Similarly, SG&A expenses are expected to increase to a range of $475 million to $525 million. This includes full year cost of the PADCEV commercial infrastructure, building our tucatinib commercial team and expanding our European capabilities.

We expect ADCETRIS cost of sales to be in the range of 5% to 6% of sales. As a reminder, Seattle Genetics book sales of PADCEV in the U.S., and we will record Astellas' 50% share of gross profit as a component of cost of sales. Marketing and development expenses are also shared equally. These are netted out in our SG&A and R&D expenses and have been reflected in our guidance.

So to wrap up, we have bold plans in 2020 and an opportunity to significantly expand the potential of our drugs to help patients.

And with that, I'll turn the call over to Roger, who will provide some of the specifics.

Thanks, Todd, and good afternoon, everyone. As Clay described, 2019 was an exceptional year for Seattle Genetics in achieving our goal of bringing important new medicines to people with cancer. Today, I will mostly focus my remarks on PADCEV and tucatinib as we have ambitious development plans for each of these exciting drugs.

I'll begin with PADCEV, where our first priority is evaluating this product across the continuum of urothelial cancer. There are 3 main components to our strategy. First, under the FDA's accelerated approval program, a confirmatory trial is required and we and Astellas are conducting the global randomized Phase III trial called EV-301 in metastatic urothelial cancer patients who've received a platinum-containing regimen and a PD-1 or PD-L1 inhibitor. Today, we announced the study has completed enrollment of 608 patients. Primary end point of EV-301 is overall survival. And in addition to serving as the confirmatory trial, it is intended to support global applications for approval.

Second, our next goal is to move PADCEV into first-line metastatic urothelial cancer. Based on encouraging data from the combination of PADCEV and KEYTRUDA, which will be updated next week at ASCO GU, we recently initiated a Phase III trial together with Astellas and Merck, evaluating this combination with or without chemotherapy. Target enrollment is approximately 1,100 patients, and importantly, through its first-line patients, regardless of platinum eligibility, PD-L1 expression or Nectin-4 expression. The trial will evaluate dual primary end points of progression-free survival and overall survival.

And third, our goal is to evaluate PADCEV in earlier stages of urothelial cancer, beginning with muscle-invasive bladder cancer. These patients find treatment, including surgical removal of the bladder, there is a high risk of recurrence of metastatic disease. We recently initiated clinical evaluation of both PADCEV monotherapy and the combination of PADCEV and KEYTRUDA prior to surgery.

Nonmuscle-invasive bladder cancer also represents a future development opportunity for PADCEV that we are currently evaluating preclinically. In these patients, available therapies are difficult to tolerate and may fail, resulting in a significant unmet medical need.

Beyond urothelial cancer, we believe the potential for PADCEV extends to other cancer types. We and Astellas recently initiated a single-seeking trial called EV-202 in a range of Nectin-4-expressing solid tumors, including breast, non-small cell lung, head and neck and gastric cancers.

I'll move on now to tucatinib, our oral tyrosine kinase inhibitor that targets HER2. We were gratified by the enthusiastic reception at the San Antonio Breast Cancer Symposium in December to the remarkable results from the HER2CLIMB pivotal trial. HER2CLIMB data give us conviction to expand upon our clinical development program in HER2-positive breast cancer and other HER2-positive cancers.

The key areas of clinical focus includes: First, evaluating tucatinib in a randomized Phase III trial in combination with T-DM1 versus T-DM1 alone in metastatic breast cancer. In this trial, called HER2CLIMB-02, patients must have previously received a taxane and a trastuzumab in the adjuvant or metastatic setting and thus represents a population receiving first- or second-line treatments.

Second, tucatinib in combination with standard treatment is being evaluated in neoadjuvant breast cancer through the I-SPY 2 trial. In addition, we are considering a trial in adjuvant HER2-positive breast cancer.

Third, the initial data from 23 patients treated with a combination of trastuzumab and tucatinib in metastatic colorectal cancer were very encouraging. After consultation with the FDA, we have expanded the existing clinical trial called MOUNTAINEER to enroll up to 110 patients with third-line metastatic disease. Importantly, this trial is intended to support a potential accelerated approval. We are also working on plans for confirmatory trials in colorectal cancer. And lastly, we are planning trials in HER2-positive solid tumors, including gastric cancer.

Next, I'll turn to ADCETRIS, which was the subject of many important presentations at the ASH Annual Meeting in December. Of note, the full year progression-free survival data from the ECHELON-1 trial in frontline Hodgkin lymphoma were presented and continued to show sustained clinically meaningful benefit of ADCETRIS+ AVD over ABVD. Peripheral neuropathy, a known side effect of treatment of ADCETRIS, continue to improve over time, with most patients experiencing complete resolution.

Very recently, the NCCN guidelines for both Hodgkin lymphoma and cutaneous T-cell lymphoma were revised with a number of positive ADCETRIS subjects. These included elderly frontline Hodgkin lymphoma, relapsed Hodgkin lymphoma and PTCL. Our ongoing and planned clinical development program with ADCETRIS includes retreatments using patients who are unfit for combination chemotherapy, novel frontline Hodgkin lymphoma combinations and relapsed/refractory produce large B-cell lymphoma.

Now I'll turn the call back to Clay.

Thanks, Roger. Before we open the line for your questions, I want to recap key upcoming activities across our oncology portfolio. They include: First, continue our strong PADCEV launch in the United States with Astellas and advancing a broad development program, including a Phase III trial in first-line metastatic urothelial cancer; second, work with FDA and other regulatory agencies on tucatinib approval and advance its robust clinical development program; third, continue to establish ADCETRIS as standard of care frontline Hodgkin lymphoma and frontline PTCL and initiate additional clinical trials; and fourth, report top line results from the TV pivotal trial in cervical cancer in the first half of this year.

As we've highlighted today, we are executing on our bold vision for the future Seattle Genetics. At this point, we'll open the line for Q&A. Operator, please open the call for questions.

(Operator Instructions) And our first question comes from Geoff Meacham with Bank of America.

I just got a couple. So the first one is on the ADCETRIS guidance. I just wanted to ask at a high level, can you talk about your expectations for PTCL? And maybe commercially, what's been the trend in the field going into 2020? And then on tucatinib, it seems like HER2 duration in the real world for other therapies is different than just looking at PFS. And so are there any commercial lessons to be learned from TYKERB or others that can be leveraged when you look to the tucatinib launch?

Okay. So we'll start with the ADCETRIS question and our guidance and trends and stuff like that. First of all, I'd like to step back and put ADCETRIS into context. This is a brand that continues to grow in the U.S. and internationally. 2019 was the first year that we hit over $1 billion in global sales. And this -- really, the last 2 years, we've doubled the sales of ADCETRIS. 2020 guidance reflects 7% to 11% growth over 2019, and that comes off of years where we had 32% and 55% growth, double sales in the last 2 years.

In frontline Hodgkin, we have 4-year PFS data that we presented in December at the ASH conference. And later this year, we expect the 5-year data. That's the gold standard, the 5-year data in Hodgkin lymphoma and frontline. So that should be helpful with docs.

In PTCL, I think you mentioned that. That's still growing and we have opportunities to increase the use, especially in non-ALCL, as the data continued to look good. But it is not the simplest exercise to displace decades-old standard of care that are entrenched. And we've been doing a great job in that, and we'll continue to do that.

Importantly, with ADCETRIS, looking to the future, thinking about guidance, we are continuing to do clinical trials and expanding our opportunities with these trials. Some of these opportunities are incremental, but some of them are big. We're looking at things, including DLBCL, elderly Hodgkin lymphoma, retreatment. And there's early-stage I and II Hodgkin lymphoma. So a lot of different things that we are doing. And like I said, some bigger opportunities like early-stage Hodgkin lymphoma, where we're not even half of Hodgkin lymphoma frontline and some are smaller.

So overall, Geoff, ADCETRIS is really -- it's a terrific first product for Seattle Genetics, and we're so excited to be expanding our product to include PADCEV and looking into the future, tucatinib.

Now you asked about tucatinib and duration and what lessons we could learn by that. I mean we're not giving guidance on that. We're not, at this point, saying how long we think patients will stay on this. It's a tablet that's taken twice a day. It's got a very good profile of efficacy and safety. Our data are really remarkable, and I think we'll learn a little bit of how this can be used initially. But we have this broad development program. And Rob or Roger, perhaps you want to talk a little bit about just what you think you see with duration of use or what the parameters are as we look at it in different settings.

Thanks, Clay. One of the key aspects of tucatinib is its tolerability. It has obviously very high efficacy. Putting in patients with brain metastases is a unique population, frankly, to be studied in breast cancer. But tolerability is also key, and we actually believe the tolerability of the molecule plays into its efficacy, that patients can stay on the drug for protracted periods of time, and that continues to suppress the HER2-signaling access.

We have patients in the program, anecdotally, who've been on the drug for years. So we are comfortable that extended duration of therapy is quite achievable. In the clinical trial itself based on progression-free survival, I think the average duration of a treatment is around about 7 months. But obviously, as we move into other areas where the duration of therapy may be dictated by the disease state, we're comfortable that tucatinib can be used for prolonged periods of time.

Our next question will come from Salveen Richter with Goldman Sachs.

So with regard to your ADCETRIS 2020 guide, can you just comment on why you're accounting for such limited growth at approximately 10% at the midpoint, just given this over 30% growth you saw last year? And is this conservatism? Or are there some dynamics at play here? And then secondly, anything you can give us regarding the early launch metrics or just qualitative feedback as you're looking and launching PADCEV?

Sure. On ADCETRIS and our guidance -- and maybe, Todd, you'll want to hop in here and give some commentary about this. I don't want to portray this as us doing anything but providing the best we can do, not conservative or not anything. I think that this is a brand that first got approved in 2011, and we have been growing and growing and growing the brand both in the U.S. and international. It is still growing, but the growth has slowed down. The rate of growth has slowed down. And -- but unlike a lot of brands that have been around for 8 years, this is a brand we're still investing in. And we have a lot of new findings and new data, and we're really excited by that.

And so perhaps, Todd could comment on -- and Roger talk about some very recent additions to NCCN. Maybe we'll start there. Roger, you talk about the NCCN. And Todd, we'll see if you have some color you want to put on this.

Sure. And so it is interesting. It's amazing, actually. The NCCN Guidelines continue to reflect data that is put out in the public domain that is valuable for patients that may not necessarily be a registration trial. A good example of that is the use of ADCETRIS together with Opdivo in the relapsed/refractory Hodgkin lymphoma, such a circumstance where the level of evidence is in rates from a 2B to a 2A, which just basically means complete consensus on the value of that.

In addition, in populations that struggle to take combination therapies such as older patients, another novel way of using ADCETRIS, which is to use it sequentially with chemotherapy, ADCETRIS followed by ABD, has also have made it into the guidelines. And that actually represents not just older patients with Stage III/IV disease, but it includes a reference to stage -- to earlier Hodgkin lymphoma with unfavorable product features in that older population.

And then in PTCL, interestingly, the ALCANZA trial is now directly referenced for risk in primary cutaneous T-cell lymphoma. And there's an acknowledgment, which we know well, that the ALCANZA trial that was done with a cut point of 10%, the guidelines now reflect the state that we know that patients who have expression levels below 10% still do respond. So the guidelines have acknowledged that population is probably broader than just what is in the trial.

And those NCCN guideline additions were this week.

Yes. (inaudible)

So this is brand new. I think it was yesterday or the day before. And so brand new additions, 3 additions to the guidelines for ADCETRIS. Todd, any additional color?

Yes. I guess, Salveen, I just commented ADCETRIS is a big important drug that helps a lot of patients globally. As Clay mentioned, we're over $1 billion now globally. We're very proud of that. We've -- in the U.S. and Canada, we've doubled sales over the last 2 years. We had 32% growth in 2019, and that was 55% in 2018.

So there's been a lot of growth, and we're continuing to invest in trials that Roger mentioned that we think can give us growth in the future. But maybe 2019 is a little bit of a catch of breath here after what's been a pretty remarkable run.

I think ADCETRIS provides an incredible base for us to build off of. We've now got PADCEV approved. We're looking to tucatinib approval. And we're in a very enviable position where, given our strength and what we have in front of us, we can really invest aggressively in trying to drive PADCEV and tucatinib into really big, important, meaningful drugs that help patients globally. So I think ADCETRIS is an important base to that story.

Thanks, Todd. And going to your second question on early PADCEV uptake and what's going on there. So what I -- first of all, I want to say that we have not provided financial guidance, and we're not going to yet. But we want to, and we want to provide it at the soonest possible opportunity, but we want to provide it when we have conviction. In that way, we'll give you a meaningful guidance.

And we really -- we were just approved towards the end of the year, and doctors were just organizing their patients. So the first full month really was in January. So where we had sales -- and it's only now February.

And so -- but having said that, we are incredibly pleased with the uptake. We kind of made some internal predictions, which are not with conviction. And PADCEV far exceeded our internal predictions. So, so far, we've been really happy with it.

Like Robin said, there's about 3,200 accounts in the U.S. that can be called upon. And out of that, about 2,800 of the accounts, we predict have the vast majority of sales. So those are the ones that we're really focused on, those 2,800 out of the 3,200. And we have -- in the first 5 weeks, we've seen 1,500 of those. But we are out there in full force talking about this really important drug at the same time that we have this full development plan.

Next question will come from Kennen MacKay with RBC Capital Markets.

ADCETRIS revenue was down slightly quarter-over-quarter. Can you maybe just help us understand what's happening on a volume basis and whether there's any impact from inventory or gross-to-net in Q4? And on the areas for ADCETRIS growth, I was wondering from the team's conversations, what needs to be seen in the 5-year ECHELON-1 data to win over some of the prescribers who have been the reluctant adopters of ADCETRIS in frontline Hodgkin's? And then secondly, on DLBCL, I was wondering if you could elaborate a little bit on the decision to pursue ADCETRIS there after walking away from potentially registrational trial in that indication several years ago? And then I had a quick follow-up.

All right. As far as the revenue and gross-to-net and all that, Todd, do you want to make a quick comment? We've really discussed this a lot already but go ahead.

Look, I guess, I wouldn't get too hung up in quarterly variability. There are different numbers of sales days. I don't want to get into that. But I'd say, to specifically answer your question, gross-to-net was fairly stable. The book of business was fairly stable. Coming into year-end, you see a little bit of stocking. I think it was probably comparable to what we saw a year ago. So I don't think that created any significant variability. So I think look at this year-over-year, and there, we had -- we put up some pretty good numbers for the year.

And your second question was about ADCETRIS 5-year data and what's important. And what I will tell you is, what's important is obviously efficacy and safety. But on the safety front, right away, this has no bleomycin. That is a bad actor. I mean that is a problematic drug for a lot of patients. You see some morbidity with it. Patients have permanent lung scarring and permanent change in their life. And they also have late problems that come up by taking bleomycin. So not taking bleomycin is something that literally every doctor we've talked to all agree is a good thing.

And what we are presenting is PFS. You may recall that when we first had our data come out with E1 a while ago, we had an agreement with FDA at looking at something called modified PFS. And we got a lot of hassle from people on why was it modified PFS and not regular PFS and all that. So we -- our data is strong, whether it's modified or regular PFS. But starting, I think, with the 3-year, we started using regular PFS just because that's what everyone asked for. And in the 4-year with regular PFS and the 5-year will be regular PFS. So no one will say to us, "Hey, how are these different? What is the differences?" We're using with the standard.

And if you see a 5%, 6%, 7% difference in the long-term survival in the 5 years, you could start saying, "It's a defined cure." Obviously, we all die of something. But oncologists look at the 5-year progression-free survival, and they equate that with cure. And we're going to be up to that. So if you can increase the defined cure rate at 5 years by 5%, 6%, 7%, whatever it is that we see in comparison to the year 4 data that we have at the same time there's no bleomycin, that's a win. And so that's what we look at.

Now you asked about DLBCL in ADCETRIS and what we're looking at. Perhaps, Roger, you want to talk about the efficient study we want to do and what we're looking for in that trial.

Well, thanks, Clay. So relapsed DLBCL has a meaningful number of patients in DLBCL, in general, that express CD30. That's the first thing. And we know that ADCETRIS is active we have data demonstrating that DLBCL is an appropriate place to evaluate, et cetera.

Beyond that, we actually know patients with a lower level of expression can also respond. So we are planning an all-comer trial, and we'll be sure to account for the CD30 expression. But we think ADCETRIS, based on its profile of efficacy and its safety profile, is a great option for a group of patients who have failed therapy and are in the space around things like CAR-T treatments and so on.

And so acknowledging the fact that this is -- that this was -- an attempt that was made earlier wasn't prosecuted I don't think, in any way, diminishes the value of us taking ADCETRIS (inaudible). Actually, we're excited. I think that the data that supports the trial is very strong. We obviously need to conduct the trial. But I think we're optimistic we may be able to get ADCETRIS to appropriately help patients with relapsed DLBCL.

Kennen, you had a quick follow-up? And let's make it a short one because there's a lot of other analysts who want to ask questions.

I appreciate the color. And lastly, I was just wondering if you could comment on what the next steps are in the ongoing dispute resolution with Daiichi Sankyo. Our work is very much sided with your stance within that resolution, so just wondering next steps.

So Kennen, we certainly saw your report, and it was very interesting. We did not know you were working on that. So it was interesting for us to see that. And your conclusion is similar to our conclusion that we have a very, very good case.

What I would say to you is that legal issues take time and go through a process. We believe that this should be an arbitration based on our 2008 agreement with them, and we're making steps towards that. And they publicly stated they would rather have to sit in court. But -- and the court will rule on it soon, whether it's an arbitration or court. But other than that, it's hard for me to give you inside guidance on this except for that we believe we have a very strong case. In the history of Seattle Genetics, 22 years, we have never proactively gone out and done a legal move like this. We are not a litigious company, but protecting our IP when we see something that's obvious is something we will do every day of the week if we need to. This is the first time we've done it, but we have to protect the IP of the company. And to us, this is pretty obvious.

Our next question will come from Andrew Berens with SVB Leerink.

I'm not going to ask one on ADCETRIS. I think there've been a lot of questions already, obviously. But can you give us some idea of how the payer discussions are going for PADCEV? Has there been any pushback on the price point that you chose? And then I have the other question on tucatinib.

Sure. I'll give a comment then turn it over to Robin. I will tell you, we've -- it's been going great. I really -- we just haven't had pushback on this at all. We think that we did a very good job in pricing this drug.

If you look at the world of oncology drug prices, there's quite a lot of drugs that were priced very high above this. And there are a number of drugs priced below it. But for the value that PADCEV brings, we think we put this in a very good spot. Robin, do you want to add any commentary?

Yes, absolutely. So we've been monitoring to see if there is any issues that are arising with PADCEV. And what we've seen is really that there are no issues, no pushback that we're seeing. We have PADCEV patient solutions in place. So if there are challenges that account comes across, then we have ways to help them out with that.

But the reality is that the launch has been going very well and a very positive reception from physicians. So it's a very high unmet need population.

Okay. And then on tucatinib, when can we expect the Mountaineer to read out now that you've expanded it? And what do you think the bar is for an accelerated approval?

Thank you for asking the question on MOUNTAINEER. So we put out data that were very strong at ESMO. And I would say it was somewhat unexpected by the audience, but there was a lot of interest in Mountaineer. And Roger and his team went to regulators and talked about this, and we have an agreement that we would take that trial and expand it. And obviously, everything is a review decision with regulators. But to take an existing trial and not restart, just expand it out to 110 patients and bring it back to regulators as a potential approval trial for registration, granted we would need a confirmatory trial, but that's pretty incredible. And we're super jazzed about that. And so that's open and cranking and -- because it's just adding on to a trial. And it is a corporate trial that we're running. And I really think we have a great chance.

We're not looking for data that's better. This isn't something where we're taking different things and combining them and wishing and hoping that we see something we haven't seen. We've seen great data in HER2-positive colorectal carcinoma. We have the combination of hitting on the outside of the cell and the inside of the cell with trastuzumab and tucatinib. And so this is something that we think is a really great opportunity. I mean this double hit on the outside and the inside really looks great. Roger, do you want to add to that? I'm sorry, I went on about that.

I do think, one, we obviously can't talk about timing. But what I would say to you, this is now a Seattle Genetics trial. So the full effort of the company and its resources are behind it. But we'll go and enroll as fast as we can and then read the trial out at the appropriate time.

Okay. One just quick follow-up. I guess since it's on top of Herceptin, it's obviously a combination. And I guess, in other indications, other drugs, the FDA has sometimes required some sort of controlled comparison. So I guess, what do you think is enough efficacy that they'd be willing to approve this on a single-arm trial?

So Andy, I -- they don't draw lines in the sand with us and write down numbers. But we showed a 52% response rate of the combination. And in published reports on using Herceptin alone, I mean you have something that's more like 15% response rate. And so we're like multiples above what we think Herceptin would be.

And we -- in our trial, we do have monotherapy with tucatinib. So we do know some of the components. So -- and a lot of work's done and been presented with Herceptin. We have monotherapy of tucatinib in colorectal, and we have the combination. I think the regulators have what they need. And I -- it feels like that's what they've indicated to us. So obviously, until we get approval, we can't make promises. But to go to regulators and have them say, you can expand this ongoing trial and we'll look at the data, and your data is pretty special, just bring us more of the same is pretty darn good. I don't even think -- and I don't even think we need data as good as we've had, doesn't have to exactly match. Can't -- obviously, it can't just go away. But we have room there.

Our next question comes from Matthew Harrison with Morgan Stanley.

I just wanted to ask about TV since no one's brought that up yet. Maybe you could just talk about what you think is the bar in that study and your confidence level around that when we get the data this year.

Thank you for asking about TV. TV is an interesting antibody drug conjugate. It binds to tissue factor. And we are working on this with Genmab, a partner of us that we work very closely with.

We presented data on this in the past, but it was part of a dose escalation in Phase I. So it is very hard to know all of the factors on this data. So we now are doing with our partners, Genmab, a bigger trial, a Phase II trial with 1 dose. So it is a large expansion into Phase II. It is potentially registerable. Now we obviously have other trials that we're working on and combination trials and a variety of things that we're excited about with TV, but this is an important trial for us.

I think that from this potentially registrational Phase II, we need to see something that's meaningful. And I think we could start by putting into context to the last drug that was approved for relapsed cervical cancer, and that was KEYTRUDA. That was approved based on a 14, 1-4, percent response rate with a duration of about a year. And that was in -- they had to screen, and that was in the PD-1 high -- or PDL-1 high, I should say, patients. And so it wasn't even all the patient population.

For us, we're looking at all patient population. And we showed from our early data, which is not as big of a trial and not our potentially registerable Phase II, but we showed something in the 20s percent response rate for this dreaded condition. If we're talking about lymphoma, that's not something people get too excited about. But if we're talking about relapsed cervical cancer, where there's very little hope and opportunity for patients, and you have a drug that could give you substantively higher response rate than the last drug that was approved, we'll just have to also watch for duration. I think the FDA has not given us a line in the sand. But I would think that if we could get more than -- and we want as much as possible, we'd love to see something very long, but I think if we could get more than 4, 5 months in duration or 4, 5, 6 -- I don't know, something more -- something substantively with duration and something with a response rate with -- in the 20s, I think we have a really good shot.

Now I will tell you that, to me, that's step one, okay? I want to be able to really help patients with relapsed cervical cancer, okay? And to me, that's going to come from probably a combination study in the future. Yes, we want to get on the market with this as a single agent. Yes, we want to have another alternative for patients who have no other alternatives. But to me, if we could get this approved, and then we could combine it with whether it's chemotherapy or I-O therapy or whatever, and we could get up to potentially 30%, 40%, 50% response rate in patients that literally have no options, that's what I'm looking to do.

So we're excited to get this into a drug and try to see if we can get this approved. We're also excited to do even better by these patients.

Our next question will come from Cory Kasimov with JPMorgan.

Just have 2 quick ones for you. So first of all, regarding your ASCO GU update next week for PADCEV, how might this differ from what we saw at ESMO in terms of is it just more patients or just longer follow-up? And then the second question I have, just curious if the 2020 guide reflects any sort of planned buildout for TV, assuming that trial reads out positive, or is that not in there yet?

So the 2020 spend guide and TV and manufacturing, I'll turn it over to Todd in a moment. I'll start with ASCO GU and PADCEV. We are going to update the trial. At ESMO, the trial was a -- it was interim data. We weren't -- we did not have mature data at the time, but we presented everything and it was incredibly well received. I would say we were one of the stars of ESMO and perhaps the star of ESMO, but that's a lot to say. But when we present the update of this trial at ASCO GU, I don't think we're going to disappoint anybody.

Todd, guidance?

On guidance -- your question with respect to TV and the guidance, I mean...

Manufacturing and stuff.

I mean that's built in to support the clinical trial that we're working on. There's some dosing work that we're still doing, but we haven't yet backed in a commercial build. We want to get to our data and see how that looks. And if we can hit the bar that Clay just articulated in the last question, then that will put us in a position to -- you'll start to hear our thoughts on how we build that out.

I hope we have that issue that we need to really spend quickly on tucatinib -- TV manufacturing.

Our next question comes from Michael Schmidt with Guggenheim Securities.

I had 2 pipeline questions, 1 follow-up on TV. We've done some work there last year already, but I was just wondering if you can help us a little bit with understanding the initial market opportunity in cervical cancer. For example, how many patients per year might be a treatment candidate should TV-204 succeed this year? And then I had a follow-up.

Well, we're not at the point now where we're giving guidance in the -- with the specificity that you are asking for. But what I will tell you is that there were about 13,000 patients in the United States that were diagnosed with cervical cancer. And this is despite having a vaccine called GARDASIL which is a phenomenal vaccine, but not everyone gets it. And in fact, when you look around the globe, not only is it just not in the U.S., but a lot of other countries, not everyone's getting it. And in fact, in some countries, it's not even in the formulary. This includes Japan and Brazil and other places.

So when you start looking at how many patients around the globe were diagnosed last year with cervical cancer, it was 575,000. That is a travesty. But -- and we would be very happy to have no business in TV and cervical cancer and pack it up and go home if everyone was taking GARDASIL. But that's not the reality. The reality is that this is a horrible, devastating disease. And if you're diagnosed with it, it's a death sentence. And we want to do something about it. But like I said, we'd love if everyone in the globe had the vaccine and this disease was wiped out. Just -- it's not really where it is.

So when I tell you, not only was there over 13,000 people diagnosed, but over 4,000 patients died in the U.S. -- or annually in U.S. with cervical cancer. So that can give you some idea of the number of patients that are diagnosed and dying each year that I think we can address. Clearly, as we get more data as we get further along, if we're going to be launching this, we'll give more detailed assessment.

Great. And then maybe one for Roger regarding PADCEV and the bladder cancer opportunity. I guess there's been some news recently, and we've seen some results from a -- we'll then see a maintenance study in frontline metastatic patients, and then KEYTRUDA was approved in the earlier-stage setting, and I was just wondering what your view is on how some of those things might potentially affect the market opportunity for PADCEV longer term.

Thanks for the question, Michael. So yes, pembrolizumab had a readout using a maintenance approach, one of the Janssen trials, which is great, that's great. Our trial designs -- such if you look, for example, in the frontline study that we are going to conduct, will include PFS and OS as an outcome. And we really see -- understanding the maintenance profile, but that's limited to people who have some degree of disease control in the front end and either responds or stable disease, it doesn't address the whole population. I think we are much more excited to try and get PADCEV to the entire population of metastatic urothelial cancer. I think that's our view. And obviously, we'll operationalize the trial with those end points in mind.

Our next question comes from Shanshan Xu with Berenberg Capital Markets.

Can you hear me okay?

Yes.

Yes. So I believe that you have a very robust ADC platform. And historically, you rarely do acquisitions. However, the acquisition of Cascadian is a very successful one. So would you revisit your M&A strategy? And I have 1 follow-up.

Sure. So we have a ongoing constant evaluation for M&A. We are actively looking. We were looking for a few years before we made the move on Cascadian. And when I look at a lot of things, you could say that we have done a heck of a lot of diligence. And the first time we really were making a move was when we tried to license -- it wasn't an acquisition, it was a license of sacituzumab govitecan from Immunomedics. And we went out at a time where nobody in Wall Street really was looking at it. Their share price was like $3 or $4 a share. And we went out to do a deal, which the courts overturned because of rationale that had nothing to do with Seattle Genetics. It was more of the activity of the prior CEO of Immunomedics. But we did keep our stock position. Todd referred to it. We've made, I think, over $200 million or something on that stock position, which the courts did not rule on. So we were able to keep that, which was part of our license deal that got overturned. And yes, we would have been happy with that license deal if it had gone on, but it didn't.

But it shows you the power of our diligence. And I give you that story because the next time you heard about our diligence with Cascadian, which is another company that was trading at low single digits. And Wall Street was not focused on it. Cascadian was a company that carried its life as Biomira. And then it struggled to stay afloat and became Oncothyreon. And then it struggled, and it became Cascadian. And after 30 years or so being a company, they had this interesting product. And it was very early, and they really needed a company that was bigger with more power and a full regulatory and manufacturing and medical and everything staffed to get this done right. And so I'm very proud that we took this from a tiny little company and acquired the company with a fair premium to their shareholders and made it into something that this is now -- we could argue, whether this is going to be -- it's not approved yet, so I can't fully argue yet, but a best-in-class HER2 tyrosine kinase and probably the type of tablet that the scientists at GSK, who were trying to make TYKERB a couple of decades ago, were envisioning, one that had high potency to inhibit tyrosine kinase and one that did not bind to EGF receptor so you could stay away from the toxicities associated with that.

So we're really excited with what we did. And to that end, we do a great job in diligence. And unfortunately, that means it turned out that there's a lot out there that has a lot of hype, and it looks good initially. But then we dig deep and we dig incredibly deep, and we find stuff that often is less savory, and we don't go forward. But you can be sure that we are out there looking in full force. And if we find something, we are not going to be shy. We are going to go out hard to do it. And I'll remind you -- Todd can also comment if you have any questions, when we decided to acquire Cascadian, the next day, we went out and raised money for that acquisition, not a penny more, we raised for that acquisition. And we were transparent, and we said this is what we want to do. And we could go and try to acquire a company that's very small or a little bit bigger. I think we have a little bit more space to do it now. Clearly, we're not going to buy a massive company. But we have a little bit more space because of bigger market cap and a little bit more -- a bigger revenue, et cetera.

But if we decide to buy something, you will be sure that we will go to Wall Street right away and say, here's what we want, here's why we want it, here's why it fits in, here's how much it's going to be and here's what we want to do financially. So we will be incredibly transparent the way we were with Cascadian. And we will go full force to do it the minute we find something.

Great. I saw that you just achieved a positive profit this quarter. How should we be thinking about the sustainability of profitability going forward?

Thank you for the question. The reason we had a profit in the fourth quarter was because of the mark-to-market adjustment we had on the IMMU shares. That was 50 -- I think $52 million or $54 million for the quarter and for the year. That's what resulted in the profitable quarter. So please don't read more into it than that because it was the result of that.

We had a great quarter, certainly. And we had a lot of milestone payments that were one-off that Todd mentioned. We had 3 or 4 really important payments that we got. So the quarter was a great quarter. There is no doubt. We were thrilled with the quarter and all the different revenue streams that we brought in but is -- we're not -- on ongoing activity, when you pull out the mark-to-market, we're not yet profitable. But thank you for bringing that up.

Our next question comes from Chad Messer with Needham & Company.

Congratulations on a strong year. So for PADCEV, that got approved quite a bit ahead of its PDUFA date. And you anticipated that, you were ready. Just wondering about tucatinib, especially given that it has real-time oncology review. When do -- you said you've got the senior sales leadership on board for that. When do you think you need to be sort of fully commercially ready for tucatinib launch?

Sure. So I'll give you a little color on that. Maybe Robin can talk about the amazingly strong progress we're making with our sales staff on tucatinib.

So we went ahead and we use RTOR for ECHELON-2, you can recall. And that one was a supplemental BLA. And at the initiation of this pilot program, RTOR at FDA, that's the only things you could put into it was supplemental BLAs. And we were able to, from submission, gain approval in 11 days. We were told that is a record. I think it still stands. Someone will obviously beat it someday. Maybe us on some other program that's a supplemental BLA.

And later, FDA added the ability to bring in a new chemical entity into the RTOR program. Now having said that, that since it's a new chemical entity, they can get a very rapid review. But they still need to have inspections of sites and all of the work that you need on the QC/QA front with manufacturing. So it's not going to be an 11-day thing, but it can be very accelerated from a standard first approval. And that has the potential -- that is why we're involved in that more because of the potential for it to move forward.

I don't know what the FDA's criteria is for accepting things into RTOR. I can say that ECHELON-2 had strong overall survival advantage, and we went in there with that supplemental BLA. And I can tell you with tucatinib, we have strong overall survival advantage.

So I think that -- I can't tell you exactly what FDA would accept into RTOR, but the 2 data sets they've accepted from us are amongst the best we've had in the history of the company. So by that regard, maybe they're being picky, and they should be for something to put a lot of effort and move forward fast. So we're really excited with that and working with FDA.

Keep in mind, we submitted that. We haven't yet passed the 60 days to where it is filed. So that's coming up in not-too-distant future from where accepted to file. So that's the next thing you should hear from us about with tucatinib. But working hard with FDA. I can tell you that it is -- they are putting a lot of effort in it, we are putting a lot of effort in it, we communicate with them a lot.

Robin, do you want to talk about the sales staff and our readiness?

Very happy to. We've already let you know that we've hired our sales leadership team. One of the great things about having the HER2CLIMB data is that it's totally attracting attention from physicians, and they're excited about the data. But also many talented sales reps and other commercial staff are excited about the data as well. And so we have a very aggressive plan in terms of hiring. We want to make sure that we are ready for the approval whenever that may come. And the great news is that Seattle Genetics already had a very strong reputation in terms of the commercial organization. And so that, on top of the positive HER2CLIMB data that is very strong, has meant that we have a lot of interest in the positions that we have opened across all of the U.S.

And so the real task for us right now is really just getting through a lot of interviews and a lot of hiring decisions. But our #1 standard is to make sure that we have a very strong, talented and focused tucatinib team. And I'm very confident we'll be ready for launch.

Yes. I don't remember exactly where we are, but I do get updates periodically. And I know that the last update I got, 2/3 of the sales staff are already on board. So just to let you know, we're not sitting back waiting, and that was a while ago. So we are really making big progress to having that sales staff at full force and getting it there.

Our next question comes from Gena Wang with Barclays.

Just 2 very quick ones. The first one is regarding PADCEV. I know it is still very early, but just wondering if you can give any color on average reimbursement process time. And the second question is regarding HER2CLIMB-02. I know you try to go for both first-line and second-line metastatic breast cancer. What is your enrollment assumption for Herceptin-naive patients? And how is the study powered?

Okay. So let's start with PADCEV and your question on the average reimbursements. It is too soon for us to really start getting into that. With time, with ADCETRIS, we were able to say, here is the standard patient and here's how many cycles of therapy, and here's how much that's worth and what they paid and all that, the gross-to-net and everything. We're able to really provide details about the duration of therapy and all that with ADCETRIS with time, when we had the data. We will do that likely for PADCEV in the future. We just are not there yet to go to that.

Now the second question you asked was about HER2CLIMB-02. And so that's the second trial, and not to confuse it with the original HER2CLIMB. Roger, can you talk a little bit about maybe the type of patients we have that could be first or second line and maybe some of the inclusion and exclusion? Because that's really all we can talk about at this point.

Sure. The key component of the population is they have to have seen trastuzumab and the taxane, and that's the key inclusion criteria. And so under that circumstance, provided those 2 drugs have been administered, whether it's in the neoadjuvant, adjuvant or metastatic session -- setting, you can imagine that there will clearly be patients who will have seen those prior to developing metastatic disease. So that would represent a frontline population. And then there are clearly patients who will have seen those in the metastatic setting and therefore represent the second-line population.

It's not possible to speculate now what the proportion of patients are. We've just begun the trial. And thanks for the question around powering, but we can't disclose details. But I can just assure you we've absolutely powered the trial appropriately based on the assumptions that we put into the study. So we expect if tucatinib plus T-DM1 is better than T-DM1 alone, we'll be able to clearly show that.

Our next question comes from Stephen Willey with Stifel.

Just quickly on PADCEV. Is it your expectation that you guys are going to get slotted in behind the FGFR inhibitors in those patients that have FGFR2, 3 alterations? And I guess when you gave your addressable patient numbers, I think, in conjunction with the approval call, did that include a haircut for those patients specifically as well? And then I just have a quick follow-up on tucatinib.

I have quick answers for the first two. We do not know exactly what you're saying, but it is not our assumption that we're behind the FGFR. That is not the assumption we're going to take. And so in the calculation, we did not pull out any of those patients.

Okay. And then just on tucatinib, I know that there was some discussion in San Antonio that there'd be some additional updates regarding the CNS subgroup data. I guess is there any kind of guidance you can provide as to when you might be able to present that?

Yes. We are doing a lot of work in that regard. Thank you for the question. It's really exciting to have the opportunity to actually look at cranial scans and start thinking about what you're getting. I mean so few drugs have an impact on PFS in patients with brain mets that this is one of the rare times you can actually look and say, "Did you have a direct impact on the tumors?" And I would say there's a decent chance that we will be presenting that type of work this year. I don't want to say for sure on anything, but I would -- I think pretty strongly about that. And obviously, we want to publish it as well. We want to present and publish that work, and that's something we're very much looking forward to doing.

Our next question comes from Andy Hsieh with William Blair.

So I am just comparing the 2 proposed labels in the EU and U.S. So in the EU it says basically 2 prior anti-HER2 treatment -- or sorry, this is about tucatinib, anti-HER2 treatment regimens and U.S. is 3. So maybe can you talk about whether the 2 populations are significantly different or whether it's a function of just treatment differences between the 2 geographies?

Sure. Roger?

Sure. Thanks, Andy, for the question. So the answer is that the labels -- the addressable populations are the same. There isn't a difference between what we're proposing for the labeled indication in the U.S. versus the EU. We chose to simplify the indication statement in the EU, and that is our proposed indication statement, I'll address that in a second, based in part on feedback that we got from an early regulatory interaction with the European Medicines Agency.

I would also just point out that these are proposed labels, these are proposed indications. And the final approved indication will -- if we get approval, will be determined in conjunction with the various regulatory authorities. But just to reiterate, we do not -- this is not a different patient population. There's not a different treatment paradigm, just a choice about trying to simplify language in an indication statement. And the key goes around words like agents versus regimens.

Right. Got it. And just a quick follow-up. In terms of the EV-302 study, I guess you can argue that Seattle Genetics and Merck probably understand the EC landscape the best. So obviously, the goal is to get the combination out to patients as soon as possible. Just curious about your thinking on interim analyses in that trial.

Yes. I would say right now. That is a fantastic question, but it is not one that we're able to address today. So keep that question in your head. It's -- your comments and your thoughts on how we could do something quicker, whether it's in 302, in another trial or whatever, is something that is under active discussion. So stay tuned. We'll be back to you on that.

Our last question comes from Silvan Tuerkcan with Oppenheimer & Company.

My first question is on TV. We've seen late last year data from CheckMate-358 Phase Ib/II trial, which kind of has comparable ORR data of Ipi/Nivo in that cervical cancer setting. Obviously, given that your Phase I trial was a dose-finding trial, so it might be lower bound. But could you just contrast like what -- how could these 2 regimen compare, especially maybe with a focus on side effects?

I don't know off the top of my head the data from that trial. Roger could probably better discuss it. What we -- what I'd point to is the last approved drug for cervical cancer, just KEYTRUDA. I don't remember the trial it was from, but it was -- showed a 14% response rate and a decent duration. We're trying to show as high a response rate and a best duration as we can for these patients that have a huge unmet medical need. Roger, do you want to add something?

Right. And Clay is making the point, Silvan, that the history of what's been approved just sort of sets the mean for what it is we would expect to be measured against. I mean it's great if Ipi/Nivo is active in cervical cancer and the way for that combination to move forward in cervical cancer, that's great. But I think we're pretty excited about TV, as Clay said, such a high unmet need. And I think our data will stand by itself. I'm not sure there's any need to reference a combination immunotherapy at this point.

Okay. Good point. And maybe one last question. Daiichi's ADC is making progress in breast cancer. And I would assume it would take share from T-DM1. Could we see a combination trial with tucatinib in the future?

I think that your question is whether the drug now referred to as Enhertu from Daiichi and AstraZeneca could be a good combination partner with tucatinib and hit on the outside of the cell with a very active antibody-directed drug conjugate and on the inside of the cell will be a very active and safe HER2 tyrosine kinase inhibitor is, I think, a fantastic trial that this -- whether we do it, whether Daiichi does it or whether 8 doctors do it independently as investigator-sponsored trials, it's going to happen in multiple ways. So I look forward to those data. I think those 2 drugs should be together. It is the right medicine.

That concludes our question-and-answer session. And now I would like to turn the call over back to the speakers for closing remarks.

Okay. Thank you, operator, and thanks, everybody, for joining us this afternoon. Have a good night.

Ladies and gentlemen, this concludes today's call. Thank you for your participation. You may now disconnect.