Good day, and welcome to the Seagen Third Quarter 2022 financial results conference call. All participants will be in listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touch-tone phone. To withdraw your question, please press star then two. Please note today's event is being recorded. I would now like to turn the conference over to Doug Maffei, Vice President, Investor Relations. Please go ahead. Thank you, operator, and good afternoon, everyone. I'm pleased to welcome you to Seagen's third quarter 2022 financial results conference call. This afternoon, we issued a press release with our results. The press release and supporting slides are available on our website in the Investors section, Events and Presentations page. Speakers on today's call will be Roger Dansey, Interim Chief Executive Officer and Chief Medical Officer, Todd Simpson, Chief Financial Officer, and Chip Romp, Executive Vice President, Commercial U.S. Following our prepared remarks, we'll open the line for questions. We aim to keep this call to one hour and ask that you limit yourself to one question to give everyone an opportunity to participate in Q&A during our call today. Today's conference call will include forward-looking statements regarding future or anticipated events and results, including the company's 2022 financial outlook, anticipated product sales, revenues, costs and expenses, potential clinical and regulatory milestones, including data readouts and regulatory submissions, potential marketing approvals and commercial performance. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference, including the difficulty in forecasting sales, revenues, costs and expenses, impacts related to the COVID-19 pandemic, and the uncertainty associated with the pharmaceutical development and regulatory approval process. More information about the risks and uncertainties faced by Seagen is contained under the caption Risk Factors included in the company's quarterly report on Form 10-Q for the quarter ended June 30, 2022, filed with the Securities and Exchange Commission, and the company's subsequent reports filed with the SEC. Now I'll turn the call over to Roger. Thank you, Doug. Good afternoon, everyone, and welcome to our third quarter call. This was a quarter where we delivered strong financial results with total quarterly revenue of $510 million, representing growth of 20% compared to the same quarter last year and reflecting robust sales across our approved portfolio. We also made substantial progress on multiple fronts, including clinical, regulatory, research, and corporate development. We presented pivotal data for Padcev and TUKYSA, and we submitted supplemental regulatory applications to the FDA for Padcev, TUKYSA, and Adcetris. We opened a new IND in our early-stage pipeline with a product candidate that targets immune cells in the tumor microenvironment, and we extended the geographic footprint for TUKYSA with a new commercialization partnership in China and other parts of Asia. Turning to our overall strategy, we are an ADC company at our core, as demonstrated by three of our four commercial products and five of our last six INDs. Moving forward, we will remain laser-focused in this area. Nevertheless, as with TUKYSA, we continue to acquire complementary assets that target tumors through mechanisms different from ADCs. In that vein, we recently licensed an innovative bispecific technology from LAVA, which addresses a target not readily amenable to an ADC construct and fits in well with our overall focus on targeted drug development. Beginning today with Padcev, our first-in-class ADC for metastatic urothelial cancer, together with Astellas and Merck, we presented data from Cohort K of the EV-103 trial at the ESMO meeting in September. As a reminder, this is a study primarily evaluating Padcev in combination with KEYTRUDA in front-line cisplatin-ineligible patients with unresectable, locally advanced or metastatic urothelial cancer. This combination demonstrated a confirmed overall response rate per independent radiographic review of 64.5% with a median duration of response not reached. The combination had a manageable and tolerable safety profile. The Padcev monotherapy arm showed a confirmed overall response rate of 45.2% with a median duration of response of 13.2 months, demonstrating its contribution to the combination. Frontline patients who are not eligible to receive cisplatin have a high unmet medical need, and we are encouraged by these data. We have submitted a supplemental BLA to the FDA to support a potential accelerated approval in the United States in mid-2023. Further development for Padcev continues, including our EV-302 global Phase III trial in combination with Keytruda in a broader population of patients regardless of cisplatin eligibility. We expect enrollment to complete before year-end, and our intention is to use EV-302 as a confirmatory study in the United States and to support submissions around the world. Beyond the frontline metastatic setting, additional studies evaluating Padcev in muscle-invasive and non-muscle-invasive bladder cancer are ongoing. Together with Astellas, we are also considering Padcev's potential in other Nectin-4 expressing solid tumors, and look forward to sharing data next year. Moving to TUKYSA, we recently filed a supplemental NDA for patients with previously treated HER2-positive metastatic colorectal cancer. The combination of TUKYSA and trastuzumab resulted in a confirmed overall response rate of 38% with a median duration of response of 12.4 months. Based upon the strength of these data, we have been granted breakthrough therapy designation as well as priority review by the FDA with a PDUFA action date of January 19, 2023. As a reminder, our Phase III trial has been initiated in frontline HER2-positive metastatic colorectal cancer with the goal of serving as a confirmatory trial in the United States and supporting global submissions. We continue to explore TUKYSA further in breast cancer with our partner, Merck. This includes HER2CLIMB-02, our Phase III study of TUKYSA in combination with KADCYLA, which completed enrollment in June. We anticipate reporting top-line data in the first or second quarter of next year. Despite the evolving treatment landscape, KADCYLA remains an important treatment option for patients with HER2-positive metastatic breast cancer. If successful, the combination of TUKYSA plus KADCYLA has the potential to strengthen TUKYSA's position in the second-line setting, particularly in patients with brain metastases, and could provide an alternative important option in the third-line setting for those patients who would otherwise have received KADCYLA monotherapy. Next to highlight are three key updates for Adcetris, which is the foundation of care in CD30-expressing lymphomas and is being commercialized outside of the United States and Canada by our partner, Takeda. First, data from the pediatric trial has been filed with FDA with a target action date of November 16, 2022. Adcetris plus chemotherapy demonstrated superior event-free survival in the treatment of pediatric patients with previously untreated high-risk classical Hodgkin lymphoma when compared to a chemotherapy regimen that included bleomycin. Second, the statistically significant and clinically meaningful improvement in overall survival demonstrated in ECHELON-1 for Adcetris in combination with AVD in patients with advanced Hodgkin lymphoma was recently published in The New England Journal of Medicine. We have submitted these data to the FDA for possible inclusion in the label. Last, and important to note, the NCCN guidelines have now been updated based on the overall survival data to designate A+AVD as a preferred treatment option for adult stage 3/4 Hodgkin lymphoma patients. Now transitioning to TIVDAK, our fourth approved product and first-in-class tissue factor-directed ADC, which we co-develop and co-commercialize with our partner, Genmab. We recently announced a regional strategic collaboration and license agreement with Zai Lab that gives them exclusive rights to develop and commercialize TIVDAK in mainland China, Hong Kong, Macau, and Taiwan. We partnered with Zai Lab given their expertise and track record of developing and commercializing innovative medicines in the region. The collaboration will support regional patient enrollment for innovaTV 301, our Phase III study of TIVDAK in patients with recurrent or metastatic cervical cancer. This global study is enrolling well and is intended to serve as the confirmatory trial in the United States and to enable global regulatory applications, including in Asia. Additional clinical development for TIVDAK continues in frontline cervical cancer and other solid tumors, including head and neck cancer. We look forward to data readouts in the coming year, which will inform our next steps in these two cancers. disitamab vedotin or DV is a late-stage novel HER2-directed ADC that utilizes our vedotin-based technology. Our clinical development program is evaluating monotherapy and combination approaches in a variety of cancers. We recently began enrolling patients into the pivotal Phase II monotherapy trial in second-line HER2-expressing metastatic urothelial cancer. We plan to initiate an additional pivotal study in bladder cancer over the next several months while continuing to explore development in other HER2-expressing solid tumors. Turning to our earlier stage pipeline. We are advancing multiple drug candidates in Phase I clinical trials in a range of solid tumors and hematologic malignancies. Next month at the annual Society for Immunotherapy of Cancer Conference, we look forward to disclosing initial Phase I data for SGN-B6A, a vedotin ADC targeting integrin beta-6. This is an antigen which is highly expressed in a variety of solid tumors, including non-small cell lung, head and neck, and esophageal cancer. In addition, we will be presenting preclinical data on SGN-BB228, a novel bispecific molecule which provides a potent costimulatory bridge between tumor-specific T cells and CD228 expressed in tumor cells. We look forward to initiating a Phase I trial for SGN-BB228 in the coming months. In September, we announced an exclusive worldwide license to develop and commercialize LAVA-1223, a bispecific T-cell engager targeting gamma delta T cells in the presence of EGFR-expressing solid tumors. We find the science compelling and look forward to advancing LAVA-1223 into the clinic in the near term. Next, I'll turn the call over to Todd, who will discuss our financial results and provide updated guidance. Then Chip will provide an update on our commercial performance before we turn to Q&A. Todd. Thank you, Roger, and thanks to everyone for joining us on the call. Our financial results continued to reflect significant advancements made across the business. Today, I'll briefly summarize our financial results and then discuss several updates to our outlook for the full year. To begin, all components of revenue showed increases in the quarter and for the year to date over 2021. This reflects strong commercial execution across our approved products, continued performance by our partners, as well as new collaborations. With that, total revenues were $510 million in the third quarter of 2022, and $1.4 billion for the year to date, representing year-over-year growth of 20% and 25% respectively. Net product sales increased to $428 million in the third quarter of 2022, and $1.2 billion for the year to date, representing year-over-year growth of 17% and 22% respectively. Royalty revenues were $44 million in the third quarter of 2022, and $111 million for the year to date. Royalty revenues for the third quarter increased by 7% over the prior year, driven by strong commercial performance by our partners, most notably Takeda with its sales of Adcetris, partially offset by foreign currency headwinds associated with the strong US dollar. Collaboration revenues were $38 million in the third quarter of 2022, and $80 million for the year to date. These reflect royalties on sales of Padcev by Astellas in its territory, as well as other collaboration activities, including an upfront license fee of $30 million from our new deal with Zai Lab signed in the quarter. Cost of sales were $108 million in the third quarter of 2022, and $302 million for the year to date. This included cost of product sales and royalties for each of our four brands, profit share amounts owed to our collaboration partners, Astellas and Genmab, as well as non-cash amortization of acquired technology costs for Takeda. R&D expenses were $385 million in the third quarter of 2022, and $987 million for the year to date. These reflect continued investment to expand the potential of our approved products and to advance our product pipeline. Third quarter results also reflected a $50 million upfront fee to LAVA Therapeutics. SG&A expenses were $210 million in the third quarter of 2022, and $605 million for the year to date. This was driven by ongoing commercialization efforts, legal costs related to Daiichi Sankyo, and other corporate activities. Regarding our financial outlook for the full year, we are increasing our guidance for Adcetris sales to a range of $805 million-$820 million. We are narrowing our guidance for PADCEV sales to a range of $435-$445 million, and we are increasing our guidance for TUKYSA sales to a range of $340-$350 million. Chip will provide further context on market dynamics related to each of our brands in a moment. We are adjusting our guidance for royalty revenues to a range of $155-$160 million, reflecting foreign currency headwinds, and we are increasing our collaboration revenue guidance to a range of $85-$90 million. Moving to expenses, we are increasing our R&D expense guidance to a range of $1.3 billion-$1.35 billion, primarily related to the upfront fee under the LAVA deal in Q3, and we are tightening our SG&A expense guidance to a range of $800 million-$850 million. Our other guidance remains unchanged. Looking forward, we plan to provide 2023 financial guidance on our next quarterly call. As we exit 2022, we have four transformative drugs that are well-established within their current indications. We have a number of ongoing trials, several with registrational intent, that are intended to support label expansions for each of our approved brands. We also have two pending FDA regulatory submissions intended to support new indications during 2023. The most significant of these is Cohort K for Padcev. However, this will not be included in our initial guidance due to the anticipated time of a potential label approval. These factors will be taken into consideration in our initial 2023 guide. With that, I'll turn the call over to Chip for an overview of our commercial performance. Thank you, Todd. Performance across the portfolio this quarter was strong and reflects continued commercial execution for our best-in-class or first-in-class product portfolio. Padcev third quarter sales were $105 million, an 11% increase over the third quarter of 2021. There were no clinical trial supply orders in the third quarter of this year, compared to $7 million in the same quarter a year ago. Excluding clinical trial supply orders, year-over-year growth for the quarter was 20%. Underlying growth was primarily driven by continued use of checkpoint inhibitors as frontline maintenance therapy, a dynamic that has helped Padcev become a U.S. standard of care in the second line setting post-platinum, post-CPI. Checkpoint inhibitors have been used in the maintenance setting for over two years, and uptake has flattened, which is limiting Padcev's near-term growth in its current indications. Meanwhile, we are looking forward to a potential label in the frontline setting in the U.S., and we are encouraged by the positive reaction to the EV-103 Cohort K results presented at ESMO in September. Our commercial teams are preparing for a potential launch in mid-2023. As a reminder, there are approximately 20,000 total addressable patients in the frontline metastatic setting in the U.S., with around 80% of these being drug-treated. 40%-50% of these are ineligible for cisplatin-based chemotherapy. If approved, the Padcev regimen would represent an important treatment option for these patients. Moving on to TUKYSA, third quarter sales were $88 million. TUKYSA performed well in the quarter despite competitive headwinds related to ENHERTU's recent approvals and increased use in the second-line plus setting, which is expected to continue into 2023. TUKYSA's performance is benefiting from extended treatment duration in approximately a third of patients, which we believe underscores its efficacy and tolerability. We have established TUKYSA's market position as a valuable treatment option for patients in the second-line plus setting, especially for those with CNS involvement. Our TUKYSA commercial teams are ready for a potential launch into the second-line plus setting in patients with HER2-positive metastatic colorectal cancer. Although a modestly sized market, the population represents a high unmet need, as existing approved colorectal cancer therapies typically offer limited response rates. Looking beyond the U.S., in the third quarter, we successfully concluded TUKYSA pricing negotiations in Germany and Canada, adding to our success in the U.K. We look forward to potentially further expanding access across the rest of Europe in the coming months. Merck is progressing regulatory submissions and reimbursement activities intended to expand TUKYSA's reach in their territories and have recently received approval in Israel and Argentina. Adcetris third quarter sales were a record $219 million, an 18% increase over the third quarter of 2021. Growth was driven by a return towards pre-COVID diagnosis rates as well as price and incremental share gains in frontline Hodgkin lymphoma, the latter of which has benefited from the unprecedented overall survival data from the ECHELON-1 trial announced earlier this year. We are pleased to see the strength of the OS data result in an elevated Category One preferred recommendation in the NCCN guidelines, and we are working to ensure broad awareness of this positive update. Finally, TIVDAK sales were $16 million for the third quarter. The Seagen and Genmab commercial teams are focused on ensuring early treatment experiences with TIVDAK are positive, with best practices being shared between clinics. We continue to promote this important treatment option for patients with such high unmet need. With that, I'll pass the call back to Roger. Thank you, Chip. As discussed today, we continue to make solid progress across the business. Looking forward, we plan to provide multiple data readouts in the coming year for TUKYSA, PADCEV, ADCETRIS, TIVDAK, and pipeline candidates such as SGN-B6A and SGN-B7H4V. Seagen is in a position of strength to continue advancing our mission of delivering cutting-edge innovation that positively impacts the lives of people with cancer. Now we'll open for your questions. Operator, please open the line for Q&A. Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your touch-tone phone. If you're using a speakerphone, we ask that you please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Today's first question comes from Michael Schmidt at Guggenheim. Please go ahead. Hey, guys. Thanks for taking my questions and congrats on the quarter. I had a question around TUKYSA market dynamics. The drug obviously has performed better than initially anticipated. Can you comment a bit more on how you think about the competitive dynamics with ENHERTU in breast cancer longer term, and how we should think about the incremental growth opportunities should ENHERTU come to succeed next year? Hey, Michael, it's Roger here. Thanks for the congrats on the quarter. It's an important question, perhaps I could ask Chip to make some comments on the commercial dynamics. Sure, Roger. As we've discussed in previous calls, ENHERTU has gained market share in the second-line setting for HER2-positive metastatic breast cancer patients. This has impacted the patient flow into the third line and later lines of therapy. We continue to anticipate this shift is gonna grow, and ENHERTU will be sequenced in the second line in front of TUKYSA, with increased use in the second line, based on their label and approval. This is gonna result again in delayed patient flow into the third line. TUKYSA has established itself as an important option for treatment in the second line setting with patients with brain mets, and we expect to continue to hold there and have a foothold, as it's been valued by physicians. Just to add some more comment on that, Chip. You know, from a. Our initial evaluation of what the impact of ENHERTU could have on TUKYSA, and our sort of timing of when that impact would occur was based, you know, in the earlier part of the year on an expectation that ENHERTU would move quite quickly. That did not actually happen. It took some time for ENHERTU to gain momentum. That competitive headwind that Chip describes, I think, you know, we believe will exist into 2023. It may be through to the sort of second half of 2023 when we see things start to stabilize. What about HER2CLIMB-02? You said we could see data in the first half of next year. How impactful would that potential label extension be, if successful? Yeah, that's a great question. Thank you. Perhaps I'll make some comments and then Chip again, if you could complete on the commercial color. Yeah. We're excited by the combination of TUKYSA with KADCYLA. KADCYLA is an important drug. It has a place, you know, for use in HER2 metastatic breast cancer. As you know, patients cycle through therapies. Fortunately, they live, you know, a good long time and have the opportunity to switch therapies. Just to remind you, HER2CLIMB-02 has the same design elements as HER2CLIMB. It includes a population of brain metastases and includes in that population, patients who will have active brain metastases. That is an important component of that trial. So from a... You know, if the trial is successful and the profile of the combination is compelling, both from a general perspective and also in that brain met population, we see, you know, TUKYSA increasing its use, in that combination with KADCYLA. Chip, do you want to add some comments? Yeah. I think there may be two meaningful outcomes from the commercial standpoint. The first is I think we can potentially expect to see increased utilization in patients in the third line regardless of brain metastasis. The second piece of that is it really puts us in a partnership position rather than a competitive position with KADCYLA. Okay. Thank you. Thank you. Our next question today comes from Andrew Berens at SVB Securities. Please go ahead. Hi. Thanks for taking my questions, and congrats on the progress, guys. I was wondering if you could give some color on the Padcev duration of treatment that was in Cohort K. I know you reported the treatment duration for the cocktail, but it's my understanding that patients could have dropped off of one of the agents and still be considered on treatment. What are your thoughts on the possibility that the FDA may want to see the randomized data for Padcev and KEYTRUDA to better understand how that cocktail should be used in cis-ineligible patients that have the option to get carboplatin plus maintenance checkpoint inhibitor? Andrew, thanks for the question. With you know, with regard to durational therapy, you're right. We have only disclosed at what point is treatment discontinued for one or other component of the combination. That sits at an average of around about 10 cycles of therapy. I think it was 9 cycles of therapy with Cohort A, which is the same essential population, and then 10 cycles of therapy with Cohort K. That's a median duration. We have not gotten into the details of how much of which particular drug is being used. I would just remind you that for this combination, as well as for the individual drugs, the major driver for discontinuation is progressive disease. Progressive disease generally, you know, triggers both drugs to be stopped, and that in the main, drugs like Padcev do not have a major sort of adverse event burden that necessarily stops their use, the most common one being peripheral neuropathy, and that's generally in the sort of single-digit range. With regard to what the agency, you know, may view, we think we have a strong package. There's a high unmet need in patients who are cisplatin-eligible. The data that we've presented based on the regulatory framework, which is overall response rate and duration of response, is substantially better than what you can expect with a carboplatin based regimen. From an evidentiary perspective, you know, we've done this experiment twice. We've had Cohort A and Cohort K. Those results have been, you know, remarkably close to each other. You know, we're confident that this combination will reproducibly result in the types of results that we've seen with Cohort K. You know, from the point of view of the agency, we can't speak on their behalf. In the end, it is an FDA call as to whether they see this as being appropriate to take, you know, a regulatory action. I can say, you know, we are confident in our position. It's important to note, in sort of partially in relation to your question, because confirmatory trials are part of the conversation right now, that we are in a very favorable position. EV-302, which is obviously a much larger trial, which has populations that include both cisplatin-ineligible and cisplatin-eligible, with a sample size, you know, in the 900 range, and including endpoints such as PFS and OS as the dual primary endpoints, but other endpoints such as ORR are also included. Enrollment is expected to finish this year. It is an event-driven trial, and so obviously, you know, we will turn our focus from completing enrollment to starting to map out when these events will occur. It's important to note that that confirmatory trial is, you know, very well advanced. I think that's an important part of our arguments around, you know, looking for accelerated approval based off a single-arm study, which is Cohort K. Okay. Thanks, Roger. Just if I could squeeze a quick one in on BV. I didn't hear you mention breast cancer in that with that molecule. I might have missed it. Is it still a priority for this drug, and do you think it could have a meaningful bystander effect like in HER2? It absolutely is a priority. We are very interested in HER2, you know, the HER2 low breast cancer population. We've not disclosed any details, but I think, you know, from an internal workings perspective, we are looking hard at that as a possible opportunity. As you know, you know, one of the important features of a vedotin payload, and we strongly believe this, and Cohort K actually supports this argument, is that, you know, combining a vedotin together with a PD-1 inhibitor does have an added advantage over the combination of two active agents. You know, utilizing or leveraging that potential value in a combination strategy is something that we're thinking about, not only for breast cancer more broadly, obviously, in other tumors, but it may be relevant in that space as well. Obviously, from our perspective, you know, generating data is an important first step in understanding what our opportunities are. I think just stay tuned. We're focused on breast cancer. We just have not, you know, brought the specifics forward yet. Okay. Thanks a lot, and congrats on the progress. Thanks, Andrew. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Please go ahead. Hi. Thanks for taking our question. This is Thomas Hudson on for Salveen Richter. Can you provide an update on the CEO search and provide a framework that you're using in finding someone? Thank you. Sure. Thanks for the question. Yes, I'm, you know, happy to report that the board is making good progress. Obviously, the characteristics of the company, you know, we are a multi-drug global oncology company, so anyone who comes in, you know, to lead the company will need the skill sets to do that. We have confidence that the board, you know, will identify and will name, you know, a strong new CEO. I don't have a timeframe for you. Obviously, it's an important deliverable, and it is something that the board is actively pursuing. Again, timing is something that I can't share. What I can say, though, is, you know, the focus of the management team, myself included, during this interim period, is to move the ball forward. We think we're comfortable that we've been successful at doing that, I think as evidenced by the progress that we've shown over the last two quarters. Thank you. Our next question today comes from Matthew Harrison at Morgan Stanley. Please go ahead. Hi. Thanks for taking our question. This is Datong for Matthew Harrison. I just want to confirm maybe some dates. I think in earlier call you mentioned that you may present some of the readout on the basket studies for both TUKYSA and Padcev. I'm just wondering what kind of. I just want to first confirm that those, you're going to present, like, some data for both TUKYSA and Padcev from those basket studies. Also I'm wondering whether you can provide more color on any particular indications you are most interested in for those two drugs. Thanks. Yeah, thanks for the question. Just a minor correction. The basket trial data we're talking about is with Padcev, you are right, and there are multiple tumors that are Nectin-4 expressing. We haven't shared the data. We have some top-line data available. As I indicated in the prepared remarks, we will, you know, present that data in 2023. The other basket trial I think we're talking about or a focus of another molecule, not so much TUKYSA, it's actually TIVDAK. Hopefully that's what you were thinking. For TIVDAK, as you know, as with many of these ADCs, there are multiple possible shots on goal from a tumor perspective. We're obviously excited with the cervical cancer opportunity. We're looking potentially to take TIVDAK into frontline cervical cancer, and we've presented our logic and our thinking behind that, and we're still building the blocks for the regimen to understand whether we have something competitive that would include TIVDAK in it. Then the other tumor which is coming into focus is head and neck cancer. We have presented some data initially, and we plan to share some more data with head and neck cancer patients, you know, with our partners, Genmab, sometime in 2023. I can't be more specific than that, but that's the plan. Thank you. Thank you. Our next question comes from Jessica Fye with JP Morgan. Please go ahead. Hi. This is JL for Jess. Thank you for taking our questions. We have a couple on Padcev and a couple on TUKYSA probably. On Padcev, regarding the first-line, cisplatin-ineligible setting, just want to confirm, do you expect priority review with the filing that you submitted? And then do you expect any off-label use in the cisplatin-eligible population following the potential label approval? In the first line, cisplatin ineligible probably next year. For example, could physicians attempt to label the patient, the eligible patients as cisplatin ineligible in order to give them access to Padcev? On the other hand, the questions on TUKYSA. Just wondering kind of your latest thinking on the evolution of the treatment landscape within HER2, penetrating to the earlier line setting. Do you believe TUKYSA would probably most be used after in HER2 from now and in the future? If so, what's the time frame that we should think about, like within HER2, penetrating to a second line, and how long would take for the patient to sequence through in HER2 and probably become more eligible, for lack of a better word, to TUKYSA? Lastly, is there any insight you could share with us regarding the proportion of TUKYSA patients with or without brain met? Or in another word, do you have a split between patients with brain met and patients without brain met that you have treated with TUKYSA so far? Thank you very much. Thank you for the many questions. I hope we can get to answer them all. I apologize if we missed. You can remind us. You know, with regard to the sort of details around our regulatory approach, you know, for Padcev and KEYTRUDA in that frontline, cisplatin-eligible population. I think we've shared we have submitted an application. We don't share details exactly, you know, what our requests are to the agency, but just in general, it is relatively correct to say that accelerated approvals are often reviewed under priority review schedule. That is just like a statement of fact. With regard to off-label use, perhaps, Chip, would you like to comment a little bit on that for Padcev, and then we'll move on to TUKYSA? What I would say is that if physicians can choose to prescribe the product in, you know, ways that they see best fit, we don't actively promote anything that is not in our label. You know, moving forward, we are looking forward to the potential of having an additional label in Padcev, and the teams are ready for when that happens. Right. With regard to TUKYSA, you did have quite a few questions in there. I think maybe what we can do is just sort of reposition TUKYSA for you in general. You know, to remind you, we have in the pivotal trial, HER2CLIMB, outstanding results. In a population heretofore not studied, including patients, you know, with brain metastases, including in that group, patients with active brain metastases, and we improved overall survival. The value that TUKYSA brings to patients with HER2-positive, you know, late line metastatic breast cancer is really remarkable and extremely valuable, you know, for individual patients. With regard to the sort of competitive dynamics, you know, because we have such a strong argument around brain metastases, and as I said earlier, because the KADCYLA, TUKYSA combination is essentially the same design, and the same eligibility criteria as we had with HER2CLIMB. You know, we would expect a meaningful number of patients in that trial to have brain metastases. I'm not going to disclose the actual number, but we expect that to be meaningful. With regard to dynamics and choices that physicians make as to how they sequence therapies, I think that often comes down to the individual patient and their requirements. We certainly don't see, and Chip can support me in this. We don't see any switches away from TUKYSA. What we're seeing sort of, you know, competitively is patients perhaps more likely to start on ENHERTU versus TUKYSA. Chip, do you want to comment a little bit about the mix of TUKYSA versus ENHERTU? Yeah. I think we're continuing to see strong utilization in second line patients with active CNS involvement. TUKYSA has become an important and established treatment for those patients. It is well-tolerated, as I mentioned in the opening remarks. We've seen about a third of patients stay on extended therapy for a time, and I think this has helped to support TUKYSA and the revenue it's generating in a dynamic, you know, and changing and evolving breast cancer marketplace. Right. Again, just on the brain mets perspective, I think your last question was around what is the proportion of patients with brain metastases. What is true is the more successful therapies are in HER2 metastatic breast cancer, the more likely are that brain metastases develop. It's sort of like a sanctuary site which can actually you know. Surprisingly, patients relatively early on may have you know brain metastases. We'll see when we see the results from HER2CLIMB-02 exactly what that proportion looks like. It's certainly enrolling in the trial. We enrolled in the trial. Thank you. Ladies and gentlemen, our next question comes from Geoff Meacham of Bank of America. Please go ahead. Good afternoon. This is Hao calling in for Geoff Meacham. Thank you for the question. Congrats on the quarter. My question is regarding Adcetris and great performance for the quarter. Really two parts. You mentioned about normalizing diagnosis rates. Just wonder, do you see it coming back to pre-COVID level, or it may be still slightly lagging compared to pre-COVID level? Then the second part is the incremental share gains. I guess the long-term OS data was really providing that momentum. Do you see that incremental share gain sort of Continue into the 2023 time frame or maybe you see the market dynamic to suggest that maybe flattening a little bit moving forward? Yeah. Thanks for the question. I think we're very proud of Adcetris. You know, this is a relatively mature brand by age. You know, it's 10 years plus. It continues to grow, which is remarkable. I believe the last 2 quarters have sort of been record-breaking quarters for Adcetris. Obviously, the factors that you mentioned, things like, you know, changes in epidemiology, and such do play a role as, you know, incrementally new data, impactful data will do that. You know, we're very pleased with Adcetris and its progress. Chip, do you want to speak a little bit more about what our sort of thinking is going forward with regards to, you know, shifts in epi and such? Yeah. Thank you, Roger, and thanks for the question. We have seen a normalization of epi back to relatively close to pre-pandemic. We saw a dip in the first quarter of this year in newly diagnosed HL patients. In addition to that, you know, the frontline OS data results have been very well-received. We're pleased with the elevated category one preferred recommendation that we have in the NCCN now, and we do think there is continued incremental growth for us in frontline. Awesome. Great. Thank you. Our next question today comes from Gena Wang with Barclays. Please go ahead. Hi. This is Sheldon, not Regina. Thanks for taking our question, and congrats on the quarter. Maybe one quick question on Adcetris and another one on Padcev. For Adcetris and Keytruda combo trial, is this still on track to report the initial data in late 2022? It seems like the trial is focused on non-small cell lung cancer in melanoma patients after progressing on PD-1. What would be your benchmark to determine whether to move forward with this indication? For Padcev, have you got any feedback from KOLs on if Padcev is approved with the Cohort K data under accelerated approval, how would the KOLs expect the uptake relative to after the confirmed EV-302 data? Thanks. Yep. Thanks, thanks for those two questions. I'll take the Adcetris plus KEYTRUDA in solid tumors questions. Chip, if you want to address the Padcev question. Firstly, there's a strong scientific argument for why we are combining Adcetris in a population of PD-1 failed patients, and that we've focused the trial on melanoma and non-small cell lung cancer. The reason for that is not that Adcetris has any activity that we believe that would be meaningful against a solid tumor, even if it necessarily expressed CD30. Much more importantly, because it turns out that Adcetris has the potential to be an immunomodulator. We have very good preclinical evidence, demonstrating that a population of T regulatory cells, so these are the cells that basically inhibit the immune system from doing, you know, doing its work, particularly when they express CD30, where they are activated. It's an activated population of Tregs that Adcetris can remove that population. Removing a T regulatory cell population from the tumor microenvironment, in a situation where there has been progression or, you know, or lack of response potentially, but progression on something like a PD-1 inhibitor, we think is a very important scientific concept to answer. We did indicate that we were hoping to get data out in 2022. It's more likely that information that we'll share data in 2023. Again, no specific timeframe, but the science is compelling, and we are conducting the clinical experiments. When we have the data at the level of maturity and completeness that we can share, we will go ahead and do that. Chip, from the Padcev side? Yeah. Thanks, Roger. First, from the commercial end, we don't have a label yet. We'll have, you know, some additional insights once we understand the parameters of the label. I will say that the KOL interactions at ESMO this year were very positive, the data was viewed as favorable and an important advancement for patients in the frontline setting. Right. It is. You know, just to add to that, it's important to note that both Padcev and KEYTRUDA are approved actually in urothelial cancer. The drugs themselves are not, in terms of their use, problematic for, you know, urologic oncologists, to use. You know, it's not. If we're successful with this application, it'll be with two, you know, approved drugs, in a combination. Bear in mind that, to date anyway, you know, successful combinations with PD-1 inhibitors that are clearly active, in urothelial cancer have not led to approvals. From the point of view of changing the therapeutic landscape and bringing, you know, potentially meaningful interventions to these patients, particularly cisplatin-ineligible patients who are often older and frail, you know, we're really compelled by a high response rate and a duration of response that was not reached. I mean, that is a remarkable outcome. We think that makes the value proposition of this combination in this vulnerable population very strong. Thank you so much. Our next question today comes from Jay Olson at Oppenheimer. Please go ahead. Oh, hey. Congrats on the quarter, and thank you for taking the question. We're curious about the target product profile for disitamab vedotin and how it compares to ENHERTU. Can you just talk about some of the key points of differentiation and also comment on the potential to combine DV with TUKYSA? Thank you. Yeah, that's a great question. Thank you, and thanks for the congratulations. So just some comments on disitamab vedotin. Obviously, the payload we know well, it's vedotin. The antibody which was selected by our partners at RemeGen, we believe is optimized for an ADC construct. It has high internalization rates, which we think is important, and obviously it binds, you know, to the HER2 target. So, you know, the actual drug construct, we think, is a very good one. As I mentioned earlier with regard to differentiation, the second piece of that is, you know, PD-1 inhibitors or PD-L1 inhibitors are part of a general landscape of oncology. Certainly from multiple points of the compass, we've been able to show that a vedotin-based ADC pairs very well with a PD-1 inhibitor. That's something that we need to work on further. Data that's been presented so far in urothelial cancer, metastatic urothelial cancer, is very compelling using the combination of disitamab vedotin, you know, together with a PD-1 inhibitor. I mean, we're excited by this compound. Our first efforts are in urothelial cancer, where there's a meaningful amount of HER2 positivity or expression. We're interested in the sort of traditional HER2 either overexpressed or amplified, but we also, as is appropriate for an antibody-drug conjugate, we're looking at lower levels of HER2 expression as well, because potentially we'll see value there. There has been some initial data which is encouraging in that regard. Our focus is on bladder, and we are interested in moving ahead in breast cancer and potentially other cancers. Your point about TUKYSA is extremely well taken, which is we basically have two assets that are in the same area. We are working on what is appropriate to do from a clinical perspective, you know, looking at that combination, including some novel aspects, you know, such as the impact of TUKYSA on the expression of HER2 on the surface and whether that's something that we can potentially leverage. I think just stay tuned. We don't have plans that we can share with you in detail, but we're very interested in exploring what value could we potentially bring forward, you know, with our two assets. Thank you very much. Our next question today comes from Gregory Renza at RBC Capital Markets. Please go ahead. Hey, good afternoon, Roger and team. Let me add my congratulations on the quarter as well, and thanks for taking my question. Roger, my question primarily centers around the Inflation Reduction Act. I just wanted to give you an opportunity to comment on the Seagen commercial portfolio as well as the pipeline. I think, namely, how is your view on pipeline prioritization as well as your external pursuits for other assets being influenced by the IRA considerations? Even maybe more appropriate for Chip as well, how should we think about longer term and any impacts of IRA with respect to Adcetris and the other commercial products? Thank you very much. Yeah. Yeah. Thanks for the question. Obviously the law, you know, is now passed. I think at the sort of highest level, we together with others in the industry see this as a negative event for innovation. It has the potential to stifle innovation and some unintended consequences of the legislation, which I think you're addressing around, you know, how do we prioritize our development programs in order to, you know, optimize the value that a drug can bring and within the confines of the act? I would say, you know, we have some very simple answers for the three main components, just so you can understand how we're thinking, you know, inside Seagen. I would remind you also, we are essentially a large molecule company, which, you know, may be somewhat more favorable in that environment. At that sort of real macro level, oncology is, and rightfully so, has this mechanism or it utilizes the mechanism of accelerated approval to get drugs to people that are making a difference and that have the highest unmet need. However, they are often at the end of therapies, and so the addressable population, you know, is relatively small. Certainly in my experience, oncology drugs are developed with that first step into late line therapy bringing value, and then, you know, there's momentum built, and you can see it in the Padcev program is exactly, you know, how we would think how to develop a drug logically in oncology. That may need to change, that the lead indication, you know, potentially being very small and limited may not be the best way for us to, you know, to develop drugs going forward. That's certainly in our thinking. Maybe, Todd, would you like to comment a little bit about the specifics of the act? Sure, happy to. I think Roger gave a really nice sort of overview of how the industry is thinking about it. I think when we look at it, and bear in mind there are a lot of elements to this that are still being defined. I think specifically as it relates to us, there's the inflation cap, there's the Part D redesign, and there's price negotiations. I think with respect to the inflation cap, this is actually something that we are dealing with now and have for a while. Our goal will be to include at least our thinking at the time as best we can into the 2023 guide that we'll put out in February of next year. With respect to the Part D benefit redesign, we think this is an element that would affect TUKYSA more so than the other brands. There, I think there are a lot of dynamics that need to be played out and frankly some more rulemaking that needs to play out, but we don't think that will affect us prior to kind of the 2025 timeframe. Then on price negotiations, we've also looked at this and don't feel that the portfolio, again, this is the biologics, would be affected by this prior to sort of the 2030 timeframe. Obviously a lot of this is in a state of flux. The law was enacted mid-August, and again, there continues to be a lot of sort of work to understand it, frankly, and clarify it, and we're by all means tracking on it. Yeah. Just to reiterate, I think from a development perspective, we're thinking very carefully about what would a new drug profile need to look like in the context, in the framework of what we think this act, you know, will end up creating from a sort of landscape and, you know, potential value perspective. That's great. Thanks for all the color, guys. Our next question today comes from Andy Hsieh with William Blair. Please go ahead. Oh, great. Thanks for squeezing me in. I have two questions. One is related to innovaTV 205 Cohort H. That's the triplet plus or minus Avastin in solid tumors. Just curious about how you think about the design. Should we think about this kind of like analogous to Cohort K, which can be, you know, chained to a randomized portion and potentially be open to an accelerated approval pathway? My second question has to do with the bladder cancer strategy, specifically in the HER2 positive population. Obviously, Padcev has shown exceptional activity there. Just curious if we know the activity of Padcev in the HER2 positive population as you plan to advance DV in that setting. That's kind of motivated by the fact that sometimes, you know, Padcev has shown activity, you know, outside of just Nectin-4-expressing tumors, you know, even FGFR genetic alterations that show really good activity. Thank you. Yeah. Andy, thanks for the question. With regard to innovaTV 205, the focus in that triplet and quadruplet cohort is to define what a profile would look like for a frontline, you know, cervical cancer study. I don't think it's in our thinking right now that if we were to head to the frontline. I accept the analogy with Padcev, but I think the cervical cancer landscape is a little bit more complex. For example, KEYTRUDA is in it. I wouldn't discount the possibility, but I think we're still trying to determine whether we have a competitive regimen. You know, once we've determined that, we will define. If that's what we choose to do to move ahead, we'll define, you know, exactly how we're gonna get there. At first blush, it feels like this would be a randomized trial, but it's, you know, we're not there yet. You know, with regard to. It's a good question around urothelial cancer. The data that's been generated with DV and urothelial cancer, particularly in the, you know, the high expressing HER2, is very compelling. Their response rates as a single agent in the 60% range. Bear in mind, you know, a HER2-directed ADC is not the same as a Nectin-4-directed ADC. They may have the same payloads, but the potential for, you know, a differentiated profile based on a biomarker-defined population, you know, together with whatever the benefit risk looks like, the efficacy and the, you know, safety and tolerability, put together, we think it's appropriate to move another option in urothelial cancer with docetaxel and abiraterone forward. I hope that answers your question. I may have missed part of another question. If I have, please just repeat it. Oh, no. Thanks, Roger. That's a very comprehensive answer. Thank you so much. Ladies and gentlemen, this concludes our question and answer session. I'd like to turn the conference back over to Doug Maffei for closing remarks. Thank you, operator, and thanks everybody for participating in our call this afternoon. Have a great rest of your day. Ladies and gentlemen, this concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.