Seattle Genetics,Inc。(SGEN) 首席执行官 Clay Siegall 于 2019年 第二季度业绩 - 收益电话会议记录

[机器翻译] 电话会议 · 2019年07月17日 · 32 次阅读

Seattle Genetics, Inc. (NASDAQ:SGEN) Q2 2019 Earnings Conference Call July 16, 2019 4:30 PM ET

Seattle Genetics,Inc。(纳斯达克股票代码:[SGEN])2019年第二季度收益电话会议2019年7月16日美国东部时间下午4:30


Peggy Pinkston - VP, IR & Executive Director of Corporate Communications
Clay Siegall - Co-Founder, Chairman, President & CEO
Robin Taylor - Chief Commercial Officer
Todd Simpson - CFO
Roger Dansey - Chief Medical Officer

  • Peggy Pinkston - IR副总裁兼企业传播执行董事
  • Clay Siegall - 联合创始人,董事长,总裁兼首席执行官
  • 罗宾泰勒 - 首席商务官
  • Todd Simpson - 首席财务官
  • Roger Dansey - 首席医疗官


Kennen MacKay - RBC Capital Markets
Matthew Holt - JPMorgan Chase & Co.
Michael Schmidt - Guggenheim Securities
Andrew Berens - SVB Leerink
Maryana Breitman - Goldman Sachs Group
Gena Wang - Barclays Bank
Tazeen Ahmad - Bank of America Merrill Lynch
Stephen Willey - Stifel, Nicolaus & Company
Shanshan Xu - Berenberg
Andy Hsieh - William Blair & Company
Silvan Tuerkcan - Oppenheimer

  • Kennen MacKay - 加拿大皇家银行资本市场
  • 马修霍尔特 - 摩根大通公司
  • 迈克尔施密特 - 古根海姆证券
  • Andrew Berens - SVB Leerink
  • Maryana Breitman - 高盛集团
  • Gena Wang - 巴克莱银行
  • Tazeen Ahmad - 美国银行美林证券
  • Stephen Willey - Stifel,Nicolaus&Company
  • Shanshan Xu - Berenberg
  • Andy Hsieh - William Blair&Company
  • Silvan Tuerkcan - 奥本海默


Good day, ladies and gentlemen, and welcome to today's Seattle Genetics Second Quarter 2019 Financial Results Conference Call. Today's conference is being recorded. For opening remarks, I'd like to turn the call over to Peggy Pinkston, Vice President of Investor Relations. Please go ahead.

美好的一天,女士们,先生们,欢迎参加今天的西雅图遗传学第二季度2019年财务业绩电话会议。 今天的会议正在录制中。 对于开场白,我想转而致电投资者关系副总裁Peggy Pinkston。 请继续。

Peggy Pinkston

Thank you, operator, and good afternoon, everyone. I'd like to welcome all of you to Seattle Genetics' Second Quarter 2019 Conference Call. With me today are Clay Siegall, President and Chief Executive Officer; A - 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. And following our prepared remarks today, we'll open the line for questions. [Operator Instructions].
Today's conference call will include forward-looking statements regarding future events or the future financial and operating performance of the company such as those, among others, relating to the company's 2019 financial outlook, including anticipated 2019 ADCETRIS sales and future revenues, cost and expenses; and the company's potential and anticipated timing to achieve future 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. Among the factors that may cause such a difference include the difficulty in forecasting sales, revenues and expenses and the uncertainty associated with the 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 quarterly report on Form 10-Q for the quarter ended March 31, 2019.
Now I'll turn the call over to Clay.

谢谢运营商,大家下午好。我想欢迎大家参加Seattle Genetics的2019年第二季电话会议。今天和我在一起的是总裁兼首席执行官Clay Siegall;A - Robin Taylor首席商务官;首席财务官Todd Simpson;和首席医疗官Roger Dansey。伴随今天的电话会议是支持幻灯片,可在我们的网站上的“投资者”部分“事件和演示文稿”页面中找到。在我们今天准备好的评论之后,我们将打开问题的界限。 [操作员说明]。



有关西雅图遗传学面临的风险和不确定性的更多信息包含在公司提交给美国证券交易委员会的定期报告中的风险因素标题中,包括该公司截至3月31日的季度10-Q表格的季度报告, 2019。


Clay Siegall

Thanks, Peg, and good afternoon, everyone. In the past few months, we've delivered on several important goals focused on growing our flagship brand ADCETRIS and continuing our evolution into a multiproduct oncology company. Our late-stage portfolio includes enfortumab vedotin, which has been submitted to FDA for approval in metastatic urothelial cancer based on the positive outcome of the EV-201 trial. In addition, we're advancing two other programs in pivotal trials, tucatinib in HER2-positive metastatic breast cancer and tisotumab vedotin in metastatic cervical cancer.
I'll begin with some comments on ADCETRIS, which is an important global product for the treatment of lymphoma. Under our collaboration with Takeda, it is now available in 73 countries. In the U.S. and Canada, we reported record ADCETRIS net sales of $159 million in the second quarter, up 18% from the first quarter of the year. This growth was mainly driven by increased utilization in frontline peripheral T-cell lymphoma. There were -- was also increased use in frontline Hodgkin lymphoma. In addition, these results reflect second quarter strength that we had previously seen with ADCETRIS. We will provide more detail on our commercial progress later in the call.
Outside the U.S., we and our partner Takeda are continuing to expand the approved indication for ADCETRIS. In frontline Hodgkin lymphoma, we received Canadian approval in May, and Takeda recently received approval in a third key country outside of Europe and Japan. This triggered a milestone payment to us of $7.5 million. To date, we've achieved a total of $118 million in milestones under our collaboration, including $47.5 million related to frontline Hodgkin lymphoma approvals in Europe, Japan and key countries.
For frontline PTCL, we submitted our approval application to Health Canada in May, and Takeda also plans to submit frontline PTCL for approval to the EMA and other health authorities this year.
Next is enfortumab vedotin, or EV, which we're developing in collaboration with Astellas. Today, we announced the BLA submission to the FDA for accelerated approval of EV in metastatic urothelial cancer based on results from the EV-201 study. The data were featured in an oral presentation at ASCO and selected for an ASCO press briefing. We are encouraged with the positive reception to these data by the physician community. In anticipation of potential approval, our launch preparation is rapidly advancing. EV is positioned to become our next marketed drug and, if approved, will expand our commercial portfolio beyond hematologic malignancies into solid tumors. We are working closely with Astellas to advance and expand the clinical development program for EV, including in first-line metastatic urothelial cancer. Roger will recap the EV-201 results as well as the clinical development plan during his remarks.
We're also advancing two other solid tumor candidates in late-stage development. These include tucatinib in HER2-positive metastatic breast cancer and tisotumab vedotin, or TV, in metastatic surgical cancer. We expect to report top line data from the tucatinib pivotal trial called HER2CLIMB later this year and from the TV pivotal trial called innovaTV 204 in the first half of 2020.

谢谢,佩格,大家下午好。在过去的几个月里,我们实现了几个重要目标,专注于发展我们的旗舰品牌ADCETRIS,并继续发展成为一家多产品肿瘤公司。我们的后期产品组合包括enfortumab vedotin,根据EV-201试验的积极结果,已经提交给FDA批准用于转移性尿路上皮癌。此外,我们正推进其他两项关键性试验项目,即HER2阳性转移性乳腺癌中的tucatinib和转移性宫颈癌中的tisotumab vedotin。

我将从对ADCETRIS的一些评论开始,这是一种治疗淋巴瘤的重要全球产品。在我们与Takeda的合作下,它现已在73个国家/地区推出。在美国和加拿大,我们报告第二季度ADCETRIS的净销售额为1.59亿美元,比第一季度增长18%。这种增长主要是由于前线外周T细胞淋巴瘤的利用率增加所致。有 - 在前线霍奇金淋巴瘤的使用也增加。此外,这些结果反映了我们之前在ADCETRIS上看到的第二季度实力。我们将在电话会议后期提供有关我们商业进展的更多详细信息。



接下来是enfortumab vedotin,或EV,我们正在与安斯泰来合作开发。今天,我们根据EV-201研究的结果,宣布向美国食品和药物管理局提交BLA申请,以加速批准EV在转移性尿路上皮癌中的应用。这些数据在ASCO的口头报告中被选中,并被选中参加ASCO新闻发布会。我们对医生社区对这些数据的积极接受感到鼓舞。由于预期可能获得批准,我们的发布准备工作正在迅速推进。 EV定位成为我们的下一个上市药物,如果获得批准,将把我们的商业产品组合扩展到血液系统恶性肿瘤以外的实体肿瘤。我们正在与安斯泰来密切合作,推进和扩展EV的临床开发计划,包括一线转移性尿路上皮癌。罗杰将在他的发言中回顾EV-201的结果以及临床开发计划。

我们还在推进后期开发的其他两个实体肿瘤候选者。这些包括HER2阳性转移性乳腺癌中的tucatinib和转移性外科癌症中的tisotumab vedotin或TV。我们预计将在今年晚些时候报告称为HER2CLIMB的tucatinib关键试验以及2020年上半年名为innovaTV 204的电视关键试验的顶线数据。

Lastly, I want to highlight the first FDA approval from one of our technology licensees. Polivy, or polatuzumab vedotin, is an ADC developed by Genentech that targets CD79b. It was approved more than 2 months ahead of the PDUFA date for patients with relapsed diffuse large B-cell lymphoma. Genentech is conducting several additional trials of Polivy including in frontline DLBCL. Among several other collaborators that use our technology, GSK is advancing in ADC in late-stage development, targeting BCMA. This ADC has climbed in BTD designations, and GSK has stated that they are planning a regulatory submission of the second half of this year.
At this point, I'd like to introduce our Chief Commercial Officer, A - Robin Taylor who joined Seattle Genetics in May. Robin was most recently at AstraZeneca, and before that, he spent more than 17 years at Genentech. He's contributed to the global commercial development and strategic marketing of several successful oncology drugs. His skills are well suited to driving our global commercial presence, including the planned launch of EV, as well as other potential drugs emerging from our pipeline such as tucatinib. We are pleased that he has joined the team. Robin?

最后,我想强调我们的一位技术许可证持有者的首次FDA批准。 Polivy或polatuzumab vedotin是由Genentech开发的靶向CD79b的ADC。对于复发性弥漫性大B细胞淋巴瘤患者,它在PDUFA日期之前提前2个月获得批准。 Genentech正在进行几项Polivy试验,包括前线DLBCL。在使用我们技术的其他几个合作者中,GSK正在推进ADC的后期开发,目标是BCMA。该ADC已经在BTD指定中攀升,GSK表示他们计划在今年下半年提交监管报告。

在这一点上,我想介绍我们的首席商务官,A - Robin Taylor,他于5月加入了Seattle Genetics。罗宾最近在阿斯利康(AstraZeneca)工作,在此之前,他在基因泰克(Genentech)工作了17年多。他为几种成功的肿瘤药物的全球商业开发和战略营销做出了贡献。他的技能非常适合推动我们的全球商业存在,包括计划推出EV,以及我们的管道中出现的其他潜在药物,如tucatinib。我们很高兴他加入了团队。罗宾?


Thank you, Clay. I'm tremendously excited to have joined Seattle Genetics at this transformational time. I was drawn to the company based on the strong leadership team, the innovative science and the clear focus on patients as demonstrated by the continued investment in new indications for ADCETRIS and the exceptional late-stage pipeline. This is an important time for the commercial organization with the planned launch of EV and pivotal data anticipated for tucatinib later this year.
Let me turn now to our second quarter results. ADCETRIS net sales in the U.S. and Canada were $159 million in the second quarter, an increase of 30% compared to the same quarter in 2018. For the first half of 2019, ADCETRIS sales were $294 million, a growth rate of 35% for the first half of the year compared to the first half of 2018.
We attribute the growth in Q2 to 3 main drivers. First, we've observed continued strong uptake of ADCETRIS plus CHP in CD30 expressing PTCL following the U.S. approval of this indication in November 2018. This is driven by the positive ECHELON-2 data including the overall survival advantage that showed a 34% reduction in the risk of death compared to CHOP. Second, we have seen continued growth of ADCETRIS in Stage III and IV frontline Hodgkin lymphoma. This reflects a positive reception to the 3-year PFS data from ECHELON-1 trial reported at ASCO. In addition, there has been an increase in patient engagement with growth in unique visitors to our online resources and downloads of the ask-your-doctor brochures. This encourages patients to ask their physicians about all available options for frontline treatment of Hodgkin lymphoma. The update to the NCCN Guidelines in April 2019 may also have contributed.
And third, we have historically observed the strongest sequential growth between Q1 and Q2 for ADCETRIS with continued but more moderate growth in other quarters of the year. Based on these historical patterns, we are maintaining our guidance of full year 2019 ADCETRIS net sales in the range of $610 million to $640 million.
Finally, we're actively preparing for the commercial launch of enfortumab vedotin with our partner Astellas. Sales force hiring is very close to complete, and we are beginning training activities to ensure that we're fully prepared for launch. Having participated in multiple successful oncology drug launches over my career, I have been pleased with the depth and rigor of the preparations of the commercial team at Seattle Genetics to date. I'm confident that we will be ready for the EV launch upon FDA approval.
Let me turn now to Todd to provide the finance update.


现在让我谈谈第二季度的结果。 ADCETRIS第二季度在美国和加拿大的净销售额为1.59亿美元,与2018年同期相比增长了30%。在2019年上半年,ADCETRIS的销售额为2.94亿美元,增长率为35%。与2018年上半年相比,今年上半年。

我们将第二季度的增长归因于3个主要驱动因素。首先,我们观察到在2018年11月美国批准该指征后,CD30表达PTCL持续强烈吸收ADCETRIS CHP。这是由ECHELON-2阳性数据推动的,包括总生存优势,显示减少34%。与CHOP相比死亡的风险。其次,我们已经看到ADCETRIS在III期和IV期前线霍奇金淋巴瘤中持续增长。这反映了对ASCO报告的ECHELON-1试验的3年PFS数据的积极接受。此外,患者参与度越来越高,我们的在线资源的独立访问者和咨询医生手册的下载量也在增长。这鼓励患者向他们的医生询问有关霍奇金淋巴瘤一线治疗的所有可行方案。 2019年4月对NCCN指南的更新也可能有所贡献。


最后,我们正积极准备与我们的合作伙伴安斯泰来商业推出enfortumab vedotin。销售人员的招聘工作已接近尾声,我们正在开展培训活动,以确保我们为发布做好充分准备。在我的职业生涯中参与了多次成功的肿瘤药物发布,我对西雅图遗传学商业团队迄今为止的准备工作的深度和严谨感到高兴。我相信,经FDA批准,我们将为EV发布做好准备。



Great. Thanks, Robin, and thanks, everyone, for joining us in the call this afternoon. So today, I'll summarize our financial results for the second quarter and year-to-date as well as provide 2 updates to our financial outlook for the year. Total revenues were $218 million in the second quarter and $414 million for the year-to-date in 2019. This included record ADCETRIS net sales in the U.S. and Canada of $159 million in the second quarter and $294 million for the first half of the year. Growth in 2019 primarily reflects the frontline label expansions in Hodgkin lymphoma and PTCL and the other dynamics that Robin described.
Royalty revenues in the second quarter of 2019 were $23 million compared to $21 million in the second quarter of last year. For the first half of 2019, royalty revenues were $39 million compared to $36 million in the first half of last year. We expect ADCETRIS royalties to increase throughout the year as Takeda sales grow and as increasing sales trigger higher royalty rates. As a reminder, royalty revenues in 2018 included Takeda's portion of third-party royalty obligations paid on ADCETRIS, some of which expired in 2018. Therefore, despite the increases in sales by Takeda, royalty revenues grew at a lower rate while cost of royalty revenues decreased. Going forward, royalty revenues will also reflect amounts earned on net sales of collaborator ADCs, such as Polivy. However, this did not contribute to second quarter results and is not included in our guidance.
Collaboration revenues, which includes amounts earned under our ADCETRIS collaboration with Takeda and our ADC deals, were $36 million in the second quarter and $81 million for the first half of 2019. This included the earned portion of $13 million in milestones achieved in the second quarter and $43 million in the first half of 2019, most notably by Genentech's recent approval of Polivy and Takeda's approvals of ADCETRIS in frontline Hodgkin lymphoma.
R&D expenses were $164 million in the second quarter and $322 million for the first half of 2019. The increases over 2018 primarily reflect investment across our pipeline primarily on our late-stage programs, EV, tucatinib and TV.
SG&A expenses were $82 million in the second quarter and $163 million in the first half of 2019. These increases reflect commercial efforts to support ADCETRIS in frontline indications as well as costs related to our late-stage pipeline programs. We ended the second quarter with $376 million in cash and investments. This is in addition to $107 million in Immunomedics at the end of the second quarter. These shares are mark-to-market, which causes variability in our financial results and is not core to our business. These results -- this resulted in a noncash investment loss of $43 million for the second quarter, which was slightly higher than a similar noncash gain in the first quarter.
Lastly, I want to highlight 2 updates to our 2019 financial guidance. First on revenues, given the recent milestones under the Takeda and Genentech deals, we are increasing our guidance for collaboration revenues to a range of $110 million to $125 million. And secondly on SG&A expenses, in anticipation of the EV BLA submission announced this morning, we proceeded with hiring substantially all the enfortumab vedotin U.S. sales organization. As a result of this, we are increasing and narrowing guidance for SG&A expenses to a range of $335 million to $360 million. Our other guidance remains unchanged.

非常好。谢谢,罗宾,谢谢大家今天下午的来电。所以今天,我将总结第二季度和今年迄今的财务业绩,并为我们今年的财务前景提供2个更新。第二季度总收入为2.18亿美元,2019年至今为4.14亿美元。其中包括第二季度美国和加拿大的ADCETRIS净销售额为1.59亿美元,上半年为2.94亿美元。 。 2019年的增长主要反映了霍奇金淋巴瘤和PTCL的前线标签扩张以及罗宾描述的其他动态。




第二季度的SG&A费用为8,200万美元,2019年上半年为1.63亿美元。这些增长反映了支持ADCETRIS前线指标的商业努力以及与我们后期管道计划相关的成本。我们在第二季度以3.76亿美元的现金和投资结束。此外,第二季度末,Immunomedics还增加了1.07亿美元。这些股票是按市价计算的,这导致我们的财务业绩变化,并不是我们业务的核心。这些结果 - 导致第二季度非现金投资亏损4300万美元,略高于第一季度类似的非现金收益。

最后,我想强调2019财务指南的2个更新。首先是收入,鉴于最近Takeda和Genentech交易的里程碑,我们正在将协作收入的指导范围提高到1.1亿美元到1.25亿美元。其次是关于SG&A费用,由于预计今天上午宣布的EV BLA提交,我们继续雇佣了所有enfortumab vedotin美国销售组织。因此,我们正在增加并缩小对SG&A费用的指导,范围为3.35亿美元至3.6亿美元。我们的其他指导保持不变。

Now I'll turn the call over to Roger.



Thanks, Todd, and good afternoon, everyone. As Clay mentioned, the positive EV-201 pivotal trial results were featured as an oral session at ASCO in early June and are also part of the subsequent Best of ASCO program. Among metastatic urothelial cancer patients who've received both the platinum regimen and the PD-1 or PD-L1 inhibitor, the confirmed response rate was 44% by blinded independent central review, including a 12% complete response rate. For context, single-agent chemotherapy, which is the current standard of care in the setting, shows limited activity with a response rate of approximately 10% with complete responses rarely obtained. Responses in EV-201 were observed across all patient subgroups, including those with liver metastases, have particularly poor outcomes. The median duration response was clinically meaningful at 7.6 months.
EV was tolerable with a manageable safety profile. The most common treatment-related adverse events included fatigue, alopecia, decreased appetite, rash and peripheral neuropathy. Notably, the results are consistent with earlier the Phase I experience in the same heavily pretreated patient population. Based on these results, we and Astellas have submitted a BLA to the FDA seeking accelerated approval of EV. As a reminder, we have Breakthrough Therapy designation in this patient population.
The remarkable activity of EV monotherapy in patients with multiply treated metastatic urothelial cancer provides substantial development opportunities for EV to address a wide array of unmet medical needs. Our EV development plans is focused on 4 key areas. First, enrollment is ongoing in the second cohort of the EV-201 trial of metastatic urothelial cancer patients who proceed to PD-1 or PD-L1 1 treatment but are ineligible for cisplatin and are platinum-naïve. Second, the ongoing confirmatory randomized trial EV-301, which is intended to support global regulatory submission continues to enroll well. Third, the ongoing EV-103 trial, which combines EV with pembrolizumab and/or platinum chemotherapy in the first-line metastatic setting. This is the precursor to a frontline randomized trial, and we expect to report data from the EV plus pembrolizumab cohort later this year. And fourth, trials are being planned in earlier stages of urothelial cancer such as muscle invasive bladder cancer as well as other Nectin-4 expressing tumors.
I'll move on now to ADCETRIS, which was subject numerous presentations at ASCO as well as the European Hematology Association and the International Conference on Malignant Lymphoma meetings. Across these 3 congresses, we reported on several important data sets. First, we showed that with an extended follow-up in the ECHELON-1 trial, the PFS benefits for ADCETRIS plus AVD determined by investigators was maintained. The 3-year PFS was 83.1% compared to 76% in the ABVD arm, a difference of 7.1%. Importantly, consistent improvements in PFS was observed among patients treated with the ADCETRIS regimen across the majority of prespecified subgroups, including disease stage and prognostic score. Second, analyses of several trials, including ECHELON-2, showed responses in non-Hodgkin lymphoma patients across all levels of CD30 expression. These data supports the notion that there may be no specific expression level required for efficacy. And third, multiple abstracts highlighting the activity of ADCETRIS in combination with nivolumab, including in Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Importantly, ADCETRIS plus nivolumab was recently added to NCCN treatment guidelines for second-line Hodgkin lymphoma.



EV单药治疗在多重治疗的转移性尿路上皮癌患者中的显着活性为EV提供了大量的发展机会,以解决各种未满足的医疗需求。我们的EV发展计划主要关注4个关键领域。首先,在转移性尿路上皮癌患者的EV-201试验的第二个队列中进行入组,这些患者进行PD-1或PD-L1 1治疗,但不符合顺铂,并且是未经铂金的。其次,旨在支持全球监管提交的正在进行的确认性随机试验EV-301继续报名。第三,正在进行的EV-103试验,将EV与pembrolizumab和/或铂化疗联合应用于一线转移。这是前线随机试验的前身,我们预计将在今年晚些时候报告来自EV加pembrolizumab队列的数据。第四,正在计划在尿路上皮癌的早期阶段进行试验,例如肌肉浸润性膀胱癌以及其他表达Nectin-4的肿瘤。

我现在转到ADCETRIS,在ASCO以及欧洲血液学协会和恶性淋巴瘤国际会议上进行了多次演讲。在这3次代表大会上,我们报告了几个重要的数据集。首先,我们表明,通过ECHELON-1试验的延长随访,保持了由研究者确定的ADCETRIS加AVD的PFS益处。 3年PFS为83.1%,而ABVD组为76%,相差7.1%。重要的是,在大多数预先指定的亚组(包括疾病分期和预后评分)中,使用ADCETRIS方案治疗的患者中观察到PFS的持续改善。其次,包括ECHELON-2在内的几项试验的分析显示,非霍奇金淋巴瘤患者在所有CD30表达水平上都有反应。这些数据支持这样的概念,即功效可能不需要特定的表达水平。第三,多篇摘要突出了ADCETRIS与nivolumab联合应用的活性,包括霍奇金淋巴瘤和原发性纵隔B细胞淋巴瘤。重要的是,最近将ADCETRIS加nivolumab添加到NCCN二线霍奇金淋巴瘤治疗指南中。

Lastly, we are now initiating additional trials of ADCETRIS that may result in label expansion, 2 of which I'll mention today. One trial will evaluate retreatment with ADCETRIS in Hodgkin and T-cell lymphoma patients who progress after a prior response, including in patients who received ADCETRIS in the first-line setting. Encouraging data with retreatment in the relapsed/refractory setting have been previously published. We are also initiating a trial of ADCETRIS in Hodgkin lymphoma and PTCL patients who are unfit for combination chemotherapy either due to older age or comorbidities. This is an area of high unmet need. We believe that generating data for a labeled indication is important for physicians and patients. We also expect to initiate additional label-enabling and practice-informing trials, and we'll keep you posted as our plans progress.
Next, I'd like to briefly highlight the status of our late-stage programs tucatinib and tisotumab vedotin, both of which are in registration trials. Tucatinib is a potentially best-in-class oral tyrosine kinase inhibitor that targets HER2. We are conducting a randomized pivotal trial called HER2CLIMB in heavily pretreated HER2-positive metastatic breast cancer, including patients with brain metastases. Patients in this setting have a poor outcome with standard of care treatments. HER2CLIMB enrollment is complete, and we continue to expect to report the top line results for the primary endpoint of PFS later this year.
We are also initiating this year a Phase II randomized trial of tucatinib in combination with TDM-1 compared to TDM-1 alone in the second-line metastatic HER2-positive breast cancer setting. The primary endpoint is PFS with a key secondary endpoint of OS. With this trial, we aim to ensure -- to show improved outcomes combining tucatinib with a HER2 ADC, which is a well-established standard of care in earlier lines of breast cancer. Data from a published Phase I trial support evaluating this combination.
Tisotumab vedotin, or TV, is an ADC targeting tissue factor that we are developing in partnership with Genmab. We are conducting a pivotal Phase II single-arm, single-agent trial in women with recurrent or metastatic cervical cancer where there is no standard of care and outcomes are poor. The primary endpoint of the trial is confirmed objective response. Enrollment is complete, and we are following patients for response assessment and, importantly, durability of response. We estimate reporting top line data in the first half of 2020. If positive, the trial could support a regulatory submission under the FDA accelerated approval mechanism.
Now I'll turn the call over to Clay.


接下来,我想简要介绍我们的晚期项目tucatinib和tisotumab vedotin的状态,两者都在注册试验中。 Tucatinib是一种潜在的最佳口服酪氨酸激酶抑制剂,靶向HER2。我们正在进行一项名为HER2CLIMB的随机关键试验,该试验包括大量预处理的HER2阳性转移性乳腺癌,包括脑转移患者。在这种情况下,患者的标准治疗效果不佳。 HER2CLIMB注册已完成,我们仍然希望在今年晚些时候报告PFS主要终点的最高结果。

今年我们还开始了一项二期随机试验,即tucatinib联合TDM-1与单独使用TDM-1治疗二线转移性HER2阳性乳腺癌。主要端点是具有OS的关键辅助端点的PFS。通过这项试验,我们的目标是确保 - 结合使用tucatinib和HER2 ADC的改善结果,HER2 ADC是早期乳腺癌系列中公认的护理标准。已发布的I期试验数据支持评估此组合。

Tisotumab vedotin或TV是我们与Genmab合作开发的针对组织因子的ADC。我们正在对患有复发性或转移性宫颈癌的女性进行关键的II期单臂,单剂试验,其中没有标准治疗且结果差。试验的主要终点是确认的客观反应。报名已经完成,我们正在关注患者的反应评估,重要的是,他们的反应持久性。我们估计2020年上半年的报告顶线数据。如果是正面的,该试验可以支持FDA加速批准机制下的监管提交。


Clay Siegall

Thanks, Roger. We've accomplished much in the first half of 2019, and the second half of the year is poised for many additional activities that are important to our goal of bringing drugs to patients in need. These include, first, continuing to establish ADCETRIS as the standard of care in frontline Hodgkin lymphoma and frontline PTCL and initiate clinical trials to further expand the ADCETRIS label; second, work with FDA on our EV submission in collaboration with Astellas, report initial results from the first-line EV-103 trial and expand the EV development program with several new trials; and third, report top line data from the tucatinib pivotal trial HER2CLIMB later in 2019 and advance the TV pivotal trial in cervical cancer towards top line data in the first half of next year. I'm excited by the progress we're making with ADCETRIS, enfortumab vedotin and the rest of our product pipeline. We'll keep you updated on our progress.
At this point, we'll open the line for Q&A. Operator, please open the call for questions.

谢谢,罗杰。我们在2019年上半年取得了很大成就,并且今年下半年准备开展许多其他活动,这些活动对我们向有需要的患者提供药物的目标非常重要。其中包括,首先,继续建立ADCETRIS作为前线霍奇金淋巴瘤和前线PTCL的标准治疗,并启动临床试验以进一步扩大ADCETRIS标签;第二,与安斯泰来合作,与美国食品和药物管理局合作提交EV报告,报告一线EV-103试验的初步结果,并通过几项新的试验扩展EV发展计划;第三,报告2019年晚些时候tucatinib关键试验HER2CLIMB的最高分数据,并在明年上半年将宫颈癌的电视关键试验推向顶线数据。我对使用ADCETRIS,enfortumab vedotin和我们的其他产品系列所取得的进展感到非常兴奋。我们会及时通知您最新进展。



[Operator Instructions]. We'll take our first question from Kennen MacKay with RBC Capital Markets.

[操作员说明]。 我们将从Kennen MacKay和RBC Capital Markets收到我们的第一个问题。

Kennen MacKay

For the team, first off, big congrats on the quarter. I was just wondering if you could help us understand the decision not to increase guidance here. I ask because given the recent price hike in ADCETRIS, it seems you'll squarely be within your guidance with 0 growth. And with only 3% sequential quarter-over-quarter growth in Q3 and 4, you'll hit the upper end of guidance, which seems quite doable. Is there anything we should be reading into here? And also on that topic, I was just wondering if you could help us understand the ADCETRIS inventory in Q2. Could there maybe be a week or 2 of stocking here given the June 20 price hike?

对于球队来说,首先,对本季度表示祝贺。 我只是想知道你是否可以帮助我们理解不在这里增加指导的决定。 我问,因为鉴于最近ADCETRIS的价格上涨,看起来你的0指数增长肯定会在你的指导范围内。 第三季度和第四季度的季度环比仅增长3%,您将达到指导的上限,这看起来非常可行。 我们应该在这里读到什么吗? 关于这个话题,我只是想知道你是否可以帮助我们理解第二季度的ADCETRIS库存。 鉴于6月20日的价格上涨,这里可能会有一周或两周的库存?

Clay Siegall

Thanks, Kennen. Thanks for the questions. So when we think about ADCETRIS, it's a really important brand. It's growing as a brand in U.S., growing international, and we're pleased with what we're seeing. We reiterated the guidance, and please note we're giving annual guidance. We're not giving quarterly guidance that we did while we were in the middle of getting frontline approvals, and so we reiterated $610 million to $640 million, which is 30% over 2018. And so it's a strong guidance, and we're trying to be as accurate as we can. We have a range there, and we have good connection with docs, and our 3-year PFS data with E1 was particularly important, and E2 data was spectacular. You know that, not only with PFS but with OS. But Q2 is typically strong.
Now looking out into the future, it's really hard to know exactly what we're going to get. It's hard work out there. We're continuing to displace decades-old standard of care that are entrenched at the marketplace, and we're working hard at it. We like what we see a lot. We still feel that our products are growing and that our guidance indicates that. And I would just say to stay tuned, and we're out there in full force. Our commercial teams are doing well, and we're really connecting with docs.
Your second question, Kennen, we have really no evidence that there's really any stocking, as you call it, the inventory. We really don't see that. We know that there are some big cancer centers that hold more vials than the small cancer centers because they treat more patients, but that's not really stocking. So we don't see any evidence for stocking of ADCETRIS. We deliver in real time, people order it, they get it quickly. And so we feel really good about where we are, and we just don't see sites accumulating inventory.





And Kennen, this is Todd. I want to add just one more comment. You talked about the price increase. We did have a 3.9% price increase in July, but keep in mind that we only see about half of that come through our net sales because of the discounting and the gross to net, particularly around PHS share of our business, which is pretty significant.

而Kennen,这是Todd。 我想再添加一条评论。 你谈到了价格上涨。 我们确实在7月份增加了3.9%的价格,但请记住,我们只看到大约一半来自我们的净销售额,因为折扣和总净额,特别是我们业务的PHS份额,这是非常重要的。

Kennen MacKay

That's really quite helpful context, especially given the current environment and I think important to remember. Maybe just one follow-up for Clay and maybe also for Robin, just wondering if you can help us understand the changes that you've been making with the ADCETRIS sales force here. It seems like, tracking the website, there's been quite a bit of hiring going on here. Is that also sort of pulling into the increased ADCETRIS sales that we saw in Q2? And is that responsible for the SG&A guidance increase? Or is that more the EV sales force?

这是非常有用的背景,特别是考虑到当前的环境,我认为重要的是要记住。 也许只是Clay的一个后续行动,也许也是Robin的后续行动,只是想知道你是否可以帮助我们了解你在这里对ADCETRIS销售人员所做的改变。 看起来,跟踪网站,这里有相当多的招聘。 这是否也有助于我们在第二季度看到的增加的ADCETRIS销量? 是否负责SG&A指导的增加? 或者更像是EV销售人员?

Clay Siegall

First of all, thanks for mentioning we had a good quarter, and we're very proud of that. It is really more related to the last thing you said, the EV sales force. We thought it would be important to have some of our salespeople from ADCETRIS go to the EV program for continuity and connection, and so we replaced some of the people on the ADCETRIS sales force. Robin, do you want to talk about the folks that we're getting, the type of people that are looking to come work with us both on ADCETRIS and EV?

首先,感谢提到我们有一个很好的季度,我们为此感到非常自豪。 这与你说的最后一件事,EV销售人员有很大关系。 我们认为让一些来自ADCETRIS的销售人员进入EV计划以实现连续性和连接非常重要,因此我们替换了ADCETRIS销售人员中的一些人。 罗宾,你想谈谈我们得到的人,那些希望在ADCETRIS和EV上与我们合作的人吗?


Yes. No, what I'd say is we are seeing very strong interest in Seattle Genetics. The hiring on the EV sales force, as I mentioned, is almost fully complete, and we have a lot of interest in those rules. We did have a few folks come over from the ADCETRIS sales force over EV and, of course, you -- what you saw online with some of the backfills for those positions. But I would say that we've got a really high-performance group with great depth of oncology experience for the EV sales force.

是。 不,我要说的是我们对西雅图遗传学非常感兴趣。 正如我所提到的,EV销售人员的招聘几乎完全完成,我们对这些规则很感兴趣。 我们确实有一些人来自ADCETRIS销售人员对EV的影响,当然还有你 - 你在网上看到了这些职位的一些回填。 但我要说的是,我们有一个非常高效的团队,对电动汽车销售人员有着深厚的肿瘤学经验。


Our next question is from Cory Kasimov with JPMorgan.

我们的下一个问题来自Cory Kasimov和摩根大通。


This is Matthew on for Cory. So for my first question, I'm trying to understand the potential impact of the international pricing index proposal on ADCETRIS pricing, and I was wondering if you could provide any qualitative or quantitative commentary in that regard should this policy be implemented.

这是马修对科里的看法。 因此,对于我的第一个问题,我试图了解国际定价指数提案对ADCETRIS定价的潜在影响,我想知道如果能够实施这一政策,您是否可以在这方面提供任何定性或定量评论。

Clay Siegall

Thanks, Matt. Look, we're aware of the issues and closely track them. It's certainly dynamic. There's changes literally daily or frequently. We're paying attention like any biotech or pharma company is. Ultimately, we believe fully that innovative medicines that provide meaningful benefits will continue to be valued by patients and physicians and payers. ADCETRIS is a first-in-class drug. EV, another drug that we believe will be first in class, and these are drugs that really have an impact on patients, and they're valuable. And so we're watching, not sure what will happen exactly. I think you're as sure of it as we are.

谢谢,马特。 看,我们知道这些问题并密切跟踪它们。 它肯定是动态的。 字面上每天或经常发生变化。 我们像任何生物技术公司或制药公司一样关注。 最终,我们充分相信,提供有意义的益处的创新药物将继续受到患者,医生和付款人的重视。 ADCETRIS是一流的药物。 EV,另一种我们认为会在课堂上首发的药物,这些药物确实会对患者产生影响,而且它们很有价值。 所以我们正在观察,不确定究竟会发生什么。 我认为你和我们一样确定。


Got it. And then my second question is on tucatinib and the initial data expected this year for the HER2CLIMB. Just curious what you're hearing from KOLs in terms of what PFS value or hazard ratio would be clinically meaningful in the context of all the other available treatments in the space.

得到它了。 然后我的第二个问题是关于tucatinib以及今年HER2CLIMB的初步数据。 只是好奇你从KOL中听到的PFS值或风险比在空间中所有其他可用治疗方案中具有临床意义。

Clay Siegall

Sure. We're really excited about HER2CLIMB and coming forward with data later this year. Roger, do you want to talk a little bit about the context of what's out there in the world?

当然。 我们对HER2CLIMB感到非常兴奋,并在今年晚些时候推出数据。 罗杰,你想谈一谈世界上那里的情况吗?


Sure. Yes. It's a good question. So the HER2CLIMB trial has some unique aspects to it, particularly the patient population that's been enrolled with a very high frequency of patients with brain metastases, so there's an extremely high unmet need of the population. The trial design is a triplet versus a doublet with tucatinib added on to trastuzumab and capecitabine, we think is a thoughtful design that may result in positive outcomes. In terms of what is a meaningful delta, I think it's very hard without seeing the data to make any specific comments on that. Again, there isn't really a total control that you can absolutely map to, and the unmet need is very high. So everything is a relative decision, and I think that's about where we can go at this point. But we're excited as Clay said. The trial enrolled well. We're hoping to get the readout by the end of the year, and of course, we'll know at that time.

当然。 是。 这是一个很好的问题。 因此,HER2CLIMB试验有一些独特的方面,特别是患有脑转移患者频率非常高的患者人群,因此对人群的需求极高。 试验设计是三联体与双联合使用替卡西尼加入曲妥珠单抗和卡培他滨,我们认为这是一种深思熟虑的设计,可能会产生积极的结果。 就什么是有意义的delta而言,我认为如果没有看到数据对此做出任何具体评论,那将是非常困难的。 再一次,你真的没有完全可以映射到的控件,而且未满足的需求非常高。 所以一切都是相对的决定,我认为这就是我们现在可以走到哪里。 但克莱说,我们很兴奋。 该试验很好。 我们希望在今年年底之前获得读数,当然,我们当时也会知道。


We'll take our next question from Michael Schmidt with Guggenheim.



Congrats on a good quarter from me as well. I had a question again on the ADCETRIS sales number for this quarter. It sounds like -- and correct me if I'm wrong, but it sounds like much of the ADCETRIS sales growth was driven by increased use in PTCL, and I was just wondering if you could comment a little bit more about what do you see in terms of market dynamics in PTCL right now, for example. What market share do you have in frontline treatment at the moment? And are those rates comparable in the different subtypes of TCL?

祝贺我和我一样好。 我对本季度的ADCETRIS销售数字再次提出疑问。 这听起来像 - 如果我错了就纠正我,但听起来很多ADCETRIS的销售增长是由PTCL的使用增加所驱动的,而我只是想知道你是否可以更多地评论你看到了什么 例如,就目前PTCL的市场动态而言。 您目前在一线治疗中占有哪些市场份额? 在TCL的不同亚型中,这些比率是否具有可比性?

Clay Siegall

Thank you for your questions, Michael. So first of all, as we said in the prepared remarks, we think that as we track this, our growth in revenue was attributed to both the E2 regimen, which is in PTCL growth, as well as in the E1. Now in the E2, we're not going to report the different subtypes. We can tell you that they are being used in all the subtypes as far as what we can find, but we're not going to report specifics about that. We also don't report the specific market share. What we can say is that we predicted that it would take a number of quarters to get bigger and bigger market share because this was a regimen that we were displacing, CHOP specifically in PTCL, that was around for almost 3.5 decades. So this is -- it's not that easy to displace these entrenched therapies. Now the good news with the E2 regimen is we had not only PFS data but OS data.
And so now let's switch to E1, the E1 regimen for frontline Hodgkin lymphoma, and there, as you know, we experienced a little headwind in the past. We had 2. We got a lot of early adopters, and then we had some docs that said, "Look, I know how to treat frontline Hodgkin lymphoma. I've been doing it for decades well, and you're showing us data that's only of limited duration of follow-up. We'd like to see some more." So this year, for instance, we have shown now 37 months of follow-up data, and the data actually improved with time. So now if you just look at PFS, good old-fashioned PFS, and you look at 37 months, we are now 7.1% better in PFS. And that's important because while you can't yet call these cures, these are long-term disease survival, and once you get past 5 years or the definition of a cure for oncologists, we can start calling it that. But it is likely that a lot of these patients will go out long, and hopefully, within the not-too-distant future, we can really look at what could be a cure rate increase in Hodgkin lymphoma.
And going from the 2-year data that we produced when we first got approval to the 37-month data that came out with PFS, I think that caught a lot of doctors' attentions. And so they looked at this, they saw it, and they were more comforted by that because we don't yet have OS, which in E1, in the E1 regimen of frontline Hodgkin lymphoma, was not contemplated to have yet. So there was nothing wrong. It just takes a while. With E2 in PTCL, the standard of care wasn't nearly as good as it was with E1, the Hodgkin regimen. So I really understand what doctors are saying. I understand that they wanted to see a little bit more aging of our data, and the data improved with age so I think that's a big deal, too.

谢谢你的问题,迈克尔。首先,正如我们在准备好的评论中所说,我们认为,随着我们追踪这一点,我们的收入增长归功于E2方案,即PTCL增长,以及E1。现在在E2中,我们不会报告不同的子类型。我们可以告诉您,就我们能找到的内容而言,它们被用于所有子类型,但我们不会报告具体内容。我们也没有报告具体的市场份额。我们可以说,我们预测需要花费几个季度才能获得越来越大的市场份额,因为这是一个我们正在取代的方案,特别是PTCL的CHOP,已经存在了近3.5年。所以这就是 - 取代这些根深蒂固的疗法并不容易。现在,E2方案的好消息是我们不仅拥有PFS数据,还拥有操作系统数据。




Okay. Then I had a pipeline question regarding tisotumab vedotin. I know the initial indications, obviously, ferocad count but I was just wondering when we might learn about the potential of that agent in other solid tumors.

好的。 然后我有关于tisotumab vedotin的管道问题。 我知道最初的迹象,显然是ferocad计数,但我只是想知道我们什么时候可以了解该药物在其他实体肿瘤中的潜力。

Clay Siegall

Yes, we're definitely looking at cervical cancer. Roger, can touch on a little bit of generally what we're looking at with TV?

是的,我们肯定在看宫颈癌。 罗杰,可以谈谈我们正在看电视的一点点吗?


Sure. So the program is configured to evaluate cervical cancer, as you mentioned, in a pivotal trial with data readouts hopefully in early -- or in 2020. The -- but we have other efforts going on. So we in fact have a basket trial, which is looking at tumors that express tissue factor where TV it potentially has a role, and that's an ongoing trial at the moment. We haven't read out data yet. But obviously, when we do, we'll present that. We also have an asset going on specifically in ovarian cancer. So we have a number of different trials outside of cervical cancer exploring the potential for TV in other diseases.

当然。 因此,正如您所提到的,该计划被配置为评估子宫颈癌,在一项关键的试验中,希望在早期或2020年进行数据读数。但是我们正在进行其他努力。 因此,我们实际上进行了一项篮子试验,该试验正在研究表达组织因素的肿瘤,其可能在电视中发挥作用,而目前正在进行试验。 我们还没有读出数据。 但显然,当我们这样做时,我们会提出这一点。 我们还专门研究卵巢癌的资产。 因此,我们在宫颈癌之外进行了许多不同的试验,探索其他疾病中电视的潜力。

Clay Siegall

And what I would add also is we actively speak with our partner Genmab often about trying to maximize TV. So just so that you know, we're excited about the product and working hard on it.

我还要补充的是,我们经常与我们的合作伙伴Genmab谈论试图最大化电视节目。 所以,您知道,我们对产品感到兴奋并努力工作。


And maybe one piece to add is we in fact do have the beginnings of combination trial with TV and pembrolizumab as well. So that's up and running.

也许还有一件要补充的是我们实际上确实有电视和pembrolizumab组合试验的开始。 这样就可以了。


We'll take our next question from Andrew Berens with SVB Leerink.

我们将接受来自Andrew Berens和SVB Leerink的下一个问题。


Congrats on the quarter, guys. I also had two questions, one on PTCL given the prepared comments. And I know you said you wouldn't talk about different subgroups, but is this a disease or opportunity that we should think off as a prevalent opportunity? Or is it really new patients that are driving what you're seeing? Is there a possibility patients are going to get ADCETRIS through multiple lines of therapy when they relapse since it's more of a prevalent disease?

恭喜这个季度,伙计们。 我还有两个问题,一个是关于PTCL给出的准备评论。 我知道你说你不会谈论不同的小组,但这是一种疾病或机会,我们应该将其视为一个普遍的机会吗? 或者是真正的新病人正在推动你所看到的? 当患者复发时,患者是否有可能通过多种治疗途径获得ADCETRIS,因为它更像是一种流行疾病?

Clay Siegall

So on PTCL, look, we're out there talking about the data on -- for incident patients, and so that's what we're looking at, newly diagnosed incident patients. So we don't have a lot of data on prevalent. I mean we still have approval to treat relapse patients, and that's one of our labels, especially in ALCL and some other, in CTCL. But we are really focused on the newly diagnosed patients and working with our commercial team and doctors to get newly diagnosed patients ADCETRIS CHP because the data is so clearly positive. And not just on PFS but on OS and you look at the Kaplan-Meier curves and you'd be hard-pressed to find bigger whitespace between Kaplan-Meier curves in clinical trials. This is a really positive data set that I feel that patients and doctors should really look at this before jumping into a different therapy because they can really be benefited.

那么在PTCL上,看看,我们在那里谈论有关事件患者的数据,这就是我们所看到的,新诊断的事件患者。 所以我们没有很多关于流行的数据。 我的意思是我们仍然批准治疗复发患者,这是我们的标签之一,特别是在CTL中的ALCL和其他一些标签。 但我们真的专注于新诊断的患者,并与我们的商业团队和医生合作,以获得新诊断的患者ADCETRIS CHP,因为数据非常明显。 不仅仅是在PFS上,而是在操作系统上,你看看Kaplan-Meier曲线,你很难在临床试验中找到Kaplan-Meier曲线之间更大的空白。 这是一个非常积极的数据集,我觉得患者和医生应该在进入不同的疗法之前真正关注这一点,因为他们真的可以受益。


Okay. And then one of the things we've heard from some of the community docs is that buying and billing the patient is a real concern for some of the docs with private practices. I was wondering if you guys have heard that. And if so, what efforts could be done to kind of waylay some of those fears and financial concerns of the clinicians?

好的。 然后我们从一些社区文档中听到的一件事是,对某些私人实践的文档来说,购买和计费患者是一个真正的问题。 我想知道你们是否听过这个。 如果是这样的话,可以采取哪些措施来解决临床医生的一些担忧和财务问题?

Clay Siegall

We haven't really heard much about it at all, I have to say. As far as physicians getting reimbursement in PTCL, which is I think what you're looking at, we really have not heard that there's issues out there. We think that our market share is growing in this space as we predicted. We think it was going to take some time to grow and entrench a previously entrenched therapy, and it's -- we're pretty much on track for what we thought the growth rate would be on a quarter-to-quarter basis with the E2 regimen in PTCL. So I don't view what you said, this buying and billing thing, as an issue.

我不得不说,我们根本没有听到太多关于它的内容。 至于医生在PTCL获得报销,我认为你在看什么,我们真的没有听说那里有问题。 我们认为我们的市场份额正如我们预测的那样在这个领域增长。 我们认为这需要一些时间来巩固并巩固以前根深蒂固的治疗方法,而且 - 我们认为,我们认为随着E2方案,我们认为增长率将在四分之一的基础上实现。 在PTCL。 所以我不认为你所说的,这个购买和计费的东西,作为一个问题。


It wasn't limited to E2. I was talking about ADCETRIS and really Hodgkin's lymphoma is, I think, where these comments originated.

它不仅限于E2。 我在谈论ADCETRIS,我认为真正的霍奇金淋巴瘤起源于这些评论。

Clay Siegall

I have to say we're just aren't hearing it in the way you are, so I don't know where this information comes. I'll certainly explore this with the commercial team, but I don't think we are seeing this. Todd, you have a comment?

我不得不说我们只是听不到你的方式,所以我不知道这些信息来自哪里。 我肯定会和商业团队探讨这个问题,但我认为我们没有看到这一点。 托德,你有评论吗?


Well, I was just going to say, the other thing to keep in mind is we have an incredibly efficient model, where a site can order drug today and they'll have it tomorrow. So there isn't this need to buy ADCETRIS and hold it because of a concern or a fear that it's going to take weeks and weeks and weeks for your drug to show up. We're literally overnight shipping.

嗯,我只想说,另外要记住的是我们有一个非常有效的模型,一个网站今天可以订购药物,他们明天会有。 所以没有必要购买ADCETRIS并持有它因为担心或担心药物出现需要数周,数周和数周。 我们真的是隔夜送货。


We'll take our next question from Salveen Richter with Goldman Sachs.

我们将接受Salveen Richter与Goldman Sachs的下一个问题。

Maryana Breitman

This is Maryana Breitman for Salveen. We had a couple. One, we were wondering, with the NCCN updates for Hodgkin lymphoma, do you have any color on changes to prescriber activity due to updated guidelines? And we were also wondering about tucatinib opportunity in metastatic breast cancer, especially in patients with brain metastases, how you're thinking about that opportunity, how you're thinking about going into that market.

这是Salveen的Maryana Breitman。 我们有一对。 其中一个,我们想知道,随着NCCN对霍奇金淋巴瘤的更新,由于更新的指导原则,你对开处方活动的变化有什么颜色吗? 我们也想知道tucatinib在转移性乳腺癌中的机会,尤其是脑转移患者,你如何考虑这个机会,你是如何考虑进入那个市场的。

Clay Siegall

Thank you for the two questions. Concerning the NCCN that you asked, we think that certainly we like the new wording with NCCN, but it's not really -- it's hard to know what that impact will be or what that impact was. We think that the 3-year PFS data that we showed at ASCO and we think that the response from doctors, we think is the most valuable thing that we have because we could tell that they look at that closely.
With NCCN, that also connects with how pathways are and how doctors prescribe it, and those are things that evolve slowly. Pathways don't meet very often at all, and that's -- it takes its own life, and we're not really part of that. But the data and the way doctors respond to this aged data that's improved and really give benefit to the patient, that's really what we think is the most important thing for the increased E1 regimen sales that we're seeing.
Now you asked about tucatinib and the opportunity. Tucatinib is something that -- is a drug that we think could be a best-in-class drug. It's clearly not the first of the HER2 TKIs out there. There are a few of them, so it's a validated pathway. But our goal is to really raise the bar and get to that next level with helping patients with a very potent drug but one that doesn't buy into EGF receptor and cause all that toxicity that you would have with some of the other HER2 TKIs.
As far as the specific benefit in talking about the size of the population, it's a little early for us to do that. We're still doing -- working on our pivotal trial, and it's an event-driven trial. We have guided to later this year for data to come out. And then let's just see what the data -- what happens with the data. And there's plenty of time in the future to talk about the specific opportunity. And I really think it depends on the data.
The primary endpoint is all the patients put together. And then the secondary endpoint includes importantly brain metastases. So this is a unique trial design with a couple of different data sets that will result from the data. And I think that looking at the opportunity for this will really depend on whether this works on all patients, including brain met patients, what works most on one or another set of patients. Then we could adequately start addressing your question. But until then, we'll hold off on it and are excited to address this question in the hopefully not-too-distant future later this year.

谢谢你提出这两个问题。关于您提出的NCCN,我们认为当然我们喜欢NCCN的新措辞,但事实并非如此 - 很难知道这会产生什么影响或影响是什么。我们认为,我们在ASCO展示的3年PFS数据,我们认为医生的反应,我们认为是最有价值的,因为我们可以告诉他们,他们密切关注这一点。

通过NCCN,这也与通路如何以及医生如何处方相关联,这些都是缓慢发展的事物。通路根本不常见,那就是 - 它需要自己的生命,而我们并不是真正的一部分。但是数据和医生对这种老化数据做出反应的方式得到了改善,并且确实给患者带来了好处,我们认为这对于我们所看到的增加的E1方案销售来说是最重要的。

现在你问了关于tucatinib的机会。 Tucatinib是一种我们认为可能是同类最佳药物的药物。它显然不是HER2 TKI中的第一个。其中有一些,所以这是一个经过验证的途径。但我们的目标是真正提高标准并提升到一个新的水平,帮助患有非常强效药物的患者,但不会购买EGF受体,并导致您对其他一些HER2 TKI产生的所有毒性。

至于谈论人口规模的具体好处,我们这样做有点早。我们仍在做 - 致力于我们的关键性试验,这是一个事件驱动的试验。今年晚些时候我们已经引导数据出来了。然后让我们看看数据是什么 - 数据会发生什么。未来有充足的时间来讨论具体的机会。我真的认为这取决于数据。



We'll take our next question from Gena Wang with Barclays.

我们将接受Gena Wang与Barclays的下一个问题。

Gena Wang

Also a follow-up with tucatinib, maybe I will ask. Wondering if you can remind us the event rate of a PFS, and also if the trial designs do -- designed to detect 50% PFS improvement. And another related question regarding the brain met patient, what is the percentage of patients you plan to enroll?

也许是对替考替尼的随访,也许我会问。 想知道你是否可以提醒我们PFS的事件发生率,以及试验设计的确如此 - 旨在检测50%的PFS改善。 关于大脑的另一个相关问题是患者,您计划入选的患者百分比是多少?

Clay Siegall

Okay. So I got your 3 points there. So the event range for the PFS we have not reported, and that's something that we keep confidential. The amount to detect a 50% improvement also is internal information, and that's not something we'd be reporting. We had said that we are planning to enroll, and I know it has, this is true because all the patients are enrolled, that we have roughly half the patients have pre-existing measurable brain mets. And that makes -- that's one of the uniqueness of this trial. We're really addressing a major unmet medical need.

好的。 所以我在那里得到了3分。 因此我们没有报告PFS的事件范围,这是我们保密的事情。 检测到50%改善的数量也是内部信息,而这不是我们要报告的内容。 我们曾经说过我们计划报名,而且我知道它有,这是真的,因为所有患者都参加了,我们大约有一半的患者已经预先存在可测量的脑膜。 这就是 - 这是这次试验的独特性之一。 我们真正解决了未满足的医疗需求。

Gena Wang

Great. And I have one quick follow-up regarding ADCETRIS' quarter revenue. So you mentioned that the majority -- the growth is driven by frontline PTCL. Is it fair to say out of $24 million quarter-over-quarter growth close to $20 million would be from frontline PTCL? And should we expect the future growth mainly driven by the PTCL revenue?

非常好。 我有一个关于ADCETRIS季度收入的快速跟进。 所以你提到大多数 - 增长是由前线PTCL驱动的。 可以公平地说,在前线PTCL中,接近2000万美元的季度环比增长将达到2400万美元吗? 我们是否应该预期未来的增长主要受PTCL收入的推动?

Clay Siegall

I think our prepared remarks said that we're really pleased with the growth in frontline PTCL but we also have growth in frontline Hodgkin lymphoma. We did not look at breaking that apart nor do we plan on breaking apart. I think looking forward, we continue to see that we are getting increased market penetration, and that goes for PTCL, which was approved like almost a year later than Hodgkin lymphoma. Maybe it was early in 2018 to late in 2018. So maybe a little less than a year but -- so frontline Hodgkin lymphoma has been out there a little longer, and its growth rate is probably a little slower at this point just because it's out there a little longer than frontline PTCL. But both are growing, and we're really pleased with what we're hearing from docs out there.
And I know we had a bunch of questions on guidance. It's hard to really give guidance on this. We are in uncharted territory in frontline Hodgkin, frontline PTCL. And the data we have is great. The aged data is great. Doctors are rallying to this. And we're out there trying to do the best we can by patients. And what I would say is stay tuned on this, and we'll provide you with whatever data and follow up that we can when it's appropriate.

我认为我们准备的评论说我们对前线PTCL的增长非常满意,但我们也有前线霍奇金淋巴瘤的增长。我们没有考虑打破这种分歧,也不打算分手。我认为展望未来,我们继续看到我们的市场渗透率正在提高,而PTCL也是如此,它被认可比霍奇金淋巴瘤晚了近一年。也许它是在2018年初到2018年末。所以也许不到一年但是 - 所以前线霍奇金淋巴瘤已经出现了一段时间,而且此时它的增长速度可能稍慢,因为它已经出局了有一点比前线PTCL长一点。但两者都在增长,我们对从那里的文档中听到的内容感到非常满意。



We'll take our next question from Tazeen Ahmad with Bank of America.

我们将接受Tazeen Ahmad与美国银行的下一个问题。

Tazeen Ahmad

Clay, I just wanted to get a sense on the sales force that Todd had talked about you guys have hired. How big of a sales force do you anticipate you'll need for EV in the U.S.? And do you plan on hiring all of the salespeople at once? And then secondly for tucatinib, as that data reads out, I guess, what kind of data should we expect at the top line? What level of efficacy would you consider to be clinically meaningful? And how important is it for you to show a better safety profile than currently approved treatments vis-à-vis especially diarrhea rates?

克莱,我只是想了解托德曾经谈过你们雇佣过的销售人员。 您预计在美国需要多大的销售人员才能使用EV? 你是否计划一次雇佣所有的销售人员? 然后其次是tucatinib,因为数据读出来,我想,我们应该在顶线预期什么样的数据? 您认为具有临床意义的疗效水平如何? 对于您来说,显示出比目前批准的治疗方案更好的安全性与特别是腹泻率相比有多重要?

Clay Siegall

So those are two different questions. Let's start talking about the sales force for EV, and I'd like to turn it over to Robin to kind of explain our thoughts here. Robin?

所以这是两个不同的问题。 让我们开始讨论EV的销售力量,我想把它转交给Robin来解释我们的想法。罗宾?


Sure. Thanks, Clay. So we've worked really closely with Astellas to size the sales force to ensure that we have a broad reach to health care practitioners who treat metastatic bladder cancer. We'll have, with Astellas, an equal number of reps in the field. We will utilize our existing commercial infrastructure for activities such as mass market distribution, but we will also have some brand-specific roles such as the dedicated EV marketing team. And that's really sort of where we stand, which is an equal partnership with Astellas here.

当然。 谢谢,克莱。 因此,我们与安斯泰来密切合作,确定了销售人员的规模,以确保我们能够广泛接触治疗转移性膀胱癌的医疗保健从业人员。 我们将与安斯泰来一起在该领域拥有相同数量的销售代表。 我们将利用现有的商业基础设施进行大众市场分销等活动,但我们也将拥有一些品牌特定的角色,如专门的电子营销团队。 这就是我们的立场,这与安斯泰来在这里是平等的伙伴关系。

Clay Siegall

So the second question is on tucatinib and talking about efficacy and the safety profile. And for sure the reason we acquired Cascadian to largely get this drug is that we saw a really exciting drug from a safety standpoint because it didn't bind to a EGF receptor, and a really exciting drug from an efficacy standpoint in single-arm studies. I'll repeat that, single-arm studies. And the onus is on us to perform in a randomized study in order to get registration. So Rog, can talk about some of what -- give context to where we are?

所以第二个问题是关于tucatinib并讨论疗效和安全性。 可以肯定的是,我们获得Cascadian以获得这种药物的原因是我们从安全的角度看到了一种非常令人兴奋的药物,因为它不与EGF受体结合,而且从单臂研究的功效观点来看,这是一种非常令人兴奋的药物。。 我会再说一遍,单臂研究。 我们有责任在随机研究中进行登记。 所以Rog,可以谈谈一些什么 - 给我们的位置提供背景?


Sure. So as you know, HER2CLIMB is fully enrolled. Just to reiterate some of the points, this is a high unmet need population with a substantial proportion of patients with brain metastases. There is really no historical precedent that we can actually define what the potential for the control arm would be. Based on the profile of tucatinib, its highly selective HER2 addition, its lack of inhibition of EGFR. That is a potential best-in-class molecule. Those characteristics are key to both its efficacy and its safety and its tolerability.
So as Clay said, the data that's been generated with single-arm trials are obviously very encouraging, including with tucatinib and TDM-1, which is why we've proceeded to start another Phase III trial. But until we see the data, it's really -- we can't really make any statements about what the potential treatments will look like.

当然。 如您所知,HER2CLIMB已完全注册。 只是重申一些观点,这是一个高度未满足的需求人群,其中有相当大比例的脑转移患者。 实际上,我们没有任何历史先例可以确定控制臂的潜力。 基于tucatinib的特征,其高选择性HER2的添加,其对EGFR的抑制作用不足。 这是一种潜在的同类最佳分子。 这些特征是其功效和安全性及其耐受性的关键。

正如Clay所说,用单臂试验产生的数据显然非常令人鼓舞,包括使用tucatinib和TDM-1,这就是我们开始进行另一项III期试验的原因。 但在我们看到这些数据之前,我们真的无法对潜在的治疗方法做出任何陈述。

Clay Siegall

What I can say, Tazeen, one thing I can add is that you've seen a lot of data sets come out from other trials. And when you look at PFS in this type of population, it's always measured in terms of months. So the first thing I could tell you from that, whenever I see that in my decades of doing cancer work, it says to me loudly, unmet medical need.
So we're in an area where patients need something. They don't just walk away saying, "Yay, there's drug X or drug Y. I'm cured." It's not where it is. We're talking a lot of these patients, they get a drug and respond for -- measured in months. So we have a really big important area to go into.
And when you have brain metastasis, which literally half the patients get, there's not anything really out there. So it's a grim prognosis, and we're trying to really do a good job and help patients and work on this drug. So data, it's coming soon sometime this year. We are incredibly excited.
And I'll remind you, we really loved all the data from single-arm trials. We just thought they were outstanding, and this was the right drug. But we do not yet have the randomized data and FDA rightly wants in this setting with all the other drugs. They want to see randomized data. And we're up to that challenge, and we're looking forward to reporting it.


所以我们在一个患者需要的地方。他们不只是走开说:“是的,有药物X或药物Y.我已经治好了。”它不是它的位置。我们正在谈论很多这些患者,他们得到药物并做出反应 - 用数月来衡量。所以我们有一个非常重要的领域。



Tazeen Ahmad

Okay. And then just on safety, Clay, to wrap that up, how are you thinking about diarrhea rates? Do you think that's an important differentiator in this population? Or is it, as you said, when you have PFS in the months that this is a high unmet medical need area, and any improvement is a good improvement?

好的。 然后就安全,克莱来说,把它包起来,你怎么想腹泻率呢? 你认为这是这个人群中一个重要的差异化因素吗? 或者,就像你说的那样,当你在几个月内有PFS时,这是一个高度未满足的医疗需求领域,任何改善都是一个很好的改善?

Clay Siegall

I would go back to our early data on this drug because obviously we've not reported data from this pivotal trial. And early data shows a dramatic difference in any GI toxicity. You just don't bind EGF receptor. I'll remind you that both the first two HER2 tyrosine kinase inhibitors that were approved both bind to HER2 and inhibit the tyrosine kinase but both of them bind to EGF receptor. And I don't believe that they were screened to not bind to EGF receptor. I think they were screened specifically for the HER2 TKI activity. Whereas tucatinib was screened with not only getting something potent for HER2 TKI but screened that it didn't bind to EGF receptor. So this is what's unique about this drug.
And if you look at the safety profile for literally hundreds of patients that were treated in single-arm trials, it's -- from a standpoint of comparison to the others that are out there, it's pretty dramatically different. So I think that I feel very confident about safety profile. We're -- we just didn't know is in a randomized trial versus active competitor, how would you -- how would it come out? And Roger, do you have anything? Do you want to add anything to that?

我会回到我们关于这种药物的早期数据,因为很明显我们没有报告这项关键试验的数据。早期数据显示任何GI毒性都有显着差异。你只是不结合EGF受体。我要提醒你,前两种被批准的HER2酪氨酸激酶抑制剂都与HER2结合并抑制酪氨酸激酶,但它们都与EGF受体结合。我不相信他们被筛选不与EGF受体结合。我认为他们是专门针对HER2 TKI活动筛选的。而对tucatinib进行筛选时不仅能够获得对HER2 TKI有效的物质,而且筛选出它不与EGF受体结合。所以这就是这种药物的独特之处。

如果你看一下几百名接受过单臂试验治疗的患者的安全性,那么从相对于其他患者的比较的角度来看,这是非常不同的。所以我认为我对安全概况非常有信心。我们 - 我们只是不知道是在一个随机试验中与活跃的竞争对手,你怎么样 - 它怎么会出来?还有罗杰,你有什么事吗?你想添加任何东西吗?


No, I do. So I think just as a case in point around the safety profile, I'll just remind you that HER2CLIMB is a blinded -- is a placebo-controlled trial. And in general, placebo-controlled trials can only be done if you're unable to tell which drug you're on, placebo or the active agent. So that's an important point to remember. And secondly, in a disease like breast cancer, which is a chronic disease, tolerability is key. If you're taking a drug twice a day and you can't take it for too long, it's not just is it a safety issue. It can potentially feed into efficacy as well. So I think those 2 points are really of some consideration.

不,我做。 所以我认为就安全概况而言,我只是提醒你,HER2CLIMB是盲目的 - 是一项安慰剂对照试验。 一般而言,安慰剂对照试验只有在您无法分辨您使用的药物,安慰剂或活性剂时才能进行。 所以这是一个值得记住的重点。 其次,在像乳腺癌这种慢性疾病这样的疾病中,耐受性是关键。 如果你每天服用两次药物并且你不能服用太长时间,那么这不仅仅是一个安全问题。 它也可能有助于提高疗效。 所以我认为这两点确实值得考虑。


We'll take our next question from Stephen Willey with Stifel.

我们将接受Stephen Willey的下一个问题和Stifel。


Congrats on a really good quarter. Just a quick question on PTCL and one on tucatinib. So just curious to what extent screening for CD30 expression may or may not represent a rate-limiting step for ADCETRIS right now in PTCL, either from just the utilization or reimbursement perspective. And I guess how does the recent data demonstrating that the ADCETRIS benefit is agnostic to CD30 expression potentially change that?

恭喜一个非常好的季度。 关于PTCL的一个简单问题和关于tucatinib的一个问题。 因此,仅仅从使用或报销的角度来看,CD30表达的筛选在多大程度上可能或可能不代表ADCETRIS目前在PTCL中的限速步骤。 我想最近的数据如何证明ADCETRIS的益处与CD30表达无关,可能会改变这种情况?

Clay Siegall

So certainly, at ASCO you saw the presentation from the docs that said that they had responses whether patients were CD30 high or CD30 low or even CD30 without even being able to -- through histology be able to see it. Now when you -- historically, we've looked at all these patients, and you can look them with histology.
Histology has a very big gray area background noise. So when you get down to lower levels of CD30, it's impossible to know whether it's positive or negative. You can just say, histology and negative, but that doesn't mean negative. And you look at molecularly and -- we are hard-pressed to find a lymphoma that's -- a T-cell lymphoma that's CD30 negative when you look at it molecularly. And also, CD30 is an activation antigen, and it kind of goes up and down. And when you look at different nodules, you can even find different amounts of CD30 within the same patient. So it is a very complicated scenario where the prediction would be that all patients respond because CD30 is there in all and can go up and down. And in fact, that is exactly what the doctors showed in their presentation at ASCO.
So I think to the utility of it in different subtypes and based on all our data and everything we know, I think we have a really good case there that doctors should use this and it could benefit patients. So I certainly don't think that hurts. And you had a second question on tucatinib?

当然,在ASCO,您看到了文档的演示文稿,他们说他们对患者CD30高或CD30低甚至CD30有反应,甚至无法通过组织学能够看到它。现在,当你 - 从历史上看,我们已经看过所有这些患者,你可以用组织学来看待它们。

组织学具有非常大的灰色区域背景噪声。因此,当你降低CD30的水平时,不可能知道它是正面的还是负面的。你可以说,组织学和消极,但这并不意味着消极。而且你从分子上看 - 我们很难找到一种淋巴瘤 - 一种T细胞淋巴瘤,当你从分子上看它时CD30阴性。而且,CD30是一种活化抗原,它有点上下起伏。当您观察不同的结节时,您甚至可以在同一患者体内找到不同数量的CD30。因此,这是一个非常复杂的情况,预测所有患者都会做出反应,因为CD30一直存在并可以上下移动。事实上,这正是医生在ASCO的演讲中所表现出来的。



Yes, just a quick follow-up on that then. I guess, if there were a mechanism by which you could remove that CD30 expression requirement from the label, would that change the narrative of uptake, do you think?

是的,那就是对此的快速跟进。 我想,如果有一种机制可以从标签中删除CD30的表达要求,那会改变摄取的叙述,你觉得呢?

Clay Siegall

Our requirement on there is if -- I mean in Hodgkin lymphoma, it's not there at all. And in T-cell lymphoma, it's just says CD30 positive. So it's not like -- I mean it could be a trace of it and be positive. So we don't find it as an impediment at all, quite frankly.

我们的要求是 - 我的意思是在霍奇金淋巴瘤中,它根本不存在。 在T细胞淋巴瘤中,它只是说CD30阳性。 所以它不是 - 我的意思是它可能是它的痕迹并且是积极的。 坦率地说,我们根本不认为这是一个障碍。


Okay. And then just for clarification on tucatinib, I know that you're talking about another study here in combination with TDM-1 in the second line. Just want to clarify if the initiation of that trial is contingent upon HER2CLIMB data.

好的。 然后只是为了澄清tucatinib,我知道你在谈论另一项研究,结合第二行的TDM-1。 只想澄清该试验的开始是否取决于HER2CLIMB数据。

Clay Siegall

Roger, do you want to comment on that?



No, it's not. It's the -- we believe it's the right time, tucatinib, all the properties we've described. This is again a validated pathway, and we've generated the Phase I data which supports the combination. And we think it's the right time to proceed in that direction.

不,这不对。 它是 - 我们相信这是正确的时间,tucatinib,我们所描述的所有属性。 这又是一个经过验证的途径,我们已经生成了支持该组合的第一阶段数据。 我们认为现在是朝着这个方向前进的最佳时机。


We'll take our next question from Shanshan Xu with Berenberg Capital Markets.

我们将接受Shanshan Xu与Berenberg Capital Markets的下一个问题。

Shanshan Xu

I have one question for Roger. If the upcoming readout of HER2CLIMB is positive, how should we think about expanding indications beyond breast cancer for tucatinib? And I have one follow up for EV.

我对罗杰有一个问题。 如果即将发布的HER2CLIMB读数为阳性,那么我们应该如何考虑扩大乳腺癌以外的适应症? 我有一个跟进EV。


Sure. Thanks for the question. So as we all know, we have tucatinib being incorporated into us by looking at neoadjuvant applications. You see HER2CLIMB in the multiple-treated population. We're now moving into second-line metastatic breast cancer. We have an investigator-initiated trial called MOUNTAINEER, which has data combining tucatinib together with Herceptin in a third-line-plus colorectal cancer population. We hope to have that data out later this year.
I think, again, if tucatinib turns out to be the potential best-in-class, it realizes its potential than anywhere that a TKI can have a role in a HER2 expressing tumor is where we will want to go. So that includes CRC. It includes other stages of breast cancer, potentially gastric cancer. There are other cancers that are HER2 expressing that could be of interest as well. So I think if we have a real molecule here we will flesh out the development plan as appropriately, fully as we can.

当然。 谢谢你的提问。 众所周知,通过研究新辅助应用,我们将tucatinib纳入我们的行列。 您在多重治疗人群中看到HER2CLIMB。 我们现在正在进入二线转移性乳腺癌。 我们有一项名为MOUNTAINEER的研究者发起的试验,该试验的数据包括将tucatinib和赫赛汀联合用于三线加结直肠癌人群。 我们希望在今年晚些时候获得这些数据。

我认为,再次,如果tucatinib成为潜在的最佳类,那么它实现了它的潜力,而不是TKI可以在HER2表达肿瘤中发挥作用的任何地方,这是我们想要去的地方。 所以这包括CRC。 它包括乳腺癌的其他阶段,可能是胃癌。 HER2表达的其他癌症也可能是有意义的。 因此,我认为如果我们在这里有一个真正的分子,我们将尽可能充分地充实发展计划。

Clay Siegall

I think it's a good proposition for a breast cancer oncologist if our data turns out the way we think it could with HER2 clients to have a tablet that's well tolerated and really works. I think would be -- this would be a really important drug and will get a lot of use in -- and will be in many different line and -- of therapy, in breast cancer and outside of it. So go ahead, you had an EV question?

我认为对于乳腺癌肿瘤学家来说,这是一个很好的建议,如果我们的数据证明了我们认为HER2客户能够拥有一个耐受性良好且真正有效的平板电脑的方式。 我认为 - 这将是一种非常重要的药物,并将在乳腺癌及其外的许多不同的疗法和治疗中得到广泛应用。 那么继续,你有一个EV问题?

Shanshan Xu

Yes, I absolutely agree with your commentary on tucatinib. One follow up on EV. So we witnessed a very impressive data of EV-201, which is a third-line trial. In EV-201 the median OS is only 2 to 3 months shorter than the standard of care in frontline urothelial carcinoma. So I believe this is actually in everyone's interest to move EV into the pivotal trial of the frontline urothelial carcinoma. In the past ASCO, we saw that it took CALGB-90601 almost 5 years to achieve its full enrollment. So Roger and Clay, what are potential drivers to accelerate enrollment for frontline urothelial carcinoma trial for EV?

是的,我绝对同意你对tucatinib的评论。 一个跟进EV。 因此,我们目睹了一个非常令人印象深刻的EV-201数据,这是一个三线试验。 在EV-201中,中位OS仅比前尿路上皮癌的标准治疗短2至3个月。 因此,我认为将EV转变为前线尿路上皮癌的关键试验实际上符合每个人的利益。 在过去的ASCO中,我们看到CALGB-90601用了将近5年的时间才达到完全注册。 那么罗杰和克莱,加速EV前线尿路上皮癌试验的潜在推动因素是什么?

Clay Siegall

First of all, I want to make a commentary before getting to your question on EV. We have not had a single question from many analyst or comment from any analyst to the speed with which we submitted EV. We busted our back and submitted this much faster. We guided that it will be submitted sometime this year, and it's July. And we submitted it in the middle of July, so this is months ahead of where most if you had in your models. I think most of you had sometime in the middle of fall in your models. So I would like the analysts to notice that, which I think will translate into getting this product on the market faster.
And it's an important product that doctors are screaming for. So this is part and parcel into we're trying to make a difference in patients' lives, and we, together with Astellas, worked like morning, noon and night on getting this to a submission because it's important, okay? This isn't just a Wall Street thing. It's a patient thing. And so I want everyone to notice how fast we worked on this. Secondly, we are excited about the potential of EV in frontline, and there's a lot of different approaches. Roger, do you want to give context to that?




Sure. So if you can look back into the EV 103 trial, and you can understand what our potential choices are. It's EV is the backbone, with a PD-1 inhibitor, plus/minus chemotherapy. Those are the types of choices that we're facing. I must say I agree with you. This frontline metastatic urothelial cancer is still a high unmet need. I think personally if we come up with a very thoughtful, considerate, acceptable trial design, the excitement around the combination of EV with other drugs, once we have that data presented that would support that will drive a lot of the enrollment. Bladder cancer has changed because all of the immunotherapies that come in, and there's a lot of interest now. And bladder cancer doctors are focused on moving trials ahead, whereas in past times where there was really just chemotherapy versus chemotherapy, not an interesting question, not an exciting question to answer. That's possibly why the CALGB trial was so slow. I would hope that we would be way quicker than anything like that.

当然。因此,如果您可以回顾一下EV 103试验,您就可以了解我们的潜在选择。 EV是骨干,有PD-1抑制剂,加/减化疗。这些是我们面临的选择类型。我必须说我同意你的意见。这种前线转移性尿路上皮癌仍然是一个很高的未满足需求。我个人认为,如果我们提出一个非常周到,体贴,可接受的试验设计,将EV与其他药物结合起来的兴奋,一旦我们提供了支持这一点的数据将推动大量的注册。膀胱癌发生了变化,因为所有的免疫疗法都进来了,现在有很多兴趣。而膀胱癌医生则专注于提前进行试验,而在过去几乎只有化疗与化疗相比,这不是一个有趣的问题,而不是一个令人兴奋的问题。这可能是为什么CALGB试验如此缓慢的原因。我希望我们比这样的事情更快。


We'll take our next question from Andy Hsieh with William Blair.


Andy Hsieh

Congratulations to the Seattle Genetics team. It's nice to see that inflection point commercially. So I have two questions. One is probably for Roger. So could you remind us the specificity and potency of tucatinib, specifically pertaining to HER2 mutants, and if that is potential differentiator versus other oral TKIs?

恭喜Seattle Genetics团队。 很高兴看到商业上的拐点。 所以我有两个问题。 一个可能是罗杰。 您是否可以提醒我们tucatinib的特异性和效力,特别是与HER2突变体相关的,如果这是与其他口腔TKI相比的潜在区别?


Thanks for the question, Andy. We are interested in the mutant population. We haven't studied it, so that's something that we need to potentially move forward on. Tucatinib is very similar to neratinib in terms of its HER2 selectivity and potency. They are very close. So the ability to inhibit the target with tucatinib is as good as any other sort of the most potent inhibitor currently available, which is neratinib. Again, coming back to the HER2 mutants, we're interested. Again, anywhere where there's a potential role for tucatinib, we need signal find. So that's for our future efforts.

谢谢你的问题,安迪。 我们对突变种群感兴趣。 我们还没有研究过它,所以我们需要继续前进。 就其HER2选择性和效力而言,Tucatinib与neratinib非常相似。 他们非常接近。 因此,用tucatinib抑制靶标的能力与目前可用的任何其他最有效的抑制剂一样好,即neratinib。 再次回到HER2突变体,我们感兴趣。 同样,在任何可能对tucatinib有潜在作用的地方,我们都需要信号查找。 这就是我们未来的努力。

Clay Siegall

Andy, we believe that -- and this is based on data like with Herceptin, for instance, in HER2 TKIs when you keep pressure on the tumor in a patient, the patient does better. And that's what you see with other agents. And one of the things about these HER2 TKIs is if they're really toxic you can't keep pressure on the tumor. You have to discontinue and not enable the patient to get therapy. So it's not -- as Roger said before, it's not just a safety issue, it also relates to efficacy. And that's what we saw when we did a lot of diligence on this. We saw that this could change the paradigm and raise the bar and allow for a TKI to keep pressure on the tumor for a substantive period of time, and that's really what's important.

安迪,我们相信 - 这是基于像赫赛汀这样的数据,例如,在HER2 TKIs中,当你对患者的肿瘤施加压力时,患者会做得更好。 这就是你和其他代理商所看到的。 关于这些HER2 TKI的一个问题是如果它们真的有毒,你就不能对肿瘤施加压力。 您必须停止并且不允许患者接受治疗。 所以它不是 - 正如罗杰之前所说,它不仅仅是一个安全问题,它还与功效有关。 这就是我们在这方面做了很多努力时所看到的。 我们看到这可能会改变范式并提高标准并允许TKI在相当长的一段时间内对肿瘤施加压力,这才是真正重要的。

Andy Hsieh

Just as a follow-up, and this pertains to EV. So most of the time when you go from early Phase Ib to Phase III of any pivotal studies, you take sort of a response rate PFS duration penalty. Just curious, have you identified kind of any factors that contribute to just the impressive consistency across these -- the early-stage pooled analysis and the 201 top line results?

就像后续行动一样,这与EV有关。 因此,大多数情况下,当您从任何关键研究的早期阶段Ib进入阶段III时,您会采取某种响应率PFS持续时间罚分。 只是好奇,您是否已经确定了哪些因素可以促成这些因素之间令人印象深刻的一致性 - 早期汇总分析和201个顶线结果?

Clay Siegall

I will tell you that the clinical team at Seattle Genetics and certainly had been the case prior to Roger joining, but even emphasized more with Roger is we don't want to get too overexcited about Phase I data unless we do blinded third-party reviews and things like that. So we want to look at not just responses. We look at confirmed responses. So when you see Seattle Genetics' data for Phase I and it says confirmed responses, the chance that, that will repeat in a bigger study is pretty high because these have already been stared at, where I see a lot of times companies put out data, and they're unconfirmed responses. And then you see that later, and it's a much smaller response rate and much less duration, and all these things. And that's because they weren't as fastidious as we are. We're more interested at this point -- or at all points in Seattle Gen's history, we've been interested in actually making substantive improvements in patients lives with unmet medical needs and not just getting a little bit of hype on some drugs. So we want the real data out there, and I think that's what contributes to our early-stage data matching pretty closely to the pivotal because we do it the same way, with the same rigor. Roger, any addition?

我会告诉你,西雅图遗传学的临床团队在Roger加入之前肯定是这样的,但是甚至更加强调Roger,我们不希望过于过度兴奋第一阶段的数据,除非我们对第三方评论进行盲法和那样的事情。因此,我们不仅要考虑回应。我们看一下确认的回复。所以当你看到西雅图遗传学的第一阶段的数据并且它说明了确认的答案时,在一项更大的研究中重复的可能性相当高,因为已经盯着这些,我看到很多时候公司发布了数据,他们是未经证实的回应。然后你会看到它,这是一个小得多的响应率和更短的持续时间,以及所有这些东西。那是因为他们并不像我们那样挑剔。我们对这一点更感兴趣 - 或者在西雅图根历史的所有方面,我们一直有兴趣实际改善患者生活中未满足的医疗需求,而不只是对某些药物进行一些宣传。所以我们想要那里的真实数据,而且我认为这对于我们的早期数据匹配非常接近关键因素,因为我们以相同的方式,同样的严谨性。罗杰,还有什么?


Two other comments. So firstly, good drugs really work, and when they really work, they really work again and again. That's certainly one part of this. The other is just bear in mind the sample sizes are not 10 patients or 20 patients. We're talking 100 plus. And so the variability around those contrast intervals is much smaller than a very small sample size where you can potentially get yourself in a misled. So it's great that the data is reproducible. You're right. Many times, the Phase I experiences that Clay described degrade over time, and that's obviously not something that anyone likes to see. But certainly, with EV, we have not had that experience. And so it does bode well for the future of the drug.

另外两条评论。 首先,好的药物确实起作用,当它们真正起作用时,它们真的一次又一次地起作用。 这当然是其中的一部分。 另一个是牢记样本量不是10名患者或20名患者。 我们说100加。 因此,围绕这些对比度间隔的可变性远小于非常小的样本量,在这种情况下,您可能会误入歧途。 因此,数据的可重现性非常好。 你是对的。 很多时候,Clay描述的第一阶段经历随着时间的推移会降低,这显然不是任何人都喜欢看到的东西。 但当然,有了EV,我们还没有那种经历。 因此它对药物的未来有利。

Andy Hsieh

Super helpful context.



We'll take our final question from Silvan Tuerkcan with Oppenheimer.

我们将从Silvan Tuerkcan和奥本海默那里得到我们的最后一个问题。

Silvan Tuerkcan

Congrats on the quarter and the submission. Could you please give us a little bit more color on your prelaunch activities for EV outside of the sales force, such as maybe interactions with payers you have? And also is there any strategy that leaps out at you in terms of how you can roll this out quickly in terms of what centers to target?

祝贺季度和提交。 您是否可以在销售人员之外的EV预发布活动中为我们提供更多颜色,例如您可能与付款人进行互动? 还有什么策略可以在你如何根据目标中心快速推出这个策略的过程中突然出现?

Clay Siegall

First of all, I will thank you for the question. I mean we are putting in a very large amount of effort on our prelaunch activities for EV, and it's across the board in lots of different areas. I mean this is -- this drug's the real deal. So we're not going in for a soft launch. We're going in for the full launch. No soft, light share in EV for sure. Robin, you want to put this in context?

首先,我将感谢你提出这个问题。 我的意思是我们正在为EV的预发布活动投入大量的精力,而且它在很多不同领域都是全面的。 我的意思是这 - 这种药是真正的交易。 因此,我们不会进行软启动。 我们正在进行全面发布。 在EV中没有柔软,轻盈的份额。 罗宾,你想把它放在上下文中吗?


Yes, certainly, Clay. Like any new product launch, you need to be prepared for everything that you're going to be doing at approval. And as you say, that's not just preparing the sales force in terms of the training materials, it's also understanding the payer environment. It's preparing the rest of the organization, and also outside of commercial. So on the medical side, our medical affairs organization will be prepared. And of course, we've been preparing for months already, even more than a year in terms of thinking through the brand strategy and how we're actually going to position this product in the market. And so all of these elements -- and I think what I said is that my experience in oncology launches, what I saw coming into Seattle Genetics is the team that is very prepared. I was really impressed.

是的,当然,克莱。 与任何新产品发布一样,您需要为将要批准的所有内容做好准备。 正如您所说,这不仅仅是根据培训材料准备销售人员,而且还了解付款人环境。 它正在为组织的其他部门做准备,也在商业之外。 所以在医疗方面,我们的医疗事务组织将做好准备。 当然,我们已经准备好了几个月,甚至超过一年的时间来思考品牌战略以及我们如何实际将这个产品定位于市场。 所有这些元素 - 我想我说的是我在肿瘤学方面的经验,我看到进入西雅图遗传学的是那个做好充分准备的团队。 我印象非常深刻。

Silvan Tuerkcan

Great. And do you expect an AdCom [ph]?

非常好。 您是否期望AdCom [ph]?

Clay Siegall

We can never make a comment on whether there's an AdCom [ph] or not. It's not our decision. But we do have breakthrough therapy designation, and I think that -- I don't want to handicap this, actually. But we're thinking pretty positively about this drug. Roger, any addition?

我们永远不会评论是否存在AdCom [ph]。 这不是我们的决定。 但我们确实有突破性的治疗指定,我认为 - 实际上,我不想让这个有所障碍。 但我们对这种药物的看法非常积极。 罗杰,还有什么?


Agree. I agree.

同意。 我同意。

Silvan Tuerkcan

Maybe just quickly for tucatinib, I think that brain metastases will be very important, and it's great that you're studying it. What -- do we have seen any data on activity in brain metastases to date in earlier trials? And will this data be top line at the same time you may put top line to PFS of the entire trial? Will it be mature enough at that point?

也许只是快速用于替考替尼,我认为脑转移非常重要,你正在研究它是很好的。 什么 - 我们在早期试验中看到过有关脑转移活动的数据吗? 这个数据是否会成为顶线,同时您可能会将整个试验的PFS列为顶线? 那时它会成熟吗?

Clay Siegall

So there has been data early on in looking in single-arm trials, not in a randomized setting, at brain metastasis, and it was relatively really nice data. That was something that stuck out at us as we reviewed this, that we were surprised with -- not surprised but we were pleased, I should say, with seeing the data in brain mets that we did with a single-arm trial. Yes, you have to do this in a randomized trial to prove it, but the data in brain mets was well -- was better, considerably better, than you would've expected to see in populations of brain met patients based on looking at other drugs in historic studies. But you have to do the randomized study. So that's that. Roger, any other comments on this?

因此,早期有关于单臂试验的数据,而不是随机设置,脑转移,这是相对非常好的数据。 当我们对此进行评论时,我们感到非常惊讶 - 这并不令我感到惊讶,但我们应该说,我们很高兴看到我们用单臂试验做的脑部数据。 是的,你必须在一项随机试验中做到这一点来证明这一点,但是大脑中的数据很好 - 比你期望在脑部患者群中看到的更好,更好,基于看其他人 历史研究中的药物。 但你必须做随机研究。 就是这样。 罗杰,还有其他任何评论吗?


I agree. For the data that we've generated, clearly tucatinib is active in brain metastasis. I think there's no doubt. And so it's a matter of how active in the combination that we're testing. With regard to what we'll release top line, I don't think we'll get into any specifics about what data would be obtained in that release.

我同意。 对于我们生成的数据,显然tucatinib在脑转移中具有活性。 我认为毫无疑问。 因此,我们正在测试的组合中的活跃程度如何。 关于我们将发布的顶线,我认为我们不会详细了解该版本中将获得哪些数据。

Clay Siegall

Yes, that's premature to say what we'll exactly release. Now our goal would be to release everything that we possibly can while retaining the ability for doctors to present this at an appropriate peer-reviewed large conference. And I mean breast cancer work is normally presented at conferences such as the San Antonio meeting, which specializes in breast cancer, but also it is at ASCO and ESMO and some other cancers. But the San Antonio conference is clearly the premier breast cancer conference. Or it's evolved to being the premier breast cancer conference. It didn't use to be that way, but it is now.

是的,现在说出我们将要发布的内容还为时过早。 现在我们的目标是释放我们可能做的所有事情,同时保留医生在适当的同行评审的大型会议上展示这一点的能力。 我的意思是乳腺癌工作通常出现在会议上,例如专门研究乳腺癌的圣安东尼奥会议,但也有ASCO和ESMO以及其他一些癌症。 但圣安东尼奥会议显然是首要的乳腺癌会议。 或者它已经发展成为首屈一指的乳腺癌会议。 它不是那样用的,但它现在是。


Ladies and gentlemen, this concludes today's question-and-answer session. I would like to turn the conference back to your speakers for any additional or closing remarks.

女士们,先生们,今天的问答环节结束了。 我想将会议重新发送给您的发言人,以获取任何其他或结束语。

Clay Siegall

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

好的。 感谢操作员,感谢大家今天下午加入我们。 祝你晚安。


Ladies and gentlemen, this concludes today's conference. We appreciate your participation.

女士们,先生们,今天的会议结束了。 感谢您的参与。


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