Genmab A/S (OTCPK:GNMSF) Q2 2019 Results Conference Call August 14, 2019 12:00 PM ET
Genmab A / S（[OTCPK：GNMSF]）2019年第二季度业绩电话会议2019年8月14日中午12:00东部时间
Jan van de Winkel - President and CEO
David Eatwell - CFO
- Jan van de Winkel - 总裁兼首席执行官
- David Eatwell - 首席财务官
Kennen MacKay - RBC Capital Markets
James Quigley - J.P. Morgan
Wimal Kapadia - Bernstein
Connor Meehan - Morgan Stanley
Michael Schmidt - Guggenheim
Peter Verdult - Citi
Peter Welford - Jefferies
Michael Novod - Nordea
Graig Suvannavejh - Goldman Sachs
Emily Field - Barclays
- Kennen MacKay - 加拿大皇家银行资本市场
- 詹姆斯奎格利 - J.P.摩根
- Wimal Kapadia - 伯恩斯坦
- Connor Meehan - 摩根士丹利
- 迈克尔施密特 - 古根海姆
- Peter Verdult - 花旗
- Peter Welford - Jefferies
- 迈克尔诺维德 - 诺尔达
- Graig Suvannavejh - 高盛
- 艾米莉菲尔德 - 巴克莱
Welcome to Q2 Report 2019 Conference Call. During this telephone conference, you may be presented with forward-looking statements that include words such as believes, anticipates, plans or expects. Actual results may differ materially, for example, as a result of delayed or unsuccessful development projects. Genmab is not under any obligation to update statements regarding the future, nor to confirm such statements in relation to actual results, unless it is required by law.
Now, I would like to hand the call over to your speaker today, Jan van de Winkel. Please go ahead, sir.
欢迎参加2019年第二季度电话会议。 在此电话会议期间，您可能会收到前瞻性陈述，其中包括诸如信念，预期，计划或预期等词语。 实际结果可能会有很大差异，例如，由于延迟或不成功的开发项目。 除非法律要求，否则Genmab没有义务更新有关未来的陈述，也无义务确认与实际结果相关的陈述。
现在，我想把这个电话交给你的演讲者Jan van de Winkel。 请继续，先生。
Jan van de Winkel
Hello and welcome to the Genmab conference call to discuss the Company's financial results for the quarter ended June 30, 2019. Our CFO, David Eatwell is joining me on today's call.
Let's move to slide two. As already said in the introduction, we will be making forward-looking statements. So, please keep that in mind as we go through this call.
Let's move to slide three. The second quarter of 2019 brought transformational change to Genmab as we began the process of becoming a dual-listed company, a process it’s concluded with a great success in July, as Genmab is now trading on both the NASDAQ Copenhagen Stock Exchange, and the Nasdaq Global Select Market in the U.S.
I'm very proud to share with you that with the closing of our offering, Genmab achieved the largest biotech IPO by market cap in 20 years, the largest IPO of American Depository Shares by European healthcare company, and the second largest U.S. IPO ever by a biotechnology company. This tremendous accomplishment will not only help us to achieve our ambitious 2025 vision of having our own product on the markets and the pipeline of knock-your-socks-off antibodies, we believe that it'll increase Genmab’s visibility as a world class innovation powerhouse within the biotech industry and among key thought leaders and academia and in the financial community.
We also built upon our already successful relationship with Janssen during the quarter with the signing of an agreement to collaborate exclusively on the next-generation CD38 antibody product candidate, HexaBody-CD38. We saw encouraging preclinical data from HexaBody-CD38 in multiple myeloma, lymphoma and leukemia models, and believe it has significant potential to extend the promise of CD38 targeted therapies beyond what is currently available to patients.
Additional developments for our pipeline occurred in May with the first patient dosed in the first in-human Phase 1/2 trial of DuoBody-PD-L1x4-1BB in solid tumors. This is a product candidate we are co-developing with BioNTech, and we are looking forward to watching its progress through the clinic.
More recently, at the beginning of July, Horizon Therapeutics submitted a Biologics License Application for teprotumumab, a product that Genmab created for the treatment of active thyroid eye disease. If approved, teprotumumab will become the third product originally created by Genmab to enter the market.
Of course, DARZALEX also experienced significant momentum over the past few months, first and foremost with the highly anticipated approval from the U.S. FDA, based on the Phase 3 MAIA trial of daratumumab combined with lenalidomide and dexamethasone in patients newly diagnosed with multiple myeloma, who are ineligible for autologous stem cell transplant. The combination of lenalidomide and dexamethasone or Rev/Dex is broadly used in the U.S. for this patient population. And we are extremely pleased that these patients will now have the opportunity to add DARZALEX to their treatments.
As important as this approval is, it was not the only key recent development for DARZALEX. The U.S. FDA also granted priority review to the supplemental Biologics License Application based on an impressive aggressive data from the Phase 3 CASSIOPEIA. This combined daratumumab with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma, who are candidates for autologous stem cell transplant.
当然，DARZALEX在过去几个月也经历了显着的发展势头，首先是美国FDA的高度期待，基于Daratumumab联合来那度胺和地塞米松治疗新诊断为多发性骨髓瘤的3期MAIA试验，没有资格进行自体干细胞移植。来那度胺和地塞米松或Rev / Dex的组合在美国广泛用于该患者群体。我们非常高兴这些患者现在有机会将DARZALEX添加到他们的治疗中。
U.S. FDA set a PDUFA date of September the 26th. And while, mostly a European regimen, we very much look forward to the possibility of this combination becoming yet another option for multiple myeloma patients in need.
And then, just after the end of the quarter, we reported top line data from the Phase 2 GRIFFIN study of newly diagnosed patients with multiple myeloma eligible for high dose chemotherapy and autologous stem cell transplantation who were treated with either daratumumab in combination with lenalidomide, bortezomib and dexamethasone or VRd versus VRd alone. The study met its primary endpoints, demonstrating a higher percentage of stringent complete responses for the patients who received daratumumab as part of their treatments. This data builds on the efficacy and safety data for daratumumab as a frontline treatments for transplant eligible multiple myeloma patients as seen in the CASSIOPEIA study and it also underlines Janssen decision to begin the Phase 3 PERSEUS and Phase 3 CEPHEUS studies of daratumumab in combination with the same therapies, VRd, for certain frontline multiple myeloma indications.
In mid-July, Janssen also submitted application for approval of the subcutaneous formulation of daratumumab to regulatory authorities in both the U.S. and Europe. Should these submissions lead to approval that would provide patients with the subcutaneous delivery option that reduces treatment time from hours to just five minutes, not only would this be more convenient for patients, but as we saw with the COLUMBA study data, presented at the 2019 ASCO Annual Meeting in Chicago, and the 24th European Hematology Association Annual Congress in Amsterdam, infusion-related reactions are both mild and significantly reduced with this formulation of daratumumab.
Lastly, sales of DARZALEX continue to be very strong with net sales reaching over $1.4 billion in the first six months of 2019, resulting in DKK 1,169 million in royalties to Genmab.
I'm now pleased to hand over the call to David to present our financial results for the first six months of this year. David?
Thank you, Jan.
Over the next few slides, I'll highlight the results for the first six months of 2019 as well as this year's financial guidance.
Starting with the income statement. The revenue for the period came in at DKK 1,365 million. That's an increase of DKK 174 million, or 15% compared to the first half of 2019. The increase was primarily driven by higher DARZALEX royalties, driven by year-on-year increase in DARZALEX sales of 49%. And that was partly offset by the Arzerra onetime payment of $50 million or DKK 304 million in 2018.
As anticipated, the total expenses for the first half of 2019 were DKK 1,254 million, an increase the DKK 522 million or 71%. This was driven by the advancement of our clinical products including enapotamab vedotin and tisotumab vedotin as well as our other pipeline products and new CTAs. As planned, we also increased the number of employees to support our pipeline expansion.
For our operating result. We had an operating income of DKK 111 million in the first half of 2019 compared to DKK 459 million in the same period in 2018. The decrease of DKK 348 million or 76% was driven by higher operating expenses and the one-off payment from Novartis in Q1 2019.
The net financial items were a net income of DKK 93 million in the first half of ‘19, compared to DKK 132 million in the first half of 2018. The main driver for the variance between the two periods is foreign exchange rate movements, which positively impacted our U.S. dollar denominated portfolio and cash holdings for both periods, but to a lesser extent in 2019.
The corporate tax expense for the first half of 2019 was DKK 47 million, compared to DKK 132 million in the same period in 2018. The estimated annual effective corporation tax rate for the first half of ‘19 was 23%, compared to 22% in the first half of 2018.
And that brings us to the net result, which was a net income of DKK 157 million for the first half of 2019 compared to DKK 459 million in the same period of 2018.
Now, we move on to slide five and the revenue. Revenue breakdown by category is shown on the left hand side of the slide. In the first half of 2019, royalties were the largest portion of revenue at DKK 1,181 million compared to DKK 709 million in 2018. The increase of DKK 472 million or 67%, was driven by the higher DARZALEX royalties, which were partly offset by lower Arzerra royalties. There were no license fees in the first half of 2019 compared to the DDK 336 million shown in the first half of 2018. The decrease again was driven by the one-off payment of DKK 304 million from Novartis, which occurred in Q1 2018. And that was due to the amendment of Arzerra/ofatumumab license and collaboration agreement.
Reimbursement income accounted for DKK 164 million in the first half of ‘19 compared to DKK 106 million in the first half of ’18, an increase of DKK 58 million or 55%, driven by increased activities under our collaboration agreement with Seattle Genetics, and BioNTech.
The graph on the right bridges the revenue between the two periods. The largest increase was DARZALEX royalties, which grew from DKK 695 million in the first half of 2018 to DKK 1,169 in H1 2019, an increase of DKK 474 million. The royalties were based on the Janssen’s DARZALEX sales of $1,403 million, and that's in the first half of ‘19 compared to $943 million in the same period in 2018. The substantial increase at $460 million or 49% was driven by continued strong uptake in the U.S., EU and Japan. The cost reimbursement increase again was primarily driven by the advancement of our collaboration products with the Seattle Genetics and BioNTech. And the last time, the largest decrease in revenue was the one-off Arzerra payment from Novartis.
正如预期的那样，2019年上半年的总支出为12.54亿丹麦克朗，增加了5.22亿丹麦克朗或71％。这是由于我们的临床产品的进步，包括enapotamab vedotin和tisotumab vedotin以及我们的其他管道产品和新的CTA。按计划，我们还增加了员工数量，以支持我们的管道扩建。
现在，我们继续下滑第五和收入。按类别划分的收入细分显示在幻灯片的左侧。在2019年上半年，特许权使用费收入的最大部分为11.81亿丹麦克朗，而2018年为7.09亿丹麦克朗。增加了4.72亿丹麦克朗或67％，这得益于更高的DARZALEX特许权使用费，其部分被低于Arzerra版税。与2018年上半年显示的3.36亿丹麦克朗相比，2019年上半年没有许可证费用。再次减少的原因是诺华公司2018年第一季度一次性支付3.04亿丹麦克朗。这是由于Arzerra / ofatumumab许可和合作协议的修订。
Next, the expenses and operating income on slide six. The change in expenses between the first half of 2018 and 2019 is aligned with our strategic focus to achieve our 2025 vision. And you can see the growth drivers in the graph on the left hand side of the slide. There was an increase in the operating expense of DKK 522 million, which was driven by the accelerated investment in our clinical and preclinical product portfolio. In fact, 63% of the total expense increase was due to the additional investment in our pipeline of products, including the advancement of enapotamab vedotin, tisotumab vedotin and advancing the new programs to INDs in 2019 and beyond.
The FTE costs have also increased year-over-year as well. And we continue to undergo controlled growth to support our robust product pipeline and continued efforts to build commercial capabilities. We had 478 FTEs at the end of June, an increase of 55% from the end of June 2018.
Looking at the chart on the right, you can see a decrease in the operating result from an operating income of DKK 459 million to the DKK 111 million that we discussed earlier.
Now, let’s discuss the 2019 guidance on slide seven. We are updating and slightly improving our 2019 financial guidance, which was initially published on February 20, 2019. Starting at the top of slide seven, we have the table that shows a comparison with the revised guidance compared to the previous guidance for 2019.
We now expect our 2019 revenue to be at DKK 4.8 billion. This is an improvement or an increase of DKK 200 million. This is due to the higher royalty income from DARZALEX sales. We also anticipate our operating expenses will be DKK 2.75 billion, an increase of DKK 150 million, driven by the advancement of our product pipeline, as well as the addition of new projects. I will discuss both of these items in more detail in just a moment. Taking together, the result with an operating income of DKK 2.05 billion, an increase of DKK 50 million, compared to the previous guidance.
Now, if we move to the bottom of the page, we can take a closer look at the key elements of our revenue. Our projected revenue consists of DARZALEX royalties of nearly DKK 2.9 billion, based on Genmab’s estimate of DARZALEX sales of $3 billion in 2019. This increase from our previous guidance for DARZALEX royalties of just under DKK 2.7 billion is due to positive impact of exchange rate movements. We expect DARZALEX sales to rapidly advance in 2019 with the growth in U.S. market share, both in the frontline and the second line setting where we anticipate long duration of treatment and increased number of patients on treatment.
In Europe and the rest of the world, we’ll also continue to see more countries coming on stream and expect to see the continued introduction in frontline multiple myeloma with daratumumab plus VMP.
As a reminder, the average royalty for the $3 billion of sales is just under 15%, and on sales above $3 billion, we’ll have a royalty rate of 20%. You'll also note that the anticipated DARZALEX royalties continue to exceed the total expense base.
接下来，幻灯片六的费用和营业收入。 2018年上半年和2019年之间的费用变化与我们实现2025年愿景的战略重点相一致。您可以在幻灯片左侧的图表中看到增长动力。运营费用增加了5.22亿丹麦克朗，这是由于我们临床和临床前产品组合的加速投资所致。事实上，总费用增加的63％是由于我们的产品系列的额外投资，包括enapotamab vedotin，tisotumab vedotin的推进以及2019年及以后将新计划推进到INDs。
We continue to project daratumumab milestones of DKK 1.5 billion in 2019, which relate to the sales based milestones. This includes $150 million milestone for exceeding $3 billion of sales in a calendar year, as well as a milestone for exceeding $2.5 billion of sales in a calendar year. So, expect to see these milestones to be achieved towards the back end of the year in Q4 2019. The remainder of the revenue mainly consists of cost reimbursement income related to our collaborations with Seattle and BioNTech DuoBody milestones and Arzerra royalties.
Now, let's turn to slide eight and look at the expense details. On the top of this slide we show that we're investing in three main areas, project investment, personnel costs and business support control, in line with our previously communicated strategy to achieve our 2025 vision. The largest cost at nearly 60% of the total is our project investment, and it directly relates to the success and the advancement of our pipeline. The next largest cost is the personnel costs. At the end of 2018, we had around 377 FTEs, and we anticipate this will increase to about 560 by the end of this year. Again, the investment in increasing resources is directly driven by the success of our pipeline. The business support investment relates to all of the other support functions, and growth is across all support areas, including enhancing technologies and systems, and early investment in commercial as well as investment in other functions.
Moving to the bottom of the slide are broken out our most significant area of investment, the project cost into more detail. On the left, we have a pie chart with our total project investment of DKK 1,625 million. About half of that amount will be invested in our two most advanced projects, tisotumab vedotin and enapotamab vedotin. In comparison, for the next eight projects, including several projects already in the clinic, we’ll invest around DKK 625 million. Interestingly, if you add these together, then we'll invest DKK 1.4 billion in our top 10 programs, which continues to be about 50% of our total expense base.
On the right hand side, we've broken out our next largest cost of the FTEs and show you the increase of 180 that I mentioned earlier. 73% of the increase relates to R&D employees, 18% for business support functions, and 9% for our earlier investment in medical affairs and commercial functions. As you’d expect, in 2019, we're continuing to project to be cash flow positive, and our priority the capital allocation is to continue to increase the investment in our preclinical and clinical pipeline and invest to achieve our vision for 2025. Note that as usual our 2019 guidance does not include any new potential deals.
Now, I'd like to turn the call back over to Jan to give you an update on our 2019 goals. Jan?
移动到幻灯片的底部是我们最重要的投资领域，项目成本更加详细。在左边，我们有一个饼图，我们的项目总投资为16.25亿丹麦克朗。其中约一半将用于我们最先进的两个项目，即tisotumab vedotin和enapotamab vedotin。相比之下，在接下来的八个项目中，包括已经在诊所的几个项目，我们将投资约6.25亿丹麦克朗。有趣的是，如果你将这些加在一起，那么我们将在我们的十大计划中投资14亿丹麦克朗，这仍然是我们总支出基数的50％左右。
Jan van de Winkel
Let's move to slide nine. We continue to experience solid progress across all areas of development during this year. We have met two of the three goals related to daratumumab with the approval in the U.S., based on data from the MAIA study and the data from the Phase 3 COLUMBA trial, which was announced in the first half of 2019. All that remains is the U.S. FDA decision on the submission based on CASSIOPEIA data, and as I mentioned, we anticipate this by the end of September.
We also expect to announce daratumumab data presentations at upcoming medical conferences, including 13 Janssen submitted presentations at September 17th International Myeloma Workshop which takes place in Boston. Data from the CASSIOPEIA, MAIA, COLUMBA and PLEIADES trials have been accepted for presentation. And excitingly, the important GRIFFIN data will be featured during a plenary session at this meeting. One of four daratumumab abstracts accepted for oral presentation during the events.
For ofatumumab, we anticipated data from the two large Phase 3 trials of the subcutaneous formulation and relapsing multiple sclerosis or MS. If the data is positive, it could give ofatumumab new life as potential treatment for relapsing MS.
As I stated last quarter, along with Seattle Genetics, we're continuing to move tisotumab vedotin program forward with the start of new studies. And we have already completed enrollment of the Phase 2 trial in recurrent or metastatic cervical cancer. While the first half of 2019 was mostly focused on daratumumab news, we also look forward to the rest of the pipeline growing, potentially exponentially during the second half of this year with a number of key data sets expected to be presented at upcoming medical conferences.
We also expect to file at least one more IND or CTA, in addition to the CTAs already submitted for DuoBody-PD-L1x4-1BB and DuoBody-CD40x4-1BB.
So, as you can see, as exciting as the first half of 2019 has been for Genmab, this will momentum will continue as we move into an equally new-rich second half of the year, both for daratumumab as well as for a number of our proprietary clinical programs.
Let's move to slide 10. That ends our presentation of Genmab’s second quarter 2019 financial results. Operator, please open the call for questions.
[Operator Instructions] Your first question comes from the line of Kennen MacKay from RBC Capital Markets. You may ask your question.
[操作员说明]您的第一个问题来自RBC Capital Markets的Kennen MacKay。 你可以问你的问题。
Hi. Thanks for taking the question, and congrats on the recent progress the upped guidance and U.S. listing. My question primarily relates to Arzerra in MS. After our recent initiation, this is one of the major sources of pushback from investors, not because my estimates are too high, but because investors think they are high enough. Could you maybe talk a little bit about sort of differentiation within the MS market if the Phase 3 trials are successful, and maybe provide any sort of anecdotes for computing in this market on convenience, and just sort of how that competitive dynamic shakes out? Thank you again for taking the question.
你好。 感谢您提出问题，并祝贺最近的进展指导和美国上市。 我的问题主要与MS中的Arzerra有关。 在我们最近启动之后，这是投资者反击的主要来源之一，不是因为我的估计太高，而是因为投资者认为他们足够高。 如果第3阶段试验成功，你可以谈谈在MS市场中的某种差异化，并且可能在这个市场中提供任何类型的便利计算轶事，以及这种竞争动态如何摆脱？ 再次感谢您提出问题。
Jan van de Winkel
Thanks, Kevin, and welcome to the team. Thanks for the initiation. We are delighted to have you on board as a covering analyst. And I'm delighted to give you an answer on the MS perspective for ofatumumab. We think that this molecule is highly differentiated from all cases and other CD20 antibody by Roche. Because it's a fully human antibody which can be given subcutaneously, it's a much higher affinity antibody. You need about 3.9-fold less of the antibody per year than you need for Ocrevus. It’s very, very good Phase 2 data, as a SubQ formulation, we believe that actually the convenience of SubQ formulation is going to be massive in MS because this is a chronic disease that you cannot cure, but you can only control that with drugs. I think, there is a need for new drugs, and that need is I think underscored by the very-rapid penetration with Ocrevus which Roche's observed over the last two years, as you and I know. And I think with a potentially differentiated profile, I think ofatumumab could actually do quite well. And I think, I've seen your projections. And I know that Novartis already calls ofatumumab a potential candidate blockbuster very, very quickly on all of their presentations. We actually can’t wait, Kennen, to see the data from the two large ASCLEPIOS trials which we expect very soon now. And we are convinced that the product is differentiated from Ocrevus, shows good efficacy and very good convenience that will actually do quite well in the MS market. I think, there's not many other, I think examples, I can give you from our products in MS with the similar profile where a SubQ formulation versus an IV formulation can be used as a benchmark. But, I think Ocrevus is I think showing that new products in a very competitive market can actually do quite well.
Next question comes from the line of James Quigley from J.P. Morgan.
下一个问题来自J.P. Morgan的James Quigley。
I've got a question on DARZALEX and transplant patients. So, the GRIFFIN data was reported and strong but statistically significant level was a little bit more relaxed than in other trials. Given this and given U.S. doctors’ commentary around the strength of VRd in transplant patients, do you expect any pushback from U.S. doctors? And then, secondly, with the PERSEUS trial looking to read out in 2029 as per clinicaltrials.gov, Sanofi seems to that -- J&J may have left the door open a little bit for this population. Do you have any comments there on why J&J weighted for the GRIFFIN data rather than starting a Phase 3 like it did with CASSIOPEIA? And also, what impact would CASSIOPEIA potentially have, given that VTd is a European investment? Thank you.
我有一个关于DARZALEX和移植患者的问题。 因此，GRIFFIN数据报告强劲，但统计上显着的水平比其他试验稍微放松一些。 鉴于此并且考虑到美国医生对移植患者VRd强度的评论，您是否期望美国医生有任何阻力？ 然后，其次，随着PERSEUS试验在2029年按照clinicaltrials.gov进行宣读，赛诺菲似乎就是这样 - 强生公司可能已经为这个人群打开了一扇门。 你对J＆J为GRIFFIN数据加权而不是像CASSIOPIAIA那样开始第3阶段有什么评论吗？ 而且，鉴于VTd是欧洲投资，CASSIOPEIA可能会产生什么影响呢？ 谢谢。
Jan van de Winkel
Thanks, James, for the question on the GRIFFIN data. We believe that data is incredibly strong. This is underscored by not only the primary endpoint hits and we used indeed a different significance level because this was Phase 2 trial. This is basically a setup in order to see whether we have the clinically meaningful difference with daratumumab in addition to VRd. And this is not a Phase 3, like the PERSEUS trial. But, I can tell you that all the secondary endpoints were hit very, very nicely, and you will see the very soon, I think in the IMW conference in Boston in the second week of September. But, this will be featured -- the abstracts may also become available before that time, James, and the data is just nothing sort of stunning. So, we think that actually the GRIFFIN data can, when published, lead to compania [ph] listing and potentially can also lead to doctors having the option to potentially use it actually before the PERSEUS trial reads out. Janssen of course cannot promote for the drug until we have a formal label for dara plus VRd.
I think that Sanofi’s comments should be taken with a grain of salt. I mean, that's what I wish, of course, they could see there. I think that given that the GRIFFIN data follows the very strong CASSIOPEIA data, CASSIOPEIA is more difficult for me to give you an estimate from, because this is a very much European type regimen. But of course, doctors could see that and the GRIFFIN follows the same trend as what was seen with CASSIOPEIA with another image. I mean, the docs may also decide once these data published and in the public domain from GRIFFIN to simply use VRd in the frontline setting. And I think we'll have to seek, James, how this pan out, but I think the coming two, three weeks will be very, very exciting as we see it for the potential in frontline with DARZALEX.
谢谢James，关于GRIFFIN数据的问题。我们相信数据非常强大。这不仅强调了主要终点命中，而且我们确实使用了不同的显着性水平，因为这是第2阶段试验。这基本上是一种设置，以便观察除了VRd之外我们是否与daratumumab具有临床上有意义的差异。这不是第3阶段，就像PERSEUS试验一样。但是，我可以告诉你，所有次要终点都非常非常好，你会很快看到，我想在9月的第二周在波士顿举行的IMW会议上。但是，这将是特色 - 摘要也可能在那之前可用，詹姆斯，数据只是令人惊叹。因此，我们认为实际上GRIFFIN数据在发布后可能会导致compania [ph]列表，并可能导致医生在PERSEUS试验读出之前可以选择实际使用它。在我们为dara加VRd制作正式标签之前，Janssen当然不能宣传这种药物。
The line of Wimal Kapadia from Bernstein is open.
Hi. Great. Thanks for taking my question. Wimal Kapadia from Bernstein. So, my question is on the SubQ. Could you just walk me through exactly how the administration works in terms of pretreatment and waiting times? I think, there’s been some suggestion taking into account all the time required outside of the five-minute injection, it can still be relatively lengthy. So, could you just remind us of the details, please? Thank you.
你好。 大。 谢谢你提出我的问题。 来自伯恩斯坦的Wimal Kapadia。 所以，我的问题是关于SubQ。 您能否直接告诉我管理在预处理和等待时间方面的工作原理？ 我认为，有一些建议考虑到五分钟注射之外的所有时间，它仍然可能相对冗长。 那么，你能告诉我们细节吗？ 谢谢。
Jan van de Winkel
I don’t have that exact detail here, Wimal, available. But I do know that you need to pre-dose with corticosteroids but only for the -- I think the first two injections; from the third injection on, corticosteroid pre-dosing is not used by all the doctors in the COLUMBA trial. And I think that Janssen is certainly looking into whether we actually do need to pre-dose with corticosteroids and other drugs, before the SubQ administration. So, I think that may very quickly change that we need that pre-dosing. And then, what I want to remind you of Wimal is that is of course -- that is only relevant for the monotherapy use of daratumumab because in many of the combination therapies dexamethasone is already used or steroids are already used. And that doesn't -- basically doesn't change, doesn't change the treatment combination. So, only for monotherapy, the first two doses, I think are a little bit more lengthy than the five-minute injection with daratumumab. From the third dose on, I think many doctors already stop the pre-dosing and just immediately give the drug. And in combination therapies, it’s not -- the discussion is not relevant because the corticosteroids anyhow used already in combination with like revlimid and other drugs.
我没有那里的确切细节，Wimal，可用。但我确实知道你需要给皮质类固醇预先给药，但仅限于 - 我认为前两次注射;从第三次注射开始，COLUMBA试验中的所有医生均未使用皮质类固醇预先给药。我认为，在SubQ管理之前，Janssen肯定在研究我们是否确实需要使用皮质类固醇和其他药物进行预先给药。所以，我认为这可能很快改变我们需要预先给药。然后，我想提醒你的是，Wimal当然是 - 这只与daratumumab的单药治疗有关，因为在许多联合治疗中已经使用过地塞米松或者已经使用了类固醇。而且这不会 - 基本上不会改变，不会改变治疗组合。因此，对于单一疗法，前两种剂量，我认为比用daratumumab注射五分钟更长。从第三次开始，我想很多医生已经停止了预先给药，并立即给药。在联合疗法中，它不是 - 讨论不相关，因为皮质类固醇无论如何已经与类似revlimid和其他药物一起使用。
Thank you very much.
Jan van de Winkel
We have advantage with SubQ, you have lower infusion-related reactions, with the IV as well. So hopefully, that will be less of a challenge going forward.
The line of Matthew Harrison from Morgan Stanley is open.
Hi, everyone. Thanks for taking my question. This is Connor Meehan on for Matthew Harrison. We were just wondering -- or sorry, two questions quickly. We were just wondering quickly about DARZALEX and amyloidosis and about the timing of the Phase 3 and what you guys would think is a good result. And then, just one quick question on AXL after that.
嗨，大家好。 谢谢你提出我的问题。 这是马修哈里森的Connor Meehan。 我们很快就想知道 - 或者抱歉，两个问题。 我们很快就想知道DARZALEX和淀粉样变性以及第3阶段的时间安排以及你们认为好的结果。 然后，在此之后只有一个关于AXL的快速问题。
Jan van de Winkel
So, thank you, Matthew. Also, welcome to you. Thanks for setting a coverage and welcome here to the coverage -- covering team. Amyloidosis, the ANDROMEDA trial is a rapidly progressing; it could actually lead to an interim -- potential interim readout in the coming months. Before the full readout of all the data, I do want to remember you that of the 19 Phase 3 trials that the DARZALEX, all [ph] the six which is read out all have read out on the very positive interim and the same could happen for the ANDROMEDA, ANDROMEDA study. And in a positive scenario, Matthew, that could already happen in the coming months.
And what would we expect, I mean the data upto now from the Run-in [ph] patients is incredibly good, very, very high levels of percentage of patients getting into very dramatic hematological responses. So, we would expect the data to be very good based on the Run-in data, and based on the data already presented form I think three -- a total of three Phase 1/2 studies earlier on.
所以，谢谢你，马修。 另外，欢迎你。 感谢您设置报道，欢迎来到覆盖范围 - 覆盖团队。 淀粉样变性，ANDROMEDA试验正在迅速发展; 它实际上可能导致未来几个月的临时潜在临时读数。 在完全读出所有数据之前，我确实想要记住，在DARZALEX的19个阶段3试验中，所有[其中]所读出的六个都已经在非常积极的过渡时间读出并且同样可能发生 对于ANDROMEDA，ANDROMEDA的研究。 在一个积极的情况下，马修，这可能已经发生在未来几个月。
我们期望得到什么，我的意思是来自Run-in [ph]患者的数据是令人难以置信的好，非常非常高的患者百分比进入非常显着的血液学反应。 因此，我们希望数据基于Run-in数据非常好，并且基于已经呈现的数据，我认为有三个 - 之前总共有三个阶段1/2研究。
Great, thank you. And thanks for the warm welcome. Just quickly on the actual antibody. Could you guys just provide some background on your conviction in the long expansion cohorts, and I guess why you've chosen that over other disease types? And would you guys expect to see responses here, or are you looking for durability and stable disease, would you see those two things as positive?
太好了谢谢。 并感谢您的热烈欢迎。 只需快速了解实际抗体。 你们可以在长期扩展队列中提供一些关于你的信念的背景吗？我猜你为什么选择其他疾病类型？ 您是否希望在这里看到回应，或者您是否在寻找耐久性和稳定的疾病，您认为这两件事情是积极的吗？
Jan van de Winkel
Yes. I can give you some perspective, but I can tell you that actually the coming months we do expect to present data from the lung cohort. This is purely data-driven, Matthew. So what we've done is we have looked at different tumors over express AXL based on very strong preclinical data. But once tumors over express AXL, they become refractory to chemotherapy and to immunotherapy, as well as to small molecule inhibitors. And they are very difficult to control, and we've gotten some very strong preclinical data that AXL-ADC or enapotamab vedotin is a very potent killer of those tumors. With overexpressed AXL in lung cancer that was already quite clear during the dose escalation. And we have expanded the expansion cohort by a very large number of patients and we hope to present you the initial, I think, 26 or so patients’ worth of data. And then, we will -- we hope to present definitely at a response rate level. And I think it's a bit too early to look at durability, Matthew. But, we're also developing an assay to actually screen patients for AXL expression potentially for the next clinical study. And I think that will all become quite clear at the data presentation at an upcoming medical conference, and we will flag that up to you in the coming weeks.
是。我可以给你一些观点，但我可以告诉你，实际上未来几个月我们确实希望从肺群中提供数据。这纯粹是数据驱动的，马修。所以我们所做的就是基于非常强大的临床前数据我们研究了不同的肿瘤而非快速AXL。但是，一旦肿瘤过度表达AXL，它们就会变得难以接受化疗和免疫疗法，以及小分子抑制剂。而且它们很难控制，我们得到了一些非常强大的临床前数据，即AXL-ADC或enapotamab vedotin是这些肿瘤的一种非常有效的杀手。在肺癌中过度表达的AXL在剂量递增期间已经非常清楚。我们已经扩大了大量患者的扩展队列，我们希望向您提供初始的，我认为，26个左右患者的数据。然后，我们将 - 我们希望绝对以响应率水平呈现。我认为现在看耐久性还为时尚早，马修。但是，我们还开发了一种分析方法，可以在下一次临床研究中实际筛查患者的AXL表达。而且我认为在即将举行的医学会议上数据演示都会变得非常明确，我们将在未来几周内向您提供这些信息。
The line of Michael Schmidt from Guggenheim is open.
I had a couple of pipeline questions as well. The first one is on tisotumab vedotin. I know you mentioned you have fully enrolled the Phase 2 study cervical cancer. But I was just wondering if you could just briefly update us on your activities in other accounts or types and maybe help us understand what the gating factors are to potentially advancing the ADC in other cancer types as well? And then the second question was on the DR5 HexaBody. I know you guided to, first, presentation of first clinical data later this year there. So I just wondering if you could help us guide expectations around the quantity of the clinical data potentially and maybe what tumor types might be most responsive to DR5 at -- based on preclinical data?
我也有几个管道问题。 第一个是tisotumab vedotin。 我知道你提到你已完全注册了2期宫颈癌研究。 但我只是想知道你是否可以简单地向我们介绍你在其他账户或类型中的活动，也许可以帮助我们了解在其他癌症类型中可能推进ADC的门控因素是什么？ 然后第二个问题是关于DR5 HexaBody。 我知道你首先在今年晚些时候介绍了第一份临床数据。 因此，我想知道您是否可以帮助我们根据临床前数据指导对潜在临床数据量的预期，以及可能对DR5最敏感的肿瘤类型？
Jan van de Winkel
Thank you, Michael. And also, you, a warm welcome for joining the covering team of analysts and for the initiation report. We are very pleased with that. So welcome. The tisotumab vedotin studies in cervical cancer, you will see more and more of our studies coming online. We started the Japanese study and we finished recruitment in the 204, potential pivotal study as we flanked up. We're also doing a basket study with 4 tumor, solid tumors where we expect actually data early next year. Seattle Genetics is operationalizing that study with 4 different solid cancers and they are doing a second study with ovarian cancer also based on signals we have already seen in the Phase 1/2 setting and we hope to present data from the basket study in the first half of next year. And also very early next year, we hope to potentially give you the primary readout of the Phase 2 cervical cancer study.
And the tumors chosen here, were in the basket study, were chosen based on the, either the very strong preclinical data for pancreatic cancer but for the other 3 tumors were chosen because of the data we observed in the Phase 1/2 trial, the Phase 1/2 setting. So they are all tumors with -- can very, very strongly [indiscernible] tissue factor that target tisotumab vedotin, and there's a very good correlation between tumors overexpressing tissue factor and the ability of tisotumab vedotin to kill those tumors effectively. So more data in the beginning part of next year for both the basket study, Michael, and for the cervical cancer potential pivotal Phase 2. Then, as it relates to HexaBody-DR5/DR5, we are doing dose escalation studies in 7 different tumors. All tumors we have previously, other companies, there have been a total of 5 companies with 9 compounds targeting DR5 in the clinic in the years before. And we have chosen tumors, Michael, where other companies at least got some initial positive results. So we have 7 -- a basket of 7 different tumors. We're doing different dose frequencies and different dose levels evaluated in these different tumors. You may see before the end of the year, some early indication of the dose escalation part of the trial, Michael. But more full data expected in 2020 at a medical conference.
谢谢你，迈克尔。此外，您热烈欢迎加入分析师覆盖团队和启动报告。我们对此非常满意。非常欢迎。 tisotumab vedotin在宫颈癌研究中，你会看到越来越多的研究上线。我们开始了日本的研究，我们完成了招聘，这是我们两侧潜在的关键性研究。我们还在进行了一项有4个肿瘤，实体肿瘤的篮子研究，我们期望明年早些时候有实际数据。西雅图遗传学正在对4种不同的实体癌症进行研究，他们正在根据我们已经在1/2阶段设置中看到的信号进行第二项卵巢癌研究，我们希望在上半年提供篮子研究的数据明年。而且在明年很早的时候，我们希望能够为您提供第2阶段宫颈癌研究的主要读数。
在这里选择的肿瘤，在篮子研究中，根据胰腺癌的非常强的临床前数据选择，但是因为我们在1/2期试验中观察到的数据选择了其他3个肿瘤，阶段1/2设置。因此，它们都是具有 - 非常，非常强烈[音频不清晰]组织因子的肿瘤，其靶向tisotumab vedotin，并且过度表达组织因子的肿瘤与tisotumab vedotin有效杀死这些肿瘤的能力之间存在非常好的相关性。因此，对于篮子研究，迈克尔和宫颈癌潜在关键阶段2，明年开始的更多数据。然后，由于它与HexaBody-DR5 / DR5有关，我们正在对7种不同的肿瘤进行剂量递增研究。我们以前的所有肿瘤，其他公司，在前几年共有5家公司，其中9种化合物针对DR5。我们选择了迈克尔肿瘤，其他公司至少得到了一些初步的积极成果。所以我们有7个 - 一篮子7种不同的肿瘤。我们在这些不同的肿瘤中进行不同的剂量频率和不同的剂量水平评估。您可能会在年底前看到一些早期迹象显示试验的剂量升级部分，迈克尔。但预计到2020年医学会议会有更多的完整数据。
The line of Peter Verdult from Citi is open.
It's Peter from Citi. A question for Jan and a request for David, please. Jan, on the CD3xCD20 bispecific, from the posters and data that we've seen so far, stacks out well against the [indiscernible] asset and the [indiscernible] assets. But it looks comparable to the Roche assets that's been taken forward into development at the Roche Group. So just, can you remind us, are you going to have an oral presentation at ASH? And how you see your bispecifics stacking up against what we see as the best-in-class one right now, which is Roche? And then lastly, is it still possible that we could see a partnership on this asset side by year-end, talking about signing a partnership deal with your [indiscernible] rights? Just wondering whether the temperature is still hot there. And then, David, just on the request. You usually provide a helpful quarterly update on U.S. penetration rates for DARZALEX by line of therapy, wondering whether you would be willing to provide that for Q2 or anything on early data on metrics from the first month launch in the U.S.
Jan van de Winkel
Well, thanks, Peter for the questions and I will start with the CD3xCD20 bispecific. This antibody, preclinically as you rightly state is basically about a hundredfold more potent preclinically than the Regeneron molecule and one of the Roche molecules, [indiscernible] , and it is similar in activity to the RG 6026 molecule from Genentech. We believe that this molecule is actually more potent than the Roche and Regeneron molecules, it's the furthest advanced in the clinic and we base that on studies in monkeys, where we showed actually at much lower doses, much more long-term depletion of the target cells, Peter. And it's actually so potent that it happened at much lower doses. So we can actually give subcutaneous injections without any complex formulation. So we believe it's highly differentiated from the lead Regeneron and Roche progress and you referred to the RG 6026 program that recently ran into some severe cytokine release syndrome toxicity, as you know. And also, the efficacy at the latest data sets from Roche was underwhelming. So the molecule which looks similar preclinically doesn't look that good in the clinic, we believe. So we actually believe that we have a highly differentiated molecule, plus huge attention from different companies and speaking with us about potentially partnering that molecule already flattened to the markets, Peter, that we need a partner because I think we need to -- we are going to go for the full market. We're not going for a niche market with this molecule. We believe that we understand the CD20 fields very well and we have a differentiated molecule and we need a very, very, I would say, aggressive and very capable partner to be the military style move in that molecule, because we are a little bit late of course on Regeneron and Roche for that CD20 market. But I can assure you that the interest level is very, very high.
A partnership before the year end, I think that's a little bit too quick. It is definitely possible. But I would say though, a potential partnership in 2020 is more likely, Peter, given how sometimes these partnership discussions can take time, and we have done a number of them now. So I think it's unlikely to happen before the end of the year. But definitely, the interest level is sky high.
What level of presentation? We have submitted an abstract to ASH and we haven't heard back from ASH. So I don't know, Peter, whether it will be an oral presentation or what type of presentation. We will flag that up to you and to the market once we hear from the American Society of Hematology. That's probably where I should leave that at. And David, the floor to you for the second question from Peter.
好的，谢谢，彼得的问题，我将从CD3xCD20双特异性开始。这种抗体，在您正确陈述的情况下，临床前基本上比Regeneron分子和罗氏分子之一（[音频不清晰]）强大约100倍，并且其活性与Genentech的RG 6026分子相似。我们相信这种分子实际上比罗氏和Regeneron分子更有效，它是临床上最先进的，我们的基础是猴子的研究，我们实际上在更低的剂量下显示，更长期的目标消耗细胞，彼得。它实际上是如此有效，它发生在更低的剂量。因此，我们实际上可以进行皮下注射而无需任何复杂的配方。所以我们认为它与领先的Regeneron和Roche的进展有很大差异，你提到了最近遇到一些严重的细胞因子释放综合征毒性的RG 6026计划，如你所知。此外，罗氏公司最新数据集的功效也令人沮丧。因此，我们认为，在临床上看起来相似的分子在临床上看起来并不那么好。所以我们实际上相信我们有一个高度分化的分子，加上来自不同公司的巨大关注，并且与我们谈论可能已经将这个分子已经扁平化到市场的伙伴，彼得，我们需要一个合作伙伴，因为我认为我们需要 - 我们是打算进入全面市场。我们不打算用这种分子进入利基市场。我们相信我们非常了解CD20领域，并且我们有一个差异化的分子，我们需要一个非常非常，我会说，积极和非常有能力的合作伙伴成为该分子中的军事风格，因为我们有点晚了当然还有Regeneron和Roche的CD20市场。但我可以向你保证，兴趣水平非常非常高。
Thank you very much, Jan. Thanks for the question, Peter. So each quarter, I'll only go through -- give you a few highlights on the IQVIA brand impact data. As a reminder, that's a 3 months rolling average data and we do now have that market survey data for June. So, overall, market share continues to grow for daratumumab. We are now at the end of June at 18% market share. That compares to about 15% at the beginning of the year. Obviously, if this was the June data, really too early to see any impact of MAIA DRd in the frontline setting and overall in the frontline multiple myeloma, which is about 3%. So that's the big area that we have the opportunity to grow with these new approvals in the newly diagnosed patients. What we are quite excited about for the June data was the second line setting. We're continuing to see inroads and gains in the market share. To give you an idea, at the end of 2018, we had a market share of 27%. That moved nicely up at the end of March to 29% and quite a nice leap at the end of June to a now 34% market share. Also consistently, we're seeing throughout all of the periods not only reaching new highs in the market share but also that the new patient start data is consistently higher than the market share. So that's of course indicating to me that we've got further to go with the patient stacking with higher NPS coming through. That means that market share should continue to grow. And that second line is quite important for us because of the long duration of treatment, that means that the patients are staying there a long time. And get the patient stacking, we're getting more sales through from those U.S. patients.
In terms of the third line setting, that's more sort of consistent, that's bouncing around somewhere between the 45%, 48%. The June number was 45%, which I think is about where we were expecting. And in that third line setting, the most popular regime was the Dara Pomalyst Dex combination, that was about 20% of that 45%. Fourth line, staying consistent. March was 39% and it was 40% for the June period. So again, staying fairly consistent there. We said at the beginning of the year, really, the place for us to win in 2019 was the gain in the market share and that's what we're seeing. I was very pleased with the 34% at the end of June. We said we were probably likely be around flattish in the third line and maybe slightly declining in the fourth line and that seems to be coming out. Of course, the big thing for the second half of 2019 is our MAIA, daratumumab, Revlimid Dex combination, too early to really see any data movement on that yet but we are watching IMS and Symphony data over the next few months and hope to see some inroads in the newly diagnosed multiple myeloma setting.
非常感谢，Jan。谢谢你提出这个问题，彼得。所以每个季度，我都会经历 - 给你一些关于IQVIA品牌影响力数据的亮点。提醒一下，这是3个月滚动平均数据，我们现在有6月份的市场调查数据。因此，总体而言，daratumumab的市场份额继续增长。我们现在在6月底的市场份额为18％。相比之下，年初约为15％。显然，如果这是6月份的数据，那么看到MAIA DRd在前线设置和前线多发性骨髓瘤中的任何影响确实为时尚早，大约为3％。因此，这是我们有机会在新诊断的患者中获得这些新批准的重要领域。我们对6月数据感到非常兴奋的是第二线设置。我们将继续看到市场份额的进入和增长。为了给你一个想法，在2018年底，我们的市场份额为27％。在3月底，这种情况很好地上升至29％，并且在6月底实现了相当大的飞跃，目前市场份额为34％。同样，我们在所有时期都看到，不仅市场份额达到新高，而且新患者的起始数据始终高于市场份额。所以这当然向我表明，我们已经进一步与患者堆叠更高的NPS通过。这意味着市场份额应该继续增长。由于治疗时间长，第二行对我们来说非常重要，这意味着患者在那里停留很长时间。让患者堆叠，我们从这些美国患者那里得到更多销售。
就第三线设置来说，这更具有一致性，它在45％，48％之间徘徊。 6月份的数字是45％，我认为这是我们期待的地方。在第三线设置中，最流行的制度是Dara Pomalyst Dex组合，约占45％的20％。第四行，保持一致。 3月为39％，6月期间为40％。所以再次，在那里保持相当一致。我们在年初说过，真的，我们在2019年赢得的地方是市场份额的增加，这就是我们所看到的。我对6月底的34％感到非常满意。我们说我们可能在第三线可能会处于平稳状态，并且可能在第四线略微下降，这似乎正在出现。当然，对于2019年下半年来说，最重要的是我们的MAIA，daratumumab，Revlimid Dex组合，现在还没有真正看到任何数据运动，但我们正在观察未来几个月的IMS和Symphony数据并希望看到在新诊断的多发性骨髓瘤设置中取得了一些进展。
The line of Peter Welford from Jefferies is open.
Just real quick question on the operating spend, please. Just curious how much of the increase, the OpEx is related to FX as well, both in the other hand, actually underlying increase? And I wonder, I appreciate you're probably going to stay and wait until the December update. But can you give us just sort of big picture, your thoughts I guess on going into 2020? How we should think about the spend, I guess relative to what we see this year, obviously with regards to year-on-year. And also, when should we start thinking about I guess potential initial spent for tisotumab assuming that the data are positive, if then for the commercial operations? And obviously you've yet to sort of build out. So just point of clarification on ANDROMEDA as well on amyloidosis. You mentioned the interim. But just to be clear, is that study fully recruited yet? It isn't marked with a tick on your report.
请关于运营支出的快速问题。 只是好奇有多少增加，OpEx与FX有关，另一方面，实际上是潜在的增长？ 我想知道，我很感激你可能会留下并等到12月更新。 但是，你能否给我们提供一些大图片，我猜你想进入2020年？ 我们应该如何考虑支出，我猜相对于我们今年看到的情况，显然与年度相关。 而且，我们什么时候应该开始考虑我猜tisotumab的潜在初始花费假设数据是正数，那么商业运作呢？ 显然你还没有建立起来。 因此，只需澄清ANDROMEDA以及淀粉样变性。 你提到了临时。 但要明确的是，这项研究是否完全招募了？ 它没有在报告上标记。
Jan van de Winkel
Peter, I think you sneaked in a few more questions. So I will start at the last one. The ANDROMEDA study has an interim which can be run actually in the coming months, potentially. So that is in the trial description. And I'm not sure that, that is fully enrolled. But the interim can definitely be run. And so then, I will probably pass the other 3 questions over to David.
彼得，我想你还偷了几个问题。 所以我将从最后一个开始。 ANDROMEDA研究有一个临时的，可能会在未来几个月实际运行。 这就是试验说明。 而且我不确定，那是完全注册的。 但是过渡期绝对可以运行。 那么，我可能会将其他3个问题转交给大卫。
Yes. In terms of the operating expense, we did actually plan a slightly higher FX rate for the operating expense compared to the revenue when we did the original guidance. So not too much of that increase going up DKK 150 million is down to FX. The main 3 things that are really driving that is one of our existing programs at CD3xCD20 and that's just the advancement and good progress that we're making with that particular program. The rest of the -- most of the expense increase is down to 2 particular projects which were new and were not included in our internal budgets or our external guidance. The first one is the HexaBody CD38 with Janssen, our next-generation CD38. That deal as you know we announced on June 11. So we are ramping up expenditure on that program both on the preclinical and starting the commitment for CMC cost.
And the second one was the BliNK CD47 license that we announced on July 12. That's where we're licensing that CD47 to go into a bispecific using our DuoBody technology and again we're ramping up expenditure on that program in the second half of 2019 and we're beginning to make some commitments around that program. So, really, it's 1 program advancing, 2 new programs which are an addition. And as always, when we issue our guidance, the guidance does not include any new potential deals. So I guess really all positive on the expense side. It's increased investment. It's increased investment in the R&D for potential new products and potential new R&Ds to come forward in the next year or so.
And in terms of next year's, we're probably a little bit early to get into next year's expenditure. As we've seen for this year, 60% of our total expenditure is our project investment. I'd expect again in 2019 that the largest proportion will be on those projects. And again, very much like this year it'll be heavily weighted to the most advanced programs. Good news with tiso, of course that we are sharing those costs on a 50-50 basis. You won't see that in the operating expense line but of course you do see it as a credit coming back from Seattle Genetics in the revenue line. The other expenditure is really going to depend on the level of progress of a particular program. So they're difficult to predict at this stage. Everything is continuing very nicely at this particular point. They're very novel, they're very differentiated programs. It really depends if they're continuing to bounce. If we can find the therapeutic windows, if there is no tox profile, then we're very happy to increase the expenditure or as we prefer to look at it, increase the investment in those programs as we go forward. Of course, we've got the 2 BioNTech programs. Again, we are sharing those costs on a 50-50 basis with BioNTech. So that does help to defer the net cost of those programs at the end of the day.
On tiso, the first commercial with -- starting to become true in the U.S. on the -- as a reminder, Seattle Genetics will take the lead on the U.S. market. But that means that we will be contributing to some of their cost for the program. And of course the whole thing on a global basis is 50-50. But we are building up our commercial. I mean, it's relatively small numbers. As you saw on the headcount chart, out of our 180 employees, just 9% of those are in medical affairs and commercial. And we do see sort of medical affairs growing before the commercial. We have got some strategic commercial people that we hired. Of course we're a little ways away from actually getting into the sales force and particularly with Europe. That will come a little later for tiso, so not really much impact in 2020. Hopefully, that will give you some answers.
是。就运营费用而言，我们实际上计划的运营费用略高于我们执行原始指导时的收入。所以不会增加1.5亿丹麦克朗以上的增幅。真正推动的三件事是我们现有的CD3xCD20计划之一，而这正是我们在特定计划中取得的进步和良好进展。其余部分 - 大部分费用增加归结为2个特定项目，这些项目是新的，未包含在我们的内部预算或外部指导中。第一个是带有Janssen的HexaBody CD38，我们的下一代CD38。正如您所知，我们在6月11日宣布了这笔交易。因此，我们正在加快该项目的开支，包括临床前和开始承担CMC费用。
在tiso上，第一个广告 - 在美国开始变为现实 - 作为提醒，西雅图遗传学将在美国市场上起带头作用。但这意味着我们将为该计划的部分成本做出贡献。当然，全球范围内的全部事情是50-50。但我们正在建立我们的商业广告。我的意思是，这个数字相对较小。正如您在人员排行榜上看到的那样，在我们的180名员工中，只有9％的员工从事医疗和商业活动。我们确实看到在商业广告之前增长的一些医疗事务。我们雇佣了一些战略商业人士。当然，我们距离实际进入销售队伍还有一段距离，特别是在欧洲。对tiso来说会稍晚一点，所以2020年的影响不大。希望这会给你一些答案。
The line of Michael Novod from Nordea is open.
Just a follow-up to Wimal's question on the SubQ. If you could just talk about the communication but there's also a discussion at ASCO around post monitoring, around 3 hours from KOLs that J&J requires 6 hours of post monitoring from the, with the first SubQ infusion. And thereafter, it's up to the patient's discretion. Can you just explain what is, to say, why that monitoring is required for the SubQ? And then just a small one for David. Why don't you use a higher dollar for the milestones when you do it for the royalties?
仅仅是关于SubQ的Wimal问题的后续行动。 如果您可以谈谈沟通，但ASCO也会围绕监控进行讨论，距离KOL约3小时，J＆J需要进行6小时的后期监控，并进行第一次SubQ输液。 此后，这取决于患者的自由裁量权。 您能解释一下为什么SubQ需要监控的原因吗？ 然后只是一个小大卫。 当你为特许权使用费做的时候，为什么不用更高的美元用于里程碑？
Jan van de Winkel
Thanks, Michael, for the question. I think it is just safety in the COLUMBA study, Michael, for the, for watching for the infusion-related reactions. But I must say that I don't know the exact reason for the 6-hour monitoring period, but I understand from Janssen is that it tends to get shorter and shorter and shorter. A bit more experience on physicians with the SubQ formulation. But we may have to ask you, to follow up with you, Michael, to give you further perspective on that. David?
谢谢，迈克尔，这个问题。 我认为这对于COLUMBA研究来说只是安全，迈克尔，因为观察输液相关反应。 但我必须说，我不知道6小时监测期的确切原因，但我从Janssen了解到，它往往越来越短，越来越短。 使用SubQ配方的医生更多经验。 但我们可能不得不问你，跟进你，迈克尔，给你进一步的观点。 大卫？
Yes. We thought it was about 3 hours for that monitoring. But again, with the SubQ, we get lower infusion rate of reactions. I know it's really -- nearly all of them are related to the first [indiscernible], so I think still there's a huge advantage with the SubQ, once you get to the second, third and beyond infusions. So I think that will really cut down the time compared to where we are today with the IV format. In terms of milestones, you're absolutely right, Michael, I left those in at the, around DKK 1.5 billion. As you know, those 2 sales related milestones in total are $250 million. As I said, they're going to come in right at the end of the year. I don't know where the U.S. dollar/Danish kroner exchange rate is going to be at the end of the year. But the complete transparency, look, if you take that $250 million, use the exchange rate we had at our original guidance of 6.00, that gives you the DKK 1.5 billion. If we use $650 million, the same as I've done with the royalty income, then that would give us DKK 1,625 million, so that will give us DKK 125 million upside, not too material on the total revenue that we have in guidance of 4.8 million. But sure, we get both of those milestones, the rate stays at 6.5, then we'll have a little upside here at DKK 125 million.
是。我们认为监测大约需要3个小时。但同样，使用SubQ，我们可以降低反应的输注速度。我知道它确实 - 几乎所有这些都与第一个[音频不清晰]有关，所以我认为，一旦你进入第二，第三和超越输液，SubQ仍然有一个巨大的优势。所以我认为与IV格式相比，这将真正缩短我们今天的时间。就里程碑而言，你是绝对正确的，迈克尔，我留下了大约15亿丹麦克朗。如您所知，这两个与销售相关的里程碑总计为2.5亿美元。正如我所说，他们将在年底进入正确的状态。我不知道美元/丹麦克朗汇率在年底会在哪里。但完全透明，看看，如果你花费2.5亿美元，使用我们原先指导的6.00的汇率，这给你15亿丹麦克朗。如果我们使用6.5亿美元，就像我对特许权使用费收入一样，那么这将给我们16.25亿丹麦克朗，这将给我们1.25亿丹麦克朗的上行空间，对我们在指导中的总收入不太重要480万。但可以肯定的是，我们获得了这两个里程碑，速度保持在6.5，然后我们将有1.25亿丹麦克朗的优势。
The line of Graig Suvannavejh from Goldman Sachs is open.
Goldman Sachs的Graig Suvannavejh系列开放。
Congrats on all the progress and on the IPO. Two questions if I can. Just one, on the next-generation anti-CD38 HexaBody, can you remind us on where there is the ability to improve over DARZALEX and what you're trying to achieve there? And when we might see some data from that program? And then secondly, just on teprotumumab. Can you remind us what the financial arrangement is with Horizon on that candidate and how are you seeing the opportunity?
祝贺所有进展和IPO。 如果可以，我有两个问题。 只有一个，在下一代反CD38 HexaBody上，你能否提醒我们哪些方面有能力改进DARZALEX以及你想在那里实现什么？ 当我们看到该程序的一些数据时？ 然后，就在teprotumumab上。 您能否提醒我们Horizon对该候选人的财务安排是什么？您是如何看到这个机会的？
Jan van de Winkel
Thanks, Graig. Nice to speak with you. Let me address both questions. The next-generation CD38 HexaBody is super potent in killing CD38 positive target cells, Greg, including the cells that cannot be hit by daratumumab because daratumumab is very sensitive to certain threshold level of CD38. And this CD38 HexaBody molecule can actually much more potently kills cells, not only multiple myeloma cells which cannot be killed by daratumumab anymore, but also cells from leukemia and lymphoma tumors and we tested a very large battery. Hopefully this year, you will see some preclinical data. We are preparing the molecule for the clinic, for evaluation in the clinic. We do 2 trials initially. One in multiple myeloma, one in diffused large B-cell lymphoma, where it's a huge unmet medical need. Now we have very strong preclinical data and we hope that we can actually move the molecule in the clinic in 2020. So, it will take some time before you see data from the clinical study, Graig. But hopefully, some preclinical data this year at a scientific conference.
Then, the second question on teprotumumab. We originally created that molecule for Roche, under a Roche interaction. It's a partnership that we set up in 2002 and we got a very nice single digit royalty, mid-single digits royalty from Horizon for teprotumumab if that molecule hits the market, which we hope it will be quite soon. So it can become a nice income driver for Genmab.
谢谢，格雷格。很高兴与您交谈。我来解决这两个问题。下一代CD38 HexaBody在杀死CD38阳性靶细胞Greg方面非常有效，包括daratumumab无法击中的细胞，因为daratumumab对CD38的某些阈值水平非常敏感。而且这种CD38 HexaBody分子实际上可以更有效地杀死细胞，不仅是不能被daratumumab杀死的多发性骨髓瘤细胞，而且还有来自白血病和淋巴瘤肿瘤的细胞，我们测试了非常大的电池。希望今年你会看到一些临床前的数据。我们正在为诊所准备分子，以便在诊所进行评估。我们最初做了2次试验。一个多发性骨髓瘤，一个在弥漫性大B细胞淋巴瘤中，这是一个巨大的未满足的医疗需求。现在我们有非常强大的临床前数据，我们希望我们能够在2020年实际在临床中移动分子。因此，在您看到临床研究数据Graig之前需要一些时间。但希望今年在科学会议上有一些临床前数据。
然后，关于teprotumumab的第二个问题。我们最初是在罗氏相互作用下为罗氏创造了这种分子。这是我们在2002年建立的合作伙伴关系，我们获得了一个非常好的单位数版权使用费，来自Horizon for teprotumumab的中等单位版税，如果该分子进入市场，我们希望它很快就会出现。所以它可以成为Genmab的一个不错的收入驱动因素。
The line of Emily Field from Barclays is open.
I was just wondering if you could comment on just sort of how are you thinking about your growing cash balance particularly in light of the funds raised via the IPO in the U.S. and just how you're thinking about using these proceeds because obviously you have so much going on with your internal pipeline. Just how you, I would assume that it's going to be used a decent amount to acquire external assets, just sort of what your overall philosophy towards M&A is in the context of your growing cash.
我只是想知道你是否可以评论你如何考虑你的现金余额增长，特别是考虑到通过美国IPO募集的资金，以及你如何考虑使用这些收益，因为显然你有这样的收益 你的内部管道很多。 就你而言，我会假设它会被用来获得相当数量的外部资产，而这正是你对并购的总体理念是在你不断增长的现金背景下。
Jan van de Winkel
Thanks, Emily, for the question. I will start with this and then I will ask David to chip in also. First of all, we will use the cash to accelerate all programs. As we are already doing, as David said, this year, with some new molecules we bring into the pipeline, Emily. But the whole strategy of the company is actually focused on identifying the next 2 clear winners, clinical winners, and then maximize the potential. And then if one does, then we can easily spend $400 million to $500 million per program if you do military style, parallel clinical development. And that's the #1 goal for the company. But of course, you're also looking at scouting opportunities to in-license either products or technologies as we have done with the partnership with Janssen on the next-generation CD38 antibody and with the BliNK CD47 antibody recently. We have done the Immatics partnership last year, Emily. And you will see -- you can expect to see more partnerships, strategic partnerships of the company where we would potentially also spend more and more capital on. We're also watching the landscape very, very carefully for next-generation technologies which we think would complement our technology base, Emily. And of course with the cash now on the bank, we actually -- we can actually move very swiftly and very quickly to actually broaden the technology base of the company, both product-wise and technology-wise. And you'll see examples of each one of those in the coming time, I believe. David, you want to give further color?
谢谢，艾米莉，这个问题。我将从这开始，然后我会要求大卫进入芯片。首先，我们将使用现金加速所有计划。正如我们已经在做的那样，正如大卫所说，今年，我们带来了一些新的分子，艾米丽。但该公司的整体战略实际上集中在确定接下来的两位明确的获胜者，临床获胜者，然后最大化潜力。如果你这样做，那么如果你做军事风格，并行临床开发，我们可以轻松地为每个项目花费4亿到5亿美元。这是该公司的首要目标。但是，当然，您也正在寻找机会，以获得许可产品或技术的许可，就像我们与Janssen合作开发下一代CD38抗体和最近使用BliNK CD47抗体一样。我们去年完成了Immatics合作伙伴Emily。你会看到 - 你可以期待看到更多的合作伙伴关系，公司的战略合作伙伴关系，我们可能也会花费越来越多的资金。我们也非常非常仔细地观察下一代技术的景观，我们认为这些技术将补充我们的技术基础Emily。当然，现在银行的现金，我们实际上 - 我们实际上可以非常迅速地，非常迅速地实现公司的技术基础，无论是产品方面还是技术方面。我相信你会在未来的时间里看到每一个的例子。大卫，你想要进一步的颜色？
I think you sort of summarized it well there, Jan. I think our role -- it just gives us that ability, increases our financial strength and strategic flexibility. So we can maximize the value from any partnerships and also commercialize select products as we desire. But with that additional capital that we've got, it means we can negotiate from a position and strength any deals that we do. Jan mentioned CD3xCD20, it gives us to capabilities and the choices and also means that we can go into any negotiations that would go into, on an equal footing. No great change to the strategy overall. No great plans for large M&A. So it's really more of the same and continue with our financial discipline.
我认为你在那里总结得很好，Jan。我认为我们的角色 - 它只是给了我们这种能力，增加了我们的财务实力和战略灵活性。 因此，我们可以从任何合作伙伴关系中最大化价值，并根据需要将选定产品商业化。 但是，凭借我们已经获得的额外资本，这意味着我们可以从一个位置进行谈判并加强我们所做的任何交易。 Jan提到了CD3xCD20，它为我们提供了能力和选择，也意味着我们可以在平等的基础上进行任何谈判。 整体战略没有太大变化。 对大型并购没有好的计划。 所以它真的更相同，并继续我们的财务纪律。
The line of James Quigley from J.P. Morgan is open.
On DARZALEX guidance, you kept it flat at $3 billion. Now that you've got the approval from [indiscernible] can you tell when you originally expected the approval in the guidance? And on top of that, if you back out what you implied from the J&J sales, it's around about an $80 million one-off, so how does that factor into the guidance?
在DARZALEX指导下，您将其保持在30亿美元的水平。 既然您已获得[音频不清晰]的批准，您能否告诉您最初预期在指导中获得批准的时间？ 最重要的是，如果你退出强制销售所暗示的内容，一次性约为8000万美元左右，那么这个因素如何影响指导？
Jan van de Winkel
I think James, I'll pass these questions to David. David?
Sure, yes. A lot of different moving parts and bits and pieces that are in there. I mean, we're quite pleased with where we are at the half-year point. We've got about, Janssen's net sales, about $1.4 billion. As you know, the target for the year is $3 billion. So that means we got to get $1.6 billion in the second half. It's great to have that contribution at that pricing accrual adjustment in there. It means that I wouldn't expect any change to that or any, a repeat of that in the second half overall. But, I think we're well-positioned here, with that $80-odd million of price adjustment, we do get to keep that, we do get royalties on that. So that does help with our overall target for the year. But really, the same thing as we said at the beginning of the year, we're looking for the U.S. to grow from $1.2 billion to about $1.7 billion, growth of $500 million in 2019. We expect most of that growth to come from the second line and we talked about the gain in market shares earlier. The newly diagnosed multiple myeloma, approved on June 27, would I have liked it to have been approved a month or so earlier? Sure. But I think, it's approved now. I mean originally, we said around $200 million of incremental expectation in the frontline. We do, remember, have the advantage in the frontline setting. So, for the second half of 2019, all of these new patients coming in postapproval are going to be on the higher dosage of daratumumab. Remember, we've got weekly dosing and biweekly before we go onto the once every 4 weeks. So that means the dollar value per patient is always the highest in that first 6 months and that means every frontline patient on DRd is going to be a high contribution patient for us in the second half. So we still expect a nice growth coming in the U.S. from the frontline setting.
In terms of the rest of world, we've been pleased with some of the data we've seen so far. What they learned -- launched in frontline multiple myeloma with DVMP, that's going very well. We are seeing further penetration in Spain and Italy. As you know, they were fairly late to get their approvals. Earlier this year, we even saw the U.K. get approval in the second line with a combination with Velcade. And then the France reimbursement was agreed towards the end of June and I think that now means there's an opportunity in France with the reimbursed price both in monotherapy and the combination with Velcade and the combination with Revlimid that we can start to see France moving up as one of the EU5 countries, but really moving up the ranking tables to probably where it should be. Further growth in Japan as well to look forward to in the second half. As Jan mentioned earlier, we have filed for DVMP in the frontline setting in Japan and when we saw the original launch in Japan, it picked up very quickly, it was adopted very quickly in the relapse setting. And then finally, we also had approval in China for the monotherapy. I'm not going to project what the Chinese sales were, if we find that places like Japan, I find that difficult to predict, I think China will be even more difficult. But having the approval in China is a great start. So, a lot to look forward to in the second half and I would say with that pricing adjustment for around the $80-odd million in there as well, as I said, we got to keep that and we're still looking forward to get that $3 billion of net sales in 2019.
就世界其他地区而言，我们对迄今为止看到的一些数据感到满意。他们学到了什么 - 用DVMP在前线多发性骨髓瘤中发现，这种情况非常顺利。我们看到西班牙和意大利的进一步渗透。如您所知，他们获得批准的时间相当晚。今年早些时候，我们甚至看到英国联合Velcade在第二线获得批准。然后法国的报销在六月底达成一致，我认为现在意味着法国有机会在单一疗法和与Velcade的结合以及与Revlimid的组合中获得报销价格，我们可以开始看到法国向上移动EU5国家之一，但真正将排名表提升到应有的位置。日本的进一步增长以及下半年的期待。正如Jan先前提到的那样，我们已经在日本的前线设置了DVMP，当我们在日本看到最初的发布时，它很快就恢复了，它在复发环境中很快被采用。最后，我们还在中国批准了单药治疗。我不会预测中国的销售情况，如果我们发现像日本这样的地方，我发现难以预测，我认为中国将更加困难。但在中国获得批准是一个很好的开端。因此，在下半年期待很多，我会说那里的价格调整大约在80美元左右，正如我所说，我们必须保持这一点，我们仍然期待得到2019年的净销售额为30亿美元。
The line of Wimal Kapadia from Bernstein is open.
That is actually one from James' original, first question at the start of the call. Do you happen to know how much of the Revlimid first line use is in monotherapy versus in combination with Velcade. So what I'm really trying to get is a sense of the DRd opportunity versus the future DVRD opportunity, just based on the current split?
这实际上是詹姆斯在电话会议开始时的第一个问题。 您是否碰巧知道Revlimid第一线用于单药治疗与使用Velcade相比有多少。 因此，我真正想要获得的是DRd机会与未来DVRD机会的感觉，仅基于当前的分裂？
Jan van de Winkel
Do you know that's a question -- do you have an answer for Wimal?
你知道这是一个问题 - 你对Wimal有答案吗？
No I haven't got accurate data on that, Jan. I think the other open question will be, we'll need to see more detailed data for it is that the DRd combination going to be cross-trial comparison. But is it going to be comparable with RVd? So I don't think it's just necessarily, are you going to go from Rd to DRd? Or you could possibly going to go from RVd to DRd? And I think that will be another comparison that's made as well. But I think the data we've seen from there has been very impressive. The PFS numbers, the SCR numbers, the NRP negative key numbers, whichever sort of scorecard you look at it on, and I think DRd is an excellent combination in the frontline setting. And we do have the dara RVd combination trials ongoing and the GRIFFIN data which you'll see in more detail coming up in the not-too-distant future. So I think DRd should take -- I'm anticipating a good market share for DRd in the frontline setting.
不，我还没有得到准确的数据，Jan。我认为另一个未解决的问题是，我们需要看到更详细的数据，因为DRd组合将进行跨试验比较。 但是它会与RVd相媲美吗？ 所以我不认为这只是必然的，你会从Rd到DRd吗？ 或者你可能会从RVd到DRd？ 而且我认为这也是另一种比较。 但我认为我们从那里看到的数据非常令人印象深刻。 PFS号码，SCR号码，NRP负值密钥号码，无论你看到哪种记分卡，我认为DRd是前线设置的绝佳组合。 我们确实正在进行dara RVd组合试验和GRIFFIN数据，您将在不久的将来更详细地了解这些数据。 所以我认为DRd应该采取 - 我预计DRd在前线环境中的市场份额很大。
There are no further questions at this time. Please continue, sir.
Jan van de Winkel
So, thank you for calling in today to discuss Genmab’s financial results for the second quarter of 2019. We look forward to speaking with you all again soon.
Ladies and gentlemen, that does conclude our conference for today. Thank you for participating. You may all disconnect.
女士们，先生们，今天的会议结束了。 感谢您的参与。 你可能都断开了。
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