Hello, and welcome to the Genmab Q4 2020 Conference Call. Throughout the call, all participants will be in listen only mode and afterwards, there will be a question and answer session. And just to remind you, this conference call is being recorded. 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 an obligation to update statements regarding the future, nor to confirm such statements in relation to actual results, unless this is required by law. Please also note that Genmab may hold your personal data as indicated by you as part of our Investor Relations outreach activities in order to update you on Genmab going forward. Please refer to our website for more information on Genmab Today, I'm pleased to present Jan van den Wenkel. Please go ahead
with your meeting.
Hello and welcome to the Genmab conference call to discuss the company's financial results for the period ended December 31, 2020. With me today to present these results is our CFO, Anthony Pergano. And then for the Q and A, we will be joined by our Chief Development Officer, Judith Klimowski Our Chief Operating Officer, Anthony Monsigni and Tai Yamadi, who as of March 1, will be our Chief Medical Officer. Many of you You may already be familiar with Tai from his participation in events like our 2020 Capital Markets Day and the 2021 JPMorgan Conference. I would like to take a moment to say how thrilled we are to welcome him as a member of Genmab's executive management team.
With his leadership and proven track record of success and innovative thinking, he makes our strong team even stronger. I look forward to working with him and the rest of the team as we continue to grow our organization and evolve into a fully integrated Biotech Innovation Powerhouse. Let's move to Slide 2. As already said, we will be making forward looking statements. So please keep that in mind as we go through this call.
Let's move to Slide 3. Genmab is focused on the development of innovative antibody products with the potential to transform cancer treatments and improve the lives of cancer patients. For over 20 years, we have not wavered in this commitment. In 2010, we linked this core purpose to an extremely Effective strategy by focusing on our core competences of being able to identify the very best disease targets, Develop differentiated next generation antibody technologies and create unique best in class or 1st in class antibodies, We have been able to turn Genmab's world class science into a robust proprietary pipeline and approved medicines, effectively allowing us to build a sustainably profitable and successful biotech. I'm very pleased with our track record of success, but we are only just getting started.
With the first regulatory submission, along with our partner Cgen For tizotumab vedotin, we are closer than ever to achieving of our ambitious 2025 vision. And well, this leads me to slide number 4. I'm extremely proud of the recent BLA submission for tislelomab vedotin, the first of our products where Genmab has 50% ownership of the program. If approved, dizotamab vedota would be the 1st in class therapy and we believe it has the potential to become an important treatment option for women with recurrent or metastatic cervical cancer who have disease progression on or after chemotherapy. We look forward to providing you with an update on this submission in due course.
While this BLA submission was a milestone for our company, It is one of many that we reached over the past 12 months. So now let's move to Slide 5 and look and take a look at some of our more recent achievements. 2020 was a transformational year for Genmab. We have a strong foundation of innovative science and an unparalleled history of repeated R and D success. Over the course of the past few years, we strategically built on this foundation with the goal of evolving into a fully integrated end to end biotech.
Because of our exceptionally talented world class team, we reached an inflection point in this journey in 2020 with a series of key events. 1st among these is our collaboration with AbbVie, which marks a landmark achievement for the company. This collaboration allows us to both and accelerate the development and commercialization of 3 of our bispecific antibody products including aporitamab and it further strengthens our already very strong financial position. 2020 is our 8th year of profitability With an impressive 139% increase in operating profit versus 2019. Our strong balance sheet allows To continue to strategically invest in our capabilities and differentiated product pipeline as will be discussed by Anthony in more detail.
These investments are already showing themselves in the way our pipeline is expanding and maturing. Thanks to our productive R and D engine, We ended 2020 with 7 programs in the clinic where we have at least 50% ownership and 2 of these abgaritumab and tisotumab vedotin are now in Phase 3. And it's not only in our own pipeline where we see Janmab's innovation in action. Janssen's dual body product amivantamab became the 1st dual body to both receive breakthrough therapy designation from the FDA and be submitted for regulatory approval in both the U. S.
And in Europe in 2020. Should amivantema be approved, it would continue our Solid track record of success in creating approved medicines that are developed and commercialized by other companies. So now let's move to slide 6 And look at these successes. DARZALEX, COSIMTA and TEPESA, Genmab created therapies marketed by our partners All had firsts in 2020. DARZALEX is now a major blockbuster that has redefined the treatment of multiple myeloma.
In 2020, a subcu formulation was approved in both the U. S. And in Europe, making it the first and Only subcu CD38 monoclonal antibody approved for the treatment of multiple myeloma. Subsequently, this formulation was approved in the U. S.
And AL amyloidosis, making it the very first FDA approved treatment for this devastating disease. A second subcu medicine approved in the U. S. In 2020 was subcutaneous ofatumumab or Cosimpta for relapsing MS. This is the first piece of therapy that can be self administered by patients at home.
With the recent positive opinion from the CHMP, We are hopeful that Kacinta will soon become available for relapsing MS patients in Europe as well. Then finally, Tepesa, This became the 1st and only FDA approved medicine for the treatment of thyroid eye disease. We are enthusiastic about the future of these medicines As they exemplify our commitment to applying our world class antibody expertise to create differentiated antibody therapeutics with the potential to fundamentally improve patients' lives. And of course, the collaborations for these three medicines have provided us With the financial foundation of our current success with recurring revenue from royalties on DARZALEX to CIMTA and TEPESA, which we can use to invest further in the business to deliver our inspirational vision. And at this point, I will now turn the call over to Anthony.
Anthony, please go ahead.
Great. Thanks, Jan. Let's move to Slide 7. We've never been in a better position to achieve our vision of transforming the lives of cancer patients. And in 2020, we've continued to execute against our priorities despite the challenges of COVID.
My objective today is twofold. First, to explain why 2020 has been yet another remarkable year for Genmab and second, to provide our guidance for 2021, which is set to be another very strong year. I want to start by reminding you of the robust foundation we've continued to strengthen. We grew recurring revenue by 50% in 2020. That's due to royalties from DARZALEX, TEPEZZA and KOSIMTA And that's ensured an 8th consecutive year of profitability.
Our strong balance sheet and growing recurring revenues allowed us to continue to invest in our business and our pipeline in a very focused and disciplined way. And an important part of this has been to continue to build the team and capabilities to enable us to succeed. So let's look at those revenues in a bit more detail on the next slide. We saw continued strong performance for DARZALEX in 2020. You can see that in the chart on the left.
Overall, DARZALEX sales grew by 40%. That's net sales of nearly DKK4.2 billion which translates to DKK4.4 billion in royalty revenue. This exceptional growth was driven by continued strong market shares across all lines. The softness you can see in Q2 was a direct effect of COVID. Sales quickly recovered with significant growth in H2 2, fueled in part by the continued uptake of the subcu formulation.
So DARZALEX remains a key driver of our revenue as you can see on Slide 9. Looking at the graph on the left, you can see that there were 2 main drivers for the higher revenue in 20 2nd, recurring revenue grew by 50%. That's primarily due to DARZALEX royalties, which were up 41%. And we also saw additional recurring revenue growth from TEPEZZA and COSIMTA royalties. Partially offsetting these two items was lower milestones in 2020.
As well as increasing revenues, we also increased investment As you can see on the next slide. Total operating expenses came in just a touch below DKK3.8 billion in 2020. And here, you can see where we invested. We accelerated our investment into our product portfolio, especially the advancement of both EFCO and dual body PD L1-four-1BB. We've also spent more on expanding our team, hiring key team members to support our growing product pipeline.
And we've continued to build our commercial capabilities and invest in systems to support our expansion. Finally, we are leveraging the AbbVie collaboration by utilizing their And significant financial contributions to further accelerate and broaden our partnership programs. Now, let's look at our financials as a whole On slide 11. Here you can see our summary P and L. In 2020, revenue came in at DKK 10,100,000,000, kroner, an increase of over $4,700,000,000 compared to 2019.
The increase was primarily driven by the upfront payment from AbbVie and Operating income was $6,300,000,000 compared to $2,600,000,000 in 2019. Our net financial items amount to a loss of $409,000,000 which was primarily driven by 2 partially offsetting items. First, unrealized foreign exchange rate losses related to our U. S. Dollar denominated cash and investments due to the move lower in the dollar.
And second, an unrealized gain on our investment in CureVac. Then we have tax of $1,100,000,000 which equates to an effective tax rate of 19.4%. It's important to note at this rate is positively impacted by some one time items in 2020. By contrast, our rate was around 24% in 2019 and this is probably more reflective of what we would expect moving forward. And that brings us to our net income of $4,800,000,000 So By any measure, 2020 was an extremely strong year.
I'll now turn the call back over to Jan to discuss
Thanks, Anthony. Let's move to slide 12. Our maturing pipeline is the result of a world class R and D engine. Our novel approaches to disease target discovery and unique next generation antibody technology platforms allow us to create truly differentiated antibodies that will further fuel our own pipeline with potential 1st in class and best in class therapies. We are highly confident that our technologies will continue to grow our pipeline because we have already been doing this.
On the right, you see the impressive progression resulting from our productive R and D engine and Responding clinical development programs in our pipeline over the last 5 years. In 2016, we only had 2 product candidates in the clinic. We anticipate more than 8 programs underway by the end of this year in more than 20 clinical trials. And our pipeline is not just growing, It is also rapidly maturing. We started the year with 2 products abcuritumab, antisotamab vedotin in Phase 3 And we are planning for additional Phase 3 trials to start in 2021.
So now let's move to Slide 13 and take a closer look at the 2 key areas of investment in our pipeline for 2021. To continue to deliver on Genmab's promise Of creating and developing truly differentiated antibody therapeutics, we intend to continue to significantly invest in the development of both abcuritumab And dual body PD L1-four-one BV. We are continuing to focus on these particular products Given our belief in their potential to become important new treatments, should they eventually be approved. Starting with At olitumab, we believe this could be a best in class product. This confidence comes from both the clinical data we have seen and format subcutaneous route of administration, a feature that differentiates it from other CD3, CD20 bispecifics.
Along with AbbVie, we are planning a highly comprehensive and aggressive development plan for this product across a variety of hematological malignancies and lines of treatment. Dual body PD L1-four 100 and B, one of the products that we are developing along with BioNTech, Has the potential to be 1st in class and to provide Genmab with a truly differentiated 1st in class bispecific next generation checkpoint immunotherapy. There is a high unmet medical needs to improve on checkpoint immunotherapies and we are encouraged By the first clinical data presented at SITC last year. Given the potential for these products to be either 1st, our best in class, there are significant potential across multiple oncology indications and unmet medical need for patients. We remain focused on further accelerating these programs.
This reflects our clear priority of developing differentiated therapeutics for patients as fast and as broadly as possible. I will now turn the call back to Anthony to discuss our 2021 guidance. Anthony?
Thanks, Jan. Let's move to slide 14. Before I provide you with our guidance, I'd again like to spend a moment The underlying framework and the related key drivers. First off, let's think about our revenue profile. On the left, you can see component parts of our current and future recurring revenue streams.
Starting with the approved products where we receive royalties, we're looking forward to the Continued growth and expansion of DARZALEX in 2021 beyond. You can also see Kasimpta and Tepesa. As we've heard from our partners, These are both potential blockbuster products. So we're really excited about the potential of these 2 recurring revenue streams for the years to come. We've also got 2 potential additional revenue streams in the future.
We submitted the BLA for tazotamepodone earlier this month. At the end of last year, Janssen submitted a BLA and an MAA for amivantamab. If these products are approved, They'll bring our total number of approved products to 5. Now on to our focused approach to investment shown on the right. We'll continue to invest for sustained success with focus and disciplined investment in our pipeline.
And as highlighted by Jan, we'll accelerate and expand our We'll also ensure we are ready to launch should tazotamivudotin and in the future eptridimab be approved. As well as investing, we will of course remain focused on the bottom line and we fully intend to deliver a 9th consecutive year of profitability. Let's take a closer look at an important component of our recurring revenue growth, DARZALEX sales on slide 15. Here, we are on a clear path to market leadership in multiple myeloma. For 2021, we anticipate that DARZALEX sales We'll continue to ramp up and we expect sales to be in the range of $5,200,000,000 to $5,600,000,000 There are 3 drivers underpinning this First, there is significant opportunity for further market share gains in Frontline.
2nd, the rapid conversion to the subcu version is expected to continue. And 3rd, with 8 approved indications in the U. S, we anticipate continued strong market shares across all lines of therapy. So DARZALEX is really continuing to deliver for us. Now let's take a look at the components of our revenue on Slide 16.
For 2021, we anticipate another year of strong revenue growth, excluding of course the AbbVie up We're projecting DARZALEX royalties to be in the range of DKK 4,900,000,000 to DKK 5,300,000,000. Recurring revenues in total, including royalties for Tepesza and Casimpta are anticipated to increase approximately 20%. It's useful to unpack This recurring revenue growth a bit more. Now starting with sales from our products marketed by partners. As you've heard, We're expecting Dara to grow by around 30% in 2021.
And both TEPEZ and KOCIMTA are also well positioned for strong growth this year. As we translate these very strong product sales into royalties, we do have some significant headwinds in 2021. But in our mind, these aren't reflective of the very strong underlying fundamentals. More precisely, total recurring revenue growth takes into account a negative impact of around 20 percentage points to the growth of DARZALEX due to 2 items. First, lower FX.
The 2020 average rate for the dollar kroner was around 6.5 and for 2021, we're assuming a flat 6. 2nd, reduction in royalties because of the ongoing arbitration with Janssen. Here, we've reduced our guidance To reflect Janssen's continued reduction of its royalty payments. This does not in any way reflect our position on the ongoing arbitration. And of course, we intend to continue to vigorously defend our contractual rights.
The impact of these two items It's between DKK800 1,000,000,000 to DKK1 1,000,000,000 and the split between the two items is roughly fifty-fifty. Turning to non recurring revenue, we also see some nice growth here, which will be driven by reimbursement revenue from our collaborations with BioNTech and Seagen and other milestones. Looking at our total revenue, we're expecting revenue of DKK 6,800,000,000 to DKK 7,500,000,000 with DKK 7,200,000,000 at the midpoint. Now let's move to slide 17 to take a look at our investment profile for 2021. Before highlighting our investments, I'd like to take a step back and put these investments in the context of our overall strategy and a very significant growth opportunities in front of us.
Our 2025 vision has acted as a guiding light for us. It focused on our core purpose to meaningfully impact the lives of cancer patients. And today, we've reached an inflection point where we find ourselves with an exciting pipeline that is maturing with 2 potential product launches in the next couple of years and with more to come. And that's a great place to be. But it also means we've now reached a point where there's a strong rationale to invest.
We've got all the ingredients to become a fully integrated BioSec powerhouse. Clearly, we're building the team and capabilities to enable us to succeed in this. As well as driving better patient outcomes, this will capture more value for our shareholders. So with that background, let's look at our investment priorities for 2021. Our total OpEx is expected to be between DKK 5,500,000,000 and kroner 5,800,000,000 and this fully reflects the investment priorities I shared with you at our Capital Markets Day.
Priority number 1 is filing and launching tazotamab vedotin. 2 is accelerating the development and launch of EPCO. 3 is expanding dual body PD L1-four-1BB and priority number 4 is standing up our commercialization capabilities In the U. S. And Japan, this is essential to realizing our full potential.
To support this growth, we're building Our teams and systems to evolve the organization for continued success. So these are our immediate priorities, but we're not just focused on today. In line with our vision, we're also very focused on long term value creation. So here we're investing to progress our early stage pipeline to generate the next wave of IND candidates. We're also investing to ensure that we maximize the value of our current technologies and that we stay right at the forefront of antibody science.
Finally, let me provide some context around the AbbVie collaboration. They're equally excited about accelerating and broadening EFCO as well as our other partner programs and you can see their expected step up in contributions in 2021. Now having looked at the framework and the constituent parts, let's look at how this all comes together on Slide 18. Here you can see our 2021 guidance. We expect our revenue to be in the range of DKK 6,800,000,000 to DKK 7,500,000,000.
As you can see, most of this is made up of recurring revenue. For operating expenses, we expect to be in a range of DKK 5,500,000,000 to DKK5.8 billion. This step up in investment is fully in line with our strategy and our focus on creating long term value. Putting all this together, we're still planning for substantial operating income in 2021 in a range of DKK1 1,000,000,000 to k2,000,000,000 Now for my final slide, let me provide a few closing remarks. In summary, we've created strong and growing recurring revenue streams.
And that gives us a strong backbone of significant underlying profitability. And we're investing those revenues in a highly focused way to realize our vision and capitalize on the very significant growth opportunities in front And on that note, I'll hand you back to Jan to discuss our key priorities for 2021.
Thanks, Anthony. Let's move to slide 20. Essential to our success in 2021 are key priorities for the year. With the recent submission of the tisotamab vedotin BLA, we are on track towards reaching these goals. In addition to the possibility of our first product on the market with our partner Cgen, We are also planning along with our partner AbbVie to accelerate development of our potential best in class epcalirizumab with the advancement of expansion cohorts and additional Phase 3 trials.
You may recall that the first patient was In the first Phase 3 abcuritumab trial in January this year. We will also focus our resources on continuing to further Sightingly, we anticipate to move at least one more proprietary product into late stage clinical development during 2021. We very much look forward to updating you on a number of our clinical programs over the course of this year. And we will continue the strategic development Our internal capabilities with the goal of building a smart commercialization model as we aim to not just create medicines that transform cancer treatments, But to provide these medicines to doctors and patients in the most effective way possible. Finally, As Anthony discussed, we expect to further strengthen our already extremely solid financial foundation.
Let's move to slide 21. As evidenced in the previous slides, we are very close to reaching our inspirational 2025 vision. Our vision has acted as a guiding light for It has focused us on our core purpose to fundamentally improve the lives of cancer patients. And this core purpose is linked to a laser sharp strategy that will allow us to build a profitable and very successful biotech. Today, we have reached an inflection point in our exciting journey where we find ourselves with 2 potential product launches in the next couple of years And with Marzocomm, as we evolve into a leading fully integrated biotech innovation powerhouse.
And let's move to our final slide. Slide 22, that ends our presentation of Genmab's 2020 financial results. Operator, please open the call for questions.
And our first question comes from the line of Peter Verdult of Citi. Please go ahead.
Yes, thank you. Peter Verdult, Citi. Yes. And we'd love to be talking about the pipeline exclusively, but maybe we could have 2 questions. 1 on the royalty rate for Anthony and then one on the pipeline.
Andy, just want to understand the royalty rate guidance a little bit better because we all knew that J and J were withholding The Halozyme or the share they thought you owed on the Halozyme patent from Q2, but you've got an exit royalty rate in the high teens for 2020 in Q4 and an implied royalty rate that is below 16 for 2021. Now I know FX is a component, But I. E. Is the delta and the change versus expectations in the market, is that a function of J and J withholding half of the Hey, Lazyme Royalty. Or is there something more broadly going on with the royalty rate structure that J and J have decided to withhold?
So just I just want to drill down a bit more on that given the importance of the near term valuation. And then secondly for Dan, for Judith or Tahi, just on those assets where you have or enjoy over 50% economics, Can you just give it a little bit more specific about what incremental data we will see in timing, be it for EPCO, GEN1046 or the 4 1BB CD40 program, just when what we might see incrementally and when this year. Thank you.
Thanks, Peter. Why don't we hand over the first question to Anthony Pagano and then I will take the
Deris sales grew by 40% in 2020 and we're estimating growth of around 30% in 2021. In absolute dollar terms, the quantum of sales has been growing over the last number of years, adding around $800,000,000 in 20 18, $1,000,000,000 in 20.19 $1,200,000,000 in 20.20. Now looking at our Adara royalty for 2021, we're estimating Royalty is the midpoint of around $5,150,000,000 This represents growth of around 17% compared to the growth in the underlying sales of around 30%. Now there are really 3 building blocks to get to the royalty rate. At the midpoint, you have Dara sales of $5,400,000,000 Secondly, you have the estimated effective royalty rate of 17.2% in 2021.
And then third, you have the dollar kroner foreign exchange rate. Now if you multiply these through and you use the average 2020 FX rate of just over 6.5 and you would get estimated royalties for 2021 of around $6,100,000,000 As I just noted, we're assuming royalties of 2021 for 2021 of $5,150,000,000 So this difference of around $900,000,000 is due to 2 items. First, The lower dollar kroner rate and here again, Peter, we've assumed a flat 6. And second, of our guidance, we've reflected Janssen's withholding or reduction of royalty payments due to the ongoing arbitration. So Peter, in summary, it really is down to these two items, FX and Janssen's continued with reduction of the royalty payments To Genmab, but as I mentioned, the underlying fundamentals remain very, very strong.
So Anthony, can I chance my arm here? Are you It seems to me that J and J are effectively asking you to pay half of that Halozyme royalty. Is that a fair assessment?
So Peter, at this point, I think I tried to give as much color as I can. We talked about the total impact this year due to these two items FX and as well as Janssen's continued withholding a reduction of the royalty payment amounting to $900,000,000 or so. And that roughly speaking, this $900,000,000
And then see whether we can ask Judith or Tay to step in there. We will have multiple data set this year, Peter. For aporitamab, we expect more data from the dose escalation, more follow on data, depth of responses, duration of responses, Potential data of the expansion cohorts which are growing very well. During this year, we haven't yet decided anything on timing. For the PD L1-four 100B program, we expect to get data from the expansion cohorts, Peter, we have multiple ongoing orders starting up.
For the CD441BB1, we expect data this year From the dose escalation, we have not decided yet with BioNTech on timing. And we also expect data from some of the earlier programs like the Duo HexaBody CD37 program, some of the other programs like the DR5, DR5 HexaBody program. And potentially, Peter, even from the hexa body CD38 program, but it all depends on how we are impacted by the pandemic, whether We can actually rapidly progress in those studies, but we are and of course, what I forgot to mention is, of course, we expect data from daratumumab Potentially from Phase 3 trials this year via Janssen. So this will be a very data rich year. We will give you in time, Peter, when we have decided which conferences to target and which timing to take for the different clinical trials, we will give you further Color as we always do on the timing, but this will be a very data rich year with GenMark proprietary programs.
I think one of the most Data which is up to now, Peter.
Thank you.
Thank you.
Our next question comes from the line of Emily Field of Barclays. Please go ahead.
Hi. Thanks for taking my question. Just Question of efgoritamad. Coming out of ASH with Mohsen and Glofit, Roche seem to be targeting kind of a more niche commercial strategy positioning It's a gentler asset for maybe more elderly or frail patients and GloFit is a stronger asset. I was just wondering, as you're building your commercial Assuming that, that is your belief.
And then, on that potential asset that could be moving into late stage development this year, is that one The assets potentially that's part of the AbbVie collaboration. Thanks.
Thanks, Emily, for the questions. I will hand over the first one to Tahira Amari first to give you a feeling for how we think about abtaritamab. But let me first take the second question from you, Emily. We actually have a number of candidates and we believe that we can actually bring one of these candidates at least To late stage clinical development during this year, there are a number of candidates and that also includes potentially other candidates from the collaboration, but we cannot be more specific at this time, Emily. But we promise you to actually come with data, as I already said in my So to Peter, potentially also parallels by late stage clinical development initiated in 2021.
So maybe Tay, you can Give some further color on aporitumab, how we are thinking of positioning Apco in the B cell cancer landscape.
Yes, sure. Thank you, Jan, and thank you for the question. I think I wouldn't want to comment too much on Roche or Genentech strategy. Think your characterization of the positioning of these two assets certainly aligns with how we see their strategy playing out, but we've been very clear from the very beginning what we think is the advantages of apolitamap and what our strategy is in terms of developing it. And so our vision has not changed.
Our belief has not changed. We believe that we have an asset that because of the route of administration is convenient. It may avoid some of the Grade 3 cytokine release issues and continues And we'll share some data to answer the other question as well towards the end of the year probably. It continues to show efficacy that We are excited about both in terms of response written and depth of response, CRS, and our intent, and we will execute on some plans in the next Couple of months that will be publicly announced, is very clearly to develop epcoidema across the entire spectrum of B2 malignancies And across all lines and then really position it as a backbone in a modality that will transform and change treatment paradigms as they are known today.
Thanks. And just one follow-up, if I could. How many Phase III trials do you anticipate being in by the end of the year? Thank you.
We haven't I will take that one, Emily. So we haven't yet given you that number. But in time, you will see more and more Phase 3s For APCO, coming on ct.gov and potentially for other molecules, but we haven't given you any number up to now.
Thank you.
Thank you. Thanks, Tay.
Our next question comes from the line of Trung Hyung of Credit Suisse.
Guidance. Can you tell us what that assumes for Faspro share of DARZALEX sales in 2021? I think it of DARZALEX in different lines of therapy for Dara. And are you seeing FASTPRO uptake more in the different lines of therapy? Or is the penetration similar across those
lines? Thanks very much.
Thanks, Thuyung, for the Thanks,
Trung, for the questions. I will hand the first one over to Anthony Parcano And the second and slash third question to Anthony Monsigni to speak a bit more about penetration of Dara versus Dara Fast Pro. Anthony, can you give answer to the royalty question?
Sure. Thanks, Trung. I think the sort of step So think about this, right? We've seen rapid uptake of DARZALEX FAST PRO in the U. S.
And subcu in some countries as other parts of the rest of the world. As you all know, we have the best visibility on the U. S. Market, where currently DARZALEX Fast Pro accounts for more than 50% of DARZALEX However, key uncertainty is Rest of World where we do have more limited visibility. As with DARZALEX sales tracking in general, as I mentioned, is lower visibility in the rest of the world and it's important to note that this does account for 45 percent of total DARZALEX sales.
However, if we put this all together, we believe it's fair to anticipate and assume that more than 50% Global DARZALEX sales will be Fast Pro or subcu in 2021. So Trung, not giving you a precise number, but That gives you some direction about how we look at this, not just in the U. S, but from a global basis.
Thanks, Anthony. Maybe Anthony Montcini. Anthony?
Yes. Thanks Jan and thanks Trung for the question. I think Anthony provided a lot of the guidance I would give just to add detail on line by line penetration of FastPro. What I can say is that we're seeing Bass Pro and subcu in general be a driver of performance and it's increasing pretty steadily And similarly across lines, I would say that we're continuing to see earlier and earlier use. And I think the inherent advantages of Fast Pro are the reasons why that is.
Just to give you a flavor Of overall share though, we're seeing about the highest overall first line share at 13% and the new share continues to outpace it. And when we We query, how much of that is Fast Pro. It's pretty similar across lines. And as Anthony mentioned, we're seeing over 50% Penetration or the comparison of IV versus subcu is about a fifty-fifty split in the latest data points and that's pretty evenly
Thanks, Anthony. Thank you, Trung. Thank you.
Our next question comes from the line of Michael Novod of Nordea Markets. Please go ahead.
H1 versus H2 and whether you have into your expectations that there is a potential COVID impact in H1 and then it eases up and accelerates into H2 in regards to sales performance. And then secondly, I don't know whether you can provide some additional guidance to more specific absolute commentary to Kysimpta and Tepetza royalties besides The 40% growth in royalties you have provided already. Thanks a lot.
Thanks, Michael, for the questions. And I will hand over both to Anthony Parcannon. Anthony?
Great. So, yes, so Michael, thanks for the question. I think in terms of Dara, we really like how we exited Q4, I mean, looking at the overall sales levels for Q4, we were at $1,250,000,000 And as we've entered 2021, we like what we're seeing thus far. Don't have any particular kind of guidance or specifics around expectations on a quarterly basis or H1 versus H2, Just sort of more the broader comments that we've continued to highlight looking at Dara's overall profile with the 8 approved indications in the U. S, Looking at the main growth drivers for 2021, continued market share gains in frontline, continued uptake Of subcu and just sort of more broadly, strong market share is expected across all lines.
And in addition, just a reminder, we do have amyloidosis This coming online. So that's for Dara. If you think about then TEPEZZA and KASIMTA sales, I think it's also kind of useful This is in a broader context. We're really excited now to have 3 products that are generating recurring revenue for us and look forward to have more in the future. Both Kasimpta and Tepesha have very compelling propositions for patients and we think they have very strong growth profiles moving forward.
For 2021, we expect each of these programs to grow significantly. We're not guiding, Michael, specifically for these two products, We can provide a bit of more color if we dig into our revenue guidance. We're estimating total recurring revenue to be around DKK 5,300,000,000 to DKK 5,900,000,000 And of that amount $400,000,000 to $600,000,000 relates to Tepesa and Casimpta. And as you just highlighted, this represents 40% growth compared to 21. Now for Tepesa, 2020 was just a remarkable launch year.
I mean the progress that was made there is just really unbelievable. But same as you, we've heard about what appear to be some short term supply disruptions. We have to be mindful of that for Tepesa, an overall remarkable launch year for 2020. For KASIMTA, the U. S.
Approval came in late August, in 2020 And to initiate access, Novartis has provided a significant amount of Cosympta free of charge for U. S. Patients. As we've heard, Novartis anticipates that a majority of the sales in the 1st couple of quarters here of launch will continue to be free goods, but expects the share to increase over time as reimbursement progresses. And finally, to start thinking about Kasymptom where some additional growth could come from, we certainly to be looking at The recent positive CHMP approval in January and in conjunction with that, Novartis is awaiting marketing authorization in EU.
So Michael, hopefully that gives you some additional color both for Dara, but also for
Perfect. Thanks a lot. Thanks, Michael. Thanks, Anthony.
Our next question comes from the line of Michael Schmidt
Tracey and with Janssen. I'm just curious around the timing. What is a reasonable Time frame when investors might potentially expect resolution. Is that something that could happen in 2021? Or is it a longer term process beyond that?
And then on the pipeline, I was wondering on the dual body PD L1-four-1BB product with BioNTech.
Thanks, Michael, for the questions. I will definitely hand over the second question to Tahi on PD L1-four hundred and one BB. We could speak a bit more about the expansion cohorts. Let me focus on the arbitration case. There's very little we can say.
And as I already said publicly, Michael, the timing is inherently uncertain, but you summed it up quite well. Yes, it could be concluded in 2021, But it could also potentially move into 2022. And it's very, very difficult to predict actually what Timing is in these arbitration cases. It's our very first, I can assure you, and I hope this will be our last arbitration case. But I think we cannot give you any further color at this time, because this is inherently uncertain.
Let me ask Tahi to give you a bit more color more precisely on the expansion cohorts and the next steps there. Tahi?
Sure. So yes, so first, I would say the expansion cohorts out of the first neuron trial for PA1-fourteen BB were built To do two things, to help us understand the biology of hormone maybe in very distinct Defined patient populations post IO or IO naive, but Diseases that are not necessarily amenable to checkpoint inhibition. And then obviously, in the second part to if we were to see a signal there to provide us with a path forward from a development point of view in these different indications. And so the answer to your question is the answer Always the same. What we need to see is data that makes us believe that as a single agent, we have a A high level of confidence that we provide a valuable opportunity to these patients.
And so there might be situations where there is a single agent path. And similarly, we will in the near future also show and publicly announce some plans where we will then generate data in combination. There will also define development plans. So I think it is essentially the answer To your question, I hope that clarifies it. Do we see enough single agent activity in a given indication?
Or do we see an opportunity to combine in a given indication. Thanks, Tariq.
Thank you
so much.
Thanks, Michael.
Our next question comes from the line of Matthew Harrison of Morgan Stanley. Please go ahead.
Great. Thanks for taking the question. I guess, 2 for me. 1, maybe you could just comment, You obviously
have a lot of assets that
are in development by others. Any this year where you would expect, some meaningful data that we Could see in terms of those potential royalty assets. And then secondarily, maybe just another question on 41BB. We've seen a couple of people advancing 41BB monotherapy assets recently. Just wondering how you're looking at the sort of competitive landscape of 41BB assets right now?
Thanks.
Thanks, Matthew. I will take the first question and definitely the next one the second one will go to Tai who can give you a bit more color on our 2, 401BB targeted bispecifics and how they actually Position themselves in the competitive landscape. But let me now walk over some of the assets with other companies, Which is which are created with Genmab Technology Base. Amivantamab for lung cancer can actually end up on the market this year. And those contains data in lung cancer from Janssen on amivantamab, it's called breakthrough therapy designation that is filed in the U.
S. And in Europe End of last year, we expect more data from aminhontamab, which can potentially already lead to royalties at the end of this year to Genmab. Then there is 2 other assets, 2 other bispecifics, both made with the dual body technology, Mathieu, teclistamab and talcretamab. They're both in Phase 2 And they both will come with data we believe this year from the Phase onetwo or even Phase 2 setting also from Janssen. And they could also in the future lead to product filings and royalty income via recurring revenue to Genmab.
And there is, of course, Novo Nordisk with MIM-eight, the anti Factor-nine Factor-ten hemophilia, a bispecific antibody, which is also in Phase 2 As we speak and we believe that at some point Nova will also start speaking about the Phase III data with MIM-eight. And there is a number of other compounds in the clinic like with BMS and anti IL-eight antibody. There is also an IL-fifteen antibody from Genmab technology in the clinic. And I think for those molecules, Matthew, the timing is less Certain because we don't hear that proactively from these partners. We see updates from many times annual reports to us.
But I think there is a good chance that this year we will get meaningful data from Janssen, from Novo Nordisk and potentially from BMS on some of these clinical studies. And now turn over the for the second question to Tay to really Put some perspective on where how we position our 2 bispecific study versus the landscape of 401BB monotherapy approaches?
Well, I mean, I would say, it's probably fair to say, as you're alluding to that there is an increasing activity in the The other one phone will be increasing the expectation that maybe through Utilization of the intelligently designed bispecifics, you might be able to harness the biology phone maybe. It's probably also fair to say that The first asset that has actually shown in the clinic is the 1046. So we have 2 assets that Jan was alluding to, 1046, the PD L1 form will be and CD44 will be. And all I can say to this is that we are very focused I'm bringing them as expeditiously and as intelligently forward as we believe as possible. And We've so far been quite expeditious in the development of these assets and the generation of data, and we continue to do so.
Actually, all there is to say.
Thanks, Thijs. Thanks, Matthew.
Our next question comes from the line of Carsten Lundborg Maerssen of SEB. Please go ahead.
Thank you very much. Just one question, I think. On your 2020 achievements, you had listed some HexaBody DF5 Phase III advanced dose escalation, but you didn't really get to that milestone in 20 2020 and there are no pauses that you should anticipate in 2021, but it's not listed as a 2021 trailer. So I was just wondering if you could give us an update on where you are with the DR5, DR5 and what you expect to show us from that
Thanks, Carsten, for the question. And I certainly updated the market During the recent JPMorgan conference on where we are with the DR5, DR5 program, but I will ask Judith Klimovsky to give you some further color, Carsten, where we are and what we are going to do next with that program. Judith?
Yes. Thank you, Jan. Thank you, Carson. So as Jan already mentioned, We assumed enrollment last year. We came to a dose that is So we are following the data very closely.
The aim is to see whether we can go as a single agent and So more to come as when the data becomes appropriate to be
Thank you. Thank you. Thanks, Carsten.
Thanks.
Our next Question comes from the line of Jonathan Chang of SVB Leerink. Please go ahead.
First question, can you discuss the development strategy and timelines for tislelumab vedotin in tumor types beyond cervical cancer? And second question, can you discuss the reasons for confidence that ekiridumab could succeed in CLL? Thank you.
Thanks, Jonathan, for the questions. The first one on tisotumafedotin, I will hand over to Judith. And the second one on the CLL and eperitamab, Very good question. I will hand over to Tahi. Judith, can you start on tisotamafedotin in other cancers than cervical?
Yes, sure. Thank you. Thank you, Jonathan. So as you know, Cigen is operationalizing 2 studies, 1 in ovarian cancer and The other one called basket study, including 4 solid tumor types based on the premise that tissue factor is overexpressed in a variety of solid tumors. Those studies are ongoing and actively recruiting, as you can see from clinicaltrials.gov.
They're exploring these different tumor types and different dose scales. We cannot Firmly commit to when this data become available, but we expect to have Some of those data later this year. And based on the data, we will further define what could be the role in these different indications.
Thanks, Judith. Over to Tahi for the CLL EPCO question. Tahi?
Sure. So I mean biologically, T cell XpresCAD20, they have p cells as well. There is evidence that the mechanism of T cell redirection can be effective in CLL. I think I mentioned as a Capital Markets Day, if you look at the initial Ken paper by Karl June of his introduction of the CAR technology was actually in pre CLL patients. I think there are some concerns In the field around safety based on some observations that have been on other programs, which is, of course, a concern.
And so our belief has been that because of our so far, it's quite Say what not say what, but safety profile that avoids these great cytokine releases that we will be able to dose patients with trials. We have started Phase 1 study and we have not seen anything that would preclude this. And so we fundamentally believe like in any other BCM malignancy if the expression of the target is there That with the power of this T cell redirection in the dual body, we will be able to redirect T cells and see efficacy. And Cielo is one of the diseases that we're looking at.
Thanks, Tay. Thanks, Jonathan, for the question.
Our next question comes from the line of Wimal Kapadia of Bernstein. Please go ahead.
I data for a key trial in first line DLBCL, which could this year, which could change the standard of care from R CHOP to PCHP. So should that trial be positive, how should we think about Genmab and AbbVie in terms of how they pivot their trial programs, given this is probably one of the most lucrative indications And then secondly, Jan, you mentioned the CD37 asset. When I've looked at this asset in the past, at least from a preclinical The product seems to be quite efficient at binding to B cells, but low binding to T cells, NK cells and neutrophils. So to me that kind of suggests its Stronger, this could be one of the lower risk early stage assets. So just giving your thoughts here would be great.
And then tied to that, how should we think about combinations for this product with other mechanisms in action because again early data suggests this could be quite synergistic and one of the reasons why AbbVie partner So just appreciate your thoughts on that comment as well. Thank you.
Thanks, Wimal, for the questions. I think I'm going to hand them over first to Tahi And then potentially add to that as it relates to combinations depending on what Tay describes. Tay, can you start with those questions?
Well, I'll start with the first one, which was the question on polyb. Well, My general first comment is there is always a study going on somewhere that may change the standard of care. So it's one has to be careful, But as obviously we've been to be aware of this, our full EV is a Vedotin. We have some experience with Vedotin because it's the same payload actually They are affected, but they come with their own set of toxicities. Notably, in their trial design, as I'm So you're aware, the vincristine is actually being replaced with polyvinyl.
So we'll have to see what the data is and How meaningful the data will be when it reads out. And so that's probably all there is to say on that. The other question was around the potential combination in the pipeline.
For CD37, for CD37.
I think it's early to say at this point. But Jan, I think in the call indicated We anticipate possibly to also share some initiatives, first, new and dose escalation data on CD37. And obviously, Assuming that CD37 is safe and assuming that CD37 has efficacy as a single agent in the combination of 2 different targets with Two distinct mechanisms has always been part of our thought process and is certainly part of our strategy.
And what I could add, there, Vimal, is one of the obvious candidates, of course, is potentially EPCO to basically combine it with The CD37 target is antibody because CD37 and CD20 are co expressed for many targets, but there are many, many more Combination is possible, and I think more to come in the coming time. Great. Thank you. Thank you. Thanks, Tahi.
And we have no further time for questions. So I'll hand back to our speakers for closing comments.
So thank you for calling in today to discuss Genmab's financial results for 2020. If you are not able to get to your question or you come up with a question later, please reach out to our Investor Relations team. We hope that you will all stay safe and remain healthy and very much look forward to speaking with you all again soon. And this concludes the call for today. Thank you.
This now concludes our conference call. Thank you all for attending. Participants, you may disconnect your lines.