Thank you for joining us today for the Genmab Capital Markets Day. Please welcome Jan van de Winkel.
Good morning, good afternoon from Genmab's state-of-the-art facilities in Princeton and Utrecht. I'm Jan van de Winkel, President and CEO of Genmab. Our 2020 Capital Markets Day event may look a bit different than in the past years, since for the safety of all participants and attendees, we are fully virtual this year. As always, we have many exciting presentations for you from a variety of Genmab speakers, and we are looking forward to a lively Q&A session at the end. Slides from today's presentation will be available for download on our website immediately following today's event. As a reminder, this presentation may contain forward-looking statements, and as such, may contain certain risks and uncertainties. Next slides.
I'm really pleased that today you will have the opportunity to hear from a variety of Genmab team members, all of whom share a passion for our core purpose of improving the lives of patients. It now gives me great pleasure to introduce today's speakers. Today you will hear from our experienced Executive Management Team, including myself, our Chief Development Officer, Judith Klimovsky, our Chief Financial Officer, Anthony Pagano, and our Chief Operating Officer, Anthony Mancini. We will also have exciting and insightful presentations for you from Tahi Ahmadi, our Senior Vice President and Head of Oncology, Kate Sasser, our Corporate Vice President and Head of Translational Research, David Satijn, our Vice President of New Antibody Products, and Rob de Jong, our Director of Antibody Research and Technology. Let's now turn to our agenda for today's event.
In 2018, the focus of our Capital Markets Day was transformation and our plans for the future. Now, just two years later, I'm extremely pleased to tell you that the future we were planning for is here and now. We are well on our way, not only to reaching our ambitious 2025 vision of launching our own product, but also to evolving into a fully integrated biotech innovation powerhouse, supported by our strong financial foundation, maturing and expanding differentiated product pipeline, our next-generation proprietary antibody technologies, strategic partnerships, and growing capabilities. If you're new to Genmab's story, well, then you're in for a rare treat. As while we may have been in business for 21 years, our exciting journey is truly only just beginning.
As you can see here, after a brief introduction, we will move to Princeton, and Anthony Pagano will provide you with an overview of our strong financial foundation. Next, Judith Klimovsky will share an overview of our innovative, differentiated pipeline and our growing world-class capabilities. We will come back to Utrecht for presentations from Rob de Jong and David Satijn on our innovative next-generation antibody technologies, including a closer look at our truly differentiated DuoBody technology. We will seamlessly move back to Princeton to hear from Tahi Ahmadi, who will share the exciting first clinical data from DuoBody PD-L1/4-1BB that was also unveiled this week at SITC. Kate Sasser will give you more information on our translational research and approach to data sciences.
Anthony Mancini will then set the stage for a discussion of our later-stage assets, epcoritamab and tisotumab vedotin, including how we are preparing to meet the unmet medical need of patients and move them into the commercial space. Let's get started with today's event and review just why we are so effective and progressing well on the road to reaching our ambitious 2025 vision. For over 20 years, we have not wavered in our commitment to Genmab's core purpose of improving the lives of patients by creating and developing innovative antibody products. In 2010, we linked this core purpose to an extremely effective strategy. By focusing on our core competencies of being able to identify the best disease targets, develop differentiated next-generation antibody technologies, and creating unique, best-in-class or first-in-class antibodies. In this way, we have been able to turn Genmab's innovative science into medicines.
This has effectively allowed us to build a profitable and successful biotech. I'm extremely pleased with our track record of success, but we are only just getting started. We are getting very close now to successful achievement of our 2025 vision to have our own product on the market that has transformed cancer treatment. Next slide. We have been so successful and are so close to achieving our vision because Genmab is a world-class antibody innovation powerhouse. This is a phrase you may have heard from me many times over the years, and today we will share with you how our innovations are already transforming cancer treatment and why we are so confident that we are building a company that can go even further.
Because we are not only an innovation powerhouse but also an integrated one with growing capabilities and strategic partnerships that are allowing us to evolve into a fully integrated biotech. Now let's take a closer look at what exactly we mean when we say innovation powerhouse. Earlier this year, the journal "Nature" published a very impressive paper. It described key transformative waves in drug development over time, starting with aspirin, which we all know. It took more than 30 years before its mechanism of action was identified. People knew that it worked, but not how it worked. Of course, it's the how that today allows us to create more effective and targeted medicines for patients. The first monoclonal antibody entered the market in the mid-1980s, and now there are over 90 FDA-approved antibody therapeutics available to patients.
Biologic drugs are playing an ever-important role in medicine, especially as they are evolving. Starting with Mylotarg, the prototype molecularly targeted medicine against acute myeloid leukemia. Now the next wave of innovation focuses on multi-specific drugs, as you see here on the slide. This includes bispecific antibodies that are responsible for over 60% of the growth of the antibody market over the coming years. We have actually over 75% of Genmab's pipeline based on our DuoBody technology, including therapeutic candidates in our proprietary clinical pipeline like epcoritamab and DuoBody PD-L1x4-1BB, and assets in our partners' pipelines including Mim8 by Novo Nordisk, which just went into phase II in the past few weeks, and amivantamab by Janssen, which is already in a very large randomized phase III, and Janssen is preparing for filing this year with the FDA.
The rest of our pipeline is either created via our HexaBody, HexElect, or next generation ADC technology. We are excellently positioned for transforming the treatment of cancer with unique multi-specific antibody drugs. Next slide. While our world-class insight into antibody biology and disease targets positions us well to create novel and differentiated therapeutic candidates, we know that working collaboratively with strong partners will take us even further. Some of our strategic partnerships provide us with access to high quality, unique disease targets and cutting-edge technologies. Others, like our collaborations with AbbVie, Seagen, and BioNTech, will help us bring our next generation antibodies to patients in need much faster than we could do on our own. Of course, partnerships have also provided us with the financial foundation for our current success.
DARZALEX is now a backbone therapy for multiple myeloma, with the potential to expand even further with this year's approval of the convenient subcutaneous formulation and the recent submissions in the U.S. and Europe for a new indication, AL amyloidosis. In 2020, we also had the highly anticipated approval in the U.S. of Kesimpta, a subcutaneous ofatumumab formulation for treatment of relapsing MS by Novartis, as well as the very rapid approval and extremely successful launch of TEPEZZA for treatment of Thyroid Eye Disease by Horizon Therapeutics. To share with you more about Genmab's very strong financial foundation, I would now like to welcome Anthony Pagano, our CFO. Anthony, the floor is yours.
Great, t hanks, Jan. We've never been in a better position to achieve our vision of transforming the lives of cancer patients, at the same time, create value for shareholders. My objective today is to explain why I say that with such confidence. I want to start by reminding you of the very strong foundation we've built. You can see the key elements here. First, at the very core is great technology. We've built a rich pipeline and several novel technology platforms. In fact, we're excited by the prospect of potentially launching two of our own product candidates in the coming years. Second, we're leveraging partnerships with industry leaders and innovators to enable us to do more and faster. Third, we've got a very focused and disciplined approach to investment and capital allocation. We're seeking to drive better outcomes for patients as well as ultimately create shareholder value.
Finally, another cornerstone of our foundation is the strength of our financials. Sound balance sheet and growing recurring revenues affords us a great platform to invest for the future. Let's look at those revenues in a bit more detail. Our successful investment strategy is enabled by these growing recurring revenue streams. Assume we meet consensus expectations for 2020, and we think that's a reasonable assumption, then we'll have increased our revenues fivefold since 2016. What's even more encouraging is that we've grown the recurring revenue component, shown in the green bars here, by nearly 9x over the same period. There are three drivers of these recurring revenues. First, DARZALEX. Here we're looking forward to further growth as DARZALEX continues to transform the treatment of multiple myeloma. We've also got Kesimpta and TEPEZZA, which were launched earlier this year.
Both are potential blockbusters according to Novartis and Horizon Therapeutics. Of course, that all adds up to significant cash flows, which we can use to invest further in the business to deliver our vision. As you can see on the next slide, we're well on our way. Our 2025 vision has acted as a guiding light for us. It's focused us on our core purpose to meaningfully impact the lives of cancer patients. Today, we've reached an inflection point where we find ourselves with two potential product launches in the next couple of years, and with more to come. That's a great place to be. 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 biotech powerhouse. Let me expand on that.
We want to get our pipeline, and especially our two near-term product launches, to as many patients as possible, and we want to do it as quickly as possible. As you can see, we plan to retain at least 50% ownership of our pipeline products. We also intend to directly influence and control the development and commercialization of our new products. 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. Ultimately, this is about focused execution. How are we going to do that? You can see here the three key areas where we are investing. First, in research, we're investing to ensure that we can build on our strong track record. As you know, we've invested in state-of-the-art facilities in the Netherlands and here in Princeton.
We continue to invest in new technologies and formats. Second, for development, we're really focused on scaling up so that we can expand from early to late-stage development. Third, we're also investing significantly in commercialization. We've put a strong leadership team in place, and we're now expanding the team to enable us to bring our new products to market. Underpinning all this is investment in key enabling functions to both support growth and manage risk. Finally, we see significant potential to drive insights through data sciences all across our value chain, we're investing to do just that. That's the theory. What does this look like in practice? What you can see on the next slide is our priorities for where we are going to invest. On the left, you can see our priorities for today. Priority number one is filing and launching tisotumab vedotin.
Two is accelerating the development and launch of epcor. Three is expanding DuoBody PD-L1/ 4-1BB. Priority number four is standing up our commercial capabilities, both here in the U.S. and also in Japan. This is essential to realizing our full potential. These are our immediate priorities, y ou'll hear a lot more about these from the team later in the session today. We're not just focused on today. In line with our vision, we're also very focused on long-term value creation. Here, we're investing to progress our early-stage pipeline and 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, we continue to look for good ideas and innovation outside the four walls of Genmab, including adjacent technologies.
While on the subject of external opportunities, let me turn now to partnerships. We've achieved a huge amount with partnerships over the years, and they will remain an important part of our business as we look to the future. Not surprisingly, we're evolving the nature of the partnerships we sign up to. You can see that evolution on this slide. Clearly, our historical partnerships based on out-licensing have been great for generating the very significant cash flows that underpin the business today. As you know, we're now focused on partnerships which give us more control and the ability to get to more patients and faster. Going forward, partnerships will continue to play a vital role as we build out our business. They allow us to bolster our internal strengths while leveraging external ideas and capabilities.
Hopefully by now you've got a good feel for the strength of our foundation, the clarity of our strategy, our priorities for investment, and our continuing appetite to create value through partnerships. What does it all add up to? This next slide shows what consensus expectations are for our recurring revenues over the next five years. As you can see, the future looks very promising. Just looking at our three existing products, our recurring revenue is expected to grow more than 2.5x . On the left, you can see the component parts of our future recurring revenue streams. As I covered at the start, that's DARZALEX, Kesimpta, and TEPEZZA, and each of these products are well-positioned to provide significant cash flow and growth in the years to come. As potential upside to our existing royalty streams, Janssen is making significant progress with their DuoBody programs.
Most advanced is amivantamab, which has received breakthrough therapy designation and is expected to be filed with the FDA later this year. Finally, and most importantly, our two potential near-term launches of tisotumab vedotin and epcoritamab. Together with Seagen, we look forward to submitting a BLA for tiso, with the goal to make this potential treatment option available as quickly as possible. In addition, we continue to invest in multiple clinical trials to potentially expand this opportunity. For epcor, we are working with AbbVie on a broad and comprehensive development plan to realize its full potential. This includes trials in several B-cell malignancies, trials across multiple lines of therapy, and we also plan to explore epcor as both a monotherapy and as a combination therapy. We shouldn't forget that the AbbVie partnership includes approximately $3 billion in potential milestones, which could further bolster revenue growth in the coming years.
You can see there is significant potential for strong growth in recurring revenues through to 2025, with our own Genmab products expected to contribute significantly to this growth. For my final slide, let me pull this all together for you. We've got a very strong foundation, great technologies, and an exciting pipeline, a highly capable team that we continue to strengthen, really meaningful partnerships with innovators and industry leaders, and strong financials both from a balance sheet and cash flow perspective, giving us the capacity to invest. We've got a clear strategy focused around driving better patient outcomes and creating long-term shareholder value. We've got two near-term product launches, these give us a strong rationale to make focused investments to get the most from the opportunities ahead. Thanks. Now I'd like to turn it over to Judith.
Thank you, Anthony, for the introduction, and good morning, good afternoon to everyone joining us today. As Jan noted, we have an ambitious vision. By 2025, we will have our own product on the market that will transform cancer treatment. Today, we would like to share with you the recent progress we have made that indicates we are well on track to reach this vision. Through Genmab's more than 20-year journey, we have taken steps towards our goal of improving the lives of patients. Now, more than ever, we are delivering on this promise, and we will not rest until we have fully delivered. In the next few slides, I will provide you with a high-level overview of what we have accomplished and why this is just the beginning. This slide illustrates how Genmab's pipeline has evolved over time.
Let's review the last four years and how we have grown the breadth, depth, and maturity of our proprietary pipeline. On the left, we have a chart showing the total number of product candidates in the clinic year by year since 2016, beginning with nine in 2016 and expanding to 23 by 2020. The chart on the right represents the growth and stage advancement of our proprietary pipeline. In 2016, Genmab had only two product candidates in the clinic, one in phase I and one in phase I/II. Today, we have eight product candidates in the clinic. One of them completed a phase II study, and we are planning our first BLA in partnership with Seagen. This progress is the result of our continuous investment in R&D and commitment to innovation. Listed here are all the compounds created by Genmab Science and Technologies.
Those at the top are the eight compounds owned by Genmab, defined as no less than 50% ownership. Notably, most of our product candidates are first in class, illustrating the innovative nature of our pipeline. This is the result of our differentiated proprietary technologies, novel approaches to target discovery, and collaboration with partnerships. Our innovative science and technologies have also contributed to 15 products being developed by our partners, appearing in the slide at the bottom. Among them, the approved medicines DARZALEX, Kesimpta, and TEPEZZA. We will continue to invest in research and development because science is the engine that will allow us to maintain this pace of innovation in the years to come, turning what was yesterday's dream into tomorrow's reality. We are confident that we will be able to continue to build and advance our pipeline on a strong foundation of cutting-edge science.
This confidence is based on our track record of success and the multifunctional integration of R&D, which makes Genmab special. We have a deep understanding of antibody biology and targets, multiple next-generation technologies, and diversification in our pipeline. From this diversified and rich pipeline, we identify likely winners and maximize their potential. Another critical component of what we do are our many strategic collaborations and partnerships, which are a very efficient way to enhance our ability to do even more. More research, more projects, scale up those projects. Finally, we believe that data science and real-time integration of translational research are key to accelerate development and ensuring the right therapies get to the right patients. Taken all together, these are the pillars that support Genmab's past and future success, our solid science, driven by data, and our collaborative approach through all aspects of research and development.
Now, let's take a closer look at two key factors in our future success. In this slide, partnerships. This slide gives an overview of many of our current partnerships and collaborations. These are not collaborations with just any partner, but with particularly complementary partners in terms of technologies, capabilities, and knowledge. As you can see, we have a variety of collaborations across the whole ecosystem of pharma, biotech, and academia, which will help us to continue to create innovative next-generation antibodies and to potentially make them available for patients faster. The other key factor is people. We have added capabilities such as medical affairs and data science. We are strengthening our R&D teams with key talent and growing our internal competencies to become an end-to-end biotech. Now, if you attended our prior Capital Markets Day, you had the opportunity to experience firsthand our state-of-the-art facilities in the Netherlands.
We will give you another glimpse with a video tour of our cutting-edge labs in Princeton. Kate Sasser, our head of translational research, will be your tour guide. Enjoy.
Genmab is trying to transform cancer therapy by turning antibodies and antibody science into novel medicines for cancer patients. Cancer is a very formidable enemy, i t's fast-moving and it evolves very quickly. Cancer patients, they don't always have a lot of time, and so we want to be able to deliver fast therapies to them that are novel, innovative, that have limited side effects, and that ultimately will be more effective. At Genmab, we're continuing to grow and expand our capabilities in many different areas so that ultimately we can become an end-to-end biotech company that can deliver amazing antibodies to patients. In order to deliver on the promise of creating a cancer-free world, Genmab is doubling down on our scientific focus.
We're really making sure that we continue in our solid foundation of being data-driven by developing additional capabilities around data science and translational medicine, including some of the labs that you see here in our Princeton site, where we have expanded our translational research focus. Our philosophy on the translational research side is that we want to be able to really understand in depth our drug products, how they work, what their mechanism of action is, and the patients that those products are going to reach. The way that we're doing that is really incorporating deep scientific research around our clinical trials. We collect patient samples during the trials to really do broad, in-depth genomic, proteomic, lots of detailed analysis, so that we can understand how the patient's tumor biology is working, and also how their immune response may be counteracting the tumor that's developing.
This knowledge really gives us then an advantage to be able to tailor our therapies for those patients specifically. In the future, we hope to really be able to direct the right therapy to the right patient at the right time. Across all of our Genmab sites, we're really focused on the problem at hand of treating cancer, and so our research teams, both in Utrecht and in Princeton, are connected in many different ways. We use technology to stay connected, to share data in real time, to look at data together, to collaborate on experiments, and ultimately to drive the science forward regardless of geography. Success means that we can develop some of the best antibodies in the world, and that they're super effective and ultimately transform cancer therapy.
I really believe that the future can capitalize on all of the amazing biology that we're seeing today, that we can learn from advances in technology and science to ultimately be able to transform cancer therapy and create, hopefully, a cancer-free world.
I hope you enjoy the virtual tour, i t will be great to see you in person at our next Capital Market Day. I would like to introduce now Rob de Jong, who will expand on our proprietary technology. Rob, the floor is yours.
Thank you, Judith. At Genmab, we are truly fascinated by antibody molecules. Can't help it, we just love them. The power of our natural immune system inspires us to create therapeutic antibodies that have a real impact on the lives of patients with cancer and their families. To do so, we want to deeply understand basic immunological principles, down to the smallest molecular details illustrated here. Our curiosity and scientific knowledge fuel our passion to translate science into innovative technologies and into products that have the potential to transform the treatment of cancer patients that need them. Let's have a look at Genmab's antibody technologies now, starting with our bispecific antibody platform, DuoBody. Bispecific antibodies were conceived decades ago, faced challenges limiting their application as therapeutics. Upscaling was hampered by low yields and poor stability. There was risk of immunogenicity due to heavy engineering of the antibody backbones.
Complex material production made it challenging to determine what concentration of binding specificities create the very best bispecific product. You may have wondered why DuoBody products have such a high hit rate and low attrition in clinical development, so I will summarize key DuoBody advantages. In brief, illustrated by more than 10 DuoBody programs currently in the clinic, with the invention of DuoBody, we solved all of these issues. DuoBody molecules are made from two parental IgG antibodies, each with a single point mutation that exchange half molecules in controlled reducing conditions. Reoxidation yields stable DuoBody molecules at over 90% efficiency.
This minimal engineering preserves regular IgG1 structure, stability, and functional properties such as long half-life or PK, and it minimizes immunogenicity risk. DuoBody can make use of any known IgG antibody sequence because original heavy light chain pairing is preserved and a common heavy or light chain is not required. Our discovery timelines are minimized by a fully automated process that can convert panels of parental antibodies into DuoBody libraries in the final therapeutic format, which enables us to quickly spot the winners. Another key advantage is seamless upscaling. Our GMP manufacturing is compatible with IgG standard unit operations. The DuoBody exchange process has been scaled up with multiple CMOs and collaboration partners. We also have identified the CD3 arm used in T-cell redirection and a inert backbone used in, for example, agonistic applications.
Actually, being able to reuse parental antibodies in different clinical programs increases the speed and decreases the cost of development substantially. Moving on, o ur HexaBody technology is a platform for the discovery and development of potentiated IgG antibodies. Only after binding to the cell surface, HexaBody molecules assemble into organized teams of six termed hexamers that can force target clustering and induce outside-in signaling or trigger complement activation. HexaBody signaling induction differs from regular antibodies because HexaBody does not depend on cross-linking by immune cells. HexaBody preserves IgG1 like PK and stability, and our investigational HexaBody products have provided us with clinical and manufacturing experience. If we want the best of both worlds, we turn to DuoHexaBody, a combination of DuoBody and HexaBody that creates potentiated bispecific antibodies. DuoHexaBody combines the benefits of dual targeting with the benefits of target clustering, preserves IgG1 like PK and stability.
Within our DuoHexaBody-CD37 program, we get our clinical and manufacturing experience with the platform. In summary, our suite of proprietary antibody technologies enables to create knock-your-socks-off product candidates. We need this diversity in technologies because products have very different molecular requirements depending on their application or the biology of the target or target combination. At Genmab, we feel uniquely positioned to make the most of target combinations. We use DuoBody, we use DuoHexaBody, and we pre-clinically investigate applications of our novel HexElect technology that increases the therapeutic index of antibody drugs by maximizing selectivity and potency at the same time. Our technology platforms also make us a partner of choice, as shown by our numerous partnerships that help us build our pipeline of truly differentiated first-in-class or best-in-class products. Now David will talk about how the DuoBody technology is used in new product applications. David.
Thank you, Rob. In this part of the presentation, we will highlight the use of our DuoBody bispecific antibody platform for the generation of new products. New products which either activate the immune system or kill tumor cells in a direct manner. How do we approach this? An interesting observation is that cell-cell trans communication can be mimicked by bispecific antibodies. The cartoon in this slide represents different immune cells and tumor cells. Further, a subset of immune activating and immune inhibiting cell surface proteins are depicted in green and red at the interface between the different cell types. Protein-protein interactions on the surface of different cell types can induce and transmit a communication signal, resulting in, for example, activation or dampening of an immune response. Bispecific antibodies bind to two different epitopes, either on the same cell or on different cells.
Cell-cell trans interaction is a unique feature of bispecific antibody molecules. Cell-cell trans communication can be mimicked by bispecific antibodies and applied for different product applications. We use our unique DuoBody antibody technology for the generation of bispecific antibodies. The DuoBody platform enables for the generation of large libraries of bispecific antibodies. Depending on the number of targets, the size of the antibody panels, hundreds of thousands of DuoBody variants can be screened and tested. With standard bispecific discovery processes, the antibodies with the best characteristics as monoclonal antibody is often picked for the generation of the bispecific lead. The DuoBody platform enables for the generation of large libraries of bispecific antibodies, screening in an unbiased and empirical approach. This enables the selection of the best bispecific lead candidate based on functional criteria. This slide explains the identification of new immune oncology products with our DuoBody platform.
The cartoon on the left represents different immune and tumor cells, which express immune costimulatory and coinhibitory proteins from the B7, CD28, and TNF receptor superfamilies. These proteins play an important role in the activation of the immune system. Agonistic and blocking antibodies can mimic the activation or inhibition of these costimulatory and coinhibitory proteins. We performed functional, unbiased, high-throughput DuoBody screens testing multiple different targets from these families. Several thousands of DuoBody variants have been generated. These high-throughput functional DuoBody screens identified DuoBody PD-L1 x 4-1BB, which is also known as GEN1046, and DuoBody CD40 x 4-1BB, also known as GEN1042, as product candidates. This slide explains our CD3 DuoBody application for the T-cell mediated kill of tumor cells.
When both T-cell and tumor cell are bound by the CD3 DuoBody molecule, a cytolytic synapse is formed, leading to killing of the target cell, which is independent of the co-stimulation of T-cells. The functional screening of multiple B-cell targets and the use of different high and low affinity CD3 arms allows for the identification of the optimal target pair for the T-cell mediated kill in B-cell malignancies. We created and screened several hundred DuoBody molecules made up of several dozen B-cell targets and used both affinity, the high and low CD3 affinity variants for screening. A high affinity CD3 arm and one of our CD20 clones was selected for this product concept, which is now known as epcoritamab. Here you see a summary of the different DuoBody trans-activating product applications that we are developing pre-clinically and are progressing in the clinic.
The upper part represents the cells of the innate immune system. Macrophages and natural killer cells can also be targeted using DuoBody for tumor-specific and enhanced induction of ADCC or ADCP-mediated tumor cell kill. Identification and generation of product concepts targeting macrophages or NK cells is in progress using tumor-specific and innate checkpoint targets, performing functional DuoBody screens. At the moment, DuoBody-based product applications for enhanced immune modulation and T-cell-mediated tumor cell kill are most advanced. One of these products is DuoBody PD-L1x4-1BB, also known as GEN1046. Now I like to hand over to our head of oncology, Tahi Ahmadi, who will tell you more about this exciting program.
Thank you, David. GEN1046 is a first-in-class, next-generation checkpoint immunotherapy, jointly developed by Genmab in partnership with BioNTech for the treatment of advanced solid tumors. GEN1046 is designed to block PD-L1 on tumor and/or immune cells within the tumor microenvironment or draining lymph nodes, and simultaneously activate 4-1BB on antigen-experienced T-cells as well as NK cells. The Fc portion of 1046 is silent, and consequently, the Fab arm binding PD-L1 blocks the PD-1/PD-L1 axis, while 4-1BB is conditionally activated only when the PD-L1 arm is bound. This focuses 4-1BB activation on the tumor immune synapses and is intended to avoid or reduce some of the systemic toxicities that have been observed with 4-1BB agonism in the past. A detailed mechanism of action video has been uploaded onto the registration website. I would encourage you to check it out.
GEN1046 also highlights the power of our DuoBody platform, and both Rob and David alluded to the ability to screen several thousands of antibody combinations in order to identify the right set of clones with the appropriate biophysical properties to harness the therapeutic potential of the proposed mechanism of action. In this specific case, the conditional activation of 4-1BB. The first human trial for GEN1046 started in May of last year. The program exemplifies our vision for drug development at Genmab. We concluded a dose escalation from 25 mg all the way up to 1,200 milligrams flat dose. As we proceeded with the dose escalation, we continuously integrated the emerging clinical, pharmacokinetic, as well as translational data together with existing preclinical models and the scientific knowledge of 4-1BB biology. This allowed us to understand the pharmacologically complex target engagement and identify the optimal dose of GEN1046.
We've initiated dosing on the expansion cohorts within less than a year from the first patient dosed. Kate Sasser will discuss some of the model data that informed the selection of the recommended phase II dose in a few moments. The expansion cohorts listed on the right side of this slide are meant to explore opportunities for GEN1046 in disease settings of either checkpoint-naïve tumor types, those in which checkpoint inhibition reports limited single-agent activity, and that can serve as a clear benchmark, or in cancers that are refractory or relapsed after checkpoint inhibition. These data sets will help us to further elucidate the differentiated biology and clinical opportunities for 1046 and its unique mechanism of action.
As we continue to generate data, we will also explore opportunities to combine GEN1046 with other modalities in a rational scientific manner, which will inform our next steps in the clinical development plan. In the next few slides, I will summarize some of the key data that have been presented by Dr. Melero as part of the virtual SITC conference this week. We enrolled a total of 61 patients across the range of doses explored. The study population, as presented here on this slide, was heavily pre-treated with a median of three prior lines of therapies. Majority of cancers enrolled are considered to be less likely to respond to immunotherapy. 38% of the patients had received prior checkpoint inhibition with either a PD-L1 or PD-1 antibody alone or in combination, and frequently in more than one line.
In terms of the safety profile, we observed six dose-limiting toxicities across the entire dose range, but importantly, did not reach the MTD, and there doesn't really seem to be a clear dose toxicity relationship. We do see transaminase elevations, again, across the entire dose spectrum in about 26% of the patients. The 10% of these patients experiencing Grade 3, but this has been manageable so far. The LFT elevations resolve, and we have been able to re-expose patients even with Grade 3 LFT elevations to GEN1046 without meaningful transaminase elevations at subsequent exposures. As I mentioned earlier, the patient population within the dose escalation represents a broad mix of cancers, which are either not necessarily considered to be sensitive to immunotherapy or have failed checkpoint inhibition. Nonetheless, two-thirds of the patients achieved stabilization of the disease.
In many cases, over a prolonged period of time, partial responses were observed in four patients, two of which with non-small cell lung cancer, both of these patients had failed prior checkpoint inhibition. We started enrolling patients across all expansion cohorts presented at SITC an early snapshot from Cohort 1. These are patients with non-small cell lung cancer that have failed both platinum-containing doublet chemotherapy and checkpoint inhibition, either alone or in combination. The study includes a comprehensive translational research component, which Kate will expand in a few moments, that will allow us to further define the characteristics of the responders. On the left, you see a waterfall plot for the 12 patients with post-baseline assessment, three PRs, two of which are confirmed and ongoing. The third unconfirmed response is also still ongoing on treatment. Three additional patients achieved stable disease, all are continuing treatment.
Six patients discontinued due to progressive disease. On the right side, you see the spider plot. This is preliminary data, and we intend to present a larger data set of the entire cohort of 40 patients at an upcoming medical conference. We are very encouraged by the initial efficacy signal and early evidence of durability we are observing in these patients with non-small cell lung cancer, who for the most part meet the criteria for primary resistance to checkpoint inhibition. I hand over to Kate to talk a little bit about the translational aspects of this program.
Thank you, Tahi. As you heard earlier, we have built a translational research organization which is closely integrated with both our discovery and clinical development functions. Our efforts for GEN1046 have really been focused on real-time integration of PK, biomarker, and clinical data to further understand the safety, efficacy, and biological activity of GEN1046. Especially since this bispecific agent is unique in that it targets both the PD-1, PD-L1 axis and the 4-1BB co-stimulation pathway. Our PK data here on the left demonstrates that GEN1046 has a peak concentration shortly after the end of infusion and a mean half-life between two and 10 days. After repeat dosing, you can also see some accumulation in the periphery at doses above 80 mg. Not shown here, but further evaluated by the PK and biomarker team, was the ability of the bispecific to form trimers in the tumor.
Based on quantitative modeling, peak trimer formation in the tumors occurs at 100 mg. On the right-hand side, you can see a profile of the pharmacodynamic biomarkers in our patients, where we monitored for known biological mechanisms of action for both PD-L1 and 4-1BB activities, including cytokine production. In this case, showing interferon gamma and IP-10, as well as changes in peripheral T- cells, showing activation by Ki-67 of both cytotoxic CD8 T- cells and also memory T- cells. We determined that all the biological and functional activities for GEN1046 were induced at lower dose ranges between 25 mg and 200 mg, but were diminished at the higher doses of GEN1046 above 400 mg.
This totality of PK, modeling, and biomarker data, combined with the safety and efficacy which Tahi just presented, led us to select 100 mg every three weeks as the dose for moving forward in the current expansion cohorts. In addition to dose escalation and selection, the team has been focused on further understanding of the right patient populations that will gain the most benefit from GEN1046. We're incorporating robust biomarker profiling as part of our study, including PD-L1 expression, shown here underneath the waterfall plot. PD-L1, as most of you know, is a known biomarker predictive of response for other checkpoint inhibitors. As you can see underneath the PD-L1 expression, we have several patients who were primarily refractory to checkpoint inhibition, even with PD-L1 expression. Yet they have gained clinical benefit from GEN1046, indicating to us that this mechanism of action is much broader than PD-1, PD-L1 inhibition.
We are incorporating additional biomarker profiling to fully understand which patients can benefit the most from the dual PD-L1/ 4-1BB targeting. This program, in a way, highlights our Genmab philosophy you heard earlier for how we intend to utilize translational research to help speed the development of our antibody therapeutics. As oncology is becoming more and more complex, we see this as a differentiating component of Genmab, and we're building our R&D teams to be fully integrated and data-driven with this in mind. We're also expanding our partnership model to incorporate collaborations in areas that can add synergy to this R&D approach. Tempus is one of these new partners that you've heard about earlier in the year. We are partnering with Tempus on multiple fronts.
They are a sequencing provider for our clinical trials, but much more than that, we're using this molecular data to understand our patients in the context of their much larger real-world datasets. We are also working with Tempus on using large datasets to find and validate novel targets of interest, which can be married to our antibody technology, which you heard about earlier, to ultimately develop new antibody products in a faster and more data-driven manner. To tell you more, here's a short video featuring Ryan Fukushima, the COO of Tempus, talking about our unique partnership.
The main reason why we decided to partner with Genmab was really sort of a shared goal, a shared goal of doing things differently, really approaching drug discovery, translational research in a new way, especially when you think about leveraging computational biology, machine learning, drug discovery expertise together to really do things differently. We approach it as, "Hey, we have a shared goal," and actually build teams together and actually work side by side. With that shared goal of designing and building better therapeutics for these patients, and now that we can actually generate, organize not just patients' clinical history, but also generate the genomic data, the transcriptomic data, we can leverage that data to make the best decision for an individual patient.
The promise behind precision medicine or personalized medicine is really not just a hope and a dream, it's actually being implemented and delivered at the point of care today. My hope and what I've seen so far is that we can actually start using data from the real world to drive some of the key decisions that we wanna make in terms of what assets to bring forward or what assets to design with things like monoclonal antibodies, or even things beyond that. I'm excited to see how we can scale that and do that many, many times over in a much broader way. If I was to boil it down to one statement, I think that this collaboration, we can change the way drug discovery and translational research is performed for the industry.
We have a real opportunity to not just focus on data and insight, but really harness the capability and the promise of multimodal data, machine learning, computational biology approaches. When we have better drugs in the market, we can then start personalizing care more often. We're starting to see it already in oncology, where when you pair the right drugs and the right patient at the right time, great things can happen.
Hopefully you enjoyed that inspiring video of how we collaborate with companies like Tempus. Now I would like to hand it over to our Chief Operating Officer, Anthony Mancini.
Thanks so much, Kate, for an exciting look at all the advances being made in Genmab's foundational technologies for GEN1046 and beyond. We're also making meaningful advances towards becoming a fully integrated biotech leader. As you know, the entire team at Genmab is driven to achieve our 2025 vision to build a pipeline of knock-your-socks-off antibodies and for a Genmab-labeled medicine to transform cancer treatment. To achieve this vision, it will take each of the three key elements that are on this slide. First, our foundation, the discovery of innovative antibodies, which we heard a little bit about earlier. Second, the continued strengthening of our development capabilities. Third, now we're in the process of building the important next piece of the equation, commercialization. We're making great progress scaling up the commercialization efforts at Genmab. It's all about focus and a thoughtful, deliberate approach.
First, the focus is on our priority products and priority partnerships, and our late-stage development products and partners are shown here, epcoritamab, our bispecific CD3/CD20 antibody partnered with AbbVie, and tisotumab vedotin, our Tissue Factor-targeted antibody-drug conjugate, which we plan to commercialize with Seagen. A deliberate focus in the near term on priority markets. For us, that's the U.S. and Japan. We've made great progress already appointing talented key leaders as part of the global commercialization team and to lead in each key market. We continue to attract top-tier talent from top oncology companies to join our team. Along with our partners, we're making great progress in building the strategy and the plans to achieve impactful launches. We'll now spend a little bit of time digging more into epcoritamab and tisotumab vedotin.
For both of our late-stage development assets in collaboration with my R&D colleagues, we'll describe the target patients and the unmet medical need, as well as the size of the market opportunity. We'll then take a look at, in greater detail, the clinical data and provide a bit of a market perspective on the potential of each asset. Epcoritamab, as many of you know, is being studied in diffuse large B-cell lymphoma, or DLBCL, and follicular lymphoma. These are the two most common types of non-Hodgkin's lymphomas. Epcoritamab has the potential to also be useful across a broad range of B-cell malignancies. Let's have a look at the DLBCL patient. Unfortunately, DLBCL patients have a poor prognosis, with about 36% of U.S. patients dying within five years of diagnosis. In refractory patients, it's even more concerning, with about 80% mortality within two years.
The patient pictured here is Gemma. She's not a typical DLBCL patient, as she's actually a lot younger. She is a patient that's near and dear, as she shared her personal story with the entire Genmab team and how it impacted her quality of life. DLBCL accounts for about a third of lymphomas in the U.S. and is the most common form of non-Hodgkin's lymphoma. It's a disease that's typically diagnosed in an older population, and upon progression, can have a really major impact on patient quality of life. There really is a high unmet medical need, particularly in recurrent and refractory DLBCL, due to the fact that there's a low duration of response and relatively poor long-term outcomes with current salvage therapies. Really, we think there's significant opportunity for novel treatments in this space.
This chart shows the number of patients with DLBCL treated in the U.S., the five largest European markets, and Japan. Disease prevalence of DLBCL is likely to increase by about 2% per year, primarily due to the aging population. Epcoritamab is being studied in the third-line plus DLBCL space, shown here, which accounts for just a little over 9,000 patients. Also, as you can see here, should epcoritamab demonstrate a benefit in earlier lines of therapy, you can see that the potential is significant. With that, I'll ask Tahi Ahmadi to take us through the exciting data we've seen to date with epcoritamab.
Thank you, Anthony. We at Genmab, together with our colleagues at AbbVie, fundamentally believe that the mechanism of T-cell redirection against CD20 has the potential to truly disrupt and transform the treatment paradigm for patients with B-cell malignancies across all lines of therapies. Epcoritamab continues to show data that supports its potential for best-in-class. The data shown here was recently publicly released as part of an ASH abstract. There will be an oral presentation at ASH in a few months. All seven patients with relapsed refractory diffuse large B-cell lymphoma achieved a response at the recommended phase II dose of 48 mg or higher. Among them are four patients post-CAR therapy, t hree of those were refractory to the prior CAR therapy. It's worth noting that at the time of this abstract, most of these patients had only one post-baseline scan at week six.
Similarly, all patients with follicular lymphoma treated across a wide range of doses achieved a response. I'd like to note that two of the three patients dosed after the institution of PET imaging, and although PET imaging was not initially part of the protocol at the time it was initiated as a first human trial, achieved a CR based on PET and CT. These data will be updated in a presentation by Martin Hutchings with a larger number of patients at the recommended phase II dose of 48 mg, as well as a longer follow-up and durability of response. We continue to see a tolerable safety profile, m ost AE reports, such as pyrexia, tachycardia, or hypotension, being related to cytokine release.
It is important to note that cytokine release syndrome is actually a composite term of multiple AEs, which we are deliberately collecting separately in our trials in order to accurately understand the safety profile of epcoritamab at this point in time. CRS is generally restricted to the first cycle. It is observed in a little bit more than 50% of the patients and is all Grade 1 or 2. Injection site reactions are all Grade 1, and generally a self-limited first injection phenomenon. In summary, as the data continues to mature, we like what we see, both in terms of efficacy as well as tolerability. Give you a bit of a flavor of what a response looks like. Here, a short clinical vignette; t his is a case of an elderly lady with diffuse large B-cell, refractory disease.
Three prior lines of therapies within a short period of time of less than two years. Documented progression on her last line. Best response she achieved on all three lines was stabilization of disease. This is a patient of the 12 mg cohort first presented at last year's ASH. The PET and CT imaging on the right allow you to appreciate the significant disease burden at the time of enrollment. She achieved a PR at the first assessment, and with continued treatment, achieved a CR, and she continues to be at remission at this point now, a year later. We started the first human trial in June of 2018 at a priming dose of 4 μg , and we determined the recommended phase II dose based on a sophisticated PK/PD model, which incorporated PK modeling work, translational data, and clinical efficacy.
It's another example of the vision that both me and Kate have already talked about when we talked about GEN1046, that we have at Genmab of a truly integrated approach to drug development. The details of this particular modeling approach will be presented at ASH this year. Pretty much two years after the first patient was dosed and enabled dose in this study, we initiated two expansion cohorts that are now actively enrolling patients with relapsed refractory diffuse large B-cell lymphoma and follicular lymphoma, and are intended to generate data that could support accelerated approval. A third expansion arm for patients with relapsed refractory mantle cell lymphoma will also open for recruitment very soon. To complement our single-agent data sets, we initiate 3013-02. This is a basket safety study of epcoritamab in combination with several established backbones across multiple lines in both diffuse large B-cell and follicular lymphoma.
R-CHOP in newly diagnosed high-risk diffuse large B-cell. R-squared, the combination of lenalidomide and rituximab in relapsed refractory follicular lymphoma, bendamustine and rituximab in front line follicular lymphoma. In combination with induction therapy for those patients who are transplant eligible, as well as with GemOx for those who are ineligible for auto transplant. The study is now open and actively enrolling patients. To extend our development across the spectrum of B-cell malignancies, we also initiated 3013-03. This is a phase Ib study of epcoritamab as a single agent in relapsed refractory CLL. It is a Genmab-sponsored study, but has the support of key European CLL study groups, and is meant to define the safe dose and schedule for epcoritamab in CLL, as well as to generate early evidence of clinical efficacy in these patients that have failed or are intolerant to BTK inhibition.
Again, the study is also now actively enrolling patients. To conclude the presentation of our current ongoing clinical activities, we publicly announced last week the initiation of the first phase III of epcoritamab as a single agent, randomized against the investigator choice of either R-GemOx or bendamustine plus rituximab in patients with relapse or refractory diffuse large B-cell lymphoma, with at least one prior line of therapy and who are either ineligible or failed auto transplant with a primary endpoint of overall survival. As I alluded to in the beginning, we, in partnership with AbbVie, have a broad and ambitious vision for the development of epcoritamab, and we have been accelerating the clinical program over the last couple of weeks and months, including a PK safety study in Japanese patients that is very well underway.
These trials form the building blocks as we, together with AbbVie, plan to initiate several additional studies in the upcoming months. I hand it back to Anthony.
Thanks again, Tahi. What are customers thinking about this class? I can tell you that there's already high enthusiasm and awareness for this new mechanism of action. CD3/CD20 antibodies are being seen as the next major opportunity in non-Hodgkin Lymphoma. The rationale for this is that opinion leaders and oncologists and hematologists who've had a chance to get their hands on this have a very favorable perception of the efficacy and safety profiles in the class. As Tahi showed, with strong single-agent overall response rates and complete responses, as well as a manageable safety profile, we believe this class has the potential for a lot. It also has the potential for subcutaneous administration, which can offer both patients and healthcare providers a convenience advantage, and may help favorably impact the rate and severity of cytokine release syndrome, and ultimately result in fewer hospitalization complications.
The initial therapeutic profile emerging for epcoritamab as a single agent is clearly very encouraging, with very high overall response rates and a manageable safety profile. The convenient route of administration through an easy-to-administer 1cc small volume injection and a low rate of high-grade CRS can also be an important differentiator for the product. In summary, epcoritamab has the potential to be best in class and to positively impact DLBCL patients by delivering deep durable responses and improve survival along with a manageable safety profile. It is clear that epcoritamab also has the potential to be very competitive beyond DLBCL in other B-cell malignancies with high unmet medical needs, such as the ones shown here, such as follicular lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma, with potential utility in each in combination as well as in earlier lines of therapy.
In conclusion, epcoritamab has shown very promising efficacy and safety as a single agent in late-line DLBCL, and based on its overall profile, we believe it also has significant potential to be beneficial across patients with B-cell malignancies. Let's transition to tisotumab vedotin. As you know, we've been developing tisotumab vedotin, or TV, in a collaboration with Seagen. As we announced on our Q3 call last week, we're really pleased to have finalized a joint commercialization agreement whereby Genmab will co-promote TV in the U.S. and lead all commercialization efforts, including booking sales in Japan. Seagen will lead operational execution of future clinical trials, as well as commercial operational activity in the U.S., the EU, and China. All of the major markets, and that for this agreement is the U.S., Japan, Europe, and China, will be a 50/50 cost and profit split with Genmab.
In markets outside these major markets, Seagen will commercialize and Genmab will receive royalties in the mid-teens to mid-20s based on net sales performance. Of course, we'll continue to work together on all strategic decision-making related to the development and commercialization of TV. The first indication that we're pursuing for TV is in metastatic or recurrent cervical cancer, where tissue factor is highly expressed. TV also has the potential to be useful in other solid tumors where tissue factor is highly expressed. Let's take a deeper look. What about the patients with advanced cervical cancer? Although metastatic or recurrent cervical cancer impacts a relatively small group of women, it's characterized by really very poor outcomes. The woman shown here is Linda. She's a cervical cancer patient who also shared her journey with our team, and it's really clear that better treatments are needed for patients like her.
This cancer is diagnosed at a relatively young age and tends to impact more women in a lower socioeconomic status. In addition to dealing with a cancer diagnosis, many of these patients feel the stigma due to the link to HPV infections. Lastly, the prognosis for patients diagnosed in the later stages is very poor, with a mortality rate of 83% in five years. The need for better treatments is high, as recently approved options also have a relatively low overall response rate at less than 15% and relatively poor overall survivals in the six to nine month range. This next chart shows, again, the number of women treated with metastatic cervical cancer in the U.S., the five largest European markets, and Japan. The market size in second-line plus metastatic cervical cancer is around 6,000 patients, with just over 3,700 patients in the U.S. and Japan.
It's a relatively modest initial patient population, but we believe it represents a meaningful opportunity as the unmet medical need is significant. Now, Judith Klimovsky will present the most recent TV clinical data. Judith?
Thank you, Anthony. The following slides were presented at a late-breaking oral session at the 2020 virtual ESMO Congress. InnovaTV 204 is a phase II single-arm global study of tisotumab vedotin in patients with recurrent or metastatic cervical cancer. Patients that progress on doublet chemotherapy with bevacizumab, if eligible, receive tisotumab vedotin once every three weeks. The primary endpoint was confirmed objective response rate, ORR, assessed by independent review committee. Clinically meaningful and durable responses were observed. Confirmed ORR was 24%, with 7% complete responses. At the median follow-up of 10 months, the median duration of response was 8.3 months. Responses were generally consistent across most evaluated subgroups. A picture is worth a thousand words. Shown here, a clinical vignette of a 42-year-old patient with a very aggressive disease, as we see in the notes. As the images reflect, she got a CR that lasted 8.5 months.
Secondary efficacy results shown in this slide. Median PFS was 4.2 months, and median overall survival, 12.1 months. The most common treatment-related adverse events included alopecia, epistaxis, nausea, conjunctivitis, fatigue, and dry eye. Most were Grade 1 or 2. We are pleased that this data was very well received by the medical community and for the potential of TV to become an option for patients with recurrent or metastatic cervical cancer. In partnership with Seagen, we are actively working, preparing for our first BLA. I will turn the presentation back to Anthony.
Thanks so much, Judith. We really believe TV can play a leading role in the second-line plus metastatic cervical cancer segment. As Judith outlined, the efficacy, durability, and safety profile across all comers in second-line plus patients can provide a new and valuable alternative to currently approved therapies. If you consider the fact that data with checkpoint inhibitors shows only about a 14% overall response rate in a subpopulation of PD-L1 positive metastatic cervical cancer patients, it's clear that the TV data is compelling, as it shows a meaningful benefit regardless of PD-L1 status. Clearly, an all-comer approach is simpler for clinicians, primarily in the community, who are treating this disease, as screening patients for a biomarker isn't needed. This profile is based on a single agent TV activity.
We think that's the beginning, and we're hopeful that the combination of TV with checkpoint inhibitors in this setting can lead to even better overall response rates. We've seen with our partner, Seagen, showing other vedotin ADCs have demonstrated improved responses in combination with PD-1s in other malignancies, and this is something we're exploring with our partners. Based on the product profile and upon a successful regulatory review, we have an opportunity to position TV as a first-in-class ADC with a strong efficacy and manageable safety profile in a metastatic cervical cancer population across all comers, regardless of PD-L1 status. Almost three-quarters of oncologists that we surveyed stated that they would prescribe TV within three months of it being available based on the impressive overall response rates and duration of response.
About half of those would recommend TV to their peers and believe it meets a significant unmet need in their practice. Clearly meaningful potential for patients with metastatic and recurrent cervical cancer, and that's our main focus in the near term. To conclude, and to tie back into the near-term priorities that we covered earlier in the presentation, we're making excellent progress standing up our two priority markets, the U.S. and Japan. We're continuing to work closely with our partners to bring these two exciting late-stage development assets to patients, and in so doing, Genmab is well on its way to achieving our 2025 vision. Thank you, and with that, let me pass it back to Jan van de Winkel.
Thank you, Anthony. Let's conclude with a look at where we have been and where we are going. Here's a glimpse of our 21-year history and some of the milestones that have propelled us to where we are today. As you can see to the far right, 2020 has been yet another record year for Genmab, and there are now more than 20 Genmab-created antibody therapeutics in active, full-blown clinical development. All the events that you see here, and many others, have led to the inflection point at which we find ourselves today. While our 2018 Capital Markets Day was aspirational, our 2020 Capital Markets Day shows that we have already begun to deliver on our promise, and how we will continue to do so over the next 20 years and beyond.
Because we are only at the beginning, we are well-positioned for continued success, built upon a solid financial foundation as described by Anthony Pagano, and our expanding capability shared with you by Judith and Kate. As Rob and David discussed, our unique differentiated proprietary antibody technologies will continue to allow us to be at the forefront of the next transformative wave of innovation in medicine. Supported by our strategic partnerships, as mentioned by Judith, we are already delivering on our promise as our pipeline matures and we move our later stage therapeutic candidates forwards and hope that this will soon progress, as Anthony Mancini has discussed, to the ability to address unmet medical needs with our own first products on the market.
Taken together, we are clearly on the path to very soon becoming a fully integrated biotech innovation powerhouse that continues to meet our core purpose of fundamentally transforming the lives of cancer patients. Thank you all for your attention over the last two hours or so. We are now pleased to answer your questions. If you would like to ask a question, please click on the Raise Your Hand icon at the bottom of your screen. You will then be announced, and your microphone will be unmuted when it's your turn to ask a question. If you would rather like to ask a question via text, you can then click on the Q&A icon and type in your question, and then a member of our investor relations and communications team will then reply to you directly. Who wants to start?
We have Michael Schmidt from Guggenheim. Michael, please ask your question.
Hey guys, t hanks for this overview. Super interesting how much progress the company has made. I just had a couple on GEN1046 and some of the SITC data. Maybe first, could you just help us understand how you ended up selecting the 100 mg dose as recommended phase II dose? I'm trying to better understand the dose response here, i t looks like your pharmacodynamic analysis kind of points to maybe an inverse correlation there with dose, and help us understand what your thoughts are behind that, and then I had a couple follow-ups as well. Thanks.
Thanks, Michael, for the question, and you're definitely right. Many of these bispecifics can have bell-shaped curves. I would like to propose that Tahi Ahmadi handles this question. Tahi?
It's a very good question. I think as you think about how we selected the dose, there are two dynamics that you have to consider. One is the pharmacokinetic behavior of bispecifics in general, dealing with two targets and two different target-mediated clearances, and how that impacts the dose. The second one is the biology of agonists. It's well known that there is some element of a bell-shaped curve dose efficacy response that doesn't really necessarily go linear. We picked the dose not necessarily by safety at all. Actually, it was primarily driven by the PK translational components, a strong modeling approach around what we call trimerization, the idea of PD-L1 having to be bound on a PD-L1 positive cell, 4-1BB having to be bound on a 4-1BB positive cell by an antibody, so that's the trimer. We tried to model the optimal trimerization concentration.
Kate talked a little bit about this, and I don't know if you want to allude a little bit more onto some of the data that went into the model.
The data that we showed you was primarily focused on the peripheral PK, where we start to see some accumulation in the periphery above 80 mg. The team, as Tahi mentioned, also did really nice quantitative modeling looking at intratumoral PK and the expectations there. There we see that, again, 100 mg was the dose where we expected optimal trimer formation. Interestingly, this was also the dose where we would still expect between 60% and 75% full occupancy for PD-L1, shown by other checkpoint inhibitors. We felt that this range, based on also the PD biomarker data that you ask in your question, and there we showed some today, but we've looked, of course, at many other biomarkers associated with T- cell activation, expansion, and functionality. Combining all of that data together really suggested that the 100 mg q3 weeks would be the optimal dose.
How confident are you that there is no liver signal? When we look at the ALT and AST elevation frequencies, they look somewhat similar to what had been seen with urelumab early on. I'm just curious what your thoughts are on that front.
Maybe, Kate, you want to take it or let's Tahi. Well, Tahi for that. Tahi?
I think as I presented this, and I think also as Dr. Melero presented this at SITC, we do see transaminases. We find them so far to be manageable, t hey are also probably more manageable because we have actual clinical activity, which was not necessarily the case in the past. The biology that drives the transaminases may also be a little bit different in our situation. Nonetheless, we see, as I said, a third of the patients have ALT elevation, 10% have Grade 3. It has not precluded us from continuing exposing patients.
I think it's important to know, as I touched on it in the presentation, that we actually were able to re-expose patients after they have experienced Grade 3 toxicities, and they appear in these cases that we have, and we are still dealing with a relatively small data set, able to tolerate the exposure to GEN1046 with less transaminase elevations afterwards.
Thanks, Tahi. What I can say, Michael, is that we are still actively recruiting in this trial. We have now up to nine expansion cohorts, so this is continuously progressing, and there seems to be a very good level of enthusiasm, both with the doctors and the patients to progress this trial. Let's see how data looks next year. As Tahi has already alluded to, we'll get more data next year, in 2021, w e probably have to keep it with this. Are there any other questions?
Next question we have is from James Gordon, from JP Morgan. James, go ahead and ask your question.
Hello. Hopefully, can you hear me okay?
Perfect. James, welcome.
Great, t hanks. Yeah, James Gordon, JP Morgan. A couple of questions, please. One was on 4-1BB/PD-1. The data clearly shows promise in PD-L1 high expression on small cell cancer patients who have failed IO. You did mention a couple of other subgroups, but can you talk about which other subgroups are you most bullish about, and what data do you have that justifies that? That would be the first question about 4-1BB. The second question, which mechanisms are you most excited about combining the agent with? Also, a question on epcor. On Wednesday night, we saw Xencor and MorphoSys announce a collaboration. Combining MONJUVI with a CD3, CD20, i s that an exciting approach? Is that something that maybe you need to do as well to keep up with them, or are there other combos that could be more interesting for a CD3, CD20?
A third and final question, just in terms of news feeds, there loads of news flow in 2020 on the pipeline. 2021 looks like it'd be a little bit quieter maybe, i s that fair? Is there lots of other stuff to sustain the pipeline momentum in 2021? What do we need to look forward to for next year, please?
Thanks, James. Some good questions, I can tell you. I think Tahi, we can handle the PD-L1, 4-1BB question. What are we most excited about? Maybe speculate a bit, or give James color, Tahi, on what we could combining it with there? What are we thinking about? Maybe also then progress with epcor after that. The CD19 combination with the MorphoSys antibody. CD19 and CD20, of course, are co-expressed, James, we know this concept quite well. Maybe Tahi, you can add a bit on that as well. We'll park the 2021 question, I think, James, this is going to be an absolutely fantastic year, a very data-rich year. We'll give you some further color, you will warm up completely on that after Tahi answers the first three questions. Maybe Tahi, over to you.
Very good. GEN1046 first. As Jan said, and I touched on this in my presentation as well, we are actually actively enrolling in all cohorts. They'll be also generating data there, and we will be sharing the data with you, in the near future. The reason why the lung cancer cohort was part of the SITC abstract is essentially function of when the abstract was due, and the patients that were enrolled at that time point. If you look at the dose escalation, just to give you a little bit of a hint, there is also an ovarian cancer patient who has a very long duration of response. Actually still in response. There's also a triple-negative breast patient that responded. There is a number of signals that make us quite excited about what we see, but it's still low numbers.
We'll be able to share this data very, very soon, I think, because we are very aggressively enrolling on these expansion cohorts. That's GEN1046. CD3, CD20, epcoritamab, w e are starting to generate safety data with a number of backbones. In the beginning, we are clearly focused on the generation of data with backbones that help us drive very expeditiously our strategy towards an approval. That does not preclude, and we will continue to generate data in combination with other experimental drugs. I think it's fair to say that the CD19 antibody from MorphoSys, now partnered with Incyte, is a very interesting compound in that space as well. We will look at these combinations as well as others as well.
Okay. Thank you very much, Tahi. A bit on 2021, and I will definitely ask Judith Klimovsky to step in there in a sec. What you can expect, James, is a lot of data on PD-L1/ 4-1BB. Potentially near the end of the year. On other programs like the DuoHexaBody-CD37, which is well progressing. The second BioNTech program, the CD44/ 4-1BB program, is also progressing very rapidly. Of course, other cancers with tisotumab vedotin, we expect data from Seattle in 2021 for five other solid tumors, and we are very excited about that product, as you could hear today from Anthony and also from Judith. Of course, you will see a fantastic expansion of epcoritamab in multiple phase III and several different settings.
Hopefully we get a feeling in the new year for a very exciting program, James, HexaBody-CD38 and next generation CD38, which we are going to move into the clinic in the coming months. We have filed IND and CTAs already this year or second IND this year. Hopefully by the end of next year, we get a bit of feeling for the safety. Because at ASH this year, James, you will see some further preclinical data, not only in multiple myeloma, but also in diffuse large B-cell lymphoma and acute myeloid leukemia, and we are very excited about that data. Of course, we don't know, James, whether this will be safe in human patients. I think I will stop here and see whether Judith see some further light for you, James, to warm up for 2021. Judith?
Yes. Thank you, Jan. I think that Jan provided a very detailed answer. I would say, in general, we are looking to continue to mature the pipeline, progress the agents, and understand better next steps. As Tahi alluded, this parallel expansion cohorts in GEN1040 [sites] will guide us on next steps, which will be super exciting, and continue to mature epcor. Of course, the BLA filing is in our radar screen as the potential first approval for Genmab in partnership with Seagen and the new IND. Overall, it's continue to grow the breadth, depth, and maturity of the clinical pipeline, plus continue the innovation in research technologies and targets that has led us to where we are today.
Thanks, Judith. What I forgot to mention, of course, is HexaBody-DR5/DR5. I think also more data there next year, James. Hope that makes you a bit happier. Maybe we can move to the next question.
Next question we have from Truong Nguyen from Credit Suisse. Go ahead and ask your question.
Hi, guys. I hope you can hear me. I have three if I can. The first one on 4-1BB, just a clarification. I may have missed it, I don't know, but in the summary waterfall plots of the 4-1BB data, the best relative change from baseline was a partial response from another cancer. Could you just tell us what that tumor type was? Second question on epcor. In the presentation, you noted there's a preference for sub-Q dosing, but when I've spoken to KOLs, one of the things that we've had them raise is that IV is actually quite convenient because DLBCL patients have ports already for the administration of R-CHOP and also weekly labs. Also prescribers, they may favor IV because of the better economics of an IV over a subcutaneous dose.
Do you think there's going to be any hesitation from prescribers wanting to administer a sub-Q dose? Have you got an IV dose of epcor also in development? Finally, I'm sorry to kind of keep asking this question, you're very clear on the investment that you need in the short term to grow into the long term. You're moving tisotumab into the U.S. and into Japan. You're expanding aggressively with 4-1BB with BioNTech. I think we understand this, perhaps can you just give us some help on how we should think about the cost lines as you become a commercial biopharma and get to that 2025 ambition? Thanks very much.
Thanks, Truong, for the questions. Very good questions. I think I will hand over the first two to Tahi, the 4-1BB, the waterfall plot, the patient data. That's a quick one, e pcor as well. For sub-Q dosing, what I want to remind you of, Truong, is that the doctors we speak with are super enthusiastic about the potential for sub-Q version of the antibody because of the fact that we and they believe that in the future, we are moving towards an era where we will not use chemotherapy anymore. Chemo, patients will not have direct intravenous lines, and we probably will treat them with either combinations of antibodies, hopefully sub-Q or antibodies with small molecule inhibitors. We're going to test that also in the clinic fairly soon as Tahi has described. I will let Tahi give some further color there.
The last question about how are you going to see Genmab move to the next phase as a fully integrated commercial biotech? Cost-wise, I will ask Anthony Pagano to give you a bit more color, Truong. Today is not the time to give you guidance for 2021. Beyond that, we will try to give you an even clearer picture to what Anthony already showed in his part of the presentation after we ask Tahi to comment on the first two. Tahi, can you take the 4-1BB and the epcor sub-Q questions for Truong?
Sure. If I understood the question correct, the question was related to the waterfall plot for the dose escalation. There's four patients who responded; t wo patients with non-small cell lung cancer, b oth of them were primary refractory to checkpoint inhibition. One patient with triple-negative breast and one patient with ovarian cancer. What you already, I think, can appreciate that the responses that we see here and then also in the Cohort 1 that we presented are in patients that are not necessarily usually expected to respond to current available immunotherapies. It's a differentiated pattern of responses completely. Hope that is the question that you asked and that I answered that question. As related to epcoritamab sub-Q, I think it's important to also remember why we started the sub-Q program with epcoritamab.
It started with the observation that in the cyno safety monkey studies, the administration of subcutaneous epcoritamab was going to avoid or was avoiding the peak Cmax on the PK and the peak on cytokines. We believe that this allows us to be a little bit more tolerable. We have a 50% rate of cytokine release, but it's all Grade 1 and Grade 2 so far, i t's only in the first cycle. It's a little bit different than what some of the other programs have been described. You also asked, I think, a question of how confident we are at the recommended phase II dose. 48 mg is the recommended phase II dose. I had mentioned that in the ASH abstract, seven out of seven patients responded. It's pretty good response rate. We will see more on that data at ASH.
We obviously initiated a phase III that's going to enroll any moment with that dose. We are very confident that 48 mg is the appropriate dose for epcoritamab.
Thanks, Tahi. Truong, you will get a lot more firework on epcor at ASH in the oral presentation, we can promise you today. Let's move to Anthony Pagano and then ask Anthony for a bit further color for Truong on how we should think about our stepping up our investments into the future, as you already explained. Anthony, m aybe you can give Truong a bit more clarity and concrete information if you're open for that. Otherwise, you will park that till February next year.
No, happy to do so. Thanks, Jan, and thanks, Truong. Maybe it's useful to provide a bit of context and a framework for how we sort of think about this, right? It starts with our proven track record, our strong foundation, and our exciting growth opportunities. Let's first start with this proven track record, and let's start there on the R&D or business side. We've had just an absolutely tremendous hit rate and productivity rate. We look at our novel tech platforms we've developed, we look at three marketed products, and we look at our exciting pipeline. Now, it is absolutely phenomenal. On the financial side, in terms of our proven track record, we've stayed true to our strategy. We've stayed focused and disciplined, and we've run a profitable business and built a strong balance sheet.
I'll leave it for you to judge, but for me, this is truly exceptional. If we look at our strong foundation and our exciting growth opportunities, you've heard a lot about these today from my colleagues. In summary, we have all the ingredients to become a fully integrated biotech powerhouse. We have these two near-term potential product launches and very clear set of priorities. Given that, it's up to us to figure out what the right investment levels are, and that's exactly what we're going to do. We'll continue to be focused and disciplined in our approach. As I've talked about previously, being focused and disciplined has two sides to that coin. On the one hand, it's about taking a stepwise approach, de-risking investments when you can, and making tough decisions along the way.
The other side of the coin, in terms of being focused and disciplined, is really around when you have these exciting growth opportunities to really make sure that they get the focus and capital that they deserve. That's exactly what we're going to do. Hopefully this gives you some context, Truong, on how we think about investing here at Genmab, continue to be focused and disciplined. Finally, in terms of our guidance, we'll come back to that at our earnings release in February.
Thanks, Anthony. Truong, the sum up is focus on the potential winners and kill the other programs which are not differentiated or truly differentiated. That in combination will give us a very sharp profile towards the future. Hope that is okay with you for the moment, Truong. Maybe move on to the next question.
We have Sachin Jain from Bank of America Merrill Lynch. Sachin, go ahead and ask your question.
Hi there, Sachin Jain here from Bank of America. I hope you can hear me clearly. Just a few questions, if I may. Firstly, on epcor into ASH and an update of the DLBCL data you've referenced. There's some focus on how the 29% CR rate improves with further follow-up. Just to frame expectations on that data, what do you think a benchmark is that you've seen from competitive assets that we should view as a benchmark, acknowledging the different patient baseline characteristics across studies? Second, on epcor combos. You briefly touched on an answer to an earlier question, but at the time of the AbbVie deal, there was some discussion of combinations with some of AbbVie's proprietary pipelines, Imbruvica, Venclexta, and then combos with CD37. I just wondered whether there was any update on that. On 4-1BB in your news flow answer, Jan, you referenced imminent conference.
I wanted just to avoid our speculation if you could reference which conference you're targeting. Last question is on a couple of assets which haven't really been a focus today, HexaBody-DR5/DR5 you mentioned some updates next year, w here are you with that? AXL- ADC, no mention in the slides and not mentioned in news flow due next year, a ny update there? Thank you.
Thanks, Sachin, for the questions and for attending. The first two questions on epcor I will pass over to Tahi. Then the PD-L1/ 4-1BB, we haven't yet decided which conferences to send our data to. We are very rapidly moving up the number of patients in nine expansion cohorts there, Sachin. We cannot give you an update today, w e will do that in future events. We definitely have the ASH review meeting on December 8th. That may be a time that we can give you further color on that. I will actually pass the fourth question over to Judith Klimovsky to give you a bit more color on where we are with the HexaBody-DR5/DR5 program and with enapotamab vedotin, where we also expect data this year, Sachin.
Let's first move to Tahi to answer the epcor questions, the benchmark, basically, Tahi, for the diffuse large B-cell lymphoma data. What should we let Sachin and other analysts focus at or think about or dream about, and then hopefully be better at upcoming ASH. I leave it now to you, Tahi.
Sure, t hank you for the question. Not an easy question to answer, actually. The response rate as you look at them across the field of CD20, there's a little bit of a fluctuation. If you just focus on diffuse large B-cell, in terms of what has been reported for the different assets based on response rate and CR rate. Some of it may be a reflection of the biological properties, s ome are more potent than others maybe. There's another component that needs to be considered, and that is the duration of exposure and the time of response assessment. If you look at our CR data in the ASH abstract, I mentioned this, most of these were at week six as the first response assessment. We know that the responses deepen over time.
If you think about benchmarks, I would say it's probably fair to say across the spectrum that the highest ceiling of ORR is somewhere in the public domain, 70%. For the two Roche and Genentech as well, so the Regeneron component, maybe Regeneron a little bit higher, and the CR rate is high 20%, 30%. I cannot preview the data will be presented at ASH. I do think that I mentioned this, and we continue to believe that epcoritamab is the best in class, and it will show itself.
Thanks, Tahi. Maybe a bit on combination therapies with ibrutinib and Venclexta and other potential small molecules we are thinking about and will likely move into action in clinical trials. Tahi?
Question on the combination with ibrutinib and venetoclax. We are obviously talking to our colleagues at AbbVie, I'm working right now actively on a strategy for where best to position these combinations, we will see some activity on this in the near future.
Thanks, t hanks, Tahi. Then maybe over to Judith. Maybe you can give a bit of color, Judith, on where we are with the HexaBody-DR5/DR5 program and what can be expected on the enapotamab vedotin program going forward. Judith?
Yeah. Thank you, Jan. Thank you for the question. HexaBody-DR5/DR5, our first HexaBody in the clinic. As we all know, in December last year, we shared that after a short clinical hold, we resumed enrollment. This is what we have done along the year. We are in the process of collecting data, activity, and safety to determine the therapeutic index for this compound. Stay tuned, more to come as we collect data and understand better the benefit-risk based on the new data that we are getting. For enapotamab vedotin, as we all know, we present the data on one of the expansion cohorts, the lung cancer, last year in September. We already shared that the study required fresh biopsy because AXL is an inducible target. It was a little bit delay behind projections in terms of enrollment.
We think that we have the right critical mass of data that assess safety, efficacy, and biomarkers. Based on this totality of the data, we will decide next steps. Stay tuned, m ore to come as our teams are actively working on collecting all this data, cleaning, and putting all together for us to understand better where we stand.
Thanks, t hanks, Judith. Thanks, Sachin, for the questions. Let's move to the next question.
We have Michael Novod from Nordea. Michael, go ahead and ask your question.
Thanks a lot. It's Michael Novod from Nordea. First of all, congrats with running a very professional and smooth virtual CMD. Just to start with that. First on maybe HexaBody-CD38 and maybe you can just remind us how fast can you run this? We see good data, and can it also be run in a sub-Q version? We can see that the uptake on sub-Q DARZALEX is obviously stunning. Just to get a feeling of whether this can be done also quickly with the HexaBody-CD38. Secondly, maybe that's both for CFO and also for Anthony Mancini. The size of the organization, I think Truong was trying to get an answer on the cost base going forward. Maybe you can talk a bit about the size of the organization going forward.
What is needed in order to run an efficient commercial operation in the U.S. together with AbbVie, of course, for epcor, also in Japan leading the commercial efforts there, just so we can get sort of a feeling of how this is building. Lastly, to the sort of the revenue slide. I still don't really understand the sort of that slide. Maybe it's just me, the consensus around $3 billion in revenues in 2025, you show the $ 1.9 billion, you show some upside. Do you think the consensus at $3 billion in revenues in 2025 is conservative? Is that what that slide is about to tell us?
Thanks, Michael, for the questions. Thanks for attending, and thanks for the congratulations. I can tell you it's a military operation here in Utrecht and in Princeton, so I'm happy that we didn't lose the connection and that things went fine up to now. Thanks for mentioning that. That's greatly appreciated on behalf of the team working on the Capital Markets Day. HexaBody-CD38, I'm going to propose to move it over to Tahi to say a little bit about the clinical trials, t he two trials which we are planning there, how fast we can potentially run them, and also the aspect of whether we could conceptually think about a subcutaneous formulation for the HexaBody-CD38. While Tahi is thinking about that, let me introduce Anthony Mancini for the Q&A for the first time, I think, on this Capital Markets Day.
Anthony, a little bit of color, please, on the potential size of the U.S. and Japanese organization, not jeopardizing, of course the competitive positioning versus competitors who are listening into this Capital Markets Day at the same moment. Why don't you give maybe some color to Michael Novod on the potential size of the U.S. and Japanese operations for TV, epcor, and give him a bit to work on for his modeling so that it improves in the coming time.
Thanks.
Anthony?
Thanks, Jan, I'll try my best. Thanks, Michael, for the question. I think, as we said earlier, we're really focused on making sure that we're focused and deliberate, and we're really focused on the two products in the two priority markets. Some of the drivers of what we'll look at that will shape resourcing decisions in those two markets are the size of the target audience and the size of the opportunity. What I can say is that we're working very closely with our partners to make sure that we're investing to win, so that we can make the biggest impact, but we're also doing it appropriately to the size of the opportunity. I think we can provide, Michael, more details as and when we achieve a launch, and to Jan's point, not jeopardize any of our competitive positions, both for TV and epcor.
Thanks, Anthony. Maybe move over to Tahi now for HexaBody-CD38, maybe a little bit of color on how fast we can run the dose escalation in multiple myeloma, Tahi, and the potential of a scenario for a sub- Q version.
How fast can we run the HexaBody-CD38 program? I would say we gave you two programs today where we talked a little bit about speed of execution, that's epcoritamab from Genmab to the initiation or the announcement of a phase III, two years. PD-L1 GEN1046 from first-in-human to defining the recommended phase II and opening expansion cohorts in nine or 10 months. I think we can move fast. We are with the INDs filed, and we are looking forward to initiating the trial and see the first patient in those escalations. As it relates to sub-Q, that's certainly something that we are thinking about as the program continues to evolve.
Thanks, Tahi. Maybe the last question, Michael, to Anthony Pagano, to give you a bit more color on the revenue. Anthony?
Yep. Thanks, Jan. Michael, maybe just put a bit more perspective onto the projections that we provide today. You're correct, these are looking at consensus moving forward. Really what we're trying to show is that based purely on the three existing marketed products, DARZALEX, Kesimpta, and TEPEZZA, that we're looking at our potential revenue growth of more than 2x . I mean, these are examples of products with very strong product profiles, excellent partners, very committed partners, and ongoing investment to sort of further solidify their position and potentially grow the market opportunity. We think, looking at that, just based upon the three existing products, we have very significant and meaningful growth for the years to come. It doesn't stop there.
If we look at the royalty streams, most advanced is amivantamab, but this could potentially be, as I mentioned, be filed later this year with the FDA, and it could add to that recurring revenue stream. That's not what's most exciting for us. What really is most exciting about is adding on top of that our own products. We talked a lot today about the near-term opportunities, tisotumab vedotin and epcoritamab. Michael, no specific numbers for you today. We spoke a lot about our strong foundation, our exciting pipeline, the near-term growth opportunities. The future for Genmab is very bright. Today, I just want to give you a bit of glimpse that even based upon the existing products, we're looking at significant growth moving forward.
Thanks, Anthony. Thanks, Michael, for the questions. Move on to the next one.
We have Carsten Lønborg from SEB. Carsten, go ahead and ask your question.
Yep. Thank you very much, Carsten from SEB. I think I have only maybe one or two questions left. The first one is for epcoritamab, the first phase III trial you're conducting here. Would it be possible for you to share what level of response would you normally see in the control arm of bendamustine and rituximab in this type of patient population? Whether now it's a plus one prior lines of treatment, is there also sort of a maximum where you maybe will be enrolling patients that are a little bit less sick than what we have seen so far?
Thanks, Carsten, for the questions. I think this is a question for Tahi. Tahi, a bit on the control arm, the bendamustine, rituximab arm, in the same population of diffuse large B-cell lymphoma. The second sub-question on the prior lines of treatment, maybe the range there. Tahi?
Yeah. The question related to the expectations...
Bendamustine, rituximab arm
...on the control arm. It's actually two?
Yeah.
Gemcitabine oxaliplatin and bendamustine rituximab. For bendamustine rituximab, it's a little bit easier because there is a contemporary data set that shows a response rate of roughly around 30%. I should point out that in Diffuse Large B-cell, you would like to focus on the CR rate, because in front line Diffuse Large B-cell, a non-CR response is actually considered to be a failure. Consequently, really the prognosis, even for those patients who response is dismal, in the contemporary data sets, it's like six to seven months overall survival. The same is probably true for GemOx, t hey are probably comparable [audio distortion]. Thinking about a somewhere seven to eight months for the control population. That gives you a little bit of a, I think, good sense of what the current available therapies are offering for these patients.
In terms of prior lines of therapies, I think Martin Hutchings will go into great detail. I think the median prior lines of therapies in diffuse large B-cell are three, and for the follicular lymphoma are five, and those escalation cohort. These are very heavily pre-treated, refractory patients. Again, I mentioned the fact that now a number of these patients also came in with prior CAR therapy. Those who came in with prior CAR therapy actually had been refractory to prior CAR therapy. It's really, in the dose escalation for sure, an end-stage population that has no options available.
Thanks, Tahi, for the further color. Thanks, Carsten, for the questions. Let's move to the next question.
We have Jonathan Chang from SVB Leerink. Jonathan, go ahead and ask your question.
Hi, guys. Thanks for taking my questions and wonderful presentation. Definitely knocked my socks off. A couple of questions on epcor.
We can hardly hear you, Jonathan. Maybe you can speak up.
Can you hear me?
Now we can hear you better. Yes, this is a clearer line.
Great, t hanks for taking my questions. Wonderful presentation, definitely knocked my socks off. A couple questions on epcor. First, how should we be thinking about positioning of epcor versus CAR- T in the B-cell malignancies treatment landscape? Second question, how much of an issue is CRS for epcor as you think about the potential to move into earlier lines of treatment across the different B-cell malignancy opportunities? Thank you.
Thanks, Jonathan. Thanks for the kind words on the execution, I am happy that you like our knock your socks off type metaphor, which means of course, fantastic, super differentiated product pipeline. That's still turbo language, I think, for pharma people. Let's move to Tahi for the epcor questions. Tahi, can you handle them? How is the positioning versus CAR- T and the CRS issue for epcor?
Sure. First I would say that chimeric T-cells, CAR- Ts, in many ways are the proof of the concept that engaging T-cells can lead to significant deep responses in lymphomas. The advantage of epcor vis-a-vis CAR- Ts, I think, are obvious. It's off the shelf, so you don't have to deal with the manufacturing issues, the delay from identifying the patient to providing the therapy. The cost that comes associated with that therapy, both direct and indirect. Also the toxicities as they have been described for CAR- Ts in terms of CRS as well as neurotoxicity. As it relates to epcor, the cytokine release syndrome seems to be very much a first cycle phenomenon.
Indeed, it will be interesting to see if in combination with backbones that allow to reduce the tumor burden, the cytokine release will actually be even less because there must be some. It's presumably a relationship between the number of tumor cells that are CD20 B- positive and the T-cells that are available. But given the fact that it is purely a cycle one phenomenon, we feel very confident that it can be combined, which is another differentiating aspect to CAR- Ts, which have not been able to combine with other backbones, which opens completely different development opportunities. I said this very strongly in the beginning of the presentation, we truly believe that epcoritamab has the potential to completely transform the B-cell landscape across all lines. And if you look at the O2 study, we're clearly thinking about frontline as well.
Thanks, Tahi. Thanks, Jonathan, for the remarks and for the questions. On to the next one.
The next question we have is from Emily Field from Barclays. Emily, go ahead and ask your question.
Hi. Thanks for taking my question. I don't think we've gotten an update on the basket trial in other solid tumors for tisotumab vedotin. Perhaps if you could just let us know when perhaps we may get an update on that. Just also on amivantamab, if you could just remind us how you'll be booking the royalties for that. I know it will be sold by Johnson & Johnson, but just any thoughts on how big that asset could be. Any of the other in-licensed assets as part of that collaboration with Johnson & Johnson that we should be looking forward to hearing about in the future. Thank you.
Thanks, Emily, for the question. The basket data has indeed been moved out of this year. We have announced that at Q3 last week, Emily, we expect that data to be available in 2021 via Seagen, and the same holds for the ovarian cancer data, but no specific timing has been given. Some of these studies have been impacted, Emily, by the COVID-19 era. I think we can probably park it there. The second question for amivantamab, I will pass over to Anthony Pagano. Before I do that, let me give you some further color on the seven bispecific programs with Janssen, which are in the clinic right now, out of the 14 that have been activated. This is an amazing hit rate, which has already been said before. Not seen with any other bispecific platform before.
Teclistamab is now in phase II, and talquetamab is in phase I. Both will be presented in an oral presentation at ASH. For most of these, we get single-digit royalties. For amivantamab, we get up to double-digit royalties because we created actually the antibody arms as well as we handed over the DuoBody technology platform, which Rob and David spoke about to Janssen, so we get a higher royalty there. I'll leave it up to Anthony to give you some further color. I think that Janssen, Emily, has already flagged amivantamab, teclistamab, and talquetamab as candidate blockbusters in their recent overview. We are super excited about the quality of these programs. We look forward to the ASH presentations. This is just following the lines which have been introduced by Rob today, that by using DuoBody, you get an unbelievably high hit rate.
What I want to remind you and other listeners of is that in the 21 years that Genmab is in business, we actually filed 37 INDs in total, and 23 of these programs are today in full-blown clinical development, an almost over 60% hit rate, not seen before by any other biotech company we are aware of, Emily. Having said that, I will stop bragging and then move over to Anthony Pagano to make it a bit more concrete on how to book the royalties for amivantamab when it hits the market, hopefully in 2021. Anthony.
Great. Thanks, Jan. You've done an excellent job really setting the stage. Maybe what I could add, Emily, is just sort of put this into context again into our financial framework. We have the recurring revenues, that they're growing along multiple dimensions, and we're reinvesting that capital back into our business. A product like amivantamab could provide us with another lever of growth in terms of our recurring revenues. In terms of the mechanics, this would be booked like any other royalty, based upon net product sales of amivantamab, should it be approved, which could potentially, assuming it's filed later this year, maybe comes next year in 2021. That could just add back to our recurring revenue strength and growth. This again would be booked like any other royalty, and as Jan alluded to, it's up to potentially double digits.
Looking beyond amivantamab, I think just looking at it from a financial perspective, there's a handful, a number of other potential products that are in various stages of development. There is a potential for one or more of those ultimately to come to market and then further add to a recurring revenue stream moving forward. Hopefully, Emily, that gives you a little bit more context and color and helps you out with the P&L modeling.
Thanks, Anthony. To add to what Anthony said, Emily, I can tell you that Mim8, the bispecific antibody for hemophilia from Novo Nordisk, has recently started phase II, taking some nice milestone payments to Genmab in Q4. You will see that in the full-year report, that is also good news. Also there, that program is really moving forward aggressively. Pre-clinically, as you and I know, Novo Nordisk has actually described data showing that this molecule is over 15-fold more potent than one of the Roche components, Hemlibra, targeting Factor 9 and Factor 10. Yet another example of a bispecific product made with the DuoBody technology Rob described, which seems to be very differentiated and doing well in the clinic. Let's move to the next question.
We have Asthika Goonewardene from Truist Securities. Asthika, go ahead and ask your question.
Hello, Asthika.
Hi, can you hear me okay?
Yes, perfect.
Lovely, t hank you so much. Thanks for taking the questions and really appreciate all the color that's been given today, guys. Let's start with GEN1046. On the dosing side, it makes sense why for an agonist action, a lower dose might be a better approach here. I'm wondering, maybe to Kate, if she can answer the question. In the patients who received several cycles of therapy, are you seeing similar gamma and CD8 activation after maybe four or more cycles of therapy? Are kind of seeing a linearly consistent cytokine profile there? To maybe Tahi. You mentioned that in the epcor expansion cohorts, those may be registrational. I just want to clarify if I heard that correctly.
Could you elaborate what is the path to market in those three tumor types, CLL, FL, and MCL, of those expansions that you see, what have maybe the regulatory agencies set as the bar here. Finally on epcor, something we saw with some of the other CD20 and CD3s, is that as they recruited more patients and were able to figure out ways by step-up dosing or adapting the tumor burden, they were able to lower their level of CRS, in a broader patient population. Roche did a great job of that one with mosunetuzumab. The question to you is, how are you planning on approaching this, and what kind of Grade 3, 4, and also importantly, Grade 2 CRS rates do you think you can achieve?
Thanks, Asthika, for the questions. The first one indeed, hand over to Kate, the GEN1046 program. Kate, the agonistic activity, cytokine profiles, maybe you can handle that first.
Yeah, happy to, t hanks for the question. In terms of what we see as we move forward into longer terms and longer dosing with GEN1046, we do see in some patients continued signs of T-cell activation. Some of them we showed you today, the interferon-gamma and other cytokines, granzyme B, as an example, associated with T-cell functionality, but also continued T-cell expansion, cytotoxic T-cells, and importantly, we think the memory T-cell component. It's still early days, w e'll have to watch as we continue to have more patients at later time points, but w e do think that we're getting continued T-cell activation.
Thanks. Thanks, Kate. Let's move over to Tahi and the expansion cohorts or the potential accelerated approval path which we could take there. Can you set the bar and diffuse large B-cell lymphoma, Tahi, and follicular lymphoma. Maybe you can address that.
The first part of the question is easier than the second part. The expansion cohorts are set up as phase II registration and enabling studies with all the bells and whistles that come with that, including an independent review of response. They are clearly intended to generate data that we believe, if it is meeting a certain threshold, and I don't think I want to go into this discussion here on what we believe the regulator considers to be a threshold, but I think we are confident the data that we have shown, if it continues to hold up, would exceed that threshold. Data generated would then allow for an accelerated approval on these expansion cohorts for sure. On the question around cytokine release, it might sometimes not be clear, so I want to make this clear that everybody knows this. We're also stepping up in the dose.
The first dose given is 160 μg on day one, followed by 800 μg on day eight, and then 48 mg is the first full dose. We do employ a step-up regimen as well in order to control the release of cytokines. As it relates to what we can do, continue to do to reduce Grade 2 cytokine release, as you ask, t here's a couple of things, s ome are related to how different companies report cytokine release at this point. As I said, it's a composite endpoint, and everybody kind of figures out how to actually describe it, whether they describe it as cytokine release or as components of what then constitutes cytokine release, meaning pyrexia or hypotension separately. I would encourage you in some of the public datasets to look also at the components of cytokine release as they are reported individually.
Clearly, a lot of this has to do with also the utilization of IL-6 and also the experience of investigators, how to manage the drug in an appropriate manner. We have increased our mitigation plans as it relates to steroids that are given in the first couple of injections, which has helped control. We're continuously obviously working on optimizing to make this as patient-friendly and as safe as possible.
Thanks, Tahi and Asthika. I think we have four more questions to go, and we have only 10 minutes, so I think we probably keep it with this. What I can tell you is focus on ASH. Best in class means potentially not only the safety but also the efficacy and the combination of those. I think that is going to be very exciting at upcoming ASH. Maybe the next question.
We have Graig Suvannavejh from Goldman Sachs. Graig, go ahead and ask your question.
Hello, Graig. Graig, you're on mute. Are you still there? Maybe we can switch to another question first and then get Graig back.
Sure. We have Peter Welford from Jefferies. Go ahead, Peter, and ask your question.
Hello, Peter.
Hi, t hanks Jan. I've got just three questions, I'll be brief. Firstly, just on the role of the combinations that you're looking at with epcoritamab. I'm curious why you've not considered Revlimid alone, only R-squared. Have you also looked at all using Rituxan to protect the cells, I guess the healthy B- cells prior to epcoritamab? Is there any data you have so far on use of Rituxan in addition to epcoritamab? Secondly, quickly, Jan's mentioned a number of times nine expansion cohorts rather than seven, I think. Is one of the additional expansion cohorts, sorry, this is the 4-1BB, ovarian, what's the other one? Just so we can understand what the nine are.
Thirdly, just on the accelerated filing that was asked in the prior question. Just curious there, whether you can comment on the potential bar for accelerated filing, given obviously there are competitors who are also pursuing that, and how, I guess, accelerated filing could change depending on you being potentially second, third, to pursue that sort of pathway in those settings. Thank you.
Thanks, Peter, for the questions. The first and the third question are definitely going to Tahi. The second question I can handle myself. It's not in the public domain what the other two cohorts are, so we keep that as a secret here. What I can tell you, Peter, is that we are continuously adding new expansion cohorts, and we still see good recruitment in the GEN1046 trial. More of that to come in 2021. Tahi, maybe on the combinations with Rituxan and why epcoritamab has not been chosen as the only antibody to combine with. Tahi?
I think if I understood the question, why would we combine in the safety study with lenalidomide, rituximab? If you think about this regimen, R-squared is approved in follicular lymphoma and relapsed refractory. It's a building block that we are thinking about using now. It doesn't preclude us, once we've generated the safety, at some point to interrogate the idea of whether we should leave a CD20 antibody out. We know from our preclinical data that the presence of a CD20 antibody certainly doesn't negatively impact the efficacy of epcoritamab. There is no negative here. Then the other question was whether...
Filing strategies.
...the accelerated approval.
Filing strategies.
The accelerated approval from the competitor. The regulation in the U.S. on this approach is that actually an accelerated approval from one component or one company, one drug, does not preclude an accelerated approval in the same indication by another. It's not blocking, because it's not considered to be a full approval. As we are, in terms of what the estimations are, how far we are behind, I hope if there's one thing that you take away is that may not be as far behind as you may fear, others may have hoped.
Having said that, we'll leave that as a cliffhanger, Tahi, and give it back. Let's see whether we have Graig back from Goldman Sachs. No, not yet. Maybe another question, because I know we have two more to go.
Graig, can you try speaking?
We don't hear Graig. Maybe Graig can type in the questions, and you can read it for us. That may be the best solution here.
Sure. We'll move on to Rushee Jolly from Bernstein. Rushee, go ahead.
Hi. Rushee Jolly, Bernstein, t hanks for taking my questions. Firstly, on the PD-L1/4-1BB, my understanding was always that the 4-1BB activity was conditional on the PD-L1 expression. Yet the patients in the escalation cohort with non-small cell, where you saw signs of clinical benefit, seem to have low PD-L1 scores. Could you provide maybe an initial comment or initial view on the importance of PD-L1 expression levels to the molecule's activity? Secondly, another question on HexaBody-CD38. Jan, do you see this as being Dara 2.0, or do you see a broader potential beyond multiple myeloma? Here, I'm thinking of CD38-positive tumors where Dara doesn't have a single-agent efficacy, so things like T-LBL cell. Thank you.
Thanks for the questions. The first one is definitely for Kate. Let me first handle the HexaBody-CD38 question. Pre-clinically, we see that we can actually kill target cells. It is a CD38- positive, but much lower levels of CD38 than we can do with daratumumab, and that includes tumors like diffuse large B-cell lymphoma, acute myeloid leukemia tumors, and also some other tumors which are not really sensitive to daratumumab. This molecule could, when safe, could actually broaden the market beyond the market for daratumumab, and that could even include solid tumors. One of the characteristics of this molecule is that it is much more effective in inhibiting the ecto-enzyme enzymatic activity of CD38, which is believed to be involved in the suppression of the immune system.
When you block that more effectively, this could be an excellent candidate also for bringing it back in solid cancers, but that's speculation right now. We first need to see that this molecule is actually safe in human patients. We cannot wait to see data from the clinic, and hopefully we'll get that in 2021. Having said that issue, I will give it over now to Kate to give us a bit more color on the importance of PD-L1 binding by PD-L1/ 4-1BB for the activity profile of that molecule. Kate?
Yeah, thanks for the question. We're definitely monitoring PD-L1 expression, as you saw in the data we presented here, and I'll point out a couple of things. One is that most of the patients who've had checkpoint inhibition, as you saw in the data, also have PD-L1 expression to levels at least greater than 1%. A couple of the patients that had good responses to our PD-L1/ 4-1BB did not have fresh biopsy samples. We're trying to further interrogate and get those samples from patients. What we do see; w e would expect that we need some level of PD-L1 to induce conditional activation. However, we also know from our own data and from looking at other data sets that are available, that there's some synergy and probably amplification between these two targets.
As you get PD-L1 binding and T- cell activation, you may get more 4-1BB. We're definitely monitoring this, and we'll be, of course, collecting a lot of additional data. It could be that there's other biomarkers. We expect other biomarkers beyond PD-L1 to be informative for us on which patients will respond best.
Thank you very much, Kate. Let's move to the next question. Maybe we have the typed one from Graig.
From Graig we have...
Or not.
...where do you see the epcoritamab position in the CLL space?
Okay, epcor position in the CLL space. I think we have already put one of the CLL trials on the ct.gov website. Tahi, can you give further color on the development of epcoritamab in chronic lymphocytic leukemia?
Sure. I always start that by saying that if you think back, the original New England Journal article on CAR-Ts was actually three CLL patients. I remind people of that because that is the one B-cell malignancies where CAR-T actually have not really shown any efficacy really in a meaningful, comprehensive manner. CLL, without a doubt, is in dialogue between the disease and the immune system. This has been published all the way back in the late 1990s by John Gribben and others. We are interrogating this right now in the relapsed/refractory space in post-BTK, because that's the easiest, most straightforward path to show and explore safety, and then hopefully also efficacy, in CLL patients.
Importantly, I think we are also going to show you some plans in the near future where we will try to interrogate the efficacy and safety of epcoritamab in situations where maybe the disease burden is a little bit less to increase the opportunities for a bispecific to show its efficacy. I think it ties back to a question that came earlier around the ability to combine with AbbVie's proprietary compounds. We will also in CLL explore combinations with ibrutinib, venetoclax, and maybe even other not publicly known assets.
Thank you very much, Tahi. That's very clear. Let's see whether there are any other questions left.
Graig is also asking, what are the BD priorities, tuck-in technologies versus tuck-in assets versus small co M&A?
Thank you very much, Graig, for that question on BD strategy and execution. I will hand that over to Anthony Mancini. Anthony, a bit of color on our BD strategy.
Yeah. Thanks, Jan, and thanks, Graig, for the question. I think we covered a little bit of this through the presentation from Anthony Pagano, Certainly our primary focus right now is on delivering against the 2025 vision to become an integrated biotech leader. Of course, in parallel, we are continuing to actively explore partnerships, products, and technologies in a disciplined and focused way as ways of either getting there faster or in a complementary way to our areas of focus. I think I touched a little bit on it in the Q3 call in a similar way. All I can say is that we're continuing to actively explore all three buckets.
Thank you very much, Anthony. We have now basically 20 partnerships, key partnerships, seven pharma partnerships, and then 13 biotech or tech partnerships. That number will definitely increase, Graig, in the coming years, because we believe that Genmab needs to be better and better connected with the outside world, not only with biotech and pharma and data sciences companies, but potentially also with other industries in the future like medical electronics industries, maybe some logistical industries in the context of our commercial phase. We definitely believe that to be networked and well connected in this world will optimally position the company for future success. We are very, very active in watching the landscape and working on that proactively, and more news to come in the future, so stay tuned. Maybe the next question.
Our last question will be from Kennen MacKay from RBC. Kennen, go ahead.
Hi, can you hear me okay?
Perfect, p erfect, Kennen. Thanks.
Great.
Thanks for joining.
Thanks for taking the question, Jan. For GEN1046, just wondering if you could talk a little bit about your confidence that the hepatotoxicity and LFT elevations that we're seeing aren't going to be sort of dose-limiting or negatively impact the efficacy profile. Also wondering if this is sort of a 4-1BB class effect, given we have seen it with some other 4-1BB targeting agents. Secondly, was just hoping you could comment a little bit on the anti-tumor activity in the dose expansion cohort in non-small cell lung cancer, and the discontinuation rates there, whether that's different than some of the other solid tumors for one reason or another. Thanks so much. I really enjoyed the day today.
Thanks, Kennen. Both of these questions I will hand over to Tahi. He is a busy guy today, so we should pay him well. Tahi, maybe you can address both of the questions from Kennen.
I'll try to address the question that I think I heard because it was not totally clear here.
Hepatic toxicity, is it a class [audio distortion].
First question was on hepatic toxicity, and I think we spoke about this very clearly, w e see transaminase elevations. It seems to be manageable with the institution of steroids very early. It seems to be that patients can be re-exposed to GEN1046, and it has not precluded us from picking the right dose or escalating doses, frankly. We have very few patients who discontinue due to AEs on this phase so far. A lot of the patients stay on this drug for quite some time. That was the first question.
Second question is on the expansion cohort, the lung cancer expansion cohort.
Cancer patients. If that was the question, I think I mentioned this before, the two non-small cell lung cancer patients, I hope that was the question. Both of them a PR, t hey both were refractory to prior checkpoints. Both of them have by now progressed, if that was the question. It's important, these were first human trial patients with their own limitations also in the protocol. I think that's the question I understood.
The question is basically, can you further elaborate on the discontinuation rate of these patients with lung cancer in the expansion cohort, Tahi? Anything more you can say?
In the expansion cohort, as much as I can say about what is presented. The 12 patients that we presented, six had a PD and discontinued because of progression of disease. Three patients had a stable disease. They are all on treatment and continuing. Three patients had a PR, t hey're all ongoing.
Thank you very much, Tahi. Since we have one minute, 30 seconds left, I think I'm going to close here. Thank you all for a very energizing and dynamic Q&A session. If you didn't have the time for your question or didn't get through in the right way, please reach out to Andrew Carlsen, who is also on the line here, and he will follow up. Thank you all for joining us today and for your support over the past years. This has been truly transformative for Genmab. Most thanks go actually to the exceptional speakers who have joined us today in Utrecht and in Princeton. We look forward to even more exciting events in the future. That concludes today's webcast. Have a nice weekend. What we always say at Genmab in this difficult era is keep optimistic and stay safe.