Good morning and good afternoon to everyone on the call. Thank you for joining us on the five-part series of interactive webcast events, which will highlight Sanofi's progress in R&D. The event today will focus on our oncology strategy and ASCO updates. As usual, you can find the slides for this call on the investors page of our website at sanofi.com. As part of the momentum building around our pipeline, following today, we will host our next R&D investor event on June 11th, focused on DUPIXENT. We are also excited to confirm that the inotuzumab phase II-B data has been submitted and accepted by a peer-review journal. inotuzumab investor event will be scheduled around the planned publication date.
Moving to slide two, I would like to remind you that information presented in this call contains forward-looking statements and involves known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC, our Document d'Enregistrement Universel for a description of these risk factors. With that, please advance to slide three, let me introduce our speakers today. With me on the call are Paul Hudson, our CEO. John Reed, Executive Vice President, Global Head of Research and Development. Dietmar Berger, Senior Vice President, Global Head of Development and Chief Medical Officer. Alexander Zehnder, Global Franchise Head, Oncology. Peter Adamson, Global Oncology Development Head. Paul will make some introductory remarks, after which John will outline our R&D strategy in oncology.
Dietmar, Alexander, Peter will then provide updates on selected assets, namely SARCLISA, LIBTAYO, NTC 005, and SERD. John will then wrap up with concluding comments. We will close with a Q&A session. Joining for Q&A will be Bill Sibold, Executive Vice President, Sanofi Genzyme. Dmitry Wiederschain, Head of Immuno-Oncology Research, Laurent Debuchy, Molecular Oncology Research Head. With that, I'd like to turn the call over to Paul. Thank you.
Well, thank you, Felix, good morning, good afternoon to everyone on the call. I'm really excited to introduce our ASCO Oncology event. Also to make sure that you get to fully appreciate our bench strength and the people you're going to meet today. I think while there are challenges digitally, I think there is a huge opportunity to be more inclusive and see just how strong our teams are, I look forward to that continuing. You know, in light of COVID-19 and lockdowns, we assessed our plan for the June 23rd R&D day. We didn't want to cancel it like some of our peers have done. We're fully aware of the limitations of virtual, like I mentioned. We set up a series of short ones. We did the BTKi.
I think we had some great feedback on that, and we focused on our in and around our key assets. It's a better format to allow you to get deeper into the pipeline, again, interact with some of our R&D leaders. We hope you enjoy it. We have great momentum in our oncology pipeline with a number of exciting data readouts from our four emerging oncology anchor assets. Today we're going to focus on our last stage oncology portfolio and in particular LIBTAYO, SARCLISA, CEACAM5, and of course our SAR439859, our priority assets in onco. We also have an exciting early-stage pipeline based on innovative molecules from cutting-edge platforms, and we'll talk to you about some of those on June the 23rd, including a deep dive on THOR-707, our first IL-2 from the Synthorx acquisition.
For Sanofi, oncology is a long-term commitment, and I'm confident we can deliver outstanding patient benefit and compete successfully in this space. I'll be honest, we're further along than I expected when I joined Sanofi last year. I think you know me well enough to appreciate that I like to compete, and I like to do it with the strongest possible hand, and I feel like that hand is getting stronger all the time. As the tagline states, we are just getting started. Let's go to slide five. Everything starts with our science, and that we intend to transform into commercial leadership. I think they go together. At Sanofi, we already have a wealth of scientific understanding and leading capabilities with truly cutting-edge platforms, including ADCs, multi-specifics, and Nanobodies.
We're going to focus on four key disease areas in onco, multiple myeloma, lung, skin, and breast cancer, and with the ambition to shape our four anchor assets into blockbuster medicines. To improve patient outcomes in our four key core disease areas, we're focusing on developing novel combos based on and around the four. I hope by the end of our presentation today, you'll agree that our four anchor assets are not only very attractive, but also from a standalone standpoint. I believe that shaping our assets in best-in-class backbones, our leading platforms will enable us to generate first-in-class medicines, position Sanofi as a partner of choice, especially in our focus areas. Slide six. Let me now introduce you to the four assets and our ambition, how we plan to shape those into blockbusters.
Starting with SARCLISA, Dietmar, our Head of Development, will take you through a scientific journey to showcase how we're building the evidence towards our emerging best-in-class profile in multiple myeloma. You've seen we've got news even as of today. We have had strong news flow for LIBTAYO in skin and in lung cancer. Whilst nobody has been able to match KEYTRUDA in first-line lung so far, I believe we now can, and that's an important step for us. Alexander, who heads our commercial oncology operations, will talk to you about how competing in skin cancer today and how we intend to expand into our new segments, capitalizing on what we think are very competitive clinical data sets.
Moving to CEACAM5, in the last months, I've learned a lot about antibody drug conjugates, and I'm getting increasingly excited about 701, our lead ADC, and also our ADC platform that we're building up in research. Peter, and welcome, Peter, our Head of Oncology Development, will educate you on our ambition for our first-in-class CEACAM5 targeting ADC for lung cancer and other solid tumors. 701 is for 25% of the non-squamous cell, non-small cell lung cancer patients with high expression of CEACAM5. And for reference, there are more patients with high expression of CEACAM5 than lung cancer patients with driving mutations such as EGFR and ALK mutation. Last but not least, Peter will also discuss our third data just presented at ASCO, which increases our confidence that we have a very differentiated molecule on our hands.
859 is perhaps the only SERD with an appropriate safety and tolerability profile that's so critical in HR-positive breast cancer, where women, of course, take their medicines over extended periods of time. We believe our profile allows us to move significantly ahead of the competition, and that could be years ahead of the competition and reach the market as early as 2022. We intend to shape our SERD-859 into the new standard of care endocrine backbone to improve patient outcomes and take a commanding market position in the segment. Each of these four assets individually have the potential to transform patient lives and to establish Sanofi amongst leaders in oncology. On slide seven, I spoke about the momentum in our onco pipeline. And to be honest, you can see it here, it's been an exciting few months for Sanofi Oncology.
With approvals for SARCLISA, our first internally developed oncology anchor asset in the U.S. and now in the EU with its first indication in relapsed and refractory third-line myeloma patients. Two of our pivotal studies were stopped early as interim due to overwhelming efficacy. LIBTAYO in first-line non-small cell lung cancer and SARCLISA in second-line multiple myeloma. We've been presenting our PoC data at ASCO for SERD, CEACAM5, and I'm especially proud that both molecules are entirely internally developed at Sanofi. And like SARCLISA, are wholly owned by Sanofi. And I think you understand the importance of that as we go on to deliver on our financial commitments as well as those for patients.
Not shown on this chart is the incredible progress we've made shaping the development programs to deliver critical and differentiated data sets for our anchor assets and our early-stage portfolio, which will be the source of hopefully a lot more excitement in the coming years and months. In short, we're delivering on our ambitions and translating our words into actions as we continue to build our oncology franchise. Having set the scene, it seems like an appropriate time for me to hand over to John to outline our strategy in more detail. And let me add that John himself has an impressive scientific experience in oncology.
He's what I would call an authority in this therapeutic field. His long list of oncology credentials include leading the P unit at Roche, bringing some of the pipeline through, co-founding a biopharma company that approved an onco medicine, and of course, former editor-in-chief of AACR. On top of all this, he's a very good guy. John, over to you.
Well, thank you, Paul, and welcome to everybody on the call. As Paul intimated, today's investor report is particularly personal for me because the topic is oncology. While as head of R&D at Sanofi, I love all our therapeutic areas equally, I would say oncology has a special place in my heart, stemming from the roughly 25 years of fundamental basic and translational research that I did in the area prior to joining pharma. As Paul referenced, my former laboratory actually published more than 900 papers on topics that address subjects such as oncogenic and growth factor receptor signal transduction, mechanisms of chemoresistance, barriers to apoptosis in cancer cells. Now with immuno-oncology in the limelight, it's probably relevant that my PhD was taken in immunology, and my doctoral dissertation was actually on interleukin-2. That was back when there were only three interleukins.
I'm a little embarrassed to say now there are about 40. When an academic, I also actively served on various committees, consortia, and collaborations with the National Cancer Institute, the AACR, the ACS, and was active in oncology cooperative groups, ECOG, CALGB, and DIG, and served on editorial boards of multiple medical journals, including editor-in-chief for one of the AACR's journals devoted to cancer experimental therapeutics. Where I'm going with all this is that when I agreed to join Sanofi two years ago, one of the clear mandates was to get Sanofi back into oncology in a meaningful way, and that's what we aim to do. We're on a journey, and as the title of our event stated, we're just getting started. Therefore, I would ask you to consider today's event a progress report for an R&D organization that's early on the road back to oncology.
We're making rapid progress on multiple fronts. Today, I'll highlight just two of those very briefly on the next slide nine. First, I want to introduce you to some of the growing talent base at Sanofi. Very important, clearly, is who is on the bus as you take this journey. So you'll get exposure, I think, for the first time to some of our talent in oncology. I would note that the first major hire I made at Sanofi was to bring on board my former colleague, Dietmar Berger, to head development. Dietmar has led teams that have put 14 new medicines on the market, 12 in oncology, two in hematology. In addition, we recently recruited Peter Adamson to head oncology development. Prior to joining our team, Peter managed a large budget as a head of an oncology cooperative group.
Peter is impressively a presidential appointee to the National Cancer Institute's National Cancer Advisory Board. You'll also hear today from Alexander Zehnder, who heads the oncology business franchise at Sanofi. Alexander is himself a physician who knows what it's like to take care of cancer patients. He led the Avastin franchise at Roche Genentech prior to joining us and has significant experience in building great brands in oncology. Next slide. Besides building the strength of the oncology talent at Sanofi, we're also making rapid progress in expanding our toolbox of therapeutic platforms for designing the next generation of cancer therapeutics. You'll see only a touch of this today because most of these molecules are still pre-clinical or in early clinical development.
The repertoire of molecules that we are now capable of building includes, of course, traditional small molecules and monoclonal antibodies, and you'll see examples of those today. In addition, we've established in-house platforms for bispecific and tri-specific antibodies. We've established in-house platforms for antibody drug conjugates. You'll hear about one of those today. We've secured, through acquisition of Ablynx, access to the world's most advanced platform for nanobody drugs, which has enormous potential for the next generation of multi-specific molecules. Through the acquisition of Synthorx, we've established access to a leading, if not the leading, synthetic biology platform for expanding the genetic code to make a new class of biologics, starting with engineered lymphokines for immuno-oncology. We also have collaborations for exploring mRNA therapeutics platform.
All these platforms are either in the clinic or approximately 12 to 18 months from the clinic, which is super exciting for an R&D guy like me to be at the forefront of innovation and design of new types of cancer medicines. With this talent and with these powerful tools to fuel our engine for discovery and development, I am confident that Sanofi will successfully make the journey to leadership in oncology as we address the unmet needs of patients who struggle with cancer. Let's move to slide 11 now. Slide 11 outlines our near-term oncology ambition. As step one, we seek to lay a foundation for Sanofi's return to oncology with four lead assets that address four oncology indications having significant unmet need and affecting large numbers of patients, namely myeloma, skin, lung, and breast cancers. In myeloma, this represents, as we know, still an incurable disease.
To be sure, substantial progress has been made in the past 20 years due to the introduction of modern therapies, with median survival increasing from about 30 months in around 2000 to about 70 months today in 2020, so over the last 20 years. However, still patients relapse, and achieving a response becomes harder after each relapse. With our wholly owned anti-CD38 antibody, SARCLISA, we're seeing very deep responses in the refractory setting in both the second-line and third-line settings. Now, for the first time at ASCO, we presented data from the first-line setting in newly diagnosed multiple myeloma showing minimal residual disease negativity exceeding 60%. These deep responses are critical to delaying progression to the next relapse for as long as possible. To achieve even deeper responses, we're exploring novel combinations, which will be described later by my colleague, Dietmar Berger.
Skin cancer is one of the most prevalent cancer types. Most of these neoplasms, fortunately, are diagnosed early and hence have good prognosis. When progressed to advanced stages, five-year survival rates remain poor. With LIBTAYO, our Regeneron-partnered anti-PD-1 antibody, we were the first checkpoint inhibitor to address the unmet need in metastatic and locally advanced cutaneous squamous cell carcinoma based on the high response rates and outstanding durability of responses that we've seen. We're building on this success in non-melanoma skin cancer with our recent data in basal cell carcinomas, which will provide a new treatment option for those patients, giving them access for the first time to an effective immunotherapy.
Finally, we're exploring novel immuno-oncology combinations both in melanoma and non-melanoma skin cancers with the ambition to define the new standard of care for these malignancies where the majority of patients do not currently benefit from the available immunotherapies, thus leaving much room for improvement. Besides myeloma and skin, lung cancer is an obvious place for Sanofi to play, given our historical presence in that indication with medicines like TAXOTERE. Progress has been astonishing in patients with driver mutations, where we're seeing now good long-term outcomes with around half of patients enjoying five-year overall survivals. For the majority of lung cancer patients who don't have driver mutations, long-term outcomes remain poor.
The five-year overall survival statistics are improving thanks to the introduction of checkpoint inhibitor therapy, probably approaching around 20% now. We clearly have much room for improvement when one considers that on average, only about a third of lung cancer patients respond to cancer immunotherapy. That very few of these patients achieve a complete remission. Clearly, lung cancer patients need better treatment options. Sanofi currently has two late-stage molecules in development for lung cancer. One of these molecules is again LIBTAYO, the PD-1 inhibitor. We recently reported strong results in front-line non-small cell lung cancer with high PD-L1. Today, we will provide more insights into the data, though a full disclosure of the results from the Phase III trial will not occur until the ESMO conference.
I won't spoil Alexander's presentation. I would note that so far, no checkpoint inhibitor has been able to match KEYTRUDA's efficacy in front-line lung cancer. Have a look at the new data and see for yourself what LIBTAYO is doing. The importance of LIBTAYO for Sanofi is that it lays a foundation in lung cancer for us to build upon with the next generation of immuno-oncology combinations. Our second molecule in lung cancer is an antibody-drug conjugate. The first of this modality for us at Sanofi. This first-in-class molecule, which was invented in our laboratories in the Paris area, is dubbed 701. It is a monoclonal antibody binding the oncofetal antigen CEACAM5, conjugated with a cytotoxic compound that attacks microtubules. As you know, anti-tubulin agents such as taxanes are very effective in lung cancer. The problem is that most patients are unable to tolerate them.
In clinical practice, very few patients are able to receive the recommended number of treatment cycles. Using the ADC concept to target the chemotherapy where it is needed while sparing normal tissues, we've been able to generate compelling POC data showing improved efficacy with less toxicity. Our ambition is to establish 701 as a new standard of care for CEACAM5-positive lung cancer patients in the second-line setting after failing front-line checkpoint inhibitor with or without chemotherapy. Building from there, we will explore this ADC in the front-line setting in combination with anti-PD-1, attempting to replace some of the standard untargeted toxic chemotherapy drugs with this targeted and more gentle option for those patients whose tumors express CEACAM5. Finally, moving to breast cancer.
Huge improvements have been achieved in the treatment of breast cancer in the last 40, 50 years, driven by increased awareness, early diagnosis, and of course, new therapeutics. Endocrine therapy for hormone receptor-positive breast cancer was pioneered in the '80s and in fact, was the first form of targeted therapy for all of oncology. As you know, endocrine therapy aims to shut down estrogen receptor signaling. Unfortunately, interfering with estrogen receptor signaling is incomplete with currently available therapeutics, setting the stage for the emergence of resistance, which happens all too frequently. In the metastatic setting, five-year survival rates remain low at 28%. Even for stage 2 and 3 patients with regional disease, in the absence of further progress, today, 14 out of every 100 women diagnosed with breast cancer this year will no longer be alive five years from now.
This is where our oral estrogen receptor degrader, dubbed 859, comes in. Our SERD has the potential to offer patients a better backbone endocrine therapy that is both more efficacious because it essentially completely degrades the estrogen receptor with a once-daily oral medicine, and that is also well-tolerated with an excellent safety profile that makes it easier for breast cancer patients to take when long courses of therapy are involved, particularly in the adjuvant setting. The recent updates from the ASCO conference illustrate poignantly the need and the opportunity for a next generation of adjuvant therapy for hormone receptor-positive breast cancers. If we succeed in our aspirations with these four anchor indications, Sanofi can transform the lives of millions of patients around the world. Let's move to slide 12. This slide shows how the young but growing oncology portfolio at Sanofi maps against our four core disease areas.
As step 2 in our return to oncology, we will strive to build upon the late-stage foundational assets and the additional mechanisms from the early portfolio that can be combined to arrive at best-in-disease combination therapies. In hematological malignancies, our anchor asset is SARCLISA, a conventional monoclonal antibody. Conventional format, but unconventional in binding a unique epitope on CD38 that sets SARCLISA apart. Behind SARCLISA, we have next-generation anti-CD38 molecules with either FC engineering of the antibody to improve efficacy through engaging immune cells in what's called ADCC, as well as an innovative tri-specific antibody designed to summon tumor-killing T cells into the attack on myeloma cells. These will be positioned particularly for patients who have failed conventional anti-CD38 antibodies.
We won't have time today to go into the details, molecular analysis of tumors and preclinical data provide compelling rationale for combining other molecules in our early development portfolio with these CD38-targeting molecules. In skin cancer, looking beyond cutaneous squamous cell carcinoma and basal cell, we have a number of molecules that we will combine with our anchor asset, LIBTAYO. For example, our internally invented anti-TGF antibody for inhibiting production of immunosuppressive regulatory T cells and for improving trafficking of T cells into solid tumors. THOR-707, the non-alpha IL-2 from Synthorx acquisition that stimulates selectively proliferation of tumor-fighting CD8-positive cytolytic T cells and natural killer cells. mRNAs encoding very immunostimulatory proteins from the BioNTech collaboration that we introduced by injection directly into solid tumors in attempt to reawaken T-cell immunity, converting non-inflamed cold tumors into inflamed hot tumors.
In lung cancer, we're also exploring anti-PD-1 combinations with our internally derived TGF-beta antibody and THOR-707, as well as with small molecule SHP2 inhibitor that is partnered with Revolution Medicines. In fact, the SHP2 target is exploited in two ways. First, as a potentiator of checkpoint inhibitors through the role of SHP2 as an intracellular mediator of the immunosuppression by PD-1. Second, because of SHP2's well-established role in oncogenic growth factor receptor signal transduction pathways, such as in EGFR mutant lung cancers, where we're testing SHP2 in combination with next-generation EGFR inhibitor, osimertinib. In breast cancer, we look forward to sharing new data presented at ASCO on our anchor asset, SERD, later in this presentation.
Most, if not all of the seven early-stage compounds listed here will reach the stage of proof of principle or even proof of concept in the next 18-24 months. Importantly, as I intimated when I spoke about the expanding repertoire of Sanofi's platforms for inventing cancer-fighting medicines, we have multiple preclinical oncology drug discovery projects underway that we expect to yield 3-4 development candidates annually. You'll hear more about those molecules in the coming months and years. Moving to slide 13, we have listed for you several of the ongoing studies of our oncology portfolio. The list is not meant to be comprehensive, but provides some insights into the evolving and emerging Sanofi oncology pipeline. We'll look forward to sharing future data as these molecules reach milestones in their development journeys.
If we can move to slide 14, I'll now hand things over to my friend and colleague, Dietmar Berger, our Global Head of Development and Chief Medical Officer, who will update you on our anti-CD38 antibody, SARCLISA. Dietmar?
Thank you, John. Moving to slide 15. It's my pleasure to take you through the exciting story of SARCLISA, especially on a day where we have received the approval for Europe, and we will for the first time presenting our data on our second-line study, IKEMA. I want to start by tackling a central question up front. We do understand that many of you consider SARCLISA a me-too compound. To state it very clearly, we disagree. Eventually, it's all about the data, and I believe the data generated so far, including the mechanism of action, preclinical results, as well as clinical readouts in the third, second, and first-line myeloma setting, highlight SARCLISA as a differentiated and potentially best-in-class molecule. It starts with the fact that SARCLISA is an anti-CD38 monoclonal antibody with a differentiated mechanism of action.
It binds to a different epitope than other CD38 antibodies, preclinical evidence supports different levels of immunologic activity, apoptosis induction, and cytotoxicity. Clearly, we need to prove the relevance of those mechanistic differences in the clinic. The first building block in this regard was the ICARIA study in the late-line myeloma setting. ICARIA in third line and later therapy was our first pivotal study, and it demonstrated the longest progression-free survival ever observed in a triplet with pomalidomide and dexamethasone. This is exciting data and our first piece of evidence in support of our differentiated profile. ICARIA has also been the first randomized pivotal study in third-line plus myeloma, so there's really no good evidence with which to compare it. We need to look at the second study here. IKEMA is our second pivotal study, this time in the second-line refractory setting.
As we announced a few weeks ago, IKEMA has hit the primary PFS endpoint early. The full IKEMA data will be presented at next week's conference of the European Hematology Association. The embargo on the data in the late-breaking abstract has come up barely an hour ago, so we're very excited to report now a 47% risk reduction of progression or death for SARCLISA in a triplet with carfilzomib and dexamethasone. Cross-trial comparisons are always challenging, but in contrast to ICARIA, where we really didn't have a lot to compare with, it's a bit more straightforward to put the IKEMA data into context. In this setting, we have the CANDOR study, a phase III trial that's largely similar to IKEMA with a fairly comparable patient population, and it evaluates daratumumab on the exact same KD backbone. You will see that IKEMA compares favorably to PANDORA.
The IKEMA data is our second piece of evidence supporting a differentiated clinical profile, and our confidence is building in SARCLISA's emerging best-in-class profile, especially looking at the hazard ratio, depth of response, MRD negativity, and safety profile in IKEMA. In addition, at this ASCO, we're presenting early data from two studies in the first-line myeloma setting. Again, the data are highly encouraging. We are looking forward to the readouts of our phase III studies in newly diagnosed myeloma patients starting next year. While we were several years behind in terms of data generation in the refractory setting, our timelines in first line are competitive, as we're generating data from modern quadruplets of anti-CD38 plus VRd or KRd. Let's take this step by step. Let me take you through our journey so far and our exciting new data.
Moving on to slide 16, I have already mentioned SARCLISA's differentiated mechanism of action. SARCLISA targets a different epitope than other CD38 antibodies and has demonstrated multiple effects involving natural killer cells, monocytes and macrophages, as well as T cells. Among the more important aspects are the inhibition of CD38 ectoenzyme activity, induction of apoptosis, immunomodulation, and antibody and complement-dependent cytotoxicity. On slide 17, let's look at some of those mechanisms and the differences versus other CD38 antibodies. First, on the left, SARCLISA is a more potent inhibitor of CD38 ectoenzymatic activity, as can be seen in this first panel. CD38 is thought to be the dominant enzyme for the generation of adenosine, which is thought to be immunosuppressive in the bone marrow of myeloma patients.
Inhibition of CD38 enzymatic activity and reduction of adenosine levels may result in a less immunosuppressive bone marrow microenvironment, leading to increased immunologic activity against myeloma cells. As shown in the middle panel, SARCLISA directly induces apoptosis of myeloma cells without requiring FC cross-linking. This is important because it's in contrast to other CD38 antibodies that seem to require FC gamma receptor-mediated cross-linking for activity. The third panel on the right describes cytotoxicity in the absence of effector cells. SARCLISA induced significant cytotoxicity against CD38 positive myeloma cell lines in the absence of effector cells, an effect that we don't see with the daratumumab surrogate in the same experiment. In our view, these and other preclinical data are clear evidence that SARCLISA is not purely a me-too, but a differentiated antibody with intriguing mechanistic characteristics that may lead to a transformative profile in the clinic.
Let's now take a look at the clinical data for SARCLISA so far. Beginning on slide 18 with a previously reported ICARIA study in the relapsed refractory third-line class myeloma setting. The addition of SARCLISA to a pomalidomide dexamethasone backbone increased progression-free survival by five months. This is a heavily pretreated myeloma patient population, and we saw the effects across all subgroups, taking median progression-free survival to an unprecedented 11.5 months. These data supported SARCLISA's U.S., and now European approval, in relapsed and refractory myeloma patients who have received at least two prior therapies. ICARIA is the only randomized pivotal trial in this setting so far. Just to provide some background of the landscape of other trials in this setting, here you can see that published studies of two other biologics added to the same pom dex backbone did not match SARCLISA's absolute PFS benefit.
In addition to the efficacy benefit, there was also a low level of treatment discontinuation due to adverse events with SARCLISA. Today, we're tremendously excited to add the IKEMA clinical data in the second-line setting to this picture, which will be covered in depth next week at EHA. On slide 19, the IKEMA trial results will be described in full as an oral late breaker presentation at the European Hematology Association meeting on June 14 by Professor Philippe Moreau from Nantes in France. With the embargo now lifted on the abstract, I can share some of the details with you today. As announced, this trial was stopped early as an interim analysis based on SARCLISA's significant reduction in the risk of disease progression or death compared to the control arm.
Sarclisa, in combination with carfilzomib and dexamethasone, or KD for short, reduced the risk of disease progression or death by 47% compared to KD alone, for a hazard ratio of 0.53. Secondary efficacy endpoint also dramatically favored the Sarclisa cohort, including the complete response rate of 40% versus 28%, and the portion of MRD negative or minimal residual disease negative patients at 30% versus 13%. We believe these findings will be relevant for patients and for the oncology community. Complete responses and MRD negativity describe what we call the depth of response. Deeper responses generally mean better myeloma control and potentially longer treatment-free intervals for patients. In addition, we observed an encouraging safety profile consistent with prior findings for Sarclisa, with a lower number of treatment discontinuations for adverse events in the Sarclisa cohort at 9% versus 14%.
With the primary PFS endpoint of the IKEMA study hit early, we are in a position to prepare for rapid discussions and a submission with regulatory authorities. On slide 20, we want to put the IKEMA data into context and briefly remind you of the key features of the CANDOR study that evaluated daratumumab on the same KD backbone. With all the caveats of cross-trial comparison, patient characteristics of both studies seem quite similar, for example, in terms of median age and number of prior treatment lines. As you can see, the results of our IKEMA study compare favorably to the results of CANDOR, both in terms of efficacy looking at the PFS hazard ratio, complete responses, and MRD negativity, but also safety, including the rate of treatment discontinuation. Slide 21. Let's now look at the potential use of Sarclisa in first-line therapy.
This slide highlights two encouraging early data sets for Sarclisa in newly diagnosed patients presented at this ASCO. Starting with a GMMG, German Myeloma Group concept trial on the left. This is an investigator-sponsored study investigating the MRD negativity rate in high-risk, newly diagnosed multiple myeloma patients treated with Sarclisa, carfilzomib, lenalidomide, and dexamethasone, or Isa-KRd, with or without subsequent autologous stem cell transplantation. This data has actually been selected by ASCO as one of the highlights of the day at this year's conference. An interim analysis was conducted for the first 50 patients who were mostly transplant eligible. Results showed a highly impressive 100% overall response rate with an equally promising 61% of patients negative for minimal residual disease.
The GMMG concept trial uses the quadruplet regimen of Sarclisa plus KRd, which will also be the backbone of Sarclisa's first-line transplant-eligible phase III study to be conducted with the European Myeloma Network. The chart on the right-hand side summarizes data from Sarclisa's phase I-B study in newly diagnosed transplant-ineligible patients, also shown at this conference. This 44-patient study used the standard of care backbone VRd, and another less commonly used regimen called Vcd. Results showed an overall response rate of 93% with Vcd and 100% with VRd, with a proportion of patients without minimal residual disease at 53% and 38% respectively. As a reminder, two of Sarclisa's ongoing first-line phase III studies, IMROZ and GMMG, used the same VRd backbone.
On slide 22, with the promising results for Sarclisa at hand, we are looking forward to the readout of our studies in newly diagnosed myeloma patients, starting with IMROZ in the transplant-ineligible setting next year. At present, there are no CD38 VRd or KRd-based quadruplets approved for newly diagnosed myeloma patients. Specifically looking at VRd backbone, we believe we are running neck to neck with other biologics in terms of generating first-line data with those modern quadruplets. We are excited about our soon-to-be-initiated third pivotal study in newly diagnosed transplant-eligible myeloma patients. This is the first pivotal study that will evaluate a CD38 KRd quadruplet. We will conduct this study with the European Myeloma Network. This will be our second pivotal study conducted with the Myeloma Cooperative Group.
Finally, we are planning the Ithaca study, which will evaluate Sarclisa with lenalidomide and dexamethasone in the high-risk smoldering myeloma setting. Moving earlier in the treatment paradigm may push the boundaries of myeloma therapy and offer the potential to achieve long-term PD3 outcomes for patients. On slide 23 now, let me briefly lead you through the addressable patient numbers, average months of therapy, and estimated timeline for our Sarclisa program. Move to the next slide, please. Overall, I want to highlight that we are studying Sarclisa in a broad patient program across all relevant stages of myeloma therapy, with a potential for patient benefit along the entire patient journey. Can we move one back, please? Perfect. In Sarclisa's currently approved relapsed/refractory third-line plus setting, on the left here, the average treatment time runs from seven to 10 months, with more than 30,000 addressable patients in the U.S. and EU5.
Adding an approval in second-line would roughly double the eligible patient number and significantly extend the average treatment time, this time to 16 months. Today, the second, third, and fourth-line settings combined are roughly a $10 billion market. By the time we consider first-line patients, the number of those eligible for treatment with Sarclisa potentially would rise to over 110,000 patients. In short, as we roll out the indications to address increasingly earlier lines of treatment, we see the potential for Sarclisa to become a blockbuster drug, especially if our thesis proves correct that we have in our hand a best-in-class anti-CD38 antibody. If you have any questions about the commercial components of this analysis, please do me a favor and direct them to Alexander rather than to me.
On slide 24, I want to highlight our commitment to multiple myeloma and our aspiration to build a leadership position in this setting based on our emerging best-in-class profile for Sarclisa, as well as the opportunities afforded by our exciting early-stage portfolio that John spoke about in hematology and oncology. We plan to augment the activity of Sarclisa through a series of novel combinations, including T-cell bispecifics, a TGF-beta inhibitor, and THOR-707, our exciting non-alpha IL-2. We also intend to deliver improved next-generation molecules, including an FC-engineered anti-CD38 with enhanced antibody-dependent cellular cytotoxicity, and a first-in-class bispecific that combines binding to CD38 with T-cell stimulation through CD28 and CD3. These may be particularly useful after patients have failed the first-generation conventional anti-CD38 molecule. Lastly, for Sarclisa itself, we plan to offer additional routes of administration so that dosing can be tailored to patient needs and preferences.
To this end, we have started early studies evaluating a patient-centric subcutaneous delivery system. Moving on to slide 25 and summarizing our ambition for SARCLISA, I want to leave you with a few key messages. First, anti-CD38 are not the same, and we believe that SARCLISA has a genuinely differentiated clinical profile that is based fundamentally on its unique mechanism of action. Second, the evidence is mounting that SARCLISA is the best-in-class molecule. This started with a demonstration of the longest PFS observed in the relapsed/refractory third line plus myeloma setting, the ICARIA study, and is supported by exciting new data, the IKEMA study, which shows the greatest reported risk reduction of progression or death in the second line setting when added to a KD standard of care backbone. Third, we strive to replicate best-in-class data in our pivotal first-line trials, and some of them are ongoing already.
Early data from signal-generating studies presented at this ASCO are highly encouraging. In conclusion, with SARCLISA as our anchor asset in myeloma, we aspire to significantly elevate the standard of care for patients that were suffering from this disease. I would like to thank you for your attention, and I'll hand over to Alexander Zehnder, our global oncology franchise head, to provide an update on LIBTAYO.
Thank you very much, Dietmar, and welcome to everybody. Slide 27 sets out our ambition for LIBTAYO, which is based on three pillars. First, we have already established leadership in non-melanoma skin cancer based on very impressive data in locally advanced or metastatic cutaneous squamous cell carcinoma. On May 5th, we have reported an equally impressive data set in second-line basal cell carcinoma, and this is the first checkpoint inhibitor data set in BCC. Second, LIBTAYO's new compelling first-line monotherapy data in non-squamous lung cancer should enable us to gain share in this highly competitive but also highly attractive market space. In addition, we are awaiting the readout of our second pivotal trial in lung cancer in 2021. That should allow us to secure a broad first-line label across all segments.
Third, we will strive to establish LIBTAYO as a backbone for first-in-class combination with internally developed and partner molecules in selected oncology indications to further improve patient outcomes. On slide 28, let me dive a bit deeper into our strategy in non-melanoma skin cancer. We are the first to deliver patient benefit with a checkpoint inhibitor in three important patient segments. The prevalence of non-melanoma skin cancer may be underappreciated, but it's not insignificant, and the unmet need in this patient has not been addressed by other checkpoint inhibitors before we did. Starting on the left with CSCC, or cutaneous squamous cell carcinoma, LIBTAYO has demonstrated unprecedented objective response rates and deep, durable efficacy. At this congress, we have presented data showing that neither the median overall survival nor the median duration of response was reached with a median follow-up of at least 60 months across different patient groups.
Across all groups, and this is really interesting, we have seen the complete response rates increasing over time of up to 20% in the group with the longest follow-up. Moving to the second piece in the middle, to BCC, we recently announced positive data from our cohort of patients with locally advanced or metastatic disease. Of the almost 30% of patients with locally advanced disease who had a response, 85% of those maintained the response at one year, which is much longer than currently approved therapies with a duration of response of less than seven months. On the right, the phase III in adjuvant CSCC, which is a much larger opportunity, is ongoing.
Based on the very compelling data for a pilot in neoadjuvant , we are hopeful on behalf of our patients that we will be able to deliver substantial benefit also in earlier stages of the disease. The data shown in the third panel on the right here was presented at last year's ESMO Conference, where we showed an impressive 55% pathologic complete response and a total of 70% of total pathologic response. Looking at the commercial opportunity of non-melanoma skin cancer on slide 21, it shows that in only two years post-launch, LIBTAYO is the number one prescribed checkpoint inhibitor in CSCC, reflected by steadily growing global sales. Currently, in the U.S., four out of five patients who get treated with an anti-PD-1 get LIBTAYO, we managed to build a $300 million indication from scratch in less than two years, we are only getting started.
With our ambitions to further expand, especially to the earlier lines of therapy, we see significant growth potential. On slide 30, turning to an even larger commercial opportunity in non-small cell lung cancer. Non-small cell lung cancer is by far the largest commercial opportunity for checkpoint inhibitors. In 2019, PD-L1 sales for metastatic non-small cell lung cancer were almost $10 billion, with a large majority of sales generated in first-line. As you know, there's only one PD-1 antibody which has been commercialized as monotherapy in first-line non-small cell lung cancer and high expression. We aim to capture a portion of this large market, starting with our expected initial non-small cell lung cancer indication in the PD-L1 high expressers, then moving to patients independent of PD-L1 status. On slide 31, let me focus on the strong monotherapy 1624 clinical data set.
On April 27th, we released the headline results from our first pivotal trial study for LIBTAYO in non-small cell lung cancer, which evaluated a single agent LIBTAYO versus traditional chemotherapy in patients with high expression of PD-L1. We reported a 32% risk reduction for progression and death, or a hazard ratio of 0.676. That was the overall ITT analysis of the data, which included all patients recruited into this study. Today, we present our modified intent to treat analysis. The modified intent to treat analysis only includes patients with an accurate assessment of PD-L1 expression in their tumors, removing patients who did not qualify as patients with a more than 50% PD-L1 expression. Basically, these are only patients that are really true expressers, those are comparable to the patient population that was included in both KEYNOTE-024 and KEYNOTE-042.
This modified intention-to-treat analysis shows a higher risk of reduction of 43% compared to the previous analysis, or a hazard ratio of 0.566. Perhaps this should be not surprising, as we know that patients with lower expression of PD-L1 will spend less well to anti-PD-1 single agent therapy. Looking at this data, I hope you agree that this is compelling. Far, none of the other checkpoint inhibitors has been able to match KEYTRUDA's efficacy in first-line non-small cell lung cancer. We have just showed that we can match KEYTRUDA, or perhaps even do a bit more than that. We are hopeful that we are able to replicate this data in our chemo combination first-line study 16-113, which includes patients irrespective of PD-L1 status and which is depicted on the chart on the right side.
We expect to have data from this trial as early as next year. With these two studies combined, this should put us in a strong position to get a broad label for LIBTAYO in first-line non-small cell lung cancer across all segments regarding the PD-L1 expression. This should allow us to compete in the first-line setting, offering patients the best possible treatment for their disease. Even though, through the introduction of PD-L1s and PD-1s as monotherapy and combination with chemotherapy, the treatment of cancer for many types of cancer has been transformed. Nevertheless, still many patients are not able to benefit, and more different approaches are needed. Therefore, we are exploring LIBTAYO with a range of modalities in combination with internal and external backbones to really find new approaches and help even more patients.
On slide 33, I'm aware that some of you have questions around our ambitions for LIBTAYO. I hope that based on the data we've seen, and we were able to share with you today, our ambitions have become clearer. To summarize, LIBTAYO is already the standard of care in advanced CSCC, which had no previously approved therapies. LIBTAYO is making a dramatic difference for these patients. Building on this, we are convinced that we can execute on our broad first-to-market strategy across non-melanoma skin cancers, including advanced CSCC, adjuvant CSCC, and advanced basal cell carcinoma. Our recent impressive data set in non-small cell lung cancer patients is another proof of point for the highly competitive profile of LIBTAYO in this largest indication for checkpoint inhibitors. We are looking forward to sharing with you the full data set at an upcoming medical conference.
We are looking forward to compete in this setting after approval, hopefully in 2021. We won't stop here. We are committed to improve outcomes for patients. We intend to leverage LIBTAYO through novel proprietary combinations from our platforms and with external partners in lung cancers as well as other tumors. Now, I would like to hand over to Peter Adamson, our Oncology Development Head.
Well, thanks very much, Alex. Welcome everyone, and thank you for joining us on today's call. I joined Sanofi just about two months ago. I'm excited to be part of a company that's committed to becoming the leader in cancer development. Let me jump in and talk to you first about our anti-CEACAM5-701, a first-in-class CEACAM-targeted ADC. I'm soon going to show the data that highlights how 701, we believe, are going to join the increasing number of successful ADC approaches to the treatment of patients with cancer. These are the building blocks. Building block 1. We want to become the standard of care for patients with non-small cell lung cancer who have tumors that have high expression of CEACAM5 and progress on initial therapy.
We've already shown our proof of concept, where we had an objective response rate of 20%, and we quickly have pivoted to our now pivotal monotherapy study. We're also pursuing combination studies with VEGFR-2 inhibitors in second-line. Where we obviously want to go next is shown in block 2. Once we have fast and broad adoption in second-line, we want to move to first-line, and our aim is to become a cornerstone therapy in combination with PD-1. We will soon initiate a proof of concept in first-line in combination with a PD-1 inhibitor, and then we will pivot to a study that shows its superiority. Lastly, in block 3, we're going to be exploring how anti-CEACAM5-701 may have efficacy in a range of tumors known to express CEACAM5.
I will share a strategy of how we're using this platform to deliver complementary payloads for tumors that are not known to be sensitive to anti-tubulin agents. Let's move to slide 36. Anti-CEACAM5-701 is a highly specific antibody designed to deliver payload specifically to the tumor cell. It has all the properties one wants to see in an ADC. It begins and its foundation rests on target selection. CEACAM5. CEACAM5 is a member of the carcinoembryonic antigen, or CEA gene family. CEACAM specifies cell adhesion molecule 5. What's important is that this cell surface glycoprotein is highly expressed on tumor cells but has very limited expression on normal cells. Payload selection. Well, we've chosen to use DM4, a maytansinoid, a highly potent anti-tubulin toxin. On a molar base, it's 100 times more potent than the taxanes. Importantly, the linker is stable in plasma.
Once the antibody engages the target, delivers its payload, the linker is cleaved, and importantly, one can get a favorable bystander effect. Again, all the qualities we want to see. Let's move to slide 37. We're currently developing 701 for anti-tubulin-sensitive tumors with high CEACAM5 expression. Shown on the right are the brown stains from a range of tumors, and on the left shows the relative prevalence and outlines our strategy. Now, I'm going to return to colon cancer, which we know has high CEACAM5 expression. That's where the CEA story began. However, colon cancer is generally not a tumor that's sensitive to microtubular toxins, and I'll show you how we're going to use the platform to attack those tumors. Let's look at some of the data, and let's jump to slide 38.
Shown here is the outline of our first-in-human study, phase I, phase II study. We quickly determined the maximum tolerated dose for this drug delivered on a Q2-week schedule, then interrogated tumors that had both high expression and moderate expression, as well as other cancers. We look at slide 39, you'll begin to understand why our enthusiasm for this drug is increasing. Our study was in a population of patients that were heavily pretreated. If you look at the bottom of your slide, you can see these patients had advanced disease, had received a median of three prior regimens, up to 10 prior regimens, and importantly, majority had been exposed to anti-tubulin agents as well as anti-PD-1 or PD-L1 agents. Very heavily pretreated. That's why we were encouraged when we saw the results being shown now on slide 40.
Let's begin on the right side of slide 40, which shows the waterfall plot. It's really a waterfall plot that you want to see in a heavily pretreated population with refractory disease. We had a disease control rate of 64% and a significant number of objective responses. The outcome and duration are shown on the swimmer's lane plot on the left. Again here, a median duration of response of 5.6 months, and a number of patients had remarkably durable response to the disease. This has increased our enthusiasm for this ADC being able to deliver for patients with high CEACAM expression in non-small cell lung cancer. Let's drill down a little bit more on its efficacy by looking at slide 41. Here I want to return to the importance of not only having the right antibody, but delivering the right payload.
When we look at our patients who had an objective response, and overall in high expressers, this represented 20% of patients, we explored, what did it matter as far as what they received before? I would say it should not come as a surprise that patients who had received and progressed on a prior taxane had a lower response rate, 15%. The point here is that the payload matters. You have to match the payload to the disease one is treating, as well as to the population of patients one is treating. The other point of this slide is it probably gives a better directional arrow as far as what we can expect of this agent when we move it forward. Patients who had not previously been exposed to a prior tubulin agent had a 28% overall response rate.
Again, the arrows are all pointing in the right direction. Our strategy of matching payload to tumor, I think, is supported by the data here. Let's move to slide 42. The other important part of an ADC is its safety profile, and 701 certainly has a favorable safety profile, as shown here. I'm going to highlight some of the adverse events that we've seen. Let me begin by the keratopathy or the ocular event. That was the most frequent clinical adverse event. This is an adverse event that we've seen with other ADCs conjugated to maytansinoids. It may be, generally speaking, a class effect of these, but most importantly, this has been very readily managed with either a dose delay or dose reduction.
When it does occur, and in this case, it occurred in about 10% of the population, it was well managed and only a small percentage of patients actually required a dose reduction. Overall, dyspnea was the most frequent serious adverse event, reported in about 5% of patients. In all cases, it was believed to be a symptom of progressive disease by clinicians taking care of these patients. Here's where the advantage of an ADC over a taxane becomes evident. There is a much improved hematologic and GI toxicity profile. We had a very clean profile in this regard, and it shows the potential of how we can use a targeted agent, deliver the right payload, and have a much better profile for patients. Let's move to slide 43.
Here, we show our strategy that we want to move 701 across all lines of treatment for patients with non-squamous, non-small cell lung cancer. In second line, we have CARMEN-LC03, our pivotal monotherapy randomized trial that will move this agent forward in second and later lines. We're exploring combinations with ramucirumab. We then, as I said, want to move this into first line, and we believe it has great potential in first line. Our CARMEN-LC05 study will be exploring this in combination with a PD-1 inhibitor, setting the stage for a pivotal first-line study. We think 701 is going to address an important need for a significant subpopulation of patients with non-small cell lung cancers. Let's move to slide 44. Shown here gives you some perspective of the size of this subpopulation.
On the left panel, we look at eligible patients in second or later lines. We know the size of the population for patients whose tumors have mutations in EGFR who have mutated ALK. The population of patients with CEACAM5 expression is larger than those populations, and we think will meet a significant unmet need. That population is simply going to increase when we move it into first line, as shown on the right side of this slide. Moving to slide 45. Here is a high-level overview of the strategy. We have a novel CEACAM5 ADC. We already know how we can deliver a very potent payload for tumors that generally are believed to be sensitive to anti-tubulin toxins. We're exploring lung, but we will move into gastric, breast, and pancreatic cancer.
We know that the payload is important, so we have a plan to use this platform to introduce novel complementary cytotoxic agents for tumors such as colorectal cancer that are not responsive to tubulin toxin. As importantly, this platform will allow us to deliver immunostimulants that we can target the immunostimulant directly to the cancer. The selection of a rational payload is important and central to expanding our strategy. In summary, on slide 46, we are confident and have a clear ambition to become a first in class CEACAM5 targeting ADC. We have efficacy and its favorable safety profile demonstrated in patients with high CEACAM5 expression in second and later lines.
We believe this is going to offer a new and important treatment options for these patients and will become a standard-of-care in second-line for patients who have progressed on other IO treatments, and we aim to become the cornerstone of first-line therapy. Lastly, we do plan to take this platform into areas beyond lung cancer. With that, we're going to continue and I'm going to shift gears and you get to look at a picture of me once again. Let's move to slide 48 and let me talk about our SERD-859. We believe 859 has the potential to be a best-in-class endocrine backbone therapy for patients with hormone receptor-positive breast cancer. These are the pillars of our strategy. It begins with our faster market, single agent in second-line for patients with metastatic breast cancer.
Importantly, we have a clear recruiting advantage here because the safety profile of 859 does not require us to utilize cardiac monitoring. A very clean profile, and we believe that's going to offer a real competitive advantage as we move our program forward. We're also looking at combinations with PI3K inhibitors. Moving to building block two, combination strategies with CDK4/6 inhibitors. Here I need to digress for a moment because we all saw the information that came from the PALLAS study, where in an adjuvant setting, the addition of palbociclib, a study was stopped for futility. Clearly for the community, this was disappointing news. There is such a need to improve upon adjuvant therapy for early breast cancer. The entire community was disappointed by these results. I want to state, though, that as disappointing as the results were, it doesn't change our current strategy.
Our pillar two strategy, which I'll discuss in a moment, is unchanged because a CDK4/6 inhibitor is well-established in this population of patients with metastatic breast cancer, and we will build upon those combinations. I do think the failure in the adjuvant setting raises a profile of establishing a SERD as an important addition, adjuvant therapy, which we aspire to, and I'll return to that. Coming back to where we are in the second pillar, we are confident because of the safety profile of our agent to be able to combine this. We do not see bone marrow suppression with this agent, therefore, we think it will combine well with a CDK4/6 inhibitor, and we will have a proof of concept later this year before initiating our phase III pivotal trial. Our third pillar is to expand to patients with early breast cancer.
I'm going to share some exciting news about a collaboration with I-SPY. Let's move to slide 49. 859 profile provides the potential for this drug to become the new standard endocrine backbone for patients with hormone receptor-positive breast cancer. It has all the elements that you want to see in a future oral SERD. Efficacy, potent, broad estrogen receptor degrader. Safety, we have not seen cardiotoxicity, hepatotoxicity signals to date. Tolerability, no grade 3 events. Combinability, a clean hematologic profile. Treatment, it will be oral. Why do we think this is so important? It's shown on the right side of the slide. We know endocrine therapy is the backbone of treatment across all stages of breast cancer, whether it's a SERM, whether it's an aromatase inhibitor, whether it's the only currently available SERD, fulvestrant.
It is a critical component that forms a foundation for either an early breast cancer, some patients receiving cytotoxic chemotherapy in first-line metastatic, a CDK4/6 inhibitor, and so forth. Our goal is to have 859 become the endocrine backbone across all lines, all the way into early breast cancer. Let's move to slide 50. This is a design of our AMEERA-1 trial, where we explored single monotherapy dose escalation and arrived at a recommended dose. We're currently completing our expansion phase in combination with palbociclib. Here, again, a very heavily pretreated population of patients with almost half having more than 3 lines of prior therapy. Data from this was presented at ASCO this past weekend, let's take a look at it in a little bit of detail now. Move to slide 51.
For SERD or any endocrine therapy, we and others believe that clinical benefit rate is perhaps the most relevant metric when one is interrogating an anti-estrogen therapy. Overall, we saw a 36% clinical benefit rate. Importantly, we saw efficacy in both wild type as well as mutant receptor. We again see directional signs of what we can expect as we move this agent forward. As I'm going to show you in a moment on the right here, prior treatment matters in trying to interpret clinical benefit rate. When we look at a subpopulation who had not received a prior SERD or a CDK4/6 inhibitor, we had in this exploratory analysis, a 64% clinical benefit rate. Let's look at that in a little more detail on slide 52.
What you see at the bottom of slide 52 are results from arms of studies that have previously been performed for different targeted agents, but all in comparison to a fulvestrant control arm. The clinical benefit rate for all those studies of fulvestrant was in the 30%-35% range. What's important to state here is the patient populations have evolved. Those patient populations hadn't previously been exposed to a CDK4/6 inhibitor, to an mTOR inhibitor, or to fulvestrant. In contrast, our study, AMEERA-1, a high fraction of patients were exposed to one or more of those prior therapies. When we select out a subpopulation, and again, I'm always cautious for a post-hoc analysis or for exploratory analysis with small numbers, I would take with a grain of salt the magnitude of the effect.
It is the directional arrow, again, that when we look at patients who haven't received prior exposures, the clinical benefit rate is quite favorable. Let's move to slide 53. Here is, I think, an essential part of any SERD that is going to become standard, a clean safety profile. One needs a clean safety profile if one is going to become a backbone across lines of treatment. In the left upper panel, you see that we experienced relatively low frequencies of treatment-related adverse events of Grade 1 or 2, and no treatment-related adverse event greater or equal than Grade 3. A remarkably clean safety profile. There are other oral SERDs in development. Those oral SERDs, Grade 3 events are emerging, and importantly, cardiac signs are emerging with bradycardia for both agents, as well as some signs of visual disturbance.
We have a great confidence in our safety profile. I want to take this moment to look at a deeper level on the bottom part of this slide and talk about the molecular anatomy of a SERD. SERDs have a degrader side chain, and shown here, the degrader side chain is in green. It's the amino fluorine side chain, and it has a chemical scaffold, shown in the blue box, and it's the scaffold that really is responsible for the high affinity binding to the estrogen receptor. If one looks on the right side at other SERDs in development, to be frank, it doesn't take a medicinal chemist to notice that there's homology, there's structural similarity. Our SERD on the left, the scaffold is quite distinct. I think it has been very gratifying to see this molecule move forward with a profile that has emerged.
Let's move to slide 54. Here, I'm going to go back to the preclinical data because it is always nice to see that the preclinical data, in fact, predicted for what we've seen in the clinic. In this case, we saw no significant bone marrow suppression. On the left side, no significant suppression in the animal model on hemoglobin. On the right side, no significant changes in neutrophil count. That, in fact, did predict for a lack of bone marrow suppression when we've gone to the clinic. Slide 55 is a high-level overview of where we are. AMEERA-3 is our monotherapy randomized trial, which will go against the physician choice of endocrine therapy. AMEERA-1, the combination with a CDK4/6 will lead to a pivotal trial with AMEERA-5, and in early breast cancer, we will follow AMEERA-4 with moving a SERD into the adjuvant setting.
Most importantly, we are confident that we will reach market at least one year ahead of other SERDs in development. That one year may be a conservative estimate, but the clean safety profile, the lack of cardiac monitoring, as well as the efficacy data, has given us this confidence. We are leading the way here, and we are looking forward to moving this into earlier lines and ultimately into the adjuvant setting to improve the outcome. Let me shift for a moment and talk about a new collaboration shown in slide 56. It's a collaboration with the I-SPY network. Many of you are familiar with I-SPY. It is one of the most productive platforms in drug development for patients with breast cancer. It really has accelerated development of a range of investigational agents for these patients.
Shown on the upper right is the general paradigm for the current I-SPY. The opportunity that emerged is the current I-SPY 2 trial rests on a cytotoxic chemotherapy backbone, in this case, combinations with a taxane and an anthracycline. Clearly, there are patients with high risk early breast cancer, shown here in the blue circle, who may not benefit from cytotoxic chemotherapy, and that's where this collaboration comes in. It will be for patients with high risk early-stage breast cancer who would not benefit from neoadjuvant chemotherapy. While it's designed as a feasibility endpoint, it's really building on the paradigm of using biomarkers, interrogating agents, in this case, on top of a SERD backbone, and then adaptively adding to the trial based on those results from surgery following neoadjuvant chemotherapy.
We're very excited to partner with this premier group and to again now fill a significant gap by bringing the SERD into the platform for patients who shouldn't receive a cytotoxic chemotherapeutic backbone. Where are we now? Let's move on to slide 57. We believe that the data that's emerging supports our ambition that 859 becomes a best-in-class endocrine backbone therapy across all treatment lines. If one looks at the target profile that we set out in developing the oral SERD, we believe we have ticked off all the boxes. We have a highly competitive clinical benefit rate. From a safety standpoint, importantly, no bradycardia signals, no QTc prolongation, no significant liver enzyme elevations. Tolerability, no Grade 3 treatment-related adverse events. That includes Grade 3 nausea, vomiting, and dizziness. Importantly, no visual disturbances.
Given the current landscape of treatment for patients with breast cancer, the clean hematologic profile shows no significant myelosuppression. Slide 58. We want to be the best in class. We think we can get there. Compelling efficacy, safety, and tolerability. We're moving quickly. We're aiming for initial approval in 2022, at least a year ahead of our competitors, and the lack of bone marrow suppression will help pave the way. With that, let me turn it back over to John.
Thank you, Peter. It's great to have you on the Sanofi team, I must say. Let's move on to slide 61 as we wrap up here. You can see we're investing at scale to rapidly bring innovations to oncology patients, spanning four core disease areas, multiple myeloma, skin, lung, and breast cancers. As we get started on our road back to oncology, we intend to build our portfolio around the four foundational anchor assets that we have featured today, SARCLISA, LIBTAYO, the anti-CEACAM5 ADC-701, and our SERD 859, which each have differentiated clinical profiles and offer unique patient benefits in large indications with significant unmet need.
We've already made significant progress in the clinic in the past year, demonstrating the high quality and the significant potential of these molecules, which ranges from our first in class, ADC-701, to SARCLISA and our internally invented oral SERD 859, which are showing strong potential for best-in-class profiles, to LIBTAYO, for which we see a variety of utilities that include our first in class positions in non-melanoma skin cancer and the potential to combine LIBTAYO with our novel IO portfolio molecules as we pursue the next generation of drug combinations for cancer immunotherapy. These four molecules provide the foundation for our return to oncology and for bringing future benefits to patients struggling with breast, lung, or skin cancers or with myeloma. Moving to slide 62, here are some highlights of the oncology news flow that we expect in the coming 18 months.
Key events in the 2nd half of this year will be the presentation of the LIBTAYO front line non-small cell lung cancer data at a medical congress, namely ESMO. For the SERD, we expect to have the POC data readout in combination with palbociclib, and we would then follow that with our initiation of the pivotal AMEERA-5 study in the front line metastatic setting. We look forward then in 2021, next year, to several readouts, and these would include pivotal results for the SERD 859 in the 2nd line and 3rd line hormone receptor-positive metastatic setting as monotherapy. We also expect randomized data from the first of our pivotal studies of SARCLISA in newly diagnosed myeloma patients. To top it off, we expect six potential POCs in the next 18-24 months for earlier molecules in the Sanofi oncology portfolio.
Among these, I would highlight the potential for a POC study of the SHP2 inhibitor in combination with the MEK inhibitor, cobimetinib, as well as a phase I-B proof of principle readout in combination with PD-1. We expect to have go, no-go POC readouts for the TGF-beta inhibitory antibody, another internally invented asset, in a range of tumors and in combination with PD-1 or other molecules. We also anticipate POC data for our T cell engager in AML, and you'll start to see other T cell and soon NK cell engagers flowing into the pipeline from the laboratories. We'll be well along by then with the subcu formulation of SARCLISA. Last but certainly not least, we expect proof of principle for our non-alpha IL-2 molecule, THOR-707, in lung cancer.
As you can see, we have an exciting couple of years ahead of us with much more to come as molecules move from the laboratory into the clinic. On slide 63, we'll wrap up here, and I'll just remind you that Paul talked earlier to this slide, which represents Sanofi's ambition in oncology. We're working at a rapid pace to transform our strong science into a first generation of strong products that provide Sanofi with an anchoring position in modern oncology, and then transition to novel best-in-disease combinations, becoming, we hope, the partner of choice in selected areas of cancer medicine. Finally, I would mention that this is the first time in anyone's recent memory that Sanofi has held an ASCO analyst event. With the momentum building in our pipeline, I promise you that it won't be the last.
With that, I'll hand things over to Felix to start the Q&A, and I will serve as moderator for the questions. I would remind you to try to limit them to two questions each. Thank you for your attention. Thank you for your interest.
Thank you, John. We will now open the call to questions. As a reminder, given that we are running over time, we would ask all our analysts to limit their questions to one each, if that is possible, in order to give your colleagues also a chance to ask a question. Thank you very much. Operator, can you please open the Q&A session?
The first question is from the line of Wimal Kapadia from Bernstein. Please go ahead.
Thank you very much for taking my question. Wimal Kapadia from Bernstein. Just on Sarclisa. Clearly, I appreciate the efficacy differences and great data today. How do we think about commercialization of the product? I just want to get your views on, will the efficacy differences be enough to compete with the DARZALEX subcu in the minds of the physicians? Tied to that, the list price that we've seen look like they're similar to DARZALEX. Just to get your thoughts on, will price be a lever that you use in the interim until you have your own subcu Sarclisa on the market? Thank you.
Thank you for the question. I think, in oncology, generally, efficacy is what wins the day, and I think that's what's going to matter most to patients and their physicians. Let me ask, maybe first, Dietmar, just to say a little bit about the subcu space since you referenced that, then hand it over to Alexander to talk a little more about the commercial strategy. Dietmar, just a couple comments on the subcu first.
Right. I want to point out that the importance of subcu is different in different lines of therapy. Patients in later lines of therapy have ports very often. Also, these are elderly patients, so a subcutaneous injection is not always simple, especially if you're looking at a larger volume. We have started our work on subcu with different ways of administrating SARCLISA subcutaneously, for example, with a device that allows you to inject, I want to say, in a more patient-friendly manner. We will move that forward quickly. I still believe that efficacy is important in this space, and that we need to realize that the impact of subcu will be very different in different spaces.
At the time when you go into earlier lines of therapy and into maintenance, that's where it's more important, and that's where we will have our subcu ready as well. Alexander?
Yeah. Before Alexander-
Yeah. I just want to-
The other thing I just wanted to add is that in the early going with our subcu, we already are confident that the bioavailability of SARCLISA is such that this will not be a heavy lift to achieve a subcu formulation. We see excellent bioavailability. We don't have to do any special tricks like hyaluronidase, et cetera, in order to deliver SARCLISA via the subcu route. Over to you, Alexander.
Yeah. Maybe I just want to emphasize a few points. One, even with subcu, patients will still need to go to the hospital, right? To get the subcu injection. Even in our own IV program, now we brought the infusion duration down to 30 minutes, actually, with the third infusion, right, which brought it down quite significantly. Just to emphasize, the KOLs we've spoken so far, they were really excited about the data that they've seen. Now to your question on pricing, we actually did price. We gave a lot of thought into what would really be the best commercial strategy, if you want, for SARCLISA. Actually, we did price it at a slight discount on an infusion basis compared to other available agents in that space.
We believe the commercial strategy really supports the strong data that we've seen in ICARIA and now in IKEMA as well.
Great. Thank you very much.
Next question, please.
The next question from the phone is from the line of Richard Vosser from J.P. Morgan. Please go ahead.
Hi. Thanks for taking my question. It's a question on the SERD. Perhaps you might talk about the half-life and how confident you are in terms of the 24-hour coverage of the drug on the basis of what you know. Just added to that, we've seen some other SERDs have some elements of partial agonism. If you could just give us an idea of the data that you've collected around amcenestrant to prove that that's not the case as well. Thanks very much.
Thanks for your question, Richard. We're good on both of those, maybe I'll let Peter provide the answers to you. Peter?
Yeah. I think you summed it up. We do have coverage. We have a half-life that gives us coverage and gives us a wide margin as far as receptor degradation.
I'm not aware of any agonistic effects that we've seen with the agent either, but we have a wide margins as far as degradation is concerned at the doses and exposures we're achieving.
Right. No, we don't have any agonism, we also have Laurent Tabouret, I think, on the call today if we need more detail on that. It's clean in that regard too. It's a complete antagonism and no mixed or partial agonism component to the molecule. Very nicely crafted molecule from our chemists in the Paris area.
Thanks very much.
The next question from the phone is from the line of Jo Walton from Credit Suisse. Please go ahead.
Thank you. Jo Walton from Credit Suisse. I'm going to take you back to SARCLISA, if I may, and the choice of Kyprolis in your backbone. Given the recent data that we saw at ASCO, which showed that Kyprolis in first line had some tox issues, do you think that that's going to be less used by doctors? I wonder if you could give your view on the pretty good BCMA data in later lines that we also saw at ASCO this year.
Yeah. Thanks for those questions. Excellent questions. I'll get started a little bit and then ask Dietmar to jump in. With Kyprolis, I think the issue there is it does seem to be emerging as the most effective backbone therapy, I think that's logical that physicians and patients will want to build on that. It does set a high bar, clearly, as we try to add a biologic to that and show that there is additional benefit in progression-free survival. I think it's important to have experience with that as one of the backbones. As you saw, we're doing both that, both KRd and VRd. With the BCMA data, indeed, we find the T-cell engager mechanism to be interesting, and it's something that we're bringing forward ourselves.
We have a collaboration right now with Regeneron, with a couple of different BCMA bispecifics that are in development. We'll see how those progress over the next few weeks and months. Dietmar, anything to add?
You're referring to the data of VRd versus KRd, we believe it's really important to generate data with different backbones. That's where phase III studies with different backbones like VRd, like KRd, come in. Obviously, the space is emerging, we need to look at that moving forward. These are some of the most important regimens in first line, these combinations will also be important to evaluate. The BCMA combination is, again, another pillar that we're evaluating, as John has said, how we look at myeloma therapy is you've got these different pillars of therapy, patients are cycling through some of these combinations. It will be important to generate data with those different combinations, BCMA is another mechanism of action that we want to combine with.
Next question, please.
The next question from the phone is from the line of Peter Verdult from Citi. Please go ahead.
Thank you. Peter Verdult, Citi. Two questions, LIBTAYO and SARCLISA. Just when interpreting that lung data, you did some smart things like excluding never smokers, which I don't think the KEYNOTE studies did. Regardless, Regeneron sounded pretty confident on their call last night that they could get the modified ITT data in lung on the label following discussions with FDA. My question is it too early to ask whether the same applies for EU, Chinese, or Japanese label discussions? Secondly, on SARCLISA. The KOLs that we've always spoken to have always argued that isatuximab is no worse than Darzalex, of course, you have some data pointing in some indication that it might be better. In the next 12 months, we're going to see HexaBody-CD38 data.
My question is, can you talk a bit more, I know this is long-term, but more about your second-generation CD38 that you're developing and when we might see data from that asset? Thank you.
Okay, good. We have two questions, one on LIBTAYO and what the label is going to look like. We have had meetings with the FDA. To my knowledge, Dietmar, correct me if I'm wrong, I don't think we've started those dialogue yet with EMA or China, but maybe you can comment on that, and then we'll come back to the SARCLISA question.
Yeah. For LIBTAYO, obviously the regulatory discussions have started. It's really difficult to speculate, and I will not speculate on regulatory interactions with some of the other agencies. Clearly the objective is to point out the mITT data, which is the data with the companion diagnostic that allows us to reliably identify a PD-L1-positive patient population that's also similar to the diagnostic that was, or the same diagnostic that was used with KEYTRUDA, and we'll definitely move forward with those discussions. The never smoker question, obviously, if you think about the mechanism of action for checkpoint inhibitors, smoking does increase your tumor mutational burden. Never smokers are those that have a higher ratio of monogenetic causes for non-small cell lung cancer. Clearly, we're going to have good discussions with regulatory authorities about the overall benefit in the mITT population.
Yeah. Again, I think it's the right population because it's the one that actually do have PD-L1 greater than 50%. The study, because of challenges with making the diagnostic available in all territories, had included a number of patients that turned out not to have the requisite percentage of PD-L1 positivity. If you pull them out, then you're really looking at the intended population that the study was meant to enroll. Anyway, let's move to SARCLISA, the second-gen molecules. My colleague, Dmitry Bytchenko, who heads oncology discovery for the immuno-oncology portion of the portfolio, is here with us, and those molecules came out of his shop. Maybe we can ask him just to comment on them, and maybe then, Peter, I think one of the questions was, when might we see some data from them? And Peter might have some insights on that.
Dmitry, can you just describe those molecules a little bit for the audience, and then we'll see if Peter knows more about when we might have data?
Sure, John. We have developed two next-generation anti-CD38 assets. One is really capitalizing on our experience with isatuximab. We're calling this molecule CD38 Fc engineered. We noted, and as Dietmar pointed out earlier today, that ADCC is the primary mechanism of action for isatuximab. It's a significant driver of efficacy, as we believe it. We developed a molecule with enhanced ADCC functionality, and this is already in dose escalation in phase I. I'm sure Peter will be able to speak to the timing of the first readouts with that molecule. The second one is a completely different mechanism of action. It is indeed a tri-specific T-cell engager, which engages CD38 and also through CD3 arm, brings T-cells in close proximity to multiple myeloma cell to enable efficient killing.
Differentiating feature of this molecule is the presence of anti-CD28 arm, which allows T-cells to proliferate more robustly, to live longer, generally enhances their multiple myeloma killing activity. Also incidentally, certain multiple myeloma cells actually express CD28. We may have enhanced targeting through dual binding to CD38 and CD28 on multiple myeloma cells. Both of these assets, as John said, were developed internally. They are now in phase I clinical trials, and we hope to see first readouts in the coming years.
I would just add, with respect to the Fc engineered molecule, which is designed to have better ADCC, antibody-dependent cytotoxicity, of course, our non-IL2, THOR-707, is an excellent combination partner with that because it expands the numbers of NK cells, natural killer cells, and that's the cells that then do the killing through that mechanism. That's a nice combination opportunity, I would just say about the tri-specific, I think we'll see if we can thread the needle on therapeutic index, the aspiration would be to have a CAR T-like activity in a molecule rather than having to go through the elaborate procedure of genetically engineering cells through that kind of a design. We'll see how it behaves in the clinic. Anything else to add, Peter?
I think you've covered it, John. I think we will have the data emerging in 2021 from the tri-specific. We are on track for that.
Thanks. Super helpful. Thank you.
Thank you all. Good. Next questions.
The next question from the phone is from the line of Tim Anderson from Wolfe Research. Please go ahead.
Thank you so much. A couple questions. SARCLISA hitting a different epitope. I think different mAbs within a given class do this, and it does not always mean that it leads to a different clinic versus other members in the class. If you're confident in class product, can we assume that at some point you'll have blanks at least as a comparator arm in some of your trials? If not, maybe just go head-to-head with it. Come back to LIBTAYO and this issue of smokers. You and Regeneron frequently compare data sets to Merck's KEYTRUDA in setting, but it is apples to oranges because you guys never smokers. I'm wondering why to do that, and I guess more importantly, does this leave potential slightly narrower label, and do you think it commercially?
All right. Thank you for your questions. On the SARCLISA and the question of whether eventually we would do a head-to-head study, I think that's unlikely, but I'll let Dietmar take that. For the Regeneron, I think Dietmar, you might take that as well in terms of the comparison of the different populations and the never smoker issues, since you commented on that already a few moments ago. Dietmar?
Yeah. For the question of SARCLISA, we have not planned a head-to-head study at this point in time. We feel it's important to really establish data first with the triplets in first line to also move into the smoldering myeloma setting, and we just not focused on the comparison versus other CD38. We believe the key argument is around differentiation is not only the different epitope, right? It's literally looking at preclinical data, then third-line plus setting, the second-line setting, and what we hope to see in the first-line setting. That will be the picture that we're looking forward to. When you also look at the timelines for some of those combinations, they are actually competitive when you look at the first-line setting. Really looking forward to see those data.
With regard to LIBTAYO, I think we're speculating here a little bit, with regards to discussions with regulatory authorities. We'll need to see how those discussions emerge. As discussed before, the never smokers are a specific population that anyway has a higher rate of monogenetic tumors. It's also a small population that we're talking about also here in these clinical studies. Obviously, the scientific hypothesis, as stated, is around tumor mutation burden, is around neoantigen load. At the same time, we do believe the overall data for LIBTAYO is highly competitive and very comparable to what has been seen with KEYTRUDA, which really encourages us regarding the competitive positioning of the molecule.
Thanks, Dietmar. LIBTAYO for us is really a foundational in a, thinking particularly in lung cancer. Let's remember, it gives us a foundation in lung around which we can build. As I said in the beginning, I don't have to remind everyone that while we're all excited with what PD-1s do for patients with lung cancer, there's still a lot of room for improvement, right? There's maybe a third-ish or so of patients who have responses. Almost none of them are complete responses. The key now is to build with additional combinations on top of that. We mentioned that we will take our antibody drug conjugate as one combination partner. We mentioned we're doing SHP-2 inhibitor as a combination partner. We're doing TGF-beta as a combination partner. We're doing THOR-707 as a combination partner. All those will be going forward in lung.
As LIBTAYO becomes established as at least one of the background PD-1s, it looks like it's working well and shows a competitive profile in lung. It gives us something to build on as we move to our novel combos. Should we move on to the next question?
The next question from the phone is from the line of Graham Parry from Bank of America. Please go ahead.
Thanks for taking my question. First one's on CEACAM5 and your faster market strategy. Based on the data you've got to date, is there a potential here to actually file in last-line lung cancer KEYTRUDA failure patients based on the response and response duration data you've got already? The second is on the SHP-2. Just if you could help us understand what the target profile is, what you're expecting to see from the data in 2021, and then what your next steps for pivotal trials would be on that asset. Thank you.
Okay. I'm going to let Peter take the CCAM question and get started also on the SHP question. Perhaps, if we need additional help on that, we've got Laurent Reboul from our Molecular Oncology Group, who was spearheading that collaboration with ReMed, and he can also probably jump in. Peter, over to you.
Yeah, I may ask for some help from some of my colleagues as far as the regulatory strategy on this one, John, as for the second line versus the later lines. I'm going to pause on that one, and maybe we can circle back, because I don't want to give a wrong answer on that. Maybe either Alex or others more experienced in that realm can comment.
I would say certainly the thought has crossed our mind. We've been pursuing, I guess, a more traditional path to do a randomized study against Taxotere, going as monotherapy ADC versus Taxotere. The thought has crossed our mind. Dietmar, are you knowledgeable of any of the regulatory interactions along those lines?
Of course, we had some discussions along those lines. Remember, this is a limited data set. Obviously, in a biomarker-defined population, which is beneficial. The data that we have in hand at this point will not lend itself to an immediate submission. Obviously, as we have the phase III study ongoing, as we generate really a larger, what I call it, totality of data in this setting, we will reevaluate the fastest path to submission.
Okay, there was a question about SHP2. I think it was more the timing. I do not know if we have that in our slide. We have a couple different combos underway. As you are probably aware, SHP2 with cobimetinib, SHP2 with the EGFR inhibitor, osimertinib, SHP2 with the KRAS inhibitor from Amgen, and then a SHP2 PD-1 combo are all being explored. I think data will be trickling in next year, various times. Anything else to add, either Dietmar or Peter, on that?
Yeah, if I can add. The question was also with regard to the strategy moving forward and what are we going to do, obviously, with the molecule when it comes to potential phase III. I just want to mention that we have set up together with our partner, with Revolution Medicines, a program that looks at different, what I call, prototypic questions. You look at the combination with a KRAS inhibitor together with EGFR, you look at the combination with a tyrosine kinase inhibitor, with the EGFR inhibitor. We are also looking at combination with checkpoint inhibitors, because there may be, if you look at the mechanism of action, a potential impact on immunotherapy approaches. We are really in the signal-generating stage at this point.
If we see convincing activity in one of those areas, and that is what we are talking about, generating these data and reading them out then in 2021 and 2022, then we can move very quickly, obviously, because the mechanism is attractive. When you think about SHP2 KRAS or SHP2 KRAS checkpoint inhibitor, we can move that forward really substantially.
Okay. Thank you for your question.
Operator, we may have time for another two, maximum three questions. Please go ahead. Everyone maybe only ask one question at a time. Thank you.
The next question from the phone is from the line of Mark Purcell from Morgan Stanley. Please go ahead.
Yeah, thank you for taking my question. Mark Purcell, Morgan Stanley. On the CEACAM5 platform, could you help us understand the overlap of CEACAM5 with EGFR, ALK, and other targets such as TROP2, HER2, and lung cancer, given the latter two have competitive ADCs targeting them. Given that there could be combinations here, could you help us understand the combinability with other agents from a tolerability perspective, such as checkpoints? If I could squeeze in just on the same, on the platform, the speed to IND with other cytotoxics, can you help us understand your plans here to further leverage the bystander effect? What should we expect here in terms of increased membrane permeability or potentially greater ratio of payload to antibody with future iterations of this platform? Thank you.
Well, thank you for your questions on CCAM. The data that Peter presented were showing those patients that are CEACAM5 positive who do not have mutations in EGFR receptor or ALK. The data there have already split those out to provide a unique population. There obviously is some overlap. I'll let Peter talk a bit more about what he knows or doesn't know on the issues of specifics on the overlap. There's several different things to consider, including PD-1, as you mentioned. It makes it a bit complicated. On the bystander, Peter, if you could start on that. We have Dmitry on the line here again, whose team designed that antibody, and maybe he could help supplement your answers there.
No, thanks, John. I think getting back to the overlap with the EGFR mutant, ALK mutant, the slide we showed was an estimate pulling away those that we know would have the EGFR therapies or the ALK therapies. It was more of a conservative estimate, but there is going to be overlap. As far as patient numbers, we try to look for the population that was distinct. As far as combinations, yeah, there is a Venn diagram. These are not linked in any way. It is sometimes a little challenging at this point to get real hard numbers without some confidence interval around what the overlap would be. As far as bystander effect, I will turn that over to Dmitry. We know, of course, how the payload is delinked and that the payload can permeate membranes.
Dmitry, do you want to speak more as far as how that might be leveraged?
Sure. I think there was also maybe a question around combo with PD-1, PD-L1. We certainly have preclinical evidence that a combination of CEACAM5 ADC with a checkpoint actually improves efficacy, and it's not surprising because of the induction of immunogenic cell death in the tumor, which when combined with a checkpoint blockade, really improves outcomes. With regard to the next generation of CEACAM5 ADCs, I think Peter spoke to it a little bit, and we're very excited to be moving forward in a number of directions there. First and foremost, really seeking a differentiated payload, and it's differentiated from tubulin binder DM4, because as you can imagine, not all tumors are sensitive, intrinsically sensitive to tubulin binders. We're very interested in expanding the breadth of anti-CEACAM5 ADCs by conjugating them to novel cytotoxics with a differentiated MOA, and also to immunostimulants.
In that process, we're actively exploring a number of linkers, a number of modifications to the molecule in order to enhance its efficacy. These projects are advancing in preclinical development.
Thanks for your question. I would just remind you guys, cytotoxicity is something that Sanofi has quite a bit of prior knowledge around. You can imagine that our libraries are full of interesting molecules in that regard. Good. Should we move on? Do we have time for another question or two? How are we doing, Felix?
One last question, operator. Thank you.
Sure. The last question from the phone is from the line of Peter Welford from Jefferies. Please go ahead.
Hi. Thanks for squeezing me in. Just wanted to ask a question actually on the SERD 859 and coming back to ASCO. We obviously saw, as you said, the well-tolerated data, but we also saw the PARSIFAL study being presented as well, which showed that with the CDK inhibitors, the effect of the benefit of endocrine versus, on the other hand, the aromatase inhibitors, was somewhat nullified. I just wonder therefore how you can put that in the context of how you think about developing the SERD in combination with CDK inhibitors in early first-line breast cancer, and how potentially those results could impact your thinking around the trial design. Thank you.
Yeah. No, thank you for your question. It's clearly, I think, the question of the hour in the aftermath of those data at ASCO. Peter, why don't you start, Dietmar, you can supplement if there's anything you feel that you want to add on top of Peter's comments. Peter?
Yeah. No, thanks, John. Yes, I think that has caught everyone's attention, including ours, as far as how we might refine our strategy moving forward and the combinations moving forward. It doesn't undermine the fundamental strategy as far as the foundational element of a SERD. The strategy, I think, has potential to evolve as we move this forward. Dietmar, perhaps, given your extensive background in this realm, you can comment.
Yeah, just briefly, two comments. First of all, there have been a variety of surprising data with the palbociclib at ASCO, between PALLAS and PARSIVAL, we're obviously carefully evaluating how this impacts our strategy. For the combination of a hormonal drug with the palbo, obviously, in the first-line setting, we just need better drugs. We need better anti-hormonal drugs. There seems to be a ceiling that is seen with palbo and letrozole and aromatase inhibitor, and then a SERD like fulvestrant. We would like to break that ceiling. We feel our drug is a better SERD. We don't have the dosing limitations that you see with fulvestrant, and we hope that definitely we can achieve better efficacy. We feel that combination needs to be studied.
The other component here is that the usage of a SERD, we're talking about this a lot as a backbone therapy, and we mean it as a backbone reaching from adjuvant to first-line, where you see the combination with the CDK4/6 to second-line, third-line and beyond. In some of those areas, obviously, usage will not be with palbociclib or a CDK4/6 inhibitor, but also in monotherapy. It's important to conduct all these studies, that's where the real potential is for another SERD, both in these monotherapy settings, in combination. We're conducting other studies, for example, with CDK4/6, as you know, with a PRMT inhibitor, we'll see those data.
Thank you, Dietmar and Peter. Well, I think that concludes what time we have for questions. We're at the end of the hour now. I want to thank everyone for your interest. Sorry we couldn't get to everyone's questions. I'm sure we can do follow-ups with the help of our investor relations colleagues. Again, just really exciting progress in the pipeline. We're on a journey to bring Sanofi back into oncology. I think you can see the anchor assets on which we'll build and try to make an impact for patients in these four disease areas as a starting point. We look forward to providing future updates as we take this journey. Thank you.