Good morning and good afternoon to everyone on the call. Thank you for joining us on the second of five part series of interactive webcast events, which will highlight Sanofi's progress in R and D. Event today will focus on our oncology strategy and ASCO updates. As usual, you can find the slides to 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 and D Investor Event on June 11, focused on Dupixent.
We are also excited to confirm that the nercetamab Phase 2b data has been submitted and accepted by a peer reviewed journal. The nercetamab 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 contain forward looking statements and involve 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 and also our Document d'Orchestraments in U. S.
Cell for a description of these risk factors. With that, please advance to Slide three and 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 and D strategy in oncology. Giedma, Alexander and Peter will then provide updates on selected assets, namely Zaclisa, Libtayo, anti CEACAM5 and SERD.
John will then wrap up with concluding comments. We will close with a Q and A session. Joining for Q and A will be Bill Sivolt, Executive Vice President, Sanofi Genzyme Dimitri Wintershine, Head of Immuno Oncology Research and Laurent DeBusch, Molecular Oncology Research Head. With that, I'd like to turn the call over to Paul. Thank you.
Well, thank you, Felix, and
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 bank strength and the people you're gonna meet today. I think while sort of challenges digitally, I think there is a huge opportunity to be more inclusive and see just how strong our teams are, and I look forward to to that continuing. So, you know, in light of COVID nineteen and lockdowns, we we assessed our plan for the June 23 r and d day.
We didn't want to cancel it like some of our peers have done, but we're fully aware of the limitations of virtual, like I mentioned. So 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 and key leaders We hope you enjoy it.
So we have great momentum in our oncology pipeline with a number of exciting data readouts from our four emerging oncology anchor assets. And today, we're gonna focus on the la on the on our last stage oncology portfolio and in and in particular Libtayo, Sarclisa, TCAM five, and, of course, our SERD eight fifty nine, our priority assets in ANCA. 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 23, including a deep dive on THOR seven zero seven, our first in from the Syntherex 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.
So everything starts with our science and that we intend to transform into commercial leadership. We think they go together. At Sanofi, we already have a wealth of scientific understanding and leading capabilities with truly cutting edge platforms, including ADCs, multispecifics, and antibodies. We're gonna 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 floor.
And 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 stand alone standpoint. So 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. So let me now introduce you to the four assets and our ambition, how we plan to shape those into blockbusters. Starting with Sarclisa, Deepmar, 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. And 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 you 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 datasets. Moving to CEACAM five in the last months, I've learned a lot of how to anti drug antibody drug conjugates, and I'm getting increasingly excited about seven zero one, 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 c camp five targeting ADC for lung cancer and other solid tumors. Seven zero one is for twenty five percent of the nonsquamous cell, non small cell lung cancer patients with high expression of TCAM five. And for reference, there are more patients with high expression of TCAM5 than lung cancer patients with driving mutations such as EGFR and ALK mutation. Last but not least, Peter will also discuss our SERD data just presented at ASCO, which increases our confidence that we have a very differentiated molecule on our hands.
Eight fifty nine is perhaps the only SERD, 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-eight 59 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. The approvals for Sarclisa, our first internally developed oncology anchor asset in The US 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 POP data at ASCO for SERD, CEACAM five, and I'm especially proud that both molecules are entirely internally developed at Sanofi. And like Sarclisa, are wholly owned by Sanofi, 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 the chart is the incredible progress we've made shaping the development programs to deliver critical and differentiated datasets for our anchor assets in our early stage portfolio, which will be the source of hopefully a lot more excitement in the coming years and months. So in short, we're delivering on our ambitions and translating our words into actions as we continue to build our oncology franchise. So 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, is what I would call an authority in this therapeutic field. And his long list of oncology credentials include leading the peer at Roche, bringing some of the pipeline through, cofounding a biopharma company that approved the OncoMedsin, 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. And while as head of r and 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 of fundamental basic and translational research that I did in the area prior to joining pharma. As Paul referenced, my 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, and cancer cells. And now with the immuno oncology in the limelight, it's probably relevant that my PhD was taken in immunology, and my doctoral dissertation was actually on interleukin two.
That was back when there were only three interleukins. I'm little a embarrassed to say now they're 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, ECCOG, c l a g b, 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. So 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 and D organization that's early on the road back to oncology. But we're making rapid progress on multiple fronts. Today, I'll highlight just two of those very briefly on the next slide, 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. And so you'll 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, Deepmar Berger, to head development. Deepmar 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 cancer National Cancer Advisory Board. And you'll also hear today from Alexander Zender, who heads the oncology business franchise at Sanofi Alexander. He 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. So 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 preclinical or in early clinical development. But 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. But in addition, we've established in house platforms for bispecific and trispecific 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 multispecific molecules. And through the acquisition of Synthorix, 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.
So all these platforms are either in the clinic or approximately twelve to eighteen months from the clinic, which is super exciting for an r and d guy like me to be at the forefront of innovation design of new types of cancer medicines. So 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 twenty years due to the introduction of modern therapies with median survival increasing from about thirty months in around 2000 to about seventy months today in 02/2020, so over the last twenty years. However, still patients relapse and achieving response becomes harder after each relapse. With our wholly owned anti c d thirty eight antibody Sarclisa, we're seeing very deep responses in the refractory setting in both the second line and third line settings. And 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 sixty percent.
These deep responses are critical to delaying progression to the next relapse for as long as possible. And to achieve even deeper responses, we're exploring novel combinations, will be described later by my colleague, DeMar Berger. Skin cancer is one of the most prevalent cancer types. Most of these neoplasms fortunately are diagnosed early and hence have good prognosis. But when progressed to advanced stages, five year survival rates remain poor.
With Libtayo, our Regeneron partnered anti PD one 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 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. And 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 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.
However, 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, approaching around twenty percent now, but we clearly have much, much room for improvement when one considers that on average, only about a third of lung cancer patients respond to cancer immuno immunotherapy and that very, 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-one inhibitor.
We recently reported strong results in frontline non small cell lung cancer with high PD L1. Today, we will provide more insights into the data, though a full disclosure of results from the Phase III trial will not occur until the ESMO conference. I won't spoil Alexander's presentation, but I would note that so far, no checkpoint inhibitor has been able to match Keytruda's efficacy in frontline lung cancer. So have 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 is Sanofi. This first in class molecule, which was invented in our laboratories in the Paris area, is dubbed seven zero one. It is a monoclonal antibody binding the oncofetal antigen c cam five conjugated with a cytotoxic compound that attacks microtubules. As you know, antitubulin 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. So 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. So our ambition is to establish seven zero one as a new standard of care for c cam five positive lung cancer patients in the second line setting after failing frontline checkpoint inhibitor with or without chemotherapy. Then building from there, we will explore this ADC in the frontline setting in combination with anti p d one, attempting to replace some of the standard untargeted toxic chemotherapy drugs with this targeted and more gentle option for those patients whose tumors express CKM5.
Fourth and finally, moving to breast cancer. Huge improvements have been achieved in the treatment of breast cancer in the last forty, fifty years driven by increased awareness, early diagnosis, and, of course, new therapeutics. Endocrine therapy for hormone receptor positive breast cancer was pioneered in the eighties and, in fact, was the first form of targeted therapy for all of As you know, endocrine therapy aims to shut down estrogen receptor signaling. Unfortunately, interfering with the receptor estrogen receptor signaling is incomplete with currently available therapeutics, setting the stage for the emergency resistance, which happens all too infrequently. So in the metastatic setting, five year survival rates remain low at twenty eight percent.
And even for stage two and three patients with regional disease, in the absence of further progress, today, fourteen out of every one hundred women diagnosed with breast cancer this year will no longer be alive five years from now. So this is where our oral estrogen receptor degrader to the eight five nine 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.
So 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 two in our return to oncology, we will strive to build upon the late stage foundational assets, adding additional mechanisms from the early portfolio that can be combined to arrive at Bessen 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. But behind Sarclisa, we have next generation anti c d 38 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 trispecific 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 c d 38 antibodies. We won't have time today to go into the details, but molecular analysis of tumors and preclinical data provide compelling rationale for combining other molecules in our early development portfolio with the 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 seven zero seven, the non alpha interleukin two from Synthorix acquisition that stimulates selectively proliferation of tumor fighting c d eight positive cytolytic t cells and natural killer cells and mRNAs encoding various stimulatory proteins from the BioNTech collaboration that we introduce injection directly into solid tumors in attempt to reawaken T cell immunity, converting non inflamed cold tumors into inflamed hot tumors.
And in lung cancer, we're also exploring anti PD-one combinations with our internally derived TGF beta antibody and THOR-seven zero seven as well as with small molecule SHIP-two inhibitor that is partnered with Revolution Medicine. In fact, the SHIP-two 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-one. And second, because of SHP2's well established role in oncogenic growth factor receptor signal transaction pathways, such as an EGF receptor mutant lung cancers where we're testing SHIP2 in combination with next generation EGF receptor inhibitor, osimertinib. And 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 eighteen to twenty four 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 three to four development candidates annually, and 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 evolving and emerging Sanofi oncology pipeline. We'll look forward to sharing future data as these molecules reach milestones in their development journeys.
And if we can move then 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 were for the first time presenting our data on our second line study IPMA. I want to start by tackling a central question upfront.
We do understand that many of you consider Sarclisa a me too compound. And 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 highlights 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 and 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. And the first building block in this regard was the EKARIA study in the late line myeloma setting. EKARIA 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 formalidomide and dexamethasone. This is exciting data and our first piece of evidence in support of our differentiated profile.
But EKARIA 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. So we need to look at the second study here. And IKEAMA is our second pivotal study, this time in the second line refractory setting. As we announced a few weeks ago, IKEAMA has hit the primary PFS endpoint early. The full AYKEMA 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 are very excited to report now a forty seven percent risk reduction of progressional deaths for Sartiva in a triplet with carfilzomib and dexamethasone. Cross trial comparisons are always challenging. But in contrast to IKARIA, where we really didn't have a lot to compare with, it's a bit more straightforward to put the IKEAMA data into context. In this setting, have the PANDARS study, a Phase III trial that's largely similar to IKEAMA with a fairly comparable patient population and it evaluates daratumumab on the exact same Kb backbone. You will see that AYKEMA compares favorably to CANDOR.
The AYKEMA 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 akema. In addition, at this ASCO, we're presenting early data from two studies in the first line myeloma setting. And 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. And while we were several years behind in terms of data generation in the refractory setting, our timelines in first line are competitive as we are generating data for modern quadruplets of anti CD38 plus VRd or KRd.
But 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 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 exoenzyme 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 exoenzymatic 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. Therefore, 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 cell. Sarclisa induced significant cytotoxicity against CD38 positive myeloma cell line in the absence of effector cell, 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 Sartisa is not purely a MeToo, but a differentiated antibody with intriguing mechanistic characteristics that may lead to a transformative profile in the clinic.
So let's now take a look at the clinical data for Sarkeza so far. Beginning on Slide 18 with the previously reported EKARIA study in the relapsedrefractory third line plus 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 effect across all subgroups, taking median progression free survival to an unprecedented eleven point five months. These data supported SACLISSA U.
S. And now European approval in relapsed and refractory myeloma patients who have received at least two prior therapies. ZUKARIA is the only randomized pivotal trial in this setting so far. But 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 POMDAX backbone did not match Sakhalisa'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.
So today, we're tremendously excited to add the iQIYAMAR clinical data in the second line setting to this picture, which will be covered in-depth next week at EHA. So on Slide 19, the AYKEMA 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 of death by forty seven percent compared to KD alone, for a hazard ratio of zero point five three.
Secondary efficacy endpoint also dramatically favored the Sarclisa cohort, including the complete response rate of forty percent versus twenty eight percent and the portion of MRD negative or minimal residual disease negative patients at thirty percent versus thirteen percent. 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. EFA 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 SACLISA with a lower number of treatment discontinuations for adverse events in the SACLISA cohort at nine percent versus fourteen percent.
If the primary PFS endpoint of the IPMA study hit early, we are in a position to prepare for rapid discussions and then a submission with regulatory authorities. On Slide 20, we want to put the AYKEMA 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 AYKEMA 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 discontinuations. 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 the 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 one hundred percent overall response rate with an equally promising sixty one percent of patients negative for minimal residual disease. The gmmG concept trial uses the quadruplets 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 summarize data from Sarclisa's Phase Ib 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 VCB.
Results showed an overall response rate of ninety three percent with VCD and one hundred percent with VRd, with a proportion of patients without minimal residual disease at fifty three percent and thirty eight percent, respectively. As a reminder, two of Sartisa's ongoing first line Phase III studies, IMRAOS and gmmG, use the same VRd backbone. On Slide 22, with the promising results for Sartisa at hand, we are looking forward to the readout of our studies in newly diagnosed myeloma patients, starting with IMROS 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're excited about our soon to be initiated third pivotal study in newly diagnosed transplant eligible myeloma patients, and this is the first pivotal study that will evaluate a CD38 KRd quadruplet. We will conduct this study with a European myeloma network, and this will be our second pivotal study conducted with the myeloma cooperative group. And finally, we are planning the IFAK 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 PD-three outcomes for patients. On Slide 23 now, let me briefly lead you through the addressable patient numbers, average month of therapy and estimated time line for our Sarclisa program.
Move to the next slide, please. Overall, I want to highlight that we are studying Sartisa 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 relapsedrefractory third line plus setting on the left here, the average treatment time runs from seven to ten 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 sixteen months. Today, the second, third and fourth line settings combined are roughly a $10,000,000,000 market. By the time we consider first line patients, the number of those eligible for treatment with Sarclisa potentially would rise to over one hundred and ten thousand patients.
In short, as we roll out the indication to address increasingly earlier lines of treatment, we see the potential for Sartisa to become a blockbuster drug, especially if our thesis proves correct that we have in our hands 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 SACLISA 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 bispecific, a TGF beta inhibitor and THOR-seven zero seven, our exciting non alpha IL-two. 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. And 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 SARCLIZA is the best in class molecule. This started with a demonstration of the longest PFS observed in the relapsedrefractory third line plus myeloma setting, the EICARIA study, and is supported by exciting new data, the IKEAMA study, which shows the greatest reported risk reduction of progressional death in the second line setting when added to a KAD standard of care background. Third, we strive to replicate best in class data in our pivotal first line trials, and some of them are ongoing already. And early data from signal generating studies presented at this ASCO are highly encouraging. In conclusion, with Sartreza as our anchor asset in myeloma, we aspire to significantly elevate the standard of care for patients 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 5, 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. And 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 sixteen 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 twenty percent 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 thirty percent of patients with locally advanced disease who had a response, eighty five percent 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. Now on the right, in Phase III the Phase III in ADUANCE CSCC, which is a much larger opportunity, is ongoing. And 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 70% of total pathologic response. Now 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-one GALIXIO and we managed to build a $300,000,000 indication from scratch in less than two years. And 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. And in 2019, PD L1 sales for metastatic non small cell lung cancer were almost $10,000,000,000 with a large majority of sales generated in first line. And as you know, there's only one PD-one 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 and then moving to patients independent of PD L1 status. Now on Slide 31, let me focus on the strong monotherapy sixteen twenty four clinical data set.
On April 27, we released the headline results from our first pivotal trial study for in non small cell lung cancer, which evaluated single agent Libtayo versus traditional chemotherapy in patients with high expression of PD L1. And we reported a thirty two percent risk reduction for progression and death or hazard ratio of zero point six seven six. That was the overall ITT analysis of the data, which included all patients recruited into the study. Today, we present our modified treat analysis. The modified intent to treat analysis only includes patients with an accurate assessment of PD L1 expression in their tumors and removing patients who did not qualify as patients with a more than 50% PD L1 expression.
Now basically, these are only patients that are really true expressers and thus are comparable to the patient population that was included in both KEYNOTE-twenty four and KEYNOTE-forty two. Now this modified intent to treat analysis shows a higher risk of reduction of forty three percent 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-one single agent therapy. Looking at this data, I hope you agree that this is compelling. So far, none of the other checkpoint inhibitors has been able to match KEYTRUDA's efficacy in first line non small cell lung cancer.
And we have just showed that we can match KEYTRUDA or perhaps even do a bit more than that. Now we are hopeful that we are able to replicate this data in our chemo combination first line study, 16113, 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. And this should allow us to compete in the first line setting, offering patients the best possible treatment for their disease.
Now even though through the introduction of PD L1s and PD-1s as monotherapy in combination with chemotherapy, the treatment of cancer for many types of cancer has been transformed. But nevertheless, still many patients are not able to benefit and more different approaches are needed. So 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. And I hope that based on the data we've seen and we are able 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, and 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, ADUANCE CSCC and advanced basal cell carcinoma. Our recent depressive 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. And we are looking forward to sharing with you the full data set at an upcoming medical conference. And we are looking forward to compete in this setting after approval, hopefully in 2021.
And 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. And now I would like to hand over to Peter Adamson, our oncology development head.
Well, thanks very much, Alex, and, 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. But let me jump in and talk to you first about our anti CCAM seven zero one, a first in class CCAM targeted ADC. And I'm soon going to show the data that highlights how seven zero one, 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 one, we want to become the standard of care for patients with non small cell lung cancer who has 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 twenty percent, and we quickly have pivoted to our now pivotal monotherapy study. We're also pursuing combination studies with VEGFR2 inhibitors in second line. But where we obviously want to go next is shown in block two.
So once we become 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-one. We have, we will soon initiate a proof of concept in first line in combination with the PD-one inhibitor, and then we will pivot to a study that shows its superiority. And lastly, in block three, we're gonna be exploring how anti CCAM seven zero CCAM five seven zero one may have efficacy in a range of tumors known to express CCAM five, and then 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 antitubulin agents. So let's move to slide 36.
Anti CEACAM five seven zero one is a highly specific antibody designed to deliver payloads specifically to tumor cells. It has all the properties one wants to see in an ADC. It begins and the foundation rests on target selection. So CCAM five. CCAM five is a member of the carthenoembryonic antigen or CEA gene family.
CAM specifies cell adhesion molecule five. What's important is that this cell surface glycoprotein is highly expressed on tumor cells but has very limited expression on normal cells. Halo selection. Well, we have chosen to use DM4, a metanthanoid, a highly potent antitubulin toxin on a molar basis a 100 times more potent than taxanes. Importantly, the linker is stable in plasma.
So once the antibody engages the target, delivers its payload, the the linker is cleaved, and importantly, one can get a favorable bystander effect. So, again, all the qualities we want to see. Let's move to slide 37. We're currently developing seven zero one for antitubulin sensitive tumors with high CCAM5 expression. So shown on the right are the brown stains from a range of tumors, and on the left shows a relative prevalence and outlines our strategy.
Now I'm gonna return to colon cancer, which we know has high c cam five 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. But let's look at some of the data, and let's jump to Slide 38. And shown here is the outline of our first in human study, phase one, phase two study.
We quickly determined, the maximum tolerated dose for this drug delivered on a q two week schedule and then interrogated, tumors that had both high expression and moderate expression as well as other cancers. If we look at Slide 39, you'll begin to understand why our enthusiasm for this drug is increasing. So 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 had all majority had been exposed to antitubulin agents as well as anti PD-one or PD L1 agents. Very heavily pretreated, and that's why we were encouraged when we saw the results being shown now on slide 40.
So let's begin on the right side of slide 40, which shows the waterfall plot. And it's really a waterfall plot that you want to see in a in a heavily pretreated population with refractory disease. We had a disease control rate of sixty four percent and a significant number of objective responses. Now the outcome and duration are shown on the swimmer's lane plot on the left. And, again, here, a median duration of response of five point six months, and a number of patients had remarkably durable response to the disease.
So this has increased our enthusiasm for this ADC being able to live to deliver for patients with high CCAM expression in non small cell lung cancer. Let's drill down a little bit more on its efficacy by looking at slide 41. And here I want to return to the importance of not only having the right antibody but delivering the right payload. So when we look at our patients who have an objective response, and overall in high expressers, this represented twenty percent of patients, We explored, well, what did it matter as far as what they received before? And 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, fifteen percent.
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. But 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 twenty eight percent overall response rate. So, again, the direction is the arrows are all pointing in the right direction, and 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 seven zero one certainly has a favorable safety profile as shown here. Now I'm gonna highlight some of the adverse events that we've seen, and let me begin by the keratopathy or the the ocular event. That was the most frequent clinical adverse event. Now
this is an
adverse event that we've seen with other ADCs, conjugated to metanemoids. 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. So when it does occur, and in this case, it it occurred in about ten percent of the population, it was well managed, and only a small percent of percentage of patients actually required the dose reduction. So overall, dyspnea was the most frequent serious adverse event, reported in five or five percent of patients. But in all cases, it was believed to be a symptom of progressive disease by clinicians taking care of these patients.
But here's where the advantage of an ADC over attacksane becomes 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 seven zero one across all lines of treatment for patients with nonsquamous, non small cell lung cancer. In second line, we've had we have CARMIN LCO three, 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, wanna move this into first line, and we believe it has great potential in first line. So our CARMIN l c o five study will be exploring this in combination with a PD-one inhibitor setting the stage for a pivotal first line study. We think seven zero one 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.
So shown here gives you some perspective of the size of this subpopulation. So 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. So moving to slide 45, here is a high level overview of the strategy.
We have a novel CEACAM-five ADC. We already know how we can deliver a very potent payload for tumors that generally are believed to be sensitive to antitubulin toxins. We're exploring lung, but we will move it to 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.
So the selection of a rational payload is important and central to expanding our strategy. So in summary, on slide 46, we are confident and have a clear ambition to become a first in class CCAM5 targeting ADC. We have efficacy and a favorable safety profile demonstrated in patients with high CCAM5 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. And lastly, we do plan to take this platform into areas beyond lung cancer.
So 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 eight fifty nine. We believe eight fifty nine 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 our fast to market single agent and second line for patients with metastatic breast cancer.
Now importantly, we have a clear recruiting advantage here because the safety profile of eight five nine does not require us to to utilize cardiac monitoring. A very clean profile, and we believe that's gonna offer a real competitive advantage as we move our program forward. We're also looking at combinations with PI3 kinase inhibitors. Moving to building block two, combination strategies with CDK foursix inhibitors. And here I need to digress for a moment because we all, excuse me, we all saw the the real information that came from the PALLAS study where in an adjuvant setting, the addition of palbociclib, a study was stopped for futility.
Now 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. So our pillar two strategy, which I'll discuss in a moment, is unchanged because a CDK foursix 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 the profile of establishing ASERD as an important addition adjuvant therapy, which we aspire to, and I'll return to that. So 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 the CDK foursix inhibitor, and we will have a proof of concept later this year before initiating our phase three pivotal trial. And our third pillar is to expand to patients with early breast cancer, and I'm going to share some exciting news about a collaboration with EyeSpine.
So let's move to Slide 49. Eight fifty nine 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 wanna 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 three events. Combinability, a clean hematologic hematologic profile.
And 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 serum, 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 in early breast cancer, some patients receiving cytotoxic chemotherapy, in first line metastatic, a CDK4six inhibitor, and so forth. Our goal is to have eight fifty nine 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 MIRA one trial where we explored single monotherapy dose escalation and arrived at a recommended dose. And 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 three lines of prior therapy. Data from this was presented at ASCO this past weekend, but let's take a look at it in a little bit of detail now.
Move to Slide 51. So for Assert or any endocrine therapy, we and others believe that clinical benefit rate is perhaps the most relevant metric when one is interrogating an antiestrogen therapy. And overall, we saw a thirty six percent clinical benefit rate. Importantly, we saw efficacy in both wild type as well as mutant receptor. And we again see directional signs of what we can expect as we move this agent forward.
And 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 CDK foursix inhibitor, we had, in this exploratory analysis, a sixty four percent clinical benefit rate. But let's look at that in a little more detail on slide 52.
So 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 thirty percent to thirty five percent range. But what's important to state here is the patient populations have evolved. So those patient populations hadn't previously been exposed to a CDK foursix inhibitor, to an mTOR inhibitor, or to fulvestrant. In contrast, our study, IMiR-one, a high fraction of patients were exposed to one or more of those prior therapies.
So when we select out a subpopulation, and again I'm always cautious for a post hoc analysis or for exploratory analysis with small numbers. So I would take with a grain of salt the magnitude of the effect, but 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. So here is, I think, an essential part of any surge 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 experience relatively low frequencies of treatment related adverse event of grade one or two and no treatment related adverse event greater or equal than grade three, a remarkably clean safety profile. There are other oral SERDs in development. Those oral SERDs, grade three events are emerging. And importantly, signs, cardiac signs are emerging with bradycardia for both agents as well as some signs of visual disturbance. So we have great confidence in our safety profile, but 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.
So SERDs have a degrader side chain. And shown here, the degrader side chain is in green. It's the aminoflurane 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.
So 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.
And 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. And 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.
So Slide 55 is a high level overview of where we are. AMIRA three is our monotherapy randomized trial, which will go against the physician choice of endocrine therapy. AMIRA one, the combination with a CDK foursix, will lead to a pivotal pivotal trial with AMIRA five. And in early breast cancer, we will, follow AMIRA four with, moving a SERD into the adjuvant into the adjuvant setting. Most importantly, we are confident that we will reach market at least one year ahead of other SERDs in development.
And 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. So 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.
And it really has accelerated development of a range of investigational agents for these patients. So shown on the upper right is the the general paradigm for the current I SPY, but the opportunity that emerged is the current I SPY two trial rests on a cytotoxic chemotherapy backbone, in this case combinations with ataxane and enantracycline. 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. And 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.
So 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. So where are we now? Let's move on to slide 57. We believe that the data that's emerging supports our ambition to become that eight fifty nine becomes the 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 three treatment related adverse events. That includes grade three nausea, vomiting, and dizziness. And importantly, no visual disturbances.
Given the current landscape for treatment for patients with breast cancer, the clean hematologic profile shows no significant myelosuppression. Slide 58. We want to be the best in class, and 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 before of our competitors, and the lack of bone marrow suppression will help pave the way. So 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 innovation 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 featured today, Sarcalisa, Libtayo, the anti cCam five ADC seven zero one and our SERD eight fifty nine, 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 seven zero one to Sarclisa and our internally invented oral SERD eight five nine, which are showing strong potential for best in class profiles, to Libtayo, which 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 eighteen months. Key events in the second half of this year will be the presentation of the Libtayo frontline non small cell lung cancer data at at a medical congress, namely ESMO. For the SERD, we expect to have the POC data readout in combination with pavlociclib.
And we would then follow that with our initiation of the pivotal AMERA five study in the frontline metastatic setting. We look forward then in 2021 next year to several readouts, and these would include pivotal results for the SERD eight five nine in the second line, third line hormone receptor positive metastatic setting as monotherapy. We also expect randomized data from the first of our pivotal studies with sarcoleza in newly diagnosed myeloma patients. And to top it off, we expect six potential POCs in the next eighteen to twenty four months for earlier molecules in the Sanofi Oncology portfolio. Among these, I would highlight the potential for a POC study of the SHIP2 inhibitor in combination with the MEK inhibitor, cobimetinib, as well as phase one b proof of principle readout in combination with p d one.
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 p d one 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. And we'll be well along by then with the sub q formulation of Sarclisa. Last and but certainly not least, we expect proof of principle for our non alpha IL-two molecule THOR-seven zero seven in lung cancer. So as you can see, we have an exciting couple of years ahead of us with much, much more to come as molecules from the move from the laboratory into the clinic.
So on Slide 63, we'll wrap up here. And I'll just remind you that Paul talked earlier to this slide, 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 to partner 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 a NASCO analyst event. But with the momentum building in our pipeline, I promise you that it won't be the last.
And with that, I'll hand things over to Felix to start the Q and 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 question. As a reminder, and given that we are running over time, we would ask all analysts to limit their questions to one each, if that is possible, in order to give your colleagues also a chance to get to ask a question. Thank you very much, operator. Can you please open the Q and A session?
The first question is from the line of Vimal Kapadia from Bernstein. Please go ahead.
Thank you very much for taking my question. Vimal Kapadia from Bernstein. So just on Sarclisa, clearly, I appreciate the efficacy differences and great data today. But how do we think about commercialization of the product? I'm just getting just want to get your views on, will the efficacy differences be enough to compete with the DARA subQ in the minds of the physicians?
And then tied to that, the list price that we've seen look like they're similar to DARA. Just to get your thoughts on what price be a lever that you use in the interim until you have your own subcu subcutaneous on the market. Thank you.
Yeah. Thank you for the question. You know, I I think, you know, in oncology, generally, efficacy is what wins the day, and I think that's what's gonna matter most to patients and their physicians. But let me let me ask maybe first Deepmar just to say a little bit about the sub q space since you referenced that and then hand it over to Alexander to talk a little more about the commercial strategy. So Deepmar, just couple comments on the subcu first.
Right. The subcu space is obviously important because we want to provide choices to patients. But 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 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 sarcis subcutaneously, for example, with a device that allows you to inject, I want to say, a more patient friendly manner. And we will move that forward quickly, but 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 than that's where we will have our subcu ready as well. Alexander?
Yes. But before Alex, other thing I just wanted to add is that in the early going with our subcu, we already are confident that the bioavailability of Sarclese is such that this will not be a heavy lift to achieve a SubQ formulation. We see excellent bioavailability. We don't have to do any special tricks like hyaluronidase, etcetera, in order to deliver Sarclisa via the SubQ route. So over to you, Alexander.
Yeah. Maybe I just wanna emphasize a few points. One, you know, subcu, even if it's subcu, patients will still need to go
to the hospital, right, to get the
subcu injection. And even in our own IV program, now we brought the infusion duration down to thirty minutes, actually, with the third infusion, right, which which brought it down quite significantly. And just to to emphasize, you know, 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 got we got a lot of thought into, you know, what would really be the best, you know, commercial strategy, if you want, for Circlusa.
And, actually, we did price it at a slight discount on an infusion basis compared to other available agents in that space. And we believe the commercial strategy really supports the strong data that we've seen in IKARIA and now in akema as well.
Great. Thank you very much.
Next
question, please.
The next question from the phone is from the line of Richard Bosser from JPMorgan. Please go ahead.
Hi. Thanks for taking my questions. Just a question on the third. And perhaps you might talk about the half life and how confident you are in terms of the twenty four hour coverage of the drug on on the basis of what you know. And then just added to that, just, we've seen some other SERDs have some, elements of partial agonism.
So, if you could just give us an idea of the data that you've collected around August to to prove that that's not the case as well. Thanks very much.
Thanks for your question, Richard. No, we're good on both of those, but 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. And I'm not aware of any agonistic effects that we've seen with the agent either, but we're have wide margins as far as degradation is concerned that the doses and exposures we're achieving.
Right. No. We don't have any agonism. And we also have Laurent DeBouche, I think, on the call today if we need more detail than that. But it's a it's clean in that regard too.
It's a complete antagonism and no, you know, mixed or partial agonism component to the molecule. So very, 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 Walton Joe from Credit Suisse. Please go ahead.
Thank you. Joe 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 the first line had some tox issues. Do you think that that's going to be less used by doctors?
And whilst on the same subject, 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.
Yes. Thanks for those questions. Excellent questions. I'll get started a little bit and then ask Deepmar to to jump in. But, yep, you know, with Kyprolis, I think the the issue there is it does seem to be emerging as the most effective backbone therapy.
And so 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. But but 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 BRD. And with the BCMA data, indeed, we 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 different BCMA bispecifics that are in development, and we'll see how those progress over the next few weeks and months. Deepaar, anything to add?
Yes, sure. You're referring to the data of VRd versus KRd. I believe it's and 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, and we need to look at that moving forward.
But these are some of the most important regimens in first line, and these combinations will also be important to evaluate. The BCMA combination is, again, another pillar that we're evaluating, as John has said. And how we look at myeloma therapy is you've got these different pillars of therapy, right? And patients are cycling through some of these combinations. So it will be important to generate data with those different combinations, and BTMA is another mechanism of action that we want to combine with.
Next question, The
next question from the phone is from the line of Peter Verdot from Citi. Please go ahead.
Thank you. Peter Verdot, 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. But 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, is it too early to ask whether the same applies for EU, Chinese or Japanese label discussions? Secondly, on Cyclisa, the KOLs that we've always spoken to have always argued that isatuximab is no worse than DARZALEX. And of course, you have some data pointing in some indication that it might be better. But in the next twelve months, we're going to see Hexabody CD38 data. So 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. So we had two questions. One on Libtayo and what the label is gonna look like. We have had meetings with the FDA, to my knowledge, Deepmar, 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.
Yes. 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. But 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 for non small cell lung cancer. But, clearly, we're we're gonna have good discussions with regulatory authorities about the overall benefit in the MICT population.
Yeah. And, I I think it's the right population because it's the one that actually do have p d l one greater than fifty percent. You know, the 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 p d l one positivity. So if you pull them out, then you're really looking at the the intended population that the study was meant to enroll. Anyway, let's move to Sarclisa, the second gen molecules.
I my colleague, Dmitry Vuishain, who heads oncology discovery for the immuno oncology portion of the portfolio is here with us, and, you know, those molecules came out of his shop. So maybe we can ask him just to comment them on them, and and maybe then, Peter, if if you had I think one of the questions was when might we see some data from them, and Peter might have insights on that. But 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. So 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. So we developed a molecule with enhanced ADCC functionality. And this is already in dose escalation in phase one. I'm sure Pierre will be able to speak to the timing of the first readouts in that with that molecule. And the second one is a completely different mechanism of action.
It is indeed a trispecific T cell engager, which engages CD38 and also through CD3 arm brings T cells in close proximity to multiple myeloma cells 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. And also, incidentally, certain multiple myeloma cells actually express CD28, so we may have enhanced targeting through dual binding to CD38 and CD28 on multiple myeloma cells. So 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 alpha l two, THOR seven zero seven, 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. So that's a nice combination opportunity. And I would just say about the tri specific, I think, you know, that's we're we'll we'll see if we can thread the needle on therapeutic index, but the aspiration would to have be to have 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 of a design. So let's we'll we'll we'll see how it behaves in the clinic. Anything else to add, Peter?
Yeah. No. I think you've covered it, John. We're I I think we'll have the data emerging in 2021 from the bispecific. So we're we're on track for that.
Thanks, all. Super helpful. Thank you.
Alright. 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 of questions. I think different mAbs within a given class do this, and it doesn't always mean that at least to a different clinic versus other members in the class. So if you're confident using class product, can we assume that at some point you'll have legs at least as a comparator arm in some of your trials? If not, maybe just go head to head with it.
Have they come back to Libtayo and this issue of smokers? So you and Regeneron frequently compare data sets to Merck's KEYTRUDA setting, but it is apples to oranges because you guys never smoked smokers. So I'm wondering why you're to do that? And I guess more importantly, does this leave potential slightly narrower label? And do you think it may be 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 D'Mar take that. And then for the Regeneron, I think, Dheemer, you you might take that as well in terms of, you know, the comparison of the different populations and the never smoker issues since you you commented on that already at one a few moments ago. So, Dheemer?
Yes. For the question of Sarkiso, 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're just not focused on the comparison versus other CD38. But 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. And when you also look at the timelines for some of those combinations, they are actually competitive when you look at the first line setting. So 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 anyways 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.
Yes. Thanks, Deepar. Again, Libtayo for us is really a foundational in seeking 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, and I don't have to remind everyone that while we're all excited with what p d ones do for patients with lung cancer, there's still a lot of room for improvement.
Right? There's maybe a or so of patients who have responses. Almost none of them are complete responses. So, you know, the key now is to build with additional combinations on top of that. We we mentioned that we will take our antibody drug conjugate as one combination partner.
We mentioned we're doing SHIP two inhibitor as a combination partner. We're doing TGF beta as a combination partner. We're doing THOR seven zero seven as a combination partner. So all those will be going forward in lung. And so as Libtayo becomes established as at least, you know, one of the background PD-1s that 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 Perry Graham from Bank of America.
So first one is on CEACAM5 and your fast strategy. Based on the data you've got to date, is there a potential here to actually file in last line lung cancer key treater failure patients based on the response duration data you've got already? And then the second is on the SHIP-two. 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 the asset?
Okay. I'm going to let Peter take the CEACAM question and get started also on the SHIP question. Perhaps if we need additional help on that, we've got Laurent DeBusch from our molecular oncology group who was spearheading that collaboration with RevMed, and he can also probably jump in. So, Peter, over to you.
Yeah. And 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. So I'm going to pause on that one and maybe we can circle back because I don't wanna I don't wanna give a wrong answer on that. So maybe either Alex or others with more experience in that realm can comment.
Yeah. I I would say, certainly, the thought has crossed our mind. You know, I I you know, we've been pursuing, I guess, a more traditional path to do a randomized study against the against Taxotere going monotheer it's monotherapy ADC versus Taxotere, but the thought has crossed our mind. DeMar, do you are you knowledgeable of any of the regulatory interactions along those lines?
Yeah. Of course. The the We had some discussions along those lines. Remember, this is a limited data set. Obviously, in a biomarker defined population, which is beneficial, but the data that we have in hand at this point will not lend itself to an immediate submission.
But 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 CHIP two, and I think it was more the timing. So I don't know if we have that in our slide. We have a couple different combos underway, as you're probably aware, ship to with cobembin, ship to with the EGF receptor inhibitor, osimertinib, ship two with the KRAS inhibitor from Amgen, and then a ship two p d one combo are all being explored. I think data will be trickling in next year at various times.
So anything else to add either, Deepa or Peter, on that?
Yes. If I can add, Deepa. The question was also with regard to the strategy moving forward and what are we going to do, obviously, with the molecule it comes to potential Phase III. I just want to mention that we have set up together with our partner, with Revolution Medicine, a program that looks at different, what I call, prototypic questions. So you look at the combination with a KRAS inhibitor together with Amgen, you look at the combination with a tyrosine kinase inhibitor, with the EGFR inhibitor.
We're 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. And we're really in a signal generating stage at this point. If we see activity, convincing activity in one of those areas, that's what you're talking about, generating these data and reading them out then in 2021 and 2022, then we can move very quickly, obviously, because mechanism is attractive. When you think about CYP2 plus KRAS or CYP2KRAZ 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 and 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.
Yes. 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 trope and HER2 in lung cancer, given the latter two have competitive ADCs targeting them? And then given that there could be combinations here, could you help us understand the compatibility with other agents from a tolerability perspective such as checkpoints?
And if I could squeeze in just on the same on the platform, the speed to IND with other cytotoxics, could you help us understand your plans here to further leverage the bystander effect? And when should we expect 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 CEACAM. The data that Peter presented were showing those patients that are c cam five positive who do not have mutations in e g f receptor or alk. So the data there have already split those out to provide a unique population, but there there obviously is some overlap. So I'll let Peter talk a bit more about what he knows or doesn't know on the issues of specifics on the overlap. It's there's several different things to consider, including PD one, as you mentioned, so it makes it a bit complicated.
On the bystander, Peter, if you could start on that, but we have Dmitry on the line here again whose team designed that antibody, and maybe he could help supplement that your your answers there.
Yes. No, thanks, John. So 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, and so it was more of a conservative estimate, but there is going to be overlap. So as far as patient numbers, we try to look for the population that was distinct. As far as combinations, yeah, I mean, there is a Venn diagram.
These are these are not linked in any way, so 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 I will turn that over to Dmitry. We know, of course, how, the payload is is delinked and, that the payload, can permeate membranes. But, 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-onePD L1. We certainly have preclinical evidence that combination of CKM5 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 the checkpoint blockade really improves outcomes. With regard to the next generation of CKM5 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 differentiated from tubulin binder DM4 because as you can imagine, not all tumors are sensitive, intrinsically sensitive to tubulin binders.
So we're very interested in expanding the breadth of anti ctm5 ADCs by conjugating them to novel cytotoxics with a differentiated MOA and also to immunostimulants. And 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.
Yes. Thanks for your question. I just remind you, yes. Cytotoxicity is something that Sanofi has quite a bit of prior knowledge around. So you can imagine that our libraries are full of interesting molecules in that regard.
Operator, do want to on? We have time for another question or two.
One last Sure. Question, operator. Thank
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 eight fifty nine and coming back to ASCO. We obviously saw, as you said, the well tolerated data, but we also saw the PASSIVAL study being presented as well, which showed that with the CDK inhibitors, the effect of the benefit of endocrine versus, on the other hand, aromatase inhibitors was somewhat nullified. I just wonder that how you can put that in the context of how you think about developing the surge in combination with CDK inhibitors in early line first line breast cancer and how potentially that those results could impact your thinking around the trial design? Thank you.
Yeah. No. Thank you for your question. It's it's it's clearly, I think, the question of the hour and the aftermath of those data at ASCO. Peter, why don't you start?
And I think then, Deidmar, you can supplement if there's anything you feel that you want to add on top of Peter's comments. So Peter?
Yes. No, thanks, John. And 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 ASERD, but the strategy, I think, is, has potential to evolve as we move this forward. But, Deepamore, perhaps given your extensive background in this realm, can comment.
Yeah, just briefly two comments. Of all, there has been a variety of surprising data with palbociclib at ASCO, right, between PALLAS and Parsabal. And we are obviously carefully evaluating how this impacts our strategy. For the combination of a hormonal drug with terrible, obviously, in the first line setting, we just need better drugs, right? We need better anti hormonal drug.
There seems to be a ceiling that is seen with palbo letrozole and aromatase inhibitor and then a surge like fulvestrant. We would like to break that ceiling. We feel our drug is a better third. 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.
Then the other component here is that the usage of a surgery, 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 CDK4six to second, third line and beyond. And in some of those areas, obviously, usage will not be with palbociclib or CDK4six inhibitor, but also in monotherapy. So it's important to conduct all these studies, that's where the real potential is for another SERD, both in these monotherapy settings, but then also in combination. We're conducting all those studies, for example, with CDK4six, but then also, as you know, with the PI3K inhibitor, and we'll see those data.
Thank you, Deepmar and Peter. Well, I think that concludes what time we have for questions. We're at the end of the hour now. So 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 and try to make a impact for patients in these four disease areas as a starting point. So we look forward to providing future updates as, as we take this journey.
Thank you.