Hello, everybody. I'm Yongjin Liu, the Global Head of Research Research at Sanofi. My expertise is in immunology. My thirty years research experience has generated three innovative medicine in the clinic in the field of oncology, immunology and allergy.
Hi, my name is Dietmar Berger. I'm the Head of Global Development and the Chief Medical Officer for Sanofi. I'm a hematologist oncologist by training and I'm excited to work on a broader portfolio in Sanofi. I'm in clinical development because bringing new drugs to patients is really what I'm passionate about.
Hi, I'm John Shiver, Head of Vaccine R and D. It's a to participate in this event today. We're doing all we can to accelerate the pipeline and focus on the programs that are most impactful for bringing new vaccines to prevent significant infectious disease. And I look forward to working all together to accomplish that mission. Thank you.
Good morning and good afternoon to everyone, and welcome to Sanofi's virtual R and D event. I'm Felix Lauscher with Investor Relations. The Sanofi leadership team is excited to spend the next two point five hours with you to share Sanofi's unique R and D capabilities, platforms and disease pathways. If you are unable to view the presentation during the event, you can find the slides on the Investors page of our website at sanofi.com. Moving to the next slide.
I would like to remind you that information presented during this event contain forward looking statements that 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 Dans Regis sur Mer Universelle for a description of these risk factors. With that, please advance to the next slide, and let me take you briefly through the agenda for today. Paul Hudson, our Chief Executive Officer and John Reed, Global Head of R and D, will open the day with their introductions. Members of the R and D and commercial leadership teams will then present their respective areas of expertise.
We will have a round of Q and As following the first two sessions and then a second round of Q and As at the end of the presentation. I would like to briefly provide the instructions for our two Q and A sessions. You have two options to participate in Q and A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question.
At that time, please make sure you unmute your microphone. Option two, you may submit your question by clicking the Q and A icon at the bottom of your screen. Your question will be read by our panelists. Before I turn the event over to Paul and John for the introductions, we will share a brief video with you showcasing Sanofi's three recent R and D events as well as a preview of our planned nerselumab event. Today is the fourth in a series of five R and D events highlighting the accelerating pipeline momentum building within Sanofi R and D.
The virtual format of these events demonstrates our proactive approach to use technology to meet with you during these unprecedented times.
If our oral small molecule one hundred sixty eight meets our target profile, it has the potential to deliver against all five treatment dimensions, which would make this brain penetrant BTK inhibitor not just best in class, but the best in disease molecule across the spectrum of MS. One which could potentially offer high efficacy in both relapsing and progressive forms of MS, a strong safety profile plus the ultimate convenience of a once daily oral medication.
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 CEACAM5 ADC, seven zero one and our SERD eight fifty nine, which each have differentiated clinical profiles and offer unique patient benefits large indications with significant unmet need.
Dupixent's unique dual pharmacology not only compares high efficacy with specific systemic inhibition of key upstream and tissue master regulators IL-four and IL-thirteen of the Type two pathway, but also accomplishes this with a strong safety profile. I hope after seeing all these data, you will share some of our excitement. I hope you also get a sense that we're just getting started to take advantage of the unique molecular and clinical profile of Dupixent to make major inroads in a whole range of established and emerging type two inflammatory conditions.
What I learned from this experience is just how vulnerable babies are. If there is anything that we can do to take this one virus and this one sickness off of a new parent's plate, it's worth it.
Well, good morning and good afternoon to everybody. Thank you for joining us for such an important event. As we've mentioned already, we've covered a lot of ground this year. And for me, it feels in particular special to be able to share not only the momentum that we're building, but also importantly to share a wider group of scientists and contributors throughout the next several hours that you can start to see the bench strength that our company has. You know, it's been, ten months for me, and it's been incredible to see the confidence starting to build and the play to win mindset starting to show itself.
At this point, we're digging deeper and looking harder at the things that we have and the things that can change the practice of medicine. We're going more ambitiously. We're going more actively, and we're going in a bigger scale in the areas where we think we can change the practice of medicine. I'm proud and, in many ways, privileged to take up this position at this point as we start to share the hidden gems of our pipeline and continue to add to them. Next slide, please.
So as you saw from the video and as you can see now, we've been on a bit of a journey, and it would have been easy perhaps given the difficult circumstances externally to defer an r and d day or to hold it off or reconvene, later in the year. There's been a couple of important learnings for me from this. One that our science is way better than people think, and we know we have some convincing to do. We know we are still a show me story, and we've gone out and led from the very beginning back in April with the BTKi story to get people to understand just how rich and high quality our science is. We put it out there for debate.
We've been very pleased with how it's been received. And, we've you've got used to seeing and meeting some of our teams. We've done this virtually as we do today, and I think we've shown how agile this company actually is. I think there's a perception that we couldn't perhaps pivot so fast to a new way of working. And touch wood without any technical malfunctions today, I think we'll have shown people what is exactly possible.
Next slide, please. So we identified some key assets back in the Capital Markets Day in December, and we've made extraordinary progress right across absolutely every single area. You know, in the past weeks alone, for Dupixent, we've had approval in six to eleven year olds in atopic dermatitis in The US. We've had approval as recently as last week in China for such a huge unmet need. And, of course, we've had extremely strong data in eosinophilic esophagitis.
And finally, we made the decision after a rigorous hurdle to overcome to go deeper into COPD. We've been saying from the very beginning, we think this is a 10,000,000,000 plus asset, and we do that stood on the shoulders of incredible science and unmet patient needs successfully matched. And so we feel confident that the data that is building will position us very well to deliver on that. We see, of course, the longer term data with fiduceron and the annualized bleeding rates, which will be best in class on a month a true monthly dosing schedule that in itself, we think can be game changing. Our SERD and the POC data we shared at ASCO, again, a strong step forward.
And let's be honest, you know, in the race of the thirds, we were one of three. I really believe now that we are out on our own and one, two, or three years ahead of all of the major competition, some going back to the drawing board. So we think we're gonna play a massive part there. We have a pipeline and a product with venglustat all the way through, we hope, to GBA Parkinson's disease. And, of course, the BTKi one six eight.
What an incredible moment for this organization to have enrolled its first patient having only read out the phase two data at the beginning of at the January, February. What a moment for this organization to show the speed of which it can move. We spent a lot of time looking at our r and d productivity, and I think we all felt the same that while we could go back, forensically and in detail, we'd rather set a new benchmark, a new speed, a new hurdle for us to overcome and match it. I think with the BTKi, four months after phase two readout to have enrolled first patient says that we're serious, we're unencumbered, and we're ready to move quickly. Next slide, please.
So, of course, out of ASCO, we had very competitive data for Libtayo. We went on to have even better data with Sarclisa. So our in hand oncology assets starting to reveal differentiated profiles we think can help take share and offer additional patient benefits. As for avalglucosidase, we achieved breakthrough designation. We are a company that should be getting breakthrough designation because the quality of our science.
For sutimlimab, priority review, again, this is a sort of standard our company should and can and is operating at. And then finally, with our anti c camp five, we go into phase three ahead of everybody else, first in class, a long way ahead, and we think we can contribute in that population significantly. This is a significant amount of progress done over a very short period of time. There's not much changed in the ten months other than our belief that what we have in our hands and being much more specific about what it can do and how to win has stepped a long way forward. Next slide, please.
I'll just finish with this because I think this is quite important. Many companies can put this type of slide up and say, we believe in our r and d function because we understand the patient, the platform. We understand the deep insights required. I don't think that every company does. I think that companies play at different elements of these.
A lot of companies acquire platforms for platform's sake. It will show you today with Thor seven zero seven that we just know how to do platform and how platform becomes medicine. And that's critical for us as we take our pipeline to a renewed level of status in the industry and beyond. So I think we do fully understand what it's like to be a patient. We have deeper insights than, many other organizations, and I think we're starting to understand how to put these things together.
You'll hear from our teams today. So we have momentum. We have a lot to share. We're in the fourth of fifth events, and we're very proud of the progress that we've made. With that, I'll hand over to John Reed, our master of ceremonies.
John?
Thank you, Paul, and welcome, everyone. I'm excited to kick off this virtual R and D investor event program with you today. It's been approximately two years since I joined Sanofi to head the Pharma R and D unit, and a lot of powerful progress has been made in the past two years to position Sanofi r and d for better productivity. Now I know that many of the best community think of Sanofi r and d as a show me story, and I can't argue with you. Looking back, it's no secret that only two of the last 12 new medicines that were launched by Sanofi came from our own laboratories.
When I arrived at Sanofi, more than half of r and d our r and d investments were supporting undifferentiated molecules for which it was difficult to make a real claim of best in class potential. Even we were working on biosimilars, which is an enormous distraction from an innovation agenda, in my opinion. Plus, we had way too few first in class medicines in the pipeline. Our investments were also spread over eight therapeutic areas with more than half of the r and d budget supporting primary care as opposed to specialty care. Prior to joining the company, I had heart to heart discussions with the Chairman and members of the Board of Directors about what we needed to do to transform Sanofi's pipeline and evolve our R and D organization towards industry competitive levels of productivity.
I believe we're on the right path, and we'll share with you today a few of the highlights that illustrate that. Let's move to Slide 10. Let me start by saying a little more about how we are transforming Sanofi R and D. On this slide, you may recognize the four pillars of the company's strategy. I want to just take a minute to run through what the four pillars mean specifically for us in R and D.
The first pillar is focus, focus on priorities. As I mentioned previously, more than half of the Sanofi R and D budget historically went towards supportive primary care indications. But frankly, the company didn't have much that we could say was truly practice changing innovation coming out of that effort. So we made a tough decision to exit research on primary care indications and redeploy those resources for priority indications of oncology, immunology, and rare diseases. Indications where the science is rich with target opportunities and where the path to go, no go decision in the clinic is rapid.
Exting cardiovascular and diabetes at Sanofi R and D has been a very heavy lift. It's a massive transformation of our organization, but we're getting it done. And this frees resources to drive rapid progress in specialty care. The second pillar is called lead with innovation. Now I know every pharma company says they're innovating.
So what does this mean in the Sanofi context? Two dimensions are relevant here. First, a commitment to investing in first in class or truly differentiated best in class molecules. We're moving towards that ambition, and I'll show where we stand in a moment. The second dimension is expanding our drug discovery platforms that enable creation of highly differentiated one of a kind molecules that tackle targets and harness biology in very novel ways.
This has been accelerated by the acquisitions of Ablynx with its nanobody platform and more recently of Synthorix, pioneers in synthetic biology. Our presentation today will cover some of this innovation. I turn next to the third pillar, accelerate efficiency. We have been relentlessly improving our clinical operations and embedding digital and real world data capabilities to bring our new medicines to patients even faster. My colleague, Dietmar Berger, our Global Head of Development, will cover some of this later today.
It makes me especially proud when you see the way our people stepped up to battle against COVID-nineteen, putting clinical trials together in as little as three weeks from concept to first patient randomized, sustaining the drug supply chain through truly heroic efforts, displaying inspiring creative problem solving to keep ninety four percent of our patients on clinical studies, and that represents a portfolio of over 300 clinical trials. It's very impressive what the colleagues have accomplished. When it comes to the final pillar of reinventing how we work, we've substantially simplified our ways of working. We've streamlined governance. We've fostered greater team empowerment, and we're fundamentally reinventing the culture of Snowpier R and D.
Bimar will talk more about this later as well. Now I know that may sound trivial, but the historical context of these changes is frankly a notoriously bureaucratic company with layers and layers of required approvals and reviews and committees. For example, when I arrived at Sanofi, I discovered no less than 33 committees that made demands on the time of our clinical development teams. We cut that to three governance committees. As another example, when I arrived, it took 14 signatures and often several months for portfolio funding decisions to be processed so that a budget could be available may be made available to the team to execute.
Now it takes less than seventy two hours. These sorts of changes in Sanofi's business processes and practices have been incredibly liberating for our R and D people, allowing them to spend more of their time on the pipeline with fewer distractions. Let's move to Slide 11. If we turn to Slide 11, this transformation is allowing us to significantly accelerate our priority assets that Paul mentioned. We provided updates already on Dupixent, on the BTK inhibitor, on our SERD at the made of on We've a foundation our the team our and the We So while we're putting a spotlight on these so called priority molecules, you're probably wondering how is the overall Sanofi portfolio shaping up.
Here are the aspirations we set back in early twenty nineteen when I announced the new strategy for the Sanofi R and D. We are already close to achieving our portfolio reshaping objectives in a little than a little more than a year. As we stand here today, about 75% of the molecules in our development pipeline have the potential to be either first or best in class. Around twothree of the projects in our research pipeline are biologics, which compared to traditional synthetic molecules tend to yield faster cycle times and a higher probability of success. And finally, around two thirds of our development assets are internally derived, which, of course, brings better economics because they're wholly owned, unlike many molecules derived from external partners.
Looking at these metrics on the pipeline, together with the positive news flow that we recently announced for Dupixent, the update provided on our oncology pipeline and data from our investigational brain penetrant BTK inhibitor, I hope that you'll agree with me that momentum is indeed building its Sanofi R and D. Next slide. So let's briefly review the plans for today's program. We have four sections, platforms, pathways, patients, and capabilities that are allowing us to move with greater pace. In the platform section, we'll feature THOR seven zero seven, an engineered version of interleukin two, IL two.
THOR seven zero seven provides a perfect example of how we can use the Synthorix synthetic biology platform to develop highly innovative treatment approaches. In this case, boosting the impact of cancer immunotherapy. In the disease pathway section, we will use venglustat to illustrate how we are leveraging our understanding of lysosomal storage diseases and glycosphingolipid pathway to invent new medicines with potential applications that go well beyond our rare diseases. In the patient insight section, we will explain through fitusiran and BIV001, our expanding focus on patient insights and here illustrating our ability to understand patient needs and deliver practice changing patient offerings, in this case, for hemophilia. And finally, in the capability section or what I like to call the moving with face section, we will share with you how we have applied our scale and our platforms to rapidly battle the COVID-nineteen pandemic.
A lot of information here to digest, but I hope by the end of the event that you'll share my confidence in Sanofi's ability to continue to change the practice of medicine and deliver solutions for patients in need. So without further ado, I now hand over to Yung Joon to start the platform session where we will describe some of our unique drug discovery tools. Yung Joon?
Thank you, John. Good morning, and good afternoon, everyone. Let's move to the next slide. At Sanofi, we have built industry leading technology capacities, which allow our scientists to design better molecules, to expand the druggable universe, and to drive innovation in vaccine design. We are especially proud of three recently added capacity as highlighted here in the blue boxes, all invented and created by our scientists at Sanofi and Sanofi companies.
I will introduce the trispecific antibody platform and the nanobody platform, and Marcos will introduce the Synthorx platform. On my next slide, our protein engineers at Sanofi have created a trispecific antibody platform based on the crossover dual variable domain technology. As you remember, we highlighted our first trispecific antibody for neutralizing HIV in 2017. This trispecific antibody has entered the clinical studies with initial clinical results expected next year. This is a very important validation of our trispecific platform.
Today, I would like to show you a trispecific T cell engager for cancer immunotherapy. As you know, most, if not all conventional T cell engager are bispecific antibody targeting T cell receptor for T cell activation signal one and tumor antigen. Our trispecific antibody allow us for the first time to add a third component, anti CD 28 co stimulation at signal two, which is critical for promoting T cell survival and establishing T cell memory. Next slide. Here, our first trispecific T cell engager two five seven targeting CD 38, a human multiple myeloma antigen.
Because over ninety five percent of all human multiple myeloma express CD 28. Targeting CD 28 not only provides the T cell co stimulation signal too, but also provide a second cancer cell targeting. Our preclinical study recently published in Nature Cancer, showing that our trispecific T cell engager demonstrated a three to four log higher killing potency in vitro in multiple myeloma cells compared to daratumumab. We have already initiated our first in human study for treating relapsed and refractory multiple myeloma and non Hodgkin's lymphoma. We hope this twice specific T cell engager will achieve the level of efficacy of CAR T.
This is super exciting. On my next slide. Now we would like to show you a titra specific nanobody based T cell engager to illustrate the power of our nanobody technology. Because nanobody is one tenth the size of a conventional antibody, we can easily target more than three. Here, our first target is anti human serum albumin, a clinical validated technology for half life extension.
This nanobody is linked to two nanobodies targeting tumor antigen one and tumor antigen two. Targeting two tumor antigen is far superior than targeting one because dual targeting can provide stronger tumor binding and reduce binding to healthy normal tissues. These three nanobodies is then linked to a T cell engager such as anti CD three or anti TCR. Because nanobody can be expressed in yeast, our technology offers faster production cycle time at a lower cost. Importantly, we have one of the broadest and the dominant IP in the field of nanobody.
In summary, I have introduced two T cell engagers to highlight our trispecific antibody platform and nanobody platform. I would like to emphasize that our scientists are making a very robust pipeline for targeted therapy across oncology and immunology. Last year, Sanofi Research delivered three multi specific nanobody clinical candidate for the development. We expect to deliver three to five clinical candidate using these two multi specific technology annually for the next several years. Let me now hand over to Marcos who will talk to you about Synthorx, the latest addition to our toolbox.
Marcos.
Thank you, Yunjung, and hello everyone from sunny San Diego. Let me start by saying that at Synthorx, we're very excited about joining the Sanofi family and the quest for innovative medicines for patients. As shown on my first slide, the Syntorin platform is based on novel synthetic biology. The unique achievement of our scientific founder, Doctor. Ronsberg, and his team was to expand the genetic alphabet with the creation of a new DNA base pair that we term X and Y.
By adding X and Y to the natural DNA base pairs, AT and GC, we can expand the number of amino acids that can be used to make proteins from the naturally occurring 20 to up to 172. This vastly increases the chemical diversity available for fine tuning the pharmacology and drug properties of biologic therapeutic agents. And as shown on the next slide, we do this employing an E. Coli strain that has been a workhorse for decades for protein production of biologic drugs such as insulin. The strain is likely engineered to replicate plasmids containing the new XY base pair and transcribe mRNA and tRNA containing X and Y to be able to produce proteins containing a new amino acid at the specified position by the new XY VSPR.
Our first application is site specific pegylation of cytokines at the new amino acid residue. Cytokines are very powerful movers of immune function, yet none of them have critical drug properties and in most cases pegylation addresses that. An example is shown on the next slide. Aldeslukine, clinical IL-two, is an approved cytokine for the treatment of metastatic melanoma and renal cell carcinoma. In fact, Aldeslukine was the first immuno oncology drug driving durable responses before the term was coined much later.
But aldesukin is hard to dose because of its dual pharmacology. It induces the proliferation of tumor fighting CD8 T and natural killer cells, but it also promotes the proliferation of suppressive CD4 regulatory T cells or Tregs and activates type II innate lymphoid cells and eosinophils, which leads to eosinophilia, the driver of vascular leak syndrome or VLS. The induction of Tregs and cells triggering VLS is caused by IL-two engagement of the alpha chain of the receptor. And this is why multiple companies are developing not alpha IL-two tracks for immuno oncology indications. Next slide, please.
Our solution to the dual pharmacology of IL-two is THOR-seven zero seven, a single site specifically pegylated IL-two via via conjugation to a new amino acid residue in THOR-seven zero seven that blocks engagement of the alpha chain of the IL-two receptor, as shown on the left panel of the slide. But this is done without affecting engagement of the receptor signaling complex on CD8 T and NK cells. And because of that, THOR-seven zero seven maximally expands those cells without expanding Tregs or inducing eosinophilia, both in animals and more recently in patients, as I will show you in just a few minutes. While we were at it, we discovered a second IL-two variant, THOR-eight zero nine, currently in preclinical development. THOR-eight zero nine is tuned for weak engagement of the IL-two receptor signaling complex, as shown on the right panel cartoon, unless the alpha chain of the receptor is present at high levels.
And, of course, that only happens on Treg cells. And because of that, THOR eight zero nine selectively expands Treg without activation of CDAT or NK cells and shows therapeutic efficacy in an animal model of delayed type hypersensitivity. And the importance of this is that Treg expansion is of value for the treatment of autoimmune diseases to restore tolerance to autoantigens that elicit pathogenic responses. What is common to both THOR seven zero seven and THOR eight zero nine is that the uniquely positioned PEG chain on this IL-two variants confirms two important attributes. First, it fine tunes IL-two pharmacokinetics for optimal pharmacodynamic response and second, it shields the new amino acid from immune surveillance, eliminating the risk of anti drug antibodies.
And we have by now clinical confirmation that's the case. Next slide. Very briefly, we have previously demonstrated that THOR-seven zero seven shows the expected not alpha IL-two pharmacological profile driving in monkeys substantial expansion of lymphocytes with no eosinophil expansion. That's shown on the right panel of the slide. And moving to the next slide, today, I'm very excited to present for the first time early clinical biomarker data from our first in human study, HAMR.
And this data confirm what we have seen in our preclinical models. This slide shows promising early biomarker data comparing to the clinical stage IL-two therapeutics from Nektar and Roche. Already at the second dose level, sixteen micrograms per kilo, THOR-seven zero seven elicited robust expansion of tumor fighting CD8 T and NK cells comparable for CD8s or above for NKs, the one observed with the recommended Phase two dose of the Roche molecule and above that of nectars for both cell types and without significant expansion of Tregs and eosinophils as shown on the right panel of the slide. As I mentioned before, we have not observed ADAs in any patients. Importantly, those biomarker data allowed us to move THOR-seven zero seven into Part two of the HAMR study, combination with PD-one checkpoint inhibitors, and of course, we're very excited about this.
And on the next slide, we're showing the competitive landscape for IL-two drugs. Comparing to other IL-two molecules, we are confident that THOR-seven zero seven has the potential best in class profile when we take into account all critical drivers of the ideal target profile. Not alpha is specificity for receptors, sustained peripheral exposure, dose inconvenience, differential impacts on effector versus regulatory T cells, no observation of vascular leak syndrome, good tolerability, and low risk of anti drug antibodies. Next slide, please. While I have focused so far on pegylated cytokines in taurines, our precision cytokines, our expanded genetic alpha platform has the potential for much wider application in protein therapeutics.
Our next area of focus will be multi specific biologics to enable the design of biologics with geometry that is not possible to attain via recombinant DNA methods. Specifically, we're looking to combine the benefits of our platform with the nanowordic platform that Junjun touched on. And moving to my final slide, next slide. I want to leave you with key take home messages. First, our unique expanded genetic alphabet technology gives us the ability to turn interleukins into precision drugs for oncology and autoimmune diseases.
Our most advanced candidates, THOR-seven zero seven and THOR-eight zero nine harness the dual pharmacology of IL-two, respectively targeting not alpha and decreased beta approaches to fine tune receptor binding. In the case of THOR seven zero seven, to upregulate tumor killing cells without expansion of immunosuppressive regulatory T cells and eosinophils, and in the case of THOR eight zero nine, to suppress autoimmunity without upregulation of effector cells. As I show you, THOR-seven zero seven is already in the clinic and biomarker data suggests it could become the partner of choice for checkpoint inhibitors, and we expect Phase I results and the recommended Phase II dose by 2021. Beyond our IL-2s, we will have further precision cytokines entering the clinic over 2021 to 2023. And last but not least, the Syntaurs platform has the breadth and power to deliver for patients multiple preclinical candidates in the coming years, including nanobody targeted cytokines, nanobody drug conjugates, and multispecific nanobodies.
And of course, we're very excited about that. And with that, I would like to hand it to John Reed to take you into some of his focus on disease insights. John?
Thank you, Marcos, and it's great to have you on the Sanofi team. Having heard now about the unique drug discovery tools, let me introduce this next session where we'll focus on how we can leverage a deep understanding of the biology of disease pathways to discover new medicines that are applicable to multiple disorders. Let's move to slide 29. When I ask myself where do we have core competencies in disease biology that stand out among peer pharma companies, I see differentiated strength in two areas, human immunology and monogenic disorders or so called rare diseases. The umbrella of human immunology shown on the left of this slide encompasses our work on vaccines, immuno oncology, immunology and inflammation, multiple sclerosis, and hematology.
The science of immunology unifies Sanofi R and D across all therapeutic areas, whether seeking ways to dial up the strength of the immune system for fighting cancer or protecting against pathogens, or whether striving to dial down the immune system for autoimmunity and inflammatory diseases. In each of these therapeutic areas that are touched by Immunoscience, Sanofi has already marketed products or will soon have a marketed product, reflecting our historical success in taming the immune system through the medicines we've developed. On the right, Sanofi is a long standing market leader in rare monogenic disorders through our Genzyme heritage. Let's move to the next slide, Slide 30. First, I want to touch on immunology.
On this slide, we show an extremely overly simplified depiction of just some of these cell types that play major roles in the immune system and their interrelationships. The cell types include on the left, B cells and their progeny responsible for antibody production or so called humoral immunity for protection against many types of pathogens. In the middle are shown various types of T cells, both immunostimulatory, t h one, t h two, t h 17, and immunosuppressive regulatory T cells. Altogether, they form the foundations of cellular immunity playing master regulator roles in immune responses, both beneficial and pathological. At the lower right are depicted effector cells, particularly cytolytic killer T cells and natural killer or NK cells that provide our principal defense against virus infected cells and cancer cells.
And then various types of innate immune cells also figured prominently as either upstream or downstream protectors against pathogens or culprits in disease context. And here, we just show macrophages and eosinophils as representative examples. Next slide. Now overlaying where our approved and experimental medicines come into play, you immediately get a gist of the breadth and depth of the of Sanofi's commitment to immunoscience. By intervening at critical nodes in these complex immune networks, we can selectively modulate very specific behaviors of the immune system.
And with that, we aim to either bolster protection from pathogens and cancers or to squelch the overreactive network connections that account for autoimmunity and chronic inflammation. From this work has already come several approved products, including DUPIXENT and KEVZARA for chronic inflammatory diseases, ABAGIO and LEMTRATA for multiple sclerosis and Libtayo and Zarquiza for cancer, as well as several molecules currently in development, including the brain penetrant BTK inhibitor for MS that we've talked about, including the nonalpha engineered I l two that Marcos just presented for immuno oncology, and many others shown here and not shown here, and including our work on vaccines. My point is when you think of Sanofi R and D, think immunoscience. It is a core competency of our company. Let's move to Slide 32.
Now in monogenic disorders, Sanofi Genzyme pioneered this field, starting with enzyme replacement therapies to address a range of lysosomal storage diseases. Slide 32 shows how we built on the launch of Serizyme for Gaucher disease way back in 1994 to develop over the past two decades a portfolio spanning multiple rare genetic diseases. In our pipeline today, we are progressing lipidase alfa, the first enzyme replacement therapy for Pneumon Pig disease, And we just presented positive results from the Phase III COMMENT trial of alpha glucosidase alfa in late onset Pompe disease, which represents a next generation more potent enzyme replacement therapy. So with that background, Corinne and Pablo now are going to take you through the development of venglustat in several rare and not so rare diseases. Their presentation will highlight how Sanofi's deep insights into lysosomal biology, emanating from our decades long commitment to lysosomal storage diseases, has opened new doors of opportunity for tackling a broad range of illnesses.
We expect this to be a recurring theme as we leverage our expertise in rare diseases and parlay it into novel ways to tackle common diseases. So over to you, Karim.
Thank you, John. It's really a pleasure to be here today and talk about Venglustat. Let's move to the next slide. Venglustat is an oral small molecule invented by Sanofi scientists, one of them, my colleague Pablo here today. So to start, lysosomal storage disorders are rare monogenetic disorders where patients are born without certain enzymes located within lysosomes.
Absence of a specific enzyme leads to the accumulation of lipids called glycosphingolipids. The most common approach to treat these disorders are enzyme replacement therapies and substrate reduction therapies. Venglustat is an oral substrate reduction therapy that works by inhibiting glycosylceramide synthase or GCS, which is a central regulator of glycosphingolipid metabolism. The same biology has been implicated in some not so rare diseases with very high unmet needs. For example, polycystic kidney disease and Parkinson's disease with GBA mutations.
Next slide, please. This slide shows the broader role of glycosphingolipids. Glycosphingolipids are critical components of cell membranes and have multiple functions, which include modulating membrane proteins, cell surface signaling, and regulating pathways. Given this broad role, you can see why the accumulation of glycosphingolipids had a profound impact on patients with lysosomal storage disorders, but potentially also other disorders where a disturbance of of glycosphingolipid metabolism has been implicated. Next slide, please.
Yeah. Here, we depict how GCS acts as a central regulator of glycosphingolipid metabolism. This is a a very complex diagram, but the key take home messages are that by inhibiting GCS with venglustat, we can potentially intervene in the g l one, g l three, and GL two pathways that these respectively have been implicated in Gaucher type three Fabry and GL two gangliosidosis, as well as in autosomal dominant polycystic kidney disease and in patients with Parkinson's disease with GBA mutations. Here, this table shows that if we achieve our target profile with venglustat, it will be the best in class oral GCF inhibitor across a range of treatment dimensions. As well as the convenience of a once daily dosing, venglustat is highly selective and potent.
Once It effectively crosses the blood brain barrier, and it has the potential to address a broader range of glycosphingolipid pathologies than currently approved GCS inhibitors do. All this translating into the potential to help more patients. On this slide, we illustrate how we intend to leverage venglustat's mode of action in the central nervous system and in key organs. Because of its ability to penetrate the brain, we believe venglustat will have the potential benefit in two rare lysosomal storage disorders, namely Gaucher type three and GM two gangliosidosis. In each case, there are no currently approved treatments.
We also believe that Venlustat could offer new treatment option for Fabry since patients not receiving enzyme replacement therapy account for around forty percent of the approximately three thousand diagnosed Fabry patients in The US. In addition, Fabry patients with lower disease burden are often completely undiagnosed. On the right side, you can see that the eligible patient numbers become dramatically larger when we move beyond lysosomal storage disorders. The number of Parkinson's patients with GBA mutations are around seventy eight thousand in The US. Venglustat also potentially addresses polycystic kidney disorder with PKD one or two mutations.
ADPKD is, in fact, the most prevalent monogenetic disorder and affects around a hundred and forty thousand patients in The US, representing a major unmet need and an opportunity to reach more and more patients. Next slide, please. Here, we show proof of concept that has been demonstrated in two Phase II studies. On the left, venglustat is associated with an increase in blood oxygenation level dependent signaling in Gaucher Type III patients. Change in signaling is a surrogate marker for increased functional activity in the brain and also supports our belief that venglustat is not only present but also bioactive in the brain.
On the right, you can see a clear trend towards reduced lysosomal GF3 storage in Fabry over three years, suggesting an increased and sustained beneficial effect of venglustat over time. I should also add that venglustat's safety profile in these early clinical studies has been reassuring. We have by now treated over two fifty patients and some for several years. This gives us confidence as we move into studies in younger patients since we acknowledge the importance to intervene early in the disease progress. Next.
Yeah. Thank you. My last slide describes the transformative potential of Anglustat in polycystic kidney disease. Here we see scope to improve patient outcomes compared to current standard of care Tolvaptan. Tolvaptan, in addition, in sixty nine point five percent of patients in the clinical trials, causes a side effect polyuria, which is very unpleasant and poses a risk for dehydration.
And this reinforces the need for new treatments to these patients. On the right of this slide, you can see that in the denglustat arm, kidney volume barely increased over the treatment period, whereas there was substantial rise in the untreated arm. This shows effect on the disease by venglustat in this mouse model. So based on these promising early data, we initiated the staged PKD phase three study last year. This is a study in six forty patients that in stage one uses total kidney volume as the primary endpoint, which by itself may be enough for an accelerated approval in US.
In the larger second stage, we look at endpoints associated with renal function for full approval in The U. S. And rest of the world. We have we're happy to say that we have completed enrollment in the stage one and have initiated stage two based on the favorable safety and tolerability we have seen to date. And we expect the first results by end twenty twenty one.
Let me now hand over to Pablo, who will talk to you about our plans for venglustat in Parkinson's disease with GBA mutations. Please, Pablo. Thank you.
Thank you. Thank you, Karen. It's it's great to be able to share the progress with Benglustat in all these indications. It's been a long journey, and it's great to see how Benglustat is starting to help our patients declaring clinical proof of concept as we anticipated from our preclinical studies. Now we move to slide 42.
I'm really excited to also have the opportunity to discuss why venglustat could become the first disease modifying therapy for GBA Parkinson's disease. The way I see it is a successful therapy will target the right patient with the right mechanism and the right molecule. And from a clinical point of view, GBA mutations are not only a risk factor for Parkinson's disease, but more importantly, they're associated with a more aggressive form of the disease. GBA mutations are present in about five to ten percent of Parkinson's patients, depending on the ethnicity, and the graph on the left showed the increased frequency of dementia in GBA carriers. Importantly, the accelerated disease progression in patients with GBA mutations has been observed on both motor and non motor features, which brings me to my next point, which is in the middle scheme.
From a mechanistic point of view, the acceleration of the disease can be explained by this pathogenic feedback loop, whereas the decrease in glucose herbicides activity, the GKase activity, due to the GBA mutations will lead to glycosphingolipid accumulation, which can in turn help the aggregation of alpha synuclein. The aggregated alpha synuclein can then further reduce enzymatic activity and propagate the vicious cycle. We have robust scientific data demonstrating that the reduction in glycosphingolipid by GCS inhibition can disrupt the feedback loop and reduce the pathology and even reverse phenotypes in disease models. Thus, venglustat has the potential to exert a genuine disease modifying impact in GBA related Parkinson's. And lastly, we have the right molecule to target the CNS.
You can see on the right, we show evidence of target engagement in the CNS from the phase two MOVES PD study. This was the first industry sponsored study in a genetic form of Parkinson's and includes two forty patients carrying GBA mutation. The graphic shows a clear dose dependent reduction in GL1 glycoposing lipids in the CSF after four weeks. And the study is now fully enrolled, and we expect proof of concept readout in the first half of next year. If positive, we'll move swiftly into a phase three.
Next slide, please. I want also to extend my comments for those patients with sporadic Parkinson's disease who do not carry a GBA mutation, yet they still have glycosphingolipid pathways altered. In these patients, we've been gathering preclinical evidence of the potential therapeutic benefit of venglustat. Here we have demonstrated that the loss of GKase activity, the enzymatic activity, in patients with synucleinopathies that do not carry GBA mutations, such as sporadic Parkinson's and Lewy body dementia patients, as seen on the left. In addition, by blocking GCS, nucleoside from myosin taste in model systems carrying wild type GBA alleles, in this case, we can reduce the conversion of alpha synuclein to toxic oligomers, as seen in the middle graph, as well as improve behavioral phenotypes in animal models of disease, as seen on the graph on the right.
As a consequence, when we moved to our phase three program, FDA has recommended that we include about twenty percent of patients with GBA mutations to test whether therapeutic intervention with venglustat might be more broadly applicable to the overall idiopathic Parkinson's community. In the next slide, we have additional evidence of the critical role of lysosomal and glycosphingolipid pathways from the genetics of Parkinson's disease. In these slides, we show many of the known genetic drivers of Parkinson's, LRRK2 mutations, alpha synuclein, GBA, and the lysosomal storage disease gene, and how they conspired to reduce GK's activity and lysosomal function. By inhibiting glycosphingolipids with venglustat, we could potentially restore normal lysosomal function and alter disease progression. And at Sanofi, also, the patient centric innovation means more than just novel molecules and mechanisms, as I've just explained.
We're also advancing our digital footprint. The ambition is to expedite clinical development in Parkinson's by using what has the potential to be the first validated digital endpoint for Parkinson's disease. We call it the PD FID, the Parkinson's Disease Functional Impact Digital Instrument. This is a digital tool which measures clinical endpoints and patient reported outcomes, and may allow us to better capture disease progression and achieve statistical power with fewer patients. The concept is based around a smartphone app and a device worn under wrist to capture multiple parameters of motor functions, including components of the UPDRS, the Unified Parkinson's Disease Rating Scale, which is the benchmark outcome, as well as dyskinesia, gait, balance, and patient reported outcomes.
In my next slide, this is my last slide, summarizes where are we currently stand with venglustat. I'm extremely proud of how far we've come from our initial discoveries that are now showing proof of concept in rare diseases and with diseases patients, and also a great promise to help even more patients. In the classic lysosomal storage diseases, we're running a phase twothree Gaucher type trial in GD3. We're starting pivotal phase three in GM2 ganglosidosis and preparing a phase three for Fabry. We expect to make regulatory submissions in all three indications during 2023.
For Parkinson's, the MOVES PD study I just discussed will produce proof of concept data by the first half of next year. If this supports late stage development, we will be targeting regulatory submission by the 2025 timeframe. And finally, for ADPKD, we expect pivotal results from the stage PKD trial by the end of next year, and we plan to file early in 2022. In closing, I hope Karin and I have provided with a better understanding of why Sanofi selected venglustat as one of the six potential transformative assets at the Capital Markets Day last December. We will be happy to answer any questions, and I will hand it over to Felix to start the Q and A.
Thank you.
Excellent. Thanks, Pablo. Let's move to Q and A now. For this first round of Q and A, we have twenty minutes allocated, so please limit your questions to only one. Natalie, can you please remind everyone of how to ask questions?
Thank you.
Thank you, Felix. So you have two options to participate in the Q and A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. Please make sure your microphone is unmuted.
Option two, you may submit your question by clicking the Q and A icon at the bottom of the screen. Your question will be raised by our panelists. Now we will take the first question from Wimal Kapadia at Bernstein. Wimal, please go ahead.
Great. Thank you very much. Wimal Kapadia from Bernstein. Kind of to ask on one on THOR-seven zero seven. So you highlighted several interesting differentiated factors of four seven zero seven versus peers, and in particular, the reduced CD four Treg bias, you know, would retain stimulatory activity of the CD eight and the NK cells.
But my question is why? Is it driven by the design of the product, I e, the single peg chain compared to the Nektar product, which is a, you know, nonspecifically linked to six? Is that what drives the sustained activity, or is it because some of your peers have conjugated to the anti FEP antibody? Just curious to explain, you know, what drives these differences in in the outcome. Thank you.
Yeah. Thanks for your question, Waimal. Yeah. It really has to do with the where the peg chain was positioned and the fact that it's an irreversible conjugation to that unnatural amino acid. Let me let Marcos maybe expand a little bit on that.
Sure. Pleasure. Great question. Indeed, the positioning of the PET is an irreversible chemistry. It doesn't come off, and it blocks alpha.
And this allows to substantially increase the exposure of THOR seven zero seven relative to what was possible with aldesleukin. And because of that, the high exposure at the target CD8 T and NK cells drives what I would call an optimal pharmacodynamic response for the expansion of those target cells without expansion of regulatory T cells or eosinophils.
Great. Thank you very much.
Sure.
The next question comes from Graham Parry from Bank of America Merrill Lynch. Graham?
Great. Thanks for taking my questions. It's actually a broad high level question, if I've only got the one. So you'd laid out, John, I think your first full year results, a broad range of discovery platforms at Sanofi. So you talked about some of the in house RNA, gene therapy, cell therapy, nanobodies, the monoclonal, bispecific, tris pecific antibodies, etcetera.
You're focusing in today a little bit more on select ones. But perhaps if you could just give us a feel for what the breadth of those discovery platforms you have now, which ones you've dropped? And in particular, I think gene therapy is one. You've talked a lot about having capabilities but needing to build on. So perhaps just help us to understand where you might need to expand further as well.
Thank you.
Thanks for your question, Graham. I'm gonna save the gene therapy one for later because we do have a slide, and we'll make some brief comments about our our strategy in gene therapy at the end of the program. So we'll come back to that. But with respect to the other platforms, I I think I'll let Yong Joon Lu perhaps remark on that, and maybe I'll then supplement his comments after Yong Joon describes. Yong Joon?
Thank you, John. It's very good question. So, basically, the two platform I highlighted, they are really critical to design drug that can target multiple target in one molecule. If we think about, I might need some of the best selling drug, you always hear poor responder. You always hear patient become refractory.
So we believe market multiple targeting to stop the vicious circle of the pathology is very important. So we have this very unique technology in house. We can target three. I show you. We can target four.
And if you look at the the the power of nanobody, you can link up to eight nanobody in one molecule. So for us, this is a very important platform across our immunology and immuno oncology. We are heavily invested in making out the next generation molecule within these two technology. Another area we are moving into is a structure based drug design. You know, I think that's very important.
There are many example of non drug bulk targeted become druggable. So we invest heavily in structured biology, in artificial intelligence, in collaboration with DNA encoded library. So we want to convert non drug bulk target into drug ball target. We also invest in protein degradation, and and we want to be sure our scientists are not limited by technology. Thank you.
Yeah. Thank you, Yun Yun. I guess maybe the other two things I would add, Graham, is that we're excited about the momentum building in the antibody drug conjugate space. We at the ASCO session, the the satellite event we did there, we featured seven zero one, our first antibody drug conjugate to move into late development from Sanofi. So we're anticipating doing more things with that platform.
And, for example, expanding it beyond conventional IgG antibodies into the nanobody platform where we can we can really tune the pharmacology exactly where we want it from either very short lived to very long lived molecules, and we think that'll play well in terms of an antibody drug conjugate. So, you know, that's one area. And then we're building more and more expertise around in the small molecule space around the greater technology where one makes molecules that grab the ubiquitination machinery and and aim it at a desired target. So we're doing more in that space, both internally and through external partners. Let's move on to next question, and we'll come back to that gene therapy thought at the end of the meeting, Graham.
The next question is from Pete Verdult at Citi. Pete?
Pete Verdult, Citi. Just for John, Marcus or Jung, I mean, you're clearly wanting to showcase these two platforms. Could you perhaps give the audience a bit more a steer when we're gonna see data for THOR seven zero seven, when eight zero nine might actually enter first in human studies? And on the nanobodies, are we could we get any data in 2021? Just wanna get a better steer as to how far into next year we need to wait before we see more data from these on these assets.
Thank you.
Yeah. Thanks for your questions, Peter. Marcos, why don't you take the first session on THOR seven zero seven and THOR eight zero nine? And then, Yungjun, you can give an update on when we think some of these multispecific antibodies will start to see the the the light of day in terms of appearing in the clinic. So, Marcos, over to you first.
Sure. We were delighted to present for the first time biomarker data today, early biomarker data. We intend to present further on initial biomarkers later this year. And next year, we're gonna present more complete biomarkers together with dose of the dose escalation in combination with p v one checkpoint inhibitor. And then we expect to see proof of concept for the monotherapy arm in solid tumors in 2022.
With regard to THOR eight zero nine, we expect to file an IND next year to then move into dose escalation in healthy volunteers.
Yeah. The IND would have been filed this year had it not been for COVID, Peter. So we're, you know, a couple months behind where we wish we were, but but should get in the clinic early early next year. Yongjoon, the multispecific nanobody nanobodies, up there?
Yeah. So you remember we start to integrate Ablynx to global Sanofi research exactly two years ago, and this has been a very happy marriage and a productive marriage. In 02/2019, we delivered three multi specific nanobody clinical candidates. We expect one will enter the clinic this year, and two will enter the clinic next year. And it's a such productive collaboration.
We expect the two platform will deliver three to five clinical candidates every year for the next several years. It's very exciting.
Thank you.
Thanks for your question, Peter. Next question.
Next question is from Richard Vosser at JPMorgan. Richard? Richard, can you please mention?
Yeah. Apologies. It's my fault. Thank you very much. You can probably hear me now.
So just I know it's early with 07/2007, but on the basis of the early data, perhaps you could maybe put it into context for us relative to some of the other agents that are going with p d ones and p d l ones, such as TGF beta or TIGIT, etcetera. I know Roche has and you've compared your product to to to the Roche product and IL two, and they're pushing forward with TIGIT. So just some context of the maybe the relative benefits here. Thanks very much.
Sure. Yeah. Maybe I'll make a few comments, but then I would ask either Marcos or Yungjun to perhaps chime in and supplement. But, you know, there are several mechanisms one could think about in terms of trying to improve the ability of the immune system to attack tumors and particularly solid tumors where it is a higher bar than the the liquid tumors or the hematopoietic malignancies. We think IL two is, you know, is really one of the most attractive opportunities there because of the expansion of and and when you have a well engineered version of I l two, which frankly has I l 15 like qualities, the ability to selectively expand the desired cell populations of vector t cells and k cells really allows us then to sort of dial up or amplify the immune response.
And we do intend to exploit both the T cell and the NK cell sides of that. On the NK side, for example, which I think is, you know, been somewhat overlooked by the field, we'll we'll do combinations with ADCC competent antibodies like our own Sarclisa and are planning studies in combination there to boost up the NK cells that hopefully would then allow that antibody that works in part by recruiting NK cells to attack the myeloma. We'll play that side of the equation as well as with multi specific NK cell engagers, And then we'll play the T cell side of the game as well in combination with T cell engagers, in combination with p d one, etcetera. We do also have other mechanisms in the clinic. We have a TGF eight in the clinic that is also potentially attractive with respect to reducing the production of of immunosuppressive regulatory T cells as well as perhaps helping T cells to better traffic into tumors, a few mechanisms of relevance there.
And over time, I think we'll exploit others as well. But we we're really quite excited about IL two as a very central player in both the T cell and NK sides of the attack on tumors. Marcos, Yungjun, anything to add?
Yeah. Perhaps very briefly, as as John is saying, IL-two has the potential to become a backbone agent and THOR seven zero seven because of its PV responses is really a very exciting agent. And it can be combined really with any mechanism that increases discovery of tumor agents as well as mechanisms that address the suppressive tumor microenvironment because THOR-seven zero seven is a prime activator of T cells and NK cells. So we believe that multiple combinations will be possible and will be explored as appropriate agents appear for target indications.
Yeah. So I regarding a PD one combination, we aim to treat PD-one nonresponder. So one example is our collaboration with the BioNTech. We have MRE technology. We can put four immunostimulatory molecule into one go.
So this is in phase one, and we have the second generation coming. And, also, we have a series of multispecific antibody targeting tumor cells or targeting additional immune regulatory molecule.
Good. Well, I'm reaching out help address some of your thoughts there where you may be again to use a metaphor of the brakes and gas on the car of the immune system trying to get it to attack cancer or to, you know, to drive to better results for cancer patients. We're trying to play both sides of that. We've been putting a lot of the emphasis on the gas pedal with things like IL two, taking the brakes off with things like one tone into that. We think you're really gonna need to play both sides of that to ultimately be successful.
And so that's kind of the way we're we're we're attacking that space. Let's let's go to the next question.
The next question is from Shimiz Fernandez at Guggenheim. Shimiz?
Thanks very much. Just got off the unmute. So my question actually is on venglustat. It looks like clearly an exciting opportunity. What would be the risks on the ADPKD side in terms of the data?
The the the early data looks, you know, pretty compelling, you know, and and, obviously, good animal models there. But if you could just walk us through some of the the risks that that you see to to that indication, you know, from a as as it relates to the the that product and and the mechanism. Is it, you know, clinical risk more from the perspective of the the patient population and recruiting? What have you done to sort of maximize the likelihood of success? Thanks.
Alright, Shamey. Thanks for your question. I think what I'll do is ask Pablo first just to talk about the by biological rationale, any risk associated there. Of course, you know, the the data there are contingent on animal models. But although I'm generally not a big fan of animal models, I would say this is this is one of the cases where one's confidence, I think, comes out a bit higher because, you know, you make exactly the same mutation that causes autosomal dominant polycystic kidney disease in people, and mice get exactly the same disease.
So so we we we feel more confident than usual, I would say. So let me ask Pablo to just touch on that element. And then, Corinne, you could talk on the clinical development program and the endpoints we're using, etcetera. So Pablo, over to you first.
Yeah. Thanks thanks, Chaims, for the the question. From a mechanistic point of view, John, you hit it the the the nail on the head. We tested it in several models, three models of CKD with different mutations that are the same mutation that's in the human. We know what the mechanism is working on the cilia.
And we know how the cilia reacts to the glycosphingolipid changes. And when we test in these animal models, we see a reversion of the phenotypes. So, that's from from a mechanistic point of view. There's a good translatability into the human patient population. Then the clinical development, it's a it's a different risk that I'm not gonna get into.
So, yeah, Corinne, do you wanna take the question as pertains to the clinical development plan?
Yeah. Of course, it's hard to say before we've seen the data, but I I I think I mean, the the disease pathology is clear. So so we have, you know, the specific mutations. We know that kidney volume increases and and and then kidney function decreases, and and you go to end stage renal disease if left untreated. So I think the endpoints are are very clear, and and and we are hopeful.
We we have initiated stage one where we think that kidney volume or we have agreed with regulators that kidney volume is an good endpoint to for for accelerated approval in The US. And we have already initiated the stage two based on on an external view of the stage one data. So so I I I think we feel as confident as we can feel about the clinical path forward.
There is no Thanks thanks, Corinne. I think the team's also really performed heroically to get these studies recruited in the face of a pandemic. We finished the recruitment on the so called part a of the program where we're using total kidney volume as the endpoint. That's fully recruited. We've started the second study, which will use glomerular filtration rate as the as the endpoint, which will be needed outside The US.
So, you know, despite the pandemic, you know, the clin ops team, etcetera, has done really a fabulous job in keeping patients rolling onto this study. And I think it also reflects the unmet need out there. Mhmm. There's not a lot to offer these patients. Not a lot is very attractive solution for their for their issues.
So so we're fingers crossed. We're optimistic, though, that we can make a real difference for patients with this disorder.
Okay, John. Good. John, at this point, I think we have to move on to section two to stay within our timelines, section two of our presentations. And I would like to turn the event over to Vanessa to introduce the patient insight session of today's event. Vanessa?
Thank you, Felix, and good morning, good afternoon, everyone. I hope you still have energy and have stretched your leg as I'm personally very excited to have the opportunity to discuss with you all today about the amazing hemophilia community, the needs, and what we hope our exciting pipeline will bring to these patients. And as patients are at the center of everything we do, let's listen to them first.
Some of the challenges with hemophilia are that I have to take time and infuse, which can sometimes be hard because in the mornings you can be in a rush and that's when I would usually do it. Another challenge is having to not be able to play all the sports that my friends do because they sometimes will
be playing football and stuff. I choose hobbies that don't require a lot of movement. I'll play video games or board games or or little deck builders and things like that, and I can do that sitting down. I was an athletic kid. Like, I was eight, nine years old.
I could do a dozen or more pull ups. I was a dancer. I can see those paths that I could have walked if I had maintained the ability to walk.
The main reason that we chose go question.
And
we'll drawback to is that it only takes me up to the next level of mild hemophilia. We're nervous about microbleeds. We want to make sure that his trough level doesn't get so low that perhaps he's having little bleeds before his next infusion, there are some activities that we will actually do a supplemental factor infusion for to make sure that he is fully protected. So in addition to having the Conilever in his system, we would also give him a supplemental
having to worry about whether or not I was bleeding, not having to deal with the pain associated with bleeding. I would not have to think of myself as limited as frequently as I do.
So as you've seen and heard through this patient's testimony, even if we've come a long way in treating hemophilia, even if patients are generally satisfied with what is available, there is still some way to go. As current treatments do not address all patients' needs. Each hemophilia patient experience is unique. Their age, their level of activity, their past experience, their family history, all matters in what drives their needs. What is common to all patients, though, is that currently, they have to make a trade off between treatment burden and the activities they can carry out.
If we move to slide 48, and we dig a little deeper into current treatment limitations. Today, we have two treatment approaches available for patients. The first one and and the major one is factor replacement therapy, which exactly replaces the meeting factor eight or nine in the clotting cascade for patients with hemophilia A and respectively. As natural factors, these are complex molecules that require IV to be administered. On the non factor therapy side, emicizumab currently, which attempts to substitute for factor VIII for patients with hemophilia A only, As an antibody, this molecule is amenable to subcu injection.
But its approach has limitations. Factor replacement therapies are highly effective at preventing and controlling bleeds, but they carry a high treatment burden for patients by requiring relatively frequent IV infusions. Emetuzumab, on the other hand, reduces the treatment burden as it can be dosed less frequently via subcutaneous injection. But there is an efficacy trade off here as it produces only mild level of protection against bleeds. And you've heard it from Cole and his mom, patients still need to keep on demand factor at hand.
Also, mechanistically, emicizumab does not have treatment benefit in hemophilia B, and we will come back on this later. But as you can see, we're not there yet. So in short, nothing that is currently available meets all hemophilia patients' needs. No treatment today enables patients to live active lives and achieve a quality of life comparable to someone without hemophilia, which remains our goal, and it was defined again last week during WSH Congress. So we developed fitusiran and BIV001 to address these patients' needs, and they are now two of the six potential transformative assets in Sanofi's pipeline as we highlighted at our Capital Markets Day.
So let's move to Slide 49 and talk about fundamentals and why it is very important to understand how factor levels are defining protection level against bleeds So if we begin by the bottom of the slide, with the factor level below 5%, those level leave patients vulnerable, permitting only a sedentary lifestyle, and patients are at high risk of spontaneous bleeding. If we go up and factor between 515%, those still require significant adjustments to patient's life, allowing only for mild activities, and you've seen that and heard that in the patient video. It was noting that patients at this factor levels and below still require supplemental factor for any invasive procedure. Now if you keep going up and factor level between 1540%, Those only require minor adjustments and they're low for strenuous activity.
And it's really only when you get above 40% where hemophilia patients can have a normal life, allowing them to do all the activity considered normal by you and I or non hemophilia patients. If we move to slide 50, and we come back a bit more in detail about the threat of the patients need to make today. As I mentioned, factor replacement therapies are very efficacious. They are producing high level of protection, but over a short period of time. They also benefit from many years of safety and efficacy experience.
The downside for patients rest in the peak and trough of factor levels over the course of the week, and the treatment burden associated with frequent infusion. On eloctate, the first in class extended half life still require dosing more than once weekly. And with factor in general, if you miss infusions in your schedule that has been defined, you can be at risk of this. Now if we turn to emicizumab, who captured significant patient share since launch, largely due to its improved treatment burden. But where it fails to meet patients' needs is that it produces level of protection, which are only equivalent to around nine percent of factor VIII activity, which is far below what physician would class as normal and not even strenuous.
Furthermore, the annualized bleed rate on therapy is highly variable, depending on frequency of dosing. And while it can be given weekly, every two weeks or monthly, our research tells us that only seven percent of patients opt for the monthly dosing, and this because of reduced efficacy. And indeed, from the clinical program, even on a weekly regimen, we know that half of emitizumab patients still experience some bleeds. And see from our research, we know that ninety percent of these patients have to use additional factor to treat the bleeds, meaning that patients always need to have factor at home to do dual therapy with factor and in. So overall, with current options, patients on average can have strenuous activity less than fifty percent of the time.
So now if we look at this slide, the slide 51, you understand why we're not there yet, and why we need to continue to push the boundaries of treatment burden and protection levels in order to address patients' needs. With DIV001, we do have the potential to go higher for longer. We are targeting protection for patients across the whole week with just one infusion, reducing the treatment burden compared with existing factors and improving the protection on a comparable weekly regimen to emicizumab. We also expect to improve the protect the the joint protection with factor level in the normal range for half of the week and at sufficient high levels to allow for continuous activity for the rest of the week. Our aim is with BIN BIVO-one is to be the best option for those seeking an active life.
With fitusiran, our target is to bring patient convenience and efficacy to the next level. It is anticipated that patients will require just one minute, less than one milliliter subcutaneous injection once a month, the so called one hundred eleven. And critically, we aim to deliver better protection during the entire month's dosing interval. So with that, fitusiran will really be the first true high efficacy monthly subcu therapy for all hemophilia patients AB with or without inhibitor, aiming for fifteen percent to twenty percent of factor equivalence levels, and particularly then for the patients who are seeking the ultimate convenience without treating us efficacy. And with both products, we're aiming to get more patients above the strenuous level for at least eighty percent of their time.
I will now hand over to Dietmar, our head of development, to bring you through some of the data we have to support BIVO zero one and fitusiran.
Thank you, Vanessa, and good morning, good afternoon to everyone. As a hematologist and oncologist, I have treated hemophilia patients in the clinic. And I've also been closely involved in the development of emicizumab, which, as you know, has been well accepted. But I think we can do better, and we owe it to patients to do just that. On slide 52, BIIB001 is a new class of factor therapy, which has been uniquely engineered to maintain all the advantages of factor therapy while normalizing factor eight levels in a once weekly dose.
Commentary on our recent preclinical data publication referred to BIV001 as a molecular jewel, acknowledging the addition of fusions of X10 and portions of von Willebrand factor to break the ceiling that constraints the half life of all other factor eight molecules and highlighting the elegant engineering to remove them by thrombin within the context of the activated clotting cascade. BIV zero zero one half life is almost two days. This translates into maintaining levels of factor eight at 40% or above for several days and 20% or above for five days. If I take you back to the four categories of protection that Vanessa mentioned, this means that we can potentially keep factor levels in the normal or strenuous range for the entire week so that patients can enjoy an active life without any major restrictions. On slide 53, I'm delighted to say that we just reported our first positive outcome for the phase one repeat dose study of BIF one.
This data was revealed at the World Federation of Hemophilia meeting on June 18. What you see here is that in an exploratory analysis in twenty four patients, we observed no bleeds over the four week treatment period and for at least ten days after the last dose. This compares with median prior bleed rates of forty eight of the previous year or four per month. Not only was this highly reassuring on efficacy, but the four weekly doses were well tolerated with no signs of inhibitors, allergic or anaphylactic reactions, or treatment related adverse events. This is encouraging as we look forward to the outcome of our ongoing phase three program.
Next slide, 54. I want to move now to fitusiran, which is the only therapy specifically designed to bring high protection levels to patients in a true once monthly subcutaneous format. Fituziran is an siRNA molecule with innovative mechanism of action, which rebalances the deficient coagulation cascade in both hemophilia A and B. It works by inhibiting the production of antithrombin three. This in turn results in an increase in thrombin generation, which is the ultimate goal of the coagulation cascade.
We are aware that a number of you have concerns about the safety profile of fitusiran, and this is a bit of a deja vu moment for me as you had similar concerns for emicizumab when it was in development. For fitusiran, we have carefully developed bleed management guidelines, and those were agreed with the FDA in December 2017. Since implementation of these guidelines, we have seen a favorable safety profile with no thrombotic events occurring in any compliant patients. We now have positive data with more than two fifty patients in our clinical trials and more than four years of experience for the longest treated patients. On Slide 55, we also reported important new data on fitusiran at last week's World Federation of Hemophilia, supporting the product efficacy and safety in a Phase II open label extension study.
The overall median annualized bleed rate with monthly fitusiran was 0.84 in patients with and without inhibitors. As you can see from the left hand and middle charts, there were substantial improvements in each set of patients when compared with prior treatment. For patients with inhibitors, the efficacy is at least as good as in the noninhibitor population. And this is especially important as bleeding events in the inhibitor population are hardest to treat. We observed an encouraging safety and tolerability profile for patients in this trial.
Four out of the thirty four patients were deemed to have had a serious adverse event related to study drug, but that's over a median dosing period of two point six years and a maximum of close to five years, so a fairly prolonged period. Importantly, we did not detect any cases of antidrug antibody formation. On Slide 56, with its unique mechanism of action, we believe fitusiran is a potential best in class nonfactor therapy for hemophilia patients. This slide compares its key attributes with emicizumab. In all respects depicted here, think fitusiran may transform hemophilia treatment if it meets our target profile.
It has the potential to be the first true once monthly subcutaneous injection with an annualized bleed rate of less than one, raising the standard of efficacy for all hemophilia A patients. It's also on track to be the first subcutaneous therapy to address the hemophilia B population, which in itself represents a $1,000,000,000 market in The US alone. Fituziran can be delivered in a single prefilled syringe with a low volume fixed dose. And you've heard in the patient's video that one drawback of emicizumab can be injection site pain, which may be related to a larger injection volume. Fituziran will be the first ever product in hemophilia that won't require refrigeration.
And finally, a reversal agent is available for pituziran with emicizumab stays in the body for up to six months without an option to remove it, except in plasma exchange. On slide 57, I want to wrap up. We believe patient experience will drive choice in hemophilia, and we are all well advanced in phase three studies for both of our exciting new agents. Our pivotal study of BIF-one in previously treated hemophilia A patients started last year, and we are planning for submission in the 2022. Meanwhile, two of the three ATLAS studies of fitusiran are fully enrolled, and we're close to completion of the third with a pediatric study also enrolling.
We target submission for fitusiran in a broad population of hemophilia A and B patients with and without inhibitors in the 2021. Now to slide 58. Sanofi is not stopping there, and our ultimate aim is to provide a true cure for hemophilia so that all patients can achieve a normal life. We're working on a gene therapy approach based on in vivo administration of a lentiviral vector. We believe this will overcome the shortcomings of the adeno associated viral based gene therapies currently undergoing development in terms of preexisting antibodies, declining factor eight levels, and inability to treat pediatric patients.
We expect our approach to be more durable and target entry to the clinic by 2022. With this outlook, we conclude our section on patient insights and on our exciting portfolio in hemophilia. So now moving on to our next section. I came to Sanofi roughly a year ago with fresh eyes, and I want to give you some insights into how we are improving our capabilities from a development perspective. Then my colleague, John Shiver, will take you through how we have been able to leverage this in practice with our response to the COVID nineteen pandemic.
On Slide 60, as we are moving from a primary care to a specialty care focus in r and d, it's imperative for us to build an agile and innovative development engine. This slide gives a summary of the four main dimensions we are focusing on to expand our capabilities. The first dimension is enhancing patient centricity and integrating the patient's voice more broadly into our approach to clinical development. As examples, we're embedding patient related insights into our disease strategies, as you heard from Vanessa, to help us determine and address unmet needs. We're making it easier as an example for patients to participate in clinical trials through telehealth, home delivery, digital tools, e consent, and patient portals.
The second dimension is to optimize our use of digital and real world evidence. You heard on our Dupixent r and d call how we are utilizing our proprietary Darwin platform with its access to nearly 450,000,000 live medical records to help inform our line extension strategy in type two inflammatory diseases. We are also using artificial intelligence for candidates and indication selection, and I know many of you are already aware of the efficiency opportunities that digital brings across the entire r and d process. The third dimension is focusing and simplifying our footprint. With a focus on specialty care and vaccines, we can use this as an opportunity to make our r and d operations more efficient and complement this with investment into leading edge technologies, including our recently announced Evolutive Vaccine Facility, which will be the first factory of this type across the industry.
This is a new type of manufacturing plant designed around the central unit, housing several fully digital production modules that will make it possible to produce three to four vaccines simultaneously versus only one in current industrial sites, and I find this pretty exciting. The fourth and final dimension is examining new ways of working and engagement models. As a central component, we're building an integrated development organization with full alignment around our therapeutic areas, which have end to end responsibility of the development process. John told you in December about cutting multiple layers of bureaucracy to help the efficiency and rigor of our decision making, and he referred to it today again. You've also heard about us taking smart risks, for example, making informed investment decisions based on early clinical data.
I will come back to this in a couple of minutes in the context of our BTK inhibitor. In the future, we see a place for more enhanced collaborations like the iSpike collaboration in breast cancer that we announced at our recent ASCO event as well as our important long term partnership with BARDA, which John Scheiber will speak to during his presentation. On Slide 61, I want to expand on our digital strategy. We recognize we have our work cut out in this area, but I think some of the examples you've heard about today, like the application of Darwin and the use of innovative digital endpoints in our Parkinson's studies with venglustat as well as our award winning paperless digital factory in Framingham speak to a company that is arguably developing a leadership position on several fronts. We are also looking forward to working with our recently joined Chief Digital Officer, Arnaud Robert, to accelerate our digital strategy and implementation in R and D.
There is a lot of information on this slide, so we'll just leave you with a take home that digital brings fresh opportunities to transform our company. And we have multiple pilots of full blown programs underway across the entire R and D continuum to leverage these opportunities. On my last slide, Slide 62, I said I would come back to the topic of taking smart risks and flawless execution to improve our pace and development. Our brain penetrant BTK inhibitor one six eight is an excellent example. Here, we began with phase one and two studies that were conducted one year faster than benchmarks due to efficient trial design, home delivery of study drug and other measures.
We're especially proud that we were able to maintain our studies and patient commitments despite the COVID-nineteen pandemic. Prior to phase three readout, we already began planning phase three studies across the full spectrum of multiple sclerosis. That happened at risk, and we later made the decision to rightsize the control arm in primary progressive MS so that we could accelerate study completion while still maintaining adequate statistical power. And as Paul told you earlier, we're now delighted to say that the first patient has been enrolled in our pivotal Phase III study in relapsing remitting multiple sclerosis. This is just four point five months after readout of the Phase II data.
By taking smart risks and focusing on flawless execution, we have accelerated the development of this potentially best in disease molecule and are on track to make expected regulatory submissions beginning in the 2024. With that, I want to thank you for your attention, and I hand over to John Scheiber to start our conversation on vaccines.
Thank you very much, D Mark. We feel privileged to play our part in the company's response to the COVID nineteen pandemic, which, as you know, is the largest global public health crisis in a century, which is galvanizing our industry like never before. I wanna start my presentation with a short video which underscores the urgency with which we are addressing the COVID pandemic. Very good. So slide 63 shows the landscape of more than a 160 vaccine candidates in development for COVID nineteen.
This is unique. We have never seen a single disease, which is an intensity of vaccine development in such a short time. One thing that's very important here to look at are the technologies underlying these clinical candidates. Less than half are based upon the proven vaccine technologies of recombinant protein based live virus or hold and activated viruses. These validated approaches form the basis of successful vaccines across a range of viral diseases, including influenza, herpes zoster, yellow fever, measles, and human papillomavirus to name but several.
What this means is the majority of COVID nineteen vaccine candidates around sixty percent, specifically all gene delivery based platforms such as mRNA, DNA, and vector vaccines are based on unproven platforms and have never produced a licensed vaccine. This means many of the candidates that you read about are at risk of suboptimal efficacy or safety or even outright failure. My next slide develops this theme further. So slide 64 summarizes the different safety and efficacy profiles of the main platform approaches used in antiviral vaccines. The main advantage of gene delivery based approaches is a short time it takes to deliver a clinical candidate when compared to recombinant protein vaccines where you first have to build the expression system in bacterial, mammalian, yeast, or in the case of our recombinant protein candidate, insect cells, to generate the protein.
On the flip side of the gene delivery approach are the numerous unknowns in terms of efficacy, duration of protection, safety, but also the lack of an established infrastructure for industrial scale production, which apply significant execution risk. Virus based approaches come with significant safety concerns and hence are not pursued by the western companies. So let's advance to slide 65. So on this slide, it shows our two complementary differentiated approaches that Sanofi is taking towards the COVID nineteen vaccine. By employing two different platforms, we believe we'll have a greater chance of success in achieving our goal of developing an efficacious and safe vaccine.
On the left side, you see our recombinant baculovirus based candidate, our most advanced candidate. This utilizes the same US licensed cell based technology, which we employ for the large scale manufacturing of our flu block influenza vaccine. This candidate is being developed in collaboration with BARDA and via our unique arrangement with GSK, normally our fierce rivals, but in this case, our allies who are supplying their proven ASO three adjuvant. The advantages of our baculovirus approach are this is a de risk technology with established capacity in place that we can leverage. It is unknown yet if it will require boosters to maintain an effective immune response to the virus, but these of course could be given if needed.
On the right side, you see our innovative messenger RNA vaccine approach, which is based on natural mRNA encased lipid nanoparticles. This arose from an extension of our 2018 collaboration with Translate Bio who have the only established large scale mRNA manufacturing capacity. Because of the investment we in Translate Bio had already made in these programs, we believe we can accelerate the development of our COVID nineteen candidate, and we can leverage the large scale capacity that is already in place as a result of their long history and pulmonary application, which requires large doses. In common with any innovative approach, we have not yet fully elucidated the safety profile, of course. However, it may have a differentiated safety as well as potency profile compared to be a natural versus a modified mRNA.
On slide 66, I'm pleased to announce that we are accelerating the timelines for our baculovirus candidate vaccine by two months compared with our original plan announced during our Q1 results. This is a result of a huge coordinated effort by our r and d and industrial affairs teams. On the right hand side, you see a number of levers that we're pulling to get this vaccine candidate as quickly as possible into humans, including optimizing clinical studies and production of vaccine components at risk. The result of this effort is shown in the timelines on the left. So have you obtained the necessary preclinical data in August?
We plan to start a phase one two study in more than 400 subjects in September with preliminary data expected to read out in December. Assuming this meets our target profile, we will move immediately into a confirmatory phase three program. In parallel, based on the phase onetwo data, we intend to seek emergency use authorization in January 2021 with up to a 100,000,000 doses available and to make regulatory submissions with the aim of gaining an approval as early as June. On slide 67, we show that we're working intensely with our pharma colleagues, our contract manufacturing partner, and our adjuvant supplier GSK to put in place the capacity to deliver 1,000,000,000 doses of our baculovirus vaccine in 2021. There's obviously a degree of uncertainty around this as vaccine manufacturing is uniquely complex.
Something we are acutely aware of is one of the leading vaccine suppliers for many decades. And let's not forget, we're telescoping a process that would normally take many years. The baculovirus expression system is a high yield expression system, and we aim to optimize the number of batches we run at our various facilities so that we're confident we have the capability to deliver the billion doses next year. On slide 68, I want to shift gears and update you on our mRNA vaccine candidate. Together with Translate Bio, we have screened hundreds of lipid formulations so that we get the right pharmacokinetics for the lipid nanoparticles to deliver natural messenger mRNA into muscle.
We're now at the stage of IND enabling studies for the lead nanoparticle. At the same time, we've identified multiple antigen mRNA constructs from the virus and have packaged these into lipid nanoparticles for preclinical testing. We're making good progress with our partner, and our intention is to move a candidate vaccine from this program into the clinic in the fourth quarter of this year. By applying the same urgency we have shown with our baculovirus candidate, we could potentially expedite the process in order to obtain regulatory approvals before the 2021. Where we will have major advantage over the other RNA platforms, vaccines in development is that we start with established manufacturing capabilities that can be scaled up quickly if needed.
Translate Bio has been investing in mRNA manufacturing for more than a decade and has successfully established ongoing 100 gram single batch production at its large scale facility. Translate Bio has demonstrated 250 gram single batch mRNA production, and work is underway to achieve this scale on an ongoing basis, which would allow commercial mRNA vaccine volumes to be produced. In total, this could provide us with the capacity to supply in the range of 90 to 360,000,000 doses annually by the 2021 and with the flexibility to extend to other pandemic targets. On my final slide, number 69, COVID nineteen is the biggest global health scourge for a century. The world needs multiple vaccines and the capability to supply billions of vaccine doses.
This is not a situation of winner takes all. At Sanofi, we believe we could be a key player in the fight, and we're working day and night to advance our two complementary differentiated vaccine candidates. This slide summarizes the key take homes. It is worth saying again that our recombinant protein based vaccine candidate has the best risk profile among the advanced COVID nineteen vaccine candidates in our view, and we have been pulling out all stops to accelerate our development timelines. We aim to for emergency use authorization in January 2021 with up to a 100,000,000 doses and for approval in June 2021 with the capacity of 1,000,000,000 doses in 2021.
I will leave you to read the rest of the detail, but let me just say I am proud that Sanofi is once again able to demonstrate and build upon its commitment to global public health. The urgency with which we're moving speaks to a company which is passionate, fully engaged and able to leverage our unique experience and capabilities in vaccines. With that, I would like to hand over to John Reed for his concluding remarks.
Thank you, John. I'm sure I speak for all of us when I say we're rooting for your success. Let me now bring us to a closure. Before we turn over to your questions, though, there is one loose end that I wanted to address, and this is pertaining to the question that Graham Perry asked earlier. And it concerns a question I often get, and that is about Sanofi's intentions in the field of gene therapy.
Let's move to slide 71. I think it's appropriate that I introduce this topic immediately following John Shiver's presentation on vaccines because the same know how and technology that Sanofi Pasteur has used for decades to generate live attenuated virus vaccine candidates is highly applicable to gene therapy where recombinant viruses are created that deliver the genes. We have decided to commit to establishing an AAV gene therapy platform within Sanofi from discovery to manufacturing. While we'll also tentatively explore other gene therapy approaches such as the lentivirus platform that you heard about during the patient insights section. You may not be aware, but Sanofi actually has quite a bit of experience with the AAV platform going back to our Genzyme heritage.
Several Sanofi AAV vectors were put into the clinic for ophthalmology and other indications, and a producer cell line technology was established for providing clinical supply of AAV product candidates. Over the past few years, we've been quietly establishing an internal pipeline of AAV candidates for rare neurological disorders, relying heretofore on CMOs for manufacturing. To put it mildly, however, the reliance on external contract manufacturing organizations for GMP production of clinical material has been extremely frustrating and disappointing. We've decided, therefore, to create our own bioproduction capabilities, leveraging the historical Genzyme experience and our vaccines manufacturing platforms to control the bioproduction ourselves. A fully dedicated CMC unit has been created in the Boston area and is being expanded now.
Additionally, we have commandeered one of our manufacturing facilities in the Leon area where Sanofi Pasteur is headquartered. And we'll have, by the end of this year, our own GMP grade manufacturing for clinical supply. Finally and importantly, we have reorganized our internal research to create a stand alone genomic medicines unit with a full ensemble of capabilities to produce AAV vector design, to pursue AAV vector design and preclinical development. Plus, last year, we recruited an experienced gene therapy veteran to have this unit, Christian Mueller. So within the next twelve to eighteen months, we should be in a position to provide more specific updates on our progress with establishing the AV platform in house and in generating a compelling gene therapy pipeline that aims to continue Sanofi's leadership role in providing therapeutic solutions for monogenic rare diseases and eventually, hopefully, expanding into complex diseases over time.
All right. Now to wrap up, let's move to Slide 72. I hope the previous presentations made clear what makes Sanofi R and D unique and how this is translating into transformative opportunities for patients through molecules like THOR seven zero seven, venglustat, fitusiran, BIVV001, and our COVID vaccines. Each of these molecules has the potential to change the practice of medicine, and they're examples of our strategic commitment as a company to deliver true innovation. Slide 73, please.
I want to come back to the seven priority molecules that Paul mentioned at the beginning of today's program. We expect multiple important readouts for these assets in the next several months. We remain fully committed to expanding the indications for Dupixent. In fact, even since the recent investor presentation devoted to Dupixent, we've received the approval by FDA for our auto injector. And as Paul mentioned, approval in China for atopic dermatitis, opening an entirely new and large market for Dupixent.
And we're intensely focused on accelerating development of our priority molecules with full vigor and pace. You can expect also some important results for those molecules over the coming months. Slide 74, please. Beyond those priority assets, Slide 74 shows that we also have a rich pipeline with exciting news flow coming across all our therapeutic areas over the next twenty four to thirty months. And the fact that this is such a busy slide shows the remarkable progress we are making at Sanofi R and D.
Given how slim the Sanofi pipeline was just a few years back, the density of clinical milestone readouts shown here clearly illustrates that our R and D organization is delivering with pace on our strategic framework. Next slide. To close, I'm confident that Sanofi is well positioned to deliver the next generation of medicines and vaccines. Summarizing what we communicated today, we have a broad toolbox of drug discovery technologies, including some truly unique platforms to fuel our next wave of potentially innovative medicines. Our deep understanding of disease pathways in immunoscience and monogenic disorders is helping us to identify drug candidates that could change the practice of medicine across areas of high unmet need.
Our focus on patient insights is helping us to aim our drug discovery development efforts on superior patient offerings that really matter in the day to day lives of those struggling with disease. We're driving innovative ways of working, including embedding digital into all of our processes and into our interactions with patients, with investigators and with clinical study sites. And finally, our adaptive capabilities allowed us to launch clinical trials in record time while ensuring robust business continuity during these unprecedented times of the COVID-nineteen pandemic. Slide 76. On my final slide, I think it's important to remind ourselves of what is the real motivating force in Sanofi R and D, what it is that gets us out of bed every morning and keeps us working in the night.
And that's simple. It really begins and ends with the patient. We have a responsibility to them, and that's what drives us every day. With that, I hand things over to Felix to start Q and A.
Thanks, John, and we would love to go straight into Q and A. Once again, we have a long list of analysts awaiting to ask questions. So if we could ask you to limit your question to only one. If we have time at the end of the session, then we still invite you to come back in line. But let's start with one question, please.
Natalie, can you remind everyone how to ask questions?
Thank you, Felix. So you have two options to participate in the Q and A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. Now we will take the first question of the second session from Joe Walton at Credit Suisse.
Joe?
Hello. I hope you can hear me. I've got a general one and just a very specific one on the COVID, if I could. I just wonder if you could tell us a little bit about what the regulators are looking for in terms of safety and efficacy. I can understand that by December, you may have some data on immunogenicity, but you won't have any long term safety data.
So will you be expecting an emergency use to be really narrow where there are people with high risk? So just a little bit more about that, please. And, could I also ask, and I guess this is one for Paul, a broader question about, where you think you might be looking to reinvest the money that you got from, selling your stake in Regeneron? I think most people are assuming that that is to fill up holes that may be apparent in the r and d pipeline. So, where does he feel that that would be, best invested?
Well, thanks for your question, Joe. Let me turn the first one over to John Shiver to talk about the COVID vaccine. John?
Sure, John. So, you know, the regulatory agencies are gonna have to determine what emergency use authorization guidances would be important and and beneficial, right, by by the end of the year when our data as well as other program data become available. Certainly because our phase one, two trials, there were 400 subjects and concentrated in only two doses, we're gonna have a substantial amount of safety and immunogenicity data across a wide range of of of ages. And so I think that plus the supply can certainly support that use. But, again, there's always risk benefit.
And, you know, I I think a lot will depend upon the the the quality of the how the vaccine performs, how the other vaccines are being tested to perform, and the status of the COVID pandemic at that point. If it's if it's really on the rise and and the threat is continuing to increase, it may become more urgent to, implement vaccines for that emergency use. If it is dissipating as we would all hope at that time, but may not happen, then perhaps it might make emergency use more applicable.
Alright. Thanks, John. Paul, about the proceeds from the Regeneron stock sale.
So thanks, Joe. Great question. So just to answer it as briefly as I can, the target of filling in the gaps, I think, is actually the legitimate one. First step of that was understanding what we had in our hands and think we're doing much better at that right now, and you've seen that from the series of r and d events. We're excited about things that can amplify what we already have in the pipeline as well.
We loved about Synthorx, about the use in combination. You know, the moment to exit the stake was good for both parties, like I said earlier. And so we took it because it worked. We will deploy it. That's for sure.
And the plan we have in place, the timeline on that didn't change. So we know what's on our mind and how we're gonna proceed, but it wasn't driven by that time line specifically. So we feel comfortable that over the, what, the coming months, you'll start to see us deploy the proceeds in ways that will make sense from the science that we've shared.
Alright. Thanks, Paul. Next question.
Next question is from Mark Purcell at Morgan Stanley. Mark?
Yeah. Thank you very much for for for an interesting session. My one question is on the the vaccine manufacturing build out and the legacy you're creating here. You know, clearly, you're you're scaling an existing platform with a new target in COVID, on the back of our side, and then you're establishing proof of concept on a new platform on mRNA. So could you help us understand, your ability to repurpose here, in terms of you you obviously signed a partnership, an expanded partnership on respiratory vaccines, on the mRNA side, sort of which targets are you looking at and how quickly can you repurpose?
And then on the baculovirus side, you know, how quickly can you repurpose into into flu? And just related to that, clearly, and finish is one of the challenges with flu at the moment. So could you help us understand where you are in terms of expanding on the fill and finish side and the opportunities, therefore, to touch other geographies with your flu vaccine franchise such as China?
Mark, thanks for those questions all related to the COVID vaccine. I, you know, I I guess I'll ask John to start, but we have Thomas Triomphe here with us as well who recently took the helm at Sanofi Pasteur, and I suspect he'd like to offer a comment or two as well. So, John, do you want to kick us off? And then I'd love for Thomas to also get into the discussion.
Sure, John. That'd be perfect. So, you know, with the baculovirus based, you know, manufacturing footprint we have for flu block, we actually have the capability to use that infrastructure, that manufacturing infrastructure with various shifts and the greater Sanofi network of manufacturing that's available to reach the targeted number of doses in the time frames that we talked about without impairing our flu product supply. And that's really critical because we mustn't forget how important flu is as a disease as well. And, certainly, the mixer code and and flu are very would be extremely bad in itself.
So, you know, we do think we can can meet those. We also have, you know, some networks of of CMOs who assist us as well, and as part of a greater plan for how to make the baculovirus based production, you know, available. And recall that the flu is not a full time year production to begin with, so that implies some inherent capability. For the mRNA, you know, know, Translate Bio, and we're working together, and, again, with the capacity that they've developed, you know you know, have the ability to produce what we've said already in the projected doses there, the 90 to 360,000,000, depending upon what the dose level turns out to be. And certainly, can further expand our network and and other means to expand that further, depending on what the need turns out to be.
So perhaps I'll pause there and turn there for tomorrow.
John, so you say thank you very much, John. So you said pretty much many things already. So there were different elements in the question. So so on the flu side, you understood very clearly that our goal is to be able to do COVID nineteen and flu vaccines. Both are extremely important for obvious reasons.
COVID nineteen vaccines for the pandemic threat that we are facing right now. And the flu vaccines are as important in the sense that, of course, the most project people against flu are the ones that are also most severely attacked by COVID nineteen. So, definitely, we expect a strong influenza season, and we expect to meet the demand with a strong supply, and that's very important for us. Now when it comes to mRNA, just to complement a little bit what what you said, John, I think the question was alluding to also what we are going to do with the expansion of the mRNA deal with with our partner. Here, we don't disclose for obvious reasons the targets after which we are going.
I think we've disclosed in the past that we are already working on the flu candidate that's of interest to us when we think about the next generation of flu vaccines. We are also working on a a different viral target and a different bacterial target where we are hoping to go very soon into into clinic. But for the expansion, we foresee a lot of potential opportunities, a very, very interesting target over the infectious disease space. But for confidentiality, we don't disclose the the targets we're going after.
Good. Thank you, Thomas and John. Let's move on to next question, Felix.
Next question is from Geoff Porges at Leerink. Geoff? Okay. So maybe we move to Florent Cespedes at Societe Generale. Florent?
Yes. We
can hear you. Afternoon. Florent Cespedes from Societe Generale. Thank you very much for taking my question. A quick one for Young Joon.
Please could you elaborate on the potential side effect profile of the three specific antibodies or also the nanobodies that you are developing? Because we understand that you expect better efficacy, but what about the side effect profile, please? Agreed. Me
answer your question. Yeah. Let me turn it over to Yong Joon, and I don't know how much he's able to reveal in some terms of some of the nuances of the design of those antibodies with respect to their the affinities of the relative binding units to different target antigens. But, Yunjoon, do do your best to to try to explain explain that.
Yes. So let me first comment on the safety of nanobodies. Sanofi Ablynx, We have the first nanobody product in the market. So this basically de risk the nanobody technology. We can have a safe drug.
So the rest of the RIG thing will be more depends on targets. You know? So we have to do the experiments. We have to move the molecule into the clinic. Regarding the trispecific antibody platform, we have one trispecific antibody as I introduced against HIV.
This is the broad neutralizing antibody against HIV in the clinical study. So in terms of manufacturing, safety, antibody drug effect, we derisk it all back in terms of bispecific platform. So the the key, again, will be, you know, the targeted related safety. So this will apply to all antibodies. Right?
You have to do and derisk, you know, the targeted related safety one by one by experiment, by preclinical study, and then by clinical study.
Okay, Yungjoon. Thank you. You know, perhaps some more discussion could also occur offline around the nuances of that. Good. Let's go to the next question.
Next question comes from Keir Parekh from Goldman Sachs. Keir?
Hi. Good afternoon. Thanks for taking my question, please. Based on the one that Florent just asked, if you can talk a bit about kind of what do you expect the therapeutic window of this price specifics and kind of the multi targeted nanobodies to be, kind of how much of in house expertise do you think you have as it relates to kind of getting that balance between efficacy and safety right for those agents, please? Thank you.
Okay, Theo. Thanks for your question. It's along the same lines as Jerome's question, I guess. Maybe I can try to start and then Yunjoon can kick in from there. Think this is obviously the opportunity and the challenge with the T cell bispecifics is to thread that needle between efficacy versus safety.
I I I like the fact that we often are putting two binding elements to latch on to the tumor within our constructs because that will probably allow us to go with lower doses and achieve more selectivity than a conventional two by two bispecific format. You know, we, like many others, dial down the affinity for the T cell antigen receptor as a way of trying to make sure that the T cell activation is occurring predominantly in the tumor microenvironment. And I would also say that you'll soon be seeing a number of NK cell engagers emerging from our pipeline, and we find that also an attractive area to pursue because NK cells don't make some of the same cytokines that are problematic in terms of T cells. So that'll give another way to try to tackle the problem. And all these are very synergistic with four seven zero seven as well.
So altogether, I, you know, I feel like we're well poised to take this journey. It certainly will be a journey with, you know, with its share of challenges along the way, but I feel like we're poised to do it, and then we can do it in a differentiated way. Yunjin Yunjin, anything to add?
So so good point, John. So I just want to emphasize one point. Actually, we believe scientifically by targeting two tumor antigen can provide a better safety and a better therapeutic window because our translational science really looking for two antigen expressed by the same tumor cells. And most like most of the time, the normal tissue, if they express tumor antigen, they only express one. So in this case, our bispecific antibody can differentiate much, much better binding to tumor cells versus binding to normal cells.
Okay. Next question.
I will try again with Jeff Porter at Leerink. Jeff? No. Okay. So let's move on to Steve Scala at Cowen.
Steve?
Hi. Paul and John, your former employers also talk a lot about digital, leaving their strategies are a competitive advantage. Novartis talks about the ability to monitor 500 studies in real time. Roche obviously made a couple acquisitions and owns the diagnostics business they think is important. How is Sanofi's digital strategy fundamentally different, if at all, from those two companies?
Thank you.
Yes. Thanks for your question. I'm going to let Paul start that, and then perhaps my I can supplement, John Baptiste may be able to supplement, etcetera. We just onboarded our new chief digital officer, Arnaud Robert. I I don't know if he's available.
But, Paul, why don't you kick us off?
Well, I think it is day eight or something for our new CDO, so we'll give them a break at least for another week. It's a really, really important question. So let me just take the Sanofi comparison first and the other company comparison. The first thing is that our emphasis on digital had been predominantly external collaboration. And while it starts to be applauded in many aspects, I think it left us a little under resourced in terms of delivering our own master data management architecture, accessibility, and the requisite tools of machine learning AI automation to do something both from a targeting perspective that John may mention, but also for us to be able to establish insights and take corrective action.
I think many companies have taken more of a vanity approach, big external collaborations or huge big data monitoring installations. What really matters is data that's that you can use to get insights to take action. And I think most of the industry has been pretty woeful at that. The good news, as with many things at Sanofi, we we're not we're not hanging on to something desperately that we have to unlearn. We start quickly and with agility, and we'll move right across the board.
It can be financial data led by John Bautista. It can be research and discover and development data led by John. But bottom line is I think we're taking a slightly different approach, which allow us to action more accurately in real time the data that we get. And I and I think it'll put us ahead of the pack in the industry, but it's gonna take us a year, maybe slightly longer.
Thanks, Paul. It's I think all companies are going through this digital transformation journey. I feel good about much of the progress that is underway. If I could maybe even just cite One example is in regular our regulatory environment. Sanofi has had a history of of providing 3,500 products in 80 countries around the world.
We historically had that regulatory data, all those documents and the supporting information, pharmacovigilance, etcetera, spread over more than 300 systems around the world that didn't talk to each other. Thanks to a journey we've been on, which will be completed this year, we've now brought all those data together in a single relational cloud based database that is where the data are formatted in ways that you can really manipulate them. We can apply natural language processing. We can use machine learning and AI techniques. We can automate the production of various regulatory dossiers.
So, you know, that's just an example of one of the areas where we've been investing. There are several others where I feel very good about where we stand. I might even dare say in some of those, we might be industry leading or or certainly at the head of the pack. But there's far more to do, certainly, and and particularly having data from different elements, being able to talk to each other and bring it all together in in very powerful ways. So that's what Arnaud Robert will be helping helping us to to figure out over the next several months.
Let's go to the next question.
Hey, John. Jeff Porges was able to send his questions to the q and a box. There's two questions. Does Sanofi expect to make a profit on COVID vaccines? Why should it be any different to influenza or other vaccines?
And the other question is John did not include complement in his immune system overview. Does that reflect his view of lack of activity, interest or opportunity in complement inhibition?
Well, thanks for those questions, Jeff. I think I'm going take them in reverse order starting with complement to emphasize that, no, we are very excited about the complement pathway. We're very excited about sutimlimab as our first entree into that, but it won't be the last. We have a very robust discovery program under Yung Jun and colleagues underway now. And in fact, we just nominated another development candidate that is moving into IND enabling studies now.
We we do see the complement system as another branch of the immune system, the innate immune system. We just didn't have time to squeeze everything we would have liked to into this presentation. It it it it was originally part of the presentation, actually, but we we we end up having to trim some things to not make this too long an event. So that's where we are at complement. So stay tuned.
We're we we like that pathway. And it it's it's also, I think, an exciting area because the the biology takes you in multiple different therapeutic areas. We've started in hematology, but expanding into other areas as well. On the COVID vaccine, I think I'm gonna ask Thomas to take that.
Thank you, John. So as we said before, for us, it's very important to make this vaccine accessible to the largest population and to make it affordable. That's that's the spirit with win with which, sorry, went into this. We think we have great assets to contribute to this fight against COVID nineteen. We believe we have great technological abilities.
That's why we also went with two candidates. We believe it's a race that's very important against the virus, not against each other. So so we're really all in. Now I guess the question was related also to how financially should investors look about it. It's clearly way too early to think about that right now.
We're really focused, as you've seen from John before, focused on actually making sure that we go as fast as possible to provide vaccines for the world against COVID nineteen. We are very excited to be in nonclinical stage and entering into phase one in September. As you've also seen from one of the slides from John, there are still many uncertainties to be looking looked at. For example, we look at deals. We look at very different elements that will bring us to the finish line first at the December when we see the key results from our phase one two, study.
And that's where at that point, we'll know more about the the product and and where we can move it forward with. So, really, you understand first, speed, execution, being flawless, moving forward as fast as possible on those vaccines. That's priority number one. And then, of course, in the spirit of making it accessible to the largest population and an affordable vaccine.
Alright. Great. I think we have only a few minutes left, John. Please, to the analyst, stay to one question each so that we can cover at least another two or three. Thank you.
Okay.
And the next question is from Luisa Hector at Berenberg. Luisa?
Hello. Many thanks for taking my question. So I was just wondered, how do you see patients choosing between the two very strong profiles offered by BIV BIV zero zero one and fitusiran? Will it come down to less frequent dosing versus a known safety profile? And then if I may, I did want to ask John, given that we can see the positive effects of the r and d transformation emerging already, could you comment on the metrics you're using to assess your return on R and D spend, please?
Sure.
Thanks for your questions, Rita. Vanessa, do you want to take the fitusiran versus BIVV001 with that patient centric view?
Sure. Thank you, John, and and with that, for the question. So as you've seen, today's treatment option have limitation. We've seen that patients have to make trade offs if they want to choose between treatment burden and activity restriction. And we do believe that the two products are offering the best, you know, for each needs.
If you think about patients who are really looking for improving their treatment burden, fitusiran will really be the first true high efficacy monthly sub q therapy. So those patients should definitely like move to fitusiran. Now for patients who are really looking for activity first and want to raise the level of activity as you've seen on the factor levels, BIV001 will be the treatment of choice, bringing patients to like normal levels. So that's how we believe we can really address the remaining unmet needs in this area by providing the best option to address those two main main needs.
Good. Thanks, Vanessa. And to readdress your question more generally about the R and D transformation, I think the metrics we look at are ultimately how many enemies do we generate that really transform the practice medicine? Along the way, of course, there are various things to gauge, one of which is productivity from our own internal laboratories. We're we've been on a journey there.
Yongjoon came in, I think, in 02/2016, I think it was, and began to rebuild the research teams there. We've been on a steady course of improvement. Just last year, we reached and surpassed the industry benchmarks on what it costs us to generate a development candidate. We're now slightly better than industry, and that's the first time that's happened in anybody's recent memory around Sanofi. So we're very excited about the progress we're seeing in terms of the productivity from our own laboratories.
With all of our candidates, we are really setting the first in class or truly differentiated best in class bar. So these are no longer gonna be me too drugs or that kind of a fast follower sort of approach, but really molecules that going forward will be quite differentiated. Know, another metric we put a lot of stock in is what we refer to as not just proof of clinical concept, but proof of clinical and commercial concept. It's a higher bar. It means that the asset has been sufficiently derisked and looks sufficiently promising that we're gonna invest as a company in pivotal studies.
We we've now set this POCC, proof of clinical and commercial concept, as our chief metric for the the research and early development group. It's a it's a higher bar, but one that really, I think, matters in terms of what molecules are gonna be worthy of the investment to take them forward into the market. We've also done things to try to incent the right behaviors. For example, when I came here, one of our metrics that we provided to the research team was what was how many new projects they started. We said, going forward, it's not about starting projects.
It's about ending projects. The fewer projects you have to start to end up with enemies at the other end, the better. So we took that away as a bonus of all endpoint and it put in others that we think matter more. So I think those kind of KPIs around the pipeline are certainly elements of it that will speak to having a sustainable pipeline and one that delivers innovation. So that's that's what it's really all about.
But underlying that, I think, fundamentally, is evolving the culture of the organization that really adopts this, what Paul's been calling play to to win mindset and and has that deep commitment to innovation and doing what what's really gonna matter for patients and doing that within a pace and urgency that patients will be proud of.
Great, John. I think that concludes it well. At that point, we we have to come to an end of the q and a session. Obviously, our our team is available for our analysts to take questions in the afternoon, U. S.
Time. And with that, I would like to hand it over to Paul for some concluding remarks.
Thank you, Felix. Maybe just the last few seconds. Firstly, on John's last point about R and D productivity, I think we've made incredible progress. I've said upfront. I thought we had.
I really believe that we genuinely have. I think we're definitely playing to win for sure. I just wanna connect it to the overall expectations and guidance. You know, Jean Baptiste and I laid out at Capital Markets Day that we have commitments in 2022 and 2025. We intend to deliver on those commitments without sacrificing super cool science, which means that we're happy to put the organization into a little bit more pressure to redeploy resources to finance science if we think it's gonna be best in class, first in class.
We think that's the right level of tension in organization, not disconnecting the incredible work that's going on in r and d. We have to balance that. Where we sit today, that's a really healthy tension I think we developed. So I'm delighted with that. Secondly and finally, I wanna thank all of the presenters and the people who put a ton of work into putting this together for us.
It's virtual. It's not easy even face to face, even harder virtually. I think it's been an extraordinary series of events that our comms team and others have put together. And you start to see the quality of the bench. You start to see our people authentically and open to debate the science with all those that are curious about whether we believe in it or not.
I'm very pleased and proud of the team that showed up today. I think we've just started. While the work is underway, I think we we really are going to surprise a lot of people, and we're doing things that we think will seriously change the practice of medicine. Some of you will take a bit more convincing, but I'm thrilled with how far we've come and the time we've had. And I'm excited about up and coming r and d events and days in the future.
And thanks again, John, and everybody on the team, and everybody that's put the meeting together. And thank you for all those that joined us. Thank you.