Ladies and gentlemen, good morning and welcome to CSL's annual research and development briefing. It's Mark Dehring speaking, and online with me today is Dr. Bill Mezzanotte, Executive Vice President, Head of Research and Development, and Chief Medical Officer. He is joined by several of his senior team. Also joining us once again is Bill Campbell, Executive Vice President and Chief Commercial Officer, CSL Behring. Bill will be providing us with some market insights on CSL Behring's product portfolio. Please be aware this presentation, as well as the Q&A session, is being webcast. Lastly, before we start, I draw your attention to the forward statement disclaimer within the slide deck. I'll now hand you over to Bill Mezzanotte. Bill?
Mark, and welcome to all who are joining for the 2022 virtual R&D update. I'm really excited to be hosting today. This is my sixth R&D presentation, fourth as Head of R&D. Personally, I've never been more excited to speak to you about CSL's investment in the future because of all the demonstrable progress we have made across the portfolio and in line with CSL's 2030 strategy. Let's jump right into the next slide. Here you'll see that we will have a few presentations today. First, I'll talk about the overall portfolio and give you some insights as to how our portfolio and the news that we've had recently fits into the overall strategy. Then we will go to Andrew Nash, who will give an update on research and some other events occurring within the research and early portfolio.
Following that, Jon Edelman will talk about the exciting advances in our vaccine portfolio. Steven Pascoe, our Head of Clinical and TA Strategy, will then give an overview on a number of clinical-stage programs across the portfolio of CSL Behring and CSL Vifor. As Mark said, holding the anchor position is our Chief Commercial Officer, Bill Campbell, who somehow is always the favorite speaker at R&D Day. As a reminder, Bill will focus his comments on the Behring business and not the Vifor or Seqirus business. Finally, I will return for a few closing remarks. We have a lot of exciting information to convey, so without further ado, we'll go to the next slide. Many of you will have heard Paul Perrault opine on our 2030 strategy. It's ambitious, yet focused, and plays to those core strengths that have made us successful.
While at the same time, it allows space for smart and strategic expansion, which ensures a promising future for patients, employees, the corporation, and for our shareholders. Our R&D organization and strategy is closely aligned with the overall goals set forth by Paul. Today, you will hear about specific efforts related to our therapeutic areas of focus and to our chosen strategic growth platforms, along with the general innovation we are bringing and cultivating to ensure we return a full measure of value and promise to the investment made in R&D. Next slide. As part of the end of the year results briefing, Paul shared with you this slide of the achievements that occurred in R&D during the last financial year. There were quite a few, and many we will discuss again today, but let me touch on a few of interest.
Garadacimab, our anti-Factor XIIa homegrown monoclonal antibody, is showing the promise we knew it had in both hereditary angioedema and other diseases, such as idiopathic pulmonary fibrosis. Berinert SC was submitted to the PMDA in Japan for an indication in the prevention of HAE. Since Paul showed this, we now have received approval from the PMDA and are preparing to launch this important medicine for patients in Japan. We received orphan drug designation for the plasma product haptoglobin for the treatment of the devastating condition of subarachnoid hemorrhage. We have filed for US and EU marketing approval for the first gene therapy for hemophilia B, etranacogene dezaparvovec. Our vaccine portfolio continues to progress, completing the phase 2-A study for our adjuvanted high dose cell culture vaccine, aQIVc, and it now has entered phase 2-B.
Our core products, the cell-based FLUCELVAX and egg-based FLUAD, continue to add important age and geographic expansion. Finally, on the product side, I wanna highlight the CSL964, our alpha-1 antitrypsin program for graft-versus-host disease after stem cell transplant, has moved into the phase 3 portion of that adaptive design study. This is an area of high unmet need, and transplant physicians are anxiously awaiting the results of the trial. Additionally, we announced new exciting state-of-the-art facilities in Melbourne, Marburg, and the Boston area, and also announced the joint venture with WEHI, state government, and University of Melbourne to place an incubator within the confines of our new corporate headquarters in the Melbourne Biomedical Precinct. All these positive messages bring forward an optimistic view of the future for CSL and R&D, and we will pick up again on a number of these items today.
Next slide. CSL is committed to discovering, partnering, developing, and delivering medicines that have meaningful impact on the lives of patients with rare and serious diseases and that help improve the public's health. Because of the positive impact of our medicines, we have helped to substantially bolster the long-term outlook of the CSL enterprise as a whole. This past year, spending on R&D increased to over $1.1 billion. While this is a healthy increase over the past five years, there are a few salient points to make. First, most of the increase has been funneled to new programs to strengthen our portfolio. This includes discovery research, early partnerships, physical development of the medicine or vaccine that a patient safely receives, and the clinical studies needed to achieve registration of our medicines and vaccines.
We have applied rigorous organizational efficiency to our market development and lifecycle management spend so that we are keeping these costs close to neutral over the years. Despite that thriftiness, we have been able to provide the appropriate improvement to existing products, optimize our manufacturing processes, and as you will see in a few slides, have still expanded the geographic footprint of many of our products. Our R&D investment remains in line with CSL's increase in revenue over that same time period and within the promised 10%-11% envelope of revenue. Compared to many of those companies we are successfully competing against, we are spending far less with a healthy rate of return on investment. Lastly, we in R&D do not take this investment for granted nor see it as an entitlement.
We take our role as stewards of the investment very seriously and would spend less if it weren't for so many high-quality opportunities to make a difference. We continue to look for those opportunities and prioritize those opportunities that have the best chance to bring value to our patients and to you. Next slide. Beyond operational budget, CSL has also devoted multi-year capital budget to upgrading aging laboratories and enhancing collaboration space to spur innovation and support our growing global talent base. If you look from the bottom and move counter-clockwise, our new facility in Waltham, Massachusetts, will support CSL's growing R&D vaccine portfolio, including our next generation of mRNA vaccine technology and seasonal and pandemic influenza vaccines.
The custom-built facility consists of approximately 140,000 sq ft overall, with 54,000 sq ft being lab space and with an ability to house about 300 full-time employees. All ongoing R&D programs currently taking place in Cambridge, Massachusetts, will transition to the Waltham facility in the coming months. Construction of CSL Melbourne, our new global headquarters in the Parkville Biomedical Precinct, is on track for completion in late March 2023, when CSL will take occupancy of the building. The facility will house around 800 overall employees, including product development teams from throughout CSL R&D. It will include leading-edge laboratories along with space for external collaborators, innovators, and startups.
The facility is just 500 meters from the Bio21 Institute, where CSL Behring's early-stage research team has been based for over 10 years, and this will further enable collaboration with other researchers in this multidisciplinary biomedical precinct. This type of close proximity to so many biomedical research facilities is rarely enjoyed by biotechnology companies, and we plan to fully exploit this advantage. The new R&D campus in Marburg, Germany, opened its doors in September and is the new home for about 500 CSL R&D employees. This building is almost 40,000 sq m, including 7,400 sq m of internal laboratory space and additional collaborative laboratory space, and in over 10,000 sq m of overall working space, along with a state-of-the-art vivarium. It will be CSL's largest R&D center worldwide and uniquely combines all of our disciplines under one roof.
The new R&D building also offers space for collaboration partners such as universities, institutes, and biomedical centers that are present all over the region. As one of the homes for our future innovation, innovative sustainability was at the forefront of our mind when we designed this building. It was constructed according to German KfW eligibility criteria for green financing and is consistent with the sustainable development goals of the UN. Finally, construction on a new state-of-the-art commercial manufacturing facility in Tullamarine is well underway, with plans to be operational in 2026. This facility plans to produce next-generation cell-based seasonal and pandemic influenza vaccines, as well as antivenoms and Q fever vaccines. While the R&D footprint in this building will be small, it will follow the playbook of facilities in Broadmeadows, Kankakee, Holly Springs, Bern, and now St.
Gallen, where we have dedicated R&D staff to both support and enhance our established manufacturing processes while they also contribute to innovations in product manufacturing and development. Next slide. Speaking of facilities, here is a current map of the locations around the world where we work. CSL R&D is currently comprised of over 2,000 scientists working in 10 countries in R&D centers. Like the M600, which are strategically located near universities, institutes, and biomedical centers. This footprint puts us in key strategic areas of the world, important for accessing partners, innovation, and talent. With the addition of a Zurich location in Switzerland and one in Spain, we have only strengthened the relatively untapped potential to connect with European biotech. It also positions us well to deliver on what you will see on the next slide.
As I mentioned a few minutes ago, we have used our market development dollars wisely, collaborating with our local and regional commercial units to register our plasma vaccine and recombinant products to new patients around the world. I hope you agree that the list here of extensions and geographic spread is impressive. Regulatory expertise is an often underappreciated part of a world-class R&D organization. I am proud to say we have built extensive capability in this area, and this map is partial proof of that capability. Next slide. As I said previously, the strategy of R&D is closely aligned with CSL's overall 2030 strategy. Of course, we need to build for a future even beyond 2030. If I were to sum up the key components of our strategy, they would be on the boxes on the left.
First, to strengthen our core competencies, and we are doing just that across influenza, iron, and of course, plasma. These efforts include some of the yield programs for IG and for flu cell culture and future work to support the iron franchise. To build strategically and scientifically across our TAs, to explore disruptive innovation and be willing to disrupt ourselves if it is for the betterment of patients, to expand into adjacent disease areas or into complementary platforms in known disease areas, and to embrace the external environment, or as I like to say, to be of the world and for the world. If you look at recent R&D related news since the start of the new financial year, and these five depict that, these news items are well aligned with our strategic imperatives and often linked to more than one of them.
I will touch on all of these briefly now and come back to them during the presentation. Starting from the left, recently we announced a strategic option and license agreement with Translational Sciences to license TS23, a first-in-class anti-alpha-2-antiplasmin monoclonal antibody. TS23 is being developed to dissolve thrombi that cause serious complications such as pulmonary embolism and acute ischemic stroke. If this is successful, this medicine would be a strategic addition to both our hematology and cardiology TAs. This product is entering phase 2 now, and Steve will talk about it. Just yesterday, we announced our exciting new partnership with Arcturus Therapeutics, of course, subject to regulatory approval to access their late-stage saRNA vaccine platform technology to develop and commercialize vaccines for COVID-19, influenza, multipathogen pandemic preparedness, and other selected respiratory viral pathogens.
Arcturus is a U.S.-based biotechnology company focusing on developing mRNA and saRNA for use as vaccines for infectious diseases and the treatment of rare diseases. As Jon will touch upon, saRNA, the next generation mRNA vaccine technology, offers the potential for improved immune responses, lower dosing, and favorable safety and tolerability compared to currently marketed mRNA vaccines. Arcturus, of course, is the first company to achieve success in a major phase 3 vaccine efficacy study involving over 16,000 participants using a self-amplifying mRNA vaccine. This collaboration offers a lot, including late-stage platform with scaled-up manufacturing capabilities, which complement our significant expertise in vaccine research and development. By leveraging this technology expertise and resource of both companies, we can strengthen and accelerate our product development programs.
I already touched upon our expanded R&D footprint in areas of the world where a state-of-the-art space will optimize external collaboration. In addition, in Melbourne, we announced with our partners the establishment of a biotech incubator at CSL's new headquarters that will have space for up to 40 startups. Andrew will touch upon this, but this incubator collaboration has had a major positive influence on the startup environment in Victoria. Of course, we have been advancing our own internal pipeline, which will serve to strengthen our offerings across therapeutic areas. Two disruptive therapies are in late stage and will be discussed by Steve. First, our homegrown garadacimab being developed as a long-term preventive treatment for patients with hereditary angioedema, and the patient-focused offering of this medicine is incredible. Notably, etranacogene, a late-stage collaboration effort with uniQure, which has the potential to be the first gene therapy for hemophilia B.
We will show recently released data and durability modeling suggesting this medicine may offer patients a real chance at durable relief from their disease. Finally, the acquisition of Vifor, now CSL Vifor, announced in August brings a strong, exciting, and complementary portfolio of therapies in nephrology, dialysis, and iron deficiency. We recently reviewed the opportunity at Capital Markets Day. I'll come back and touch on some of the things we talked about that day. Taken together, these five very prominent and newsworthy recent items show that we remain both opportunistic, but also grounded in our fundamentals and strategy so that we continue to add meaningful value to patients, CSL, and to you, the shareholders. Next slide.
At Capital Markets Day, you heard a lot from CSL senior leaders about our excitement for the Vifor acquisition, including the assets for patients on dialysis and those patients with iron deficiency. Steve will touch upon some of these projects in his talk later on. I'd like to spend some time focusing on the portfolio impact of this deal, particularly how the CSL Vifor assets and capabilities might enhance those of the legacy CSL organization. One of the unique offerings of CSL Vifor is that their other leading franchises in dialysis and nephrology are competitively positioned and powered by their partnership with Fresenius Medical Care in the form of a joint venture, which is called the Vifor Fresenius Medical Care Renal Pharma. Quite a mouthful. This partnership was forged in 2010 and has achieved global leadership in the treatment of nephrology care.
VFMCRP harnesses the combined expertise and know-how of CSL Vifor's strong pharmaceutical expertise with FMC's leading kidney care capabilities even beyond dialysis. It's a unique business model that comes with a strong and loyal patient population in over 4,200 dialysis clinics. The partnership also provides access to patient data, improves clinical trial design by access to real-world data, and enables faster clinical trial execution. It truly accelerates innovation and improves the drug development process through close collaboration and the sharing of ideas, which we intend to further leverage in the years to come. Of course, the combination is a natural funnel for high-quality external assets, making CSL the partner of choice in nephrology. Next slide. We are very excited about the promise and potential of CSL Vifor's R&D portfolio. The cardiorenal space, in particular, is quite complementary to what CSL Behring was already doing.
This graphic was also shown at our Capital Markets Day and depicts the journey patients with kidney disease might undergo. On the top are CSL Vifor's in-line assets, but on the bottom I've added the combined pipeline therapies that the CSL enterprise has today to help practitioners manage the complications and improve the outcomes in these patients. The combined CSL portfolio already targets some of the morbidities and opportunities present along this disease continuum. Those assets outlined in green are products from CSL Vifor, while those outlined in red are CSL Behring assets. Steve will be reviewing most of these, so I only want to touch briefly. Starting with prevention or slowing of kidney damage, we have sparsentan in phase 3 and a number of earlier stage immunology products that may have the benefit of combating diseases that impact the kidney.
In the chronic kidney disease space, INS-3001 is a subcutaneous calcification inhibitor currently in phase 1. In AEGIS-II, our 18,000+ patient phase 3 study evaluating the efficacy of CSL112, demographic data suggests over 20% of study participants have evidence of chronic kidney impairment upon entering the trial. For dialysis patients, SNF472 for the rare condition of calciphylaxis is completing phase 3, and we have just initiated a phase 2 trial of our anti-IL-6 antibody clazakizumab for the prevention of MACE events. We, of course, are also actively studying clazakizumab for the treatment of antibody-mediated rejection in patients who have received a kidney transplantation. These current offerings are a great start, but we look forward to further opportunities that we either discover ourselves or leverage through partnerships.
This will include utilizing the vast expertise of Fresenius Medical Care, all in the service of expanding treatment opportunities for patients suffering with renal disease, diseases that affect the kidney, and for patients who have the hope of cure through renal transplantation. Next slide. I'd like now to run you through the impact of our activity over the past year since we met with you in 2021. On this slide is the portfolio that we showed coming out of R&D day last year. On the next slide, I'll show you our portfolio as of October 1. On this portfolio view, you will see a few changes. In phase two, we've added the aforementioned clazakizumab study for MACE in dialysis patients. Also, two of our assets that we have outlicensed, mavrilimumab and ablasacimab, have moved from phase one to phase two.
The etranacogene has moved from phase 3 into the filing stage. As you are aware, R&D is a multi-year process that does not adhere to our strict financial year timelines. Thus, the vast majority of products in our portfolio have made good progress throughout the year, despite the continued COVID challenges, but they just have not entered into a new stage of development and so are not mentioned here. Some programs, unfortunately, did not progress as we had hoped.
This was due to a variety of reasons, including extended time to gain health authority agreement on a clinical trial, as was the case with Kcentra in trauma, or because we elected to further explore dose finding, as was the case with aQIVc in phase 2. As was the case for some of our phase 1 program, studies involving healthy volunteer testing seem to have lagged behind the recovery and execution compared to our later stage patient testing clinical trials. One program, CSL346, for the prevention of progression of diabetic kidney disease, did in fact execute on time and top-of-the-line results were released in October. Unfortunately, while CSL346 was found to be very safe, it did not reach our efficacy threshold for continuing development, and so this program will be stopped.
If we put these results together with the acquisition of Vifor and the recent partnerships with Arcturus Therapeutics and Translational Sciences, but minus CSL346, we get the following new forward-looking portfolio. Here on this slide, you can see the impressive cumulative effect of both our recent business development activities along with our internal efforts. Besides the 50% uplift in the number of medicines, the quality of the portfolio is also impressive. In my career to date, I've had the privilege to be actively involved in the development of about seven medicines that could now be considered as standard of care, and I'm quite proud of that. However, in this development portfolio, I conservatively estimate across all stages that at least 10 of the pipeline medicines listed here have the potential, if approved, to be considered standard of care for their intended patient population.
That really excites our team and myself to continue to work relentlessly to bring these medicines through the pipeline and to the patients and public health who are waiting. With that, I'd like to turn the virtual podium over to Andrew Nash. Andrew?
Thanks, Bill, and good morning to all of you on the call. It's my pleasure today to give you an update on some of the important activities being undertaken within CSL Research. The main topic that I'd like to focus on is CSL's strategic multilayered approach to engagement with external innovators. In particular, just how we use this engagement to build a pipeline of early-stage opportunities for our R&D portfolio. Following this, I'll provide some introductory comments and background information on garadacimab. The garadacimab project provides many examples of how external innovation can lead ultimately to a successful phase 3 outcome, and my colleague, Steve Pascoe, will touch upon that phase 3 outcome in his section of today's call. Finally, I'll touch very briefly on the topic of CIDP and FcRn inhibitors, which I know is of interest to many of you.
Firstly, to CSL's engagement with external innovators. As I expect you know, the discovery and development of new therapies is highly competitive. While companies like CSL have very strong internal capability, access to external innovation is critical in order to build a high-quality and sustainable R&D portfolio. CSL, over its more than 100-year history, has an exceptional track record of external engagement. This type of collaboration has been behind much of our success in the past. We think that more than ever, collaboration with external innovators will be important to retain our competitive position and to build our portfolio. For this reason, we take a very strategic approach to our engagement with external innovators.
That approach is outlined on the right here, is multifaceted and leverages our global research sites to enable partnerships with key universities and medical research institutes and hospitals. It enables us to go out to really high-quality medical research precincts and select projects for funding and develop those collaboration initiatives. We look to partner with accelerators and incubators and venture capital funds. As most companies do, we have a strong capacity in terms of external scouting for new and disruptive technologies. We have a group within CSL Research that's dedicated to external innovation and pursues each of these strategic pillars. Looking at some of them in a little bit more detail on the left of this side, you can see that a lot of what we're doing is about creating investable opportunities for CSL.
That is going out to the medical research institutes, identifying really early promising opportunities that need to mature, and investing in those to enable them to move in to the right direction, to a point where CSL will bring them internally into our own portfolio and invest further resources into those opportunities. These early discovery projects are primarily external, and we refer to them as our stage zero portfolio. One of the approaches that we use to building this portfolio is the CSL Research Acceleration Initiative, and I'll touch briefly on that, in the next slide. The third dot point there just highlights a collaboration we announced a few years ago now, which is the Center for Biologic Therapies, a partnership between CSL and the Walter and Eliza Hall Institute.
This allows scientists at Australia's leading medical research institute to access CSL technologies to produce biological therapies against some of the new targets they're working on, and it's currently proving to be a very productive collaboration. In addition to this type of investment in early research, we also directly invest in early-stage companies within the biotech space, startup companies that have some support from VCs and other sources. As I think you know, we're a partner in the Brandon BioCatalyst funds, which enables us to access and cover a huge amount of the startup activity going on within Australia. In addition to that investment, we do invest directly in startups ourselves. A lot of what we're looking to do is really develop the Australian and particularly the Victorian innovation ecosystem.
The ability to build skills, to develop people, to create infrastructure, really creates an environment where CSL Research and CSL R&D more broadly can benefit from the innovation that will take place. We've chosen to base our global research hub within the Parkville Biomedical Precinct. As Bill mentioned, and as I'll discuss a little bit in upcoming slides, we're establishing a biotech incubator in the precinct in collaboration with the University of Melbourne and WEHI. Finally, we have our CSL Melbourne and Tullamarine facilities, which again, will increase our R&D presence and capability within Melbourne. Just touching on our approach to sourcing, you know, really early stage innovation, accessing what we call Stage Zero projects.
We have a team that looks to engage with leading universities in the medical research precincts, co-located or located near to our sites, our R&D sites. We go out to those universities, we talk to them about what CSL's areas of interest are, and we discuss how projects within their groups can be progressed with the help of CSL, taking our advice, funding from us, so that they reach a point where they create or reach a level of value that we would be willing to invest further. Having taken that 1-2 year period to mature, they can then move through into the CSL research portfolio and ultimately through into clinical trials if they prove successful. This is our CSL Research Acceleration Initiative.
It's managed by a team within research, and currently it's operating in Australia, in Europe, and in Asia. It's been a very productive process, and you can see some of the collaborations that have been initiated through the acceleration process outlined here on this slide. These projects at leading universities and medical research institutes are about novel targets, novel therapeutics. They're about platforms, drug discovery platforms, disease models and biomarkers, and they're based on a direct engagement between local academic scientists and CSL scientists. The process runs annually and the geographical expansion is continuing. Just recently, we launched our 24 process across Asia and in areas of Europe that we previously haven't been looking for innovation. A very successful approach to establishing important ongoing strategic relationships with key institutes and universities.
The outcome of all of this activity is shown on this slide. When we're out looking for these opportunities, we very much keep in mind CSL's therapeutic areas of interest. We're looking for projects in the immunology space, hematology, respiratory, CV and M, and transplant. Generally, depending on the area that we're targeting, we look to identify projects that will be an equal mix across those five therapeutic areas. At the moment, we've got about 33 projects in this Stage Zero portfolio, and a number of those we expect to move through into our internal research portfolio. The projects, although operated externally, are managed quite closely by CSL scientists so that they're always heading in the right direction.
On the right there, you can see some recent results from a collaboration that we're doing with the University of Western Australia in hypertrophic cardiomyopathy. We've isolated some peptides, tested them in an animal model, and shown that they have very promising effects in a number of parameters of cardiac function. That's the engagement with the academic community through the research acceleration and other processes, looking at really early stage opportunities that we can progress. In addition to that type of interaction, we feel that it's really important that CSL contribute to the development of the broader biotech ecosystem here in Australia. This is a really important source of innovation for us. It's an important source of expertise development.
The way we see it, the stronger the local biotech sector, the stronger the CSL will be, into the future. For this reason, we've chosen to partner with the University of Melbourne and the Walter and Eliza Hall Institute to establish really Australia's first biotech wet lab incubator that's co-located with a big pharma company. We think it's a really exciting project. It's a $95 million investment, and it will be housed across 2 floors located in our new corporate headquarters that Bill mentioned earlier, and you can see pictured there on the right. Importantly, the partners recognize that none of us have experience in running incubators and getting the best out of the companies that populate them.
We've decided to employ an independent experienced operator, and I'll touch on that briefly in a few slides. The incubator includes lab space, office space, meeting rooms, and everything that is needed for a biotech company to progress to the point where it can expand and develop. The target launch date follows on from the opening of the building and is expected to be 2024, early 2024, although we hope to really bring that forward. It'll have space for up to about 40 startups, 1,400 meters of wet lab space, 1,700 meters of office space. It's being fitted out at the moment, and it's coming together really nicely. We think when we look at this incubator that it has all of the characteristics that make incubators successful.
In setting up this project, you know, we did extensive background research looking at what it takes to make incubators successful around the world, and we looked to integrate those success factors into our incubator. Co-location with a global industry partner like CSL has been demonstrated to be very successful. Co-location in a well-established hub of science and technology, the lab space being affordable with office space available as well, state-of-the-art equipment and facilities, facilitated introduction to investors, mentoring, et cetera. We think that the offering within the incubator will be everything that small companies need to really progress their technologies and mature into successful companies. Of course, in doing that, we're hoping that those companies will provide opportunities for CSL in terms of partnerships, mergers and acquisitions, et cetera.
To make sure that the incubator is successful, as I mentioned earlier, we have appointed Cicada Innovations as the operator of the incubator. Cicada Innovations has a long track record in this space and really is Australia's flagship deep tech incubator. They have 20 years experience in developing ventures. They're Sydney-based. They have a great facility, cutting-edge labs and offices, and offer great training and mentoring services. If you look at their achievements over the last two decades, 326 startups, AUD 1.5 billion of investment, strong exits, lots of patents and lots of jobs created. When the partners look to a company to run and operate the incubator, we think Cicada Innovations is the ideal choice and will really help us make this program the success that we would like it to be.
Moving on to the next topic that I wanted to discuss today. Garadacimab has been a really important project for CSL R&D. It's a project that very nicely highlights our ability to translate early discovery science into effective and innovative therapies. It's a project where external innovation, as I said earlier, has played a really important part throughout the discovery and development phase. As you can see here, the target of garadacimab is Factor XII. Much of the research undertaken in this project over the last several years has been to really understand these biochemical pathways in much more detail and identify therapeutic opportunities. I'm really pleased to say that CSL research has really led the global field in terms of understanding Factor XII biology.
We know that Factor XII is right at the top of pathways that lead to hemostasis and therefore thrombosis. We know that it activates the kallikrein bradykinin system leading to vasodilation, and that's ultimately what leads to HAE. It's important in complement activation, the generation of plasmin, and really excitingly, we've been able to identify a role for Factor XII in terms of fibroblast and macrophage biology, which we think contributes to the pathogenesis of fibrotic diseases such as IPF. A lot of science here over many years, the creation of a new molecule, garadacimab, and opportunities in a variety of disease areas currently being pursued.
Just looking at this process in a little bit more detail, this is you know highlighting the journey we've been on within CSL research and development to really deliver a new and effective therapy for patients with HAE. Going back to the early 2000s, there was a strong external collaboration with the University of Würzburg in Germany, which identified a role for Factor XII in the formation of thrombus. The initial inhibitors we developed were isolated from insects, and while great for proof of concept, weren't ideal for human therapeutics, and that led to the development of a human Factor XII blocking antibody, or as we know it now, garadacimab.
Together with external partners at the Karolinska Institute, and here in Melbourne. We ran a number of animal models identifying a potential opportunity, therapeutic opportunity for garadacimab in the control of thrombosis associated with the exposure of blood to external surfaces, such as in ECMO, but also the role of Factor XII in conditions where vasodilation and vascular leakage is a key part of the pathology. You can see in the bottom right there, a slide that we presented at an investor day back in 2013, where we'd really just identified the role of Factor XII in this model of HAE in mice. This was a really key moment for us and really prompted us to push hard for the development of this drug.
The human antibody was produced here in Melbourne at our Broadmeadows facility and moved into a phase II study, which was published recently and shown to be very successful. As I mentioned earlier, Steve will touch on the phase III program shortly in his presentation. Now, just moving on to the topic of CIDP, its effective treatment with IVIG and the potential for FcRn inhibitors to have an impact in this area. Thus far, as I'm sure you all know, FcRn inhibitors as a class have been shown to be beneficial in autoimmune disease, where IgG autoantibodies are known to play a key and critical role in disease pathology. These antibodies and receptor-based therapeutics work by lowering circulating levels of IgG.
The FcRn receptor is the main pathway via which autoantibodies and all IgG antibodies recycle and remain in the plasma for an extended period of time. It's important to note, however, that their effect is not specific. In addition to reducing the level of autoantibodies, they do reduce total plasma IgG to as low as 10% of normal. Questions that remain to be answered include the long-term safety of such low antibody levels and the potential for variable efficacy based on residual IgG levels, as well as non-IgG autoantibodies such as IgM and IgA. These two types of antibodies do not recycle through the FcRn and therefore are not impacted by blockage of this receptor complex.
The other point to note here is when compared to autoimmune diseases such as myasthenia gravis or thrombocytopenia, CIDP is a much more complex disease, and the role and significance of IgG on autoantibodies is much less clear. Now, while the role of IgG antibodies in CIDP will be further clarified by the phase III studies that are ongoing at the moment with FcRn inhibitors, there is no doubt that IG therapy will continue to represent a proven and effective treatment for these patients. Unlike the FcRn inhibitors, IG therapy targets a number of different mechanisms. Like FcRn inhibitors, it does block the FcRn pathway and shorten the half-life of autoantibodies. Additionally, it acts directly on the effector mechanisms of autoimmune disease.
As you can see on the left of the figure here, IVIG will block Fc-gamma receptors, inhibiting cellular mechanisms of autoimmunity, and is also a potent inhibitor of complement. IVIG is a very effective treatment for CIDP because of its multifaceted mechanism of action. Beyond IVIG, CSL has a number of opportunities within our R&D portfolio that we think will provide important options for us moving forward. We do have CSL730 in a phase I study. This is an Fc trimer that blocks Fc-gamma receptors and will be important in the treatment, we hope, of autoimmune disease where Fc-gamma receptors are involved. And within CSL research, we are looking at developing some FcRn inhibitors ourselves.
We're looking at dual FcR gamma and FcR inhibitors, and we have a number of complement inhibitors in development as well. All up, I think CSL is very well-placed in the area of autoimmune disease. As a foundation, we have IVIG, a proven and effective treatment in CIDP and a range of other autoimmune disease. In our development pipeline, we have both molecules in the clinic and new options coming through within research. With that, I'll hand over to my colleague, Dr. Jon Edelman.
All right, thanks, Andrew. I'm happy to be here today to talk through some of the priorities for CSL R&D in our vaccines portfolio with you. I'd like to start with influenza and what we're doing to improve the ability of flu vaccines to offer protection. This graph is from the U.S. CDC, and it shows flu vaccine effectiveness over the past 10 years or so for all flu vaccines. You can see the effectiveness ranges from a low of 19% to a high of 60%. Now, that's a lot lower than the vaccine effectiveness we've come to expect in the age of COVID-19 vaccines, which are much higher.
I'd like to talk about some of the things that are making flu vaccines less effective than we'd like and what we are doing about it at CSL. Let's start with how the viruses that our flu vaccines target are determined. The World Health Organization keeps a close eye on flu viruses that are in circulation around the world and spends a good deal of effort characterizing those viruses antigenically. They create an antigenic map of the viruses they find every season, which they plot on a grid like this one. Viruses that are antigenically related to one another show up close together on the map.
Since flu vaccines are made from a single virus for each of the strains in the vaccine, the important point here is that the circulating flu viruses that are antigenically related to the virus used to make the vaccine are more likely to be covered by that vaccine than viruses that are antigenically distant. What the WHO is looking for is to see where the majority of flu viruses that they find fall on this antigenic map. Based on this mapping, the WHO and then the regulatory authorities around the world decide what virus to recommend as the candidate vaccine virus, which they call the CVV, to be used for the vaccine. Now, it's important to keep in mind that the majority of flu vaccines today are made in chicken eggs.
Up until 2016, all of the CVV recommendations that were made were for viruses that grew in eggs. Here's an example of that mapping from 2012, and this is for the H3N2 virus, viruses that were circulating that year. Now, the H3N2 flu strain is known to undergo a lot of change, creating new variants frequently. Each dot represents a different H3N2 virus. You can see there's this big cluster of related viruses in the upper right part of the map. Now, the bigger green and yellow dots represent the egg-based candidate vaccine viruses from that year, and you can easily see that these CVVs are pretty far away antigenically from the majority of the circulating H3N2 viruses.
This is a known phenomenon called egg adaptation, where the candidate virus must adapt to grow efficiently in eggs, and as a result, becomes less well-matched to the target virus. What this means is that if a person gets a flu vaccine that is based on a less well-matched candidate virus but is then exposed to one of those circulating viruses, the level of protection could be less. Ideally, we want a candidate virus to be right smack in the middle of the dense cluster of viruses, and it turns out that practically any of those viruses in the dense center there are able to grow efficiently in cells. This phenomenon for H3N2 was pretty common over the years, and this chart shows how often the candidate virus antigenically matched those circulating viruses in that specific season.
Now, as I said, all candidate viruses before 2016 were grown in eggs, which are the blue diamonds. You can see that the match wasn't that great for H3N2 for several years. Now of course, there are four flu viruses that circulate and usually only one predominates in any given season. If H3N2 was not the predominant virus that season, things could have been okay even with a less well-matched H3N2 vaccine. Finally, in 2016, the WHO decided to start recommending cell candidate viruses for manufacturers like us making cell-based vaccines to use, and that's Seqirus, CSL Seqirus' Flucelvax. You can see that those are the red circles here.
Even though they, the WHO did a better job in identifying egg viruses that were better matched to circulating viruses when they started to do that, the cell viruses were always better at matching to the circulating virus as you'd expect. We can illustrate this phenomenon where the red circle is the candidate vaccine virus and the white area represents the main cluster of circulating viruses. The cell-based vaccine has a good chance of antigenically matching the circulating viruses, and in some seasons, that will be better than the egg-based vaccines which have had to adapt to grow in eggs, which means that cell-based vaccines could therefore offer better protection. This turns out to be true over multiple seasons, where you see the relative vaccine effectiveness of FLUCELVAX depicted in this graph is better than the standard egg vaccines used in that same season.
That's at least one area for improvement in flu vaccines. There's another way, and that has to do with the people who get the vaccines, because it turns out that as we age, our immune system starts to lose its ability to generate a great immune response, which we call immunosenescence. That means that older adults are more prone to get the flu even when vaccinated. Because older adults also tend to have more comorbidities like heart disease and diabetes and things like that, they tend to get sicker when they get the flu. These data are also from the U.S. CDC, and they show the mortality rate due to influenza by age. This is from the 2019, 2020 flu season just before the start of the COVID-19 pandemic.
You can see that for people 50 years and older, there is a much higher chance of dying if they get the flu compared to younger folks. What can be done about this? Well, one thing we can do is to add a booster to the vaccine in the form of an adjuvant like MF59. This is what is in CSL Seqirus' FLUAD, which has been around for more than 20 years with over 100 million doses administered. The MF59 boosts and broadens the immune response in these folks, which can help to expand the protection seen. Like with the cell-based vaccine, when you look over multiple seasons, the vaccine effectiveness of FLUAD tends to be better than the unadjuvanted standard egg-based vaccines. Boosting the vaccine with an adjuvant is another strategy.
There's one more thing that can be done to improve flu vaccine performance, and that is increasing the dose of the antigen that comes in the vaccine. There is a higher antigen vaccine on the market, and it does overcome some of the challenges of standard egg-based vaccines as well, which has led the U.S. CDC just this year to preferentially recommend these vaccines for those people 65 years of age and older. That includes the adjuvanted egg-based vaccine, the higher dose egg-based vaccine, and even a recombinant-based vaccine. To summarize, we can improve by using a cell-based vaccine, adding an adjuvant, increasing the dose of antigen, and that is exactly what we are doing in CSL, combining these three proven technologies to make a high-dose MF59 adjuvanted cell-based vaccine for those at highest risk, which will enter phase three in the Northern Hemisphere of 2023.
We expect aQIVc to set the new standard in flu vaccines. At the same time, we are continuing our focus on the next generation of mRNA vaccines, which offer a lot of promise for flu and other viruses. Let me start with a reminder of the differences between conventional mRNA vaccines, like those in use for COVID-19, and the next generation self-amplifying mRNA vaccines. With conventional mRNA vaccines, the mRNA is encapsulated in a lipid coat, which protects it and allows it to enter the cells where the mRNA is used by the cell's own machinery to make the protein encoded by the mRNA, and this protein is the antigen that generates the immune response we are looking for. With the self-amplifying mRNA vaccine, we use basically the same concept, except we add in the genes for another set of proteins that code for a replicase complex.
Now, the self-amplifying mRNA vaccine is also coated in the lipid, and when it enters the cell, the mRNA makes both the replicase complex and the protein that we are targeting as antigen. But the replicase complex starts to make copies of the mRNA also, which in turn are made into the antigen. So for the same amount of vaccine administered, you get much more antigen produced and over a longer period of time, and there are several important advantages of this approach. First, because you only need a certain amount of antigen to generate the desired immune response, this means you can use a much smaller dose of vaccine with the self-amplifying approach.
Sorry, the dose of the vaccine is associated with local side effects from being vaccinated, this means that the next generation mRNA vaccine has the potential for better tolerability. Plus, the self-amplifying approach allows you to include more than one antigen in the same vaccine. The self-amplification tends to more fully activate the immune system, which means not only is the humoral system activated, which is the system that makes the antibodies that can protect parts of the body like the lung from being infected, but also the cellular immune system is activated, which augments the humoral response. If the virus happens to get past the antibody defense and does infect a cell, this system can kill the infected cell and prevent the virus from spreading inside the body.
There's one more advantage, and that is when the cellular system is activated, it tends to create memory immune cells that are capable of turning back on if exposed to the virus in the future. We wanted to put all of these advantages to the test, and I'd like to share some of our preclinical data for flu using this next-generation mRNA technology in the next few slides. To start with, we made a series of vaccines using the self-amplifying approach. We made a vaccine that contained only the hemagglutinin or HA antigen, and that's the one that is currently present in all the approved flu vaccines. Next, we made a vaccine containing only neuraminidase or NA, which is the other surface protein on flu viruses and one that tends to change less frequently. We made these as monocistronic vaccines.
Cistron is the technical term we use for the gene encoding the antigen we're targeting. We made a bicistronic vaccine that contained both the HA and NA genes, and we wanted to see if these vaccines would offer different levels of protection against the flu. To do that, we used a well-known model of flu infection in ferrets. It turns out that ferrets can be infected with human flu viruses, and they experience a very similar clinical course as we humans do. They sneeze, they cough, and the virus infects their lungs, which is something you can measure in the ferrets. This is the experimental design we used. We made three different self-amplifying vaccines, one containing only HA, one with only NA, and then a bicistronic vaccine containing both HA and NA in one vaccine. We made these vaccines against the H1N1 virus.
Next, we vaccinated the ferrets twice, as shown in the picture, and we used either 5 micrograms or one-tenth that dose, 0.5 micrograms of vaccine, ferrets by squirting that very same H1 virus that was used to make the vaccine. The live virus was injected into the nose of the ferrets, and we waited to see whether the vaccines would protect the ferrets. This is what happens if you don't vaccinate the ferrets at all. It's our control group. You just infect them with the virus. What you see is that there is lots of virus in the nose where you administered it, but also lots in the lungs. These control animals were clearly getting infected from flu. If you vaccinate the ferrets with any of these vaccines, the monocistronic versions with HA alone or NA alone or the bicistronic combo, their lungs are completely protected.
This saMRNA vaccine is working in the lung. What about the nose? Here, the story is a little different. Now you see that some of the ferrets show no or very little virus in the nose, even though we infected them in the nose four days before that. If you look, you can see that the level of protection in the nose for the vaccine containing both HA and NA, the bicistronic version, offers the same level of protection as the monocistronic HA vaccine at one-tenth the dose. This means that the NA is making a contribution to protecting the ferret and helping to clear the virus after infection. The next thing we wanted to know is if we could use this bicistronic next-generation saMRNA approach to make quadrivalent vaccines, since that's what we need for people.
To do this, we tested our constructs in mice, as shown on this slide. In this experiment, we made 5 different vaccines, one bicistronic vaccine containing HA and NA for each of the four flu viruses that are found in flu vaccines, and then a fifth vaccine that contained all four, a quadrivalent bicistronic flu vaccine. We tested these five viruses across a range of doses in mice from 100 nanograms to as low as 1 nanogram. After vaccinating the mice twice, we tested their blood to see what kind of antibody responses we could see. What we found was that for all four monovalent and the quadrivalent bicistronic vaccines, we could detect neutralizing antibodies not only against HA, but also against NA. These antibodies were able to neutralize the virus, which we know corresponds to the ability to protect against the virus.
We could see these responses at doses as low as one nanogram for all four strains. We were excited to be bringing this next-generation saRNA technology in flu into the clinic in 2023. We're also excited about the announcement that Bill mentioned that just came across the wires yesterday about our licensing and collaboration agreement with Arcturus Therapeutics to access their COVID-19 vaccine and technology. Arcturus is the first company to demonstrate the benefit of self-amplifying mRNA vaccine technology in COVID-19, and they did this from their ongoing phase 3 study in Vietnam, which, as Bill mentioned, had over 16,000 participants. They reported interim results that showed 95% efficacy in preventing severe COVID, including death, and 55% efficacy for symptomatic COVID-19 in a period of time in Vietnam when the Delta and Omicron strains of that virus were circulating.
It was an unsolicited adverse event rate similar to placebo and no reported cases of myocarditis or pericarditis. This vaccine is currently advancing into pivotal booster trials. The benefits of this collaboration to CSL are many, giving us a path to faster clinical development with a higher chance of success with additional viruses, including those with pandemic potential, and giving us access to an established manufacturing network and a library of lipids that can be used across a variety of vaccines. Of course, this agreement is subject to the customary regulatory review and approval process, and we'll be surely pleased to share our progress in future updates.
To summarize, CSL is well-positioned with our vaccine programs to offer vaccines across the spectrum of need in influenza with our cell-based vaccine for the younger crowd from 6 months of age to 49 years, and for those older adults 50 and above who need that extra level of protection with our adjuvanted high-dose cell-based vaccine. All the while developing the next-generation mRNA vaccines that offer the potential of even better efficacy, better tolerability, speed of response, and flexibility for flu and beyond. We'll be back with updates as we realize our vaccine strategy. With that, I'll hand it over to my colleague, Steve.
Thanks, John, and welcome everyone. I'd like to take this opportunity to update you on key projects in our late-stage development portfolio. First of all, AEGIS-II. If you move to the next slide, please. First of all, AEGIS-II, which is our large outcomes cardiovascular study. We currently have recruited over 18,000 subjects, and the goal is to recruit 18,200 subjects. We're confident we'll be able to close out recruitment in this calendar year. This represents a significant achievement to deliver a study of this magnitude through the pandemic and speaks well to the capabilities in the organization. Moving on, we want to focus on garadacimab, which is, as Andrew said, a homegrown product we're extremely proud of.
This is targeted at HAE. We released or we saw the phase 3 data earlier in the year. The details of this data will be released in an up-and-coming academic meeting early in 2023. What we can tell you is we're confident of the profile we have seen. We think we have a highly differentiated and competitive profile. The efficacy is compelling. The convenience of the product builds upon an auto-injector and once-monthly administration is convenient and appealing to patients. Importantly, the tolerability profile for injectable compares very favorably with the competition. The phase 3 program in the open label component, looking at safety data, is yet to read out. Once we see that, we will move towards filing, which we anticipate will be in the middle of the year.
Bill talked about our recent collaboration with Translational Sciences, and I'd just like to introduce you to the target disease area. You may well be familiar with pulmonary embolus. We're targeting a subset of that called submassive pulmonary embolus. As a reminder, a pulmonary embolus is a consequence of a thrombus that typically forms in the leg or pelvic veins and detaches and passes through the right side of the heart into the pulmonary vasculature when lodges there. You can see on the X-ray on the right a graphic demonstration of this. The left of the two pictures shows a patient having an angiogram, which is where dye is injected into the blood vessels, and you can clearly see an occlusion between the proximal and distal branch of the pulmonary artery, and a decreased vasculature in that distal vascularization in that distal component.
On the right, after the thrombus has resolved, you can see that the opacity, the opacification of the vessel indicating it's patent and you can see increased blood flow. Now, why do we care about all of this? Well, the consequences of having a pulmonary embolus are twofold. First of all, there is an increase in blood pressure and forces the right heart to pump more strongly, causing an acute strain. Secondly, there is a profound neurohumoral response that leads to hemodynamic instability. In submassive PE, it is estimated the mortality at 30 days is about 7%. The reason we're targeting submassive pulmonary embolus is in the more severe form of the disease, thrombolytics are currently utilized. In this part of the disease, thrombolysis carries a high risk of unacceptable severe bleeding, which outweighs the benefit of the therapy.
Now, it has long been the Holy Grail in thrombolytic therapy to try and develop an agent which can dissolve clots and not lead to excessive bleeding, and that is the target for our collaboration with Translational Sciences. On the next slide, an introduction to the agent and the target. TS23 is a monoclonal antibody directed against alpha-2-antiplasmin. To understand the value of this, it's important to look at, first of all, why we believe why tPA is problematic. The upside of tPA is it results in plasmin release, which leads to thrombus dissolution, which is the target for the therapeutic. It also consumes fibrinogen, which prevents the production of fibrin, which leads to new clot formation. It is this lytic state or low levels of fibrinogen throughout the circulation that leaves patients vulnerable to bleeding.
Inhibition of alpha-2-antiplasmin, however, while causing the increase of plasmin and therefore the beneficial effect, does not lead to a consumption of fibrinogen, and therefore we believe the bleeding risk will be reduced. In the bottom right-hand corner, you can see a murine model demonstrating this. On the left-hand side is the model of pulmonary embolus, and you can see in measures of embolus dissolution that tPA is effective when compared to control. TS23, when compared to tPA, is at least as effective, if not more so. Importantly, on the right, in a mouse bleeding model, you can see that tPA increases blood loss in the model significantly. However, TS23 in the same experiment did not lead to excess bleeding, which leads us to believe that there is huge potential to produce a thrombolytic with a small or no increase in bleeding risk.
Where we are in the program is Translational Sciences have delivered the phase 1 study, which has shown near maximal inhibition of alpha-2-antiplasmin and also an impact on the downstream biomarkers. The program is scheduled to go into phase 2 in Q4, and as I said, the first indication, which will act as a proof of concept, is in submassive pulmonary embolus, and subsequently, we'll be looking at other indications to expand the application of TS23. You will all be familiar with etranacogene. You will have seen some of this data before. I just wanted to remind people of what we saw in the HOPE-B study. We saw a profound and impressive decrease in bleeding rates compared to standard of care.
We also saw the Factor IX levels rose dramatically above and beyond what you'd expect with prophylactic replacement therapy. Importantly, that Factor IX level is maintained out to 18 months. What you haven't seen before is we now have seen the 24-month data and the bleeding rates and the Factor IX levels are comparable, which gives us enhanced confidence in the durability of etranacogene. On the next slide, I just wanted to outline for you why we believe that this combination is a true step up in the value proposition and the treatment benefit conferred to patients. First of all, the increased protection from bleeding speaks for itself. What is less obvious is the impact of the disease and medicalization that it has on patients.
An obvious demonstration of this is currently even well-treated hemophilia B patients are recommended to avoid strenuous sports and indeed to avoid occupations that involve some degree of risk. We believe that with the factor nine levels we're seeing here, a large number of these patients will actually be able to normalize their lives. That we believe is substantive benefit that has not been seen with any other treatments. One of the question marks you will all be familiar with with gene therapy is how long does the gene therapy work for? We've all seen examples of what looked like effective products where the efficacy or the effectiveness taper fairly quickly over time.
Now, while we have clinical data on entranacogene out to 24 months and the precursor AMT-060 out to 4 years, we have developed a model which was recently published, and you can see the data there on the right. Our predictions are that the treatment failure rate out to, for example, 10 years will be less than 1%. This information is key to our patients, providers and payers in instilling confidence in the value of this treatment. I would urge those who haven't seen the ICER draft report to read it. Their estimation that they use is effectiveness will be run out to 23 years. The package we have at the moment, we believe is going to provide a highly differentiated medicine.
As you will all know, we are currently under regulatory review with the expectation of that going well. We are ready for launch in Q1 of next year. Moving on to clazakizumab. We have two programs with clazakizumab. The first you're familiar with, which is in antibody-mediated rejection. While kidney transplants have been a huge step forward, they have a somewhat limited benefit in that graft failure out to 10 years runs to approximately 60%. The consequences of graft failure for the patient and the economics of treating the disease are profound. It means that the patient, if another kidney is not available for transplantation, which is the norm, they return to dialysis.
Something that isn't often talked about is the mortality and morbidity associated with dialysis is significant, and the quoted figure is a 50% mortality at five years. The unmet need here, we believe, is very high, and anything to be done to prolong the life of a donor organ is extremely important. We are targeting one cause of organ rejection, chronic antibody-mediated rejection, which occurs in approximately 5% of transplant recipients. The evidence for IL-6 to be a driver of the antibody-mediated rejection is compelling. There are three components to why we believe IL-6 inhibition will be important. First of all, there is a direct effect on plasma cells leading to a reduction in donor-specific antibody production. Secondly, there is an upregulation of T-regulatory cells which suppresses the immune response.
Thirdly, there is an activity mediated through IL-6 on endothelial cells which drives the vasculopathy seen in the disease. On the next slide, there's some data which I think many of you may not have seen, and this is an investigator-led study that was by Doberer et al, that was published last year. This looked at clazakizumab in the same patient group with the endpoint being a measure of renal function, GFR. In the first phase of this study, patients were randomly assigned to clazakizumab or placebo. What you can see demonstrated here is the separation of the decline and the use of clazakizumab was associated with a 60% decrease in that rate. After the twelve-week period, all patients were put under active treatment, and you can see the treatment effect persists in the previously treated subjects.
nIn the placebo-treated subjects, there is a change of trajectory which is supportive evidence for that treatment benefit. Importantly, at 52 weeks, biopsies of the transplanted kidney showed a decrease in the histopathological signature associated with this form of rejection and was accompanied by a significant decrease in the donor-specific antibodies. The reason I think this data is important is it further instills our confidence in the likelihood that the IMAGINE study will deliver a positive data set leading to an important therapeutic. On the next slide is a schematic of our IMAGINE study that we've seen before. As a reminder, this is a study primarily intended to look at graft loss over 5 years. We have now agreed with the FDA that conditional approval may be appropriate based on measures of renal function, GFR, as we saw in the last slide.
In order to do this, we need to recruit 200 patients into the study. We're on target for March of next year to see 200 patients in, who will have to follow a year, which will be followed by the filing, and we hope the conditional approval, timing will be in 2025. The second program we have with Clara is also in nephrology, but this is within dialysis patients. Now, I spoke earlier about the relatively poor outlook for people on dialysis, and a large component of this poor outlook is driven by cardiovascular events. Approximately 30% of any of deaths are associated with cardiovascular events.
The evidence base for IL-6 being a driver of that is based on a combination of data from Mendelian randomization studies, but also too indirectly from the very large CANTOS cardiovascular outcome studies, where both the level of IL-6 and subsequent reduction in IL-6 levels correlated strongly with both risk and treatment benefit. On the next slide, I've demonstrated a schematic of the planned program, the possible ESKD study. This study is designed as an operationally seamless study. Why that's appealing is it will enable us to deliver the study in a shorter timeframe than if we were doing a traditional phase 2b, phase 3. There are two components to why it's able to do that. One is we don't have the white space of protocol approval and submissions.
The second component is we will be able to identify and initiate centers for the phase three whilst the phase two is ongoing. Furthermore, as Bill said, we will be able to leverage the Fresenius network, who have a tremendous track record in recruiting in this patient population. The study itself is, the patients will, we think, take two years to enroll, and they will remain in the study for three years. We are looking for a, we're powered to pick up a 20% reduction in cardiovascular events. The study is an event-driven study, where we need 880 events to meet that target, which equates approximately to 2,200 subjects. I'm very pleased to tell you that the first patient entered the study only last week.
Another important program for us, which is just about to initiate phase 3, which you've heard about before, is Kcentra targeting hemorrhage in trauma. Trauma is a leading or the leading cause of morbidity and mortality in the under 40-year-old age group in the U.S. As you can see from the numbers, there are large numbers of people experiencing severe trauma. A high proportion of those, 35%-40%, suffer life-threatening acute major bleeding. The natural history of that bleeding is the subjects who have the bleeding controlled quickly will not die from the hemorrhage. They are still at risk from other causes of morbidity or mortality, but if the hemorrhage is controlled, they are unlikely to. If they don't die in the first six hours, they're unlikely to die later on from the hemorrhage.
What's been critical is, if we move to the next slide, it's been responsible for us delaying the start of the study, was an alignment with the FDA on the choice of primary endpoint. For us, it was a paramount point of importance. The 6-month endpoint was agreed upon, which hadn't previously been the case. We're now in a position to start the study, which we'll be initiating in Q1. The study itself is what we've described as a large, simple study, which I'll expand upon. One of the problems of conducting clinical research in hyper-acute medical settings is the prioritization of the clinical staff has to be the patient treatment.
You can imagine in busy emergency rooms, that filling out forms associated with clinical trials is a disincentive to take part and clearly unacceptable if it distracts from patient care. What we've actually designed is a study with a traditional inclusion/exclusion criteria check, but subsequent to that, the majority of the data will be collected from the healthcare records. This unburdens the staff in the first 24 and 48 hours, where they're able to focus on the patient treatment. We think this will make this highly attractive to our investigators, and it's in line with the feedback we've had from multiple groups.
The study, as I said, is scheduled to start in February and will end in July of 2026, with up to 8,000 subjects enrolling in the study. Now I'd just like to switch gears and look at some of the assets that our integration with Vifor have brought under into the R&D portfolio. The first of these is a collaboration between CSL Vifor and a U.S.-based biotech called Travere. The molecule is called sparsentan, and it's targeting two rare renal disorders, IgA nephropathy and focal segmental glomerulosclerosis. It is currently estimated in the U.S. that approximately 60,000 patients have IgA nephropathy and 40,000 have FSGS. The numbers are thought to be similar in Europe. The natural history of the disease is a slow decline into end-stage renal failure.
Currently, the treatment options are limited, and the unmet need is clear. On the next slide, which explains sparsentan's mode of action. It's a bispecific monoclonal antibody that targets both the Ang II receptor and the ETA receptor. Now, the Ang II receptor is well-known in renal disease. It's blocked by angiotensin receptor blockers, which form the basis of treatment in many renal disorders and are widely used in both of these diseases. Endothelin-1 is known to be upregulated in renal disease. It drives a vasculopathy leading to vascular inflammation and fibrosis and vasoconstriction, and it has been demonstrated in other arenas that the antagonist can block those effects. The combination of these three, we believe, will be highly effective in these two diseases.
On the right, you can see data reporting out from the interim analysis of the phase 3 studies. These measure proteinuria, which is held to be a very predictive surrogate of decline in renal function. You can see in both diseases, compared to the background ARB blocker, the effect of sparsentan shows a significant and impressive reduction in proteinuria. With the IgA nephropathy, it has been agreed with FDA the conditional approval may be appropriate based on the proteinuria endpoint, and the file is currently under review. We're anticipating the outcome of that in the second half of 2023. FSGS is somewhat behind this, and we anticipate a submission towards the end of 2023. We can move on to the next slide. Just wanted to update you on Ferinject.
This is an extremely important compound in the Vifor portfolio. It's an iron replacement therapy. Iron replacement in the context of heart failure has been getting increasing attention over recent years. It is now advocated in the European guidelines and discussed as an alternative in the US guidelines. It is, however, not a labeled indication. The current study being conducted, the HEART-FID study, is crucial to us. It's being conducted by our partners, American Regent. It will read out in the second half of 2023. This study importantly addresses the key endpoints in heart failure of death and hospitalization. Last of all, I'd like to introduce you to a disease which carries high morbidity and mortality. It doesn't need to say very much beyond the picture of how terrible this disease is.
This is a disease of vascular calcification that leads to large cutaneous lesions, which are extremely painful and prone to infection. The mortality associated with this disease is over 50% in one year, and there are no currently available treatments. The majority of subjects with this disease are on dialysis, and it affects approximately 2% of dialysis patients. SNF472 is directed against the final common pathway in vascular calcification. On the next slide, you can see data from a small open phase two study where SNF472 showed against a variety of measures, both quality of life, wound assessment tool, and pain, a significant reduction across all of those aspects. On the next slide, you'll see the SNF472 is in phase three. The study is coming towards its end.
It's a simple design with 66 patients randomly allocated into a control group or an active group. The primary readout is of 12 weeks, which focuses on pain and wound healing. After 24 weeks of follow-up, we will see the data. That data is scheduled to be available in the first half of 2023. There is ongoing discussion about the timing of regulatory submissions. Last of all, I'd like to thank you all for your attention, and I hope you share our excitement of the breadth of our portfolio, but more importantly, how it's targeted at high unmet need areas with a view to providing truly differentiated products. With that, I will pass over to Bill Campbell.
Thank you very much, Steve, and good morning to all of you in Australia. Certainly a good afternoon and evening to those of you calling in from other parts of the globe. Once again, I'm really honored to share in this presentation with my colleagues from R&D. We are truly a collaborative team, and I want to acknowledge and thank the entire R&D organization for their unbelievable and tireless effort to develop new breakthrough products for the patients and their caregivers that the commercial team has the privilege to service. With that, Rose, let's go to the next slide. I thought what I'd do is start with just a couple of highlights from FY 2022, most of which I think you'll be quite familiar with, and then I'll build on some of this as we go.
As you're aware, we delivered global revenue of AUD 8.4 billion within the Behring business. While significantly impacted by COVID, I'm extremely proud of the commercial team delivering on our promise to patients during this incredible time of uncertainty, and I'll speak a bit more about that in just a few minutes. Despite the pandemic, we continue to invest in commercial infrastructure, technology, and market conditioning to support future growth. In terms of our immunology franchise, despite a continued constrained environment, Privigen and Hizentra have remained market leaders. We have continued our CIDP expansion initiatives, and I'll share some really great data with you in just a few minutes. Within our hemophilia franchise, we continue to maintain Idelvion leadership in all key markets where we participate.
We've delivered successful launches in France and Argentina, and I'll show you some interesting data, and how the teams are doing in just a couple of minutes. We remain quite busy preparing for the launch of what we believe will be the first gene therapy in the hemophilia space with etranacogene dezaparvovec. Finally, our specialty franchise delivered strong growth from Haegarda and Kcentra, and we now have the Zemaira/ Respreeza supply challenges behind us, which should lead to nice growth in the current fiscal year. We can go to the next slide, Rose. As I've done for the last several years, I thought I'd start by framing the targeted protein market where the Behring business is focused. Overall, we see the market in these four broad segments, and they represent a combined market value of about $38 billion.
The overall market has added $10 billion in revenue growth over the last 5 years. This represents an 8% compound annual growth rate despite the last couple of years of the global pandemic and associated market impact. The immunoglobulin segment is the largest now, having grown from $9 billion to $16 billion, representing a 14% compounded annual growth rate. We have been, we are today, and I believe CSL will continue to be well-positioned to continue to lead within these broad market segments. Next slide, please. Starting with our immunoglobulin markets, this is a segment that, as you know, has grown significantly over the past 5 to 10 years. However, clearly, the last 2 years have seen growth limited by the COVID-constrained plasma collections and associated pandemic. We do, however, believe that the underlying IG demand remains quite robust.
In FY 2022, CSL Plasma collections increased significantly on a year-over-year basis, depicted here as 24%. As you know, CSL continues to invest in plasma collection centers. Importantly, we see the leading indicators of disease diagnosis returning to pre-COVID levels. We've spoken a bit about that with you in the past, but I thought what I'd do is share some data with you as an example on the next slide. This slide represents what we believe are some of the key leading indicators, in this case of infection rates leading to a primary immunodeficiency diagnosis. Shown in the slide in light blue are bronchitis, green ear infections, the gray line representing pneumonia, and the dark blue line representing sinusitis diagnosis visits. We have used this data in the past, and we continue to track it quite carefully as a surrogate to evaluate primary immunodeficiency diagnosis.
You can see clearly with the pre-COVID, these rates were very stable. You then see the precipitous drop in March 2020. Not unsurprising given the social distancing, masking, stay-at-home orders, restrictive travel, et cetera. We saw the trough on each of these four infection rates that we track trough in March 2021. Now these rates have returned to about 70% of pre-COVID levels and are continuing to increase. This is why we believe or one reason why we believe the underlying IG demand will continue to grow back to where it was pre-COVID. We go to the next slide. In terms of the CSL immunoglobulin business, we finished FY 2022 at $4 billion, down slightly from the prior year. Having said that, let me share just a few highlights.
For more than 10 years, Hizentra has been the worldwide market leader for subcutaneous IG utilization. More than 75% of our targeted physicians are using Hizentra to treat CIDP. More than 50% of the Hizentra starts in the U.S. are newly diagnosed patients, and that's been somewhat consistent for the last couple of years. We continue to see increased preference for home treatment as a result of the pandemic and the freedom that we believe Hizentra provides patients. Early in the pandemic, we adopted a fairly conservative approach to market development, and as you know, we initiated a patient-focused supply continuity strategy. In essence, we wanted to ensure that patients on a CSL IG could remain on a CSL product, and I believe we were highly successful in this endeavor.
Despite this restraint, we did grow Privigen patient share in the U.S. by about 3% on a year-over-year basis. We maintained Privigen market leadership in key markets around the globe. Next slide, please. Relative to Hizentra, we continue to invest in what I would call our flagship product. This brand, as I just mentioned, has been on the market for more than 10 years and has developed an incredible reputation over that time. We recently launched a prefilled syringe option for patients to enhance convenience, and we'll continue to enhance and refine our product offering to meet the needs of all patients. Importantly, patients continue to report favorable treatment experience with Hizentra, as you can see from the recent survey shown on the left side of the slide. Let's move to the next slide, please, Rose.
I wanted to share some recent performance data with you from our largest market, in this case, the U.S. markets. On the Y-axis are patient numbers over time represented in quarters on the X-axis. On the left side of the slide or the left panel, you can see patient growth across all indications. On the right side of the slide, I've segmented out just the CIDP segment. Hizentra continues to perform at a high level within key markets and in this case, the U.S., but we continue to see this across all of our major markets. Clearly, you can see a bit of a slowdown in growth in the third quarter of 2020 through the first quarter of 2021 due to COVID, and that's now recovered, and we largely anticipate that growth to continue on a nice upward trajectory.
We move now to the next slide. I'll touch for a few minutes on our hemophilia franchise, and first would like to highlight our flagship product, Idelvion. This is an amazing product that continues to grow significantly, delivering a 20% year-over-year growth rate in FY 2022, despite still seeing visits at physician offices somewhat constrained due to the pandemic. Idelvion has reliably delivered on its clinical profile, becoming the standard of care in hemophilia B. We've maintained our leadership across key markets and in fact delivered a couple of new launches which I'll share some data with you in just a minute. Within the hemophilia A segment, AFSTYLA is holding its patient share steady in this highly competitive market.
Within our plasma-derived factor VIII segment, we've maintained market leadership globally in the VWD or von Willebrand segment with a 55% patient share, and Humate-P revenue grew by about 4% in last fiscal year. Next slide, please, Rose. In terms of performance, Idelvion continues to perform at a really high level. I've shared a version of this slide with you over the last couple of years. Just to reorient everybody, the Y-axis is patient share, the X-axis is time. This has been updated through the second quarter of this calendar year, which is the last data point available. As you can see, we continue to add share point growth since last year.
I personally think that this is an incredibly impressive growth curve, especially when one considers the time at which we launched versus some competitors, and you look at order of entry. We move to the next slide. This is a slide I've also shown you in the past but updated through the second quarter. While it's really busy, I think that there's some really important highlights on here. First of all, Idelvion continues to perform, as I've said, at a very high level. Our overall average share is in the mid-40% range, with a range of 22% in Argentina, where we recently launched, up to 63.3%.
I mentioned a few moments ago that we recently launched in Argentina and France, and if you look at the two lines beginning Q1 2021, you see in black the launch in France, where the team has grown this business to a 43% market share in just 5 quarters. Argentina is off to a really strong start as well. We launched in France quite late, and we did that to not destroy value or to negotiate a significantly lower price in this market. Despite that, you can see the performance of the brand continues to do remarkably well even after launching well behind competitive hemophilia B products. Idelvion is truly a special product and one that we're quite proud of. You know, as I've talked in the past, this is a space we know quite well.
We've been innovators in the hemophilia B space for three decades, beginning with our plasma-derived product, MONONINE. Following that with arguably the best hemophilia B product on the market today, Idelvion. Now we are awaiting approval on what we think will be the next pure, truly transformational product in this space. I'm really proud to be associated with this company and the long heritage and history we have in the hemophilia market. We go to the next slide. We truly believe in leadership and helping transform patient care. Toward that end, we hope to be at the leading edge of the next evolution in hemophilia B with etranacogene dezaparvovec. As I just mentioned, we've been in the space for several decades, but we recognize there's still unmet needs for patients.
In particular, as we continue to dialogue with patients around the globe, we hear three major themes from them. They're looking for a more durable protection with their treatment. Secondly, they wanna really live a normal life. They don't wanna think about the hemophilia burden, and they have to do that today given the infusion schedules. Ultimately, patients express that their disease is really quite burdensome, especially from an infusion perspective. While I'm not really gonna talk more about etranacogene dezaparvovec today, as Steve pointed out and as Bill pointed out, we are moving toward approval. Following that, we will have some more dialogue around the product.
Having said that, if we do receive approval, we'll endeavor to be great stewards of this asset, and we'll continue to partner with patients and their physicians, just as we have for the last three decades in this important space. I really believe that the quote at the bottom of the slide really speaks to this next evolution, and I'm so proud that CSL has taken on this mantle, taken on this challenge, and I have no doubt we'll continue to be leaders in this space for decades to come. If we move to the next slide, Rose, I'll wrap up my presentation with a few slides on our specialty products. Our specialty portfolio contributed about $1.8 billion or 21% of the total CSL Behring revenue in fiscal 2022.
Starting with Kcentra, we had a really good year with the brand growing 18% on a year-over-year basis. Kcentra remains the gold standard for warfarin reversal in the U.S., and we believe that we still have substantial growth opportunities given that fresh frozen plasma is still used in about 40% of patients. On the hereditary angioedema side, Haegarda grew 5% year-over-year. Our recent launches in EU and Australia are still somewhat young, but exceeding our expectations to date. We continue to see the treatment paradigm shifting further from what used to be purely an on-demand market to longer-term prophylaxis, and I'll share some data in just a moment. We're certainly quite excited about the prospects of bringing the next evolution into the HAE space with garadacimab.
As I said a couple of minutes ago, following a difficult couple of years with Zemaira/Respreeza , the team working quite hard in that being a bit supply constrained, we now have those challenges behind us, I look forward to the team working diligently to regain the trust and lost patients in the marketplace. If we go to the next slide, I'll share a little bit of data on Kcentra. It continues clearly to be a shining star in our portfolio. This is a version or a somewhat similar slide to what I've shared with you in the past. On the left panel, you'll see the share of fresh frozen plasma utilization in yellow versus Kcentra in purple.
As mentioned on the last slide, FFP still accounts for about 40% of warfarin reversals. This clearly will remain our focus and clearly represents a significant growth opportunity for us. The middle panel of the slide shows you demand expressed in millions of units. This growth has been strong over the past 8 years, and I expect this to continue. On the right panel, you'll see the source of use or the sources of use for Kcentra. I'd point out that our labeled indication is for warfarin reversal only, and that is our area of focus. The team does not promote outside of this labeled indication, but I thought it would be helpful for you to see that. Next slide, Rose. This slide highlights our performance with Haegarda or Berinert SC or subcutaneous, as it's known in some markets.
The Y-axis represents the number of patients over time, and this data reflects our global business. You can see the curve reflects a positive trend continuing overall. Importantly, new patient growth in the competitive market like the U.S. is continuing. Our recent launches, as I mentioned, in the EU and Australia are exceeding expectations. Just to give you some example, within our home market of Australia, the team has done an incredible job and achieved a 70%+ patient share within one year of launch. That is an incredible accomplishment for the team. We have three large launches planned by the end of this calendar year. We're quite busy over the next several months to bring a couple of big markets such as Mexico, the U.K.
UK more formally, we have approval, but getting pricing and reimbursement in place for a couple of the SKUs, and then importantly, a big launch in Japan. Go to the next slide. As mentioned, we continue to see growth in the prophylaxis segment as new products like Haegarda and others fundamentally change the treatment landscape. The green bars represent on-demand therapy, and the dark blue is prophylaxis. These are shown by year with the exception of the current year, which we only have data through the second quarter. Importantly, more than 50% of Haegarda patients have been on therapies for more than a year and quite a few of these significantly longer than a year. We continue to see patients switch back from competing products to Haegarda given the benefits of Haegarda.
Let me wrap up my remarks on the next slide and just say in closing, the commercial team continues to execute on our long-range plan. We have pivoted now from a COVID-constrained approach to a demand generation approach, and that's particularly true in the IG segment. We anticipate strong growth in fiscal 2023, and we continue to prepare for transformational new launches such as etranacogene dezaparvovec and garadacimab in the near future. Finally, I'm extremely proud of the commercial team who's delivered a sustained level of growth over the past decade. It goes without saying, I think, this is where I'd like to end, is we couldn't deliver this performance without a strong partnership with our research and development colleagues.
The R&D team, partnering with commercial on Idelvion, AFSTYLA, Haegarda, and the CIDP indications for our IG products, have produced some of the most important products for our company and certainly for patients and the industry. Our partnership, collaboration, and support for each other is tremendous. In that spirit, I'll hand the presentation back over to my good friend and colleague, Dr. Bill Mezzanotte.
Thank you, Bill, for a great presentation, and thank you to all the presenters who have done such a great job of articulating what promise we have in our pipeline, and importantly, the capability in the commercial organization to bring these exciting opportunities to the patients who need them. I hope this came across to all of you today. I'd like to finish with a few more final thoughts, starting on the next slide. First, once again, here is the forward-looking portfolio from today. It is a rich portfolio across the phases of development, with a great balance across our therapeutic areas, across our strategic platforms of plasma, vaccines, antibodies, as well as some small molecules and across our three commercial business units.
As I stated before, at least 10 of these therapies, and probably more, have the potential to be standard of care, and quite a few have the potential to positively disrupt current treatment algorithms. We're using novel approaches to speed the development to the market. It is an exciting late phase portfolio, full of hope for patients. In the end, R&D is simply in the rewarding business of hope. Next slide. On this slide, you will see the expected full list of notable pipeline events that we believe Paul will be able to cover next year when he presents the full year's results. A number of these events have already happened or are poised to happen, but let me summarize the whole in buckets.
First, our phase 1 program should start to deliver with anumigalumab in immunology, CSL787 in respiratory, CSL889 in hematology, all completing their studies, and INS-3001 starting. In phase 2, clazakizumab will start recruiting. aQIVc for influenza, CSL200 for sickle cell disease, and garadacimab for IPF will all complete. Major phase 3 programs, CSL112 and CSL964 will finish recruiting, and a new phase 3 program with Kcentra will start. We will get much anticipated data for garadacimab, Ferinject, and SNF472, which, if positive, will initiate filing efforts. Importantly, we anticipate conditional medical approval for sparsentan in the EU and approvals for Berinert SC in Japan, Ferinject in China, and the etranacogene dezaparvovec in the US and EU. Please stay tuned. It should be another eventful year. Next slide.
In closing, I'd like to come back to the slide I showed before of our R&D strategic imperatives and enumerate the proof points as to how the strategy and our investment is really starting to bear fruit. We are strengthening our core competencies by continuing to focus on improvements to our core manufacturing processes for influenza and plasma. We are advancing a number of promising R&D programs aimed at improving yield for IG and for flu cell culture. We are not yet ready to present these data, but we hope to be able to delight you all in the second half of the decade with our productivity improvements. Our internal clinical portfolio is progressing across plasma, monoclonal antibodies, and vaccines, and now with CSL Vifor, some small molecules too. We have exciting new disruptive therapies on the near horizon for launch, etranacogene and garadacimab.
We continue to embrace the external environment using our geographic diversity to our full advantage. We have made strategic additions in complementary platforms and TAs with our new partnerships with Translational Sciences and Arcturus, and of course the introduction of our new operating company, CSL Vifor, and their expert contributions in the cardiorenal area, along with their core competency in nanomedicines and iron therapy. Lastly, we remain confident that patients will receive the full benefit of our efforts in R&D because of the world-class capabilities of our commercial teams and their equal dedication to the needs of patients around the world. With that, I would like to thank you for your attention, and now we're happy to answer any questions. Over to you, Mark.
Great. Thanks, Bill. Thanks, speakers. Ladies and gents, as Bill said, we'll move to Q&A. Questions will be queued, and in the interest of giving everyone an opportunity, as with our standard practice, please limit your questions to two. You are of course welcome to rejoin the queue should you have further questions. And of course, to register your question, please press star one. We do have some questions lined up with the first question from Andrew Goodsall at MST. Go ahead, Andrew.
Oh, thanks very much for taking my questions. Sorry, the first one's just a big picture, asking how do we think about R&D spend going forward? Obviously, you've got CSL112 ending. And if we look at the licensing collaboration that you've done, especially with Vifor, it looks to us like the total number would land well above the headline 10% of sales. Just trying to understand sort of how you're evolving your views around the total spend and the return on that spend.
how do we view our spend profile over the next few years. One of the things-
Particularly we-
Sorry?
Oh, yeah, sorry. Just particularly with you know, there's an evolving spend that sits outside the direct spend.
First and foremost, what I didn't mention was our strong portfolio management capabilities we're building to assure that we're prioritizing programs appropriately and that we are.
Expense envelope. We do look at the outward years of milestones that we are committed to, as well as to royalties afterwards. Look at it all in totality of the success those programs bring. We're still confident that we're spending within the envelope we mentioned.
Terrific. My follow-up, not something you mentioned today, but it did come up from the call last month. That's vadadustat. You probably, I'm sure you've watched the GSK vote with the FDA. Just any first reactions on that and the future of vadadustat?
I did note that vadadustat advisory committee, which voted that a positive benefit- risk assessment in patients on dialysis and not a positive one on patients not in dialysis. That's not dissimilar to the data that vadadustat put forward. We are not privy to all the regulatory interactions that Akebia is having, but it would be surprising there's not still some ongoing discussion about the dialysis space. In addition, if you've seen some of the reports, understandably, the HIF inhibitors are gonna have some challenge to establish themselves given some of the safety concerns. Of course, on the other hand, ESAs are still very effective therapies and physicians are very comfortable with them.
I would imagine vadadustat will get approved, at least in the dialysis patients, and we'll see what kind of impact it'll have long term. I think it'll be quite a while for them to get a foothold.
Thank you. Thanks, Andrew. The next question comes from Saul Hadassin at Barrenjoey. Go ahead, Saul.
Thanks, Mark. Yeah, good morning. Just a question on etranacogene. I know, Bill, you said you're not gonna comment on it too much now, but I guess assuming it does get approval in the next month or two, how do we think about transition of patients who are on Idelvion in particular and just the share shift that's likely to happen in terms of substitution? Is that the core cohort of patients that you think ultimately will look to shift to etranacogene? Or do you think you can actually grow the market, you know, on top of your Idelvion cohort? Thanks.
Thanks for the question, Saul, yeah, good morning. I think we've got a fairly, you know, long road to go here. First of all, we have to get through approval. We believe that that will happen. I guess I would characterize this opportunity as a continuing leadership opportunity. We believe that we can build in this marketplace maybe stronger and deeper position than we have today. Having said that, Saul, I don't believe that there is a ton of, you know, group of patients that'll immediately come over to gene therapy.
I think being the first in, there's a host of activities that we're gonna have to do, and then I think patients and their caregivers and physicians will need to get comfortable with, not the least of which will be, you know, the long-term data, long-term safety. There's some, you know, pricing and reimbursement and market access hoops we'll have to jump through. I'm really excited in the end for etranacogene dezaparvovec. I think this has been the hope and the dream of hemophilia treatment centers and physicians for at least 25 years, if not 30 years. I do believe in the long term, gene therapy will be a tremendous option for patients, for long-term care.
I think, Saul, to be honest with you, I think it's gonna be a very, very good opportunity for healthcare systems around the globe from a healthcare spend perspective. Having said that, we think we've got the best product on the market today, Idelvion, and we'll continue to grow that market just as we have each of the last quarters and, you know, share some data with you. We think gene therapy is a really, really important innovation, but we think it's gonna take a little bit of time for some of the questions to get answered in the commercial space. We're prepared with a suite of activities and we'll be ready to launch in the first quarter should we get approval.
I think it's gonna be a little bit of a slow build and I think ultimately a bit additive with Idelvion.
Thanks, Bill. Can I just ask one other question on the Fc space? Just the comments today about initiatives in the FcRn category. Just interested to know why that's an area of targeting for you guys, considering, I guess, how advanced some of the competitors are in that space.
Yeah. I'll let Andrew speak to that in a moment. Obviously, Immunology is one of our core areas and the space is interesting to us, whether we are interested in that exact mechanism or something peripheral to that. It is something that'll work its way over time. Andrew?
Yeah, I think, if you look at the FcRn inhibitors out there at the moment, they're all typical first generation molecules. In some areas they seem effective, but they all have issues. You know, there's the opportunity to look at where there's efficacy, you know, where there's problems and opportunities, and design molecules, new molecules that address those opportunities. You know, we're looking to be in that space, but with molecules with improved profiles.
Thank you.
Thanks, Andrew.
Next question comes from David Stanton at Jefferies. Go ahead, Dave.
Thank you very much, and good morning and good evening, everyone. I wonder if you could. You've given us an update on CSL112, and you've talked about the top line results or the last patient coming in in December. Does that imply that we might see top line results in the middle of calendar 2023 for this project, please?
No, it would take one year for those patients to complete, so their last visit will be in November, December, the tail end of the year. Data will be available two to three months after that.
So data-
Yes, sir.
More like in the early 2024 period. The data I was mentioning was demographic data, and we always know the demographic data and patients in real time to monitor that. That's the only data we know so far.
Thank you. Understood.
Into my follow-up then, or my second question is around Arcturus, and forgive me if I pronounce it wrongly, but you know, is this collaboration ultimately to bring a potential combined COVID and flu saRNA vaccine for CSL closer? You know, is that the aim ultimately in line with some of your global competitors?
The first order of business is COVID alone and applying the technology in flu, and then combination products make a lot of sense as follow on. We're looking at that and kinda take them one at a time and see how it works. But one of the advantages of the self-amplifying technology and the ability to use smaller doses for any one vaccine means that a combination vaccine might be something that'll be better tolerated because the total amount of the vaccine that you need is less than you'll see with the more conventional RNA vaccines. They're gonna have some challenges getting tolerability profiles that are acceptable for an annual vaccination, which is what would be expected for such a combination.
The idea of joining capabilities is not just time, but it's increasing probability of success over time as well. Having the ability to broaden what kind of offerings we might think about in the vaccine space.
Good. Thanks, Dave.
Thank you.
Next question comes from Lyanne Harrison at Bank of America. Go ahead, Lyanne.
Yeah, good morning, all. Can I come back to etranacogene dezaparvovec again? I know that there's a lot going on there, but can you provide some color on, you know, the sort of progress you're having around funding models with payers and what that might look like?
Lyanne, thanks very much for the question. As you might imagine, we've been fairly deep in some of these discussions around the globe. In short, I would say there's a variety of funding mechanisms, and it differs dramatically from region to region. In the U.S., we think the funding mechanism will be just as it is largely today in the hemophilia space. We've had a lot of discussion with payers around the product and pricing opportunities, and we feel fairly comfortable that we're in the right ballpark with our plans in the U.S. In Europe, each market's a little bit different.
There are discussions that are underway that would be an upfront payment with payers looking for a bit of a durability guarantee, for lack of a better word, which I think is fair and reasonable. Then that durability guarantee is different by markets depending on the cost of their current hemophilia B, how they value and how they view the incremental benefit for etranacogene dezaparvovec, et cetera. There are some discussions, although I don't think they're going to progress around an annuity-based payment system. And as you might imagine, there's a lot of issues inside of that given patient mobility, patients moving to different countries, moving out of Europe to the U.S., et cetera. The two primary pathways are the two that I mentioned kind of upfront.
The U.S. Approach that may entail some durability guarantee as well, but I would suggest if that happens, it'll be on the fairly narrow side and then perhaps a bit more of a durability guarantee over time in the European region.
Okay, thank you. My second question is for Bill Campbell. There was a very interesting graph there on PID diagnosis rates, and that shows obviously it's improving but still lagging pre-COVID rates. Where are the bottlenecks on PID diagnosis? Is that still largely due to circulating COVID-19, or is there some other reason that we should be thinking about?
I don't think that there's a dramatic bottleneck. I think clearly we're still seeing circulating COVID-19, and I think that that is, in and of itself, the primary issue. You know, rates have come back, as you see here, up to about the 70% of where they are. Office visits are still down a bit, and that's, you know, a bit of a lingering impact from COVID. Now with office visits increasing, there's a little bit of a delay in getting back into offices. By the way, I should have mentioned, not sure if I did, this is U.S. data only. It's probably the best source of data, and it's based on claims data. I think, you know, patients have learned to live with COVID. You know, you still...
I've been traveling extensively recently. You still see people that wear masks on a regular basis. You still see social distancing. You still see patients a bit apprehensive, or especially those that they may not have a diagnosis with PID yet, but they've gone through years of ongoing infections, and they're not sure why, and it hasn't gotten over the line on a diagnosis. I think patients are still somewhat reluctant to go out.
Thanks.
Thank you very much.
Thanks, Lyanne. Next question comes from Gretel Janu at Credit Suisse. Go ahead, Gretel.
Thanks, Mark. Just firstly, just with garadacimab. In HA, if it does get approved, how do you see it competing with the current products in the market, particularly with Haegarda? Will it just cannibalize those existing patients, and how should we think about that medium-term opportunity there for Haegarda if it is approved? Thanks.
I think that's probably a commercial question, so I'll start. If I got that wrong, Bill, you can add to it. You may wanna add to it anyway from the clinical side. I think, Gretel, this is going to compete really, really effectively, not only with Haegarda, and there undoubtedly will be Haegarda patients that will move over to garadacimab. There will be patients that we believe do quite well on a C1 esterase inhibitor and will stay on it. We think it'll compete really well with, you know, the other product that we compete with in the marketplace that's done, you know, reasonably well, Takhzyro. We think we have. You know, the data's gotta mature out.
We'll have to get approval, but based on what we've seen, we're quite bullish from an overall market entry and competitive basis. Having said that, I would also say there are a lot of different philosophical approaches on market entry. I am not one that believes you shouldn't cannibalize your own product if you have a better, more effective, safer product that benefits patients. We will let the market choose, but we'll be quite bullish and supportive of what we think has the potential to be best-in-class products. We have a nice market share in many markets, but if you take a large market like the U.S. and you're looking at around a high 30s% to a low 40s% market share, there's significant opportunity to grow.
While I think Idelvion and Haegarda will experience some cannibalization, there's far greater opportunity outside of Haegarda.
Gretel, just let me add to that. We're at a little disadvantage because we can't share the data until it's published in a major journal, which we hope to happen in early 2023. It's hard for us to describe, but we're confident that Haegarda and garadacimab can sit together, not dissimilar to the nice graphic John showed about the vaccine world in the future. We think there's a similar graphic to be created in the HAE space, but hard for us to share it with you until we can share the data with the world.
Understood. Thank you. Just secondly, on Arcturus, just trying to understand how does their self-amplifying technology compare to CSL's? Is there a lot of synergies between the two, or are there too many fundamental differences? Thanks.
I think the question was about Arcturus Therapeutics' technology.
It's an interesting kind of learning about the saRNA technology. For that, all the mRNA technologies. Each company that's doing work in mRNA vaccines has the same fundamental challenge in applying the technology. They take the RNA that's manufactured, synthesized, a lipid, mix them together to make the lipid nanoparticles that form the vaccine. The process of doing that is unique to each company. The lipid, the buffer, the method of manufacture of RNA, the structure of the RNA, it's all different. At the core, the technologies are all the same, but actually each one is very different. You know, that's true of Arcturus and us.
When it comes to how we'll work together, our intention is to identify the best of both worlds and progress the products that are within the deal, which include flu, COVID-19, pandemic pathogens, and other respiratory viral pathogens. We're pretty excited about kind of having this deal come all the way through and have it finally approved.
Great.
Thanks, Gretel. Next question comes from Chris Cooper at Goldman Sachs. Go ahead, Chris.
Thanks, Mark. Morning and good evening. Just on EXTRADOS first, you're clearly very confident of launch in Q1, both in U.S. and E.U. Apologies if I've missed it. When are the regulatory decisions from FDA and EMA for that opportunity?
Sorry, Chris, I think I heard you say, when are the regulatory decisions? Our action dates are in the end of November.
Got it. Thank you. The other point I wanted to cover up on, Vifor, you mentioned the importance obviously of the relationship with the Fresenius JV. It's been a platform to launch dialysis and nephrology drugs over the years. Historically, there's been various exclusivity arrangements in the space. Can you confirm if that's still the case or do you now have flexibility to be able to sell to other clinics outside of the Fresenius network?
We're not, we don't have Hervé here today, and it's so hard for me to talk about what exclusivity is and is not available. You know, what I'm excited about is the expertise that sits in there that I believe legally and within compliance, we can discuss future programs and get their insights, which is some of the hardest thing to do as a drug developer, is get good real world insights, and they have both data and expertise to do that.
Chris, perhaps we can follow up with that separately. But thanks for your questions. The next question comes from Sean Laaman at Morgan Stanley. Go ahead, Sean.
Thanks, Mark. First of all, congratulations on the incubator. That's awesome. First question on TRINIDAD. Are you able to give us some insights into the demographic opportunity by age for TRINIDAD? And do you have any insights on the use of Idelvion and versus demographics? As a first question.
Perhaps I can take that. Thanks, Sean. We're targeting patients over 18. That's where the initial studies are being done. Probably the important observation on the demographics is we're not limited by neutralizing antibody status. The broad patient population, adult patient population will be applicable for therapy. I think your second question, probably I'll let Bill Campbell answer that.
Thanks, Steve, and thanks, Sean, for the question. Idelvion's used, as you would expect, fairly broadly, will skew a little younger than 18 in some cases. The product will, you know, cannot be used in the more elderly patients who tend to be on-demand patients that are quite happy with, in some cases, plasma-derived therapy that they've been on or the hemophilia product that they've been on. There will clearly be overlap between Idelvion and etranacogene dezaparvovec for sure, as Steve said, targeting the over 18. From 18 to 60 would be a fairly large overlap with where Idelvion is used today.
Having said that, in markets like the U.S., I'll just use that as an example where we might have a 40% share, a little over 40, 43% share, I guess, in the U.S., there is substantial opportunity outside of those patients that are on Idelvion today.
Great. Thank you. Second question on Freeline Therapeutics coming down the pike, it looks like you guys will have a significant first mover advantage. Is there anything on the technical front that might give you confidence that you can hold share?
I'm sorry, on what product?
On Freeline coming down the pike with their hemophilia B treatment, FLT180a.
Your question was what has us believing we can hold share?
Yeah, correct.
I'm sorry.
When it comes down to technical front comparison of the two products, what makes TRINIDAD better?
Yeah, Look, I don't have a side-by-side comparison of the two products. I will say that our product to date has shown 24 months of durability. In fact, in a phase one study with a different version of the same construct, we have durability data now out to 5 years.
We have an AAV5 platform, as Steve said, that allows people who have neutralizing antibody AAV5 to be treated. The product has shown to be very well tolerated by patients.
Yeah. What I would say is setting the hurdle initially does create barriers for others and as well as being applicable in most patients, which is unusual effect-driven therapy. That's something that others will have to show. What's also important is the rate of transaminase rises in hepatic we've shown is small, and we don't have to give prophylactic immunosuppressants. So they're all key things that is no guarantee that others will pass. I think the other thing that's important to me is the durability issue is gonna be important. Once you get ahead in the game showing longevity, others will be launching off unsubstantiated prediction of longevity. So I think there are reasons to believe we'll have a strong defensive position, but in the end, clearly it waits to be defined by the product profile.
Right.
Great.
Thanks for answering my question.
Thanks, Sean. Next question comes from David Bailey at Macquarie. Go ahead, David.
Yeah, thanks, Mark. Hi, everyone. Just on the IG side, just thinking about some opportunities and risks at the moment. We sort of touched on the CIDP side of things. Just around FcRns, just what proportion of CIDP patients do you think might be suitable for an FcRn antagonist? Conversely, on the opportunity side, just an update on Hizentra and neuromyelitis optica and the opportunities in CLL with hypogammaglobulinemia.
Yeah, sure. I'm sorry. Yeah, sure.
Go ahead, Bill.
Sorry, go ahead.
David, thanks for the question. Maybe I'll start on the market questions, and then Steve and Bill can add to that. When you ask about the suitability and what % of patients we think are suitable for FcRn, I think the first thing I would say is, you know, it's hard to know because we haven't seen the data, and I guess we'll have to wait till the data, and I presumably you're asking for CIDP.
Sure.
matures out and we get a chance to see it. I would, you know, probably say some of the same things I've said in the past. You know, we've done the largest trial in CIDP. We know it's difficult. We know it's hard. We also know that we have two really great agents in Privigen and Hizentra that have the indication and have a multi-year lead into that marketplace. I think it, you know, it's interesting to think about some of the new technology and, you know, we'll have to see what the product looks like in the clinical trial.
Having said that, these aren't patients that are easily just gonna jump off what they've been on after a very difficult road to be diagnosed, just to try something else unless it has tremendous efficacy. It's a high bar. We believe they're already with Hizentra. It's really hard for me to say what percentile I think is suitable, at least from the commercial side. Maybe, I don't know, Steve or Bill, if you'd like to add to that from the clinical side.
Yeah. Let me just add a couple comments and then turn it over to Steve to address the second part of that question. You know, I think Andrew tried to show in one of the slides that the response to FcRNs is in part related to how many autoantibodies are circulating. You know, we just don't know in CIDP. It's not as clear as some other diseases. It could be that CIDP is a heterogeneous disease just like COPD and other diseases, in which case X percentage might respond. What that X number is, though, is hard to say out of the chute. Steve?
Yeah. No, I won't comment further on CIDP. I agree with everything that's been said. You also asked the question about. We've seen the Octapharma data that was published recently. I think this is encouraging. Our own phase 3 program is well underway, and we're looking forward to generating data there. I think the data will be compelling, and I can see a significant opportunity for IG therapy in general in the area. I believe you also asked about CLL. We had plans, excuse me, to conduct a randomized study. The world has moved on now, and the guidelines in hematological oncology now recommend the use of IG in patients with hypogammaglobulinemia.
We concluded in the end that the ability to run a meaningful clinical study, the feasibility would be low, but the ethics would be extremely difficult, and our advice was to that effect. We won't be proceeding with a randomized study approach, but we do know with the increased utilization, currently, there is an opportunity for us to take forward an evidence package based on real world data coinciding with some data we generate ourselves. We're currently very actively exploring that space because it's clearly secondary immunodeficiency is a big opportunity and currently is something that's already being realized out in the real world.
The practitioners are so convinced of the utility, they don't want to take part in the study to study the utility.
Okay, thank you. My final follow-up just on Kcentra in trauma. Just important, a label will be for growth going forward.
Sorry, you cut out a little bit. Could you please repeat that question?
Sorry, just Kcentra in trauma. Just trying to understand what proportion of use, if there's any off-label use for trauma at the moment, and then the importance of having a label to get there and speaking to specialists and what it might mean for growth going forward.
Bill, I think that's for you.
Yeah. Thanks. Thanks, Phil. I'm happy to take it. David, thanks. I'll just refer you to the slide on Kcentra. On the right-hand side was use in warfarin reversal, use in DOAC, and then the large portion in green at 49%, no prior anticoagulant use. I would offer to you that the vast majority of that in green is in the trauma space. Again, it's not an area where we obviously promote today or can promote. Having a labeled indication, I think, you know, I think we believe is highly important. It's a little bit like the analogy I would use is in CIDP. IG was always used in CIDP, in Privigen and in Hizentra in the U.S., but yet we didn't have an indication.
Having gotten the indication, we've grown that segment somewhat significantly. Then beyond that, I would say there's a lot of institutions and ER departments and maybe usage outside of hospitals when I think of trauma that would benefit dramatically for a quick reversing agent. I think it's important. I think there's clearly use and experience there, but there is significantly more use outside of where we are today. The indication would allow us to go after that on a more aggressive basis. Frankly, there's some synergy because we're in hospitals already with Kcentra. It's well known as a warfarin reversing agent, but our teams are there with IG and there's a really beautiful synergy for us, and we happen to think a really nice opportunity.
Frankly, a great, you know, if it proves to be successful, a really wonderful option for treating these patients who really are, in many cases, near life and death.
Good. Thanks, David. Next question comes from David Low at J.P. Morgan.
Thanks, Mark. I'm having a bit of trouble hearing. Just a quick one from me. We've heard CSL and the talk about the challenges for mRNA flu vaccines to make. Clearly, the investment is being made in this space. Just wondering what the expectations are now for when we might see competition, be it from CSL, be it from others, with mRNA flu vaccines, please.
I'm sorry, the question was when you might see competition from an mRNA vaccine in influenza? Is that right?
Yes, that's right.
Yeah. Thanks, David, for the question. We are in the process, as I mentioned, bringing into the clinic our own saRNA vaccine will start later in 2023. That's the start of our program. I think this licensing and collaboration agreement with Arcturus allows us to really accelerate that by having the opportunity to have multiple constructs and made and also access to the manufacturing platform that they have and the network that they have. It takes time to do vaccine development for flu and, you know, we'll have to go through the stages.
We're very confident that our bicistronic, our two-gene approach with hemagglutinin and neuraminidase in the quadrivalent form is gonna be an important differentiator for our vaccines compared to what the guys who are ahead of us are projecting. Yeah, I can't give you an exact time because, you know, development takes the time to run the studies, but we're on the track.
We don't know enough about our competitors' timelines to give you an answer there.
Okay, thanks. That's it for me.
Okay, thanks, David. Next question comes from Steven Wheen at Jarden. Go ahead, Steve.
Thanks, Mark. Just a question, sorry to take you back to FcRn, given it's about to go into a phase where it's quite a noisy or a lot of data perhaps being released. I'm curious around the safety profile that you have spoken to quite a bit over the years. What is giving you the sense, I mean, intuitively it makes sense that it would be an issue, but are you seeing any sort of real world data that might sort of give you further sort of insights into the safety profile. Are you suggesting that for FcRn to proceed, it might have to be done in combination with IG?
I don't speak for Andrew. Maybe he wants to say some things, but, you know, we haven't seen a lot of data, right? I think Andrew is speaking to the theoretical impact of dropping your antibody levels to that degree. It may turn out to be safe and may turn out to have deleterious effects, or at least infectious side effects. We'll see. To your last question about could there be a combination? Well, if there is patients who drop their IG, just like in CLL, certainly physicians will follow with their choice of how to counterbalance that. We'll have to just wait and see.
Okay. The second question I just had was more of a commercial one, just around Zemaira/Repreeza . I mean, obviously a few false starts here with regards to the availability of product. How do you sort of, I guess, break back into that marketplace, considering you know the restrictions on access to that product that you've experienced to date?
Steve, thanks for the question. It's Bill. Good to talk with you. It's a great question, and it is challenging. We've been in the alpha-1 space, as you know, for quite some time. Unfortunately, we have had some supply challenges over the years, and have built a bit of capability on reentering this marketplace. It is. You know, I would just say first and foremost, I feel badly for patients and patient access, and this has been a challenge and I feel badly for the team who's worked so hard to create this market position for us. Having said that, what we've seen in prior situations that have been somewhat similar is that the market is still a bit underserved.
We think that there's still some opportunity to grow in a couple of spaces, both in Europe and in the US. I, you know, honestly think it's gonna be a bit of a slow build back. We've got to reestablish, you know, trust and reputation in this space. But it is a space that we've been in for a long time. We've tried to be quite upfront with patients. We've tried to help find alternate sources of supply for them, as well. So I'm confident that the broad commercial team is gonna work extremely hard to get back after this. I think we'll see some uplift as we go through the next, you know, eight to nine months. But it's not gonna be easy. You know, we've had a lot of discussions.
If we couldn't come back and stay back and be a really valuable supplier and a supplier that can deliver from here forward, we should make some alternative decisions. We’ve made all the right investments in supply now, and so it's now time for us to rebuild. It's gonna take a little bit of time and effort, but this is an important space and one that we've been in, and we think we will slowly but surely regain lost ground. I suspect by this time next year when I'm presenting to you at our R&D Day or one of our financial updates, that I'll have some fairly positive news to share.
Good. Thanks, Steve. Next question comes from Mathieu Chevrier from Citi. Go ahead, Mathieu.
Hi. Good morning, good afternoon, and thank you for taking my questions. The first one is just on albumin growth's been lagging IG growth for some time, and there doesn't seem to be new developments ongoing to expand into new therapeutic areas. How do you see this and the potential switch of patients to garadacimab impacting plasma economics and then the pricing of IG over time?
Bill, would you like to?
Mark, I'm not sure if that question was directed to me or somebody else. I had a very hard time. It was breaking up. I heard something about albumin market lagging, and I couldn't hear the rest.
Yeah, maybe I can try again. Albumin growth's been lagging IG growth for some time, and there doesn't seem to be new development going on to expand the use of albumin. I just wanted to know how that combined with the potential switch to garadacimab is impacting the plasma economics as well as the pricing of IG over time.
Sure. Let me try to peel those apart a little bit. The albumin market is historically been lagging a bit on the IG side. Having said that, we spend a tremendous amount of time understanding market leader economics and being balanced between IG and albumin. As I say that, with our longer range forecast, we are largely balanced for out through the midterm, I would say, and I'll leave that to how you wanna define midterm. Having said that, there's opportunities in markets like China still. We've been a bit hand to mouth in China for the last couple of years. Yes, we are the market leader and yes, we have a really good position there.
Having said that, Mathieu, we think that there's still some opportunity there. There's, you know, an immediate opportunity in the U.S. that we have heard recently a competitor, you know, having a fairly significant shortage for the balance of the calendar year in the U.S. market. We'll continue to try to take advantage and leverage those opportunities. There are markets that we haven't entered yet. While this example is a large one and the pricing would be all over the board, we haven't entered India largely as a commercial market, and I have some strong desire to ultimately move into that space. We think that there's some interesting albumin opportunities there.
To be honest with you, it's not an area that I lose sleep on or over in the last year or 2 or 3, and I don't see that as a significant challenge. The broader issue is always plasma collection and, you know, hopeful that there's not another, you know, COVID-19 variant that impacts plasma collection. Again, I think that's a bigger concern that I have, you know, versus the balance here. The second question is, garadacimab versus Haegarda doesn't have a significant plasma economic impact to us. We use, you know, a whole lot of plasma for Haegarda today.
There's the plasma side, and then that would be way more offset, for instance, if CSL112 were to be successful. On the other side of the coin, a monoclonal antibody like garadacimab could be quite interesting from a margin perspective, you know, setting aside for a minute what we think is a really tremendous clinical profile.
Understood. Thank you. Maybe just a second one on Arcturus. I wanted to get your thoughts on the narrative bringing to market a COVID vaccine, given all the competitors out there that have been quite successful.
Yeah, thanks. Thanks for the question, Mathieu. We've been thinking about this a lot. I'll start and maybe Bill wants. Actually not. Let me own it completely. The clear direction for the COVID market in the developed countries is the booster market, right? The vast majority of people have gotten their primary series who are going to get them. The virus is showing every indication of behaving like influenza. It, like flu, is an RNA virus, and it shows, like flu, the ability to adapt and survive as a virus.
That shows up in all these different variants and variants of concern that are motivating the regulators to recommend booster doses and, you know, the CDCs of the countries around the world to recommend these booster doses. What we see, the market evolving to an endemic situation, probably seasonal, and therefore, leveraging the systems that are in place in influenza to be applied to the SARS-CoV-2 virus with recommendations for changes to the relevant strain as they come. We think that this is a real strength of ours. That's a CSL Seqirus strength.
We think that the technology that we'll have and we'll have access with Seqirus and Arcturus and the CSL R&D together are gonna position us to be competitive with the guys who are way in front of us. We have the opportunity to show the advantages of the self-amplifying element, which, as I mentioned earlier, lower doses with potential benefits there, multiple genes potentially. We could have, you know, a single vaccine that contained genes from multiple variants. We think that this is a place where we're gonna be able to compete.
Good. Thank you. Thank you, Mathieu. Ladies and gents, we do have two more people in the queue, and we have time to take those. After that, we'll need to draw to a close. I invite Shane Ponraj from Morningstar. Shane, your question, please.
Yeah. Thanks, Mark. Just one question from me. With the CSL112 study, I believe phase 3 interim data, although not public, has already been analyzed. Just seeing how enrollment is completing next month, which is 200 extra patients, is it fair that that implies the interim data was positive given you're probably recruiting less patients now than originally planned? Thanks.
Yeah. No, it's the last analysis we did was somewhat, I think, misunderstood. It was an analysis to stop the study if we saw overwhelming superiority. The fact the study has continued tells us we haven't had overwhelming superiority. It was a very high bar in the analysis, so it's not a surprise. It doesn't in any way inform us on the likely success.
Good. Thank you.
Similarly, the first two analyses were futility analyses, and only stopped it for overwhelming futility. So we're somewhere between those two.
Thanks for your question, Shane. The last question in the queue comes from Chris Cooper at Goldman Sachs. Go ahead, Chris.
Thanks for squeezing me in, Mark. Apologies for coming back to FcRn, but it is interesting that, you know, you've made a decision here to start looking at this class at this stage. Can you just confirm which indications might be of interest to you? I guess your commentary today and previously would effectively rule out CIDP. But I'm just curious from your perspective to hear which indications would make most sense. Thank you.
I'll start and then turn it to Andrew. I mean, you know, these are early research programs, and we don't always identify indications right away. There's certainly some areas that could be more interesting than others. Andrew, I'll let you speak to that.
Yeah. Look, I think the path seems fairly well trodden by those that have come through clinical trials already in terms of ITP, MG, and some ongoing CIDP studies and some other autoimmune diseases. I think for us, you know, areas like CIDP, if there's a positive outcome from the current clinical programs and other diseases that are important for our immunology franchise, will be obvious places to look.
Good. Thank you, Chris. We have no further questions in the queue, so I will draw the briefing to a close. Finally say thank you very much for your interest in CSL, and good day and goodbye.