Ladies and gentlemen, welcome to CSL's Annual Research and Development Briefing. Online with us today is Doctor. Bill Mezzanotte, Executive Vice President, Head of Research and Development and Chief Medical Officer. He'll be joined by several of his senior team. Also joining us once again is Bill Campbell, Executive Vice President and Chief Commercial Officer.
Bill will be providing us with some market insights and CSL's product portfolio. Please be aware this presentation as well as the Q and A session is being webcast. And lastly, before we start, I draw your attention to the forward statement disclaimer within the slide deck. I'll now pass you over to Bill Mezzanotte. Bill?
Thanks, Mark, and welcome once again to the CSL R and D Day, where we try in a relatively short period of time to summarize and highlight all the activities of the year. Once again, we are conducting this meeting virtually. And while I miss seeing you all in person, the feedback you provided to Mark after last year is that maybe you don't miss seeing me as much as I miss seeing you. I guess in part because that allows you to be more efficient with your time. From my perspective, what the virtual allows is for CSL to highlight And involve more of our scientific talent that reside around the world.
And they are really the ones who are driving the programs that we will highlight today. Next slide. This year, I am joined once again by our Head of Sharing Research and Chief Scientific Officer, Andrew Nash our Head of Securus R and D, Russell Baster and as Mark said, our Chief Commercial Officer, Bill Campbell. I'm also pleased to be able to introduce to you Neerdra Bavard, our SVP and Head of Strategic Operations in CSL Behring And Ethan Sotembre, our Head of Research at Securus. I'm confident you will find all of their presentations and content enlightening and thought provoking.
And as always, we'll have time for questions. Like last year, we'll concentrate the Q and A in one longer session at the end rather than split the questions into So without further ado, let me get started on the next slide. CSL is committed to discovering, partnering, developing and delivering medicines that have meaningful impact in the lives of patients with rare and serious diseases And that it helped improve the public's health. Because of the positive impact of our medicines, we have also helped to substantially bolster the long term outlook of the GSL Enterprise as a whole. We've also committed to a thoughtful use of your investment dollars.
Across the enterprise, We continue to invest between 10% to 11% of revenue in R and D. Consequent with the company's growth in revenue, we have been able to invest more absolute Funds into the programs that we believe have the greatest opportunity to bring value to patients and to our shareholders. As you see the last financial year, we crossed the US1 $1,000,000,000 mark. In general, that spend is split into 3 large buckets. The first is new product development.
This includes discovery research, early partnerships, physical development of the medicine or vaccine a person receives And the clinical studies needed to achieve registration
of our
medicines. This continues to be our biggest category of spend. The other two categories are also quite important. Market development seeks to expand our medicines to as many appropriate patients And markets as makes sense and to expand the indications of our existing medicines such as the new pediatric indication We sell that, that Russell will mention. And then importantly is a third category of life cycle management.
CSL R and D continues to spend a substantial part of our budget to optimize our current products and manufacturing processes, So that they are as robust and reliable as possible. These efforts help our operations group be as efficient as possible, Value that is then seen in return on invested capital and therefore serves as a direct benefit to you, the investor. Included in this category are ongoing efforts to improve the yield of IG, albumin and cell manufacture. If we turn to the next slide, we can see the fruits of our efforts in the product development space over the past few years. We at R and D are quite proud of the consistent stream of new products that have come to market over the past decade and this slide highlights the We've enjoyed over the past 5 years.
And while our successes have been concentrated in the immunology, hematology and influenza area, We look forward to expanding the therapeutic areas we are actively serving in the next 5 years. On the next slide, we'll show you the FY 'twenty one results of our market development efforts. Here are all the regulatory actions from global health authorities during the year across the Behring and Securus groups, which is a direct result of our filings and active engagement with the health authorities. These Decisions include new initial marketing authorization and approval, new line extension or indication approval, Expansion into new geographies and important orphan drug designations. You can see the impressive geographic spread of this activity, which helps support the regional growth in revenue that Bill Campbell will touch upon later.
Not included in this slide are the more than 1,000 yearly submissions for label updates we do for our existing products around the world to ensure that prescribers have the most up to date information regarding any changes to our medicines or vaccine. This activity helps importantly to maximize the benefit and minimize the risk of our life saving treatments. Next slide, please. Part of our evolution has been defining those therapeutic areas and scientific platforms we want to focus upon to help improve the efficiency of our efforts And to maximize both our chance of success, but also our future growth opportunities. Our 6 TAs are immunology, Hematology, Respiratory, Cardiovascular, Transplant and Influenza.
And our scientific platforms plasma fractionation, recombinant technology, gene and cell therapy and adjuvanted Cell based, egg based and self amplifying mRNA approaches to vaccine development. Through careful Prioritization and resource management, we've been able to advance programs in all of these areas while continuing to hold to our spending discipline. 3 years ago at this session, I introduced you to the concept of our therapeutic areas in the Bering organization, Co led by commercial and R and D leaders and a similar framework exists on the secure side. We believe that such a healthy dynamic tension allows us to maximize the scientific, clinical and commercial impact of the medicines we choose to develop. Such co leadership also allows us to develop deep scientific and commercial insights and expertise in the areas we choose to compete in.
We then also apply the same joint expertise as we look for partnering opportunities and business development across the span of R and D from early research through to commercialization. Such expertise, experience and focus Help pave the way for our newest exciting partnership with UniCure on the gene therapy for hemophilia B at Trinidad that you will hear about from Andrew and Deirdre. Next slide. Here is a slide you've seen from Paul Perrault that he shared at the end of the year results. You can see the progress occurring across all 6 therapeutic areas.
A number of these we will touch upon again during this call and so I won't Reiterate them now. But you can see in this slide a microcosm of what in R and D we aim to do. Advance new exciting therapies and vaccines, expand our therapies and indications into important countries like Japan and execute on meaningful new business development, all in the same year and hopefully every year. Next slide, please. I share with you here the slide we showed at the end of last year's R and D Day.
This gives you a picture of where we were when we met last year. A time, as you remember, of high uncertainty across the world, But also a time of great pride for me and how our entire organization stepped up to the challenge of trying to develop new therapies for COVID And how we continue to progress the portfolio despite the challenges of COVID. And as we have suffered 2 more waves of the pandemic since, I continue to carry that sense of pride in the organizational resilience we have shown. After more than 18 months under siege by COVID, I can share a few general themes to the disruption to R and D caused by the pandemic. Things like lab supplies have been in back order due to both supply chain disruption and the diversion of equipment ingredients to vaccine Thanks.
Animal models have been more challenging to conduct as CROs struggle with adequate staff And slots are reserved by governments to facilitate their own targeted efforts. Lab equipment needed to monitor the safety of patients And hospital based trials have been more impacted than outpatient based trials, And this is for a number of reasons. First, we've seen hospital based clinical trial staff being diverted to general clinical staff as hospitals deal with a surge of And some clinical sites have been closed altogether as hospitals become focused on COVID only morbidities. Hospital based staff, investigators and trial coordinators have been personally impacted at a higher rate than outpatient based staff. We've had investigators and coordinators become gravely ill and unfortunately even die from COVID.
The clinical burnout being experienced by many hospitals is spilling over to the clinical trial sites as well. Despite all of this, our R and D staff continue to demonstrate their resourcefulness and shifting plans and working with sites To find alternate ways to schedule visits and tests, source supplies and still progress our portfolio, Which they have. Great stuff. Next slide, please. Speaking of COVID, we of course took part in many efforts on the COVID front.
As you'll hear from Russell in a few minutes, In Australia, we partnered with the University of Queensland on the SARS CoV-two vaccine. Phase 1 immunogenicity was excellent. Unfortunately, The appearance of a false positive HIV test led to the difficult decision that the potential public health confusion of such false positive tests Would outweigh the potential public health benefit of the vaccine. We of course continue to proudly partner with AstraZeneca and Oxford University to manufacture their vaccine for Australia and the Southern Hemisphere. Globally, we conducted a Phase study investigating the impact of garidastimab on patients with severe respiratory distress from COVID.
While the treatment did confer some benefit, The results were not positive enough to support moving into Phase 3. We were also enormously proud of our global collaboration efforts with other plasma manufacturers to collect and manufacture a common hyperimmune that was then studied under the auspices of the U. S. National Institute of Health. Unfortunately, the study did not demonstrate any benefit as a hyper immune on top of remdesivir for patients hospitalized with complications from COVID, and so we ceased work on this therapy.
We did, however, devote our pilot plant capabilities in the U. S. To manufacture 11 large scale batches of SAB Biotherapeutics, Bovine derived humanized hyperimmune COVID therapy that is currently in a global Phase 3 trial, investigating it as an outpatient treatment in patients with earlier COVID infections. Outside of COVID, we had 3 major projects Our adjuvant and cell based vaccine for flu AQ IVC advanced into Phase 2. And as Russell will tell you, we've efficiently conducted these trials.
Caridatsumab, our monoclonal antibody against activated Factor 12 progressed into Phase And Deirdre will update you on this progress. And CSL-nine sixty four, which is alpha-one antitrypsin being investigated as both Treatment and prevention of graft versus host disease in patients having undergone allogeneic bone marrow transplantation, Completed its Phase 2 prevention trial and passed our internal stage gate into Phase 3. The treatment study is also being conducted by the North American bone marrow transplant consortium and is already actively recruiting in Phase 3. We expect the prevention trial, which we are conducting internally to enter its first patient this quarter. As you are aware, R and D is a multiyear process It does not adhere to our strict financial timelines.
Thus, there are many other products in our portfolio that have made good progress throughout the year Despite the COVID challenges, but they've just not entered into a new stage of development and so are not listed here. Other programs unfortunately did not progress as we had hoped. We made the difficult decision to terminate CSL-six 30, our plasma derived factory therapy to be developed at our RADA plant. This was a business decision and not a safety or quality issue. Our desire is to focus our efforts on our IG and albumin production programs and because of the competitive landscape in China, We did not foresee commercial success for this product.
We will instead focus our efforts on bringing our recombinant programs to China, starting with Idelvion and Astellas. Due to technical reasons and the evolving competitive landscape, We also elected to terminate our CSL-two hundred gene therapy program for sickle cell disease. We are still quite bullish on the technology we acquired from Calimmune and are applying it in our collaboration with Seattle Children's Hospital as Andrew will point out in a few minutes. We also remain committed to meeting the unmet need in sickle cell disease and our haemopexin program for treatment of vaso occlusive crises in patients with sickle cell disease continues. In last year's proposed FY 'twenty one highlights and the target launch dates, we indicated the desire to file etrenidaz, Begin our study of garidasumab in IPF and have started our trauma trial and case centric.
Based upon general class related concerns from FDA and EMA about durability of effect, we extended our etrenadev Phase 3 trial to Capture the additional data requested. We feel strongly we can meet this new regulatory standard and we will therefore be prepared to file this year as Deirdre will discuss. Our IPF trial was delayed for a number of logistical reasons, but as Andrew will discuss, we are now poised to start. And finally, due to the aforementioned challenge in activating hospital related trials and based on some additional feedback from experts, We paused the start of the Kcentra trial and made some additional trial refinements. But now it's ready to go and on the next slide, I'll talk to you about the Kcentra trial.
Trauma remains a major cause of morbidity and mortality around the world, With about 40% of trauma sufferers experiencing life threatening bleeding. Kcentra or 4 factor PCC has been providing Significant clinical benefit to patients on warfarin for a long time and data from preclinical studies for the potential benefit of Kcentra in trauma resuscitation. This trial will look at Kcentra added to the standard of care to impact early mortality after trauma. The trial will include interim analyses to optimize the number of patients needed in the trial to test our hypothesis. And we plan to start trials before the end of this financial year.
And finally on the next slide, one of the growing areas of medicine is the number of functionally immunocompromised patients Who are living longer and therefore suffering additional complications. New cancer treatments deplete B cells. Patients are living longer post transplant with the use of chronic immunosuppression. And diseases such as chronic lymphocytic With improved treatment, they are becoming more chronic diseases. But with the longer survival, the chance of a serious infectious Complication arises.
We plan to strengthen our Hizentra label as it pertains to this diffuse family of disorders, each with their own unique features. We will start with a 1 year clinical trial looking at the ability of Hizentra to reduce Infectious complications in patients with CLL and are excited to start that this year. So a lot of exciting activities occurring in R and D, and I'm happy to have you here from our scientists. So let me start by turning the virtual podium over to Andrew Nash. Andrew?
Thanks, Bill, and good morning, everyone. It's my pleasure to be here today to talk to you about CSL bearing research. My intention is to briefly cover our internal capability and strategy and to highlight one internal program that is moving into a second therapeutic indication. However, in our highly competitive sector, high quality external innovation is critical to success and sustainability of any R and D program. So in the second part of my presentation, I will focus on our approach to partnerships.
I will announce an exciting new initiative and speak to some ongoing relationships, including the progress being made by partners to which we have out licensed some of our assets. Next slide, please. Now as we have discussed previously in this forum, CSL Research is a global organization with facilities located within strong Academic precincts and or co located with our manufacturing facilities. The majority of our resources are dedicated to filling the R and D pipeline And you can see that activity on the left of the slide there. Within research, so we have other functions which contribute to the progression of projects through non clinical and clinical phases.
This includes our toxicology activity and our research and clinical Bioanalytics. Now with respect to filling the pipeline, we are structured in a way that optimizes our access to external innovation If you look at the bottom left there, we have a group dedicated to research external innovation. We have High quality scientists leading our therapeutic area research activity and we have all of the functions and capabilities that you would Now for each of CSL's 5 TAs, we have a well developed and specific research strategy. However, above all of them is a clear underlying set of common principles. Most importantly, and you can see these principles on the left, most importantly for HTA, we are looking to discover new therapeutic candidates And that for that purpose, we have access to the 3 technology platforms that Bill described earlier.
We have a lot of expertise built up over many years in plasma and recombinant proteins And we have a developing expertise in cell and gene therapy and we are looking to leverage collaborations with external experts to really build in that area. Beyond looking for new therapeutic opportunities, we are also looking for additional high value opportunities for our existing clinical and on market assets. And I have an example of this type of activity in the next few slides. Next slide, please. So within the CSL research team, we have world leading experts in the biology of to 12 and on the role of Factor 12 in disease pathogenesis.
On the left there, you can see that as a key mediator of bradykinin production, We know that the activation of Factor 12 plays a central role in hereditary angioedema. And for this reason, we are developing garidazumab, a Factor 12 inhibitor for the treatment of its indication. A Phase 3 study of garidasumab in is currently underway and my colleague, Deirdre Bovad will 12 in the biology of macrophages and fibroblasts. And you can see an outline of this on the right hand side of this slide. We have now discovered that this role of Factor 12 in the biology of these cell types appears to translate into a role for Factor 12 as a mediator of fibrosis in lungs and other tissues.
Next slide, please. So what we have shown using both access to clinical patients and experimental animal models Is that there is a really clear increase in factor 12 in lungs with idiopathic pulmonary fibrosis. We can take increased Factor 12 in the lungs and we can also detect a signature for this activity in the blood of these patients. Looking towards experimental data in animal models, we can see and other strategies, we can see that garidazumab inhibits Factor 12 induced fibrotic function from primary lung fibroblasts and we know that factor 12 promotes M2 macrophage differentiation And reinforces the IL-six feedback loop, which contributes to fibrosis. We know that in a whole variety of animal models, blocking factor 12 with an analog of CSL-three twelve or garidasumab inhibits fibrosis in these models.
This includes in models of lung fibrosis, liver fibrosis and renal fibrosis. On the right hand side of this slide, you can see some analysis from lungs of patients with progressive fibrosis. And you can see the expression of Factor 12 increased in compared to non disease controls. We expect a Phase 2 study to commence in this indication in the second half of financial year 'twenty two. Now moving on to the second part of my presentation, I'd like to highlight some of the activities and progress being made through our external innovation efforts.
As noted earlier, this activity is critical to our success as an R and D organization, and we have a well formed and targeted approach, the main pillars of which are shown here on the right. Today, I'd like to highlight one new and a number of ongoing examples of how we collaborate and partner with major academic institutes and smaller biotech companies. You can see on the left of this slide, a list of the companies that we are working with, plus a number of the academic institutions. This by no means covers all of those that we're working with, but I will from this group highlight a number of examples. Next slide, please.
Now first up, I'm very pleased to announce today that we are setting up a new partnership with one of Australia's leading medical research institutes, the Walter and Eliza Hall Institute. Going forward, we are establishing the Center For Biologic Therapies. This will be a jointly funded initiative based in the Parkville precinct with equal amounts of funding from CSL and the Hall Institute. Its purpose will be to discover novel biological therapies for the treatment of serious unmet medical needs. It will provide for Wiha opportunities for translation of their research and better commercialization outcomes And for CSL, it provides a potential new pipeline of opportunities.
Importantly, from a broader context, it addresses a gap in biologics in Australian Medical Research and will assist in developing the Australian workforce expertise and career opportunities for scientists in Australia. We have a long history of collaborating with the whole Institute. Both CSL and WeHi have been key features of the medical research landscape for over 100 years now. And this partnership that we're announcing today will further solidify and Advance that long term relationship. Next slide, please.
Now moving on to gene therapies. As a second example of our external innovation, I'd like to update on our relationship the Seattle Children's Research Institute, which is directed towards the development of gene therapies for primary immune deficiencies. Firstly, however, it may be helpful to briefly highlight the different gene therapy technologies CSL is pursuing. My colleague, Deidre Brevard will shortly update you on recent progress with etranidase. Etranidase is an adenoassociate with virus based gene therapy for the treatment of hemophilia B.
For this therapy, an AAV Seratoid 5 is used to deliver and express The Padua variant of Factor IX, the AAV travels to the liver where it infects hepatocytes and expresses the gene of interest. Importantly, it does not integrate into the host genome. 2 important features of this therapy are that we Understand and see from our clinical studies that AAV5 appears to be somewhat resistant to the effects of pre existing antibodies. And this is important in the context of previous exposure of patients to AAV infection. Secondly, the use of the naturally occurring Padua variant of Factor IX is very important.
And you can see the importance of this in the graphs shown on the left here. The Factor 9 Padua variant has increased specific activity. What this means is that you need to deliver less protein for the same amount of Factor IX activity. In these two graphs, where patients have been delivered either wild type Factor IX, that is normal Factor IX or the Padua variant. You can see on the graph on the left that the amount of Factor IX in circulation for both of these is around the same.
However, when we measure Factor IX activity in the graph on the right, You can see a really dramatic increase in fact, in line with the Padua variant. And this is the result of the increased specific activity that we were talking about. These studies were done in non human primates and this result translates into humans. The second approach to gene therapy that we are As outlined on the right and is where we are trying to correct a mutation in blood cells that results in an ineffective immune response And ultimately, what is diagnosed as primary immune deficiency. To do this, we harvest patient blood stem cells and use a lentivirus vector to integrate the correct gene into the genome.
These cells are then transferred back into the patient where if the right conditions have been So to further expand on the second approach, We entered into an agreement with the Seattle Children's Research Institute in 2020. We chose the Seattle Children's Search Institute because of a long history of expertise in both primary immune deficiency and gene therapy. Our lead collaborator there, Professor David Rawlings is a world expert in this area and has a vast experience in treating these patients in developing novel therapies. To date, the institute has treated over 400 patients with CAR T cell therapies and is developing therapies with us for primary immune deficiency. The platform, as I've discussed, is ex vivo hematopoietic stem cell gene therapy.
The technologies we're using are lentiviral gene therapy, but we also will be looking at approaches to gene editing. And in this collaboration, the PIDs that we are focused on are with Scott Aldrich syndrome, X Now just highlighting the Wiscod Aldrich program for a minute. This disease is caused by a mutation in the WAS protein, which is Involved in the structural integrity of B cells and other immune cells and the mutation leads to a severe immune deficiency. It's rare with an incidence of about 1 in a 100000 male births and it leads to bleeding, eczema and recurrent infections and is most typically treated with IG. The design of the vector you can see below the text there, it incorporates A wild type WAS gene, a promoter to drive expression and importantly, a short hairpin technology that comes to us care of Calimmune and which allows us to select for expression of this gene in patients into which stem cells Have been transplanted.
You can see there that Wiscod Aldrich represents a relatively minor proportion of the total PID patients, But along with agammaglobulinemia and hyper IgM, it's a great place for us to start because of The fact that the gene, the target gene is very well known and characterized. We expect a Phase onetwo study to commence in the first half of for year 'twenty three. Next slide. Now I'd like to move on and touch upon Some of our out licensed projects. Coming through CSL research along with our Collaborative programs and our internal programs are a number of assets, which either don't fit squarely within our focus areas Or require technology and expertise that CSL is unable to bring to bear.
These assets still retain very significant value And we seek to exploit that value through selecting biotech partners to drive those molecules through development for And I'm going to touch on 2 examples of this today. Next slide, please. So Aslan is a NASDAQ listed company with offices in Singapore and the U. S. And in 2019, CSL granted Aslan full global rights to develop and commercialize CSL-three thirty four, now known as ASLAN 4.
ASLAN004 is a 1st in class monoclonal antibody that targets the IL-thirteen receptor alpha-one of the Type II IL-four and IL-thirteen receptor and in doing this inhibits both IL-four and IL-thirteen activity. This differentiates it from dupilumab, which also inhibits IL-four and IL-thirteen, but which targets a different receptor subunit in the complex and inhibit signaling through both the Type 2 receptor and the Type 1 receptor. Now, as I'm sure you're all aware, dupilumab is a very effective therapy and in 2021 had sales approaching €5,000,000,000 per annum. Unfortunately, administration of dupilumab leads to conjunctivitis in up to 30% of patients And the team from Aslan are hoping that this may not be the case for Aslan-four. Next slide, please.
Now, ASLAN recently announced some very exciting data from their multiple ascending dose study of ASLAN 4 in patients with moderate to severe atopic dermatitis. 3 doses were tested with the top dose of 600 milligrams selected for an expansion cohort. The primary endpoint was safety and tolerability and the secondary endpoint was clinical efficacy As measured by percentage change in the eczema area severity index or EASI. There were 16 patients, Evaluable patients in the 600 milligram group and 13 placebo patients. The drug was safe and well tolerated With importantly, no cases of conjunctivitis observed.
Significant improvements in clinical score, as we can see In the table on the right hand side of this slide, if we focus on the number of patients experiencing a 70% reduction In EASI, we see a 69% risk reduction a 69% reduction with ASLAN 4 Compared to a 15.4% reduction with placebo, a significant and very impressive result. Now following this encouraging data, Aslan plan to commence a Phase IIb study prior to the end of the year. Next slide, please. Now the 2nd biotech Partnership I'm going to talk about is our relationship with Kinixa. So AstraZeneca and CSL granted global rights to Kynixa to develop and commercialize mavrolizumab in 2017.
Prior to that time, AstraZeneca had been developing mavolimumab for rheumatoid arthritis and while the drug progressed through Phase 2b studies And we're safe and very effective in over 5 50 patients, development was halted for reasons of strategy and focus. And ultimately, CSL and AstraZeneca agreed to license the molecule to Kinixa for further development. Now the antibody targets the GM CSF receptor alpha chain and is a potent inhibitor of GM CSF, which is a key mediator of inflammation and autoimmune disease. Now, Kynixa currently have a number of studies underway. They have a Phase 3 study in progress, a Phase twothree in progress and another either commenced or shortly to commence.
In a Phase twothree in patients with severe COVID rate related respiratory distress, mavralimumab reduced the need for mechanical ventilation and improved DEVIVAL. Enrollment in the Phase 3 part of that study remains ongoing. The Phase 3 portion of the clinical study has already enrolled over 400 or 600 patients and Kynixa expects data from the Phase III to be available in the Q1 of 'twenty 2. Next slide, please. Now just focusing on the other indication Kynixa pursuing, which is joint cell arteritis, a rare autoimmune disease.
In a Phase 2 study, GCA patients were treated with either Mavri or placebo for 26 weeks, while their dose of steroid was tapered. The primary endpoint was time to first disease flare and the secondary endpoint was sustained remission through the week 26. The graph on the right shows the treatment with mavrolimimab led to a significant increase in the probability of sustained release sustained remission rather at week 26. A Phase 3 study, as I mentioned, is either ongoing or just about to start. Now to my final slide, please.
So in summary, CSL bearing research is Creating and progressing a sustainable portfolio of early stage opportunities. We are continuing to innovate in areas of business strength And for each of our therapeutic areas, we are looking for new opportunities in which there is unmet medical need. We have the 3 drug discovery platforms that we are Apply across the 5 TAs, we have a lot of expertise in these. But I think importantly, as evidenced by the new partnership with the Walter and Eliza Hall Institute, We are leveraging these in house technologies to support our external innovation. We're expanding capacity and capability across global Research sites and we are continuing to invest in external innovation and that extends from investment in venture capital to long term strategic collaborations of the type that I've described today.
So with that, I would like to hand over to my colleague, Deirdre Bovard.
Thank you, Andrew, and good morning, everyone. On behalf of our dedicated R and D team, I'm pleased to provide you with an update today on some of our ongoing development programs. We're also very grateful to the dedication of the healthcare providers And staff at our study sites and most importantly to the patients who volunteer to participate in our clinical trials, Especially in the context of significant impacts the pandemic has had on healthcare systems and on their daily lives. And now I'll highlight some of the data and the progress across our programs starting with CSL-one hundred and twelve.
We continue
to advance the development of CSL-one hundred and twelve, which is a short term therapy administered along with optimal medical care for patients suffering a recent heart attack that are at high risk for recurrent adverse cardiovascular events. The intended benefit of CSL-one hundred and twelve is in the very high risk 90 day period after a heart attack, Where other secondary preventative measures have not yet had impact. Treatment in our AEGIS II study is initiated within 5 days And patients are followed out to 3 65 days post treatment. The pandemic has continued to impact enrollment in our clinical studies. And as you heard from Bill, this is particularly For those conducted in hospitals for a variety of reasons and Aegis II is no exception.
However, for those institutions that have been able to continue, the interest and engagement in our Aegis II program remains high, and we currently have More than 14,000 patients enrolled. Earlier this year, we passed our 2nd futility analysis, which was an important hurdle for the program. Now the 3rd interim analysis is the final one before the end of the study, and it is anticipated to Before the end of our fiscal year. This analysis is designed primarily for efficacy And if the outcome is overwhelmingly positive, it could trigger the end of patient recruitment, but that would not be trial as all patients would continue until they complete. We will update you on the outcome in real time if we plan any action based on it Or if not, at an upcoming investor event.
And as before, all we'll be able to share is a decision, not any specific data, As CSL receives only a recommendation as to whether we should stop or continue patient recruitment. So Andrew just shared with you an update on our gene therapy programs that included entranidaz, and I'm going to expand on the ongoing and development program in these next couple of slides. Gene therapy has the potential to offer functionally curative benefits to people with hemophilia B By enabling functional Factor IX levels to be generated by their own body, and we're very excited to be partnering with UniCure on this promising treatment. As announced back in May, CSL acquired the exclusive global license rights to commercialize entranidaz, which is Umicure's AAV5 gene therapy program. The IND will be transferred to CSL And the global submissions to BLA and MAA are planned for the second half of our fiscal year.
We will also be responsible for our future clinical development And of course, as just mentioned, the commercialization of the product. The ongoing clinical development program Includes a Phase 2b and a Phase 3 study. The Phase 2b study was an open label, single dose, single arm trial using PDUFA factor IX in adult males with severe or moderately severe hemophilia B. The Phase 3 study, which is referred to as HOPE B, is similarly designed with the same population And those patients that are on prophylaxis treatment and with or without pre existing neutralizing antibodies to AAV5. And on the next slide, we'll show the data from the HOPE B study that UniCure presented earlier this year.
So on this slide, you see HOPE B 12 month data. The graph on the top right shows the mean Factor IX activity through week 52. These results demonstrate stable and durable endogenous Factor IX activity post treatment. And as you can see, there's increased activity levels in the mid to normal range with a mean of 41.5 IUs per deciliter at week 52 that's noted by the blue dots on the chart. Importantly, that Factor IX activity was seen similarly in patients both with and without neutralizing antibody.
96% of the patients discontinued their prophylaxis by week 26 And remain prophylaxis free at week 52. Additionally, we do continue to follow the patients that were dosed in the Phase to be trial now for an average of about 2.5 years and their Factor IX activities remain stable And in that same mid to normal range. These very promising Factor IX results translate into a meaningful clinical outcome with the reduction in annualized bleeding rates as seen in the table on the bottom right. The adjusted annualized bleeding rate Reduced on treatment as compared with the lead in period going from 3.9 ABR during lead in to 1.33 on treatment for an approximate 66% to 57% reduction. And the majority of patients did not report any bleeding during the 52 weeks after dosing.
We are looking forward to the upcoming submission of this data and adding entradadaz to CSL's innovative hematology product portfolio. For the rest of the presentation, I'm going to highlight programs from our immunology portfolio. Starting with exciting new investigations with Hizentra, our 20% subcutaneous IG, which is uniquely positioned to address unmet needs of patients. Part of CSL's focus is this overarching strategy to continue to explore the beneficial uses of Hizentra, And you heard Bill mention one earlier with the study in patients with CLL. Well, systemic sclerosis and dermatomyositis are 2 rare diseases that we believe could benefit from the immunomodulatory effect of IG and where we believe an effective subcutaneous therapy for these patients would offer unique benefit.
SCC is a rare, heterogeneous, multisystemic, progressive autoimmune disease with significant morbidity And the highest mortality among the systemic autoimmune diseases and affects anywhere from 3.8 to 34.1 People for 100,000. It's also 3 to 4 times more commonly seen in females than males, No current treatment addresses all of the multisystem impact of the disease, which presents with hardening of the skin, Inflammation and scarring of internal organs and endothelial injury. And it's important to note with this population That the skin is pathologically changed and we're giving them fluid under the skin. So it's critical to establish Data that will allow us to understand the absorption and bioavailability as well as evaluating the safety for these patients. And we're doing so in a Phase 2 study that I'll review in
a moment. Dermatomyositis
is another severe autoimmune disease where we believe Hizentra could have impact. It is an inflammatory condition that leads to muscle weakness and skin changes with high associated morbidity and mortality and affects 14 in 100,000 people. There is a high unmet need for long term treatment without systemic side effects. So now moving on to our first Hizentress study, SURPASS. SURPASS is the Phase 2 study where we'll evaluate the safety and bioavailability of Hizentra in adults with systemic And to the best of our knowledge, this is the first subcutaneous IG study in SSC.
And as you see by the schematic, the patients are screened and then randomized into a crossover design To receive either Hizentra or Privagen in the 1st 16 weeks of treatment and then the alternate treatment in the 2nd 16 weeks. And in this way, the patients serve as their own control in a very efficient study design. I'm happy to share this ongoing study has fully enrolled ahead of targeted schedule and is anticipated to complete in 2022. We look forward to sharing those results in the future. And now on to the 2nd Hizentra study, RECLAIM.
RECLAIM is a global Phase 3 study of PIZENTRA in adults with dermatomyositis. This is a 1 year, double blind, randomized controlled trial that compares PIZENTRA to with a primary endpoint of responder status based on the DM Total Improvement Score. The study was initiated in 2019 and enrollment has been affected by the pandemic. However, our investigative sites are still very engaged And that enrollment momentum has been steadily increasing, enabling us to reach 50% of our enrollment target. Our teams continue to work very closely with our investigators to keep that momentum going.
So now I'm going to shift to hereditary angioedema and CSL's continuing commitment to improving available options and offering optimal treatments for the full range of patients with HAE. HAE is an autosomal dominant Genetic condition that is characterized by recurrent episodes or recurrent attacks of swelling at specific parts of the body as seen in the picture on the right. The swelling is characterized by unpredictable onset, severity, duration and attack location and can be life threatening. HAE affects 1 in 10,000 to 50000 people and our strategy for meeting the needs of these patients Includes the 2 programs I'll review next. The first one that I'll speak to is the investigation of our ciaridazimab, CSL's 1st in class fully human monoclonal antibody that you heard about earlier from Andrew.
And the second is in Hey Garda. As you know, we've launched HEICARTA around the world for patients with HAE, but it is not yet available to patients in Japan, Where the prevalence of the disease is similar to the global prevalence rate. We have investigated HEYGARDA in an open label single arm Phase 3 Bridging Study in Japanese Patients, and I'm excited to share those results with you. But first to garidafimab. As Andrew described earlier, garidesimab inhibits Factor 12 and this inhibition locks the pathway of edema upstream in the inflammatory path Right.
Thereby preventing the characteristic swelling attacks. Last year, we had the opportunity to present the exciting results from our Phase 2 study that you see on this slide. These results have recently been accepted for publication in a major scientific journal coming out soon. The results from this dose ranging study demonstrated that garidesimab significantly reduced the mean number of monthly HAE attacks Compared to placebo. And as you see, there was a significant mean reduction in HAE attacks in all three dose groups.
In the center, you'll note an impressive 98.94% mean reduction in HAE attacks per month for the 200 milligram dose group as compared with placebo. It is this 200 milligram dose that we've taken into our Phase 3 global program that I'll review on the next slide. So this diagram provides the overview of our clinical development program for garidesimab in HAE, and I'm going to focus on the vanguard Phase 3 program on the right. Caridazimab is the 1st CSL monoclonal antibody that we have taken into Phase 3 development, which is an exciting advancement in the continuing evolution of our portfolio. The top red box shows our pivotal Phase 3 study, which is a double blind placebo controlled study being conducted globally.
In this study, 60 patients of Type 12 HAE Of at least 12 years of age were randomized to receive either monthly subcutaneous eridefimab at 200 milligrams or placebo. The primary endpoint of time normalized number of HAE attacks during treatment will be assessed at 6 months. The study was initiated at the start of 2021 and has completed patient recruitment 2 months ahead of projection despite the COVID challenges. The bottom red box depicts our global Phase 3 open label safety extension study That also started at the beginning of 2021. 150 patients are being enrolled into this study, including Treatment experienced patients from the Phase 2 and the Phase 3 pivotal studies as well as treatment naive patients that are enrolled We are progressing well in the VANGRAD program and we expect it to be completed in 2022.
And upon that completion, we're targeting global submissions in 2023. We also anticipate garetezumab to be the 1st CSL product to launch with both prefilled syringe and auto injector for enhanced patient convenience. Now moving on to HEYGARDA. The HEYGARDA Phase 3 study I mentioned in Japanese patients Completed earlier this year, again, ahead of schedule. Presented here are the results from that study.
Alongside a comparison of our previously presented and very positive global Phase 3 pivotal study results, which are on the left. I'll talk through the Japan Phase 3 study results that are on the right and want to start by drawing your attention to the top right box, Well, you'll see that the median attack rate was reduced from 3.6 per month during run-in to 0 on treatment or a 100% reduction. On the graph in the bottom right box, you'll see the Japan study results for patients with an equal to or greater than 50% attack reduction on treatment as compared with the run-in period. If you look there to the red column on the left, You'll see that 100% of the patients achieved this target of at least a 50% reduction in attack. And if you look at the red column to the right, you'll note that nearly 2 thirds were attack free.
Now when you compare these results to the global study results on the left, you'll note that the efficacy in the Japan study Is similarly impressive to the global pivotal study. So overall, this study demonstrated significant prophylactic And with this, we will submit a JNDA as planned next year. So what I've been able to share today is only a Snapshot of our robust R and D portfolio. And as you heard Bill mention earlier, we continue to advance across all of our therapeutic areas and scientific platform. You also heard from Andrew how our scientists continue to grow an innovative pipeline for the future for both our Through both our internal discovery efforts and our external collaboration.
The therapeutic focus our teams bring is what's Continuing to drive the progress in our later stage Phase II and III portfolio. And there are many other innovations that I'm not able to review today In other novel monoclonal antibodies and novel plasma proteins
such
as those listed here That are also continuing to progress through the portfolio. Additionally, our patient focus is what leads our team to continue to and expand some of our established products that we mentioned such as Hizentra, Kcentra and Hey Garda with new indications, new markets and patient friendly presentations. In fact, All of the work and the progress that my colleagues and I share today is underpinned by our unwavering patient focus. Our more than 1700 R and D colleagues around the world work every day to fulfill CSL's goal to be a trusted, reliable innovator That is driven by its promise to save and protect lives. And again, we could not do this without the partnership and the dedication healthcare providers and staff at our study sites and most significantly, the patients who volunteer to participate in our clinical trials.
It's together that we deliver on our promise to patients. And with that, I'll thank you very much for your attention and I'll now turn it over to Bill Campbell, our Executive Vice President and Chief Commercial Officer. Phil?
Thank you very much, Deirdre, and good morning to all of you in Australia. I'm certainly missing my trips to Melbourne and Sydney And wishing we were together in person. Rose, if you could bring up my title slide. I'm once again honored to join my R and D colleagues for this presentation, and I'll have Great comments, I think, along the way on the terrific products that they've handed over to the commercial team in years past. My presentation today will follow a similar format to the ones I've gone through with you in years past.
I'll share some highlights along our commercial journey, including some performance data that I think you'll find quite interesting. So with that, Rose, I'll take the next slide. And I'll begin with some key highlights from fiscal 'twenty one. As you know, we finished the year on the bearings side of the business at $8,600,000,000 plus 6 percent on a constant currency basis. Despite the pandemic, I'm really proud that we continue to provide access to all of our broad portfolio of products to patients around the world.
In our core immunology franchise, underlying IG demand remained really strong through the pandemic. Importantly, we delivered a strong 15% revenue growth for Hizentra and we've demonstrated continued success with at CIDP, which I'll highlight shortly. As you've heard previously, we delivered significant year over year growth of 61% following the normalization of albumin in China as a result of the GSP license we put in place. And maybe just an editorial comment on that to say I'm extremely proud of the broad organization who worked Relentlessly around the clock to ensure that all of the product, all of the back office systems, all of the certifications that needed to happen, Happened on time at an extremely high level. And I'd also like to give a congratulations and a job well done to my commercial team on the ground China for this and we'll talk more about that in a few minutes.
Within our hemophilia franchise, We maintained a Delvion leadership in key markets and had strong performance by our Von Willebrand disease product. Our specialty business continues to perform well despite the pandemic. We gave We demonstrated strong growth from Hey Garda and Kcentra. And with regard to Hey Garda, we had more patients at any time since launch I'll share some very exciting data with you and a 14% revenue growth in FY 'twenty one. With Kcentra, we've seen a continued penetration versus pressed frozen plasma, and I'll provide more color on this and these other areas Shortly.
Rose, we'll go to the next slide.
As we've done in each year, I'd like to frame the overall market Over the last 5 years, the targeted protein therapeutic market has grown from 27,000,000,000 to about 37,000,000,000 The market growth reflects a compound annual growth rate of 6%. With the global pandemic certainly having impact The market over the last 5 or 6 quarters. Clearly, CSL has outperformed the market historically. And the last comment that I would make on this slide is that the IG segment, as you know, continues to grow at a healthy 12% rate. On the next slide, I'll start to provide some additional color on our key business segments and product performance.
So let me start with the immunoglobulin market. COVID-nineteen certainly has had and still has an industry wide impact on plasma collection. Underlying demand for IG, however, continues to remain strong. There are ongoing significant patient Needs and PIDP and as you heard earlier, expanding use for SID given the increased use of administration. This is an area we know exceedingly well.
And as you all know, we've been working on this for well over a decade now. Go to the next slide. So let me begin to frame some individual performances. Overall, our immunoglobulin business delivered FY 'twenty one sales of $4,200,000,000 up 3% on a constant currency basis. While 3% is okay, it's certainly not the typical growth rate we expect.
It's certainly not Typical growth rate in IG that all of you expect. The global pandemic has certainly provided significant headwinds, Especially as it relates to plasma collection, stay at home orders, fewer doctor visits and all the other things that we've talked about. Having said that, our flagship product, Hizentra, grew revenue on a year over year basis of 15% And remains the clear subcutaneous market leader. We have seen a step change in preference for at home treatment and subcutaneous use, and I'll talk about that more in a minute. We've seen a continued uptake in CIDP with both iCentra and Privagen, And these are both areas that remain relatively new for us.
We have secured Medicare Part B reimbursement, which was really important for us in CIDP in the U. S. Marketplace. On the IVIG side, supply tightness Certainly intensified by COVID-nineteen, supply was a bit tenuous before COVID and has only become more so. Pravagen volume was impacted by partly COVID, but certainly the shift to Hizentra as well.
I would say, as I've mentioned earlier, the global demand remains strong in our core indications. In the bottom portion of the slide, I've included some data I thought you'd find really interesting. The chart reflects our mix Relative to volume in the U. S. Market for Hizentra over the last Hizentra and Privagen over the last 5 years.
HAGENTRA has grown from 27% of our volume to now approaching 40%. And we'll move to the next slide and I'll share a couple of reasons So the left side of the slide has summary data from patient market research that we conducted. And while the studies are quite voluminous, I just highlighted 4 key items for you. Not surprising, patients looking for more flexibility and better time management. They're having problems finding a vein at times.
Clearly, COVID-nineteen Impacted their ability to get to an infusion center and just the difficulty overall of getting in and going through the IV infusion centers. So I guess I would summarize this by saying, Isentra provides more control to the patient on dosing, dosing schedule and certainly place of administration. As mentioned, we've been dedicated to this area for more than a decade. I think COVID-nineteen has helped that, But this is an area that we've been highly involved in for many, many years. Hizentra is the number one product Used worldwide for primary immune deficiency and the only subcutaneous IgE approved for use in CIDP.
There's certainly significant long term experience with Hizentra with on market experience now exceeding 10 years of real world experience. And we continue to lead and we will continue to lead within the subcutaneous space as we bring more innovation and trials as you heard from Deirdre as well as other treatment options to patients. So we'll go to the next slide, please. We continue to garner the largest market share in the subcutaneous space at 60%, While the line for Hizentra looks flat and looks similar to what I shared with you last year, this market overall has grown During the same time period, clearly the last year and a half has impacted the overall growth rate in the space. Let me share one more important piece of data with you on the next slide.
This slide shows the Performance of Hycentra in CIDP across our core regions. The y axis represents numbers of patients and the x axis So as a reminder, we launched Hizentra in the CIDP space just 3 years ago. During this time, we've added significant numbers of new patients. And while this growth is excellent, We've certainly been impacted by COVID over the last 4 to 6 quarters. Office visits from our sales team were impacted early in the pandemic We'll move to the next slide.
We'll transition now to the hemophilia portfolio. While our overall revenue was down 4% in We saw really nice growth with Idelvion in our products for bovinevratinci. Idelvion remains the clear standard of care for hemophilia B. We have seen strong performance in our key markets such as the U. S, Germany, Italy, Switzerland and Japan.
And we've had some recent strong launches in France, Spain and Taiwan that will continue to provide growth for us through this fiscal year and beyond. Within the hemophilia A space, Asthila was impacted by competitive market dynamics and reduced doctor visits during COVID-nineteen. Our plasma derived Factor VIII products maintain market leadership globally in the Von Willebrand disease space With a strong 56% patient share, and Humei, in particular, delivered strong revenue growth of 13% in the U. S. Rose, we'll go to the next slide.
Relative to Idelvion, you can see our strong position About 7 key markets in aggregate. We continue on our growth journey, having added 2 points of market share in the last year alone, With an overall market share now of 45% across this group of 7 countries. Maybe more interesting to you is the data on the next slide. Across these seven markets, The team has delivered a market share of 28% to 62% with an average, as I mentioned, of 45%. We take a great deal of pride in this performance.
Adelvion launched just 5 years ago and certainly well behind other products But the team has performed and the brand and product have performed extremely well. We go to the next slide. This slide provides a similar view, but for Apstella now. As you all know, this is a highly competitive market segment with 15 to 20 products depending on the market you're in. Yes, the team has done an excellent job with market shares just under 10% in markets like Germany and Italy, And the average across these 7 at 5%.
While not a typical CSL bearing performance, A very good share given the incredibly crowded market space. We can go to the next slide, please. Building on our 3 plus decades in hemophilia and leveraging our strong relationship within this community, We hope to launch the 1st gene therapy product for hemophilia B in the future, as you heard from both Andrew and Teirdre. While it's premature to spend more time on this product now, I hope I'll be able to talk to you about our plans and commercial approach with this exciting breakthrough in the future pending FDA and EMEA approval. CSL has been And we'll continue to be a strong supporter of hemophilia and a leader within this space.
Next slide, please. The transition to our specialty business. In this segment, our revenue was up 2% just under 1,800,000,000 This segment, like others, was impacted by the global pandemic as well as some manufacturing challenges that we faced with HUMIRA and VASPRISA. Having said that, Kcentra grew 7% last year and remains the absolute gold standard for warfarin reversal in the U. S.
There remains substantial growth opportunities with FFP still used in about 40% of the patients with forefingerneversal need. And we've now seen the demand back to pre COVID levels in the U. S. As hospital visits and elective surgery have largely returned to normal. On the right side of the slide, we believe Hey Garda or Barren or subcutaneous as it's known in some parts Europe offers best in class efficacy.
We continue to see patient growth with fiscal year 2021 delivering the most patient since launch in the U. S. With respect to Zimura and RISPRISA, As I mentioned, we needed to implement some manufacturing updates and are investing to enhance supply chain to ensure future supply availability. Let me provide a bit more color on the next couple of slides. So with this next slide, Starting with Kcentra, we continue to grow this brand year over year.
While the number of surgeries were down during the early part of the pandemic, As I just mentioned, we've seen a more return to normal and a strong underlying growth for the brand more recently. There are still 1,700,000 patients on warfarin with 25,000 new patient starts per month. HeyCentra growth is driven by strong efficacy versus FFP, and we're continuing to penetrate the large Teaching Hospital Systems in the U. S. On the right side of this chart, on the right side of the slide on the top, you've seen These two charts before, the y axis on the top shows warfarin patients by therapy In the X axis, our calendar year in quarters.
Kcentra crossed over FFP about 5 quarters ago And continues to grow quite nicely. This is data through calendar Q4 'twenty. We only get this data on a 6 month basis and the next 6 months of data will be available mid November. The bottom right side of the chart, as you've seen before, we continue to see strong underlying demand for this Really important product, and I suspect that we'll continue to do so in the years ahead as you've seen some of the plans for our Our product in the trauma space.
Next slide, please. This is a
piece of performance data I thought you'd be interested in. The chart shows the number of patients on Hey Garda or Varenter subcutaneous over time. Despite new product launches, HEYGARDA continues to grow. And in fact, as I mentioned a minute ago, we have the most patients Launch in highly competitive markets like the U. S.
Our European and Australian new launches are exceeding expectations. Our team in Spain achieved a 55% patient share within a year of launch, and we have 5 additional launches planned by the end of fiscal 'twenty 2. If we go to the next slide, We believe there's still a big opportunity for Hey Garda in the future or in fact with CSL312. This is a market that remains in transition. You can see 4 years ago, the PROPI segment represented about A quarter of all patient utilization and as of last calendar year, the Prophase segment represented almost 40% of patient share.
Hey Garda has a proven record of extremely high efficacy and safety. And as a result, we continue to see patients Switch back from competing products to AGRTA given the benefit and efficacy that it provides. We believe strongly that efficacy ultimately drives patient preference in this segment. We remain really excited about the future of AGRDA and our place within the treatment of HAE. We'll go to the next slide.
And I want to end my presentation by providing you with a sense of How we've done with our new product launches that our R and D colleagues have provided for us and they have been great partners. Over the last 4 years, we've launched 5 products, 4 plus years, 5 products Adelvion, Astella, Hey Garda, CIDP for Hizentra globally and CIDP for Pravagen in the U. S. Collectively, these launches have About $1,700,000,000 in revenue last year, representing 20% of total bearing business. These were products again that didn't exist 5 years ago.
Together, these products have grown at a compounded annual growth rate of 80 6% with strong individual performances as you've seen on the right side of this slide. We're very proud of our performance with new products with several such as Adelvion and Hey Garda representing some of the most successful launches in our industry. Our legacy products like Privagen and Hizentra, albumin, Kcentra and others Continue to grow and have a strong underlying demand for them. And as you can see, we're performing at a really high level with new product launches. And I believe that this bodes really well for our future growth.
If we go to the next slide and my last slide, I would leave you with the thoughts that in summary, I believe we're executing extremely well on our commercial strategy. We have strong underlying demand across the portfolio, as you've heard, both on the legacy brand and new product side. We have certainly faced headwinds from COVID, but continue to remain highly focused. We've delivered balanced regional and key market growth historically. Our new products are contributing significantly to growth and now represent 20% of revenue and we have a robust new product pipeline to fuel growth.
Products that you've just heard about from the R and D team, including etranidaz, Kcentra and Trauma, CSL-one hundred and twelve, girdasimab and others. So with that, I'd like to conclude my presentation. Thank you for your time. And I'll turn the presentation now over to my colleagues from Securus, Doctor. Russell Vassar and Ethan Sethepembre.
Russell and Ethan, to you.
Thanks, Bill. We're delighted to be able to give an update on Securus' research and development over the last 12 months or so. And if we can just see the first slide, Rose. And just to give you a snapshot of where we've come from over the 6 years that Securus has been in existence. I think it's fair to say that we've really been at the center of driving a change in the influenza vaccine market towards a differentiated landscape using new technologies such as the MF59 adjuvant and the cell culture technologies away from the traditional 3 strain and egg technologies have been used up to recently.
There's still a place for all of those technologies, but it's emerging that we're moving away from egg towards vaccines that are now showing proven benefit over the traditional approaches. And in terms of Securus' focus and the investment we're making, We're moving towards really optimizing our use of those technologies and you'll see that at the top of the picture, mention of AQRBC, which is where we've combined the MF59 adjuvant and the cell culture vaccine into a new seasonal vaccine that's under development, which will and of course, the self amplifying mRNA that we've been researching for a while. And the focus that Ethan and I will bring to this presentation is why we think that both of these vaccines have a complementary and important potential role in the future of improving Influenza Vaccine Outcomes. Just in terms of milestones over the last year, and it's Somewhat fortuitous, the timing this week, we had some flurry of terrific news last week, starting with Publication on Thursday in the world's leading medical journal, New England Journal of Medicine, of the results from A study of Flucelvax in children ages 2 to 17 really and the importance of this study was that it's the first new influenza vaccine to show efficacy in children for 20 years.
And really, it's an important step in the progress of helping prevent flu in this age group. And based on this study and the submission of an immunogenicity study in infants 6 months to 4 years based on a study we did that completed last year. The FDA on Friday granted us approval for extension of the age indication in the U. S. Of Flucilvax down to 6 months.
And the critical importance of this is now we can provide Flucilvax to the whole population in the U. S. For which influenza vaccines are recommended. And we can start sort of participating in pediatric tender markets that we previously didn't have access to, a really important and pleasing coincidental juxtaposition of outcomes. The FDA, just The FDA review was over 9 or 10 month period.
We've had important other approvals for Fluzilvax as we move towards really establishing That 6 months and up indication around the world, we've had important approvals of the 4th strain flu And in terms of the AQIVC seasonal vaccine, we've undertaken 2 Phase IIs. 1 is using a standard formulation and another way we've been exploring different doses of the adjuvant and the antigen and the results of which we'll read out in the next month or so. And based on these two studies, we'll be able to make a decision about proceeding to Phase 3 with the optimal dose in the future. Aligned with Our real experience in our projected expectations of demand for the cell culture vaccine around the world, where we started at the end of last year building a new factory, our 2nd full cell culture factory globally Based on the Holly Springs plant in Victoria, in Melbourne, close to the airport here, which will open in about 5 years' time. It's a very significant investment from CSL and Securus, indicating our optimism for this technology and our faith in the Australian manufacturing landscape.
It is we are certainly driving this investment, but it's in partnership with the Australian government, which we've had a very for a very long period, a very important relationship within providing influenza pandemic readiness for the event that What's happened in the last couple of years happens in the future with flu, but also provision new facilities provide Q Fever vaccine and anti venoms. We have, as you many of you will be aware, we have important relationships with a number of governments. And of particular note in the last Couple of months, we reached agreement with an arm of the U. S. Government, the Biomedical Advanced Research and Development Authority or BARDA to in our relationship with the U.
S. Of helping provide pandemic preparedness there of developing 2 vaccines through the early clinical proof of concept with an emerging bird virus referred to as H2. Many of you would be familiar with the H5 bird flu for which we actually have an adjuvanted cell cultured vaccine that was recently approved in the U. S. Called Ordens.
Well, this will be a similar one of the vaccines that we're developing will be similar to that, but based on H2. But in a vote of confidence for our technology that we'll describe to you, Ethan will describe to you in more detail, we were also agreed to develop an H2 with using self amplifying mRNA. And this is a multi year project that will take us through to early proof of clinical proof of concept. Just as sort of to describe what's happened in the last 12 months around influenza vaccine and COVID. And to give you a bit of more granularity behind some of the Data we showed you at the annual results and at the general meeting.
I think it's well recognized intriguingly that flu's Gone to very low levels in terms of flu illness, but we are very worried about the reemergence and I won't go into detail, but Certainly, public health authorities are keen for us to around the world for us to be maintaining influenza vaccination, so we remain as protected as possible. And we've seen that play out in last year in an approximately 20% increase in the number of doses The web distributed and the industry's distributed since the previous years and that's shown on the panel on the left and the light gray bar. In our experience, in the panel on the right, what we can show you is that this has been largely driven by an increase in Demand for these newer technologies, the cell culture vaccine, flu cervix in black and adjuvanted vaccine, flu add in gray And they've undergone a really important boost in the demand and we see that as ongoing. And that sort of gives us gives the rationale as to why we're keen to expand our manufacturing footprint. And these are data this is really sort of an update from data we've shown you previously and it's purposefully an eye chart and It's really the data we've accumulated over the last 5 years of real world evidence.
And this is just to remind you, this is where we look at Beyond the clinical trials, what the health impact of our vaccines is in real in the marketplace once they're given to the general And we have access to a variety of available public health databases as well as conducting some of our own research. And these analyses cover often tens, hundreds of thousands and sometimes millions of vaccinated people. And the power of these data is in the numbers of subjects that we can examine and the simplicity of the outcomes we're looking at. And on the left, we're looking at flu adds, so the benefit of 3 strain flu adds, MF59 vaccine And the upper 2 major rows in blue and white are against 3 and 4 strain egg vaccines and the lower part of that chart is against the major other differentiated vaccine, high dose flu zone. And just the straight line is where the vaccines are similar against those outcomes, major medical visits or hospitalizations, or to the right, they favor FLUAD.
So there's a benefit, a reduction in those outcomes favoring FLUAD. And you can see there consistently year after year, we're seeing A benefit of the FLUAD MF59 adjuvanted vaccine over 3 and 4 strain unadjuvanted vaccines and at least Similar sort of benefit from Fluad compared to high dose TIV. On the right, we show something similar with Fluzelvax. It's been for the 4 strain vaccines been around a little less time. And so there's fewer comparisons, but we can still see over a number of years consistently compared to egg based vaccines, a benefit, a reduction in these important medical outcomes.
So this is certainly convincing us and it's convincing the market place that these are providing real healthcare benefit and that's why we're investing in the AQIBC project and as well as our manufacturing expansion. Just to note, Bill did mention what we did with What we've been focusing on with regard to COVID vaccines, and Ethan is going to talk to the science behind AQ IVC and self amplifying mRNA. Just to mention, these two projects have been our biggest priorities in terms of our capabilities. We did We have had a longstanding research activity in self amplifying mRNA. We did make constructs for COVID And they performed really well, pretty much like all the other mRNA vaccines that have been developed.
However, our investment In mRNA and our focus in the time of Securus was and our priority for that project really meant that we weren't in a position to respond to the COVID, the needs of the COVID pandemic. We couldn't have developed the vaccine as well as do these other high priority projects in a way that would have met the urgent public need. So that's sort of just to sort of give you a sense of where what we're focused on in the last 12 months. So with that, I'll hand over to Ethan to give you more of an update on the science.
Great. Thank you, Russell. Russell just showed you all a few ways we're bringing innovations in influenza vaccines right now to people around the world. I'm going to talk a little bit about the future of influenza vaccine. Securus has a long history of generating vaccines Influenza, and as you know, we are a leader in influenza vaccines.
We work as a partner with the global system that has place to track influenza, propose vaccine candidates and ultimately make and deliver vaccines for those who need them. Generating an influenza vaccine has its challenges, suitable to the virus and interplay of the virus with the human immune system. On this slide in the center there, I've highlighted 4 of those challenges. Influenza has 4 co circulating subtypes, Each one can antigenically drift from season to season. In the population, there is significant pre existing immunity The older influenza strain and that pre existing immunity itself can reduce how people respond to new strain.
And this is particularly relevant in Older adults where they may also have waning immunity due to immunosuppence. And at the younger end of the spectrum, The very young children have developing immune systems, which can also be harder to stimulate. So how are we addressing Well, to augment our current vaccines, we aim to address the challenges in 2 different ways. 1, to take advantage of our Proven technology by combining protein and adjuvant, and I'm going to talk you through that particular vaccine. And then also using the self amplifying mRNA platform, which I'll go to in more detail.
So on the next slide, I'll show you Our protein based vaccine, which we're generating using 2 new or 2 advanced technologies that we have in Other vaccines that we have. One is MF59. That's been shown to increase the breadth and magnitude of the antibody response, Which also allows for dose sparing in case of pandemic and mammalian cell culture produced protein antigen That allows for closer match when there are egg adaptive mutations that can make the derived vaccine antigenically Further away from the circulating viruses. And I'm actually showing that on the left side, which I'll walk through. Here, that diagram on the left Explains how the adjuvanted cell culture quadrivalent influence vaccine is intended to work.
This is a graph of antigenic distance where viruses are masked And the closer boxes are antigenically, the shorter the antigenic distance and hence more antigenically like they would be considered. While the further apart they are or any two dots on this graph are further apart, they would look less Like each other and not the same to your immune system, so they would be recognized as antigenically different. Every season, the goal is to target a vaccine Circulating strain to which you would be exposed or at least potentially exposed. And this would give you the greatest opportunity to be protected. The red dot in the middle is, well, let's say the chosen vaccine candidate virus that matches the circulating strain.
But the reality is, flu acts as a swarm of closely related viruses. So in reality, The lighter green oval represents the viruses that are circulating for a particular subtype. So I show here egg based vaccines are represented by the yellow circle. And in some cases, the candidate vaccine viruses that are grown in eggs have egg adapted mutation, which means their coverage is not centered on the circulating strain, Slightly offset. As you can see with the yellow circle, the dot is still within the edges of that yellow circle.
So with Some extent. Additionally, to improve the vaccine 59 to it, which extends the breadth of the response, Making the coverage greater and that's represented by the dotted line around the yellow circle. And we get greater coverage when you add the access. With mammalian cell culture vaccines on the other hand, Pega additions can be avoided, which means the coverage area shown in green there It's centered on your chosen target strain. And combining both mammalian cell culture, which is now centered on the circulating strain And MF59 adds event to increase the coverage, should allow for a very strong response, targeted to exactly what we're looking for.
So let's take a look at the next slide. Here, we're exploring efforts, including increasing the antigen dose. The left panel shows the clinical data on the dose of particular antigens are increased. As you can see, At the higher doses, the immune response is increased. The center panel shows what I described in the Figure on the last slide relating to MF59.
Here individuals are immunized with either a trivalent egg based influenza vaccine or trivalent adjuvanted egg based vaccine, Hey, TIV and TIV. We found that when we compared the responses to the adjuvanted TIV versus the un adjuvanted TIV, the responses were higher And MF59 was in the formulation. So the adjuvanted vaccine raised stronger responses than the unadjuvanted vaccine, which is As you would expect, and also on the last slide represented that larger response. Overall, the adjuvant The guacamole vaccine is being designed to pull a variety of these key levers and should result in a very strong protein based vaccine. But that's not the only way we believe we can improve upon standard influenza vaccines.
So the next slide Speaks about RNA technology. And RNA based technology has shown true value in response to the SARS CoV-two pandemic. Such success that 1st generation technology has generally derisked some concerns around the technology. It should be recognized that this technology was actually under development for quite some time by many groups. In fact, one of those groups was Securus.
On the next slide, Securus has a long history in research for this 2nd generation technology, this self amplifying mRNA technology that I'm going to describe. Our work began years ago focused on the basics of the technology and testing in the variety of viral disease areas. Caturis has worked directly On both pandemic and seasonal influenza vaccines, as well as, as Russell mentioned earlier, the SARS CoV-two vaccine. Work in multiple disease areas has helped further the research in designing improvements as we continue to try to do that. And as Russell mentioned, this has culminated in award from the U.
S. Agency BARDA to develop an H2VAC platform. And I think that is a testament to the nature and quality of the platform. So what are the differences between the most common embodiments of this mRNA Technology. Well, the next slide shows a figure that contains the 2 main RNA technologies that are out there.
The 1st generation mRNA vaccines shown on the top, act by delivering RNA encoding a gene of interest to DSO, that's that Red Deepgram's business center there. There, once in the cell, the RNA uses the cellular machinery to make the protein of interest. And so essentially that cell access the factory to make the protein that you're interested in. In the case of SARS CoV-two, this would be the spike protein, Which is the main viral antigen and that's the antigen that are in the vaccines that are the RNA based vaccines that are out there currently. These proteins that have been generated are then picked up by the immune system and immune responses rate.
So how does that differ from the self amplifying RNA vaccine? Well, the 2nd generation self amplifying RNA technology is shown on the bottom, has an important difference. While the original RNA Encodes for an antigen of interest. This self amplifying RNA encodes also for a replicate. And that's that blue represented by that blue color.
When the RNA is delivered into the cell, the replicates is made And allows us for amplification in that cell of the RNA that it codes for the gene of interest. So You can see in the center there, the replicates form the protein is generated and then more copies of the mRNA is made. This allows each of those copies to then make protein from each of those copies, Which ultimately leads to an amplification of the amount of protein being made. As before, this higher amount of protein Then generates a strong immune response. And I'll show you some data on that shortly.
So first, I'll show you on the next slide, I wanted to highlight some differences between seasonal influenza and SARS CoV-two. These are 2 very different pathogens And the challenges for them differ as well. SARS CoV-two has one main circulating virus that may potentially drift antigenically, But at the moment, we don't know if this is seasonal as for flu or something else. Also, there is no limited There is no limit to pre existing immunity, and that could further adjust the immune response. So in the case of COVID, you don't see that pre existing immunity, unlike for flu where there is pre existing immunity.
Overall, this shows that when we're looking at 2 data, and it may suggest how well it works currently for SARS CoV-two, it may not be the same For seasonal influenza because there are so many other factors that make it more complicated. So overall, we may expect lower efficacy than we've seen in SARS CoV-two. So on the next slide, let's delve a little bit more into the key elements of the samRNA platform. The first is the RNA payload. As described earlier, there are genes that encode for the replicon, I'd show that there on a replicate, which is the element that amplifies the RNA itself.
Because of this ability to amplify the RNA, we can More easily include additional genes of interest on the same RNA. As shown here, I show it as a bisistronic construct that shows 2 genes of interest. By including multiple antigens on a single RNA, we can have greater control over the expression of the genes, which may lead to increased vaccine safety As we have cleared control of what's there. The second key element is the lipid nanoparticle and that mediates entry and protects the RNA from degradation. This is an essential element and the components that make up the LNP to drive reactogenicity.
Hence, developments that further improve this LNP Can lead to decreased reactogenicity, which is obviously key. So let's take a look at the next slide. I'll Show you here some data demonstrating how the assay mRNA platform makes more proteins in vivo than the 1st generation mRNA technology. So in this experiment, we immunized animals with 1 microgram of either FA mRNA, which is shown there in pink, or mRNA, the black line, Expressing the protein that we could measure in vivo. We looked at the expression of that protein over a period of days post vaccination.
You can see from the expression data on the chart that the mRNA generated its highest response after vaccination And then decreased over time. So initially, you see a high response, which then decreases over time. On the other hand, if you follow the pink line, The fMRI reached peak expression by day 7 and then dropped off. FMRI overall expressed about 100 fold more protein than mRNA in the system. This supports the idea that lower doses of FA mRNA may be needed to raise the same or better responses as compared to greater amounts of mRNA, so hence the doses can be lower.
For season 1 influenza, where there are these poor circulation strains, being able to use a lower dose per strain Could lead to lower reactogenicity and vaccines with fewer side effects. While this is a key difference between the technologies, One of the key questions is how does this relate to the immune response? Yes, we have the protein being generated, but what does that mean? So, on the next slide, I'll show you the 2 main arms of the adaptive immune response. The B cell response shown on the left side at the origin to generate protective antibodies and a T cell response on the right side that generates CD4 positive T cells, which increase the B cell response in part And CD8 positive T cells that can destroy infected cells, thus reducing infection severity.
Of particular relevance For RNA based vaccines, is this generation of those CD8 T cell responses? Most common protein based vaccines are targeted to generate protective Antibodies essentially that T cell arm and left side. So with RNA and particularly the self amplifying mRNA, we see large increases in antigen specific CD8 positive T cells. So we actually are stimulating strongly that arm of the immune system. For influenza in particular, These CD responses may drive further protection, but in another level of protection and they can be targeted to even more conserved epitopes, Which could potentially lead to a broader response.
So on the next slide, I'll show you some examples of the immune response to 2 viral targets, It's Darus CoV-two and it's Glenda. So let's start by looking closely at the T cell responses generated by fmRNA or mRNA. So here on this slide is the results of the immunizing animals with FA mRNA expressing the standard SARS CoV-two spike protein used in the current mRNA vaccine. This is shown in red. We use the same approach, The same animal species and the same assays that that published in the report of Corbett et al.
That showed responses in animals to the Moderna vaccine and as shown in blue. As you can see in red and consistent with other data, the simplifying mRNA vaccine generates substantial amounts of CD4 T cells. In both cases, the Self amplifying mRNA vaccine generates more antigen specific T cells than mRNA. And in some ways, this links back To what we described earlier about the expansion of the amount of protein being generated, thanks to the amplifying aspect of the replicate. So on the next slide, I show responses to influenza hemoglobin.
So here we're looking at the antibody responses and we immunized animals with 2 doses of monovalent As a mRNA vaccine containing either just one subtype normally found in the quadrivalent influenza vaccine like H1, H3, BVictoria or B Yamagana, or we immunize the animals with a quadrivalent mixture of each monovalent samRNA. This is labeled quad SA mRNA oncRAP. And finally, we compared the response to adjuvanted QIV vaccine, so essentially the adjuvanted protein version of a vaccine. As you can see, as you look across the graph, Overall, we saw that the responses were essentially similar to either the monovalent self amplifying mRNA, The same subtype when mixed in a quadrivalent si mRNA vaccine or the adjuvantic-two ID vaccine. This says that the antibody response can be quite strong.
And if you consider that in addition to this antibody response, One has improved CD4 and CD8 T cell responses. As I showed on the last slide, the vaccine may be quite protective. So the question may be, do these responses translate in vivo to protection or ameliorate infection? Well, we asked that question. So take a look on the next slide.
We asked this in the context of SARS CoV-two. So here, we tested the ability of SARS of an SA mRNA SARS CoV-two vaccines to protect cancers in a SARS CoV-two challenge model. The immunized animal 2 times with self amplifying mRNA, including for the spike protein Similar to what is in the existing mRNA vaccines, this is shown in blue. We immunize the animals with the FA MRA vaccine that we coded for that S protein Gene plus the nucleocapsid antigen, so 2 proteins as shown in red, and we compared these vaccines to adjuvant and spike protein vaccine in green for a placebo shown in gray, shows you sort of the two ends of the spectrum. After the animals were immunized, we challenged them with a matched SARS CoV-two virus and looked at viral titers on 4 days posted infection.
What we saw was very promising results. On the left side, these are the viral titers that the lung was on day 4. As you can see, relative to the PBS immunized animals, all groups At undetectable levels of virus. So, they're very, very low levels of virus, implying that the vaccines were protected. On the right side, these are the fighters from the nasal turbinates.
This is an important measurement and It partially represents the likelihood of transmission of the virus. As you can see, of the vaccines that we tested, The famRNA spike vaccine, in blue, had substantially reduced titers and all of the famRNA Overall, that contained S also has reduced titers. So this demonstrates that the vaccine is effective in protecting these animals from viral challenge. And we are very excited to see how the data on immunology that we described earlier is actually translating to protection in animal challenge models. So with that, let me pass back to Doctor.
Batson.
Just a brief summary of where we're going. So Over the next year, what we expect to be able to show you when we come back in 12 months. So we'll continue with Fluzilvac's licensure really, as I mentioned, driving the age range down. In fact, we anticipate The approval in the Australian environment down to 2 years by the end of this calendar year. We're conducting a study for FLUAD Quad, extending the age range down to 50.
We believe there's certainly a public health need and possibility of generating good data in that space. We've actually commit that study in the Northern Hemisphere this calendar year. AQIVC, as I mentioned, we'll get the data from both of our studies and Before the end of this calendar year, we'll make a decision about the right dose to take to Phase 3 and we anticipate starting that study for Northern Hemisphere 2022. So in the second half of twenty twenty two, we'll commence that program, which is very exciting and that should read out After about 1 season, we anticipate that study. And I guess the excitement for us about AQIBC with all that we've described is With technologies that have already been given together and demonstrate the benefits that Ethan and I have described to you, We think that that program has a high likelihood of regulatory success and probably and most importantly of being a real benchmark for influenza vaccines.
And then we're investing now with, I guess, confidence that in our self amplifying mRNA program that's really being brought about by the success of the technology in addressing COVID. We are focusing on influenza And we'll commence our GLP tox study by the end of this year in anticipation of commencing a seasonal influenza program and pandemic influenza program in the second half of twenty twenty two. So in summary, Our vision, I think we've tried to describe to you our vision of the future. We believe AQIBC has a chance to be The best flu vaccine in the more immediate term, using proven safe technologies, it doesn't require complex Supply chains to get distributed, we think it has a terrific safety profile. We think that's got a high chance of regulatory success, as I said, and being a new benchmark.
We see this as complementary to mRNA And we and others that have just talked about the potential for mRNA influenza vaccination, We're excited, but we're also cautious from many years of experience of what to expect. Influenza is a different virus and Ethan's touched on many of the points, But there are practical issues like the side effects that we're observing with mRNA vaccines and how acceptable that rate of side effects might be in a yearly seasonal flu vaccine that the complex supply chain, the need for 4 times the amount of least 4 times the amount of mRNA, all suggest to me that we will need to tread Carefully and be thoughtful about our program. We'll invest hard in this and make it go as fast as possible, but we're not in a time of a pandemic. So there's not the same global urgency and there are existing influenza vaccines that work pretty well. So I think the environment external to us is also different and the requirements of information and for regulatory approvals will also be more stringent than they have been with COVID.
So for a variety of reasons, this is exciting, but it will provide many challenges that we are anticipating. So with that, I'll hand back to Bill Mezzanotte.
Thanks, Russell, And thanks to all the presenters for the very clear presentation and for representing CSL so well. We go to the next slide, please. Here is our new updated clinical phase portfolio as of October 2021 and what we'll be showing you the next time we get together. We're very happy with the balance across the therapeutic areas and across phases, ensuring we have a chance to make a meaningful difference in patients' lives for the foreseeable future. Speaking of the future, on the next slide, I'd like to
show you the expected Approval is
coming. This year, we plan to submit HEYGARDA for approval in Japan for HAE based upon the great results Diedrich shared with you earlier. And we hope to gain approval in the upcoming calendar year after submission. Then we will follow with many exciting opportunities that we've been discussing at these R and D days over the past And of note, we now include Idelvion in China. This is an opportunity to bring a fantastic medicine to a large group of patients With an unmet medical need.
Our portfolio will also hopefully mature with products on the market in 2 more of our therapeutic areas, cardiovascular and transplant areas. And of course, 2 important Themes that Russell and Ethan discussed will hopefully be improved in this time period as well. So stay tuned. And then lastly, on the next slide, what do we hope to show at the end of this financial year. Here are the events we hope to be on the slide when Mark and Paul talk to you at the end of our fiscal year 2022.
These opportunities represent some major advances in patient care and major advances For the CSL portfolio, so let me just highlight a few. In the immunology space, We will look at we will talk about garedasimab completing Phase 3 study enrollment, hopefully. HeyGuard is submitting to the PMDA as we mentioned and Hizentra CLL initiating a Phase 3 study. In hematology, Kcentra will initiate the Phase 3 study for treatment of massive hemorrhage associated with severe traumatic injury. And of course, edronidaz will submit in both in Europe and the U.
S. Transplant, we will begin the Phase 3 study with CSL-nine sixty four for the prevention of GvHD. In respiratory, we will complete now Phase 1 and B of the CSL-seven eighty seven nebulized ID program, which we did not discuss today. And we will initiate, as Andrew mentioned, the garidastimab Phase 2 study for idiopathic pulmonary fibrosis. In cardiovascular, we will complete the 3rd interim analysis for CSL-one hundred and twelve.
And if there is nothing at least early, then by then at the end of the fiscal year, we will I'll let you know that we passed that successfully. Finally, in influenza, The AQ IVC program will complete Phase 2 safety and immunogenicity. And of course, already we've had the flu cell vax Quadrivalent U. S. Approval in 6 months and over.
So an exciting rest of the year to come With a lot of good news hopefully to share with you. And so with that, I'd like to go to the last slide, turn it thank you for your attention And turn it back to Mark to moderate the question section. And Mark, you may have to do a little extra moderation in case we have a little difficulty hearing some of the questions. Thank you, everybody. And now over to Mark.
Good. Thanks, Bill. And ladies and gentlemen, the questions, they will be queued. And in the interest of giving everybody an opportunity to ask questions, please limit your questions to 2. You are of course welcome to rejoin the queue should you have further questions.
Our first question comes from John Deacon Bell at Citigroup. But before we start, Zoe, operator, could you open up the lines and just remind people how to queue for questions?
Thank
Good. Thanks, Zoe. So first question, John Deakin Bell at Citigroup. Go ahead, John.
Thanks very much, Mike. My first question is just on CSL-one hundred and twelve. I'm just trying to get a better handle on the impact that the pandemic has had on this. So if we went back to 2019 R and D Day pre pandemic, there were some timeframes set out that appear to have taken a little bit longer. I mean, can you just go back and remind us what you're expecting in 2019 and what you're expecting now, just so we're clear
So I think, Mark, the question was what were we expecting in 2019 And what are we expecting now? I would say that in 2019, we would have expected to be Basically done enrollment now. And now we're expecting to finish enrollment Sometime in the middle of 2022. And that will then Require another year when the final person is enrolled to complete the trial and then data analysis can start And the filing can commence soon after data now.
Okay. And so just to be clear on the question, so you're saying target launch FY 'twenty three to 'twenty six, will it given all of that, It's most likely to be closer to 24 or 25 at the earliest. Would that be fair?
I
think sorry, we are having a little technical difficulty. I think what you said We'll probably be filing in 2024, which is correct.
Thank you very much. And my second question just relates To the CSL 730 ST Multimer, which you didn't mention today and it's not Anything progressing over the next 12 months. I note that your that argenx has obviously filed in PDUFA for the Myasthenia gravis, an indication later this year. Can you just and then obviously, since we spoke last time, UCB Stott, it's Strahl, CIDP. Can you just give us your updated view on where the whole FCRN Program is and how you expect it to impact the business over the next 3 to 5 years?
So the question I believe was on the impact of SCRNs In the CIDP and other space. And I'll let Andrew maybe talk about that. He's talked about that in the past, The impact. I think first your question was on CSL-seven thirty and we've turned to a subcutaneous version of that And we continue to progress that, but it remains in Phase 1 because we changed to a subcutaneous formulation. As far as CIDP, UCB did stop their program.
Others have Proceeded in CIDP, I think the jury is still out on whether it will or will not have an impact there. I guess we're a little bit more on the side believing it will have less impact, but we have to remain we have to wait See what the data show. But maybe Andrew, you want to comment a little bit more on that?
Yes, sure, Bill. And I think you made the right points. I mean, It's just worth considering the overall IG market, where we know that around 50% of product is used to treat immune deficiencies And the other 50% is used to treat autoimmune diseases such as CIDP and MG. And clearly, the Patients that have immune deficiencies, primary or secondary, won't be treated by the FcRn inhibitors. So it's that portion of the market, which is autoimmune disease and whether it's neurology or rheumatology or whatever.
The question is, which indications in that area Mediated or driven by auto antibodies. And clearly, MG and ITPR, And that's why most of the companies in the FcRn space started there. I think when you look at that autoimmune space and think about the IG market, NGI and ITP combined are a very small portion of that segment of the market. So we don't see we think that they'll potentially be important products in those indications, but not significantly impacting on IG. The importance of autoantibodies in CIDP, which is A much more complex disease, as I think you know, is much, much less clear.
And As Bill mentioned, UCB, for that reason, amongst others, discontinued their study. But I guess ultimately, we'll see with the Phase 3s that are ongoing.
Thanks very much.
Thanks, John. Ladies, gents, we're having a little challenge with audio and I encourage you to either pick up your handset or do what you can to help us on that front. But we'll now move to the next question, which comes from Andrew Goodsall at MST. Go ahead, Andrew.
Thanks very much and let me know if you can't hear well, but just picking up where John finished, I guess, just are there other areas of your Portfolio where some of the new non protein approaches you think could encroach upon what you're doing with current placement products on I'm thinking that all for 1 or any other areas, I guess, that you feel you might be deficient or would want to
Mark, can you please repeat the question that was asked?
Yes. So Andrew, I'll paraphrase for you. It was looking at other proteins similar to what's happening in IG, potential threat of FcRn's there. Is there anything happening in the Alpha-1 space or any of other proteins within our portfolio? Is that a fair summation, Andrew Goodsall?
Yes, that's it. That's it. Yes. Thanks.
Is there any other are we doing any work or is there any other Disruptive work going on. I think that was not clear to me.
Yes, just where you feel that Just like FCRN, we need to, I guess, understand where the risk might be. Yes. Thank you.
So Andrew, there's a number of approaches being tried in, for instance, alpha antritsine. I mean, there is gene therapy going on. There's some There's even a gene editing program going on in Alpha-1. In fact, there may be even Some recombinant approaches going on that have been we've looked at in the past as well. Whether they can prove that they have the impact, of course, partly is mechanistic, But partly it's been how do they prove there that they can be a replacement for the Alpha-1.
That's been a difficult area of regulatory clarity for a while already. So we don't see anything immediate on the horizon. There was a couple of Alpha-one programs Earlier this year, they were discontinued for disappointing results. So we wait and see what else And other than that, in other areas of the portfolio, I don't foresee anything And then near term.
That's great. And if I could just change in course a little bit, could I clarify if you've got anything Continuing on a COVID fact, specifically anything perhaps that might come about with a contract with the Australian government or anything you might be doing University of
Queensland. That's all I think that's to you.
Yes, I'll take it on. Andrew, we continue to collaborate with the University of Queensland. We're providing MF59 adjuvant. They have an ongoing program. We will continue and complete our contractual obligations around AstraZeneca manufacture to 50,000,000 doses.
Beyond that, it appears that the world's going to be well supplied and Australia in particular will be well supplied. And we our priorities, I mentioned for SA mRNA is influenza, not COVID.
And is there any update at all on that government contract?
The AstraZeneca one you made?
No, just the Australian Government's desire to have domestic manufacturing in R and A.
Sorry, the ATM. We're still waiting for the Australian government to sort of announce what their next steps are.
Thank you.
Good. Thanks, Andrew. Next question comes from Chris Cooper at Goldman Sachs. Go ahead, Chris.
Thanks, Mark. Just first off for Russell, you mentioned in your closing comments there that you'll be investing hard into mRNA and flu. Look, I obviously appreciate it's very early stage, but how are you thinking about the development strategy in that program? I know your comments you plan to enter Phase 1 by the end of calendar 'twenty three. Presumably, you're looking to Phase 1 data in middle of 'twenty three.
And do you think you can do this alone or do you need to collaborate?
So there are a couple of elements to that. We do use contract houses to help us in well known places, because it's initially a complex manufacturing approach that can get simplified over time. So We are seeking partners to help us there, but largely contract houses. We'll be doing the influenza vaccine program independently, That's our own. We will pandemic and seasonal tied together.
We'll be doing, as I mentioned, both The priorities on getting the seasonal progressing. We are looking at ways in which we can move that ahead without The normal wait for seasonal sort of the seasonal cadence because normally we can only start studies at the beginning of each winter, so we only have 2 chances per year. But We think with this program, we might be able to move it outside of that until we get to the final stages of it. So we're looking at ways in which we can keep that moving quickly. But I guess, I would still stress that it's really important.
We know that flu He's given across the whole population year in, year out. And it's really some of the challenges that are evident with COVID that As we think about flu that are acceptable with COVID, we don't think we'll be accepted with flu. So we're just we've got to make sure we understand that. So there's a sort of fine balance between speed and not being too hasty and finding you mess it up.
Good day.
Thanks. And just shifting gears on to Kcentra. I mean, my understanding was that this is already being used 7% in trauma cases. Could you just sort of help contextualize for us what just coming clinical work is going to do for the revenue potential in that drug?
I'll start and maybe Bill, I'll turn it over to you. I mean, I can't comment on the There is a new expanded Label in Europe and there is some greater use of this, but in the United States, it's not In our label. And so it allows for some promotional capabilities of case entrant and pharma. And so therefore formularies and other things can change their approach to the use of Phil?
Thanks, Bill and Chris, thanks for the question. It remains a really exciting opportunity for us. You're correct. There is A fairly significant volume of Kcentra used off label and used in a variety of areas, trauma being 1. It is organic use.
We don't and can't promote for that as Dewey will know. We think Doing the study will significantly advance the scientific information, knowledge around the product, How to use the product appropriately, certainly de risk our business as well because now it will be on label. It provides us the opportunity to go in and we're already in these large teaching hospitals And to provide that insight to grow the brand. And Chris, I would say, there's a similar analogy to Pravagen in the U. S.
Where we didn't have a CIDP indication in the U. S. Until just a couple of years ago, as you know, And we were dramatically underrepresented there and having the promotional ability there has helped us significantly. We see a very similar approach in with Kcentra in trauma.
Thanks, Chris. Next question comes from Saul Hodeson at Barrene Joey Capital. Go ahead, Saul.
Thank you. Yes, just Two questions from me. Following up on that last question about Kcentra, I mean, I just want to be interested to know, you seem to go down this path with fibrinogen with the REPLACE study quite Quite a few years ago and that was a difficult study to run. And in any acute trauma and bleeding, it seems like The protocols are difficult to put in place. So what gives you confidence that this Phase III will be any different to what the difficult process for the fibrinogen product?
Yes, thanks for the question. And it's part of the reason I said that we spent some extra time getting this ready And why we didn't initiate it immediately. So we have been working closely with academic, Medical center and trauma specialists to make sure that the protocol we're conducting actually Meshes well with the trauma protocols that they're using and that the measurement that we can do It is measurable and easy to define because part of the issues in the Hi, Bernadette. It's Sotivayev in the endpoint as well. And between the use of the product in a protocol That's center friendly, along with the cooperation of really Some international experts and a steering committee that we think is quite impressive and then an endpoint that not only the FDA likes, but I think is Easy to quantify, all it gives us more confidence than we do.
Great, thanks. And just one other, I think Probably the first time we've heard about gene therapy in the primary immune deficiency setting, at least from CSL. If you look at the various subtypes of PID, I'm just wondering how many of those would lend themselves to sort of specific gene editing Protocols, if you look at the pie outside of sort of common variable, what percentage of the remaining subtypes could in theory be Traited using gene therapy at the time.
Yes, I'm going to let Andrew speak to that because I think it's sort of a now and maybe in the future Question that could evolve, but Andrew?
Look, I think, just thinking back to that pie chart, There's quite a number of smaller PIDs where the underlying genetic lesion is well characterized and they're amenable to gene therapy, whether it be gene replacement or gene editing. So we're targeting 3 in particular, which we think is a good place to start. Common variable immune deficiency, more complex, but an area that's a subject of intense research at the moment with the genes involved in those in that disease being characterized and much better understood as we go forward. We think gene therapy will find a place in primary immune deficiency alongside of IG, How long that takes and how widespread it becomes really depends on how the science pans out. But we actually have discussed it Before in previous R and D days, we think the collaboration with Seattle is critical to our success.
We've aligned ourselves It's really one of the leading medical research institutes and we're progressing nicely at the moment.
Thank you.
Thank you, Saul. Next question comes from Sean Larman at Morgan Stanley. Go ahead, Sean.
Good morning, Mark, and good morning, everybody, and thanks for taking My question is related to gene therapy, but I am going to start asking about garidazimab. So you introduced that to us a Couple of years ago now I think and was originally set out as a treatment for HAE, but you talked to moving further up the biochemical pathway and For opening other treatment markets and indeed you talked about the different fibrosis today and the applicability of garidazimab to that. But I'm wondering, you also talked about gene therapy and I'm wondering if you move further down that or up that biochemical pathway, if there is a gene associated with this. And so therefore, it might lend itself to gene therapy as well downstream to the one for all Treatment for both HAE and some of those fibrosis. Thanks.
Yes. I mean, I'll let Andrew comment in a moment. But sure, there's a speculation that could be a gene related Issue or a therapy that could target this gene as well, Whether that's an editing approach or whether that's a purchase of sell and do third, I'm not sure. But Andrew?
Yes, there's a bunch of things that have been proposed or ongoing at the moment, ranging from repairing of the C1 gene to actually going in and knocking out mediators like Callicryne and Factor 12, actually Changing the integrity of the genome. I think the point here is that there is going to be a very, very high bar for those therapies. With something like garidasumab, you're going to have a once a month subcutaneous dose that effectively Q is the disease, as you saw, response, 98% reduction in attack rates. So Just how really in gene therapy approaches, gene editing, very difficult To get it right, the procedures are tough. How they compete against such a therapy that's so effective and so convenient for patients.
I think it's going to be pretty tough for them, but the activity is ongoing.
Great, thank you. And just Sorry, go ahead.
Yes, I just wanted to further on that. I mean, I think Andrew is right. Because there are so many diseases like this that We could talk to the same thing and it's going to come down to the, of course, the quality of the gene therapy, the seriousness of the disease And the quality of the other existing therapies adds to the impact of the gene therapy, I think. Probably each disease will be disease by disease and we'll find out as we go along.
Sure, sure. And I guess this might be an unknown question, but I guess if you look at all that portfolio of diseases that immunoglobulin treats, Very different diseases, but treating you with the same product. And you've talked about gene therapy and going down that pathway for primary immune deficiency. Is it too naive to think there might be a root cause that you could actually have a gene therapy product that really supplant More than just the immunology portion of your IG portfolio, but extends into neurology as well or is it just too unknown?
Yes, I
think that's unlikely. As Andrew said a few minutes ago, First, let's start with the fact that IgE is a remarkable molecule that sometimes acting as a In new booster, right? And then other times, there's an immune modulator studies that Deirdre outlined. So right away, it's doing 2 different things and I'm not sure that in fact that the polyclonal IG is doing it in exactly the same way. And then you get down to what actually the deficit in each of these diseases and they're again quite different.
You start Quickly slicing and dicing these larger groups into much smaller groups And you end up I think with an array of individual phenomena that the human body has Over time remarkably created this molecule or group of molecules that makes this difference. So I think maybe even look far, far down and say there'll be a number of different therapies Taking its place, but I doubt there'll be one therapy that goes there.
Great. Thank you. Fascinating. Appreciate your answers. Thank you.
Good. Thanks, Sean. Next question comes from David Stanton at Jefferies. Go ahead, Dave.
Yes. Good morning and good evening. Thank you Thank you for taking my question. Look, we've seen the EU recently expand the indication for use of plazentra in more secondary immuno deficiencies It's now indicated as a replacement therapy for all patients with secondary immunoefficiencies compared to only some With CLL and multiple myeloma. What and maybe a question for Bill, what does that mean for over the medium term for demand Growth in Europe for Hizentroflip.
Thanks, David. I think you met Bill Campbell, so I'll jump in if that was the case. It is an interesting opportunity for us, Both the Pravagen and Hizentra, we have seen strong growth as I've talked in the past inside the SID space. We think it will continue that growth in the EU. We think that doing a broader clinical trial, In particular for the U.
S. Market as well will lead to additional growth. Much like in many other places, as you know, We do benefit from organic off label use. Having a specific indication and allowing us to go in and talking The right customers with the right message and instructions on how and where to use and providing that partnership, We feel is just a strong will provide a strong uplift in the business. So listen, the IG market has Continue to grow.
As you know, there's not enough IT right now to satisfy all this demand. And as we return to kind of pre COVID collections on plasma and have more IG, We think it'll just expand ongoing use for the brand. Bill, did you want to add something to that?
No, Bill, I think that's great.
And my second question maybe for Bill Campbell as well as a follow-up to that question. Could you give us some idea of what you think off label use is particularly in the U. S. For the use of Hizentra in most secondary immunodeficiencies, how much more growth do you think you can get In doing this clinical trial in the U. S.
On sort of an annual basis, if it's positive.
Yes, thanks, David. We believe there's still significant Use with the indication, while we get used in SIV today, there's a lot of Hematologists that are not writing branded prescriptions, that's generic, IG. And we think we have a quite interesting story with both Pravagint and Isentra to tell in that space. The majority of our use today, of course, is on label. It's PID and now PIDP, some MG and some Hi, P.
D. There is currently a baseline SID utilization. It's far lower than what our overall share would portray.
Thanks, Dave. Our next question comes from Schrumman.
And I would just add
to that one that there are A lot of these diseases take on. It's almost as varied that constitutes the primary immunosupperciencies that constitute the secondary Starting with CLL, it's the largest group, but there's a number and we saw them actually during COVID when people weren't responding to their vaccine and I wanted to know if we had a hyperimmune that would work for them. We're trying other therapies instead, but Just saw just how many different and varied functionally inefficient people are in different categories.
Next question comes from Leanne Harrison at Bank of America. Go ahead, Leanne.
Yes. Good morning, all. In previous presentations, you have the portfolio slide include some of your preclinical candidates. And Today, you spoke a bit more about the SA mRNA. But other than that, can you talk a bit more about the fullness Of your preclinical stage and what other candidates can we expect to move to clinical trials in the near term?
Yes, I'll let Andrew discuss that in a moment. We consciously removed some of the preclinical Assets, some for IP positions, some for more clarity in the later So we're doing work across all of our therapeutic areas and beyond. And I think we will continue to have a stream of
Yes, look, I think that's right, Bill. Our preclinical research Portfolio covers all of our 5 therapeutic areas and Securus has a strong research portfolio as well. That portfolio includes really early stage discovery research that's primarily done in partnership all the way through to the optimization of candidates from recombinant technologies, gene therapies and from plasma as they move through into preclinical toxicology. So we across our Therapeutic areas, we have a number of programs in the toxicology phase. For us, it's post Stage Gate 2 And we have a number of programs approaching Stage Gate 3, which is first in human studies and they range from recombinant proteins, Gene Therapies and Plasma Proteins.
I guess, in addition as well, we have a strong focus on looking at our existing on market assets and our clinical assets and really seeking to Dan, where else they might be used, what other indications they might be effective for. And we're really taking a systems biology approach there, trying to understand where those pathways Are important in diseases and where we think we've got to lead follow that up into animal models and then through into the clinic. So There's a strong pipeline set up behind what we've been talking about today.
Okay. Thank you very much.
Good. Thank you, Leanne. Next question comes from Gretel Janu from Credit Suisse. Go ahead, Gretel.
Thanks, Mark. Good morning, all. So firstly, just wanted to touch on the ChinaVES. So given the delay to filing and then the fact that the trial was on clinical hold earlier this year, Just wondering whether this had any impact on the physician's view of the product or your view in terms of the possibility of commercial success. And so as we move towards commercialization, where are you positioning it and how quickly do you think the ramp up would be for this product?
Yes. Let me start and then I'll turn it over to Bill Campbell. So from an R and D perspective, we're fully Supportive of this product and the ultimate benefit risk profile. Yes, we were on clinical hold because of one case of Cellular carcinoma that occurred in a patient with a previous history of hepatitis B and C. That case and that patient was thoroughly evaluated with UniCure including the most up to date molecular analysis.
And they
were able to show that
the Trinidad was not integrating into the data cells and that the likely cause And in fact, the FDA convened a panel earlier in the summer, U. S. Summer, looking at the safety of these gene products, Gene therapies as a whole. And they mentioned specifically that the same case So we don't think that this is going to impact the approvability of the product at all. I think the pay was due to getting more Long term data, as the FDA wanted to ensure durability of the therapy in effect.
It trended out for over 2.5 years now in Phase 2b in patients, but And stable factor 9, as Diego showed earlier in the presentation. So we think there's been nothing that's come out of the FDA reviews of the therapy That hinders the approval of this product. In fact, we think we're in strong shape. But of course, We still have to file and get approved, but that's what we're going to say today. And Bill, I'll turn it over to you for the commercial view.
Thanks, Phil, and Gretel, thanks for the question. While I'm fortunate to have A clinical hold or a delay, I don't believe there will be any impact on commercial update.
We've had
a chance to speak with
a lot of opinion leaders around the globe, a lot of treaters, who Have been anxiously awaiting a gene therapy for a couple of decades now. So there will be, I think, because of the nature of the therapy. Some wait and see. There will be some early adopters that will embrace the product, I think Probably early on and I think it will take a bit of time for it to get established in the marketplace with most people. There's lots of education to do around the product yet.
There's Questions around durability that we're going to have to talk through with patients And their physicians and health agencies and so forth. I think ultimately, Gene therapy is the absolute promise for these patients and it's the absolute thing that they've been wanting for a long time. And I for 1, if I was an affiliate patient would be embracing this. And so will it be for everybody? Probably not.
I think it'll take some time, But I think it's a beautiful fit with Idelvion as well. I think we have the current Market leading product and I think by a lot of people's definition would say the best product out there, with 14 day dosing and 21 day dosing In Europe, very little bleeds on the product. And then the next transformation, which is Gene therapy. So I think we're in the early days with gene therapy. There are hurdles ahead.
There's Long road ahead of education, pricing and reimbursement and market access, but The promise of these therapies are really quite amazing and well, maybe not a complete cure, perhaps a functional As Andrew elucidated. So I think there's a lot of excitement. I think the community has been looking for this for quite some time and We're going to have to walk this long road with them as well.
Great. Thank you. And then just changing Topic to mRNA flu vaccine. You did mention that some of the key challenges at the moment for COVID vaccines are storage, temperature, side effects needing 2 doses. Does the self amplifying mRNA alleviate or address some of these challenges relative to the traditional mRNA that a lot of your peers are using in their Flu vaccine trials.
And is there more that you can do to address these challenges?
Ethan, why don't you have a go at that one?
Sure. Yes, what I'd say is that as far as Storage goes, that is an area of constant improvement. And so that's an area, RNA itself is relatively It's stable and so therefore one has come up with ways to avoid the instability. We are working on that, others are working on that. So there are similar challenges there.
From a dose perspective, one of the benefits would be a potential lower dose and that lower dose could lead to the lower level of reactogenicity. So that's really where there's some advantage and differentiation between the 2. And as far as the number of doses, Certainly in those for flu, we would expect that most people have been either already exposed to vaccine or the virus. So really one dose is usually sufficient for most individuals. So that would be the same case for either one.
Great. Thank you very much.
Thanks, Gretel. Next question comes from David Lowe at JPMorgan. Go ahead, David.
Thanks, Mark. If we could stick with the mRNA topic, just in terms of there are a lot of groups out there that are Starting in Phase 1 trials at least and planning to progress quickly. Just wondering if you could talk a little bit to where you see the potential threats in The timetable there, how long will it take them to perhaps get through, get a seasonal influenza vaccine approved if All went broadly according to plan.
Thanks. Thanks. I'll take that one.
Yes. Yes.
I'll take that one. Look, We think there's some numbers, some dates out there as early as 'twenty four, which we think is a bit optimistic. Even If we were starting today, we just map out when you map out the challenges we think there, it will take a bit longer than that. We think In the estimated sort of timeframe that Bill gave to the 23 to 26, we think the latter part of that time would be when we'll start to potentially see mRNA vaccines hit the market, if everything goes really well. That's our estimate.
Okay. Thank you. And just again related topic, so it would appear that egg based Vaccines, their future is looking a little bit limited. What are your expectations there? I mean, are vaccines going to be a thing of the past Perhaps by 2026, what are the plans for CSL's egg based facility?
I think we need to sort of differentiate CSL and the global sort of flu ecosystem. So, yes, we're certainly moving towards differentiated vaccines. We won't our flu cell culture vaccine in terms of the dose number the doses we can churn out, etcetera, We think we'll still have demand for FLUAD, the egg based vaccine towards the end of this decade, so we don't anticipate that winding down. On the other hand, when the new facility, the new factory in Melbourne gets up and running, we will Almost certainly be phasing out Afluria by that time because we see flucelvax, we'll have the manufacturing capacity and we don't see Apleura having benefits to being manufactured as well as it will probably be more expensive to make than Flucilvax in that timeframe. So For us, we see a move away, but certainly we'll still have Fluad.
I think part of The challenge of all these new technologies is we have to all participate in the global flu surveillance system and ecosystem that Ethan sort of alluded to or mentioned early in his chat. And that's And egg vaccines are going to have a prolonged presence in the world because there are billions of doses demand around the world, in developing countries as well as developed countries. So, I think egg is around globally for quite a while yet.
So, those countries don't use Vaccine at the moment and the efficacy is not fantastic, I mean, is it realistic to assume that they would be using egg based vaccine?
Look, efficacy is not fantastic, but if you look at and it can be improved, that's why we're all that's why we're focusing on differentiated vaccines and new technologies, but they're better than nothing. And if you have a price challenge, vaccinating your population against with an egg based vaccine is still a huge benefit to that community.
Great. Thank you very much.
Thanks, David. Ladies and gents, we've got 2 more in the queue. We'll take those after which we'll draw to a close. The next question comes from David Bailey at Macquarie. Go ahead, David.
Yes, thanks, Mark. Hi, everyone. Just in relation to China actually, determination of CSL 630, Just wondering if there's any implications for the local plasma collection there and I'm also interested to understand the pathways to launch Some of the recombinant products within hemophilia going forward.
Sure. Thanks. I'll take the first and then I'll turn it over to my colleague, Deirdre Footeinars for the second. So, As far as the plasma collection, we are continuing to collect plasma and plan to conduct our business As it stands today with the centers we have and focusing on continuing to improve the processes there for IG And for Al Beumann. Obviously, without CSL-six thirty, the 6 and 3 will not be And we're looking at other ways that we might be able to meet that in the future.
But in the meantime, we'll continue to collect plasma In the Hubei province and processes at the rate of plant. And as far as our plans for confidence, Deirdre?
So for the near term, as Phil mentioned, we're looking to develop Adelvion and Aptola for the China market. I won't speak about launch, but for development, we're working with the authorities there as well as healthcare providers to Start of clinical trials to show how those products perform for efficacy and safety in the relevant Population within China. So it's a bit of a bridging strategy, given that they're already on market. And then as we progress The rest of our biotech portfolio will be looking to include China in our global development program wherever it's appropriate.
Yes, okay. That's fine. Understood. And then just a quick one. Clavikitumab didn't get much of a mention today.
Just wondering Where that currently sits, has there been any change since the commentary last year?
It continues to progress. A little bit of impact from COVID as well because it's one of those hospitalized protocols as I was mentioning earlier. The next big thing is we have to get to the next milestone of number of patients so that We can look at the interim analysis, but that probably will be another year at least till we get to that now.
Yes. And look, as Phil mentioned, the conduct of trials in hospitals itself has been a challenge in COVID and these patients That are clearly quite vulnerable. It's also how they're navigating healthcare systems in general Will remain a challenge in some areas, but certainly we're working very closely with our sites to make sure we continue those trials while protecting The patients that may volunteer to participate.
Yes, thank you.
Good. Thanks, David. Our last question is from Steve Wien at Jardan. Go ahead, Steve.
Thanks, Mark. Can you
hear me?
We can.
Yes, great. I appreciate this hasn't been discussed as part of your slides, but Expect this does come under R and D. I'm wondering whether or not you could give us any insight or color around the trial for Transitioning to the Terumo plasmapheresis collection platform. And any updates
I don't know that I have a latest update. I do know that the trial was conducted And I believe they have either filed or are planning to file soon, but that's about all the update I know.
Okay. And then secondly, just turning to Rispera and Zameera. Over time, that's sort of been a bit start stop with regards to bottlenecks supply chain issues. Can you provide some insight as to what's been the problem here and whether the latest efforts Something that will fix that problem, Wood?
I'll start, Bill, and then maybe you can Pickup, so there has been a few manufacturing pickups again with the Sameera line. We believe we have a fix now. We'll know about that fix Early in 2022 and we'll be able to give you an update towards the end of the year We're at the or with the full year results. I'm optimistic that we have a fix That will help clarify the supply long term for Bill.
Anything you want to add? Thanks, Phil. I'll add a little bit and Steve, thanks for the question. It has been a start Stop process, you're right. We feel badly about that.
We spend a lot of time talking Patience about our current situation and have tried to reposition product back and forth to various markets to meet the needs To the best of our ability. I like Bill, I'm very confident that the pieces that we're now putting in place We'll solve this issue. The team has spent a lot of time and effort and they brought a
lot of Effort
to getting this fixed. So I'm pretty confident that that will be the case. We have a bit longer, as Bill said, to get through the balance of this fiscal into next. And then I think we'll have it behind us once and for all.
Good. Thank you, Steve. Ladies and gentlemen, we have no further questions in the queue, so we'll draw the briefing to a close. I'd like to thank you for your interest in CSL and goodbye.