Driven by Our Promise CSL Limited Annual Report 2022/23
Contents Annual General Meeting The 2023 Annual General Meeting (AGM) of CSL Limited (ABN 99 051 588 348) will be held on Wednesday, 11 October 2023 at 10am (Melbourne time) Clarendon Auditorium, Melbourne Convention and Exhibition Centre (MCEC), South Wharf, Melbourne 3000. CSL Calendar 2023 15 August Annual results and final dividend announcement 11 September Shares trade ex-dividend 12 September Record date for final dividend 4 October Final dividend paid 11 October Annual General Meeting 31 December Half Year ends 2024 13 February Half Year results and interim dividend announcement 11 March Shares trade ex-dividend 12 March Record date for interim dividend 3 April Interim dividend paid 30 June Full Year ends 13 August Annual results and final dividend announcement 9 September Shares trade ex-dividend 10 September Record date for final dividend 2 October Final dividend paid 30 October Annual General Meeting 31 December Half Year ends About this report This Annual Report combines CSL’s financial and non-financial performance in one comprehensive account, linking our sustainability and strategic priorities to our business results. CSL conducts a detailed sustainability materiality assessment every two years, with our most recent assessment undertaken in early 2022. The prioritised results of our assessment are available within this report and on CSL.com. In addition, this year, we compared CSL’s materiality assessment with that of Vifor Pharma, and while there were minor variations, an enterprise-wide assessment will be conducted in financial year 2024. In addition to an independent audit of our consolidated financial accounts, limited assurance on a selection of corporate responsibility (CR) metrics has been provided by Ernst & Young, and an assurance statement for non-financial indicators can be found on page 81. Further, more detailed Group and sustainability information, including CSL’s materiality assessment, can be found on CSL.com (Sustainability). Legal notice: This report is intended for global use. This 2023 Annual Report is a summary of CSL’s operations and activities for the 12-month period ended 30 June 2023 and financial position as at 30 June 2023. This report covers CSL’s global operations, including subsidiaries, unless otherwise noted. A reference to CSL, CSL Group, we, us and our and similar expressions refer collectively to CSL Limited and its related bodies corporate. Some statements about products, registered product indications or procedures may differ in certain countries. Therefore, always consult the country-specific product information, package leaflets or instructions for use. For more information, please contact a local CSL representative. Brand names designated by a ® or a ™ throughout this publication are trademarks either owned by and/or licensed to CSL or its affiliates. Not all brands mentioned are used or registered as trademarks in all countries served by CSL. Forward-looking statements This report contains forward-looking statements including statements with respect to future company compliance and performance. This report also includes forward-looking statements regarding climate change and other environmental and energy transition scenarios. While these forward-looking statements reflect CSL’s expectations at the date of this report, they are not guarantees or predictions of future performance or statements of fact. These statements involve known and unknown risks and uncertainties. Many factors could cause the Group’s actual results, performances or achievements to differ, possibly materially, from those expressed in the forward-looking statements. These factors include changes in government and policy; actions of regulatory bodies and other governmental authorities such as changes in taxation or regulation (or approvals under regulation); the effect of economic conditions; technological developments in the healthcare field; advances in environmental protection processes; and geopolitical developments. There are also limitations with respect to scenario analysis, and it is difficult to predict which, if any, of the scenarios might eventuate. Scenario analysis is not an indication of probable outcomes and relies on assumptions that may or may not prove to be correct or eventuate. Readers are cautioned not to place undue reliance on forward-looking statements. Except as required by applicable laws or regulations, CSL does not undertake to publicly update or review any forward-looking statements. Past performance cannot be relied on as a guide to future performance. Non-IFRS financial information References to AASB refer to the Australian Accounting Standards Board and IFRS refers to the International Financial Reporting Standards. There are references to IFRS and non-IFRS financial information in this report. Non-IFRS financial measures are financial measures other than those defined or specified under any relevant accounting standard and may not be directly comparable with other companies’ information. Non-IFRS financial measures are used to enhance the comparability of information between reporting periods and enable further insight and a different perspective into the financial performance. Non-IFRS financial information should be considered in addition to, and is not intended to be a substitute for, IFRS financial information and measures. Non-IFRS financial measures are not subject to audit or review. CSL Limited ABN 99 051 588 348 Find out more CSL.com OFR 1 Chair and CEO message 2 2 Our Company 8 3 CSL’s Performance and Strategy 20 4 CSL’s Material Risks 26 5 CSL’s Future Prospects 28 6 Powered by Innovation 32 7 CSL’s People 40 8 Environment 46 9 Social 53 OFR 10 CSL’s Governance 60 11 Share Information 70 12 Key Performance Data Summary 73 13 Medical Glossary 74 OFR 14 Financial Performance 75
Our Purpose The people and science of CSL save lives. CSL develops and delivers innovative medicines that help people with serious and life-threatening conditions live full lives and protect the health of communities around the world. The CSL Values guide us in creating sustainable value for our stakeholders. Isabelle is an 8 year old girl from Melbourne, Australia who has received the CSL Seqirus Afluria Quad™ flu vaccine. CSL has delivered biotechnology excellence for over a century. Today, with the combined expertise of CSL Behring, CSL Seqirus and CSL Vifor, CSL’s offerings are more diverse than ever to help patients and people everywhere get the treatments they need. CSL Limited Annual Report 2022/23 1
US$2.61 billion in underlying profit (NPATA) attributable to CSL Limited Shareholders US$2.36 dividend per share for 2023 CSL Limited Annual Report 2022/23 2 1 Chair and CEO message Chair Message Dear Fellow Shareholders, I am pleased to share our results and operating review for the 2022/23 financial year. In the following pages you will see that CSL has once again performed strongly, with many operational highlights around the world. A Purpose-Driven Company To begin, I’d like to share my view on why our organisation exists. Your Board is grateful to have many long-term shareholders who have followed our story for decades. Our businesses, and certainly the science that underpins them, can be quite complex. Our purpose though is simple. The people and science of CSL save lives. We develop and deliver innovative medicines that help people with serious and life-threatening conditions live full lives, and protect the health of communities around the world. The great thing about our company is that in fulfilling this purpose, we create value for a variety of stakeholders. First and above all else, our most important task is to contribute to a healthier and more productive society. We do this by saving lives and protecting public health. Our second aim is financial growth – delivering consistent, profitable growth for our investors. It is our sustainable, financial growth that provides the fuel for more innovation and research. If done successfully, it is a great continuous loop: quality research leads to more research, which has the potential to create innovate therapies that benefits society. CSL has been able to demonstrate this over many years. Our third objective is about creating social and economic opportunities and enabling people to benefit as we grow as an organisation, be it employees, suppliers, plasma donors or research partners. Being able to create value in these ways is a great privilege, but also a responsibility. Good governance is an essential part of this responsibility. Leadership Transition The role of the Board is to guide our company in navigating the complexities of the world to create value over the long run. One aspect of this is talent: monitoring the composition of the Board and management teams so that we have the right skills to lead our company. During the year, Paul Perreault retired from his role of Chief Executive Officer (CEO) and Managing Director. The Board and I wish to acknowledge the remarkable leadership of Paul as CEO for 10 years. With Paul at the helm, CSL delivered sustainable growth and innovation with a patient-focused culture. Following a thorough process conducted by the Board, Dr Paul McKenzie was appointed as CEO and Managing Director of CSL from 6 March 2023. Dr McKenzie’s detailed work history can be found later in this report; he brings more than 30 years of leadership experience in the global biotechnology industry to CSL. He is a patient-focused leader with a demonstrated track record of leading complex organisations and delivering outstanding business results. This includes his time at CSL as the Chief Operating Officer, where he has been accountable for optimising CSL’s operations as well as growing the CSL Seqirus, CSL Behring and CSL Vifor businesses.
CSL Limited Annual Report 2022/23 3 Despite there being no changes to CSL’s non-executive Board members this year, the composition of the Board is an ever-present priority. We aim to have the right skills and expertise to navigate our industry and the broader macro environment. We believe we have a strong and complementary dynamic that will continue our long record of exceptional governance. Bruce Brook will retire as a Director at this year’s Annual General Meeting. I’d like to thank Bruce for his service over the last 12 years. His guidance has been of immense value to the Board and our shareholders. Alison Watkins will become Chair of the Audit and Risk Management Committee following Bruce’s retirement. Our Evolving Footprint As we grow and our operations become more complex, your Board continues to prioritise meeting our employees and spending time at our facilities around the world. This year we visited our European operations, including our manufacturing plants and research and development facilities in Bern (Switzerland), St Gallen (Switzerland) and Marburg (Germany). We also spent a very productive week with our Australian teams and inspected our Australian facilities. Underpinned by the confidence we have in the long-term prospects for our company, we have invested a significant amount of capital in our Australian operations over the past few years. This includes the recently completed Plasma Fractionation Facility in Broadmeadows, and our new US$530-million state-of-the-art cell-based vaccine manufacturing facility in Tullamarine, which will be operational in 2026. These investments will enhance our capacity to meet patient needs into the future. We also officially moved into our new Global Headquarters and Centre for R&D in Melbourne in March. Located in the heart of the city’s biomedical precinct, the building represents the progress CSL has made during its journey from a small, local company to the global biotech leader we are today. This is a significant milestone not just for CSL, but for Australia, and I look forward to the scientific and commercial developments that will no doubt come from collaboration in the precinct. Environment and Sustainability In August last year, we took the next step in our sustainability strategy by announcing CSL Group carbon emission reduction targets for the first time. The specific targets build on our previous work by serving as a tangible, transparent roadmap to decarbonising CSL’s operations by reducing the company’s direct and indirect emissions footprint. You can read more in the Environment section of this report, but I am pleased to see the progress we’ve already made. In addition to reducing carbon emissions, CSL is prioritising integrating environmental considerations into key business decisions; minimising end-to-end production of waste through removal, reduction and recycling; and reducing waste in our supply chain. This year, our teams will also be focusing on advancing the social pillar of our sustainability strategy. We will continue to be transparent with our stakeholders, and will share more information as our efforts progress. A Bright Future I can assure you that CSL will remain true to the formula that has largely driven our success to date. There is so much potential to make a difference to people’s lives – so many problems to solve and so much science to translate. CSL has been very deliberate about targeting areas where we know we can develop a competitive advantage. This will not change; we will remain dedicated to our strategy. But this should not be seen as a conflict with our growth aspirations. The two goals are very much complementary: our strategy is built for sustained, long-term growth. Our confidence about this is built around a few key factors. Firstly, the underlying demand for our products will remain robust. It is an unfortunate reality that patients will continue to be diagnosed with rare and serious diseases. We have a high-quality range of safe and effective products that help these patients, and will continue to do so well into the future. Secondly, our research and development (R&D) pipeline is constantly maintained and evaluated. The nature of our business means we have to think decades ahead. We have certainly done this, and a number of key prospective treatments are nearing the commercialisation phase. Importantly, we also have key early-stage options to take their place. And finally, as we grow we will benefit from the capital we have reinvested back into the business. Our global network is built for efficient, reliable supply that we aim to deliver with some of the best margins in the sector. We will continue to drive value across the organisation. The Board and I believe that CSL is in a strong position and we look forward to sharing our progress with shareholders. Brian McNamee AO Chair More on CSL.com (Investors > Financial Results and Information)
CSL Limited Annual Report 2022/23 4 1 Chair and CEO Message CEO Message Dear Shareholders, I am honoured to be writing to you as Chief Executive Officer and Managing Director of CSL, a role in which I began in March 2023. Since joining CSL as Chief Operating Officer, I have been accountable for optimising CSL’s operations as well as growing the CSL Seqirus, CSL Behring and CSL Vifor businesses. Along with the current management team, I have been intimately involved in developing CSL’s 2030 Strategy – from development to execution. My predecessor Paul Perreault was an exceptional leader and oversaw a decade of great success for CSL. I have inherited a highly motivated, valuesbased teamwith a relentless focus on continuing our purpose-driven journey of sustainable and profitable growth. Building on Success At CSL, given the essential nature of our work, the iconic history of our company, and the world-class quality of our team, I am truly humbled and, at the same time, extremely excited to be your CEO. For more than a century, we have been driven by our promise to patients. This has distinguished CSL, defining our strong position as one of the world’s leading biotech companies. Our purpose, values, and promise remain steadfast and even more relevant in today’s complex, and evolving world. The formula that has enabled CSL to deliver value for a variety of stakeholders throughout our history is proven. On page 23 you can read about 2030 Strategy. CSL will continue to follow this strategy under my leadership, but as I look forward over the medium term, I see the following five priorities: 1. Leverage our scale and execute on our commercial portfolios and innovation agendas. 2.Evolve and differentiate our vaccine platform. 3.Unlock the value and growth within CSL Vifor. 4.Drive further improvement in CSL Behring margins. 5.Be an employer of choice and a strategic partner of choice. Playing to Our Strengths I believe CSL is uniquely equipped to contribute in the next era of innovation and tomake a lasting impact on communities around the world. CSL’s many strengths position us well for the future, as shown in the following examples. • We deliver innovative life-saving medicines in over 100 countries. • Every day, more than 342 plasma collection centres enhance donor experiences and provide our critical rawmaterial to save lives. • Our R&D pipeline has never been more robust or more promising. • Productivity and efficiency remain hallmarks and competitive advantages for CSL. Our network strategy is robust, and we are bringing on new capacity and capabilities around the globe.
CSL Limited Annual Report 2022/23 5 The Board of Directors and management team are aligned in our focus. We understand our strengths and are guided by our 2030 Strategy, which defines the guardrails for accelerating sustainable and profitable growth. We unashamedly operate with long-term success in mind. This involves making smart, bold choices today that seek to benefit people and patients well into the future. This year, several important capital investments were completed. As I visited our sites around the world, I was impressed to see these, and the teams responsible for their success, firsthand. In August, we successfully closed the acquisition of CSL Vifor. The integration into the CSL group is well advanced and I want to recognise all the hard work that has gone into this so far. While we have only owned CSL Vifor for a short time we’re excited by the opportunity to grow the iron franchise, to drive new indications, expand into new geographies and improve access. In Broadmeadows, Victoria, we opened our US$600-million Plasma Fractionation Facility. This is the largest of its kind in the Southern Hemisphere, and allows us to process up to 9.2 million plasma equivalent litres per annum, a nine-fold increase on the previous capacity. In March, we opened its sister facility in Marburg, Germany. Featuring identical equipment and processes, we aim to leverage best practice to further improve the efficiency of our network strategy. Also in Marburg, after three years of construction, we opened our new US$160-million R&D site. Covering around 40,000 square metres, the M600 centre provides space for up to 500 R&D employees, making it CSL’s largest R&D hub worldwide and combining all disciplines under one roof. In March, we opened the company’s new state-of-the-art vaccine R&D centre near Boston, Massachusetts, United States. At this site, we will aim to accelerate the development of next-generation mRNA technology for vaccines and collaborate with local partners within this world class research ecosystem. Innovation Agenda These new facilities are intended to underpin the next phase of innovation for CSL. But this doesn’t happen without our people who spend their days investigating new ways to serve patients and public health. R&D, coupled with relentless and disruptive innovation across all parts of the business, has been vital to our success. CSL will continue to build a full and innovative pipeline that has the potential tomake ameaningful difference to the lives of patients and to public health. A key part of CSL’s innovation agenda is forming strategic partnerships with others. This includes partnering with Arcturus Therapeutics to develop and deliver next-generation mRNA vaccines, and with UniQure on gene therapy. At times, this means disrupting ourselves. In 2016, we launched IDELVION®, a recombinant factor IX albumin fusion protein, and it quickly became the standard of care for thousands of patients suffering from haemophilia B. However, we did not stop innovating. Haemophilia B is caused by a gene mutation, so we partnered with UniQure to commercialise the world’s first gene therapy for adults with haemophilia B, called HEMGENIX®. This year we received approval for HEMGENIX® in the United States, Europe and the UK. While there may be some patients who decide to switch from IDELVION® to HEMGENIX®, we recognise that we need to disrupt ourselves so we can make more breakthrough therapies available to those who can benefit. We must take innovation of all shapes and sizes and move it to commercial reality. This is a strategic imperative for us, and can generate speed, efficiency and value. Outlook I remain optimistic about the prospects of CSL. CSL is well placed in markets where we operate. We have a strong financial base, and we have the right leaders to guide our next phase of growth. I can assure you that our people are committed to our purpose and the great vision we share for our company. Paul McKenzie CEO and Managing Director
CSL Limited Annual Report 2022/23 6 1 Chair and CEO Message CSL’s Values CSL’s strong commitment to its values has guided us for many decades. Our Values are fundamental to our success – helping us to save lives, protect the health of people and earn our reputation as a trusted and reliable global leader. They are at the core of how our employees interact with each other, make decisions and solve problems. PATIENT FOCUS MAKE PEOPLE AND PATIENTS YOUR PASSION INTEGRITY WALK YOUR TALK INNOVATION REACH FOR THE UNREACHABLE COLLABORATION ADVENTURE TOGETHER SUPERIOR PERFORMANCE MAKE YOURSELF PROUD
Matthias works for CSL Vifor and is a packaging team leader based in St Gallen, Switzerland. He has been employed since 2016 and enjoys the sense of purpose that comes fromworking for a company that thinks about the future for both patients and employees. Matthias likes the atmosphere in the packaging team and the fact that each day brings something new. He also feels his opinions and ideas are valued when new challenges confront his team. Matthias’s story CSL Limited Annual Report 2022/23 7 Patient focus
CSL Limited Annual Report 2022/23 8 2 Our Company 40+ Countries of operations around theworld US$13.3 billion in annual revenue 32,000+ employees around theworld 2,000+ R&D employees across 10 countries 342 Plasma collection centres across China, Europe and North America US$5.1 billion in R&D investments in the last 5 years to advance product pipeline CSL at a glance
CSL Limited Annual Report 2022/23 9 Our businesses CSL Behring is a global biotherapeutics leader driven by CSL’s promise to save lives. Focused on serving patients’ needs by using the latest technologies, CSL Behring discovers, develops and delivers innovative therapies for people living with conditions in the immunology, haematology, cardiovascular and metabolic, respiratory, and transplant therapeutic areas. CSL Behring uses three strategic scientific platforms of plasma fractionation, recombinant protein technology, and cell and gene therapy to support continued innovation and continually refine ways in which products can address unmet medical needs and help patients lead full lives. CSL Behring operates CSL Plasma, one of the world’s largest plasma collection networks. As one of the leading influenza vaccine providers in the world, CSL Seqirus is a major contributor to the prevention of influenza globally and a transcontinental partner in pandemic preparedness. CSL Seqirus operates state-of-the-art production facilities in the United States, the UK and Australia and uses both egg-based and cell-based manufacturing technologies as well as a proprietary adjuvant. It has leading research and development (R&D) capabilities, a broad and differentiated product portfolio and commercial operations in more than 20 countries. CSL Vifor is a global partner of choice for pharmaceuticals and innovative, leading therapies in iron deficiency and nephrology. CSL Vifor specialises in strategic global partnering, in-licensing and developing, manufacturing and marketing pharmaceutical products for precision healthcare, aiming to help patients around the world lead better, healthier lives. Headquartered in St Gallen, Switzerland, CSL Vifor also includes the joint company Vifor Fresenius Medical Care Renal Pharma (with Fresenius Medical Care).
CSL Limited Annual Report 2022/23 10 2 Our Company CSL’s R&D Pipeline CSL’s world-class R&D organisation continues to advance as a biotechnology leader by delivering high-quality science and technologies developed by our own highcalibre scientists and innovative collaborations. CSL R&D uses its expertise in CSL’s strategic platforms – plasma protein technology; recombinant protein technology; cell and gene therapy; and vaccines technology. This means CSL can develop and deliver innovative medicines and vaccines that address unmet medical needs, help prevent infectious disease and protect public health, and help people lead full lives. CSL’s strong R&D pipeline includes potential new treatments that use these platforms and align with its leading-edge scientific expertise and commercial capabilities across CSL’s six therapeutic areas: immunology; haematology; cardiovascular and metabolic; respiratory; transplant; and vaccines. The addition of CSL Vifor allows the R&D team to build on a heritage and expertise in iron deficiency therapy and grow CSL’s presence in nephrology, with a focus on dialysis and rare disease. In 2022/23 CSL invested US$1.2 billion* in R&D across its three businesses. Looking towards 2030, R&D continues to strive to deliver on the current portfolio of prospective medicines and vaccines and build a full and innovative pipeline that has the potential to make a meaningful difference to the lives of patients and to public health. This pipeline is intended and expected to contribute new revenue streams well into future decades. * Limited assurance by Ernst & Young
CSL Limited Annual Report 2022/23 11 Immunology Clinical Registration Post-Launch HAEGARDA®/BERINERT® (C1 Esterase Inhibitor SC & IV) Hereditary Angioedema HIZENTRA® (20% subcutaneous Ig) Multiple Indications PRIVIGEN® (10% intravenous Ig) Multiple Indications Garadacimab (Anti-FXIIa mAb) Hereditary Angioedema HIZENTRA® (20% subcutaneous Ig) Dermatomyositis HIZENTRA® (20% subcutaneous Ig) Systemic Sclerosis Anumigilumab (Anti-G-CSFRmAb) Hidradenitis Suppurativa CSL730 (Recombinant Trivalent Human IgG1 Fc Multimer) Multiple Indications*† Haematology Clinical Registration Post-Launch AFSTYLA® (Recombinant FVIII) Haemophilia A IDELVION® (Recombinant FIX-FP) Haemophilia B HEMGENIX® (Recombinant adeno-associated viral vector with codon-optimized Padua derivative of Human FIX cDNA) Haemophilia B* KCENTRA® (Prothrombin Complex Concentrate) Trauma VAMIFEPORT® (Ferroportin inhibitor) Sickle Cell Disease CSL301 (α2 Anti-Plasmin mAb) Sub-acute Pulmonary Embolism* CSL889 (Hemopexin) Sickle Cell Disease Respiratory Clinical Registration Post-Launch ZEMAIRA®/RESPREEZA® (Alpha 1 Antitrypsin) AAT Deficiency Garadacimab (Anti-FXIIa mAb) Interstitial Lung Disease/Idiopathic Pulmonary Fibrosis Trabikibart (Anti-Beta Common mAb) Asthma CSL787 (Nebulised Ig) Non-Cystic Fibrosis Bronchiectasis Cardiovascular and Metabolic Clinical Registration Post-Launch CSL112 Apolipoprotein A-I (human) Acute Myocardial Infarction Clazakizumab (Anti-IL-6 mAb) End Stage Kidney Disease Transplant Clinical Registration Post-Launch Clazakizumab (Anti-IL-6 mAb) Chronic Active Antibody-Mediated Rejection CSL964 (Alpha 1 Antitrypsin) Prevention of Acute Graft-versus-Host Disease CSL964 (Alpha 1 Antitrypsin) Treatment of Acute Graft-versus-Host Disease* Vaccines Clinical Registration Post-Launch AUDENZ™ (Adjuvanted Cell-based Pandemic Vaccine) Influenza A (H5N1) FLUAD® (Adjuvanted Trivalent Vaccine) Influenza FLUAD® (Adjuvanted Quadrivalent Vaccine) Influenza FLUCELVAX® (Quadrivalent Cell-based Vaccine) Influenza FOCLIVIA®/AFLUNOV® (Adjuvanted Egg-based Pandemic Vaccine) Influenza A (H5N1) ARCT-154 (COVID-19 Vaccine)* Adjuvanted Quadrivalent Cell Culture Vaccine Influenza (aQIVc) CSL Vifor Clinical Registration Post-Launch FERINJECT® (Ferric carboxymaltose) Iron Deficiency KORSUVA®/KAPRUVIA® (Kappa Opioid Receptor Agonist) Chronic Kidney Disease-associated Pruritus 1 RAYALDEE® (Oral ext. release Calcifediol) Secondary Hyperparathyroidism 2 TAVNEOS® (Oral C5a Receptor Inhibitor) Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis 3 VELPHORO® (Sucroferric Oxyhydroxide) SerumPhosphorous control in Chronic Kidney Disease VELTASSA® (Oral PotassiumBinder) Hyperkalemia INJECTAFER® (Ferric carboxymaltose) Heart Failure in Iron Deficiency Sparsentan (Dual ETA & AT1 antagonist) IgA Nephropathy 4 Sparsentan (Dual ETA & AT1 antagonist) Focal Segmental Glomerulosclerosis4 SNF472 (Vascular Calcification Inhibitor) Calcific Uraemic Arteriolopathy in End Stage Kidney Disease† SNF472 (Vascular Calcification Inhibitor) Peripheral Artery Disease in End Stage Kidney Disease INS-3001 (Calcification Inhibitor) Peripheral Artery Disease, Aortic Valve Stenosis Outlicensed Programs Clinical Registration Post-Launch Eblasakimab (Anti-IL-13RmAb) Atopic Dermatitis Mavrilimumab (Anti-GM-CSFRmAb) Giant Cell Arteritis, Rheumatoid Arthritis 5 LASN01 (Anti-IL-11 mAb) Idiopathic Pulmonary Fibrosis, Thyroid Eye Disease *Partnered Project. †Project discontinued. 1. KORSUVA®/KAPRUVIA® is a registered trademark of Cara Therapeutics, Inc.; 2. RAYALDEE® is a registered trademark of OPKO Health, Inc.; 3. TAVNEOS® is a registered trademark of ChemoCentryx Inc.; 4. Sparsentan is licensed from Travere Therapeutics, Inc.; 5. Mavrilimumab Phase II studies in GCA & RA complete. Kiniksa evaluating development in rare cardiovascular diseases. CSL’s pipeline also includes Life Cycle Management projects that address regulatory post-marketing commitments, pathogen safety, capacity expansions, yield improvements, and new packages and sizes. Global Research and Development Pipeline 2022/23
CSL Limited Annual Report 2022/23 12 CSL’s Product Portfolio and Therapeutic Areas Therapeutic Areas Platform Plasma Protein Technology Immunology Haematology Respiratory Cardiovascular and metabolic Vaccines Transplant Recombinant Technology Cell and Gene Therapy Cell-based Adjuvant mRNA Egg-based CSL Behring CSL Behring discovers, develops and delivers the broadest range of products in the industry for treating rare and serious diseases such as haemophilia, von Willebrand disease (vWD), primary and secondary immune deficiencies (PID/SID), chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary angioedema (HAE) and inherited respiratory disease. CSL Behring’s products are also used in cardiac surgery, for burns treatment and for urgent warfarin reversal. We strive to meet patients’ needs using the latest recombinant and plasma-derived technologies as well as gene therapy approaches. Immunology CSL’s world leading immunoglobulin franchise is the cornerstone of the immunology therapeutic area and is focused on developing and delivering trusted products and technologies to serve patients with a range of serious immunologic and neurologic diseases, including primary and secondary immunodeficiencies (PID/ SID), chronic inflammatory demyelinating polyneuropathy (CIDP) and hereditary angioedema (HAE). Key CSL Behring products on the market include PRIVIGEN®, HIZENTRA®, BERINERT®, HAEGARDA® and a range of hyperimmunes. Building on CSL’s long history of providing patients with immunoglobulin products, it continues to optimise the patient experience by developing more convenient and flexible ways to dose and administer existing immunoglobulin products. Key recombinant assets are also progressing in early development to treat underserved immune-mediated diseases. CSL continues to build on its strong 40-year legacy in HAE, working to expand on current medicines to provide optimal treatments for the full range of HAE patients. Garadacimab, CSL’s first-in-class monoclonal antibody targeting activated Factor XII (FXIIa), is being developed as a prospective long-term prophylactic treatment for patients with HAE. Haematology CSL remains focused on easing the burden of disease and improving the lives of patients with rare bleeding disorders. Major advances have been made in haemophilia A and B in recent years with the launch of novel recombinant coagulation factor medicines and through the acquisition of exclusive global licence rights to commercialise HEMGENIX® (etranacogene dezaparvovec), an AAV5 (adeno-associated virus) gene therapy for the treatment of haemophilia B, which has been approved in the United States, Europe and the UK. Other key CSL Behring products on the market include IDELVION®, AFSTYLA®, HUMATE P®/HAEMATE®, BERIPLEX®/KCENTRA®, RIASTAP®/HEMOCOMPLETTAN®, VONCENTO®/BIOSTATE® and albumin. Additionally, exciting R&D efforts are underway to explore new indications in benign haematology as well as novel therapeutics in haemostasis and thrombosis. This includes initiating an important global Phase III study to evaluate the early administration of KCENTRA® (4-factor prothrombin complex concentrate) on survival in trauma patients suffering life-threatening bleeding, and a Phase II study under a licensing agreement with Translational Sciences using CSL301 (α2 anti-plasmin), a first-in-class, chimeric monoclonal antibody as thrombolytic treatment in adults with acute sub-massive pulmonary embolism. Respiratory Respiratory diseases impose an enormous burden on patients and society and are a leading cause of death and disability worldwide. In addition to CSL’s existing product, ZEMAIRA®/RESPREEZA® for patients with alpha-1 antitrypsin deficiency, CSL is investigating potential new clinical treatments for respiratory diseases using novel recombinant monoclonal antibodies and plasma-derived therapies to address this need. Trabikibart, an anti-beta common monoclonal antibody, is being investigated for the treatment of severe uncontrolled asthma and severe chronic obstructive pulmonary disease (COPD). In idiopathic pulmonary fibrosis (IPF), a severe debilitating disease, a clinical development program has started with garadacimab, the first of CSL’s compounds being explored in this disease area. CSL787, a plasma-derived, inhaled immunoglobulin is being investigated for patients with bronchiectasis. 2 Our Company
CSL Limited Annual Report 2022/23 13 Cardiovascular and metabolic CSL is focused on improving and extending the lives of patients with cardiovascular and metabolic diseases. Many patients with cardiovascular disease also have some degree of renal impairment and CSL recognises the critical need to address the unique challenges faced by this patient population. CSL112, apolipoprotein A-I (human), is being developed to reduce the risk of recurrent cardiovascular events during the 90-day high-risk period following a heart attack, the period when the majority of first-year recurrent cardiovascular events occur. If successful, CSL112 will be the first therapy to demonstrate cardiovascular risk reduction through the novel apoA-I mechanism and has the potential to transform how acute myocardial infarction patients at high risk of recurrent cardiovascular events are treated. In addition, clazakizumab, first-in-class anti-interleukin-6 (anti-IL-6) monoclonal antibody is being developed for the reduction of major adverse cardiovascular events (MACE) in End Stage Kidney Disease (ESKD) dialysis patients. Transplant While advances in transplantation techniques and therapies have markedly improved short-term patient survival, transplant rejection remains one of the greatest limitations to long-term graft and patient survival for both solid organ and haematopoietic stem cell transplant recipients. CSL is focused on developing therapies to address transplant rejection and while current solid organ focus lies in kidney transplants, this vision encompasses a broader scope to help treat patients undergoing various solid organ transplantations. In kidney transplant recipients, antibody-mediated rejection (AMR) is a leading cause of allograft loss, and there is significant unmet need for effective treatments. Clazakizumab, our anti-IL-6 monoclonal antibody, is currently being investigated in a Phase III clinical trial (IMAGINE) for the potential treatment of chronic active antibody-mediated rejection. In haematopoietic stem cell transplantation, acute graft-versus-host disease (GvHD) is a life-threatening type of rejection where the donor cells attack the recipient; it is a leading cause of mortality and morbidity following transplant. There is a significant unmet need for more effective, less toxic therapies for GvHD. We are investigating alpha-1 antitrypsin (AAT, ZEMAIRA®) for the prevention and treatment of acute GvHD in two Phase III studies. CSL Seqirus CSL Seqirus’ broad range of influenza vaccines addresses the needs of different populations around the world. In Australia and New Zealand, CSL Seqirus is also a leading provider of in-licensed vaccines and specialty pharmaceuticals. It is also the world’s only supplier of a unique range of products of national significance for the Australian Government, including Q fever vaccine and antivenoms for venomous creatures in Australia and other Pacific countries. Vaccines Developing new and better vaccines across all age groups in expanded markets is a strategic priority for CSL Seqirus. CSL Seqirus is focused on developing differentiated vaccines protecting against respiratory viruses, influenza and COVID-19 utilising innovative technologies, including further advancing our cell-based manufacturing technology, our MF59® adjuvant, and developing the next-generationmessenger RNA (mRNA) platform, targeting seasonal and pandemic potential viruses. Through these technologies, CSL Seqirus aims to enhance the immune response of those particularly vulnerable to influenza and COVID-19, such as children and older adults. The portfolio includes a number of key investigational products, including a higher dose adjuvanted cell-based influenza vaccine (aQIVc), multiple monovalent and quadrivalent influenza candidates using the sa-mRNA technology and a COVID-19 seasonal booster. In addition, our collaboration with sa-mRNA-focused Arcturus Therapeutics complements our long-term strategy in vaccines with benefits including faster clinical development with higher probability of success; application to additional pathogens including those with pandemic potential; access to an established manufacturing network; and access to lipid nanoparticles and a lipid library with application across vaccines. Key CSL Seqirus influenza vaccines on the market include AGRIPPAL®, AFLURIA®, FLUAD®, and FLUCELVAX® for seasonal use, and AFLUNOV® for zoonotic use. As a trusted partner to more than 30 countries throughout the world, CSL Seqirus is the leader in preparedness for pandemic influenza, and is constantly working to expand its offerings to new countries and to address emerging pandemic threats. Key approved CSL Seqirus pandemic vaccines include PANVAX®, FOCLIVIA® and AUDENZ®. In-licensed vaccines and pharmaceuticals Key CSL Seqirus in-licensed products on the market in Australia and New Zealand include CATIONORM®, GARDASIL-9®, IKERVIS®, PALEXIA®, REAGILA®, RYALTRIS®, XADAGO® and ZOSTAVAX®.
CSL Limited Annual Report 2022/23 14 CSL Vifor Iron deficiency and nephrological disorders pose significant unmet medical needs globally. The CSL Vifor portfolio provides a strong and rapidly growing presence in nephrology, particularly in patients requiring dialysis. CSL Vifor is committed to launching the next generation of therapies as it endeavours to truly address the full spectrum of kidney disease, with a focus on dialysis and rare disease. This is supported by a founding heritage and expertise in iron deficiency therapy, helping to support a broad range of patients. The acquisition of Vifor Pharma in August 2022 has enhanced CSL’s product portfolio, complementing existing products and offering a wider range of treatments for conditions such as chronic kidney disease (CKD), anaemia and renal disorders. Key CSL Vifor products on the market include TAVNEOS®, KORSUVA®/ KAPRUVIA®, MIRCERA®, RETACRIT®, VELTASSA®, RAYALDEE®, VELPHORO® and our iron products FERINJECT®/INJECTAFER®, VENOFER® and MALTOFER®. With the combination of resources, research capabilities, scientific insights and CSL’s patient-centred approach, CSL can develop innovative therapies, accelerate the development of novel treatments, improve patient outcomes, and contribute to advancements in these specialised fields. This expanded portfolio positions CSL to address a wider range of unmet needs in patients with iron and nephrological disorders and should support a more comprehensive range of options for patients with improved access to effective treatments leading to better disease management, enhanced quality of life and improved patient care overall. In June, we initiated further activities to progress the integration of the CSL Vifor R&D teams and programs into the overall CSL R&D organisation and processes. This includes incorporating them into our Therapeutic Areas and Project Operating Model, as well as aligning themwith our R&D governance framework. More information about the CSL Vifor R&D integration will be communicated at our annual R&D update to the market. New products to market CSL continues to broaden the geography and use of its medicines for rare and specialty diseases across the globe within the immunology and haematology therapeutic areas as well as in nephrology and iron deficiencies, and the use of vaccines to help prevent infectious disease and protect public health. Within the immunology portfolio, regulatory indication expansion and new registrations are primarily focused on subcutaneous immunoglobulin, HIZENTRA®, and our human C1-esterase inhibitor, BERINERT®, each with four new registrations including, importantly, BERINERT® S.C. Injection 2000 in Japan for the treatment of HAE. The new HIZENTRA® registrations supported indications for primary immunodeficiency (PID), a chronic disorder in which part of the body’s immune system is missing or malfunctioning, and chronic inflammatory demyelinating polyneuropathy (CIDP), a chronically progressive, rare autoimmune disorder that affects the peripheral nerves and may cause permanent nerve damage. With CIDP, the myelin sheath, or the protective covering of the nerves, is damaged, which may result in numbness or tingling, muscle weakness, fatigue and other symptoms, which worsen over time. Additionally, indication expansion was approved for HIZENTRA® for secondary immunodeficiency (SID) in two countries. SID is similar to primary immunodeficiency (PID); however, SID occurs when the immune system is compromised as a result of disease or due to an environmental factor (e.g., chemotherapy, disease complication). In CSL’s haematology therapeutic area, there is continued focus on the expansion of the current portfolio as well as the first registrations of HEMGENIX®, etranacogene dezaparvovec, a one-time gene therapy for the treatment of adults with haemophilia B. Five new registrations were achieved for our recombinant factor VIII product, AFSTYLA®, which is used to control and prevent bleeding episodes in people with haemophilia A. Four new registrations were achieved for our human coagulation factor VIII/vWF, HAEMATE® and seven for human albumin. One new registration was achieved for BERIPLEX®, our human prothrombin complex concentrate and one for BERIPLAST® P, our combined human fibrinogen, factor XIII and bovine aprotinin product. Four new registrations were achieved for HAEMOCOMPLETTAN® P, our human fibrinogen concentrate. Three new registrations and expansions were achieved for IDELVION®, our recombinant factor IX albumin fusion protein (rFIX-FP) which is used to control and prevent bleeding episodes in people with haemophilia B. For our CSL Seqirus business, FLUAD® QUADRIVALENT, our adjuvanted influenza vaccine, was authorised for persons 65 years and older in Taiwan, Brazil and South Korea. For CSL Vifor, there were seven new registrations for KORSUVA® (difelikefalin), for the treatment of moderate-tosevere pruritus associated with chronic kidney disease in adult patients on haemodialysis. Four new registrations were achieved for TAVNEOS® (avacopan) to treat adults with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)- associated vasculitis. For VELPHORO®, there were two new registrations for the control of serum phosphorus levels in adults with chronic kidney disease on haemodialysis or peritoneal dialysis. There was one new registration for VELTASSA® (patiromer sorbitex calcium) for the treatment of high blood potassium. There was one new registration, and two label expansions for FERINJECT® (ferric carboxymaltose) and one indication expansion for INJECTAFER®, ferric carboxymaltose injection, for the treatment of iron deficiency in patients with heart failure. 2 Our Company
CSL Limited Annual Report 2022/23 15 Product Registrations and Indications 2022/23* Immunology Focus and deliver enhanced patient convenience, plasma yield improvements, expanded labels and indications, new formulation science and recombinant therapies for underserved immune-mediated conditions Product Type Country/Region BERINERT® C1-Esterase Inhibitor (Human) Intravenous or Subcutaneous1 NR Japan (2000 IU); Qatar &United Arab Emirates (500, 2000, 3000 IU); Argentina (2000, 3000 IU) HIZENTRA® Immune Globulin Subcutaneous (Human) 20% Liquid NR Saudi Arabia, Qatar, United Arab Emirates, Oman HIZENTRA® Immune Globulin Subcutaneous (Human) 20% Liquid NI Switzerland, Russia (SID) Haematology Maximise the value and performance of our newand existing therapies and discover and develop new innovative therapies in benign (non-malignant) haematology AFSTYLA® Coagulation Factor VIII (Recombinant) NR Turkey (500, 1000, 2000 IU); Kuwait & Oman (250, 500, 1000, 2000, 3000 IU); Chile (250, 500, 1000, 1500, 2000, 3000 IU); Brunei (250, 500 IU) Albumin (human) 20% Behring, low salt NR Qatar, United Arab Emirates, Morocco ALBURX® Human Albumin NR Costa Rica, El Salvador, Guatemala, Trinidad and Tobago BERIPLAST® P Combi-Set Human thrombin, Aprotinin, Human Fibrinogen, Calcium chloride NR Singapore BERIPLEX® Prothrombin Complex (Human) NR Trinidad and Tobago HAEMATE® Coagulation Factor VIII/vWF (Human) NR Saudi Arabia (250, 500 IU); United Arab Emirates, Bulgaria & Algeria (250, 500, 1000 IU) HAEMOCOMPLETTAN® P Fibrinogen Concentrate (Human) NR United Arab Emirates, Malaysia, Morocco, Oman HEMGENIX® Etranacogene dezaparvovec NR United States, European Union, Great Britain IDELVION® Coagulation Factor IX (Recombinant) Albumin Fusion Protein NR New Zealand (3500 IU), Turkey (250, 500, 1000, 2000 IU); Kuwait (250, 500, 1000, 2000, 3000 IU) IDELVION® Coagulation Factor IX (Recombinant) Albumin Fusion Protein NI European Union, Great Britain & Switzerland (PUP); South Korea (21d dosing) Vaccines Develop products for the prevention of infectious diseases FLUAD® QUADRIVALENT2 Influenza Vaccine, Adjuvanted (surface antigen, inactivated) NR Taiwan, Brazil, South Korea (for the prevention of influenza in persons aged 65 yrs and older) CSL Vifor Focus and deliver products for the treatment of iron deficiency, dialysis, nephrology & rare disease FERINJECT® Ferric carboxymaltose NR China FERINJECT® Ferric carboxymaltose NI European Union, Great Britain (for the treatment of iron deficiency in patients aged 1-13 years) INJECTAFER® Ferric carboxymaltose NI United States (for the treatment of iron deficiency in patients with heart failure) KORSUVA® Difelikefalin3,4 NR Switzerland, Canada, Australia, Singapore, United Arab Emirates, Kuwait, Israel TAVNEOS® Avacopan5 NR Australia, Switzerland, United Arab Emirates, Kuwait VELPHORO® Sucroferric oxyhydroxide NR China, Thailand VELTASSA® Patiromer sorbitex calcium NR Russia * First-time registrations or registered indications for CSL products in the listed countries/regions over the reporting period. 1 In some markets, subcutaneous version of C1-esterase inhibitor is marketed as HAEGARDA®. 2 In some markets, FLUAD® QUADRIVALENT is marketed as FLUAD® QUAD and FLUAD® TETRA. 3 In some markets, KORSUVA® is marketed as KAPRUVIA®. 4KORSUVA®/KAPRUVIA® is a registered trademark of Cara Therapeutics, Inc. 5 TAVNEOS® is a registered trademark of ChemoCentryx, Inc. IU = International Unit, NI = New Indication, NR = New Registration, PUP = Previously Untreated Patients, SID = Secondary Immunodeficiency.
CSL Limited Annual Report 2022/23 16 2 Our Company Our operating review 1 Constant currency (CC) removes the impact of exchange rate movements, facilitating the comparability of operational performance. For further detail refer to CSL’s Financial Statements for the Full Year ended June 2023 (Directors Report). 2 Eleven months to FY22 pre-CSL ownership and unaudited v eleven months to FY23. CSL Behring Total revenue was US$9,290 million, up 12%1 when compared to the prior comparable period. Immunoglobulin (Ig) product sales of US$4,675 million, increased 21%1 with strong growth recorded across all geographies as global supply recovered strongly. PRIVIGEN® (Immune Globulin Intravenous (Human), 10% Liquid) sales delivered strong growth of 29%1 as demand continues to recover from the pandemic with patient diagnosis and new patient starts steadily increasing. HIZENTRA® (Immune Globulin Subcutaneous (Human), 20% Liquid) sales were up 12%1 as patient diagnosis rates continue to improve and new patients emerge. Underlying demand for Ig continues to be strong due to significant patient needs in core indications – namely Primary Immune Deficiency, Secondary Immune Deficiency and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Albumin sales of US$1,109 million, were up 11%1. Sales in China were up strongly as COVID restrictions eased. Solid growth was also recorded in the United States and Europe as supply improved. Haemophilia product sales of US$1,193 million increased 8%1. IDELVION®, CSL Behring’s novel long-acting recombinant factor IX product, achieved strong growth of 13%1 as patient interactions with health care providers increased post COVID. HEMGENIX®, the first and only gene therapy for haemophilia B was successfully launched in the United States. The haemophilia A market continued to be competitive resulting in a modest increase in sales for AFSTYLA®, a novel recombinant factor VIII product, and a decline in sales for plasma-derived products. Specialty product sales of US$1,831 million, up 6%1 led predominately by demand for KCENTRA® and ZEMAIRA®. KCENTRA® (4 factor prothrombin complex concentrate) recorded sales growth of 10%1, as social mobility increased post COVID. ZEMAIRA® Alpha1-Proteinase Inhibitor (Human) sales were up 24%1 as supply returned. Plasma Collections Plasma collections were robust with plasma volumes up 31% and now at record levels. Improved social mobility post COVID, targeted marketing campaigns and enhanced digital initiatives to attract donors all contributed to this unprecedented growth. The cost of collecting plasma, which includes donor compensation and labour, declined ~14% over the previous year end and ~17% down from the peak in March 2022. The significant increase in plasma supply underpins the company’s ability to manufacture plasma products and enables CSL to meet the underlying patient demand for core plasma products. CSL Seqirus Total revenue of US$2,031 million, was up 9%1 driven by growth in seasonal influenza vaccines, in particular FLUCELVAX® which increased 30%1. This growth was achieved against a backdrop of reduced rates of immunisation and highlights the strength of CSL Seqirus’ strategy and its high value, differentiated product portfolio. During the period: • A licence agreement was signed with Arcturus Therapeutics for next-generation mRNA vaccine technology. • The United States Centers for Disease Control and Prevention recognised FLUAD® as a preferentially recommended seasonal vaccine option for adults aged 65+ years. • Fill and finish capacity expansion now fully operational at Holly Springs and Liverpool. • Good progress was made on construction of the new cell-culture facility in Melbourne. CSL Vifor Total revenue was US$1,989 million representing approximately 11 months contribution since the business was acquired on 9 August 2022. This amounts to approximately 14% growth1,2 compared to the 11 months in FY22 before CSL ownership, reflecting solid growth across all key product areas. The integration of CSL Vifor is well advanced and the cost synergies are well on track. During the period INJECTAFER® (ferric carboxymaltose) was approved in the United States for the treatment of iron deficiency in adult patients with heart failure and FERINJECT® was launched in China in April 2023. Outlook The strong growth in the immunoglobulins franchise is expected to continue following record plasma collections in FY23. There are a number of initiatives underway to improve efficiencies which include a focus on optimising plasma collection costs, improving manufacturing yields and bringing new products to market, all of which will support the medium term recovery in CSL Behring’s gross margin. The launch of HEMGENIX®, in the United States last quarter will continue to deliver this paradigm-shifting treatment to the haemophilia B community in the United States and Europe in the year ahead. The R&D pipeline includes a number of late-stage programs nearing completion which will lead to more options for patients. CSL Seqirus is anticipated to deliver another strong year driven by demand for its differentiated products. CSL Seqirus is progressing global registrations for its next-generation mRNA COVID vaccine. For CSL Vifor, there is a focus on unlocking the value and growth within this newly acquired business. Supporting the medium-term outlook, research and development capabilities are being brought into the one R&D organisation. Nephrology and transplant therapeutic areas are being brought together and a number of patient bloodmanagement initiatives are underway that will cross between CSL Vifor and CSL Behring businesses. Further information Additional details about CSL’s results are included in the company’s 4E statement, investor presentation slides and webcast, all of which can be found on CSL’s website csl.com. A glossary of medical terms can also be found on the website.
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