CSL Ltd Annual Report 2020

One of our most important new product development projects is aQIVc, which combines cell-culture vaccine with MF59 adjuvant and will be targeted for use in older adults and children. We are in the final phases of preclinical formulation development and experimental work and plan to commence clinical trials with this product in late 2020. A critical part of protection from seasonal influenza is readiness for a future influenza pandemic. We were pleased to obtain approval from the US Food & Drug Association (FDA) earlier in 2020 for AUDENZ™, a pre-pandemic vaccine based on H5N1, the ‘bird flu’ strain, made by the cell-culture process and combined with MF59. This product now forms the basis of our pandemic support of the US. In the longer term, we are working on developing a self- amplifying mRNA vaccine, a disruptive technology with the potential to significantly improve vaccine efficacy and revolutionise manufacturing. This project is currently in preclinical research. Addressing the global COVID-19 crisis Strategic partnerships and collaborations with academia, industry and governments have been the foundation of CSL’s strategic R&D efforts to combat the novel coronavirus, COVID-19. From the time the coronavirus was first identified, CSL has been assisting in the fight against COVID-19 in a number of ways including offering expertise, technologies, equipment and materials on a humanitarian basis. Our acumen in vaccines, monoclonal antibodies, recombinant technologies, plasma technologies, manufacturing capabilities and partnerships, along with a therapeutic focus in Immunology and Respiratory, all align with the scope of this disease and, most importantly, potential vaccines and treatments. CSL has committed to the fight against COVID-19, leading several external collaborations to combat this devastating global pandemic. In April 2020, CSL recruited companies from throughout the plasma industry and, with Takeda, led the creation of the unprecedented CoVIg-19 Plasma Alliance to accelerate the development of one, unbranded plasma- derived hyperimmune therapy for treating people with COVID-19. By partnering as an industry, the Alliance aims to provide a reliable, scalable and sustainable treatment solution for patients suffering the impact of COVID-19 and to support national governments in their efforts to fight the current pandemic. Hyperimmunes are already on the market for several conditions including rabies and tetanus. If successful, the anti-COVID-19 hyperimmune globulin (CoVIg-19) may be one of the first treatments with the potential to treat individuals with serious complications of COVID-19. In addition, and building upon, the global CoVIg-19 Plasma Alliance, in May 2020, CSL Behring began development of an anti-SARS-CoV-2 plasma product with the potential to treat serious complications of COVID-19 in Australia. Working with the Australian Government, CSL will develop the product using donations of plasma made in Australia by people who have recovered from COVID-19. Plasma will be collected by the Australian Red Cross Lifeblood. CSL Behring has also partnered with SAb Biotherapeutics (SAB) who have developed a small-scale process for purification and formulation of SAB-185, a bovine-derived, but fully human polyclonal anti-SARS-CoV-2 antibody therapeutic candidate. The partnership joins the forces of CSL Behring’s leading protein science capabilities with SAB’s novel immunotherapy platform, to bring a therapy to the market as soon as possible. Together, SAB and CSL are capable of rapidly developing, registering and manufacturing natural, highly targeted, high-potency, fully human polyclonal antibodies (made using several different immune cells). CSL is also collaborating with the Coalition for Epidemic Preparedness Innovations (CEPI) and the University of Queensland (UQ) in Australia to accelerate the development, manufacture and distribution of a COVID-19 vaccine candidate pioneered by researchers at UQ. The partnership builds on a relationship that dates back to the early 1990s when CSL with UQ, and later Merck & Co., Inc., collaborated to develop the recombinant human papilloma vaccine, GARDASIL ® . CEPI and CSL are funding the development and manufacture of UQ’s ‘molecular clamp’ enabled vaccine that is combined with CSL’s recombinant manufacturing capabilities and Seqirus’ proprietary adjuvant technology MF59 for COVID-19. Funding will provide support for the Phase I safety study being led by UQ, followed by subsequent late-stage clinical trials, and industrial-scale manufacturing to allow the production of potentially millions of doses a year, should the product be approved. CSL’s R&D team in Melbourne will transfer the UQ process to CSL and make adjustments to ensure that it will scale to commercial quantities. A development and scale-up process that typically takes years is being accelerated to be completed in months. The initial phase of large-scale production of the vaccine will take place at CSL’s biotech manufacturing facilities in Melbourne, Australia. CSL anticipates that the production technology can be scaled to produce up to 100 million doses towards the end of 2021. CSL would also subcontract other global manufacturers to increase the number of doses that can be produced and broaden the geographical distribution of vaccine production. Should clinical trials be successful, a vaccine could be available for distribution in 2021. This proprietary adjuvant boosts immune response and enables less antigen to be used in each dose of vaccine, so more doses can be produced more rapidly. These include garadacimab (a novel factor XIIa-inhibitory mAb) which successfully passed through Phase II clinical development as a new type of prophylactic treatment for hereditary angioedema (HAE); a novel, humanised mAb targeting vascular endothelial growth factor-B (VEGF-B) for the treatment of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus which is progressing into Phase II and; a novel, mAb which binds to the granulocyte colony- stimulating factor (G-CSF) receptor, currently in a Phase Ib study in patients with hidradenitis suppurativa and palmoplantar pustulosis. We’re in this together – Perreault calls for COVID-19 plasma donations at White House roundtable CEO and Managing Director Paul Perreault represented the CoVIg-19 Plasma Alliance at a White House Roundtable discussion on 30 July inWashington where he urged those who have recovered from COVID-19 to consider donating plasma toward the development of a potential hyperimmune COVID-19 treatment. Perreault told U.S. President Donald Trump at the event that the call to action for plasma donations was an “important step” in making the potential treatment a reality. Photo credit: Shutterstock CSL Limited Annual Report 2020 27