CSL Ltd Annual Report 2020

Nobel Laureate David Baltimore (centre) joins, Bill Mezzanotte (right), EVP, Head of R&D and Chief Medical Officer for CSL and Andreas Gille (left), CSL Behring Senior Director and Pasadena R&D Head, in taking part in a ceremonial ribbon cutting at the biotech leader’s expanded R&D facility in southern California. centres, industry partners, non-profits and governments to address the primary scientific barriers to developing new vaccines and immunotherapies. The project will utilise biomedical and artificial-intelligence-based, machine-learning technologies to develop models of the immune system to rapidly accelerate vaccine research. Our drug delivery platforms CSL’s business, including our R&D and in-market product portfolios, has advanced considerably over the past few years and looks very different to how it did 10 years ago. New and exciting opportunities allow us to address previously unmet patient needs and these continue to drive us each day. It is important that we have the organisational design and capabilities we need to allow us to achieve sustainable growth towards 2030 and beyond. To ensure a robust and diverse innovation pipeline based on a foundation of scientific excellence, CSL Behring has evolved and strengthened its therapeutic area focus and will continue to use its three primary platforms of plasma fractionation, recombinant protein technology and cell and gene therapies to support continued innovation and continually refine ways in which products can meet patient needs. Plasma product development Plasma is a valuable, natural but limited source of many current and potentially new biological therapies and we rely upon our donors to provide this lifesaving resource. As such, CSL Behring has an obligation to maximise the development and delivery of important products from this vital resource for the benefit of patients. Maximising patient benefit from as much of the donated plasma as possible that is collected across CSL Behring’s industry-leading network, is a critical area of focus as we strive to be the industry pacesetter. Some notable examples of how CSL Behring is continuously enhancing its plasma product development are listed. – Development of processes for new plasma therapies across all of our therapeutic areas. – Innovation of existing products to provide a continuous series of life-cycle process improvements for optimal plasma utilisation with increasing product quality. Such innovations include the introduction of isoagglutinin removal technologies within the production stream to improve the safety and quality of PRIVIGEN ® . – Conducting research to refine our understanding and gain additional insight at the molecular level for CSL Behring plasma products and purification processes, by applying modern analytical testing and characterisation methods and utilising state-of-the-art analytic instrumentation to further ensure safety, quality, and reliable supply of product for patients. – Development of patient convenience enhancements that meet patients’ needs, assessing the technological landscape for the best-fit medical device, then bringing those candidate devices to process development to unite the protein therapy with the convenience device, ultimately leading to a combination product. These patient convenience enhancements represent an array of accessories, including prefilled syringes, vial reconstitution aids, aerosolising nebulisers, and autoinjector platforms. – Maintaining vigilance against emerging pathogen threats through surveillance programs and by proactively publishing data that demonstrate that CSL’s processes have the capability to remove agents, such as hepatitis E virus and coronaviruses, providing reassurance to patients and healthcare providers that our products are safe from these specific threats. Recombinant protein andmonoclonal antibody technology Following strategic investments over the last decade, the capability to develop and manufacture both recombinant proteins and monoclonal antibodies is now firmly established as a core platform. This enables both efficiencies inmanufacture and the ability to manipulate the sequence of naturally occurring proteins to achieve desired therapeutic goals such as the ability to selectively target specific biological mechanisms, enhanced potency and pharmacokinetics, resulting in more effective, highly differentiated medicines with the potential to optimise the route and frequency of delivery. These capabilities have already translated into marketed products and several assets in clinical development, such as IDELVION ® and AFSTYLA ® , from our recombinant protein platform; and several recombinant novel monoclonal antibodies (mAbs), in various phases of clinical development. Finally, CSL Behring has commenced clinical evaluation of two mAbs from our existing R&D portfolio, garadacimab (a novel factor XIIa-inhibitory mAb) and a novel, mAb which binds to the granulocyte colony-stimulating factor (G-CSF) receptor, both of which represent a unique and novel approach to treating the severe consequences of COVID-19. As demonstrated by the breadth and novelty of the pipeline, these capabilities have allowed CSL to leverage its expertise in protein biology and innate cell immunity to build a highly differentiated preclinical and clinical stage pipeline, with many of the proposed targets in areas of biology novel to the pharmaceutical industry. The value of the culture, capabilities and capacity of our recombinant protein technology platform has been brought into perspective by COVID-19, where CSL is uniquely positioned in Australia to respond to the crisis. CSL has partnered with the University of Queensland (UQ) and the Collaboration for Epidemic Preparedness Innovations (CEPI) to develop and manufacture a vaccine candidate for the COVID-19 pandemic (additional information on this partnership can be found in the R&D COVID-19 section on page 27). Transitioning from preclinical and early clinical studies to commercial manufacture requires a significant investment in process optimisation, assay development, formulation definition and product characterisation to be able to scale from thousands, to hundreds of millions of doses. Assuming success, CSL intends to use our significant capability in recombinant protein technology to honour our longstanding biosecurity commitment to Australia and its neighbours, as well as support the global effort to produce a vaccine for COVID-19. CSL Limited Annual Report 2020 25