CSL Ltd Annual Report 2020

Cell and gene therapy Cell and gene therapies are highly innovative, next- generation products that, after decades of research and development, are now starting to positively impact the lives of patients with serious diseases. For diseases with few effective therapeutic options, such as certain blood cell cancers, or where successful therapy has required a lifetime of regular symptomatic treatment, for example rare inherited genetic deficiencies, they offer the promise of a long-term cure. In light of this recent progress, CSL has made a significant global investment to both acquire and further develop capability in cell and gene-based therapies. This investment provides CSL scientists with a third therapeutic development platform that complements the longstanding and successful deployment of our plasma and recombinant protein platforms. CSL entered the cell and gene therapy field through the strategic acquisition of Calimmune in 2017. The acquisition gave CSL access to the preclinical development program for an ex vivo haematopoietic stem cell gene therapy for the treatment of sickle cell disease (SCD). CSL also acquired two platform technologies: SELECT+™ and CYTEGRITY™. These technologies are designed to address some of the main challenges currently associated with the commercialisation of stem cell therapy, including the ability to manufacture consistent, high-quality products, and to improve stem cell engraftment, efficacy and tolerability. Both technologies have broad applications in ex vivo stem cell gene therapy. The ex-Calimmune facilities in Pasadena, US, and Sydney, Australia, are now fully integrated into the CSL R&D network and our cell and gene therapy project-related activities are now progressed through global project teams that access skill sets and technical capability from the most appropriate R&D facility. The Pasadena site is in close proximity to some of the world’s premier gene therapy academic institutions and biotech companies. This proximity has allowed CSL to engage in strategic partnerships to strengthen its commitment to developing gene and cell therapies. These include partnerships with City of Hope Hospital in Duarte, California, and University of California, Los Angeles (UCLA). In June 2020, a strategic alliance was announced with the Seattle Children’s Research Institute (SCRI) in Seattle, Washington, to develop stem cell gene therapies for primary immunodeficiency (PI) diseases such as Wiskott-Aldrich syndrome and X-linked agammaglobulinemia. Expanding our gene therapy portfolio into an area of immunology well known to CSL exemplifies how we are strategically growing our capabilities in this scientific platform and are collaborating with world-class institutions to access innovation with the potential to vastly improve patients’ lives. Enabling gene therapy research The Pasadena site represents CSL’s first US-based, wet- laboratory R&D facility with a good manufacturing practice (GMP) cell manufacturing facility established to support CSL’s ex vivo gene therapy clinical development programs in Phase I and II. In addition, the laboratory space has been tripled in area and upgraded, representing an overall capital investment in excess of US$12 million. The expansion also included the addition of 845 square metres of laboratory and office space allowing for the required growth in Research, Bioanalytics, Cell Manufacturing, Clinical Operations and support functions. Since the acquisition, on-site staff has more than doubled to 50. A newly established viral vector laboratory in Marburg, Germany, has the capability to produce lentivirus in traditional flatware, adherent and suspension bioreactors. CSL is focused on the establishment of a robust and scalable viral vector manufacturing platform that can be utilised across many different gene therapy products. Aiding the process development activities is a state-of-the-art analytical laboratory that enables the scientist to test and fully characterise the viral vector. CSL is also continuing to build a strong network of collaborators across Europe and the US to further enhance CSL’s process and analytical capabilities for large-scale viral vector clinical production. Influenza vaccine technologies The core focus for Seqirus R&D is the development of better influenza vaccines based on proprietary cell-culture and adjuvant technologies. Formore than 50 years, influenza vaccine has been produced using chicken eggs to grow virus, which is then extracted, killed and purified into the vaccine components. Seqirus has pioneered the modernisation of influenza vaccine with the development of FLUCELVAX ® QUADRIVALENT, a four-strain product where the vaccine components are grown in state-of-the-art cell-culture bioreactors in our plant in Holly Springs, North Carolina, US. This approach has a variety of potential advantages, including greater efficiency of production and improved matching of the virus strains included in the vaccine, with the circulating virus infecting people. Since its inception, Seqirus has registered FLUCELVAX QUADRIVALENT inmultiple markets, introduced significant process improvements and increased production scale to meet global demand. Current activities include further geographical expansion of licensure and a number of clinical trials to support expanding the indicated age for FLUCELVAX to include infants down to six months of age. We also continue to focus on ways to improve the productivity and efficiency of the manufacturing process with the aim of boosting the number of doses we can make in a season and speeding up the time to market. An ongoing, important commitment is to gather in-market, real world evidence that provides insights into the potential benefits of FLUCELVAX. Influenza Science Cell-based Egg-based Standard risk Pandemic At-risk populations Adjuvanted seasonal TIV / QIV Seasonal TIV / QIV An important challenge in protecting the community from influenza is the waning immunity and response to vaccination of people with increasing age. FLUAD ® QUADRIVALENT combines egg-based vaccine with Seqirus’ proprietary adjuvant, MF59, an additive that acts to strengthen the immune response to vaccination. It is licensed in a number of countries and is indicated for people 65 years and older. The collection and analysis of real world evidence is also an important component of our ongoing FLUAD activities. 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