机遇及挑战

Paul D’Souza-Bento and Alex Bour Key Takeawaysfor CI Teams Key Takeaways for CI Teams The landscape for cell and gene therapies has been evolving over the past few yearswith a rise in available treatments for rare and life-threatening diseases in the lastyear alone. This is despite generally high costs of R&D and manufacturing, coupledwith the infancy of scientific understanding compared to other areas of science. Despite the increasing volume of gene therapy assets targeting hematological malignancies, significantmarket potential exists, driven by the complexities in treatment-related adverse events among approvedproducts – opportunities for further differentiation thus exists for novel therapies. As cell and gene therapies move into indications with larger disease burdens, manufacturers will have amyriad of factors to consider, including the holistic value of a potentially curative therapy on already strainedhealthcare systems, payer price-sensitivity, and a potentially depleting patient population. The curative potential of cell and gene therapies presents paradigm-shifting opportunities and challenges tothe biopharma industry, requiring CI teams with deep therapy area knowledge and access to robustsecondary and primary insights to support critical strategic decision-making at key inflection points. Gene TherapyLandscape Gene Therapy Landscape Since 2004, 32 gene therapies, including genetically modified cell therapies, have been registered covering oncology indications, including non-Hodgkin’slymphoma (NHL), acute lymphocytic leukaemia (ALL), and chronic lymphocytic leukaemia (CLL). Key players have mainly been top pharma, althoughBluebird Bio biotech tops the list with 4 assets (Figure 1 and Table 1). Source: Pharmaprojects Source: Pharmaprojects Eight of these treatments had been approved for the first time since the beginning of 2023 alone for a range of oncology and rare indications (Table 2).CRISPR Therapeutics / Vertex’s Casgevy became the first CRISPR-edited therapy approved in November 2023, specifically for sickle cell anaemia andtransfusion-dependent beta thalassemia. The approach consists of genetically-modified autologous CD34+ cells containing haematopoietic stem andprogenitor cells editedex vivoby CRISPR gene editing technology. Another treatment for sickle cell anaemia, Lyfgenia, provides a functional beta-globingene to a patient’s own haematopoetic stem cells, was approved in December 2023. The pipeline stage is also progressing with 2,092 assets in preclinical – pre-registration. Within late-stage (Phase 3 – Pre-registration), 38 candidates havebeen identified with smaller players Regenxbio and Ultragenyx Pharmaceutical leading the way with 4 assets each, whilst Novartis and Pfizer have a couplea piece. Most prevalent indications include solid cancer, bladder, and brain cancer. Overall, a combination of both large pharma and biotech top the list of players with the highest volume of gene therapies, with Roche capping the charts with28 assets, followed by AstraZeneca and Sarepta with 21 each (Figure 3). With approved treatments under their belt, Bluebird and CARsgen also havesignificantly sized portfolios. The majority of diseases included solid cancer, myeloma, acute lymphocytic leukaemia and non-Hodgkin’s lymphoma (Table 3). Cell TherapyLandscape Cell Therapy Landscape In contrast to gene therapies, there are currently 74 cell therapies approved, excluding gene-modified cell therapies, treating conditions such as burns,orthopaedic lesions and osteoarthritis. Key players are mainly non-top pharma or biotech, including Smith & Nephew, Teijin, and Bluebird Bio, with GSK andSanofi having three registered treatments each (Figure 4 and Table 4). Table 4: Most prevalent diseases targeted by approved cell therapies,excluding gene-modified cell therapies Source: Pharmaprojects Since 2023, 4 non-modified cell therapies have received first approval targeting various diseases (Table 5). In June 2023, Lantidra, a treatment consisting ofallogenic pancreatic cells derived from deceased patients, was approved becoming the first ever cell therapy for type 1 diabetes, potentially removing theneed for insulin. Amtagvi became the first approved cell treatment for advanced melanoma, in March 2024. The approach involves use of tumour-infiltrating lymphocytes derived from a tumour sample, strengthened, and infused back into the patient. Source: Pharmaprojects The number of cell therapies in the pipeline is around half of that for gene therapies, with 1,323 in preclinical – pre-registration, however, there are morecandidates (59) in late-stage (Phase 3 or pre-filing), predominantly led by non-large pharma (2 to 3 assets each). In contrast to gene therapies, topindications focus on non-oncology diseases such as COVID-19, osteoarthritis, heart, and respiratory conditions (Figure 5 and Table 6). Figure 5: Top players (by number of non-modified cell therapies in late-stage development (Phas