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New immuno-oncology modalities often establish themselves as combinations for standard ICI monoclonal antibodies
Combination treatments open up potential for improved SoC regimes in immune-oncology
Individualised treatments designed from a patient ’ s own cells or tumours are expensive and timeconsuming
Immuno-oncology modalities are growing Monoclonal antibodies have largely been the only modalities approved in the immuno-oncology space until recent years . Bispecific antibodies and ADCs have gained notable approvals recently , with many more in the development pipeline looking to capitalise on early successes . ADC in particular are seeing an upwards drive-in demand , with many big pharma companies investing heavily in this space , notably with Pfizer ’ s recent announcement of a $ 43bn acquisition of Seagen who have three approved ADCs . Therapeutic cancer vaccines have long failed to impress on the clinical stage however many recent candidates show promising Phase III results , notably OSE Immunotherapeutics ’ Tedopi , which importantly shows synergy with pembrolizumab in non-small cell lung cancer (“ NSCLC ”). Following the wave of renewed interest in mRNA , cancer vaccines are set to establish themselves as a major face of the next generation of immuno-oncology .
Blockbuster immune checkpoint inhibitors ; the late-stage SoC Immune checkpoint inhibitors (“ ICI ”) have established themselves as the SoC for late-stage treatment , with PD-1 inhibitors pembrolizumab and nivolumab generating significant revenue of $ 20.9bn and $ 8.2bn for Merck and BMS in 2022 respectively . PD-1 expression is indicative of PD-1 / PD-L1 ICI response , and current combinations with chemotherapy often do not extend the efficacy across patient subgroups . There is a race to find additional combinations beyond chemotherapy that adds synergy to current ICI ’ s and that can extend their patents and maintain blockbuster revenues . PD-1 and PD-L1 inhibitors remain the gold-standard of ICI , with CTLA-4 inhibitors such as ipilimumab often used in combination and recently , LAG-3 establishing itself as a novel ICI target with the 2022 approval of relatlimab for melanoma .
Combinations are the future within immuno-oncology Despite the success of ICI , there is great need for combinations that synergise their efforts to activate the immune system . ICI monotherapy often results in resistance or fails to achieve a response across all patients . Complementary therapies have been limited to other ICI which risk toxicity when given as a dual combination ; other modalities offer significant potential to improve response rates and efficacy . In our opinion , Immutep ’ s eftilagimod alpha (“ efti ”), a LAG-3 fusion protein that has demonstrated impressive synergy with pembrolizumab in NSCLC and head & neck squamous cell carcinoma (“ HNSCC ”) as well as impressive synergy for triple therapy with pembrolizumab and chemo in NSCLC , is the most promising combinatorial candidate particularly in NSCLC . Cancer vaccines offer a sound theoretical synergy to activate immune cells in the TME . Multiple late-stage vaccines have ICI combination trials such as BioNTech ’ s two candidates BNT111 with cemiplimab in melanoma and BNT113 with pembrolizumab in HNSCC which both show promise to become effective late-stage immuno-oncology treatments .
Personalised CAR-T and radiopharmaceuticals face supply chain bottlenecks Supply chains and technological methods are crucial aspects of an oncology treatments ’ success . CAR-T and personalised cancer vaccines show promising results , yet due to their autologous nature are difficult to scale for commercial size . CAR-T therapy has shown efficacy in liquid cancers , however , is reserved for a small number of patients as the infrastructure to isolate patient ’ s own cells is time consuming and expensive . Similarly , radiopharmaceuticals are attracting investors attention , but require stringent safety protocols in manufacturing and rapid delivery and are one of the most important features to a radiopharmaceutical company ’ s success . Companies such as ITM where this supply chain is integrated and well-constructed are well poised for larger pharma companies to acquire , in our view .
Oncology market trends
NGS is driving precision medicine in identifying targets for treatment and diagnosis
NGS costs driving oncology innovation One of the largest drivers behind cancer diagnostic and treatment innovation is the reduction in next generation sequencing (“ NGS ”) costs . This has facilitated easier identification of target antigens for both diagnosis and treatment and driven new precision medicine targets in immune-oncology . Similarly , it is facilitating liquid biopsy techniques and companion diagnostics to ensure cancer is diagnosed early and monitor disease progression . As our understanding of tumour microenvironments (“ TME ”) and heterogeneity improves , identification antigens will result in most effective treatments will streamline and should lead to improved efficacy of treatments .
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