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Drug Discovery


Bacteriophage viruses infecting bacterial cells


Collaborations also are fuelling microbiome


drug discovery, with three of the most prominent joint efforts focused on using bacteria consortiums – defined compositions of bacteria administered orally, which are emerging as a high-potential ‘bugs as drugs’ approach. Bristol-Myers Squibb (BMS) is partnering with Vedanta Biosciences to assess the efficacy of the immune checkpoint inhibitor Opdivo® in combination with Vedanta’s VE800, a bacterial consortium that activates cyto- toxic CD8+ T cells. Similarly, Merck and Evelo Biosciences are evaluating the efficacy of Keytruda® in combination with Evelo’s EDP1503, an orally-delivered monoclonal microbial oncolo- gy drug candidate. The microbiome’s role in oncol- ogy immunotherapy is also the focus of a three- year, $20 million collaboration between Seres Therapeutics and AstraZeneca, combining Seres’ manufacturing capabilities and expertise in devel- oping drug candidates targeting microbiome dys- biosis with AstraZeneca’s oncology portfolio. Taking a slightly different tack, a collaboration between Enterome and the Dana-Farber Cancer Institute aims to evaluate and develop gut micro- biome-derived antigens for cancer immunotherapy. Dana-Farber’s preclinical models will be used for in vivo validation of bacterial antigens that mimic


16


the antigens expressed by tumours and elicit a cytotoxic T cell immune response. As significant funds are invested in microbiome


drug discovery, the various players involved are employing a wide range of approaches and a diverse set of technologies. It seems the industry is taking different yet parallel paths that aim at a sim- ilar endpoint: understanding and leveraging the impact of the microbiome on disease development and treatment. Mouse models are taking centre stage in these


varied efforts. Despite known limitations that affect the translatability of microbiome research conducted in mice, mouse models are helping elu- cidate the mechanisms of the microbiome and enabling testing of therapies that could dramatical- ly alter how major diseases are treated. Current ini- tiatives demonstrate the utility of the mouse model in microbiome-related research, both in drug dis- covery and in the preclinical proving ground.


Banking on bacteria consortiums Several of the most promising initiatives in micro- biome research are banking on the viability of bac- teria consortiums as effective disease therapeutics, whether as monotherapy or in combination with other drugs. Two of the leading players in this


Drug Discovery World Fall 2019


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