Technology Platforms at SPARK Biopharma can facilitate phenotype-based drug discovery for the development of first-in-class therapeutics. We are interested in the phenotypic assay which is relevant to the diseases of interest with disease-relevant stimuli and read-outs. Particularly, we have been working on modulating immune systems. In fact, inflammatory responses are involved in the pathogenesis of various diseases and inflammation is considered to be essential to body’s healing system. However, chronic inflammation may results in a wide range of diseases such as cancer, infectious diseases, cardiovascular disease, non-alcoholic fatty liver disease, neurodegenerative disorders, diabetes mellitus, chronic kidney disease, autoimmune diseases, and so on. Treatment of inflammation has been considered as novel therapies for these diseases for a long time, culminating in the recent advent of immuno-oncology. Given the importance of inflammation in disease, we have concentrated our R&D effort on the identification of small-molecule drug candidates to control various aspects of immune system.

We are particularly interested in small molecules that can modulate the tumor microenvironment (TME). Immuno-oncology is the third generation of cancer therapy after cytotoxic chemotherapy (1st generation) and targeted chemotherapy (2nd generation). Immune Checkpoint inhibitors (ICI), antibody-based immuno-oncology, becomes the most preferred therapy and the future of cancer care. Currently immuno-oncology is only available for certain types of cancer, however doctors believe that there will be more targeted immunotherapy for essentially all cancer types. Although cancer immunotherapy has been shown to be efficacious, patient response rates vary and, more often than not, only a small subset of the patients. To improve efficacy and patient response rates, the tumor microenvironment needs to be changed from “cold tumor” to “hot tumor”, where ICI works the best. SPARK Biopharma focuses how we can modulate the tumor microenvironment and we believe that small molecules discovered from adequate phenotypic assay can do the best for this task. SPARK Biopharma developed a series of small-molecule candidates that can selectively modulate the tumor microenvironments in various strategies. These candidates induced the tumor regression by themselves, and they also showed the synergy with other ICIs and oncolytic viruses in tumor growth inhibition. This immune-modulating approach can be extended to infectious diseases, cardiovascular & metabolic diseases as our major research interest.

Ref: Furman et al., 2019. Nature Med. 25, 1822-1832