Reconnecting Synbio R&D to Manufacturing

Figure 1: Trade-off between assay cost and prediction power. The predictive power of today’s high throughput titer assays is very low. Much better correlations can be achieved in bioreactors, but even the smallest vessels are too expensive to use for large scale screening.
Figure 2: Pharma uses high dimensional data to de-risk candidates at earlier stages of development. Left panel — after a high throughput binding assay, Pharma fast-fails problematic candidates using a variety of secondary assays, including newer approaches like high content imaging (e.g., Recursion and Tempus). Right panel: Ethical concerns aside, consider the disastrous alternative, where binding assay hits are promoted directly to Clinical Trials, and failures are realized at the most expensive stages of development.
Figure 3: How to massively reduce cost and risk in scaling up Synbio products. Left panel: the current state in Synbio. Candidate strains are evaluated for titer and growth in 96 well plate high throughput assays, which are insufficient to accurately predict bioreactor performance. Poor promotion decisions mean longer timelines, higher cost to scaleup and much greater risk in manufacturing. Right panel: At Sestina, we are incorporating high dimensional data with the goal of reaching 90% accuracy in our predictions. The ability to select better strains at the high throughput screening phase and scale will be transformative for achieving manufacturing success.

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