Synlogic, Inc., (Nasdaq: SYBX) a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, announced on 4/30/19 that data demonstrating its development of a robust and reproducible process to generate a solid oral formulation of its Synthetic Bioticmedicine, SYNB1618, are being presented today at the 22nd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT). Synlogic is developing SYNB1618 for the treatment of phenylketonuria (PKU).
“We have developed a process to generate a solid formulation of SYNB1618 for oral use that makes it more patient-friendly and provides a stability profile suitable for eventual commercialization,” said Antoine Awad, Synlogic’s head of technical operations. “The data presented at the ASGCT meeting demonstrate that we can generate a solid preparation of SYNB1618 with minimal impact on cell viability and activity and improved quality attributes compared to the liquid formulation that is being used in our ongoing clinical trial. We plan to apply our solid formulation expertise across our pipeline products.”
Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a strain of probiotic bacteria (E. coli Nissle) to perform or deliver specific functions lost or damaged due to disease. SYNB1618 is designed to metabolize Phe and was engineered by inserting specific genetic circuits including a bacterial gene that encodes phenylalanine ammonia lyase (PAL). PAL is an enzyme that breaks down Phe to generate trans-cinnamic acid (TCA), which is converted to hippuric acid (HA) in the liver and excreted in urine. Thus, plasma TCA and urinary HA levels can serve as biomarkers of PAL and, therefore, of SYNB1618 activity in vivo.
As described in the ASGCT presentation, Synlogic’s scientists have successfully developed a process that demonstrates:
- batch to batch reproducibility in cell viability and activity at the 30L production scale
- improved physical quality attributes of the product; and a solid formulation that:
- is similarly active to frozen liquid in terms of consumption of Phe or production of TCA/HA in an in vitro gut simulation model and in vivo in non-human primates and a mouse model of disease
- in initial studies is stable for >90 days at 2-8◦C and >30 days at room temperature (Synlogic intends to generate shelf-life data over two years).
As a solid oral formulation with improved stability and convenience SYNB1618 has potential as a new therapy for managing blood Phe levels in patients with PKU.