SYNB1618 / Synlogic - LARVOL DELTA

Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial. (PubMed, Nat Metab) - P2 | "We previously modified Escherichia coli Nissle 1917 to metabolize Phe in the gut after oral administration (SYNB1618) and designed a second strain (SYNB1934) with enhanced activity of phenylalanine ammonia lyase. Four participants discontinued because of adverse events, and one withdrew during the baseline period. We show that synthetic biotics can metabolize Phe in the gut, lower post-prandial plasma Phe levels and lower fasting plasma Phe in patients with PKU."

Journal • P2 data • Infectious Disease • Metabolic Disorders • Phenylketonuria • Rare Diseases

Redesign of an Escherichia coli Nissle treatment for phenylketonuria using insulated genomic landing pads and genetic circuits to reduce burden. (PubMed, Cell Syst) - "The resulting strain (EcN SYN8784) achieved higher activity than EcN SYNB1618, reaching levels near when the pathway is carried on a plasmid. This work demonstrates a simple system for engineering EcN that aids quantitative strain design for therapeutics."

Journal • Infectious Disease • Metabolic Disorders • Oncology • Phenylketonuria • Rare Diseases

Robust performance of a live bacterial therapeutic chassis lacking the colibactin gene cluster. (PubMed, PLoS One) - "Deletion of pks also had no effect on the activity of strains engineered to degrade phenylalanine (SYNB1618 and SYNB1934) or oxalate (SYNB8802). Importantly, there was no significant difference on in vivo strain performance between the clinical-stage strain SYNB1934 and its isogenic Δpks variant with regards to recovery of the quantitative strain-specific biomarkers d5- trans-cinnamic acid, and d5-hippuric acid. Taken together, these data support that the pks island is dispensable for Synthetic Biotic fitness and activity in vivo and that its removal from engineered strains of EcN will not have a deleterious effect on strain efficacy."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

SynPheny-1: Efficacy and Safety of SYNB1618 and SYNB1934 in Adult Patients With Phenylketonuria (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Synlogic | Recruiting ➔ Completed

Trial completion • Metabolic Disorders • Phenylketonuria • Rare Diseases

Safety and Tolerability of SYNB1934 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=106 | Completed | Sponsor: Synlogic | Recruiting ➔ Completed

Trial completion

Development of synthetic biotics as treatment for human diseases. (PubMed, Synth Biol (Oxf)) - "This review outlines some of the unique attributes of synthetic biotics as well as some of the challenges in their development as prescription products. Regulatory considerations are discussed, and a case study of a program that has advanced into Phase 2 testing is provided: SYNB1618 for the treatment of PKU."

Journal • Review

SynPheny-1: Efficacy and Safety of SYNB1618 and SYNB1934 in Adult Patients With Phenylketonuria (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: Synlogic; N=12 ➔ 24

Clinical • Enrollment change • Metabolic Disorders • Phenylketonuria • Rare Diseases

Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering. (PubMed, Nat Commun) - "A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618."

Journal • Gastrointestinal Disorder • Metabolic Disorders • Phenylketonuria • Rare Diseases

SynPheny-1: Efficacy and Safety of SYNB1618 in Adult Patients With Phenylketonuria (clinicaltrials.gov) - P2; N=12; Recruiting; Sponsor: Synlogic; Trial completion date: Aug 2021 ➔ Jun 2022; Trial primary completion date: Aug 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

Safety and Tolerability of SYNB1934 in Healthy Adult Volunteers (clinicaltrials.gov) - P1; N=106; Recruiting; Sponsor: Synlogic

New P1 trial

Development of a mechanistic model to predict synthetic biotic activity in healthy volunteers and patients with phenylketonuria. (PubMed, Commun Biol) - "In addition, we extend a model of plasma Phe kinetics in PKU patients, in order to estimate plasma Phe lowering by SYNB1618. This approach provides a framework that can be used more broadly to define the therapeutic potential of synthetic biotics."

Clinical • Journal • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases

Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study. (PubMed, Nat Metab) - P1/2 | "We engineered a strain of E. coli Nissle 1917, designated SYNB1618, through insertion of the genes encoding phenylalanine ammonia lyase and L-amino acid deaminase into the genome, which allow for bacterial consumption of Phe within the gastrointestinal tract...All participants cleared the bacteria within 4 days of the last dose. Dose-responsive increases in strain-specific Phe metabolites in plasma (trans-cinnamic acid) and urine (hippuric acid) were observed, providing a proof of mechanism for the potential to use engineered bacteria in the treatment of rare metabolic disorders."

Clinical • Journal • P1/2 data • PK/PD data • Gastrointestinal Disorder • Metabolic Disorders • Phenylketonuria • Rare Diseases

SynPheny-1: Efficacy and Safety of SYNB1618 in Adult Patients With Phenylketonuria (clinicaltrials.gov) - P2; N=12; Recruiting; Sponsor: Synlogic; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Metabolic Disorders • Phenylketonuria • Rare Diseases

SynPheny-1: Efficacy and Safety of SYNB1618 in Adult Patients With Phenylketonuria (clinicaltrials.gov) - P2; N=12; Not yet recruiting; Sponsor: Synlogic

Clinical • New P2 trial • Metabolic Disorders • Phenylketonuria • Rare Diseases