PIPELINE
Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which completed a Phase 2 study with plans to initiate a pivotal, Phase 3 study, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria (EH) and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s proprietary, reproducible, target-specific drug design, with a focus on addressing serious medical needs in metabolic and immunological diseases.
Advancing a New Class of Biotherapeutics
Exploratory
Preclinical
IND-Enabling
Studies
Phase 1
Phase 2
Phase 3
Metabolic
Phenylketonuria (PKU)
Homocystinuria (HCU)
SYNB1934* RPDD OD
SYNB1353 RPDD ODD FT
Enteric Hyperoxaluria
Gout
SYNB8802
SYNB2081
Immunology
.
IBD Program – Single Target
.
*First generation SYNB1618 for PKU received both ODD and FT designations by the FDA and orphan medicinal product designation by the EMA.
RPDD = Rare Pediatric Disease Designation granted by FDA
OD = Orphan Designation granted by EMA
ODD = Orphan Drug Designation granted by FDA
FT = Fast Track granted by FDA
“We set out to identify diseases where we could have a meaningful impact and demonstrate the power and potential of drugs based on synthetic biology, leading us to focus on rare metabolic diseases, as well as enteric hyperoxaluria as initial programs. Once we understood the underlying molecular biology behind these conditions, we could rapidly design Synthetic Biotics that could potentially provide new treatment options for patients”
— Aoife Brennan, MB, ChB, President and Chief Executive Officer
Phenylketonuria (PKU)
SYNB1934 is an orally administered, non-systemically absorbed drug candidate being studied as a potential biotherapeutic for phenylketonuria (PKU), an inherited metabolic disease marked by an inability to break down the amino acid phenylalanine (Phe), which can be neurotoxic. Lifelong, consistent control of low Phe levels is required for avoiding the serious risks and complications of PKU. Treatment options for PKU are currently limited, with a majority of individuals with PKU in need of treatment or not adequately responding to treatment. Synlogic designed its drug candidates to reduce levels of Phe in people with PKU by consuming Phe in the gastrointestinal (GI) tract, using genetic engineering of the well-characterized probiotic E. coli Nissle. Findings to date support the potential for an oral, efficacious, safe, convenient, and flexible treatment option for PKU. SYNB1618, our first generation drug candidate for PKU, has received both Orphan Drug and Fast Track designations by the US Food and Drug Administration (FDA) orphan medicinal product designation by the European Medicines Agency. SYNB1934 has received Rare Pediatric Disease Designation by the FDA.
Homocystinuria (HCU)
SYNB1353 is a novel orally-administered, non-systemically absorbed drug candidate designed to consume methionine in the gastrointestinal tract thereby lowering homocysteine levels in patients with homocystinuria (HCU). HCU is an inherited disorder characterized by high levels of homocysteine and risks including thromboembolism, lens dislocation, skeletal abnormalities, developmental delay, and intellectual disability. Treatment options for HCU are currently limited due to safety, efficacy, and tolerability. Synlogic holds worldwide development and commercialization rights to SYNB1353, which is designed to consume methionine, a precursor to homocysteine, in the GI tract. The goal of treatment in HCU is to lower and control levels of total homocysteine (tHcy). SYNB1353was granted Fast Track and Orphan Drug Designation by the FDA and is the first drug candidate developed through a research collaboration between Synlogic and Ginkgo Bioworks and the first investigational medicine developed on Ginkgo’s platform to enter the clinic. SYNB1353 has achieved proof of mechanism in a Phase 1 study using a dietary model of homocystinuria in healthy volunteers.
Enteric Hyperoxaluria
Enteric hyperoxaluria is a chronic, progressive disease characterized by high levels of urinary oxalate, the leading cause of recurrent kidney stones. Oxalate crystals can damage kidneys, potentially leading to damage that can include nephrocalcinosis, chronic kidney disease (CKD) and end-stage renal disease (ESRD). Enteric hyperoxaluria often occurs as a result of a primary insult to the bowel, such as inflammatory bowel disease or short bowel syndrome, or as a result of surgical procedures such as Roux-en-Y bariatric weight-loss surgery. There are currently no FDA approved treatment options. SYNB88802 is a drug candidate designed to consume dietary oxalate throughout the GI tract. SYNB8802 has demonstrated proof of concept through positive and clinically significant lowering of urinary oxalate in a Phase 1b study in patients with a history of gastric bypass surgery.
Gout
Gout is a complex form of inflammatory arthritis that occurs when extra uric acid in the body forms crystals in the joints. It includes symptoms such as intense joint pain, inflammation and redness, and limited range of motion in the affected joints. Current treatment options present limitations in both safety and efficacy, highlighting a need for new approaches. In addition, gout is a recognized risk factor in chronic kidney disease (CKD). SYNB2081 is a Synthetic Biotic designed to lower uric acid, as a potential treatment of gout. This is Synlogic’s second drug candidate developed through its partnership with Ginkgo Bioworks.
Immunology
In June 2021, Synlogic began working with Roche on a research collaboration focused on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease. For more information click here.