Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to initiate a pivotal, Phase 3 study, and additional novel drug candidates designed to treat homocystinuria (HCU) and enteric hyperoxaluria. 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 immunologic diseases.
Advanced Pipeline Targeting Metabolic, Immunological Diseases
in the GI tract
SYNB1353Ph 1 HV Data H2 2022
Ph 2 Synpheny-1 Data H2 2022
Phase 3 initiation
in H1 2023
SYNB8802Proof of Concept H2 2022
IBD Program – Single Target
“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) is a rare metabolic disease that manifests at birth and is marked by an inability to break down Phe, an amino acid that is commonly found in many foods. High levels of Phe can lead to serious neurological and neuropsychological problems affecting the way a person thinks, feels, and acts. Due to the seriousness of these symptoms, infants in many countries are screened for PKU at birth to ensure early diagnosis and access to treatment that can help reduce the risk of intellectual disability and other complications. To date, Synlogic has determined that SYNB1618 can lower Phe levels in healthy volunteers and patients. The company has initiated a Phase 2 study in PKU patients called SynPheny-1 (NCT04534842) to assess the ability of two drug candidates, SYNB1618 and SYNB1934, to decrease Phe levels in the blood. Learn more about the SynPheny-1 trial is available at www.pkuresearchstudy.com.
Homocystinuria (HCU) is a rare metabolic disease that is caused by an inborn error of metabolism, specifically the loss of function of the enzyme cystathionine beta-synthase, which results in excessive accumulation of homocysteine and its metabolites in the blood and urine. People with HCU face risks of complications including thromboembolism, lens dislocation, skeletal abnormalities, developmental delay, and intellectual disability. Many patients are required to comply with a rigid methionine-restricted diet and currently approved treatment options for HCU are limited due to efficacy and tolerability. In November 2021, Synlogic announced SYNB1353, an orally-administered, non-systemically absorbed drug candidate currently in IND-enabling studies and developed as part of a research collaboration with Synlogic and Gingko Bioworks. Synlogic holds worldwide development and commercialization rights to SYNB1353, which is expected to begin clinical development and report Phase 1 data in healthy volunteers in 2022.
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 no approved treatment options. SYNB88802 is a drug candidate designed to consume dietary oxalate throughout the GI tract. In a Phase 1 AB clinical trial, SYNB8802 achieved proof of mechanism in healthy volunteers during Part A of the study. The company has initiated Part B of the study to demonstrate proof of concept for lowering of urinary oxalate in patients following Roux-en-Y gastric bypass surgery.
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.
Autoimmune & Inflammatory Disease
Synlogic is also advancing research to assess the ability of novel Synthetic Biotic medicines to treat inflammatory bowel disease.