Aeglea BioTherapeutics Doses First Patient in a Phase 1/2 Clinical Trial of AGLE-177, a Potential First-in-Class Treatment for Homocystinuria


AUSTIN, Texas, June 24, 2021 /PRNewswire/ -- Aeglea BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, today announced the dosing of the first patient in the Company's first-in-human Phase 1/2 clinical trial investigating AGLE-177 for the treatment of Homocystinuria. The markedly elevated plasma homocysteine levels lead to a wide range of life-altering complications and reduced life expectancy in people with Homocystinuria. AGLE-177 is a novel engineered human enzyme therapy designed to lower the total level of homocysteine in the plasma. Aeglea anticipates providing a clinical update on the program prior to the end of 2021.

"AGLE-177 is designed to address the markedly elevated homocysteine levels that are believed to be a key driver of the risk of serious complications in Homocystinuria, and has the potential to transform management of this burdensome and life-threatening condition," said Anthony Quinn, M.B Ch.B, Ph.D., president and chief executive officer of Aeglea. "We believe this clinical trial will provide us with proof of concept of the homocysteine lowering effects of AGLE-177 in patients and provide us with the information needed to transition rapidly into a Phase 3 registrational trial."

Cystathionine beta synthase (CBS) deficiency, also known as Classical Homocystinuria, is an inherited disorder of methionine metabolism that results in elevated homocysteine and homocystine in the plasma and urine. Disease management strategies, which are limited and include dietary protein restriction with amino acid replacement either alone or with vitamin B6, and betaine supplementation, are challenging, have poor adherence and many patients are not responsive to treatment. It is estimated that there are more than 30,000 people living with Homocystinuria in the global addressable markets, which includes approximately 15,000 to 18,000 B6-non-responsive patients.

"Untreated Homocystinuria is a severe disease as a result of which individuals can develop significant complications, including visual impairment, skeletal abnormalities, reduced intellectual capacity, and recurrent thromboembolic events which may be life-threatening," said Principal Investigator Dr. Elaine Murphy, Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK. "Currently available treatment options are complex and do not always result in optimal metabolic control of the condition, leaving patients at risk of lifelong complications. There is an unmet need, therefore, for new therapies that can improve the outcomes and quality of life for this patient community."

The multicenter, open label, dose escalation Phase 1/2 trial is anticipated to enroll 16-20 patients diagnosed with Homocystinuria aged 12 years or older at sites located in the United Kingdom and Australia. The primary endpoint is the safety and tolerability of AGLE-177. Secondary endpoints include pharmacokinetic assessments as well as reduction in plasma total homocysteine levels. Patients will be dosed weekly for four weeks, with four patients in each of four dosing cohorts and an option to include a fifth cohort as needed.

About AGLE-177 in Homocystinuria
AGLE-177 is a novel recombinant human enzyme, which degrades the amino acid homocysteine and its related homocystine dimer. AGLE-177 is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of homocysteine and homocystine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177, which is designed to lower abnormally high blood levels of homocysteine, improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.

About Aeglea BioTherapeutics
Aeglea BioTherapeutics is a clinical-stage biotechnology company redefining the potential of human enzyme therapeutics to benefit people with rare metabolic diseases with limited treatment options. Aeglea's lead product candidate, pegzilarginase, is in a pivotal Phase 3 trial for the treatment of Arginase 1 Deficiency and has received both Rare Pediatric Disease and Breakthrough Therapy Designations. The Company began dosing patients in a Phase 1/2 clinical trial of AGLE-177 for the treatment of Homocystinuria in June 2021. AGLE-177 has also been granted Rare Pediatric Disease Designation. Aeglea has an active discovery platform focused on engineering small changes in human enzymes to have a big impact on the lives of patients and their families. For more information, please visit

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