Aeglea BioTherapeutics to Present Preclinical Data on New Pipeline Therapeutic for Homocystinuria at 2018 American Society of Human Genetics (ASHG) Conference

AEB4104 is a Novel Engineered Human Enzyme with Unique Specificity for Degrading Both Homocysteine and Homocystine

AEB4104 Prevents Death, Stops Disease Progression, and Reverses Liver Pathology in a Disease Model of Homocystinuria

AUSTIN, Texas, Oct. 19, 2018 (GLOBE NEWSWIRE) --  Aeglea BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage biotechnology company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer, announced that it will present preclinical data on its new pipeline program AEB4104 for homocystinuria at the 2018 American Society of Human Genetics (ASHG) conference. Preclinical data supporting the development of AEB4104 will be presented today in poster #980, titled “Improved Survival and Amelioration of Disease-Related Liver Pathology in a Mouse Model of Homocystinuria with a Novel Homocysteine Degrading Enzyme.”

Homocystinuria is an inherited disorder of methionine metabolism caused by mutations in cystathionine beta synthase (CBS) and other genes leading to elevated levels of plasma and tissue homocysteine and homocystine. High levels of homocysteine and homocystine affect multiple organ systems and cause early mortality. Current disease management, which includes dietary protein (methionine) restriction, vitamins, and betaine supplementation, is insufficient to effectively control the more severe forms of the disease.

“Good control of plasma homocysteine levels is the key to disease management but is difficult to achieve in many patients with current approaches,” said James Wooldridge, M.D., chief medical officer of Aeglea. “Our latest preclinical data on AEB4104 shows its ability to rapidly lower the disease-causing metabolites in models of classical homocystinuria (HCU).”

The presentation today describes the engineering of the human cystathionine gamma-lyase (CGL) enzyme scaffold into a novel molecule with unique specificity for degrading both homocysteine and homocystine. AEB4104 decreases homocysteine and homocystine levels in the plasma of mouse models of HCU, including the CBS deficient (CBS-/-) mouse model and the high methionine diet-induced mouse model of HCU. AEB4104 treatment rapidly lowers plasma homocysteine and homocystine levels in both preclinical models. Treatment of CBS-/- mice with AEB4104 prevents early mortality, stops disease progression, and reverses liver pathology.

“It is exciting to see our enzyme design approach translating into innovative approaches for patients with devastating diseases like homocystinuria,” said Anthony G. Quinn, M.B Ch.B, Ph.D., president and chief executive officer of Aeglea. “The compelling preclinical efficacy data with AEB4104 supports advancement of this program into IND-enabling studies and we anticipate beginning GLP manufacturing for toxicology studies in the first quarter of 2019.”
About AEB4104 (Homocysteinase) in Homocystinuria
AEB4104 is a novel recombinant human enzyme that degrades the amino acid homocysteine and its oxidized form homocystine. Aeglea is developing AEB4104 for the treatment of patients with cystathionine beta synthase (CBS) deficiency, also known as Classical Homocystinuria. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including skeletal abnormalities, cognitive impairment, psychiatric disease, and thromboembolism. AEB4104 is intended to lower the abnormally high blood levels of homocysteine to the normal range in patients with homocystinuria. Preclinical data demonstrated that AEB4104 improved important disease-related abnormalities and survival in a mouse model of homocystinuria.

About Aeglea BioTherapeutics
Aeglea is a clinical-stage biotechnology company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer. The Company is developing pegzilarginase, its lead investigational therapy, for the treatment of Arginase 1 Deficiency, as monotherapy in arginine-dependent cancers and in combination with an immune checkpoint inhibitor for small cell lung cancer. In addition, Aeglea has an active research pipeline of other human enzyme-based approaches in both therapeutic areas. For more information, please visit

Safe Harbor / Forward Looking Statements
This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, the potential therapeutic benefits and economic value of our lead product candidate or other product candidates and our eligibility to receive a priority review voucher. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 filed with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.           

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David Calusdian
Sharon Merrill Associates

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Director, Finance & Investor Relations
Aeglea BioTherapeutics