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 that dosing in the third cohort of the Phase 1/2 clinical trial of pegtarviliase for the treatment of Classical Homocystinuria is underway. Patients in this cohort are receiving 1.35 mg/kg of pegtarviliase once weekly administered via subcutaneous injection; patients in cohorts 1 and 2 received doses of 0.15 mg/kg and 0.45 mg/kg, respectively.

Additionally, the company received a letter from the U.S. Food and Drug Administration (FDA) responding to a recently submitted protocol amendment for the Phase 1/2 clinical trial of pegtarviliase for the treatment of Classical Homocystinuria. The protocol amendment, among other things, requested the inclusion of adolescent patients at clinical trial sites in the U.S. The FDA stated the protocol did not provide adequate justification and evidence to support the prospect of direct clinical benefit for pediatric patients and placed the trial on partial clinical hold for the enrollment of patients less than 18 years of age under this Investigational New Drug (IND) at this time. The company intends to address the feedback from the FDA and aims to satisfy the requirements for prospective benefit for future inclusion of pediatric patients under the IND, including in a potential pivotal trial.

The company believes that the letter will have no impact on the planned enrollment and dosing of patients aged 18 years and older in the U.S. or patients aged 12 years and older in the UK and Australia. Enrollment in the trial remains on track and Aeglea continues to expect to announce data in the fourth quarter of 2022, including data from cohort 3. The primary endpoint of the Phase 1/2 open-label trial is safety and tolerability. Three to four patients will be enrolled in each cohort and treated with four once weekly doses of pegtarviliase.

About Pegtarviliase in Homocystinuria

Pegtarviliase (formerly AGLE-177) is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its dimer. Pegtarviliase 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 total homocysteine. 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. In preclinical studies, pegtarviliase improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. Pegtarviliase 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 is investigating pegtarviliase in an ongoing Phase 1/2 clinical trial for the treatment of Classical Homocystinuria. Pegtarviliase has been granted Rare Pediatric Disease Designation. Aeglea's other clinical program, pegzilarginase, achieved the primary endpoint of arginine reduction in the PEACE Phase 3 clinical trial and has received both Rare Pediatric Disease and Breakthrough Therapy Designations. The Marketing Authorization Application for pegzilarginase is currently under review with the European Medicines Agency. 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 http://aeglea.com.

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 to future periods. 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, statements we make regarding our ability to achieve further cost-savings, the timing of announcements and updates relating to our clinical trials and related data, including the clinical data for our Phase 1/2 trial of pegtarviliase in Homocystinuria, the timing and success of our clinical trials and related data, the timing and expectations for regulatory submissions and approvals, including the MAA for pegzilarginase in Europe, our ability to obtain regulatory approval for, and commercialize, pegzilarginase, recognize milestone and royalty payments from our agreement with Immedica, our ability to enroll patients into our clinical trials, the expected impact of the COVID-19 pandemic on our operations and clinical trials, success in our collaborations, the length of time that we believe our existing cash resources will fund operations, the potential addressable markets of our product candidates and the potential therapeutic benefits and economic value of our lead product candidate or other product candidates. 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, 2022 filed with the Securities and Exchange Commission (SEC), and our 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.