Aeglea BioTherapeutics Announces Leadership Transition and Corporate Restructuring

Prioritizing Resources and Focus on AGLE-177 and the Completion of the Ongoing Phase 1/2 Trial in Homocystinuria with Interim Clinical Data Expected in Q4 of 2022

Dr. Anthony Quinn, President, CEO and Board Member, has Stepped Down from His Current Positions and Transitioned to an Advisory Role

Corporate Restructuring to Extend Runway into Q4 2023

AUSTIN, Texas, Aug. 24, 2022 /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 a leadership transition and corporate restructuring to focus resources on AGLE-177 in development for patients living with Homocystinuria.

The restructuring has further reduced the headcount of the Company resulting in an approximately 25% reduction year-to-date. The Company also plans to realize additional cost savings by transitioning patients out of the ongoing extension studies of pegzilarginase in Arginase 1 Deficiency while it engages with the FDA on a regulatory path forward. The implementation of the restructuring plan will prioritize development of AGLE-177 and result in extending the Company's cash runway into the fourth quarter of 2023. 

"The restructuring announced today increases the operational focus and capital deployment towards success of the AGLE-177 program in Homocystinuria," said Russell J. Cox, chair of the board of directors of Aeglea. "We believe AGLE-177 has the potential to become the best-in-class treatment option for these patients and we believe focused execution of the current Phase 1/2 trial and its transition to late-stage development are key strategic priorities for Aeglea."

The Company announced that Anthony Quinn, M.B., Ch.B., Ph. D., president and chief executive officer, and member of Aeglea's board of directors, has stepped down from his current positions and transitioned to an advisory role effective immediately. The board of directors has appointed Jim Kastenmayer, Ph.D., J.D., the Company's current general counsel, as interim president and chief executive officer as the Company initiates a search for a permanent replacement. Additionally, the Company's chief commercial officer, Michael Hanley, has been appointed chief business officer with expanded responsibilities in internal business operations.

Mr. Cox continued, "On behalf of the board of directors, I want to thank Anthony for his leadership and unwavering commitment to patients during his tenure. Under his leadership, Aeglea has made substantial progress over the last five years with programs for ARG1-D and homocystinuria in clinical development and a research pipeline of other human enzyme-based therapeutics. He has built a strong, capable team with the experience to advance AGLE-177 through clinical and commercial development. Aeglea will continue to benefit from Anthony's scientific and clinical expertise, and I look forward to working with Anthony in his new role as an advisor to the Company."

"It has been an enormous privilege to have led the evolution of Aeglea from a research organization to a company with development, manufacturing and commercial capabilities," said Dr. Quinn. "I am honored to have worked with the incredible team at Aeglea and am very excited about Aeglea's upcoming milestones. I look forward to continuing my engagement with the company in an advisory role."

"I and the rest of the organization are excited to continue our work and focus on our mission to change lives by bringing innovative therapies to underserved rare disease communities. Delivering data from our Phase 1/2 trial for AGLE-177 later this year is our near-term focus in advancing this mission," said Mr. Kastenmayer.

AGLE-177 is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its 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 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. Preclinical data demonstrated that AGLE-177 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.

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality. The PEACE Phase 3 clinical trial met its primary endpoint with a 76.7% reduction in mean plasma arginine compared to placebo. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels. The arginine lowering was accompanied by a positive trend in Gross Motor Function Measure Part E, a measure of patient mobility.

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 AGLE-177 in an ongoing Phase 1/2 clinical trial for the treatment of Homocystinuria. AGLE-177 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.  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.

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 AGLE-177 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.

SOURCE Aeglea BioTherapeutics, Inc.