Lens Subluxation

Streamlining of organization to focus on near-term deliverables for pegtarviliase in Homocystinuria and long-term value creation Cortney Caudill, M.B.A., has been promoted to the newly created role of chief product officer to increase focus and efficiency in the advancement of clinical programs AUSTIN, Texas, Jan. 6, 2023 /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 an update to its corporate structure. These changes are in addition to the restructuring process that was initiated in August 2022 and are intended to further streamline the organization, create operational efficiencies to support near- and long-term objectives and maximize the value of the company's two clinical programs. As part of these additional changes, the workforce of the company has been further reduced by approximately 15%. Aeglea is also halting the preclinical work on the Cystinuria and other unnamed pipeline programs. The company will evaluate potential strategic options for these programs in order to maximize value. In conjunction with these announcements, Cortney Caudill has been promoted from senior vice president of technical operations to chief product officer, effective January 6, 2023. In this expanded role, Ms. Caudill will be a strategic leader, team supervisor, and internal advocate for Aeglea's clinical programs, helping the company focus on key deliverables and resource allocation for both Homocystinuria and Arginase 1 Deficiency programs. In addition, Leslie Sloan, Ph.D., will be departing from her role as chief operating officer. "Since joining as CEO, my focus has been on reviewing all aspects of the pipeline and determining the needs for achieving our short-term objectives and enabling long-term value creation. I believe the streamlining of the organization, the continued focus on pegtarviliase and the promotion of Cortney into a newly created product leadership role will help us achieve our goals in 2023 and set us up for future success," said Jeffrey Goldberg, president and chief executive officer of Aeglea. "This is a critical moment of change for the company. It is unfortunate that a group of talented and respected employees have been impacted. We value their important contributions to the company and are committed to provide support as they work through this transition. While this is a difficult decision, we believe it is in the best path to serving our most important stakeholder – the patients and their families." Ms. Caudill joined Aeglea in 2019 and has served as a valued leader of the company's manufacturing, technical operations and pegtarviliase program teams. She has over 25 years of experience in the biotechnology and healthcare industry including leadership roles in manufacturing, site build and startup, quality, program management and business development. Prior to joining Aeglea, she was the head of Baxalta's Global Drug Product External Manufacturing Network and she was located in Zurich, Switzerland with responsibility for over 20 commercial and pipeline products. Ms. Caudill has held various roles of increasing responsibility at Cambrex, Vaxgen, Genentech, Vetter Pharma and Samsung Biologics, and started her career in the U.S. Air Force. She holds a B.S. in Biology and a B.A. in Psychology from The University of Texas as well as an M.B.A from Fordham University. "I am excited to take on this new role as we continue to focus our efforts on enrolling the Homocystinuria trial for pegtarviliase and advancing pegzilarginase through the regulatory process," said Ms. Caudill. "I'm confident in the experience and knowledge of our teams and our ability to execute in delivering on the potential of these important programs for patients and their families." About Pegtarviliase in Homocystinuria Pegtarviliase 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 Pegzilarginase in Arginase 1 Deficiency 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. 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. 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 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 Classical 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 September 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.

AUSTIN, Texas, Nov. 30, 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 the appointment of Jeffrey M. Goldberg as president, chief executive officer and member of the board of directors effective November 29, 2022. Mr. Goldberg is an accomplished biotech executive with over 25 years of experience leading teams from preclinical discovery through commercialization and previously served as president and chief executive officer of Immunitas Therapeutics. "Jeff has successfully built and managed teams across a wide variety of functions, providing strong leadership and strategic direction. His breadth of experience spans from the founding of companies to overseeing successful global launches of rare disease therapies," said Russell J. Cox, chair of the board of directors of Aeglea. "His proven ability to match business capabilities to unmet patient needs and then drive the strategy and execution needed to achieve those goals will be an important asset to Aeglea. I look forward to working closely with Jeff and welcome him to the Aeglea team." "To me, the most important and fulfilling part of my job has been being able to bring therapies forward that have had significant impact on patients' lives. Aeglea shares that mission and has built world-class programs in Homocystinuria and Arginase 1 Deficiency with the potential to benefit all the key stakeholders, including employees, shareholders, physicians, and most importantly patients and their families," said Mr. Goldberg. "I'm incredibly excited to be joining the team and helping to facilitate the mission of developing novel medicines for patients battling devastating diseases." Mr. Goldberg served as president and chief executive officer at Immunitas from 2019-2021. Under his leadership, Immunitas grew significantly, raised additional capital, and is now in the clinic with its first asset. Prior to joining Immunitas, Mr. Goldberg served as the founding chief operating officer at Akcea where he was responsible for building functions and leading teams across all aspects of the business and eventually grew the team from two employees to over 250 in multiple geographies. Mr. Goldberg played a significant role in the company's initial public offering and fundraising activities, business development and the global launch of two rare disease drugs. Prior to Akcea, he was the vice president of business operations at Proteostasis Therapeutics, a rare disease company. He also held roles of increasing responsibility at Genzyme, where he led teams through product development and global launches across multiple therapeutic areas. Mr. Goldberg has an MBA and a MS in Chemical Engineering from the Massachusetts Institute of Technology, and a B.S. in Chemical Engineering from Cornell University. Jim Kastenmayer, JD, PhD, will step down as interim chief executive officer and retain his position as Aeglea's general counsel. "On behalf of the entire board of directors, I want to thank Jim for his service and commitment to Aeglea and its mission. Jim has provided exceptional leadership during a period of critical execution and has kept the team focused on advancing the Homocystinuria program," said Mr. Cox. Following the leadership transition and as part of the related evaluation of near-term corporate and clinical development strategy, Aeglea no longer plans to announce interim clinical data from the ongoing Phase 1/2 clinical trial of pegtarviliase in Classical Homocystinuria in the fourth quarter of 2022. Enrollment in the third cohort of the Phase 1/2 trial is ongoing with two patients having completed dosing in the cohort. Additionally, the company has decided not to participate in the Piper Sandler 34th Annual Healthcare Conference and 5th Annual Evercore ISI HealthCONx Conference, both being held November 29-December 1, 2022. Aeglea looks forward to delivering a clinical update on the pegtarviliase program when more comprehensive data from the third cohort becomes available. About Classical Homocystinuria Classical Homocystinuria, also known as CBS deficiency, is a serious, progressive metabolic disorder characterized by elevated levels of total homocysteine. The accumulation of total homocysteine leads to a wide range of life-altering complications and even death from sudden catastrophic events. Serious disease complications may include thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis and Marfanoid features), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Currently, there are no approved treatments that address the underlying driver of disease. 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 . 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 Classical 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 September 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.

Top-line Phase 1 data in healthy volunteers show that SYNB1353 reduces plasma methionine by consuming methionine in the GI tract SYNB1353 has been granted Orphan Drug Designation (ODD) from the FDA for the treatment of homocystinuria (HCU) Company confirms expectations for proof-of-concept data for SYNB8802 in enteric hyperoxaluria before year-end and Phase 3 initiation of SYNB1934 for PKU in H1 2023 Organization streamlined to best support strategic priorities CAMBRIDGE, Mass., Nov. 30, 2022 (GLOBE NEWSWIRE) -- Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company developing medicines for metabolic and immunological diseases through its proprietary approach to synthetic biology, today announced that SYNB1353 has achieved proof of mechanism and positive results in a Phase 1 study in healthy volunteers treated with multiple ascending doses of SYNB1353. SYNB1353 is an orally administered, non-systemically absorbed drug candidate designed to consume methionine in the GI tract for the potential treatment of homocystinuria (HCU). The Company also shared that the FDA has granted Orphan Drug Designation (ODD) to SYNB1353 for the treatment of HCU. ODD is granted by the FDA to drugs or biologics intended to treat a rare disease or condition, which generally affects less than 200,000 individuals in the U.S. ODD-granted therapies entitle companies to development incentives including tax credits for qualified clinical trials, user fee exemptions, and the potential for seven years of market exclusivity after approval. Following the recent successful completion of the Company’s Phase 2 study in phenylketonuria (PKU), and now with proof of mechanism achieved in the Phase 1 for HCU, the Company also shared a plan to focus on advancing its clinical stage and prioritized preclinical research programs. Top-line Findings: The goal in treating HCU is to reduce and control severely elevated levels of total homocysteine (tHcy), thereby reducing risk of acute, potentially life-threatening blood clots and chronic, multisystem complications. A diet low in methionine, a precursor to homocysteine, is standard in HCU; SYNB1353 is engineered to metabolize methionine in the GI tract to prevent its absorption and conversion into homocysteine. An objective of this Phase 1 study was to assess effects of methionine consumption by SYNB1353 in healthy volunteers, assessed primarily through a dietary model using a methionine meal challenge. This dietary model was intended to capture in healthy volunteers a transient elevation in methionine following a meal challenge, in order to demonstrate proof of mechanism of consumption of methionine by SYNB1353. Top-line findings include: Dosing of SYNB1353 resulted in a reduction in plasma methionine when measured over 24-hours as area under the curve (AUC) following a methionine meal challenge. SYNB1353 was generally well tolerated. Adverse events (AEs) were all mild to moderate, transient, and predominantly GI in nature. Frequency and severity of GI-related AEs were similar in the active and control group. “We are pleased to share this important milestone for our HCU program and our second positive data readout for the Synthetic Biotic platform in 2022,” said Aoife Brennan, M.B. Ch.B., Synlogic President and Chief Executive Officer. “HCU is an extremely challenging disease and patients need new treatment options. The difficulty of current treatments, including the low methionine diet, results in many patients remaining at risk of life-threatening consequences. We are very pleased that SYNB1353 has demonstrated promise to provide a safe, oral treatment option through its novel approach, and look forward to its continued development, including evaluation for proof of concept in HCU patients.” “With today’s favorable study results, we are also sharing news of our realigned organization, now optimized to execute against our strategic priorities and create a stronger, more agile company. We are grateful for the dedication of our departing colleagues to our mission. Their tremendous contributions have helped us pioneer Synthetic Biotics, and most of all, provided hope to many patients and families in need of new treatments.” The SYNB1353 Phase 1 Study The phase 1 study included a double-blind, dose-escalation, randomized, placebo-controlled, multiple-ascending dose (MAD) design in healthy volunteers in an inpatient setting. The objectives were to evaluate the safety and tolerability, assess clearance measured with quantitative polymerase chain reaction following dosing, and evaluate the pharmacodynamic effects on plasma methionine following a methionine loading study, providing a dietary model of HCU. Synlogic has completed dosing of 30 total subjects over four cohorts which evaluated three different dose levels (3x1011, 6x1011 and 1x1012 live cells) and two different formulations at the 1x1012 dose. In each cohort, the subjects were randomly assigned to receive either SYNB1353 or a placebo (6 active/2 placebo per cohort). A methionine loading study was performed on day -1 and day 7 after an overnight fast, followed by a 24-hour collection period for the AUC assessments. Subjects were followed in the study for at least 28 days after the last dose. At the 1x1012 dose, SYNB1353 decreased plasma methionine levels, as measured by the change in AUC from baseline, by -24.8% (95% CI -36.7,-10.6) and -26.2% (95% CI -39.0,-10.9) for the two different SYNB1353 formulations, compared to -2.1% (95% CI -15.7, 13.7) in the placebo group. There were no serious adverse events (SAEs). One subject discontinued dosing due to an adverse event (AE). AEs were mild to moderate, transient and predominantly GI in nature. Frequency and severity of GI-related AEs were similar in the SYNB1353 and placebo groups (7 of 22 SYNB1353 compared to 3 of 8 placebo subjects had at least 1 GI-related AE). All subjects completing the 28-day analysis cleared SYNB1353 in feces. Full results of the study will be presented at a future medical meeting. Organizational Changes To focus resources on advancing and optimizing the value of the Company’s clinical stage and prioritized preclinical research programs, Synlogic has implemented a structural realignment, including a reduction in the Company’s workforce by 25%, which is expected to extend its cash runway into the second half of 2024. The Company estimates that it will incur approximately $0.8 million of costs in connection with the reduction in workforce related to severance pay and other related termination benefits. The Company communicated the workforce reduction on November 30, 2022 and expects the majority of the costs associated with the reduction in force plan to be incurred during the fourth quarter ending December 31, 2022 and the first quarter ending March 31, 2023. The Company may also incur other material charges not currently contemplated due to events that may occur as a result of, or associated with, these actions. Next Steps Synlogic also confirmed the following anticipated milestones: Share proof of concept data for SYNB8802 for enteric hyperoxaluria in Q4 2022 Initiate Phase 3 pivotal study of SYNB1934 for PKU in H1 2023 About Homocystinuria (HCU) & SYNB1353 HCU is a rare metabolic disease and inborn error of metabolism characterized by extreme levels of homocysteine and caused by an inherited deficiency in an enzyme known as cystathionine beta-synthase (CBS). When CBS is absent, homocysteine builds up in the blood and urine, putting patients at risk of multisystem complications, including acute thromboembolic events, optical damage from lens dislocation, skeletal deficiencies, and neurocognitive impairments. SYNB1353 is a novel, orally administered, non-systemically absorbed drug candidate designed to lower homocysteine levels in patients with HCU by consuming methionine, a precursor to homocysteine, in the gastrointestinal tract. It is the first drug candidate developed through a research collaboration between Synlogic and Ginkgo Bioworks and the first investigational medicine developed on Ginkgo's platform to enter the clinic. The U.S. Food and Drug Administration (FDA) granted Fast Track designation and Orphan Drug Designation (ODD) to SYNB1353 for the potential treatment of HCU. Synlogic holds worldwide development and commercialization rights to SYNB1353. About Synlogic Synlogic is a clinical-stage biotechnology company developing medicines through its proprietary approach to synthetic biology. Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to start a pivotal, Phase 3 study in the first half of 2023, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s reproducible, target-specific drug design. Synlogic uses programmable, precision genetic engineering of well-characterized probiotics to exert localized activity for therapeutic benefit, with a focus on metabolic and immunological diseases. In addition to its clinical programs, Synlogic has a research collaboration with Roche on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease or IBD. Synlogic has also developed two drug candidates through a research collaboration with Ginkgo Bioworks: SYNB1353, designed to consume methionine for the potential treatment of HCU, and SYNB2081, designed to lower uric acid for the potential treatment of gout. For additional information visit . Forward-Looking Statements This press release contains "forward-looking statements" that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, clinical development plans, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words "may," "could," "should," "anticipate," "believe," “look forward,” "estimate," "expect," "intend," on track,” "plan," "predict" and similar expressions and their variants, as they relate to Synlogic, may identify forward-looking statements. Examples of forward-looking statements, include, but are not limited to, statements regarding the potential of Synlogic's approach to Synthetic Biotics to develop therapeutics to address a wide range of diseases including: inborn errors of metabolism and inflammatory and immune disorders; our expectations about sufficiency of our existing cash balance; the future clinical development of Synthetic Biotics; the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology; and the expected timing of Synlogic's clinical trials of SYNB1618, SYNB1934, SYNB1353, SYNB8802 and SYNB2081 and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statements as a result of various factors, including: the uncertainties inherent in the clinical and preclinical development process; the ability of Synlogic to protect its intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading "Risk Factors" in Synlogic's filings with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Synlogic's current views with respect to future events. Synlogic anticipates that subsequent events and developments will cause its views to change. However, while Synlogic may elect to update these forward-looking statements in the future, Synlogic specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Synlogic's view as of any date subsequent to the date hereof. MEDIA CONTACT: INVESTOR CONTACT: Bill Berry Berry & Company Public Relations Phone: 212-253-8881 Email: bberry@berrypr.com Andrew Funderburk Kendall Investor Relations Phone: 617-401-9152 Email: afunderburk@kendallir.com