Company Logo Forward Looking Statements 2021 Aeglea BioTherapeutics. External 2 This presentation and the accompanying oral presentation contain "forward-looking" statements that are based on our management's beliefs and

Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview - September 2021 Exhibit 99.1 Company Logo

Forward Looking Statements 2021 Aeglea BioTherapeutics. External 2 This presentation and the accompanying oral presentation contain "forward-looking" statements that are based on our management's beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our current and future financial performance, business plans and objectives, current and future clinical and preclinical development activities, timing and success of our ongoing and planned clinical trials and related data, the timing of announcements, updates and results of our clinical trials and related data, our ability to obtain and maintain regulatory approval, the potential therapeutic benefits and economic value of our lead product candidate and our other product candidates, potential growth opportunities, financing plans, use and adequacy of financing plans, competitive position, industry environment and potential market opportunities.

Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors including, but not limited to, those related to the success, cost and timing of our product candidate development activities and ongoing and planned clinical trials; our plans to develop and commercialize targeted therapeutics, including our lead product candidate pegzilarginase and our other product candidates for the treatment of homocystinuria and cystinuria; the design, progress of patient enrollment and dosing in our clinical trials, the ability of our product candidates to achieve applicable endpoints in clinical trials, the safety profile of our product candidates in clinical trials, the potential for data from our current and future clinical trials to support a marketing application, as well as the timing of these events, the potential for preclinical studies to be predictive of current or future clinical trials, our ability to obtain funding for our operations, development and commercialization of our product candidates; the impact of the COVID-19 pandemic on our operations and clinical development activities, including on the timing of enrollment of our clinical trials; the timing of and our ability to obtain and maintain regulatory approvals; our ability to obtain regulatory approval for, and commercialize, pegzilarginase, and recognize milestone and royalty payments from our agreement with Immedica; the potential for expeditated development and review of pegzilarginase as of a result of its Breakthrough Therapy designation; the potential addressable markets of the our product candidates; the rate and degree of market acceptance and clinical utility of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our commercialization, marketing and manufacturing capabilities and strategy; future agreements with third parties in connection with the commercialization of our product candidates; our expectations regarding our ability to obtain and maintain intellectual property protection; our dependence on third party manufacturers; our ability to develop our own commercial manufacturing facility; the success of competing therapies that are or may become available; our ability to attract and retain key scientific or management personnel; our ability to identify additional product candidates with significant commercial potential consistent with our commercial objectives; and our estimates regarding expenses, future revenue, capital requirements and needs for additional financing.

Moreover, we operate in a very competitive and rapidly changing environment, and new risks may emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed herein may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Further information on these and other factors that could affect these forward-looking statements is contained in our most recent Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC) and other reports filed by the SEC. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances described in the forward-looking statements will be achieved or occur. We undertake no obligation to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Company Logo

Addressing Metabolic Imbalances to Improve the Lives of Patients 2021 Aeglea BioTherapeutics. External 3 Delivering Metabolic Harmony Aeglea BioTherapeutics (Nasdaq: AGLE)

At Aeglea, we believe that every patient deserves a chance at a better life. We are committed to helping people with rare and devastating metabolic diseases who have limited treatment options because having a rare disease doesn't mean that you are in the fight alone.

Unlocking the Potential of Human Enzymes to Deliver Life-Changing Solutions for People with Rare Metabolic Diseases 2021 Aeglea BioTherapeutics. External 4 PEGZILARGINASE IN ARGINASE 1 DEFICIENCY AGLE-177 IN

HOMOCYSTINURIA ENZYME THERAPEUTICS

PLATFORM Enhanced human arginase that enzymatically lowers arginine levels PEACE - pivotal Phase 3 trial Novel recombinant human enzyme that enzymatically lowers homocysteine levels Phase 1/2 trial Rare metabolic disease monogenic focus Most advanced program in Cystinuria Cash, cash equivalents and marketable securities as of June 30, 2021: $130.41 million (no debt)

Expected funding runway: into 2023 1Includes $1.8mm of restricted cash

Looking Beyond the Conventional with Next Generation Human Enzyme Therapeutics 2021 Aeglea BioTherapeutics. External 5 Specialized expertise in human enzyme engineering

Distinctive disease selection approach

Validated metabolite targets

Translatable disease models

Reduced toxicology risk Established manufacturing approach

Faster, smaller clinical trials

Innovative trial design to meet needs of patient communities

Favorable regulatory access Patient-centric mindset to ensure access to impactful therapies

Attractive reimbursement potential

Substantial barriers to entry

Highly efficient and targeted approach Discovery Development and regulatory Commercial Expertise and focus in rare genetic disease Efficient and agile development process Tailored, innovative market approach Company Logo

Rethinking the Potential of Human Enzyme Therapeutics 2021 Aeglea BioTherapeutics. External 6 1.Ex-U.S. license and supply agreement with Immedica to commercialize pegzilarginase in Europe and certain countries in the Middle East (European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Bahrain and Oman) 2. ARG1-D case reports ; Diez-Fernandez et al. Mutations and common variants in the human arginase 1 (ARG1) gene: impact on patients, diagnostics and protein structure considerations. Hum Mutat. 2018 Aug;39(8):1029-10502. 3. >30,000 represents estimated prevalence of Classical Homocystinuria in 38 addressable markets based on results of U.S. ICD-10 claims analysis extrapolated to global markets; all figures rounded. Sellos-Moura et al 2020 4. Castro Pereira DJ et al 2015; Leslie and Nazzal Renal Calculi (Cystinuria, Cystine Stones) (2018) Reference; Rozanski et al, Mil Med (2005); Soucie et al, JM Kidney Int (1994); Claes & Jackson, Pediatr Nephrol (2012) 27, 2031; Chillaro n, J. et al. Nat. Rev. Nephrol. 2010, 6, 7, 424-34; Biyani, C.S and Cartledge, J.J. EAU-EBU Update Series, 2006, 4, 175-183; Mattoo, A. and Goldfarb D.S. 2008 Sem. Nephrol, 28, 2, 181-191; >10,0004

Patients Program Indication Research Phase 1/2 Phase 3 Approved Addressable Market Pegzilarginase1 Immedica Arginase 1 Deficiency >2,5002 Patients AGLE-177 Homocystinuria >30,0003 Patients Research Programs Cystinuria Undisclosed Rare Diseases Company Logo

Pegzilarginase for Arginase 1 Deficiency

Pegzilarginase Program Overview 2021 Aeglea BioTherapeutics. External 8 Arginase 1 Deficiency (ARG1-D)

ARG1-D is a serious, progressive disease with early mortality and high unmet medical need due to an autosomal recessive disorder of arginine metabolism. Addressable Market: >2,500 patients

Genetic prevalence estimates U.S. Rare Pediatric Disease (PRV eligible)

Breakthrough Therapy

EU Orphan Drug Regulatory Designations: The Progressive Impact of Persistently High Plasma Arginine1-4 Infancy2-4,7,8 Initial 6-12 months may be uneventful

May present with seizures, episodes of hyperammonemia: irritability, feeding difficulties, poor appetite, nausea/vomiting, decreased alertness

>500 patients in US and EU4 + UK

>65% of U.S. genetic prevalent population identified

1. Diez-Fernandez C, et al. Hum Mutat. 2018;39:1029-1050. 2. Carvalho DR, et al. Pediatr Neurol. 2012;46:369-374. 3. Crombez EA, Cederbaum SD. Mol Genet Metab. 2005;84:243-251. 4. De Deyn PP, et al. Hyperargininemia: a treatable inborn error of metabolism. In: Guanidino Compounds in Biology and Medicine. London, UK: John Libbey Company Ltd.; 1997:53-69. 5. Prasad A, et al. J Child Neurol. 1997;12:301-309. 6. Amayreh W, et al. Dev Med Child Neurol. 2014;56:1021-1024. 7. Scaglia F, Lee B. Am J Med Genet C Semin Med Genet. 2006;142C:113-120. 8. Sin YY, et al. J Mol Med (Berl). 2015;93:1287-1296. 9. Cai X, et al. Medicine (Baltimore). 2018;97:e9880. 10. Schlune A, et al. J. Amino Acids. 2015;47:1751-1762. 11. Sun A, et al. Arginase deficiency. In: Adam MP, et al, eds. GeneReviews . Seattle, WA: University of Washington, Seattle; 2020. 12. Diaz GA, et al. Poster presented at: 13th European Paediatric Neurology Society (EPNS) Congress; September 17-21, 2019; Athens, Greece. Poster P06-34. Toddlerhood (2-4 years) 2,3,7-9 Spasticity in lower limbs (tiptoe walking)

Seizures, avoidance of protein is common and intellectual disability Childhood (5-10 years) 2,3,5,6,9 Progressive spasticity and growth impairment

Declining neuromotor and intellectual capabilities

Increasing dependence on walking aids

Decrease/loss of vocabulary/language

Adolescence (11-17 years)2,3,5,10 Potential loss of ambulation and bowel/bladder control

Severe intellectual disability Adulthood (18+ years) 2,3,11,12 Continued decline with increasing disability that may result in early mortality Enrollment completed in Phase 3 pivotal trial

Topline data in Q4 2021

Status: Company Logo

KEY AREAS: Arginase 1 Deficiency Patient Needs Not Adequately Addressed No treatments or approved therapies that effectively reduce arginine levels 2021 Aeglea BioTherapeutics. External 9 Current standard of care:

Severe dietary protein restriction

Amino acid supplementation

Ammonia scavengers Current disease management is inadequate:

Limited effectiveness

Challenging to maintain

Doesn't address non-dietary sources of arginine Delayed and un/misdiagnosed patients due to lack of disease awareness Patients not reaching target arginine levels with their current disease management strategy Ineffective treatment options result in disease progression and poor outcomes 1. 2. 3. Company Logo

Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels 2021 Aeglea BioTherapeutics. External 10 Plasma Arginine in Response to Pegzilarginase in Phase 1/2 + OLE Studies Baseline:

Baseline plasma arginine on standard disease management was markedly elevated

Median plasma arginine was 112 M

Median plasma arginine reduction was 277 M

Median plasma arginine was 99 M

10/13 patients achieved plasma arginine within the normal range (40-115 M)

13/13 patients achieved plasma arginine within the target range (<200 M) OLE - Open-label extension

1 Diaz, GA, et al, J Inherit Metab Dis. 2021;44:847-856; 2. Diaz, GA et al, Presented at 2020 European Academy of Neurology Annual Meeting 389 171 127 112 99 Line Chart Company Logo

Mobility Assessments Capture Clinical Benefit with Pegzilarginase in Phase 1/2 Trial 2021 Aeglea BioTherapeutics. External 11 Continuous Analysis

Mean Change from Baseline GMFCS - Level II/III GMFCS - Level I CE = Ceiling Effect 20 Week Analysis: 11/14 (79%)

56 Week Analysis: 11/13 (85%) Categorical Responder Analysis2 1Adapted from Diaz, GA et al, Presented at 2020 European Academy of Neurology Annual Meeting; 2Clinical Responder defined by achievement of a clinically meaningful response in one or more of three mobility assessments; GMFCS = Gross Motor Function Classification System Change from Baseline at 56 Week Analysis1 Not Assessed Not Assessed CE CE Green = Overall Clinical Responder1 Patient # GMFM-E (Units) 6MWT (Meters) Baseline Deficit 151 Endpoint Analysis 20 weeks 56 weeks GMFM-E Overall 5 units 6 units Baseline Deficit 8 units 9 units 6MWT Overall 32 m 45 m Bar Chart Company Logo

Safety Summary 2021 Aeglea BioTherapeutics. External 12 Clinical data shows pegzilarginase has a favorable safety profile

Approximately 1,8501 doses administered

Approximately 5001 intravenous doses

Most treatment-related adverse events were mild

The frequency of treatment-related adverse events decreased over time

Hypersensitivity and hyperammonemia were the most common treatment-related serious adverse events; expected and manageable 1Dose data as of June 11, 2021 Phase 1/2 Trial and Open Label Extension Study of Pegzilarginase in Arginase 1 Deficiency Company Logo

PEACE Trial Design - Single Global Pivotal Phase 3 Trial to Support Registration 2021 Aeglea BioTherapeutics. External 13 *Dosing is weekly and, if needed, modified based on plasma arginine levels with maintenance of blinding.

The first 8 weeks of the open-label extension will be blinded. All study participants remain on current disease management for the duration of the trial. Dose adjustments in the double-blind treatment period can be made to optimize plasma arginine control for levels outside the range of 50-150 M. If needed, weekly doses can be increased to 0.15 and 0.2 mg/kg or reduced to 0.05mg/kg

ARG1-D = Arginase 1 Deficiency; IV = intravenous; R = randomized. Topline data

Q4 2021 Patients with ARG1-D 2 years old Plasma arginine >250 M (mean) Baseline deficit in clinical response assessments R 2:1 Pegzilarginase 0.1 mg/kg* IV Placebo IV Open-label extension 3-4 weeks 24 weeks Up to 150 weeks Key Endpoints Analysis Rationale Primary: Plasma arginine reduction Reduction of plasma arginine compared to baseline vs placebo Based on key role of elevated arginine levels in the development and progression of clinically important disease manifestations Secondary: GMFM-E (Walking, running & jumping) Timed Walk Test (2MWT) Continuous analysis Improvement compared to baseline vs placebo Previous trial results support utility of GMFM-E in capturing baseline disease burden and clinical impact of treatment Timed walk test provides complementary insights on mobility improvements and is especially useful for GMFCS level 1 patients Simplifies analysis and reduces complexity of statistically controlling for multiple comparisons Company Logo

Attractive Commercial Opportunity for Pegzilarginase in ARG1-D 2021 Aeglea BioTherapeutics. External 14 1 Licensing and supply agreement signed with Immedica PLC in March 2021; agreement covers countries in the European Economic Area and certain countries in the Middle East, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Bahrain and Oman. Severe and progressive disease with early mortality

Easily diagnosed with simple lab test or genetic testing

No FDA-approved therapies to address underlying driver of disease

Inadequate management options in severe protein-restricted diet, amino acid supplementation, and ammonia scavengers

Suboptimal control of plasma arginine levels

Poor patient compliance due to challenges with administration Significant Unmet Need Prevalence of >2,500 Patients in Key Global Markets United States

>250 patients Western Europe and Middle East1

>900 patients Rest of World

>1,350 patients (including 700 in LatAm, 400 in Asia Pacific) Company Logo

Building the Foundation for a Successful Launch and Enduring Commercial Presence 2021 Aeglea BioTherapeutics. External 15 Patient Identification Accelerating the diagnosis and identification of patients through ongoing HCP engagement Disease Education and Awareness Driving HCP dialogue about

the devastating and progressive nature of ARG1-D Access and Reimbursement Ensuring payer understanding of the significant clinical and economic burden of ARG1-D Organizational

Readiness Establishing an internal mindset and infrastructure to meet the needs of the ARG1-D patient community

Engaging with HCP and Patient Communities to Accelerate Diagnosis, Broaden Awareness, and Deepen Understanding of ARG1-D 2021 Aeglea BioTherapeutics. External 16 Continued patient identification momentum across key markets

Results outpacing relevant benchmarks

>65% of the estimated U.S. genetic prevalence identified

Driving increased recognition and understanding of ARG1-D

THINK ARGININE : a disease awareness initiative with no-charge diagnostic testing

Engagement with key institutions responsible for significant proportion of patients

Ongoing scientific discourse to broaden awareness and deepen ARG1-D understanding and advocacy among HCP community

Thoughtful engagement with the patient community to strengthen understanding of patient journey and unmet needs Patient Identification Disease Education and Awareness Company Logo

Laying the Groundwork to Transition Smoothly to Commercial Operations 2021 Aeglea BioTherapeutics. External 17 Preliminary planning around patient services based on our deep understanding of the needs of the ARG1-D patient community

Payer profiling to understand likely coverage policies at launch

Initial payer dialogue providing key insight into disease understanding, educational opportunities, and management approaches Core commercial team in place with deep ultra-rare launch experience

Commercial formulation on stability and distribution strategy in place

High-touch patient services approach in development

Commercial infrastructure built with pegzilarginase and earlier-stage pipeline programs in mind Access and Reimbursement Organizational Readiness Company Logo

Pegzilarginase Program - Key Highlights and Next Steps 2021 Aeglea BioTherapeutics. External 18 Sustained control of plasma arginine

85% (11/13) of patients at the 56 week analysis were clinical responders

Well tolerated and the rates of treatment-related adverse events decreased over time Primary endpoint: arginine reduction; secondary endpoints: clinical outcomes, safety and PK

32 patients, randomized 2:1 (pegzilarginase: placebo)

24 weeks dosing period