Disclosures The information contained in this presentation has been prepared by Aeglea Biotherapeutics, Inc. and its affiliates, including Spyre Therapeutics, Inc. ("Spyre" or the "Company") and contains information pert

CORPORATE OVERVIEW September 2023

Disclosures The information contained

in this presentation has been prepared by Aeglea Biotherapeutics, Inc. and its affiliates, including Spyre Therapeutics, Inc. ("Spyre" or the "Company") and contains information pertaining to the business and operations of

the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subject to change without notice, and is based on publicly available information, internally developed data as well as third party information

from other sources; (b) does not purport to contain all the information that may be necessary or desirable to fully and accurately evaluate an investment in the Company; (c) is not to be considered as a recommendation by the Company that any person

make an investment in the Company; (d) is for information purposes only and shall not constitute an offer to buy, sell, issue or subscribe for, or the solicitation of an offer to buy, sell or issue, or subscribe for any securities of the Company in

any jurisdiction in which such offer, solicitation or sale would be unlawful. Where any opinion or belief is expressed in this presentation, it is based on certain assumptions and limitations and is an expression of present opinion or belief only.

This presentation should not be construed as legal, financial or tax advice to any individual, as each individual's circumstances are different. This document is for informational purposes only and should not be considered a solicitation or

recommendation to purchase, sell or hold a security. Forward-Looking Information Certain information set forth in this presentation contains "forward-looking statements" within the meaning of applicable United States securities

legislation. Except for statements of historical fact, certain information contained herein constitutes forward-looking statements which include but are not limited to statements regarding: stockholder approval of the conversion rights of the Series

A Preferred Stock; the concurrent financing and acquisition and the expected effects, perceived benefits or opportunities and related timing with respect thereto; expectations regarding or plans for discovery, preclinical studies, clinical trials

and research and development programs; expectations regarding the use of proceeds and the time periods over which the Company's capital resources will be sufficient to fund its anticipated operations; the market and potential opportunities for

inflammatory bowel disease therapies; other activities, events or developments that the Company expects or anticipates will or may occur in the future; the Company's business strategy objectives and goals; and management's assessment of

future plans and operations which are based on current internal expectations, estimates, projections, assumptions and beliefs, which may prove to be incorrect. Forward-looking statements can often be identified by the use of words such as

"may", "will", "could", "would", "anticipate", believe", expect", "intend", "potential", "estimate", "scheduled",

"plans", "planned", "forecasts", "goals" and similar expressions or the negatives thereof. Forward-looking statements are neither historical facts nor assurances of future performance. Forward-looking

statements are based on a number of factors and assumptions made by management and considered reasonable at the time such information is provided, and forward-looking statements involve known and unknown risks, uncertainties and other factors that

may cause the actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements including those uncertainties and factors described under the heading "Risk Factors,"

"Risk Factor Summary" and "Cautionary Information Regarding Forward-Looking Statements" in Aeglea's Proxy Statement on Form 14A filed with the Securities and Exchange Commission ("SEC") on August 8, 2023, as

well as discussions of potential risks, uncertainties, and other filings by Aeglea from time to time, as well as risk factors associated with companies, such as Spyre, that operate in the biopharma industry. All of the forward-looking statements

made in this presentation are qualified by these cautionary statements and other cautionary statements or other factors contained herein. Although management believes that the expectations conveyed by forward-looking statements herein are reasonable

based on information available on the date such forward-looking statements are made, there can be no assurance that forward looking statements will prove to be accurate, as actual results and future events could differ materially from those

anticipated in such statements. The Company undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The

forward-looking statements contained herein are presented for the purposes of assisting readers in understanding the Company's plan, objectives and goals and may not be appropriate for other purposes. The reader is cautioned not to place undue

reliance on forward-looking statements. Industry Information This presentation also contains or references certain industry data that is based upon information from independent industry publications, market research, and surveys and other publicly

available sources. Although the Company believes these sources to be generally reliable, such information is subject to interpretation and cannot be verified with complete certainty due to limits on the availability and reliability of data, the

voluntary nature of the data gathering process and other inherent limitations and uncertainties. The Company has not independently verified any of the data from third party sources referred to in this presentation and accordingly, the Company makes

no representation or warranty as to the origin, validity, accuracy, completeness, currency or reliability of the information in this presentation.

Aeglea-Spyre Transaction highlights

Structure: The acquisition of Spyre was structured as a stock-for-stock transaction whereby all of Spyre's outstanding equity interests were exchanged for a combination of shares of Aeglea common stock and a newly created non-voting Series A

convertible preferred stock. Financing: Concurrent with the acquisition of Spyre, Aeglea closed a $210 million private placement with a group of institutional accredited investors led by Fairmount Funds and joined by a robust syndicate of

dedicated biotechnology investors as well as additional undisclosed institutional investors. Primary use of proceeds: The proceeds from the private placement are expected to be primarily used to advance the Spyre pipeline and deliver the

following anticipated milestones: two INDs for SPY001 and SPY002 in 2024, HV PK/PD data for SPY001 in 2H2024, and HV PK/PD data for SPY002 in 1H2025. Proceeds are expected to provide cash runway into 2026.

Capitalization As of 6/20/2023* Shares

of common stock outstanding 2.6 million Pre-funded warrants 1.2 million Merger consideration Shares of common 0.5 million Shares of preferred 0.4 million Preferred conversion ratio 1:40 Total pre-financing common equivalent 18.9 million Concurrent

financing Shares of preferred 0.7 million Common equivalent 28.9 million Total capitalization (Common) 47.7 million Shares of common stock and preferred stock were issued to Spyre security holders in exchange for all of Spyre's outstanding

equity interests. Shares of preferred stock were issued to Spyre stockholders and to investors in the $210 million private placement. Each share of preferred stock will automatically convert into 40 shares of common stock upon stockholder approval,

subject to certain beneficial ownership restrictions set by each holder. Please refer to the company's SEC filings for additional information. *Note: All figures have been retroactively adjusted to reflect the company's 1-for-25 reverse

stock split that will be effective as of 12:01 a.m. Eastern Time on September 8, 2023.

TARGET PROGRAM DISCOVERY IND-ENABLING

CLINICAL a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SPY004 a4b7 + IL-23 SPY130 a4b7 + TL1A SPY120 TL1A + IL-23 SPY230 Spyre aims to transform the treatment of IBD Opportunity

for best-in-class Long-acting antibodies SC with Q8-12W dosing Rational therapeutic combinations Precision patient selection PARALLEL LEAD PROGRAMS AGAINST HIGH VALUE TARGETS HV PK/PD data expected YE24 HV PK/PD data expected 1H25

Sources: Global Data, Evaluate Pharma,

UpToDate, SVB Leerink. Inflammatory bowel disease is a growing $21B market in which biologics are the preferred modality ~1.7M IBD patients diagnosed in the US. $29.1B Crohn's disease 2021 Global IBD Market $21.1B IBD represents

a multi-billion dollar market opportunity for best-in-class biologics. Biologics are the preferred modality for moderate-to-severe patients due to superior benefit-risk profile. IBD makes up 22% of the global $100B+ I&I market. $29B+ estimated

IBD market globally in 2028.

Sources: Global Data, Evaluate Pharma,

UpToDate, SVB Leerink. Inflammatory bowel disease is a growing $21B market in which biologics are the preferred modality ~1.7M IBD patients diagnosed in the US. $29.1B Crohn's disease 2021 Global IBD Market $21.1B IBD represents

a multi-billion dollar market opportunity for best-in-class biologics. Biologics are the preferred modality for moderate-to-severe patients due to superior benefit-risk profile. IBD makes up 22% of the global $100B+ I&I market. $29B+ estimated

IBD market globally in 2028.

Despite advances, new approaches are

needed to break the efficacy ceiling and improve convenience of biologics Summary data for select agents that randomize patients post response to induction; data from labels, company reports. Vedolizumab approved in US as Q8W IV - Q2W SC

approval pending following CRL in 2019. TL1A maintenance data not available. Orals not shown (pbo-adj maintenance remission rates): Jaks - tofacitinib (27%), upadacitinib (30% 15mg, 40% 30mg); S1Ps: ozanimod (19%); etrasimod (25% - P3 Treat-through

design). Maintenance dosing frequency (weeks) UC Maintenance Remission Rates (%) Spyre target vedolizumab infliximab vedolizumab SOC today

Spyre's strategy to address

unmet needs in IBD 1 2 3 Best-in-class mAb engineering With half-life extension technology Rational therapeutic combinations Precision patient selection Three strategic pillars in an effort to create the preeminent IBD company

Spyre mAbs introduce significant

improvements over 1st generation mAbs Epitopes maintained Validated pharmacology Equivalent or better potency Potential for IP into 2040s Novel dosing profile Improved manufacturability Coverage of diverse back-up series High concentration SQ

Ability to formulate at >150 mg/mL with low viscosity Citrate-free formulation Significantly extended half-life Q8-Q12W dosing based on validated half-life extension technology Spyre mAbs exploit validated biology with modifications designed for

best-in-class properties 1 2 3 CLINICAL PRECEDENT YTE mAbs WT mAbs

Spyre is rapidly developing

combination products given clinical evidence of substantial efficacy enhancement 1 2 3 CLINICAL PRECEDENT JNJ VEGA Ph2a study Clinical remission at 12 weeks Anti-TNF Anti-IL-23 % Source: Feagan, B. G. et al. Lancet Gastroenterol.

Hepatol. 8, 307-320 (2023) Strong single-agent induction efficacy Orthogonal MOA Strong single-agent maintenance efficacy Superior safety profile Enhanced induction and maintenance efficacy Rational therapeutic combinations Illustrative Best

single agent = 26% 4 7 TL1A N=72 N=71 N=71

genetically-driven patient selection to match disease drivers with therapeutic targets 1 2 3 CLINICAL PRECEDENT TL1A studies UC clinical remission at 12 weeks PRA023 RVT-3101 TL1A a4b7 IL-23 Genetic companion diagnostic (CDx)

leveraging large-scale human genomic datasets

Spyre is building a potentially

best-in-class IBD pipeline with next-generation mAbs and rational combinations STRATEGY TARGET PROGRAM1 DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23

SPY003 Novel MOA SPY004 Rational combinations a4b7 + IL-23 SPY130 Combination therapy a4b7 + TL1A SPY120 TL1A + IL-23 SPY230 Co-lead programs IND/CTN expected 2Q24 IND/CTN expected 2H24 HV PK/PD data expected YE24 HV PK/PD

data expected 1H25 1Spyre holds an option to license worldwide rights from Paragon Therapeutics, Inc. for all programs. SPY003 license is restricted to IBD, all other program licenses are indication agnostic

Spyre is building a potentially

best-in-class IBD pipeline with next-generation mAbs and rational combinations STRATEGY TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23

SPY003 Novel MOA SPY004 Rational combinations a4b7 + IL-23 SPY130 Combination therapy a4b7 + TL1A SPY120 TL1A + IL-23 SPY230 Co-lead programs IND/CTN expected 2Q24 IND/CTN expected 2H24 HV PK/PD data expected YE24 HV PK/PD

Vedolizumab is a mega-blockbuster

product in IBD Vedolizumab estimated $5.4B revenues WW in FY22.1 Projected to sell $7.5-9.0B at peak WW.1 1. Takeda JPM 2023 presentation. Note that Takeda's FY22 is April 2022-March 2023. Sales forecast in figure: EvaluatePharma consensus

"Biologic of choice for UC is Entyvio." - US KOL Significant market share: ~36% of UC market share and ~20% of CD market share in US.1 Global sales (2014-28F) $B US/EU % market share (June 2014-June 2022)

Vedolizumab specifically binds a4b7

integrin, selectively blocking gut lymphocyte trafficking. Leading maintenance efficacy data in UC replicated in two P3 studies; efficacy on par with upadacitinib 15mg dose; superior head-to-head vs adalimumab (Humira) in UC. Clean safety profile

since approval in 2014. #1 biologic in IBD bio-na ve patients in the US.1 1. Takeda JPM 2023 presentation. Figure data sources: Vedolizumab IV and SC data from VISIBLE 1 P3 study. Ustekinumab, adalimumab, infliximab, golimumab, ozanimod,

tofacitinib, upadacitinib data from labels. Mirikizumab data from phase 3 LUCENT-2 study. *Upadacitinib data shown in lighter red is 15mg preferred dose, darker red higher 30mg dose. Maintenance studies shown included patients who achieved clinical

response at induction. "Entyvio (vedolizumab) is the safest drug and one of the most effective for UC." - US KOL Vedolizumab maintenance efficacy and exquisite safety make it preferred biologic in moderate-to-severe UC Safest

Riskiest IL-23s TNF s S1P1s JAKs 4 7 UC Maintenance Efficacy Pbo-adjusted clinical remission % *

SPY001 is designed to be

a best-in-class anti- 4 7 mAb *Entyvio SC US BLA resubmitted April 2023 following CRL in 2019. Highly potent Proven epitope Selective No 4 1 binding, no VCAM-1 adhesion blocking Favorable safety profile High

maintenance efficacy Convenient SC dosing Q8W or Q12W+ Convenient formulation High concentration, citrate free Rapid efficacy onset Patient selection approach Genetic CDx SC* *Not approved in the US SPY001 IV Q8W IV infusion Citrate formulation

Potential upside Potential upside

Spyre mAbs introduce significant

improvements over 1st generation mAbs SPY001 Epitope maintained Validated pharmacology Equivalent potency Potential for IP into 2040s Diverse coverage of lead and backup series High concentration SC Ability to formulate at >150 mg/mL with

low viscosity Citrate-free formulation may improve patient comfort Significantly extended half-life Q8-Q12W dosing based on validated half-life extension technology SPY001 target profile: Efficacy vedolizumab Citrate-free subcutaneous 300 mg

dose Q8W or Q12W dosing interval SPY001 exploits validated 4 7 biology with modifications designed for best-in-class properties

SPY001 is as potent and selective

as vedolizumab in preclinical studies SPY001 binds the same 4b7 epitope as vedolizumab. SPY001 is comparable to vedolizumab in potency and avoids unwanted interactions with a4b1. a4 Subunit b7 Subunit SPY001 Epitope Blocking

MADCAM-1 Adhesion Blocking VCAM-1 Adhesion 1. Results are not based on a head-to-head trial.

SPY001 binds to memory T-helper

cells as well as vedolizumab 1. Soler, et. al. (2009) Vedolizumab EC50 (nM) SPY001 EC50 (nM) Donor 1 0.22 0.21 Donor 2 0.27 0.30 Donor 3 0.24 0.22 PBMCs from three human donors were isolated and stained with either vedolizumab or SPY001, as

well as a basic immunophenotyping T-cell panel. Both vedolizumab and SPY001 exhibited binding on the memory T-helper CD3+CD4+CD45RO+ population. EC50 values for both antibodies corresponded well with what has previously been reported for binding to

the same population: EC50 ~ 0.3 nM.1

SPY001 has exhibited a 17-day

half-life in NHPs, nearly 2x the half-life of vedolizumab observed in multiple studies -elimination half-life of SPY001 observed at ~17 days, 70% longer than observed for vedolizumab. Spyre vedolizumab data matches half-life

observed in Takeda studies.1,2 NOTE: 1BLA 125476, Vedolizumab. 2Crawford, D. and Friedman, M. (2019). In all cases, PK data was normalized to Cmax and fit to a biphasic exponential decay curve from which the -elimination half-life was