#1SPYRE THERAPEUTICS aeglea CORPORATE OVERVIEW 24 October 2023#2Disclosures 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 expected effects, perceived benefits or opportunities and related timing with respect to the June 2023 acquisition of Spyre Therapeutics, Inc. and the concurrent financing; 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 Preliminary 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. SPYRE | 2#3Targeting new heights in the treatment of IBD SPYRE THERAPEUTICS THREE-PILLAR STRATEGY Y KE OPPORTUNITY FOR BEST-IN-CLASS LONG-ACTING ANTIBODIES SUBCUTANEOUS (SC) Q8-12W DOSING RATIONAL THERAPEUTIC COMBINATIONS PRECISION IMMUNOLOGY PARALLEL LEAD PROGRAMS AGAINST HIGH VALUE TARGETS TARGET a437 TL1A IL-23 Novel MOA a437 + IL-23 a437 + TL1A TL1A + IL-23 PROGRAM SPY001 SPY002 SPY003 SPY004 SPY130 SPY120 SPY230 DISCOVERY IND-ENABLING CLINICAL Phase 1 interim data expected YE24 Phase 1 interim data expected 1H25#4Potential best-in-class lead programs DESIGN ATTRIBUTES SPY001 (α437) IDENTICAL EPITOPE TARGETING AS VEDOLIZUMAB COMPARABLE POTENCY AND SELECTIVITY AS VEDOLIZUMAB SC EXTENDED HALF-LIFE mAb TO ENABLE Q8-12W REGIMEN INTERIM HV PK DATA EXPECTED YE 2024 SPYRE SPY002 (TL1A) DUAL MONOMER AND TRIMER BINDER PICOMOLAR POTENCY AGAINST MONOMERS AND TRIMERS SC EXTENDED HALF-LIFE mAb TO ENABLE Q8-12W REGIMEN INTERIM HV PK DATA EXPECTED 1H 2025 COMBINATIONS ✓ONLY KNOWN PORTFOLIO WITH a437, TL1A, AND IL-23 ✓ POTENTIAL TO ADDRESS ORTHOGONAL BIOLOGY TARGETING UNIFIED SC Q8-12W DOSING INITIATION EXPECTED AFTER PH1 DATA 4#5Despite advances, new approaches are needed to break the efficacy ceiling and improve convenience of biologics UNMET NEED ~1.7 million individuals are currently diagnosed with IBD in the U.S.1 There remain substantial unmet needs in IBD management, including: co OO Inadequate response or loss of response to existing therapies Side effects and safety concerns associated with long-term medication use Adherence to frequent and/or inconvenient dosing regimens UC MAINTENANCE REMISSION RATES (%) 80 60 40 20 0 C vedolizumab buk adalimumab 2 SOC TODAY² mirikizumab golimumab vedolizumab ustekinumab infliximab 6 D 4 MAINTENANCE DOSING FREQUENCY (WEEKS) SPYRE TARGET 8 10 12 Source: ¹Crohn's and Colitis Foundation. 2Summary 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). SPYRE 14 5#6Our strategy is built on three validated approaches to address unmet needs in IBD BEST-IN-CLASS ANTIBODY ENGINEERING Y HALF-LIFE EXTENSION TECHNOLOGIES TO IMPROVE CONVENIENCE¹ RATIONAL THERAPEUTIC COMBINATIONS Y COMBINATION TARGETING TO ENHANCE REMISSION RATES² PRECISION IMMUNOLOGY APPROACHES GENETIC AND BIOMARKER SELECTION TO IDENTIFY MOST LIKELY RESPONDERS³ Sources: ¹ Several half-life extended antibodies are in clinical development, with at least two commercially approved (Evusheld, Beyfortus), Rosario, M, et. al. (2017); 2JNJ VEGA Phase 2 study demonstrated approximately additive efficacy with a TNFa and IL-23 combination (~47% clinical remission at week 12) versus monotherapies (25% and 24% remission rates, respectively, Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307-320 (2023); ³Prometheus Biosciences demonstrated a ~13% increase in clinical remission rates in CDx+ patients versus all-comers, Prometheus corporate materials SPYRE 6#7Spyre is building a potentially best-in-class IBD pipeline with next-generation mAbs and rational combinations STRATEGY Potentially best-in-class mAbs Rational combinations TARGET a437 TL1A IL-23 Novel MOA a437 + IL-23 a437 + TL1A TL1A + IL-23 PROGRAM¹ SPY001 SPY002 SPY003 SPY004 SPY130 SPY120 SPY230 DISCOVERY IND-ENABLING CLINICAL Phase 1 interim data expected YE24 Phase 1 interim data expected 1H25 ¹Spyre exercised its option to license worldwide rights from Paragon Therapeutics, Inc. for SPY001. Spyre continues to hold an option to license similar rights from Paragon for all other programs. SPY003 license will be restricted to IBD, all other program licenses will be indication agnostic. SPYRE 7#8SPY001 LONG-ACTING A4B7 ANTIBODY M#9SPY001 is designed to be a long-acting anti-a437 SPYRE IDENTICAL EPITOPE TARGET AS VEDOLIZUMAB COMPARABLE POTENCY AND SELECTIVITY AS VEDOLIZUMAB SUB-CUTANEOUS, EXTENDED HALF-LIFE mAb PREDICTED TO ENABLE Q8-12W DOSING TAI 9#10SPY001 potency & selectivity matches vedolizumab SPY001 & VEDOLIZUMAB EPITOPE SPY001 and vedolizumab bind the same epitope a4 Subunit POTENT & SELECTIVE BINDING TO a437 Antibody a437¹ a4³1 aEB7 K₂ <1 nM NB² NB² SPY001 B7 Subunit Source: Data on file. Vedolizumab K₂ <1 nM NB² 1Dissociation constant (K) measured by surface plasmon resonance (SPR) 2NB = no binding by a particular antibody to a test molecule SPYRE NB² POTENT AND SELECTIVE INHIBITION OF CELLULAR ADHESION SPY001 and vedolizumab potently inhibit MADCAM-1-mediated (gut) cellular adhesion %Inhibition of Total Adhesion (Integrin-mediated Adhesion by MADCAM-1) 70 60- 50- 40- 30- 20- 10- SPY001 (IC50 = 86 PM) ● Vedolizumab (IC50 = 83 PM) ● 0.01 0.1 1 mAb Concentration (nM) 10 No inhibition of unwanted VCAM-1- mediated (CNS) cellular adhesion %Inhibition of Total Adhesion (Integrin-mediated Adhesion by VCAM-1) 70 60 50 40- 30 20- 10 0 -10 ● SPY001 Vedolizumab Natalizumab (a431) 0.001 HO T 0.01 0.1 1 mAb Concentration (nM) 10 100 10#11SPY001 has exhibited ~2x the half-life of vedolizumab in NHPs DEMONSTRATED EXTENDED HALF-LIFE IN Tg276 MICE SPY001 t1/2: 10 Days Vedo t₁/2 : -3 Days Normalized Concentration (C/Co) 0.1 0.01 0.001 0.0001 --- 0 Source: Data on file. SPYRE 10 19 Days 20 H 30 DEMONSTRATED EXTENDED HALF-LIFE IN NHPs Normalized Concentration (C/C₂) 0.1 0 IGH 15 5 HOHO SPY001 t1/2:17 Days Vedo t1/2 : ~10 Days 10 Days KA Ho 15 20 11#12SPY001 Phase 1 clinical trial design. ● SINGLE-ASCENDING DOSE SAD 1 SC SAD 2 SC SPYRE SAD 3 SC Single-ascending dose cohorts Healthy volunteers N=8/cohort (3:1 randomization) Expected interim YE2024 readout to include 2-3 SAD cohorts and is sufficient to answer key objectives with PK modeling SAD 4 IV I I I I I ● MULTIPLE-ASCENDING DOSE ● MAD 1 SC Multiple-ascending dose cohorts Healthy volunteers N=8/cohort (3:1 randomization) Two doses MAD 2 SC 12#13We aim to demonstrate the following for SPY001 in the expected interim Phase 1 readout 1 2 3 4 SPYRE HALF-LIFE ENABLES Q8-12W SC MAINTENANCE DOSING BASED ON PK MODELING POTENTIAL TO ADDRESS VEDO'S SLOW ONSET OF ACTION WITH HIGHER INDUCTION EXPOSURES ESTABLISH SPY-001 HAS FAVORABLE SAFETY PROFILE AND IS WELL-TOLERATED MINIMAL TO NO IMPACT ON ADA RATES VS VEDOLIZUMAB 13#14Expected Phase 1 interim PK data informs dose and schedule modeling for target maintenance profile 1 SPY001 VEDO SPY001 HUMAN HALF-LIFE PREDICTIONS Half-life (days) Humans NHPs Humans NHPs 10 SPYRE Q8W based on PK modeling 17 25 -35 Q12W based on PK modeling -40 43-56 days Predicted range¹ MAINTENANCE PK SIMULATIONS Q12W SPY001 Dosing Simulation based on 50d half-life Concentration (µg/mL) Source: ¹Human YTE mAb half-life is on average 3.1x of NHP half-life; Rosario, M, et. al. (2017); 2Feagan, et. al. (2013) 100 80- 60 40 20 0 0 12 24 36 Weeks (At Steady-State) SPY001 SC Q12W VEDO IV Q8W 48 SPY001 Ctrough exceeds vedo by ~1.5x 6 ug/mL Ctrough associated with maximal efficacy² 14#15A half-life of 43-56 days in a 300mg SC format is expected to offer a superior product profile for patients MAINTENANCE DOSING PROFILE SPY001 SC 300 MG CITRATE FREE VEDOLIZUMAB SC 108 MG 20 MM CITRATE SPYRE 4-6 INJECTIONS PER YEAR 26 INJECTIONS PER YEAR M -AM HEND-- HD- am did POTENTIAL FOR SEASONAL DOSING HD CM² Cim EUODP -AMH HD- HDP HD- -lin CMH -C 15#16Expected interim PK data will also inform our ability to test induction exposure-response relationship in Phase 2 UPSIDE: GREATER REMISSION VIA HIGHER EXPOSURE 2 GEMINI I: WEEK 6 CLINICAL REMISSION RATES IN UC (%) Vedolizumab¹ trough concentration quartiles (µg/ml) 38% Q4 ≥35.7 Q3 25.0-35.7 Q2 17.1-25.0 Q1 ≤17.1 Vedo W6 PBO 7% SPYRE 6% 13% 17% 22% 37% INDUCTION PK SIMULATIONS SPY001 INDUCTION SIMULATION BASED ON 50-DAY HALF-LIFE Concentration (µg/mL) 150 100 50 0 +20% Higher anti-a437 mAb exposure may lead to more rapid remission Source: ¹Vedolizumab exposure-response data from Rosario, M., et. al. (2017); Vedolizumab FDA Clinical Pharmacology Review 0 SPY001 SC VEDO IV (per label) Quartile 4: 36 µg/mL 2 SPY001: ALL modeled patients above vedo Q4 trough concentration Weeks 4 6 16#17SPY001 is designed for fully SC induction dosing with upside efficacy potential SPY001 INDUCTION DOSING PROFILE VEDOLIZUMAB SPYRE SC INDUCTION DOSING IV INDUCTION DOSING -Am WO WO Chil W2 b- W2 AM W6 W6 PATIENT-ADMINISTERED UPSIDE POTENTIAL FOR ENHANCED EFFICACY REQUIRES PHYSICIAN ADMINISTRATION / OFFICE VISIT POTENTIALLY UNDER-DOSED 17#18SPY001 is designed to match vedolizumab's favorable safety profile and low rate of ADAs VEDO IS WELL TOLERATED WITH LOW IMMUNOGENICITY¹ 3 Infection rates Serious infection rates Adverse reaction rates Malignancy rates Infusion reactions Immunogenicity rates Vedolizumab 0.85 per patient-year 0.07 per patient-year SPYRE 52% (N=1434) 0.4% (N=1434) 4% (N=1434) 6% (N=1434) Placebo 0.70 per patient-year 0.06 per patient-year 45% (N=297) 0.3% (N=297) 3% (N=297) N/A Source: ¹Entyvio prescribing information; 2Rocca, A, et al. Int J of Mol Sci, 2021; ³Domachowske NEJM 2022 ADA RATES ARE SIMILAR FOR YTE AND WT ANTIBODIES2,3 4 100 80 60 40 20 0 YTE (Half-life extension) WT 0.4% Nirsevimab (MEDI-8897; YTE) N = 483 3.6% Palivizumab (non-YTE) N = 251 25.0% Motavizumab-YTE N = 16 20.0% Motavizumab N = 16 18#19SPY001 summary SPYRE 1000 COMPARABLE IN VITRO PERFORMANCE TO VEDOLIZUMAB 晋 HTDO PK MODELLING SUPPORTS Q8-12W SC DOSING; UPSIDE POTENTIAL FOR GREATER INDUCTION EFFICACY DEVELOPING PATIENT SELECTION APPROACHES TO IDENTIFY RESPONDERS INTERIM PHASE 1 PK DATA EXPECTED YE2024 19#20SPY002 POTENTIAL BEST-IN-CLASS TL1A ANTIBODY#21SPY002 is designed to achieve an optimal anti-TL1A product profile SPYRE DUAL MONOMER AND TRIMER BINDING PICOMOLAR POTENCY AGAINST MONOMERS & TRIMERS FULLY SC, EXTENDED HALF-LIFE mAb PREDICTED TO ENABLE Q8-12W DOSING 21#22Extensive discovery campaign pursued to identify an uncompromising TL1A antibody Heavily resourced campaign employing multiple strategies and formats enabled discovery of desirable TL1A clones Strategy 1 Strategy 2 Strategy 3 Strategy 4 SPYRE Format 1 Set A Set B Set C Set D Format 2 Set E Set F Format 3 Format 4 Set G Set H Set I 1000+ CLONES MONOMER AND TRIMER BINDER PICOMOLAR POTENCY EXTENDED HALF-LIFE POTENTIAL BEST-IN-CLASS TL1A 22#23SPY002 clones are unique in binding both monomers and trimers with picomolar potency SUPERIOR MONOMER AND TRIMER BINDING¹ Greater monomer binding (M) 10-⁹. 10-10. NO MONOMER BINDING 10-10 SPYRE RVT-3101 TEV-48574 SELECT SPYRE CLONES MK-7240 Greater trimer binding (M) Source: Nonclinical data on file. 1Compared to TEV-48574, RVT-3101, MK-7240 10-⁹ SUPERIOR TF-1 APOPTOSIS INHIBITION¹ 100- %Inhibition TF-1 Apoptosis 50 0₁ 0.01 HAHH TOTECHO EN H H TEV-48574 RVT-3101 MK-7240 SELECT SPYRE CLONES 0.1 1 10 Antibody Concentration (nM) 100 23#24SPY002 is a potential best-in-class TL1A mAb Complete TL1A blockade Monomer and trimer Picomolar trimer potency Half-life extension Q8-12W dosing Source: Company materials SPYRE SPY002 MK-7240 RVT-3101 TEV-48574 24#25SPY002 is potentially the most advanced unencumbered TL1A in development Announcement dates: Source: Company press releases SPYRE April 16, 2023 MERCK Prometheus Biosciences $10.8B acquisition Global rights Oct 3, 2023 sanofi teva 50-50 licensing deal $0.5B upfront +$1B in milestones North America, Japan, Asia rights Oct 23, 2023 Roche roivant Telavant $7.1B acquisition +$150M near-term milestone U.S. and Japan rights 25#26SPY002 summary 1000 LEAD CLONES ARE MONOMER AND TRIMER BINDERS WITH POTENCY DESIGNED TO BE SUPERIOR TO SELECT ANTIBODIES SPYRE HI HUDO- ONLY KNOWN EXTENDED HALF-LIFE TL1A ANTIBODY IN DEVELOPMENT DEVELOPING PATIENT SELECTION APPROACHES TO IDENTIFY RESPONDERS INTERIM PHASE 1 PK DATA EXPECTED 1H2025 26#27ل ل ل ل THERAPEUTIC COMBINATIONS#28Spyre is unique in its portfolio approach evaluating multiple combination regimens SPYRE ONLY KNOWN PORTFOLIO WITH ¤4ß7, TL1A, AND IL-23 POTENTIAL TO ADDRESS ORTHOGONAL BIOLOGY FAVORABLE TARGET PRODUCT PROFILE WITH UNIFIED Q8-12W SC DOSING ACROSS TARGETS 28#29MOA Intestinal epithelium Blood Vessel Spyre portfolio addresses the diverse pathophysiology of IBD Blockade of a437 prevents circulating T cells from entering inflammatory gut tissues Cell Cytotoxicity and Tissue Lesion SPY001 a437 0000000 SPYRE T-cell trafficking MADCAM1 Neutralization of TL1A suppresses inflammation within gut tissue and blocks immune cell activation SPY002 ➡ TL1A DR3 Colonic Fibrosis Inflammatory cascade Neutralization of IL-23 inhibits cascade of various proinflammatory cytokines IL-23 SPY003 IL-23R ¿di Th17 maturation Inflammatory cascade Sypre is a pioneer in developing potential best-in-class mAbs against three top targets with the goal of enabling superior combinations for IBD 29#30JNJ's VEGA study demonstrated power of combination therapy despite relative weakness of components VEGA COMBINATION STUDY (N=71/ARM) -A+22% 25% Anti-TNF (Golimumab) BLACK BOX WARNING ~additive absolute clinical remission rates (induction) 24% Anti-IL23 (Guselkumab) 47% 22% 25% Combination | PROBABLE BLACK BOX NOTE: In VEGA, only guselkumab (IL-23) was continued in maintenance for the combo arm in a treat-through design; Spyre plans to use combinations in maintenance. Maintenance remission rates for the anti-TNF arm, anti-IL23 arm, and induction combination arm were 28%, 31%, and 48%, respectively.; Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307-320 (2023). SPYRE 30#31Spyre aims to build on this success with combinations of potentially best-in-class mAbs from favorable MOAS Targets Format Monotherapies lack black box warning Anti-cytokine + anti-lymphocyte trafficking Half-life extension Q8-12W dosing Source: Company materials SPYRE SPY130 a437 + IL-23 Co-formulation SPY120 a437 + TL1A Co-formulation SPY230 TL1A + IL-23 Co-formulation JNJ-'4804 TNF + IL-23 Co-formulation 31#32Combination programs summary SPYRE 1000 COMBINATION OF POTENTIALLY BEST-IN-CLASS MONOTHERAPY BUILDING BLOCKS HI TARGETING UNIFIED Q8-12W DOSING FOR OPTIMIZED PATIENT CONVENIENCE DEVELOPING PATIENT SELECTION APPROACHES TO IDENTIFY RESPONDERS SPY130 Phase 2 study initiation expected in 2025 32#33CORPORATE TEAM AND CASH RUNWAY#34Leadership and BOD Management team Cameron Turtle Scott Burrows Chief Operating Officer Chief Financial Officer Janet Gunzner-Toste SVP, Operations SPYRE APOGEE THERAPEUTICS Heidy King-Jones Chief Legal Officer Andy Spencer Justin LaFountaine SVP, Preclinical R&D VP, Corporate Development FFAIRMOUNT Josh Friedman SVP, Clinical Development bridgebio eidos aegleat a bridgebio company 93 Dragonfly THERAPEUTICS RACAPITAL Russell J. Cox Chairman MERCK abbvie Board of Directors Peter Harwin Board of Directors @abcuro Seagen Hunter C. Smith Ivana Magovčević-Liebisch Alison Lawton Board of Directors Board of Directors Board of Directors Eisai Seagen ADIMAB Tomas Kiselak Board of Directors SANOFI GENZYME 8 TG Therapeutics Michael Henderson Board of Directors PANDION THERAPEUTICS FairJourney Biologics 34#35Cash and anticipated milestones CASH RUNWAY $ 236.7M as of 6/30/2023 expected to fund pipeline into 2026 through multiple key value creation events Note: ¹As of October 23, 2023 SPYRE CATALYSTS¹ SPY001 (a437) SPY002 (TL1A) SPY003 (IL-23) COMBINATIONS EXTERNAL EVENTS 2024 EXPECTED 1H - IND/CTN 2H - PHASE 1 INTERIM DATA 2H - IND/CTN 1H PRA023 SSC-ILD P2 2H TEV-48574 P2b 2H - DUET UC/CD P2b 2025 EXPECTED PHASE 1 FULL DATA PHASE 2 INITIATION PHASE 1 INTERIM DATA IND/CTN PHASE 2 INITIATION MORF057 P2b 35#36Thank you#37Aeglea-Spyre Transaction highlights aeglea 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. SPYRE THERAPEUTICS 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. SPYRE 37#38Capitalization As of 6/20/2023* Shares of common stock outstanding Pre-funded warrants Merger consideration Shares of common Shares of preferred Preferred conversion ratio Total pre-financing common equivalent Concurrent financing Shares of preferred Common equivalent Total capitalization (Common) 2.6 million 1.2 million 0.5 million 0.4 million 1:40 18.9 million 0.7 million 28.9 million 47.7 million ● Shares of common stock and preferred stock were issued to Spyre Therapeutics Inc. security holders in exchange for all of Spyre's outstanding equity interests. Shares of preferred stock were issued to Spyre Therapeutics Inc. 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. SPYRE 38