附件99.2 公司概況 2024年10月

免責聲明 此演示文稿中包含的信息由Spyre Therapeutics, Inc.及其關聯公司（以下簡稱「Spyre」或「公司」）準備，幷包含有關公司業務和運營的信息。此演示文稿中包含的信息: (a) 截至本日期，按現狀提供，如有變更恕不另行通知，並基於公開信息，內部開發數據和其他來源的第三方信息; (b) 不打算包含可能對充分和準確評估對公司的投資必要或希望的所有信息; (c) 不應被視爲公司建議任何人對公司進行投資； (d) 僅供信息目的，不構成要約買入、賣出、發行或認購公司證券，也不構成在任何法域中要約買入、賣出或發行，或認購公司證券的邀約。若本演示文稿中表達了任何意見或信念，均是基於某些假設和限制，僅代表當前意見或信念。本演示文稿不應被解釋爲向任何個人提供法律、財務或稅務建議，因爲每個人的情形不同。本文件僅供信息目的，不應被視爲要約或建議購買、賣出或持有證券。前瞻性信息 本演示文稿中列出的某些信息包含適用美國證券法的「前瞻性陳述」。除歷史事實表述外，本文檔中包含的某些信息構成前瞻性陳述，包括但不限於有關以下方面的聲明: 關於我們產品候選品的功效、持久性效果的預期，包括人體藥代動力學模擬和給藥方案，以及安全性；關於我們潛在治療組合及其潛在益處的預期，包括人體藥代動力學模擬和給藥方案；就發現、前臨床研究、臨床試驗和研發計劃的期望，包括臨床試驗的時間安排、數據發佈和臨床試驗研究設計的預期；就資金用途和公司資本資源足以支持預期運營的時間段的預期；公司的業務戰略目標和目標；以及管理層就基於當前內部預期、估計、投影、假設和信念所作的對未來計劃和運營的評估，這可能是不正確的。前瞻性陳述通常可通過使用「可能」、「將」、「可能」，「將」，「預期」，「相信」，「期望」，「打算」，「潛力」，「估計」，「安排」，「計劃」，「計劃」，「預測」，「目標」等詞語或其否定形式來識別。前瞻性陳述既不是歷史事實也不是對未來績效的保證。前瞻性陳述基於管理層所作的一些因素和假設，且在提供信息時被認爲是合理的，前瞻性陳述涉及到管理層認爲的在某種程度上在未來可能會發生的實際結果、績效和成就可能與前瞻性陳述中表達或暗示的結果有重大不同，包括那些不確定性和因素，在公司最近的年度10-K表格中描述的不確定性和因素，「風險因素摘要」和「關於前瞻性陳述的說明」，以及公司已經提交或將提交給SEC的後續季度10-Q表格和展示8-k表格，以及不定期進行的公司相關的潛在風險、不確定性和其他陳述的討論，以及涉及生物製藥行業公司的風險因素，包括與藥物開發相關的不確定性。在本演示文稿中提出的所有前瞻性陳述均是受到這些警示性陳述和其他此類警示性陳述或本文中包含的其他因素的限制。儘管管理層相信本文件中闡明的前瞻性陳述是合理的，基於可在提供前瞻性陳述時可獲得的信息，但無法保證前瞻性陳述將被證明是準確的，因爲實際結果和未來事件可能與此類陳述中預期的結果有重大不同。除適用證券法要求外，公司無義務更新前瞻性陳述，如果情況或管理的估計或意見發生變化；本演示文稿中包含的前瞻性陳述旨在幫助讀者了解公司的計劃、目標和目標，可能並不適用於其他目的。提醒讀者不要對前瞻性陳述給予過度依賴。 行業信息 本演示文稿還包含或引用了一些根據獨立行業出版物、市場研究、調查和其他公開來源信息而基於的行業數據。儘管公司認爲這些來源一般可靠，但由於數據的可用性和可靠性受限，數據收集過程的自願性質以及其他固有限制和不確定性，這些信息不可避免地會受到解釋和完全確認的限制。公司並未對本演示文稿中涉及的第三方來源的任何數據進行獨立驗證，因此公司對本演示文稿中信息的來源、有效性、準確性、完整性、時效性或可靠性不作陳述或保證。2

在炎症性腸病治療方面邁向新的高度 我們的方法 我們的 管線 1 目標項目 臨床前期 階段1 階段2 階段3 下一代 α4β7 階段1 中期數據預計YE24 SPY001 單藥療法 階段1 中期數據預計1H25 TL1A SPY002 潛在皮下 Q8W-Q12W* 階段1 中期數據預計 2H25 IL-23 SPY003 α4β7 + TL1A SPY120 具有突破性潛力的組合α4β7 + IL-23 SPY130 潛在皮下 Q8W-Q12W* TL1A + IL-23 SPY230 1 Spyre擁有來自Paragon的SPY001、SPY002和SPY003的排他性全球許可權Therapeutics, Inc. SPY003許可受限於IBD，所有其他項目的許可與適應症無關。*SC=皮下，Q8W-Q12W劑量方案基於人類Pk模擬預期維持方案。

下一代單藥物提供了多個創造價值的機會，以及改變範式的組合。 下一代單藥物 改變範式的組合 經過工程設計的單克隆抗體： 爲設計的固定劑量組合： 效力 特異性 功效 安全性 藥代動力學 統一劑量 可製造性 配方性 降低生產成本便利性 α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 4

Each of our monoclonal antibodies build on validated biology and aim to improve efficacy and convenience Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formulatability Lower COGS Convenience α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 5

Our lead programs were chosen based on attractive risk-benefit profiles versus other MOAs Induction clinical remission rates (pbo-adjusted) by MOA 100 1 1 2 2030 IBD SALES : 2030 IBD SALES : Acquired for : Ulcerative colitis Crohn’s disease ~$8B ~$7B 80 ~$12B Stronger efficacy in Stronger efficacy in Encouraging efficacy UC CD 60 and safety profile in UC and CD 3 Gut-selective MOA Well tolerated MOA 40 ~33% Efficacy ceiling ~25% ~25% ~24% ~23% ~20% ~17% ~16% 20 ~12% Primary ~8% ~7% endpoint not met 0 W14 | W6 W12 | W12 W12 | W12 W8 | W4 W10 | W12 W8 | W12 Week No black box warning Not approved No black box warning Black box warning Cardiac monitoring Black box warning Safety α4β7 TL1A IL-23 TNF S1P JAK MOA Example TULISOKIBART Source: Studies include Entyvio UC (VARSITY, assumes a 10% historical pbo control), CD (GEMINI II); tulisokibart UC (ATREMIS-UC), CD (APOLLO-CD, study was open label and adjusted using a historical pbo rate of 16%); Skyrizi UC (INSPIRE), CD (ADVANCE); Humira UC (ULTRA-II), Humira CD (CLASSIC-1, Bio-naïve patients); Zeposia UC (TRUE NORTH), CD (YELLOWSTONE), Rinvoq UC (U-ACCOMPLISH and U-ACHIEVE), CD (U-EXCEL); 1 2 3 EvaluatePharma 2030 Consensus Sales; Merck press release; Ferrante M, et. al. J Crohns Colitis. 2021 Dec 18;15(12):2001-2010. MOA=mechanism of action. 6

Our next-generation antibodies are engineered to match or exceed the potency of first-generation molecules … SPY001 (α4β7) in vitro potency SPY002 (TL1A) in vitro potency SPY003 (IL-23) in vitro potency SPY001 SPY002 SPY003 Risankizumab Vedolizumab Tulisokibart 60 100 50 100 80 40 60 30 50 40 20 20 10 0 0 0 0.01 0.1 1 10 0.001 0.01 0.1 1 10 100 0.01 0.1 1 10 100 mAb Concentration (nM) mAb Concentration (nM) mAb Concentration (nM) Potential for comparable efficacy at similar or lower doses Potential upside: Improved efficacy with higher exposures Note: Data on file. Details on number of replicates per study are included in later sections. SPY001 assay reports inhibition of cells expressing α4β7 binding to MAdCAM-1. SPY002 assay reports inhibition of TL1A-induced apoptosis in TF-1 cells. SPY003 assay reports inhibition of cellular STAT3 signaling. Vedolizumab, tulisokibart, and risankizumab are synthesized comparator antibodies. 7 %Inhibition %Inhibition % Inhibition

… and share a YTE backbone that extends half-life at least twofold in NHPs … SPY001 (α4β7) NHP PK SPY002 (TL1A) NHP PK SPY003 (IL-23) NHP PK SPY001 t = ~22 days SPY002 t = ~24 days SPY003 t = ~30 days 1/2 1/2 1/2 Risankizumab t = ~9 days Vedolizumab t = ~6 days Tulisokibart t = ~12 days 1/2 1/2 1/2 1000 1000 1000 100 100 100 10 10 10 1 1 1 0 14 28 42 56 70 84 98 0 14 28 42 56 70 84 98 0 7 14 21 28 35 42 49 Days Days Days Greater than 2-3x half-life extension vs. competitor molecules across our portfolio Note: Data on file. Pharmacokinetic data shown is from NHP studies, details on number of animals per study are included in later sections. Vedolizumab, tulisokibart, and risankizumab are synthesized comparator antibodies. 8 Serum Conc. (μg/mL) Serum Conc. (μg/mL) Serum Conc. (μg/mL)

… supporting projected unified and less frequent dosing across our portfolio SPY001 (α4β7) Human PK Simulation SPY002 (TL1A) Human PK Simulation SPY003 (IL-23) Human PK Simulation SPY002 SPY001 SPY003 Vedolizumab Tulisokibart Risankizumab Potential unified Q8W-Q12W maintenance dosing Versus Q2W-Q8W dosing for competitor molecules Note: Date on file, figures show median +/- interquartile range. PK simulation for comparator molecules based on published clinical data. 9 Serum Conc. (µg/mL) Serum Conc. (µg/mL) Serum Conc. (µg/mL)

Each of our next-generation monotherapies are expected to be in clinical studies by 1Q 2025 SPY001 SPY002 SPY003 α4β7 TL1A IL-23 Target Comparable potency to >10-fold more potent than Comparable potency to 1,2 Pharmacology vedolizumab tulisokibart risankizumab >3x NHP half-life vs. >2x NHP half-life vs. >3x NHP half-life vs. 2 PK vedolizumab tulisokibart risankizumab ü IND-enabling GLP toxü IND-enabling GLP tox IND-enabling GLP tox Safety Ongoing Top dose NOAEL Top dose NOAEL >150 mg/mL SC formulation >150 mg/mL SC formulation >150 mg/mL SC formulation CMC 3 Target dosing profile Phase 1 Phase 1 initiation expected Phase 1 initiation expected Status ongoing 4Q 2024 1Q 2025 1 2 3 Note: Evaluated in in vitro models; Vedolizumab, tulisokibart, and risankizumab are synthesized comparators; Potential maintenance dosing profile based on human simulations from NHP PK data 10

Spyre is uniquely positioned to deliver paradigm- changing combinations Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formulatability Lower COGS Convenience α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 11

Spyre portfolio aims to address the diverse pathophysiology of IBD by targeting orthogonal pathways Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by inhibiting fibroblast activation various proinflammatory cytokines anti-IL-23 anti-α4β7 anti-TL1A Created with BioRender.com; Neurath, Markus F. Nature Reviews Gastroenterology & Hepatology 14.5 (2017): 269-278; Solitano, Virginia, et al. Med (2024). 12

A wide body of evidence supports combinations as the future treatment paradigm in IBD Clinical Nonclinical Genetic VEGA has provided POC that combos can In vitro and in vivo models support Individuals with increased expression of two break the efficacy ceiling in IBD higher efficacy for combos targets are at greater risk to develop IBD Odds ratio (95% CI) Δ+22% 200 Combination 1.0 1.1 1.2 1.3 1.4 ~additive absolute clinical IL-23 47% remission rates TL1A 150 ITGA4 (α4β7) 22% 100 25% 24% TNFSF15 (TL1A) 50 25% Combo 0 0.1 1 10 100 1000 TNF IL-23 Combination Conc. ng/ml rd 1 3 party data In-house data In-house analysis 1 Source: Data on file; Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307–320 (2023). 13 IL-17 (pg/ml)

Our portfolio of half-life-extended mAbs potentially enables quarterly, co-formulated combinations SPY001 SPY002 SPY003 Combination human PK simulation (SPY120 potential profile) SPY001 MOA α4β7 TL1A IL-23 TNF S1P JAK SPY002 Median +/- IQR Half-life extension üüü (HLE) Efficacious üüüüüü MOA Well tolerated üüü 2x Unified MOA Loading Doses Q8W-Q12W SC Maintenance Dosing 1 rd Notes: Product labels for 3 party data supports mechanisms of action without black box warnings or safety monitoring requirements. Sands, Bruce E., et al. New England Journal of Medicine 391.12 (2024): 1119-1129. mAbs=monoclonal antibodies. Human PK simulation represents median +/- interquartile range utilizing SPY001 and SPY002 individual PK simulations presented in prior slides. 14 1 Third party clinical trials Spyre molecules Serum Conc. (µg/mL)

Spyre combinations have potential being best-in-class with less frequent dosing Expected Annual Maintenance Dosing Program Targets Format Q8W-Q12W SPY120 α4β7 + TL1A Coformulation Q8W-Q12W SPY130 α4β7 + IL-23 Coformulation Q8W-Q12W SPY230 IL-23 + TL1A Coformulation TNF + IL-23 Q4W JNJ-4804 Coformulation Probable black box Q4W ABBV382/Skyrizi α4β7 + IL-23 TBD ABT-981/Skyrizi IL-1 + IL-23 TBD Q2W Note: Expected dosing regimens for SYRE molecules based on human PK simulations and competitor molecule dosing profiles are based on disclosures of the most frequently administered component molecule. Landscape not exhaustive. 15

We intend to readout Ph 1 data for each of our mAbs over the next ~12 months before initiating a platform Ph 2 study 2024 2025 SPY001 (α4β7) Interim data – YE 2024 Phase 1 üFPI – June 2024 SPY002 (TL1A) Interim data – H1 2025 Phase 1 FPI – Q4 2024 SPY003 (IL-23) Interim data – H2 2025 Phase 1 FPI – Q1 2025 Platform FPI – 2025 Phase 2 study 16

SPY001 Next-generation anti-α4β7 antibody

SPY001 is engineered to have next-generation antibody properties Identical epitope target as vedolizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed with NOAEL at the highest dose tested High concentration (>150 mg/mL) citrate-free SC formulations developed for clinical studies SPY001 Phase 1 study ongoing with interim data expected YE24 18

SPY001 potency & selectivity match vedolizumab in vitro SPY001 & vedolizumab epitope Potent and selective inhibition of cellular adhesion SPY001 and SPY001 and vedolizumab potently inhibit No inhibition of unwanted VCAM-1- vedolizumab MAdCAM-1-mediated (gut) cellular adhesion mediated (CNS) cellular adhesion bind the same α4 Subunit epitope 70 SPY001 (IC = 86 pM) 50 70 SPY001 Vedolizumab (IC = 83 pM) 50 Vedolizumab 60 60 (α4β1) Natalizumab β7 Subunit 50 50 40 40 30 30 20 20 Potent and selective binding to α4β7 10 10 1 0 Antibodyα4β7α4β1αEβ7 0 -10 2 2 SPY001 K <1 nM NB NB 0.01 0.1 1 10 D 0.001 0.01 0.1 1 10 100 mAb Concentration (nM) mAb Concentration (nM) 2 2 Vedolizumab K <1 nM NB NB D 1 Dissociation constant (K ) measured by surface plasmon resonance (SPR) D 2 NB = no binding by a particular antibody to a test molecule Source: Data on file. Vedolizumab is a synthesized comparator antibody. 19 %Inhibition of Total Adhesion (Integrin-mediated Adhesion by MAdCAM-1) %Inhibition of Total Adhesion (Integrin-mediated Adhesion by VCAM-1)

SPY001 exhibits >3x the half-life of vedolizumab in preclinical models >3x increased half-life in Tg276 mice >3x increased half-life in NHPs SPY001 t : ~12 Days SPY001 t : ~22 Days 1/2 1/2 1000 1000 Vedo t : ~4 Days Vedo t : ~6 Days 1/2 1/2 100 10 100 1 0.1 0.01 10 0 7 14 21 28 0 7 14 21 28 35 42 49 Days Days Source: Data on file. Initial group size was n=5 in mouse study (left) and n=6 in NHP study (right). Animals with suspected ADAs were excluded from half-life analysis; this did not impact the mouse study but resulted in n=5/cohort for SPY001 and n=3/cohort for vedolizumab at Day 49 of the NHP study. Vedolizumab used is a synthesized comparator antibody. 20 Serum Conc. (μg/mL) Serum Conc. (μg/mL)

SPY001 Phase 1 trial on track for interim readout of multiple cohorts by YE 2024 Phase 1 study design Phase 1 milestones ü q First subject dosed: June 2024 q Interim FIH data expected YE 2024 from SAD 5 multiple cohorts SAD 4 MAD 2 q Safety and tolerability SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA SAD 1 Single-ascending and multiple-ascending dose cohorts • Healthy volunteers • n=8/cohort (3:1 randomization) 21

We aim to demonstrate the following for SPY001 in the expected YE2024 interim Phase 1 readout ≥35-day half-life enables ≥Q8W-Q12W SC maintenance dosing based on PK model 1 Potential to address vedo’s slow onset of action with higher induction exposures 2 Establish SPY001 has favorable safety profile and is well-tolerated 3 Minimal to no impact on ADA rates vs vedolizumab 4 22

Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY001 human half-life targets Maintenance human PK simulations Q8W based on Q12W based on Half-life (days) SPY001 Q12W SC PK modeling PK modeling Vedolizumab Q2W SC 1 Humans ~35 ~40 17-22 NHPs Humans 25 Q2W SC 2 NHPs 4-14 1 2 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Rosario, M, et. al. (2017); Feagan, et. al. (2013); Range of half-life observed in vedolizumab NHP studies (BLA review) and internal Spyre preclinical studies. Vedolizumab is a synthesized comparator antibody. PK simulation for comparator molecules based on published clinical data. 23 VEDO SPY001 Serum Conc. (µg/mL)

Interim PK data expected to enable Phase 2 dose selection to maximize efficacy potential of SPY001 Potential upside: Greater remission w/ higher exposure Induction human PK simulations 1 Vedolizumab Week 14 Deep Remission Rates in UC (%) By Week 6 trough concentration quartile SPY001 SPY001 Vedolizumab Vedo Quartile 4 37% (40-100 µg/mL) Targeting majority of patients with C in Quartile 4 trough Quartile 3 31% (32-40 µg/mL) Quartile 2 Vedo W6 20% (25-32 µg/mL) Quartile 4 Quartile 1 12% (2-25 µg/mL) +25% Higher anti-α4β7 mAb exposure may lead to deeper remission 1 Source: Casteele, N. V. et al. Aliment. Pharmacol. Ther. 56, 463–476 (2022); Vedolizumab FDA Clinical Pharmacology Review; PK simulation for comparator molecules based on published clinical data. 24 Serum Conc. (µg/mL)

SPY002 Next-generation anti-TL1A antibody

SPY002 candidates are engineered to achieve an optimal profile Advancing two candidates into Ph1 with novel epitopes that optimize potency and binding profiles in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed with NOAEL at the highest dose tested High concentration (>150mg/mL) citrate-free SC formulations developed for clinical studies SPY002 Phase 1 study initiation expected in Q4 2024 26

Each SPY002 development candidate targets a distinct epitope and exhibits unique binding properties Single TL1A subunit epitope Superior or comparable potency in multiple assays Each SPY002 candidate targets a distinct Superior or comparable inhibition of TF-1 Superior or comparable inhibition of IFNγ epitope on a single TL1A monomer apoptosis secretion Duvakitug (TEV-48574) SPY002 candidates RO7790121 RO7790121 (RVT-3101) Duvakitug Tulisokibart Tulisokibart (MK-7240) 100 100 80 80 60 60 40 40 20 20 0 0 • Epitope locations were resolved by CryoEM 0.01 0.1 1 10 100 0.1 1 10 100 1000 10000 100000 mAb Concentration (nM) mAb Concentration (ng/mL) • Illustrative locations are overlayed with the crystal structure of trimeric TL1A Source: Data on file; Duvakitug not benchmarked in IFN secretion assay; Duvakitug, RO7790121, and tulisokibart are synthesized comparator antibodies. γ 27 Inhibition % Inhibition%

SPY002 candidates exhibit increased half-life in NHP compared to first-generation anti-TL1As SPY002 DC1: >2-3x Increased Half-life in NHPs SPY002 DC2: >2-3x Increased Half-life in NHPs SPY002 t : ~24 days SPY002 t : ~24 days 1/2 1/2 Tulisokibart t : ~12 days Tulisokibart t : ~12 days 1/2 1/2 RO7790121 t : ~7 days RO7790121 t : ~7 days 1000 1000 1/2 1/2 100 100 10 10 1 1 0 14 28 42 56 70 84 98 0 14 28 42 56 70 84 98 Time (day) Time (day) Source: Data on file. Notes: Group size was n=5 for SPY002 mAbs and tulisokibart at final endpoints for half-life determination; No RO7790121 detected after day 28; Duvakitug not compared in these models given low human half-life (7-10 days), ECCO 2024 abstract P633; Duvakitug, RO7790121, and tulisokibart are synthesized comparator antibodies. 28 Serum Conc. (μg/mL) Serum Conc. (μg/mL)

SPY002 Phase 1 initiation expected in 4Q 2024 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 4Q 2024 q Interim FIH data expected 1H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1q Pharmacokinetics SAD 2 q Pharmacodynamics (sTL1A) SAD 1 q ADA Single-ascending and multiple-ascending dose cohorts • Healthy volunteers Phase 1 results to inform which molecule • n=8/cohort (3:1 randomization) advances to Phase 2 development 29

Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY002 human half-life targets Human PK simulations Q8W based on Q12W based on Half-life (days) PK modeling PK modeling SPY002 Tulisokibart 1 Humans ~30 ~45 24 NHPs Humans 19 Q2-4W SC NHPs 12 1 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Spyre preclinical studies; Tulisokibart is a synthesized comparator antibody; Prometheus corporate presentation – Ph1 results. 30 TULISOKIBART SPY002 Serum Conc. (µg/mL)

Tulisokibart and RO7790121 dose responses support opportunity for improved efficacy in maintenance Clinical remission (mMayo) Endoscopic improvement W50 or W56 250 mg 48% 48% Q4W TULISOKIBART 100 mg 32% 36% ARTEMIS-UC Q4W Greater maintenance efficacy with higher doses 250 mg 56% 68% TULISOKIBART Q4W APOLLO-CD 100 mg 42% 59% Q4W 450 mg 36% 50% Q4W Greater maintenance RO7790121 150 mg 39% 39% efficacy with higher Q4W TUSCANY-2 doses 50 mg 31% 38% Q4W Source: UEGW 2024 posters OP079 and OP196; Artemis and Apollo patients were re-randomized for maintenance period while Tuscany-2 was a treat-through design. 31

SPY003 Next-generation anti-IL-23 antibody

SPY003 is engineered to have next-generation antibody properties Similar epitope target as risankizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q12W-Q24W SC maintenance dosing IND-enabling tox studies ongoing High concentration (>150 mg/mL) citrate-free SC formulation developed for clinical studies SPY003 Phase 1 study initiation expected in Q1 2025 Note: SPY003 license is restricted to IBD indications. 33

SPY003 targets a similar epitope as risankizumab with comparable potency in vitro Similar epitope to risankizumab Comparable potency in multiple assays SPY003 and risankizumab bind the SPY003 and risankizumab potently SPY003 and risankizumab potently same p19 subunit of IL-23 inhibit pSTAT signaling inhibit IL-17 release SPY003 Risankizumab 100 100 50 50 0 0 0.01 0.1 1 10 100 1000 0.001 0.01 0.1 1 10 100 SPY003 epitope mAb Concentration (nM) mAb Concentration (nM) Risankizumab epitope Source: Data on file. Risankizumab is a synthesized comparator antibody. 34 % Inhibition % Inhibition

SPY003 exhibits >3x the half-life of risankizumab in NHPs NHP PK profiles of SPY003 and risankizumab Half-life 1000 ~30 days SPY003 100 3.3-fold vs. risankizumab 10 ~9 days Risankizumab 1 0 14 28 42 56 70 84 98 Days Notes: Group size was n = 4 in the NHP studies with n = 4 and n = 3 at the final timepoint for half-life determination for SPY003 and risankizumab, respectively. Source: Data on file. Risankizumab is a synthesized comparator antibody. 35 Serum Conc. (μg/mL)

SPY003 Phase 1 initiation expected in 1Q 2025 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 1Q 2025 q Interim FIH data expected 2H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA SAD 1 Single-ascending and multiple-ascending dose cohorts • Healthy volunteers • n=8/cohort (3:1 randomization) 36

Phase 1 interim PK will confirm whether Q12W-Q24W maintenance dosing is feasible, as predicted by NHP data SPY003 human half-life targets Human PK simulations SPY003 Q12W based on Q24W based on Half-life (days) Risankizumab PK modeling PK modeling 1 Humans ~45 ~60 30 NHPs Humans 28 Q8W On-body NHPs 9 1 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Spyre preclinical studies; Skyrizi BLA. Risankizumab is a synthesized comparator antibody. 37 RISA SPY003 Serum Conc. (µg/mL)

Therapeutic combinations A paradigm-change in the treatment of IBD

Spyre is unique in its portfolio approach to evaluating multiple combination regimens Only known portfolio with half-life extended α4β7, TL1A, and IL-23 inhibitors Unified dosing potential across targets Combination toxicology studies initiated High-concentration (>150 mg/mL) citrate-free SC coformulations in development for each program Platform Phase 2 study that will include monotherapy and combo SPY120 • SPY130 • SPY230 agents expected to initiate in 2025 39

Spyre portfolio aims to address the diverse pathophysiology of IBD Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by inhibiting fibroblast activation various proinflammatory cytokines anti-IL-23 anti-α4β7 anti-TL1A Created with BioRender.com; Neurath, Markus F. Nature Reviews Gastroenterology & Hepatology 14.5 (2017): 269-278; Solitano, Virginia, et al. Med (2024). 40

JNJ’s VEGA study demonstrated the power of combination therapy in IBD VEGA combination study (N=71/arm) – Ulcerative colitis ~Additive absolute W12 MMS clinical remission rates Δ+22% 47% 22% 25% 24% 25% Anti-TNF Anti-IL23 Combination (Golimumab) (Guselkumab) BLACK BOX WARNING PROBABLE BLACK BOX Sources: Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307–320 (2023). 41

Spyre combinations are rational alternatives to combos with clinical precedent Clinical trial Precedent combination Spyre combinations & rationale 1 Spyre component exchange EXPLORER Crohn’s – Endoscopic remission % • Exchange TNF for another TNF 35% superfamily targeting agent 30% 27% • TL1A efficacy and safety appears superior on a cross-trial basis SPY120 α4β7 TNF TL1A Anti-α4β7 Anti-TNF Combination 2 VEGA UC – mMS remission % • Exchange TNF for a safer and 47% more effective class 25% 24% • Entyvio was superior to Humira in H2H clinical studies (VARSITY) SPY130 IL-23 TNF α4β7 Anti-IL23 Anti-TNF Combination 2 VEGA UC – mMS remission % • Exchange TNF for another TNF 47% superfamily targeting agent 25% 24% • TL1A efficacy and safety appears superior on a cross-trial basis SPY230 IL-23 TNF TL1A Anti-IL23 Anti-TNF Combination 1 Note: EXPLORER meta-analysis assumes a 27% remission rate for vedolizumab and 30% remission rate for adalimumab; EXPLORER included methotrexate treatment 1 2 Source: Colombel, Jean-Frederic, et al. Clinical Gastroenterology and Hepatology 22.7 (2024): 1487-1496. Feagan, Brian G., et al. The Lancet Gastroenterology & Hepatology 8.4 (2023): 307-320; 42

Combination PK exhibits expected behavior in NHPs and supports planned combination regimens SPY120 human combination PK simulation and potential dosing profile SPY120 NHP combination PK No observed difference in monotherapy PK when SPY001 dosed in combination SPY002 1000 100 10 SPY001 monotherapy SPY001 dosed in combination with SPY002 1 0 14 28 1000 100 10 SPY002 monotherapy SPY002 dosed in combination with SPY001 1 0 14 28 Days Source: Data on file. Human PK simulation represents median +/- interquartile range utilizing SPY001 and SPY002 individual PK simulations presented in prior slides. 43 SPY002 serum conc. (μg/mL) SPY001 serum conc. (μg/mL) Serum Conc. (µg/mL)

Corporate Team and cash runway

Leadership Scott Burrows Brian Connolly Melissa Cooper Paul Fehlner Joshua Friedman Janet Gunzner-Toste Chief Financial Officer Chief Technical Officer SVP, People SVP, Chief Intellectual SVP, Clinical Development SVP, Operations Property Counsel MiRa Huyghe Heidy King-Jones Justin LaFountaine Deanna Nguyen Sheldon Sloan Andrew Spencer Cameron Turtle SVP, Development Chief Legal Officer and SVP, Corporate SVP, Clinical Chief Medical Officer SVP, Preclinical Research Chief Executive Officer Operations Corporate Secretary Development Development and Development 45

Board of Directors Peter Harwin Michael Henderson Tomas Kiselak Jeffrey Albers Mark McKenna Sandra Milligan Laurie Stelzer Cameron Turtle 46

Cash and anticipated milestones 1 $426M 6/30/2024 cash 65.3M 2 Expected runway well into 2027 Shares outstanding 2024 2025 SPY001 (α4β7) Ph1 Interim data Ph1 Initiation Ph1 Interim data SPY002 (TL1A) Ph1 Initiation (1Q) Ph1 Interim data SPY003 (IL-23) Platform Ph2 Ph2 Initiation Expected external TEV-48574 Ph2b MORF057 Ph2b DUET-UC/CD Ph2b events 1 2 Notes: Anticipated milestones as of October 2024; Cash includes cash, cash equivalents, restricted cash & marketable securities as of 6/30/24; Shares outstanding on a pro forma and as-converted basis as of 6/30/24, which (i) gives effect to the full conversion of the Company’s preferred stock, and (ii) disregards beneficial ownership limitations that may limit the ability of certain holders of preferred stock to convert into common stock; see following slide for detailed reconciliation. 47

Shares outstanding As of June 30, 2024 Number of shares Common stock • Shares outstanding 50.8 • Series A preferred stock 13.8 Common stock equivalents • Series B preferred stock 0.7 Common stock and common • Total outstanding 65.3 1 stock equivalents 1 Shares outstanding on a pro forma basis, which includes (i) common stock outstanding as of 6/30/24, (ii) conversion of the Company’s Series B preferred stock as approved at the May 13, 2024 Annual Meeting of Shareholders, and (iii) the exercise of all outstanding pre-funded warrants in May 2024. 48

Thank you Engineering for new heights in the treatment of IBD