Slide 1: SPY001 SKYLINE Part A Induction Topline Results
Exhibit 99.2 SPYRE Me THERAPEUTICS VY dih SPY001 SKYLINE Part A Induction Topline Results April 13, 2026
Slide 2: Disclosures
Disclosures () aN The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre" or the “Company") and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provi
Slide 3: Agenda
Agenda Introduction dh SKYLING SPY001 Part A Induction Topline Results Summary Remarks Analyst Q&A SPYRE &. AS. & ret £ a Cameron Turtle, DPhil Chief Executive Officer Deanna Nguyen, MD SVP, Clinical Development Cameron Turtle, DPhil Chief Executive Officer Cameron Turtle, CEO Sheldon Sloan, CMO Dea
Slide 4: Introduction
Introduction Cameron Turtle, DPhil, CEO “ aA - » SPYRE THERAPEUTICS
Slide 5: IBD is a large & growing market that demands better therapies
IBD is a large & growing market that demands better therapies —_(} oa Expanding inflammatory bowel disease (IBD) market Persistent therapeutic ceiling Placebo-adjusted clinical remission rates in ulcerative colitis (UC) Global IBD Market Induction 100% ~$40B 80% 60% 40% Efficacy ceiling 20% | 0% SPY
Slide 6: Advanced combination therapy has demonstrated potential to break the therapeutic ceiling in IBD
Advanced combination therapy has demonstrated potential () to break the therapeutic ceiling in IBD a> JNJ's VEGA demonstrated near-additive remission with advanced combination Field is converging on combos Clinical remission, Week 12 v Increasing case reports 47% YY Confirmatory academic trials 25%
Slide 7: Spyre is investigating a fundamentally differentiated portfolio of advanced combination therapies
Spyre is investigating a fundamentally differentiated portfolio () of advanced combination therapies a> SPYRGE a SEORE Uncompromising combinations from first principles: Validated mechanisms of action with leading safety and efficacy Next-generation molecules engineered for best-in-class potential S
Slide 8: a4b7 inhibition may be an optimal backbone for advanced combination therapy in IBD
a487 inhibition may be an optimal backbone for advanced () combination therapy in IBD a> The only approved gut-selective mechanism in IBD‘ Mechanistically orthogonal to anti-cytokine therapies Gut-selective anti-integrin Anti-cytokine Anti-cytokine TLIA IL-23 T-cell activation & T-cell fibrosis Immu
Slide 9: SPY001 is a potential best-in-class anti-a4b7 with dosing designed to test efficacy at higher exposures
SPY001 is a potential best-in-class anti-a4B7 with dosing () designed to test efficacy at higher exposures SPY001 improves upon proven vedolizumab mechanism a> SPY001 dosing targets top quartile exposure Y Same validated epitope Y Equivalent target potency Effector function silenced @ Extended halit
Slide 10: SPY001 consistently outperformed objectives in Part A, supporting a potential best-in-class profile
SPY001 consistently outperformed objectives in Part A, () supporting a potential best-in-class profile ays ARHI from baseline Clinical remission Endoscopic improvement p< 0.0001 from baseline 40% 51% 9.2 41%2 27%' a 7.51 7 ; Vedolizumab SPY001 Vedolizumab Vedolizumab SPY001 Vedolizumab SPY001 wi14 W
Slide 11: Topline Induction Results
SPY001 Topline Induction Results Deanna Nguyen, MD, SVP Clinical Development & aA - » SPYRE THERAPEUTICS
Slide 12: SKYLINE is a two-part study, with Part B now enrolling
SKYLINE is a two-part study, with Part B now enrolling () ath SKYLING Part A: Open-label monotherapy evaluation (N = ~130) UC mMS 5-9 INDUCTION MAINTENANCE mm as Sequential . ton es Recrumnent clase -~ ve SENOUS MES) a Trial enrollment exceeded target e Part B: PBO-controlled factorial combination e
Slide 13: Today's release describes SPY001 Part A induction results
Today’s release describes SPY001 Part A induction results () ah SKYLINE Part A: Open label monotherapy evaluation a> Key topline endpoints INDUCTION Patient characteristics £ = Adults with moderately to ‘Sagi A ' severely active UC (mMS 5-9) enrollment * = Rectal bleeding subscore 21 + Mayo endoscop
Slide 14: Endpoints focus on objective measures of disease activity
Endpoints focus on objective measures of disease activity () Robarts Histopathology Index (RHI) Endoscopic Improvement Clinical Remission Direct measure of tissue inflammation Direct visualization of mucosal healing Composite endpoint aligned with regulatory guidance Nid) aD) Change in RHI Endoscopy
Slide 15: Baseline characteristics were consistent with expectations
Baseline characteristics were consistent with expectations () aS 44 Patient disposition Sex (% female) 28 Weight (kg, mean) 76 n Geographic re: Screened Europe 88% (N=91) North America 12% ' 45 es) RHI 2 10 (n, %) 34 (79%) J Baseline mMS (mean + SD) 6.8411 Mayo Endoscopy Score (MES) (n, %) Completed
Slide 16: SPY001 was well tolerated with a favorable safety profile
SPY001 was well tolerated with a favorable safety profile () SPY001 (a4B7), N=43 314%) Severe (Grade = 3) AE 1 (2%)* Drug-Related AE 0 AE Leading to Drug Discontinuation 0 Serious Adverse Event (SAE) 1 (2%)* Drug-Related SAE 0 AEs of Special Interest 0 Death ie) Most common AE (22 patients) was back
Slide 17: SPY001 met its primary endpoint and outperformed our expectations on key secondary endpoints
SPY001 met its primary endpoint and outperformed our () expectations on key secondary endpoints oy Primary endpoint Key secondary endpoints Mean ARHI at W12 from baseline Proportion with clinical remission at W12 Proportion with endoscopic improvement at W12 6 p<0.0001 Fi 4 50 40 6 30 4 51% 20 40% 2
Slide 18: SPY001 response rates were consistent between naive and experienced UC patients
SPY001 response rates were consistent between naive and () experienced UC patients oy ARHI from baseline at W12 Clinical remission at W12 Endoscopic improvement at W12 9.5 40% 51% ; | ; ; Advanced Therapy Advanced Therapy Advanced Therapy Advanced Therapy Advanced Therapy § Advanced Therapy Naive Ex
Slide 19: SPY001 demonstrated robust, consistent improvements across endoscopic and symptom measures
SPY001 demonstrated robust, consistent improvements () across endoscopic and symptom measures ay MisM@i2: o Mayo endoscopic score Rectal bleeding Stool frequency PGA score n=43 n=41 n=43 n=40 n=43 n=40 n=43 n=41 oy - &) (30%) n=25 n=14 (63%) (34%) n=17 (43%) n=26 (60%) n=11 (28%) n=4 (10%) Baseline
Slide 20: SPY001 demonstrated rapid improvements in reported symptoms and biomarkers of intestinal inflammation
SPY001 demonstrated rapid improvements in reported () symptoms and biomarkers of intestinal inflammation oy Partial Mayo score Fecal calprotectin Change from baseline + 95% Cl Fold change from baseline + 95% Cl 1 1.0 ° 0.8 “4 06 2 3 0.4 4 0.2 wo w2 W4 W6 Ws wi12 wo W6 wi2 Patients treated with SPY00
Slide 21: Summary Remarks
Summary Remarks Cameron Turtle, DPhil, CEO “ aA - » SPYRE THERAPEUTICS
Slide 22: SKYLINE Part A enrolled with leading execution
SKYLINE Part A enrolled with leading execution () gs IIment months | 9 12 | 13 | 14 a SPYRE SPYOO Se one. aoe ~130 no etonenee nt Includes three novel investigational agents Morphic MORF-057 EMERALD-1 35, Morphic «MORF-Os7—EMERALD-2 280 Prometheus Tulisokibart ARTEMIS 120 Roivant —Afmiibart«=«TUSCAN
Slide 23: The SPY001 Part A cohort enrolled a moderately-to-severely active population comparable to prior anti-a4b7 trials
The SPY001 Part A cohort enrolled a moderately-to-severely () i= Baseline RHI Mean + SD Baseline mMS active population comparable to prior anti-a487 trials oy Vedolizumab Vedolizumab MORF057 VARSITY GEMINI EMERALD-1 43 769 374 35 15.6486 19.5487 N/A 22.7+7.3 6841.1 6.1 £45" 6.0 + 1.6* 6741.1 56% N.R
Slide 24: SPY001 results across multiple endpoints supports a potential best-in-class product
SPY001 results across multiple endpoints supports a () potential best-in-class product ays Primary endpoint Key secondary endpoints RHI from baseline Proportion with clinical remission Proportion with endoscopic improvement -10 9.2 60 51% 8 75 2 6.4 40 f0% Le 6 30 27% 26% 26% 4 20 17% 2 10 0 SPY001
Slide 25: SPY001 change in RHI outperformed previously reported results in UC trials
SPY001 change in RHI outperformed previously reported () results in UC trials aN ARHI from baseline 7 SA [\F coy |) “10 4 8 -6.61 6 | -2 o4 * SPY001 ' Vedolizumab MORF057 Adalimumab Obefazimod Week 12 ' 14 12 14 8 Trial SKYLINE ' VARSITY EMERALD-1 VARSITY Ph2b Pre-specified sensitivity analysis: -10
Slide 26: SPY001's 40% clinical remission among the highest reported in UC trials
SPY001’s 40% clinical remission among the highest reported in UC trials Proportion of participants with clinical remission 4 ~ P JAK mee emIR-1240 50 4/ H H i 42%! | 40% | 40 |! i r t 32%!" | 1 30%!" 30 |} | 27% e 28% 2 26% 25%! —p4m nay. 28%" 20 4! H 18% 18%" | | at L 0 T SPY001 | Vedolzumab — MORF
Slide 27: SPY001's 51% endoscopic improvement outperformed other UC trials
SPY001’s 51% endoscopic improvement outperformed () Proportion of participants with endoscopic improvement —_—_ 5 ———— ik emir tte 60 9° 4 | 51% | 50 +i Be AT% 1 1 41% 40%! 40%! 40 | ! 37% 37% 36% 37% H H oa 33%! ao | { oats F y 30%! H ' 26% 27% 20 4; i 10 ' OT are | ateane) Moker —Tantas) Asan Tana
Slide 28: SPY001 Part A data supports its potential as one of the most promising single agents in IBD
SPY001 Part A data supports its potential as one of the most () promising single agents in IBD aN | SPYRE OD THERAPEUTICS SPY001 Part A data supports upside target product profile: i] Favorable safety profile consistent with class 5 Potential best-in-class efficacy SPY001 0467 SPY002 TLIA va Formula
Slide 29: SPY001 data support improved combination potential
SPY001 data support improved combination potential () aN SKYLINE JNJ VEGA study 80 80 Clinical remission, Week 12 Clinical remission, Week 12 60 60 47% 40 40 25% 24% 20 40% 20 0 0 Anti-a4B7 Anti-TL1A Combination Anti-TNF Anti-IL-23 Combination (SPY001) or Anti-IL-23 Potential (Golimumab) (Guselkumab
Slide 30: Catalyst rich 2026 with multiple accelerated readouts expected
Catalyst rich 2026 with multiple accelerated readouts expected {| Trial dh SKYLING Part A (Open-label) dh SKYLING Part B (Pbo-controlled) Ads SKYWAY SPYRE Milestone SPY001 Ph2 UC induction POC SPY002 Ph2 UC induction POC SPY003 Ph2 UC induction POC Initiate enrollment of Part B cohorts SPY072 Ph2 W1
Slide 31: Q&A