Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Investor Presentation (January 2026)
38 slides from Spyre Therapeutics's investor presentation, Jan 12, 2026
Slide 1: Corporate Overview January 2026
Exhibit 99.2 CORPORATE OVERVIEW January 2026
Slide 2: Disclosures
Disclosures 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 provided as
Slide 3: Pioneering long-acting antibodies and combinations in IBD and rheumatic diseases
Spyre is pioneering long-acting antibodies and combinations to redefine standard of care in IBD and rheumatic diseases Inflammatory bowel disease Rheumatic disease Potential Enable potential Potential best-in-class paradigm changing first-in-class & best-in class monotherapies combinations anti-TL1A
Slide 4: Two innovative trials provide six expected Ph2 readouts in '26
Two innovative trials provide six expected Ph2 readouts in ’26 Trial Readout Anticipated Milestones α4β7 Readouts beginning expected POC SPY001 Ph2 POC in UC readouts TL1A SPY002 Ph2 POC in UC 6 Q2 IL-23 SPY003 Ph2 POC in UC in TL1A SPY072 Ph2 POC in RA TL1A SPY072 Ph2 POC in PsA Q4 TL1A SPY072 Ph2
Slide 5: Advancing a robust I&I pipeline with exceptional financial strength
Advancing a robust I&I pipeline with exceptional financial strength Trial Indication Program Target Phase 1 Phase 2 Phase 3 Anticipated Milestones α4β7 UC SPY001 2026: Ph2 open-label POC Beginning in Q2 TL1A SPY002 2027: Ph2 pbo-controlled data IL-23 SPY003 α4β7 + TL1A SPY120 2027: Ph2 pbo-controlle
Slide 6: Next-generation antibodies designed to match or exceed potency of first-generation molecules
Next-generation antibodies designed to match or exceed the potency of first-generation molecules SPY001 (α4β7) potency SPY002 (TL1A) potency SPY003 (IL-23) potency 60 SPY001 SPY002 SPY003 100 50 100 80 Vedolizumab Tulisokibart Risankizumab 40 60 α4β7 TL1A IL-23 30 40 50 20 20 10 0 0 0 0.001 0.01 0.1
Slide 7: Engineered to be long-acting via YTE modification
Engineered to be long-acting via YTE modification YTE modification YTE-modified mAbs are returned to circulation for continued activity Antibodies are subject to YTE modification increases internal FcRn binding promotes recycling of degradation when internalized binding to FcRn, avoiding degradation
Slide 8: Demonstrated half-life extension for potential quarterly or twice-annual dosing
Demonstrated half-life extension for potential quarterly or twice-annual dosing SPY001 human PK simulation SPY002 human PK simulation SPY003 human PK simulation SPY001 SPY003 SPY002 Vedolizumab Risankizumab Afimkibart Target Profiles 2-4 2-4 2-4 Doses per year Doses per year Doses per year After loa
Slide 9: Potential paradigm-changing combination therapies in IBD
Potential paradigm-changing combination therapies in IBD Inflammatory bowel disease Rational combinations targeting diverse disease drivers TL1A SPY120 α4β7 IL-23 SPY130 α4β7 IL-23 IBD SPY230 TL1A Target 2-4 doses per year © 2026 Spyre Therapeutics, Inc. 9 Potential Q3M-Q6M maintenance dosing interv
Slide 10: Potential first-in-class & best-in-class anti-TL1A in rheumatic diseases
Potential first-in-class & best-in-class anti-TL1A in rheumatic diseases Rheumatic diseases Distinct anti-TL1A targeting quarterly or twice-annual dosing Rheumatoid arthritis Psoriatic arthritis RA Target 2-4 doses per year axSpA Axial spondyloarthritis SPY072 PsA © 2026 Spyre Therapeutics, Inc. 10
Slide 11: Uniquely positioned to enable superior product profiles in IBD and rheumatic diseases
Spyre is uniquely positioned to enable superior product profiles in IBD and rheumatic diseases Inflammatory bowel disease Rheumatic disease Advancing potential best-in-class monotherapies Advancing potential first-in-class & best-in-class anti-TL1A Enabling potential paradigm changing combinations 8
Slide 12: Ph2 trials ongoing in IBD and rheumatic diseases
Ph2 trials ongoing in IBD and rheumatic diseases Ph2 platform trial evaluating SPY001, SPY002, SPY003 Ph2 basket trial evaluating SPY072 in rheumatoid and pairwise combinations in ulcerative colitis arthritis, psoriatic arthritis, and axial spondyloarthritis SPY072 high SPY001 RA UC SPY072 low SPY00
Slide 13: Inflammatory bowel disease
Inflammatory bowel disease SeavyrS
Slide 14: Substantial unmet need remains for millions living with IBD
Substantial unmet need remains for the millions of individuals living with IBD 1 • ~2.4M individuals in the U.S. are diagnosed with IBD (~1.3M UC and ~1.0M CD) • Substantial unmet need remains due to: – Minority remission rates and lack of durability with existing therapies – Side effects and safety
Slide 15: JNJ's VEGA study demonstrated the power of combination therapy
JNJ’s VEGA study demonstrated the power of combination therapy to break the efficacy ceiling in IBD VEGA combination study • Ulcerative colitis ~Additive absolute W12 mMS clinical remission rates Δ+22% 47% 22% 25% 24% 25% Anti-TNF Anti-IL-23 Combination (Golimumab) (Guselkumab) © 2026 Spyre Therapeu
Slide 16: Replacing anti-TNF with anti-α4β7 or anti-TL1A may yield improved combinations
Replacing anti-TNF with anti-α4β7 or anti-TL1A may yield combinations with improved safety and efficacy anti-α4β7 was superior to anti-TNF in H2H UC study anti-TL1A exceeds anti-TNF on cross-trial comparison TNF TNF Absolute clinical remission – week 52 (VARSITY) Pbo-adjusted clinical remission - in
Slide 17: Spyre MOAs address diverse pathophysiology of IBD
Spyre MOAs address the diverse pathophysiology of IBD by targeting distinct pathways Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of various from entering inflamed gut tissues reduces fibrosis by inhibi
Slide 18: Combination therapy results in additive-to-superior efficacy in mouse TNBS colitis model
Combination therapy results in additive-to-superior efficacy in mouse TNBS colitis model α4β7 + TL1A α4β7 + IL-23 TL1A + IL-23 12 12 12 10 10 10 8 8 8 6 6 6 *** ** * **** *** * **** 4 **** 4 4 * ** **** **** **** **** **** *** **** 2 **** 2 2 **** **** * **** 0 0 0 -1 0 1 2 3 4 5 6 -1 0 1 2 3 4 5 6
Slide 19: SKYLINE: Phase 2 platform study in UC
SKYLINE: Phase 2 platform study evaluating three monotherapies and three combinations in UC Part A: Open-label monotherapy evaluation (N=~100) KEY ENDPOINTS OBJECTIVES UC mMS 5-9 INDUCTION MAINTENANCE P Monotherapy POC Change in RHI at W12 SPY001 (α4β7) Sequential S activation SPY002 (TL1A) Clinical
Slide 20: Comparison to other trials highlights advantage of designing portfolio from the ground up
Comparison to other trials highlights advantage of designing a portfolio from the ground up w/ unified dosing 1 TARGET-CD ARM INDUCTION MAINTENANCE (THROUGH W24) ARM INDUCTION MAINTENANCE (THROUGH W24) SPY001 Mono 1 SPY002 Mono 2 SPY003 Mono 3 SPY120 Combo 1 SPY130 Combo 2 SPY230 PBO ü Unified dosin
Slide 21: Best-in-class monotherapies provide foundation for paradigm-changing combinations
Best-in-class monotherapies provide foundation for paradigm-changing combinations for IBD Potential for best-in-indication positioning (UC example) Target product profiles 60 Monos: Comparable-to-better efficacy vs. standard of care Combos: Meaningfully improved efficacy vs. standard of care 40 Favo
Slide 22: Rheumatic diseases
Rheumatic diseases © 2026 Spyre Therapeutics, Inc. 22 All rights reserved.
Slide 23: Substantial unmet need remains for millions living with RA, PsA, and axSpA
Substantial unmet need remains for the millions of individuals living with RA, PsA, and axSpA 1 2 2 • >3M individuals in the U.S. diagnosed with RA (>1.5M ), PsA (~1M ), and axSpA (~1M ) • Substantial unmet need remains due to: – Minority remission rates, inability to control multiple aspects of dis
Slide 24: TL1A implicated in several inflammatory and fibrotic diseases
TL1A has been implicated in several inflammatory and fibrotic diseases, with strong rationale in rheumatic diseases TL1A exacerbates inflammation and fibrosis Target rheumatic diseases share mechanistic pathways with IBD, where POC is established Fibroblasts 1 POC studies T 1 | T 17 | T 9 NK | T 2 |
Slide 25: TL1A is upregulated in RA, PsA, and axSpA relative to healthy controls
TL1A is upregulated in RA, PsA, and axSpA relative to healthy controls Rheumatoid arthritis Psoriatic arthritis Axial spondyloarthritis 200 800 8000 ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ 150 6000 600 100 4000 400 2000 50 200 0 0 -2000 0 -50 Healthy Rheumatoid Healthy axSpA Healthy PsA PsA Control arthritis Control
Slide 26: Spyre anti-TL1A meets or exceeds etanercept efficacy in rat arthritis models
Spyre anti-TL1A antibody meets or exceeds the efficacy of etanercept (anti-TNF) in rat models of arthritis Superior efficacy in semi-preventative model Comparable efficacy in therapeutic model Collagen Treatment period Collagen Treatment period 8 8 Healthy Healthy Vehicle Vehicle Isotype control Iso
Slide 27: Anti-TL1A activity replicated in mouse models of arthritis
Robust anti-TL1A activity further replicated in mouse models of arthritis Anti-TL1A prevents disease and bone erosion Comparable efficacy to anti-TNF 6 4 **** **** 2 Healthy Diseased Diseased Diseased **** 0 Control Control anti-TL1A anti-TNF Healthy Disease anti-TL1A anti-TNF control control © 2026
Slide 28: Anti-TL1A improves psoriatic skin lesions in mouse IMQ model
Additionally, anti-TL1A treatment led to comparable improvements in psoriatic skin lesions in mouse IMQ model Anti-TL1A reduces skin lesions Comparable efficacy to anti-IL-23 and anti-TNF 6 4 10 Healthy control Disease control 2 **** **** **** 8 anti-TL1A anti-IL-23 **** 0 anti-TNF 6 Healthy control
Slide 29: SKYWAY: Phase 2 basket study evaluating SPY072 in RA, PsA, axSpA
SKYWAY: Phase 2 basket study evaluating SPY072 (anti- TL1A) in RA, PsA, and axSpA Sub-study A: SPY072 in moderate-to-severely active rheumatoid arthritis (RA) KEY ENDPOINTS DOUBLE-BLIND OPEN-LABEL FOLLOW UP KEY INCLUSION SPY072 Dose A Swollen joint count ≥ 4 P Change in DAS28-CRP at W12 RA 1:1:1 S T
Slide 30: SPY072 potential first-in-class & best-in-class therapy for rheumatic diseases
SPY072 is a potential first-in-class & best-in-class therapy for rheumatic diseases with quarterly or twice-annual dosing Potential for best-in-indication positioning (RA example) SPY072 target product profile 60 First-in-class anti-TL1A Comparable-to-better efficacy 40 Favorable safety profile No b
Slide 31: Catalysts & capitalization
Catalysts & capitalization SeavyrS
Slide 32: Capitalized to deliver catalyst map
Capitalized to deliver one of the industry's most compelling catalyst maps Trial 2026 2027 q SPY001 α4β7 Ph2 UC induction POC q SPY001 α4β7 Ph2 UC maintenance data Readouts beginning TL1A TL1A q SPY002 Ph2 UC induction POC q SPY002 Ph2 UC maintenance data Q2 q SPY003 IL-23 Ph2 UC induction POC q SPY
Slide 33: Cash and shares outstanding
Cash and shares outstanding 1 $783M pro forma cash as of September 30, 2025 Number of shares (M) Expected runway into 2H 2028 Common stock Shares outstanding 77.6 13.8 • Series A preferred stock Common stock equivalents • Series B preferred stock 0.7 Common stock and Total outstanding 92.1 2 common
Slide 34: Thank you
THANK YOU Engineering for new heights in the treatment of IBD and beyond
Slide 35: 2026 Part A readout: comparable safety and efficacy as in-class comparators
2026 Part A readout: Comparable safety and efficacy as in- class comparators Primary endpoint Secondary endpoints ΔRHI from baseline (W14-16) Absolute % clinical remission (W6-14) Absolute % endoscopic improvement (W6-14) α4β7 Vedolizumab Adalimumab Obefazimod TL1A 50 0 IL-23 40 -2 30 -4 20 -6 10 0
Slide 36: 2026 RA readout: aiming for comparable-to-better than SOC analogs
2026 RA readout: Aiming for ΔDAS28-CRP and ACRs comparable-to-better than SOC analogs Primary endpoint Secondary & exploratory endpoints 1 2 Placebo-adjusted ΔDAS28-CRP (W12-26) Placebo-adjusted % (W12-26) 0.0 100 80 -0.5 60 -1.0 ~30% 40 ~20% ~10% -1.5 20 ΔDAS28-CRP -2.0 0 ACR20 ACR50 ACR70 1 2 © 20
Slide 37: 2026 PsA readout: aiming for ACRs and PASI comparable-to-better
2026 PsA readout: Aiming for ACRs and PASI comparable-to- better than SOC analogs Primary endpoint Secondary & exploratory endpoints Placebo-adjusted % (W12-24) Placebo-adjusted % (W12-24) 100 80 Upside 60 Min. ~30% ~20% 40 ~15% 20 0 ACR20 ACR50 ACR70 PASI75 © 2026 Spyre Therapeutics, Inc. 37 Averag
Slide 38: 2026 axSpA readout: aiming for ΔASDAS and ASAS comparable-to-better
2026 axSpA readout: Aiming for ΔASDAS and ASAS comparable-to-better than SOC analogs Primary endpoint Secondary & exploratory endpoints 1 2 Placebo-adjusted ΔASDAS (W12-16) Placebo-adjusted % (W12-16) 0.0 100 80 -0.4 60 ~25% ~25% 40 -0.8 20 -1.2 0 ΔASDAS ASAS20 ASAS40 © 2026 Spyre Therapeutics, Inc.
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