Spyre Therapeutics : SKYLINE A SPY001 vFINAL

Published: 2026-04-13 08:10:10 ET SYRE

Published on 04/13/2026 at 08:10 am EDT

SPY001

Part A Induction Topline Results

April 13, 2026

Introduction

Cameron Turtle, DPhil

Chief Executive Officer

SPY001 Part A Induction Topline Results

Deanna Nguyen, MD

SVP, Clinical Development

Summary Remarks

Cameron Turtle, DPhil

Chief Executive Officer

Analyst Q&A

Cameron Turtle, CEO Sheldon Sloan, CMO Deanna Nguyen, SVP Scott Burrows, CFO

Kate Tansey Chevlen, CCO

Cameron Turtle, DPhil, CEO

Expanding inflammatory bowel disease (IBD) market Persistent therapeutic ceiling

Global IBD Market

Placebo-adjusted clinical remission rates in ulcerative colitis (UC) Induction

Efficacy ceiling

100%

80%

60%

~$40B

2030

~$25B

2025

40%

20%

Anti-TNF

Anti-αβ47

Anti-IL-23

S1P

JAK

JNJ's VEGA demonstrated near-additive remission with advanced combination Field is converging on combos

Increasing case reports

Clinical remission, Week 12

47%

Confirmatory academic trials

Focus of strategic investment

Anti-TNF (Golimumab)

Anti-IL-23 (Guselkumab)

Combination (JNJ-4804)

AbbVie

25%

24%

Boehringer Ingelheim

Johnson & Johnson

Lilly

Roche

Sanofi

Takeda

Source: Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307-320 (2023), remission results by mMS shown. 6

SPY001

α4β7

SPY002

TL1A

SPY003

IL-23

Validated mechanisms of action with leading safety and efficacy

Next-generation molecules engineered for best-in-class potential

Co-formulations optimized for convenient, subcutaneous delivery (Q3-6M)1

1After loading doses 7

The only approved gut-selective mechanism in IBD1 Mechanistically orthogonal to anti-cytokine therapies

α4β7

integrin

Gut-selective anti-integrin

α4β7

Immune cell trafficking

Anti-cytokine Anti-cytokine

TL1A

T-cell activation & fibrosis

IL-23

T-cell proliferation

1Blocking the α4β7 integrin inhibits its interaction with MAdCAM-1, which is predominantly expressed on intestinal endothelial cells; ENTYVIO (vedolizumab) prescribing information 8

Same validated epitope

Equivalent target potency

Vedolizumab1

Ctrough quartile (µg/ml)

SPY001 improves upon proven vedolizumab mechanism SPY001 dosing targets top quartile exposure

Top-quartile vedo exposure more than doubled remission rate

22%

13%

>2x

PBO

17%

Vedo

≥35.7 37%

25.0-35.7

17.1-25.0

≤17.1

Clinical remission %

SPY001 target

Extended half-life

Effector function silenced

High conc. SC format2

SPY001

1Vedolizumab exposure-response data from Rosario, M., et. al. (2017) 9

2 After loading doses, IV Induction tested in SKYLINE

ΔRHI from baseline

p < 0.0001 from baseline

-9.2

Clinical remission

27%1

17%2

40%

Endoscopic improvement

41%2

51%

-7.51

Vedolizumab W14

SPY001 W12

Vedolizumab W6

Vedolizumab W14

SPY001 W12

Vedolizumab W6

SPY001 W12

SPY001 was well-tolerated, consistent with the α4β7 class

Source: 1VARSITY trial, Sands, Bruce E., et al. New England Journal of Medicine 381.13 (769): 1215-1226 (N=394). 2GEMINI trial, endoscopy not centrally read, Feagan, Brian G., et al.

New England Journal of Medicine 369.8 (2013): 699-710 (N=374). 10

Trial designs differ and no head-to-head clinical trials have been conducted. Data pertain to SPY001 Induction Treatment Period.

Deanna Nguyen, MD, SVP Clinical Development

Part A: Open-label monotherapy evaluation (N = ~130)

SPY001 (α4β7)

SPY002 (TL1A) SPY003 (IL-23)

UC mMS 5-9

Sequential activation after Ph1

INDUCTION MAINTENANCE

W12 W48

Trial enrollment exceeded target

Part B: PBO-controlled factorial combination evaluation (N = ~550)

UC mMS 5-9

Target ~50:50 naïve:experienced

Anti-α4β7 and anti-IL-23 failures capped

INDUCTION MAINTENANCE

SPY001 (α4β7) SPY002 (TL1A) SPY003 (IL-23) SPY120 (α4β7+TL1A) SPY130 (α4β7+IL-23) SPY230 (TL1A+IL-23)

Placebo

Seamless enrollment after Part A

W12 W48

mMS=modified Mayo score; P=primary endpoint 12

Part A: Open label monotherapy evaluation

Key topline endpoints

ΔRHI from baseline

PRIMARY

Today's release

SPY001 (α4β7)

INDUCTION

Patient characteristics

Adults with moderately to severely active UC (mMS 5-9)

Rectal bleeding subscore ≥1

Mayo endoscopic subscore ≥ 2

Sequential enrollment

SECONDARY

SPY003 (IL-23)

SPY002 (TL1A)

% Clinical remission

% Endoscopic improvement

W12

Incidence of treatment-emergent adverse events

mMS=modified Mayo Score; RHI=Robarts Histopathology Index. Data pertain to SPY001 Induction Treatment Period. Primary endpoint of ΔRHI was analyzed using per protocol analysis

set, and t-test was applied to test against the null hypothesis of ΔRHI =0; Secondary endpoints including Clinical Remission and Endoscopic Improvement rates were analyzed using full 13

analysis set.

Robarts Histopathology Index (RHI) Endoscopic Improvement Clinical Remission

Direct measure of tissue inflammation Direct visualization of mucosal healing Composite endpoint aligned with regulatory guidance

Change in RHI

ΔRHI

Baseline W12

Endoscopy Subscore

Severe

Moderate

Mild

Normal

Baseline

W12

Modified Mayo Score

Endoscopy Subscore Stool Frequency Subscore Rectal Bleeding Subscore

W12

Endpoints are anchored in objective, centrally assessed1 measures

SPY001 (α4β7), N = 43

Age (years, mean)

Sex (% female)

Weight (kg, mean)

Geographic region

Europe

North America

88%

12%

Duration of UC (years, mean)

4.5

RHI (mean ± SD)

15.6 ± 8.6

RHI ≥ 10 (n, %)

34 (79%)

Baseline mMS (mean ± SD)

6.8 ± 1.1

Mayo Endoscopy Score (MES) (n, %)

19 (44%)

24 (56%)

Concomitant immunomodulator use (n, %)

Concomitant corticosteroid use (n, %)

18 (42%)

Number of prior advanced therapies (n, %)

Naïve 1

≥2

35 (81%)

7 (16%)

1 (2%)

Patient disposition

Screened

(N=91)

Dosed

(N=43)

Completed Induction Period1

(N=41)

SPY001 (α4β7), N=43

Subjects with any Adverse Event (n, %)

6 (14%)

Severe (Grade ≥ 3) AE

1 (2%)*

Drug-Related AE

AE Leading to Drug Discontinuation

Serious Adverse Event (SAE)

1 (2%)*

Drug-Related SAE

AEs of Special Interest

Death

Most common AE (≥2 patients) was back pain (n=2)

*Chest pain in a 68-year-old male with history of coronary artery disease and angina pectoris, type 2 diabetes mellitus, hypertension, and hypercholesterolemia who presented with chest

pain. ECG and cardiac enzymes did not show signs of a myocardial infarction. Data on file. 16

Data pertain to SPY001 Induction Treatment Period (through Week 12) with a data cut-off date of Feb 23, 2026.

Primary endpoint Key secondary endpoints

Proportion with clinical remission at W12

Proportion with endoscopic improvement at W12

40%

51%

Mean ΔRHI at W12 from baseline

-10

-8

-6

-4

-2

p < 0.0001

-9.2

SPY001

Pre-specified sensitivity analysis:

-10.6 for participants with a baseline RHI ≥ 10

ΔRHI from baseline at W12 Clinical remission at W12 Endoscopic improvement at W12

-7.7

-9.5

51% 50%

40%

38%

Advanced Therapy Naïve

Advanced Therapy Experienced

Advanced Therapy Naïve

Advanced Therapy Experienced

Advanced Therapy Naïve

Advanced Therapy Experienced

Mayo endoscopic score

Rectal bleeding

Stool frequency

PGA score

n=43 n=41

n=43 n=40

n=43 n=41

n=24 (56%)

n=9 (22%)

n=10 (24%)

n=14 (34%)

n=8 (20%)

n=19 (44%)

n=4 (10%)

n=3 (7%)

n=11 (28%)

n=26 (60%)

n=25 (63%)

n=13 (30%)

n=25 (58%)

n=4 (10%)

n=11 (28%)

n=17 (43%)

n=8 (20%)

n=17 (40%)

n=13 (30%)

n=4

(10%)

n=12 (29%)

n=16 (39%)

n=9 (22%)

n=30 (70%)

Baseline

Week 12

Baseline

Week 12

Baseline

Week 12

Baseline

Week 12

Partial Mayo score Fecal calprotectin

Change from baseline ± 95% CI 1

-1

-2

-3

-4

-5

W0 W2 W4 W6 W8 W12

Fold change from baseline ± 95% CI 1.0

0.8

0.6

0.4

0.2

W0 W6 W12

Disclaimer

Spyre Therapeutics Inc. published this content on April 13, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 13, 2026 at 12:09 UTC.