Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Corporate Update (November 2024)
31 slides from Spyre Therapeutics's corporate update, Nov 12, 2024
Slide 1: SPY001 Phase 1 Results & Corporate Updates
SPY001 Phase 1 Results & Corporate Updates November 2024
Slide 2: Disclosures
2 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
Slide 3: Agenda
3 Agenda Introduction and Executive Summary Cameron Turtle, DPhil Chief Executive Officer SPY001 Phase 1 Interim Results Deanna Nguyen, MD SVP, Clinical Development Phase 2 Platform Trial in UC Sheldon Sloan, MD, MBE Chief Medical Officer Building the Leading IBD Portfolio Cameron Turtle, DPhil Chie
Slide 4: Engineering for new heights in the treatment of IBD
4 Engineering for new heights in the treatment of IBD 1Spyre holds exclusive worldwide licensed rights for SPY001, SPY002, and SPY003 from Paragon Therapeutics, Inc. SPY003 license is restricted to IBD, all other program licenses are unrestricted as to indication. TARGET PROGRAM1 PRECLINICAL PHASE 1
Slide 5: Spyre's portfolio uniquely enables product profiles with potential superior efficacy and convenience
5 Spyre’s portfolio uniquely enables product profiles with potential superior efficacy and convenience Note: 1VEGA trial was not pbo-controlled. 0 1 2 3 4 5 6 20 40 60 80 Maintenance dosing interval (months) Pb o- ad ju st ed c lin ic al re m is si on (% ) Potential for Q3M & Q6M dosing profiles ILL
Slide 6: Entyvio is the #1 product in IBD and is forecast to exceed $8B by 2030
6 Entyvio (vedolizumab) is the #1 product in IBD by share and is forecast to exceed $8B in sales by 2030 Source: 1EvaluatePharma consensus sales forecast October 2024; 2Takeda Full-year 2023 Earnings announcement; 3Casteele, N. V. et al. Aliment. Pharmacol. Ther. 56, 463–476 (2022); IV=Intravenous.
Slide 7: SPY001 is designed to be a next-generation α4β7 inhibitor
7 SPY001 is designed to be a next-generation α4β7 inhibitor Source: Data on file. Vedolizumab comparator refers to a mAb identical in sequence to vedolizumab synthesized by Spyre for research purposes. In NHP PK study, initial group size n=6 in NHP. Animals with suspected ADAs were excluded from hal
Slide 8: SPY001 Phase 1 objectives
8 SPY001 Phase 1 objectives ≥35-day half-life enables ≥Q8W-12W SC maintenance dosing based on PK model1 Potential to address vedo’s slow onset of action with higher induction exposures2 Establish SPY001 has favorable safety profile and is well-tolerated3 Minimal to no impact on ADA rates vs vedolizu
Slide 9: SPY001 met or exceeded all Phase 1 objectives
9 SPY001 met or exceeded all Phase 1 objectives Note: 1ADA analysis pending, but no individual PK or PD profiles have been removed from the analysis due to apparent ADAs PK supports a planned Ph2 induction regimen with higher exposures vs vedo (targets all patients in quartile 4), potentially increa
Slide 10: Interim SPY001 Phase 1 results
Interim SPY001 Phase 1 results Deanna Nguyen, SVP of Clinical Development
Slide 11: SPY001 interim data includes up to months of follow up from ongoing Phase 1 trial
11 SPY001 interim data includes up to 4 months of follow up from ongoing Phase 1 trial (10/30/24 data cutoff) Trial design elements Single ascending dose follow up Multiple ascending dose follow up Design • Double-blind, pbo-controlled, first-in-human trial • Nested SAD and MAD cohorts Population •
Slide 12: Baseline demographics were well balanced across cohorts
12 Baseline demographics were well balanced across cohorts SD=standard deviation. 100 mg 300 mg 600 mg 1000 mg 1000 mg SAD Pooled 300 mg 600 mg MAD Pooled N= 8 8 8 8 8 40 8 8 16 Age, years Mean (SD) 52 (9) 46 (14) 54 (7) 40 (6) 36 (9) 46 (11) 45 (10) 38 (8) 41 (10) Female Percent 0% 13% 38% 25% 50%
Slide 13: Interim data show SPY001 was well tolerated with a favorable safety profile
13 Interim data show SPY001 was well tolerated with a favorable safety profile TEAE=treatment-emergent adverse events. TESAE=treatment-emergent serious adverse events. 1Injection site discomfort starting 6 hours after 4 SC injections and resolved 2 hours later without intervention. N (%) 100 mg 300
Slide 14: Interim data showed >90-day half-life, far exceeding expectations
14 Interim data showed >90-day half-life, which far exceeds expectations (~4-fold vs published vedo half-life) Note: Human PK data in this presentation are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head cl
Slide 15: SPY001 exhibits dose-proportional pharmacokinetics
15 SPY001 exhibits dose-proportional pharmacokinetics Note: 1Cohorts with sufficient follow up for dose proportionality assessment. SAD mean PK profiles MAD mean PK profiles Dose proportionality observed between 300 - 1000 mg1 Initial MAD PK consistent with SAD PK M ea n Se ru m C on c. (µ g/ m L) t
Slide 16: Modeled Phase 2 induction exposures exceeded those of vedolizumab
16 Modeled Phase 2 induction exposures exceeded those of vedolizumab with all patients anticipated in quartile 4 Source: 1Casteele, N. V. et al. Aliment. Pharmacol. Ther. 56, 463–476 (2022); 2Vedolizumab FDA Clinical Pharmacology Review; PK simulation for comparator molecules based on published clin
Slide 17: Population PK modeling supports Q3M and Q6M maintenance dosing
17 Se ru m C on c. (µ g/ m L) SPY001 Q3M SC SPY001 Q6M SC Vedolizumab Q2W SC Population PK modeling for SPY001 supports potential for both Q3M and Q6M maintenance dosing regimens Data on file, simulations represent median +/- interquartile range. Maintenance human PK simulations MaintenanceInduction
Slide 18: SPY001 saturated α4β7 receptors through ~12 weeks after a single dose
18 SPY001 saturated α4β7 receptors through ~12-weeks of follow up after a single dose Notes: Data shown are Mean +/- SD for each cohort at each visit; pooled placebo. (n): Placebo (2-6), SPY001 300 mg SC (5-6), SPY001 600 mg SC (6), SPY001 1000 mg SC (6). Data have been slightly offset for visualiza
Slide 19: SPY001 Phase 1 interim results summary
19 SPY001 Phase 1 interim results summary (10/30/24 cutoff) Potential for increased or accelerated induction efficacy by targeting all patients in the 4th quartile of vedo’s reported E-R relationship Ph2 induction dosing to test higher exposures Potential for as little as twice-yearly maintenance do
Slide 20: Platform Phase 2 trial in ulcerative colitis
Platform Phase 2 trial in ulcerative colitis Sheldon Sloan, CMO
Slide 21: A platform study provides an efficient mechanism to test multiple therapeutics
21 A platform study provides an efficient mechanism to test multiple therapeutics in a single indication Source: Park, Jay JH, et al. JAMA 327.1 (2022): 67-74. Platform trial primer Key benefits Placebo (common control) Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5 Randomization of new
Slide 22: Planned platform trial enables placebo-controlled readouts of monos and combos
22 Spyre’s planned platform trial enables 6 placebo- controlled topline readouts of Spyre monos and combos Notes: 1Randomization among active arms; all arms may not start and finish simultaneously Design elements Illustrative schematic Design • Master protocol platform trial • Double blind, placebo-
Slide 23: Comparison to other trials highlights advantage of unified dosing
23 Comparison to other trials highlights potential advantage of designing a portfolio from the ground up w/ unified dosing Trial arm Induction (12W) Maintenance (through 26W) Placebo Q3M SPY001 Q3M SPY002 Q3M SPY003 Q3M SPY120 Q3M SPY130 Q3M SPY230 Q3M Unified dosing intervals and formats enables
Slide 24: Platform design offers 6 ways to win at up to 40% lower cost
24 Platform design is attractive to patients and investigators with 6 ways to win at up to 40% lower cost 6 ways to win Including 3 optimized monotherapies & 3 paradigm-changing combinations Operational efficiency Up to 40% lower cost vs. individual Ph2 trials High enthusiasm With 3 combination arms
Slide 25: Building the Leading IBD Portfolio
Building the Leading IBD Portfolio Cameron Turtle, CEO
Slide 26: SPY001 is our lead program and derisks portfolio dosing profile
26 SPY001 is our lead program given its potential for combination therapy & derisks portfolio dosing profile Note: TMDD=target mediated drug disposition. Data on file for NHP half-lives. SPY001 is an ideal backbone for combinations SPY001 human t1/2 derisks dosing profile for portfolio Gut-selective
Slide 27: Revising dosing guidance across the portfolio to Q3M-Q6M maintenance
27 We are revising our dosing guidance across the portfolio to Q3M-Q6M maintenance dosing SPY001 (α4β7) Maintenance Profile SPY002 (TL1A) Maintenance Profile SPY003 (IL-23) Maintenance Profile 22 NHP Human >90 ~4-fold 24 NHP Human targets 30 NHP Human targets Q8W-Q12W Q3M-Q6M Q8W-Q12W Q3M-Q6M Mainta
Slide 28: Spyre monotherapies and combinations have potential best-in-indication dosing profile
28 Spyre monotherapies and combinations have potential best-in-indication Q3M & Q6M dosing profile Source: Product labels and disclosed clinical trials. 1Annual injections after induction doses; 2JNJ’4804 is Johnson and Johnson’s combination of Simponi (anti-TNF) and Tremfya (anti-IL-23) Expected An
Slide 29: Spyre's portfolio uniquely enables product profiles with superior efficacy and convenience
29 Spyre’s portfolio uniquely enables product profiles with potential superior efficacy and convenience Note: 1VEGA trial was not pbo-controlled. 0 1 2 3 4 5 6 20 40 60 80 Maintenance dosing interval (months) Pb o- ad ju st ed c lin ic al re m is si on (% ) Potential for Q3M & Q6M dosing profiles IL
Slide 30: Catalyst rich 2025 planned
30 Catalyst rich 2025 planned with expected Ph1 readouts on TL1A and IL-23 programs and Ph2 platform initiation 20252024 SPY001 (α4β7) Ph1 Interim data SPY002 (TL1A) Ph1 Initiation Ph1 Interim data SPY003 (IL-23) Ph1 Initiation (1Q) Ph1 Interim data Platform Phase 2 Ph2 Initiation Extern
Slide 31: Q&A
Q&A
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