Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (October 2023)
38 slides from Spyre Therapeutics's investor presentation, Oct 24, 2023
Slide 1: Corporate Overview
Exhibit 99.1 CORPORATE OVERVIEW 24 October 2023
Slide 2: Disclosures
Disclosures The information contained in this presentation has been prepared by Aeglea Biotherapeutics, Inc. and its affiliates, including Spyre Therapeutics, Inc. (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information contained
Slide 3: Targeting new heights in the treatment of IBD
Targeting new heights in the treatment of IBD THREE-PILLAR STRATEGY PARALLEL LEAD PROGRAMS AGAINST HIGH VALUE TARGETS OPPORTUNITY FOR BEST-IN-CLASS TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL LONG-ACTING ANTIBODIES SUBCUTANEOUS (SC) Q8-12W DOSING Phase 1 interim data α4β7 SPY001 expected YE24 Pha
Slide 4: Potential best-in-class lead programs
Potential best-in-class lead programs SPY001 (α4β7) SPY002 (TL1A) COMBINATIONS ü IDENTICAL EPITOPE TARGETING ü DUAL MONOMER AND TRIMER ü ONLY KNOWN PORTFOLIO WITH AS VEDOLIZUMAB BINDER α4β7, TL1A, AND IL-23 ü COMPARABLE POTENCY AND ü PICOMOLAR POTENCY AGAINST ü POTENTIAL TO ADDRESS SELECTIVITY AS VE
Slide 5: New approaches are needed to break the efficacy ceiling and improve convenience
Despite advances, new approaches are needed to break the efficacy ceiling and improve convenience of biologics UNMET NEED 80 ~1.7 million individuals are currently diagnosed with 1 IBD in the U.S. SPYRE TARGET There remain substantial unmet needs in IBD 60 management, including: 40 Inadequate respon
Slide 6: Strategy built on three validated approaches to address unmet needs in IBD
Our strategy is built on three validated approaches to address unmet needs in IBD BEST-IN-CLASS ANTIBODY RATIONAL THERAPEUTIC PRECISION IMMUNOLOGY ENGINEERING COMBINATIONS APPROACHES GENETIC AND BIOMARKER SELECTION HALF-LIFE EXTENSION TECHNOLOGIES COMBINATION TARGETING TO ENHANCE TO IDENTIFY MOST LI
Slide 7: Building a potentially best-in-class IBD pipeline
Spyre is building a potentially best-in-class IBD pipeline with next-generation mAbs and rational combinations 1 STRATEGY TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL Phase 1 interim data Potentially α4β7 SPY001 expected YE24 best-in-class mAbs Phase 1 interim data TL1A SPY002 expected 1H25 IL-23
Slide 8: SPY001 Long-Acting α4β7 Antibody
SPY001 LONG-ACTING Α4Β7 ANTIBODY
Slide 9: SPY001 is designed to be a long-acting anti-α4β7
SPY001 is designed to be a long-acting anti-α4β7 IDENTICAL EPITOPE TARGET AS VEDOLIZUMAB ü COMPARABLE POTENCY AND SELECTIVITY AS VEDOLIZUMAB ü SUB-CUTANEOUS, EXTENDED HALF-LIFE mAb PREDICTED TO ENABLE Q8-12W DOSING ü 9
Slide 10: SPY001 potency & selectivity matches vedolizumab
SPY001 potency & selectivity matches vedolizumab 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 adhesi
Slide 11: SPY001 has exhibited ~2x the half-life of vedolizumab in NHPs
SPY001 has exhibited ~2x the half-life of vedolizumab in NHPs DEMONSTRATED EXTENDED HALF-LIFE IN Tg276 MICE DEMONSTRATED EXTENDED HALF-LIFE IN NHPs SPY001 t : ~10 Days SPY001 t : ~17 Days 1/2 1/2 Vedo t : ~3 Days Vedo t : ~10 Days 1/2 1/2 Source: Data on file. 11
Slide 12: SPY001 Phase 1 clinical trial design
SPY001 Phase 1 clinical trial design SINGLE-ASCENDING DOSE MULTIPLE-ASCENDING DOSE SAD 4 IV MAD 2 SC SAD 3 SC SAD 2 SC MAD 1 SC SAD 1 SC Expected interim YE2024 readout to include 2-3 SAD cohorts and is sufficient to answer key objectives with PK modeling Single-ascending dose cohorts Multiple-ascen
Slide 13: Aims for SPY001 in the expected interim Phase 1 readout
We aim to demonstrate the following for SPY001 in the expected interim Phase 1 readout HALF-LIFE ENABLES Q8-12W SC MAINTENANCE DOSING BASED ON PK MODELING 1 POTENTIAL TO ADDRESS VEDO’S SLOW ONSET OF ACTION WITH HIGHER INDUCTION EXPOSURES 2 ESTABLISH SPY-001 HAS FAVORABLE SAFETY PROFILE AND IS WELL-T
Slide 14: Interim PK data informs dose and schedule modeling
Expected Phase 1 interim PK data informs dose and schedule modeling for target maintenance profile SPY001 HUMAN HALF-LIFE PREDICTIONS MAINTENANCE PK SIMULATIONS Q12W SPY001 Dosing Simulation based on 50d half-life 1 SPY001 SC Q12W VEDO IV Q8W Half-life (days) Q8W based on PK Q12W based on PK modelin
Slide 15: Half-life of 43-56 days in 300mg SC format expected to offer superior profile
A half-life of 43-56 days in a 300mg SC format is expected to offer a superior product profile for patients MAINTENANCE DOSING PROFILE SPY001 SC 300 MG 4-6 POTENTIAL FOR SEASONAL DOSING CITRATE FREE INJECTIONS PER YEAR VEDOLIZUMAB SC 108 MG 26 20 MM CITRATE INJECTIONS PER YEAR 15
Slide 16: Interim PK data will inform induction exposure-response relationship
Expected interim PK data will also inform our ability to test induction exposure-response relationship in Phase 2 UPSIDE: GREATER REMISSION VIA HIGHER EXPOSURE INDUCTION PK SIMULATIONS SPY001 INDUCTION SIMULATION BASED ON 50-DAY HALF-LIFE GEMINI I: WEEK 6 CLINICAL REMISSION RATES IN UC (%) 2 SPY001:
Slide 17: SPY001 designed for fully SC induction dosing
SPY001 is designed for fully SC induction dosing with upside efficacy potential INDUCTION DOSING PROFILE PATIENT-ADMINISTERED SC SPY001 INDUCTION UPSIDE POTENTIAL FOR ENHANCED EFFICACY DOSING W0 W2 W6 REQUIRES PHYSICIAN ADMINISTRATION / OFFICE VISIT IV VEDOLIZUMAB INDUCTION POTENTIALLY UNDER-DOSED D
Slide 18: SPY001 designed to match vedolizumab's safety profile and low ADA rate
SPY001 is designed to match vedolizumab’s favorable safety profile and low rate of ADAs 1 2,3 VEDO IS WELL TOLERATED WITH LOW IMMUNOGENICITY ADA RATES ARE SIMILAR FOR YTE AND WT ANTIBODIES 3 4 Vedolizumab Placebo 100 YTE (Half-life extension) 0.85 0.70 WT Infection rates per patient-year per patient
Slide 19: SPY001 summary
SPY001 summary PK MODELLING SUPPORTS COMPARABLE IN VITRO DEVELOPING PATIENT Q8-12W SC DOSING; UPSIDE PERFORMANCE TO SELECTION APPROACHES TO POTENTIAL FOR GREATER VEDOLIZUMAB IDENTIFY RESPONDERS INDUCTION EFFICACY INTERIM PHASE 1 PK DATA EXPECTED YE2024 19
Slide 20: SPY002 Potential Best-in-Class TL1A Antibody
SPY002 POTENTIAL BEST-IN-CLASS TL1A ANTIBODY
Slide 21: SPY002 designed to achieve an optimal anti-TL1A product profile
SPY002 is designed to achieve an optimal anti-TL1A product profile DUAL MONOMER AND TRIMER BINDING ü PICOMOLAR POTENCY AGAINST MONOMERS & TRIMERS ü FULLY SC, EXTENDED HALF-LIFE mAb PREDICTED TO ENABLE Q8-12W DOSING ü 21
Slide 22: Extensive discovery campaign to identify an uncompromising TL1A antibody
Extensive discovery campaign pursued to identify an uncompromising TL1A antibody Heavily resourced campaign employing multiple strategies and formats enabled discovery of desirable TL1A clones 1000+ CLONES Format 3 Format 4 Format 1 Format 2 MONOMER AND TRIMER BINDER Set A Set G Strategy 1 Set B Set
Slide 23: SPY002 clones unique in binding monomers and trimers with picomolar potency
SPY002 clones are unique in binding both monomers and trimers with picomolar potency 1 1 SUPERIOR MONOMER AND TRIMER BINDING SUPERIOR TF-1 APOPTOSIS INHIBITION RVT-3101 NO MONOMER BINDING TEV-48574 TEV-48574 MK-7240 RVT-3101 SELECT SPYRE CLONES MK-7240 SELECT SPYRE CLONES Greater trimer binding (M)
Slide 24: SPY002 is a potential best-in-class TL1A mAb
SPY002 is a potential best-in-class TL1A mAb SPY002 MK-7240 RVT-3101 TEV-48574 Complete TL1A blockade üü Monomer and trimer Picomolar trimer üüü potency Half-life extension ü Q8-12W dosing Source: Company materials 24
Slide 25: SPY002 potentially the most advanced unencumbered TL1A in development
SPY002 is potentially the most advanced unencumbered TL1A in development April 16, 2023 Oct 3, 2023 Announcement dates: Oct 23, 2023 $10.8B 50-50 $7.1B acquisition licensing deal acquisition Global rights $0.5B upfront +$1B in milestones +$150M near-term milestone North America, Japan, Asia rights U
Slide 26: SPY002 summary
SPY002 summary ONLY KNOWN EXTENDED DEVELOPING PATIENT LEAD CLONES ARE MONOMER AND HALF-LIFE TL1A ANTIBODY IN SELECTION APPROACHES TO TRIMER BINDERS WITH POTENCY DEVELOPMENT IDENTIFY RESPONDERS DESIGNED TO BE SUPERIOR TO SELECT ANTIBODIES INTERIM PHASE 1 PK DATA EXPECTED 1H2025 26
Slide 27: Therapeutic Combinations
THERAPEUTIC COMBINATIONS
Slide 28: Unique portfolio approach evaluating multiple combination regimens
Spyre is unique in its portfolio approach evaluating multiple combination regimens ONLY KNOWN PORTFOLIO WITH α4β7, TL1A, AND IL-23 ü POTENTIAL TO ADDRESS ORTHOGONAL BIOLOGY ü FAVORABLE TARGET PRODUCT PROFILE WITH UNIFIED Q8-12W SC DOSING ACROSS TARGETS ü 28
Slide 29: Portfolio addresses the diverse pathophysiology of IBD
Spyre portfolio addresses the diverse pathophysiology of IBD Blockade of α4β7 prevents circulating T cells Neutralization of TL1A suppresses inflammation within Neutralization of IL-23 inhibits cascade of from entering inflammatory gut tissues gut tissue and blocks immune cell activation various pro
Slide 30: JNJ's VEGA study demonstrated power of combination therapy
JNJ's VEGA study demonstrated power of combination therapy despite relative weakness of components VEGA COMBINATION STUDY (N=71/ARM) Δ+22% 47% ~additive absolute clinical remission rates (induction) 22% 25% 24% 25% Anti-TNF Anti-IL23 Combination (Golimumab) (Guselkumab) BLACK BOX WARNING PROBABLE BL
Slide 31: Combinations of potentially best-in-class mAbs from favorable MOAs
Spyre aims to build on this success with combinations of potentially best-in-class mAbs from favorable MOAs SPY130 SPY120 SPY230 JNJ-’4804 Targets α4β7 + IL-23 α4β7 + TL1A TL1A + IL-23 TNF + IL-23 Format Co-formulation Co-formulation Co-formulation Co-formulation Monotherapies lack üüü black box war
Slide 32: Combination programs summary
Combination programs summary COMBINATION OF TARGETING UNIFIED Q8-12W DEVELOPING PATIENT POTENTIALLY BEST-IN-CLASS DOSING FOR OPTIMIZED SELECTION APPROACHES TO MONOTHERAPY BUILDING PATIENT CONVENIENCE IDENTIFY RESPONDERS BLOCKS SPY130 Phase 2 study initiation expected in 2025 32
Slide 33: Corporate Team and Cash Runway
CORPORATE TEAM AND CASH RUNWAY
Slide 34: Leadership and BOD
Leadership and BOD () aN Management team Board of Directors £2es 8 2 0 rrows —_Heidy King-Jones __ Josh Friedman Russell J. Cox Chief Operating Oficer ChiefFinancialOficer ChiefLegal Oficer SVP, Clinical Development Chairman Hunter C-Smith Ivana Magovéevié-Liebisch Alison Lawton Board Direc! Board o
Slide 35: Cash and anticipated milestones
Cash and anticipated milestones 2024 2025 1 CASH RUNWAY CATALYSTS EXPECTED EXPECTED 1H - IND/CTN PHASE 1 FULL DATA SPY001 (α4β7) 236.7M as of 6/30/2023 2H - PHASE 1 INTERIM DATA PHASE 2 INITIATION 2H - IND/CTN PHASE 1 INTERIM DATA SPY002 (TL1A) expected to fund pipeline into 2026 through multiple ke
Slide 36: Thank you
Thank you
Slide 37: Aeglea-Spyre Transaction highlights
Aeglea-Spyre Transaction highlights Structure: The acquisition of Spyre was structured as a stock-for-stock transaction whereby all of Spyre’s outstanding equity interests were exchanged for a combination of shares of Aeglea common stock and a newly created non-voting Series A convertible preferred
Slide 38: Capitalization
Capitalization * As of 6/20/2023 • Shares of common stock and preferred stock Shares of common stock outstanding 2.6 million were issued to Spyre Therapeutics Inc. security holders in exchange for all of Spyre’s outstanding Pre-funded warrants 1.2 million equity interests. Merger consideration • Sha
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