Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Investor Presentation (October 2024)
49 slides from Spyre Therapeutics's investor presentation, Oct 15, 2024
Slide 1: Corporate overview October 2024
Exhibit 99.2 Corporate overview October 2024
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: Engineering for new heights in the treatment of IBD
Engineering for new heights in the treatment of IBD Our approach Our pipeline 1 TARGET PROGRAM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Next-generation α4β7 Phase 1 interim data expected YE24 SPY001 monotherapies Phase 1 interim data expected 1H25 TL1A SPY002 Potential SC Q8W-Q12W* Phase 1 interim data e
Slide 4: Multiple opportunities for value creation with next-gen monotherapies and combinations
Multiple opportunities for value creation with next-gen monotherapies and paradigm-changing combinations Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unifi
Slide 5: Each antibody builds on validated biology and aims to improve efficacy and convenience
Each of our monoclonal antibodies build on validated biology and aim to improve efficacy and convenience Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unifi
Slide 6: Lead programs chosen based on attractive risk-benefit profiles versus other MOAs
Our lead programs were chosen based on attractive risk-benefit profiles versus other MOAs Induction clinical remission rates (pbo-adjusted) by MOA 100 1 1 2 2030 IBD SALES : 2030 IBD SALES : Acquired for : Ulcerative colitis Crohn’s disease ~$8B ~$7B 80 ~$12B Stronger efficacy in Stronger efficacy i
Slide 7: Next-generation antibodies engineered to match or exceed potency of first-generation molecules
Our next-generation antibodies are engineered to match or exceed the potency of first-generation molecules … SPY001 (α4β7) in vitro potency SPY002 (TL1A) in vitro potency SPY003 (IL-23) in vitro potency SPY001 SPY002 SPY003 Risankizumab Vedolizumab Tulisokibart 60 100 50 100 80 40 60 30 50 40 20 20
Slide 8: Shared YTE backbone extends half-life at least twofold in NHPs
… and share a YTE backbone that extends half-life at least twofold in NHPs … SPY001 (α4β7) NHP PK SPY002 (TL1A) NHP PK SPY003 (IL-23) NHP PK SPY001 t = ~22 days SPY002 t = ~24 days SPY003 t = ~30 days 1/2 1/2 1/2 Risankizumab t = ~9 days Vedolizumab t = ~6 days Tulisokibart t = ~12 days 1/2 1/2 1/2
Slide 9: Projected unified and less frequent dosing across portfolio
… supporting projected unified and less frequent dosing across our portfolio SPY001 (α4β7) Human PK Simulation SPY002 (TL1A) Human PK Simulation SPY003 (IL-23) Human PK Simulation SPY002 SPY001 SPY003 Vedolizumab Tulisokibart Risankizumab Potential unified Q8W-Q12W maintenance dosing Versus Q2W-Q8W
Slide 10: Each monotherapy expected in clinical studies by 1Q 2025
Each of our next-generation monotherapies are expected to be in clinical studies by 1Q 2025 SPY001 SPY002 SPY003 α4β7 TL1A IL-23 Target Comparable potency to >10-fold more potent than Comparable potency to 1,2 Pharmacology vedolizumab tulisokibart risankizumab >3x NHP half-life vs. >2x NHP half-life
Slide 11: Spyre uniquely positioned to deliver paradigm-changing combinations
Spyre is uniquely positioned to deliver paradigm- changing combinations Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formu
Slide 12: Portfolio addresses diverse pathophysiology of IBD via orthogonal pathways
Spyre portfolio aims to address the diverse pathophysiology of IBD by targeting orthogonal pathways Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by
Slide 13: Evidence supports combinations as the future treatment paradigm in IBD
A wide body of evidence supports combinations as the future treatment paradigm in IBD Clinical Nonclinical Genetic VEGA has provided POC that combos can In vitro and in vivo models support Individuals with increased expression of two break the efficacy ceiling in IBD higher efficacy for combos targe
Slide 14: Half-life-extended mAbs potentially enable quarterly, co-formulated combinations
Our portfolio of half-life-extended mAbs potentially enables quarterly, co-formulated combinations SPY001 SPY002 SPY003 Combination human PK simulation (SPY120 potential profile) SPY001 MOA α4β7 TL1A IL-23 TNF S1P JAK SPY002 Median +/- IQR Half-life extension üüü (HLE) Efficacious üüüüüü MOA Well to
Slide 15: Spyre combinations potential best-in-class with less frequent dosing
Spyre combinations have potential being best-in-class with less frequent dosing Expected Annual Maintenance Dosing Program Targets Format Q8W-Q12W SPY120 α4β7 + TL1A Coformulation Q8W-Q12W SPY130 α4β7 + IL-23 Coformulation Q8W-Q12W SPY230 IL-23 + TL1A Coformulation TNF + IL-23 Q4W JNJ-4804 Coformula
Slide 16: Phase 1 data readouts for each mAb over next ~12 months
We intend to readout Ph 1 data for each of our mAbs over the next ~12 months before initiating a platform Ph 2 study 2024 2025 SPY001 (α4β7) Interim data – YE 2024 Phase 1 üFPI – June 2024 SPY002 (TL1A) Interim data – H1 2025 Phase 1 FPI – Q4 2024 SPY003 (IL-23) Interim data – H2 2025 Phase 1 FPI –
Slide 17: SPY001 Next-generation anti-α4β7 antibody
SPY001 Next-generation anti-α4β7 antibody
Slide 18: SPY001 engineered with next-generation antibody properties
SPY001 is engineered to have next-generation antibody properties Identical epitope target as vedolizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed with NOAEL at th
Slide 19: SPY001 potency and selectivity match vedolizumab in vitro
SPY001 potency & selectivity match vedolizumab in vitro 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
Slide 20: SPY001 exhibits >3x the half-life of vedolizumab in preclinical models
SPY001 exhibits >3x the half-life of vedolizumab in preclinical models >3x increased half-life in Tg276 mice >3x increased half-life in NHPs SPY001 t : ~12 Days SPY001 t : ~22 Days 1/2 1/2 1000 1000 Vedo t : ~4 Days Vedo t : ~6 Days 1/2 1/2 100 10 100 1 0.1 0.01 10 0 7 14 21 28 0 7 14 21 28 35 42 49
Slide 21: SPY001 Phase 1 trial on track for interim readout by YE 2024
SPY001 Phase 1 trial on track for interim readout of multiple cohorts by YE 2024 Phase 1 study design Phase 1 milestones ü q First subject dosed: June 2024 q Interim FIH data expected YE 2024 from SAD 5 multiple cohorts SAD 4 MAD 2 q Safety and tolerability SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA
Slide 22: Goals for SPY001 interim Phase 1 readout
We aim to demonstrate the following for SPY001 in the expected YE2024 interim Phase 1 readout ≥35-day half-life enables ≥Q8W-Q12W SC maintenance dosing based on PK model 1 Potential to address vedo’s slow onset of action with higher induction exposures 2 Establish SPY001 has favorable safety profile
Slide 23: Interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible
Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY001 human half-life targets Maintenance human PK simulations Q8W based on Q12W based on Half-life (days) SPY001 Q12W SC PK modeling PK modeling Vedolizumab Q2W SC 1 Humans ~35 ~40 17-22 NHPs
Slide 24: Interim PK data to enable Phase 2 dose selection
Interim PK data expected to enable Phase 2 dose selection to maximize efficacy potential of SPY001 Potential upside: Greater remission w/ higher exposure Induction human PK simulations 1 Vedolizumab Week 14 Deep Remission Rates in UC (%) By Week 6 trough concentration quartile SPY001 SPY001 Vedolizu
Slide 25: SPY002 Next-generation anti-TL1A antibody
SPY002 Next-generation anti-TL1A antibody
Slide 26: SPY002 candidates engineered to achieve an optimal profile
SPY002 candidates are engineered to achieve an optimal profile Advancing two candidates into Ph1 with novel epitopes that optimize potency and binding profiles in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed w
Slide 27: Each SPY002 candidate targets a distinct epitope with unique binding properties
Each SPY002 development candidate targets a distinct epitope and exhibits unique binding properties Single TL1A subunit epitope Superior or comparable potency in multiple assays Each SPY002 candidate targets a distinct Superior or comparable inhibition of TF-1 Superior or comparable inhibition of IF
Slide 28: SPY002 candidates exhibit increased half-life in NHP versus first-generation anti-TL1As
SPY002 candidates exhibit increased half-life in NHP compared to first-generation anti-TL1As SPY002 DC1: >2-3x Increased Half-life in NHPs SPY002 DC2: >2-3x Increased Half-life in NHPs SPY002 t : ~24 days SPY002 t : ~24 days 1/2 1/2 Tulisokibart t : ~12 days Tulisokibart t : ~12 days 1/2 1/2 RO77901
Slide 29: SPY002 Phase 1 initiation expected in 4Q 2024
SPY002 Phase 1 initiation expected in 4Q 2024 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 4Q 2024 q Interim FIH data expected 1H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1q Pharmacokinetics SAD 2 q Pharmacodynamics (sTL1A) SAD 1 q ADA Single-ascending and m
Slide 30: Interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible
Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY002 human half-life targets Human PK simulations Q8W based on Q12W based on Half-life (days) PK modeling PK modeling SPY002 Tulisokibart 1 Humans ~30 ~45 24 NHPs Humans 19 Q2-4W SC NHPs 12 1
Slide 31: Tulisokibart and RO7790121 dose responses support improved maintenance efficacy
Tulisokibart and RO7790121 dose responses support opportunity for improved efficacy in maintenance Clinical remission (mMayo) Endoscopic improvement W50 or W56 250 mg 48% 48% Q4W TULISOKIBART 100 mg 32% 36% ARTEMIS-UC Q4W Greater maintenance efficacy with higher doses 250 mg 56% 68% TULISOKIBART Q4W
Slide 32: SPY003 Next-generation anti-IL-23 antibody
SPY003 Next-generation anti-IL-23 antibody
Slide 33: SPY003 engineered with next-generation antibody properties
SPY003 is engineered to have next-generation antibody properties Similar epitope target as risankizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q12W-Q24W SC maintenance dosing IND-enabling tox studies ongoing High c
Slide 34: SPY003 targets a similar epitope as risankizumab with comparable potency
SPY003 targets a similar epitope as risankizumab with comparable potency in vitro Similar epitope to risankizumab Comparable potency in multiple assays SPY003 and risankizumab bind the SPY003 and risankizumab potently SPY003 and risankizumab potently same p19 subunit of IL-23 inhibit pSTAT signaling
Slide 35: SPY003 exhibits >3x the half-life of risankizumab in NHPs
SPY003 exhibits >3x the half-life of risankizumab in NHPs NHP PK profiles of SPY003 and risankizumab Half-life 1000 ~30 days SPY003 100 3.3-fold vs. risankizumab 10 ~9 days Risankizumab 1 0 14 28 42 56 70 84 98 Days Notes: Group size was n = 4 in the NHP studies with n = 4 and n = 3 at the final tim
Slide 36: SPY003 Phase 1 initiation expected in 1Q 2025
SPY003 Phase 1 initiation expected in 1Q 2025 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 1Q 2025 q Interim FIH data expected 2H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA SAD 1 Single-ascending and multiple-ascending dose coh
Slide 37: Interim PK will confirm whether Q12W-Q24W maintenance dosing is feasible
Phase 1 interim PK will confirm whether Q12W-Q24W maintenance dosing is feasible, as predicted by NHP data SPY003 human half-life targets Human PK simulations SPY003 Q12W based on Q24W based on Half-life (days) Risankizumab PK modeling PK modeling 1 Humans ~45 ~60 30 NHPs Humans 28 Q8W On-body NHPs
Slide 38: Therapeutic combinations: A paradigm-change in the treatment of IBD
Therapeutic combinations A paradigm-change in the treatment of IBD
Slide 39: Unique portfolio approach to evaluating multiple combination regimens
Spyre is unique in its portfolio approach to evaluating multiple combination regimens Only known portfolio with half-life extended α4β7, TL1A, and IL-23 inhibitors Unified dosing potential across targets Combination toxicology studies initiated High-concentration (>150 mg/mL) citrate-free SC coformu
Slide 40: Portfolio aims to address diverse pathophysiology of IBD
Spyre portfolio aims to address the diverse pathophysiology of IBD Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by inhibiting fibroblast activation
Slide 41: JNJ's VEGA study demonstrated the power of combination therapy in IBD
JNJ’s VEGA study demonstrated the power of combination therapy in IBD VEGA combination study (N=71/arm) – Ulcerative colitis ~Additive absolute W12 MMS clinical remission rates Δ+22% 47% 22% 25% 24% 25% Anti-TNF Anti-IL23 Combination (Golimumab) (Guselkumab) BLACK BOX WARNING PROBABLE BLACK BOX Sour
Slide 42: Spyre combinations are rational alternatives to combos with clinical precedent
Spyre combinations are rational alternatives to combos with clinical precedent Clinical trial Precedent combination Spyre combinations & rationale 1 Spyre component exchange EXPLORER Crohn’s – Endoscopic remission % • Exchange TNF for another TNF 35% superfamily targeting agent 30% 27% • TL1A effica
Slide 43: Combination PK exhibits expected behavior in NHPs
Combination PK exhibits expected behavior in NHPs and supports planned combination regimens SPY120 human combination PK simulation and potential dosing profile SPY120 NHP combination PK No observed difference in monotherapy PK when SPY001 dosed in combination SPY002 1000 100 10 SPY001 monotherapy SP
Slide 44: Corporate Team and cash runway
Corporate Team and cash runway
Slide 45: Leadership
Leadership Scott Burrows Brian Connolly Melissa Cooper Paul Fehlner Joshua Friedman Janet Gunzner-Toste Chief Financial Officer Chief Technical Officer SVP, People SVP, Chief Intellectual SVP, Clinical Development SVP, Operations Property Counsel MiRa Huyghe Heidy King-Jones Justin LaFountaine Deann
Slide 46: Board of Directors
Board of Directors Peter Harwin Michael Henderson Tomas Kiselak Jeffrey Albers Mark McKenna Sandra Milligan Laurie Stelzer Cameron Turtle 46
Slide 47: Cash and anticipated milestones
Cash and anticipated milestones 1 $426M 6/30/2024 cash 65.3M 2 Expected runway well into 2027 Shares outstanding 2024 2025 SPY001 (α4β7) Ph1 Interim data Ph1 Initiation Ph1 Interim data SPY002 (TL1A) Ph1 Initiation (1Q) Ph1 Interim data SPY003 (IL-23) Platform Ph2 Ph2 Initiation Expected external TE
Slide 48: Shares outstanding
Shares outstanding As of June 30, 2024 Number of shares Common stock • Shares outstanding 50.8 • Series A preferred stock 13.8 Common stock equivalents • Series B preferred stock 0.7 Common stock and common • Total outstanding 65.3 1 stock equivalents 1 Shares outstanding on a pro forma basis, which
Slide 49: Thank you
Thank you Engineering for new heights in the treatment of IBD
Spyre Therapeutics — Investor Presentation (October 2024) on 6ix