Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Merger or Acquisition (June 2023)
50 slides from Spyre Therapeutics's merger presentation, Jun 23, 2023
Slide 1: Transaction & Overview Q2 2023
TRANSACTION & OVERVIEW Q2 2023 Exhibit 99.1
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: Transaction highlights
Transaction highlights CONFIDENTIAL 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 4: Capitalization
Capitalization As of 6/20/2023 Shares of common stock outstanding 65.4 million Pre-funded warrants 28.9 million Merger consideration Shares of common 13.0 million Shares of preferred 0.4 million Preferred conversion ratio 1000 Total pre-financing common equivalent 472.2 million Concurrent financing
Slide 5: Spyre aims to transform the treatment of IBD
TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SPY004 a4b7 + IL-23 SPY130 a4b7 + TL1A SPY120 TL1A + IL-23 SPY230 Spyre aims to transform the treatment of IBD Opportunity for best-in-class Long-acting antibodies
Slide 6: Inflammatory bowel disease is a growing $21B market
Sources: Global Data, Evaluate Pharma, UpToDate, SVB Leerink. Inflammatory bowel disease is a growing $21B market in which biologics are the preferred modality ~1.7M IBD patients diagnosed in the US. 2028 Estimated IBD Market $29.1B Crohn's disease 2021 Global IBD Market $21.1B IBD represents a mult
Slide 7: New approaches needed to break the efficacy ceiling
Despite advances, new approaches are needed to break the efficacy ceiling and improve convenience of biologics Summary data for select agents that randomize patients post response to induction; data from labels, company reports. Vedolizumab approved in US as Q8W IV – Q2W SC approval pending followin
Slide 8: Spyre's strategy to address unmet needs in IBD
Spyre’s strategy to address unmet needs in IBD 1 2 3 Best-in-class mAb engineering With half-life extension technology Rational therapeutic combinations Precision patient selection Three strategic pillars in an effort to create the preeminent IBD company
Slide 9: Spyre mAbs introduce significant improvements over 1st generation mAbs
Spyre mAbs introduce significant improvements over 1st generation mAbs Epitopes maintained Validated pharmacology Equivalent or better potency Potential for IP into 2040s Novel dosing profile Improved manufacturability Coverage of diverse back-up series High concentration SQ Ability to formulate at
Slide 10: Rapidly developing combination products given clinical evidence
Spyre is rapidly developing combination products given clinical evidence of substantial efficacy enhancement 1 2 3 CLINICAL PRECENDENT JNJ VEGA Ph2a study Clinical remission at 12 weeks Anti-TNFα Anti-IL-23 Δ% Source: JNJ VEGA ECCO’22 Presentation Strong single-agent induction efficacy Orthogonal MO
Slide 11: Genetically-driven patient selection
Spyre leverages genetically-driven patient selection to match disease drivers with therapeutic targets 1 2 3 CLINICAL PRECENDENT TL1A studies UC clinical remission at 12 weeks Δ Δ PRA023 RVT-3101 TL1A a4b7 IL-23 Genetic companion diagnostic (CDx) leveraging large-scale human genomic datasets
Slide 12: 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 STRATEGY TARGET PROGRAM1 DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SP
Slide 13: 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 STRATEGY TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SPY
Slide 14: Vedolizumab is a mega-blockbuster product in IBD
Vedolizumab is a mega-blockbuster product in IBD Vedolizumab estimated $5.4B revenues WW in FY22.1 Projected to sell $7.5-9.0B at peak WW.1 1. Takeda JPM 2023 presentation. Note that Takeda’s FY22 is April 2022-March 2023. Sales forecast in figure: EvaluatePharma consensus “Biologic of choice is Ent
Slide 15: Vedolizumab binds a4b7 integrin with leading maintenance efficacy
Vedolizumab specifically binds a4b7 integrin, selectively blocking gut lymphocyte trafficking. Leading maintenance efficacy data in UC replicated in two P3 studies; efficacy on par with upadacitinib 15mg dose; superior head-to-head vs adalimumab (Humira) in UC. Clean safety profile since approval in
Slide 16: SPY001 is designed to be a best-in-class anti-α4β7 mAb
SPY001 is designed to be a best-in-class anti-⍺4β7 mAb *Entyvio SC US BLA resubmitted April 2023 following CRL in 2019. Highly potent Proven epitope Selective No ⍺4β1 binding, no VCAM-1 adhesion blocking Favorable safety profile High maintenance efficacy Convenient SC dosing Q8W or Q12W+ Convenient
Slide 17: SPY001 improvements over 1st generation mAbs
Spyre mAbs introduce significant improvements over 1st generation mAbs SPY001 Epitope maintained Validated pharmacology Equivalent potency Potential for IP into 2040s Diverse coverage of lead and backup series High concentration SC Ability to formulate at >150 mg/mL with low viscosity Citrate-free f
Slide 18: SPY001 is as potent and selective as vedolizumab
SPY001 is as potent and selective as vedolizumab SPY001 binds the same ⍺4b7 epitope as vedolizumab. SPY001 is comparable to vedolizumab in potency… …and avoids unwanted interactions with a4b1. a4 Subunit b7 Subunit SPY001 Epitope Blocking MADCAM-1 Adhesion Blocking VCAM-1 Adhesion
Slide 19: SPY001 binds memory T-helper cells as well as vedolizumab
SPY001 binds to memory T-helper cells as well as vedolizumab 1. Soler, et. al. (2009) Vedolizumab EC50 (nM) SPY001 EC50 (nM) Donor 1 0.22 0.21 Donor 2 0.27 0.30 Donor 3 0.24 0.22 PBMCs from three human donors were isolated and stained with either vedolizumab or SPY001, as well as a basic immunopheno
Slide 20: SPY001 17-day half-life in NHPs
SPY001 has exhibited a 17-day half-life in NHPs, nearly 2x the half-life of vedolizumab observed in multiple studies β-elimination half-life of SPY001 observed at ~17 days, 70% longer than observed for vedolizumab. Spyre vedolizumab data matches half-life observed in Takeda studies.1,2 NOTE: 1BLA 12
Slide 21: SPY001 utilizes proven YTE modification
SPY001 utilizes proven YTE modification to dramatically enhance half-life YTE modification typically increases mAb half-life by 2-4x versus wild-type in both NHP and human. Human YTE mAb half-life is on average 3.1x of NHP half-life. NOTE: Includes monoclonal antibodies targeting soluble antigens an
Slide 22: SPY001 formulated to maximize dosing without sacrificing comfort
SPY001 is specifically formulated to maximize dosing without sacrificing patient comfort Note: Vedolizumab SC approved in EU. US BLA resubmitted April 2023 following CRL in 2019. Vedolizumab SC 108 mg 20 mM Citrate SPY001 SC 300 mg Citrate Free 26 injections per year Potential injection site pain Se
Slide 23: Vedolizumab appears underdosed in induction
1. Rosario, M., et. al. (2017). 2. Vedolizumab FDA Clinical Pharmacology Review. Figure sources: Multi-MOA benchmark data from adalimumab label (TNFα), ustekinumab label (IL-12/23), mirikizumab LUCENT-1 study (IL-23), PRA023 P2b (TL1A), and vedolizumab VARSITY study (⍺4b7). Vedolizumab exposure-resp
Slide 24: Low vedolizumab exposures sufficient to maintain remission
Once induction is achieved, very low exposures of vedolizumab are sufficient to maintain remission Source: Feagan, et. al. (2013). Minimal difference in maintenance of clinical remission between vedolizumab IV Q4W (44.8%) or Q8W (41.8%). Ctrough ≥ 6 µg/mL is a conservative target to maintain long-te
Slide 25: SPY001 program summary and upcoming catalysts
SPY001 is a potentially best-in-class anti-a4b7 mAb with near-term de-risking studies anticipated SPY001 Preferred target in large market Clinically validated pharmacology Designed for differentiation Promising early data PROGRAM SUMMARY UPCOMING CATALYSTS 2Q2024 IND/CTN YE2024 Human PK/PD Vedolizum
Slide 26: Key value inflection in ~18 months
Key value inflection in ~18 months with Phase 1 PK data anticipated to validate SPY001 as “long-acting Vedo” Source: FactSet 30-d average market caps after event date. 1 Morphic Phase 2a single arm UC data; Prometheus RCT (UC) and single arm (CD) Phase 2.; Prometheus ultimately acquired for $10.8B a
Slide 27: 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 STRATEGY TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SPY
Slide 28: TL1A has emerged as a promising target in UC and CD
TL1A has emerged as one of the most promising targets in both UC and CD TL1A is involved in chronic inflammation and fibrosis pathways and is genetically associated with IBD. Clinical results from first-generation anti-TL1A antibodies suggest potential for highest induction efficacy across target cl
Slide 29: SPY002 is designed to be a best-in-class anti-TL1A mAb
SPY002 is designed to be a best-in-class anti-TL1A mAb PRA023 RVT-3101 SPY002 Complete TL1A blockade Monomers and trimers Highly potent Kd below 150 pM Infrequent SC dosing Q8W or Q12W+ Convenient formulation High concentration High induction remission Favorable safety profile Immunogenicity <20% AD
Slide 30: SPY002 improvements over 1st generation mAbs
Spyre mAbs introduce significant improvements over the 1st generation mAbs PRA023 clinically validates pharmacology and therapeutic effect of MOA Novel IP for composition of matter into 2040s SPY002 exploits biology that has been validated by PRA023 and is designed to be best-in-class High concentra
Slide 31: Evaluating trimeric and monomeric/trimeric TL1A blockade
Figure sources: Prometheus PRA023 P2 ARTEMIS-UC data release, December 7, 2022. Roivant RVT-3101 Release Deck, January 4, 2023. Spyre is evaluating both trimeric and monomeric/trimeric TL1A blockade for SPY002 RVT-3101 Monomers & trimers Trimers only UC clinical remission rates Pbo-adjusted % Spyre
Slide 32: De novo TL1A lead clones are highly potent and diverse
De novo TL1A lead clones are highly potent and characteristically diverse Illustrative Spyre clones observed to be more potent than leading competitors …with diverse profiles of monomer binding and/or DcR3 sparing Spyre has multiple lead clones that have demonstrated superior potency as compared to
Slide 33: Potential upside if sub-optimal dosing of first-generation anti-TL1A identified
Potential for further upside if sub-optimal dosing of first-generation anti-TL1A mAbs identified Across many mechanisms in IBD, Phase 3 data were required to assess exposure-response.1 First-in-class anti-TL1A mAbs tested single induction regimen2, providing insufficient evidence to select optimal d
Slide 34: SPY002 program summary and upcoming catalysts
SPY002 is a potentially best-in-class anti-TL1A mAb with near-term de-risking studies anticipated SPY002 Attractive target in a large market Clinically validated pharmacology Designed for differentiation Promising early data PROGRAM SUMMARY UPCOMING CATALYSTS 2H2024 IND/CTN 1H2025 Human PK/PD Existi
Slide 35: TL1A: potential I&I indication expansion
TL1A: Potential I&I indication expansion with dual anti-fibrotic and anti-inflammatory mechanism IBD SSc-ILD Expansion I&I indications FIBROSIS INFLAMMATION TL1A TL1A directly activates fibroblasts TL1A stimulates pro-inflammatory effect
Slide 36: 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 STRATEGY TARGET PROGRAM DISCOVERY IND-ENABLING CLINICAL Best-in-class mAbs (Extended half-life) a4b7 Same MOA as vedolizumab SPY001 TL1A Same MOA as PRA023 SPY002 IL-23 SPY003 Novel MOA SPY
Slide 37: Spyre portfolio addresses diverse pathophysiology of IBD
Spyre portfolio addresses the diverse pathophysiology of IBD Spyre is a pioneer in developing best-in-class mAbs against three top targets to enable superior combinations for IBD Blockade of α4β7 prevents circulating T-cells from entering inflammatory gut tissues Neutralization of TL1A suppresses in
Slide 38: JNJ's VEGA study demonstrated power of combination therapy
JNJ's VEGA study demonstrated power of combination therapy despite relative weakness of components Golimumab (TNFα) Guselkumab (IL-23) Combination N= 72 71 71 Maintenance remission* 28% 31% 48% Safety Poor (class effect) Well tolerated Mixed Despite non-optimal components, JNJ combination (JNJ-78934
Slide 39: Spyre could create optimal combinations in IBD
Program UC Induction UC Maintenance Safety Dosing JNJ-4804 TNFα + IL-23 TNFα black-box safety warning Broad immunosuppression Q4W SPY120 a4b7 + TL1A Gut-selective α4β7 backbone + Encouraging TL1A safety profile Q8-12W SPY130 a4b7 + IL-23 Gut-selective α4β7 backbone + 2nd safest class in IBD Q8-12W S
Slide 40: Rapidly advance combination programs in parallel in Phase 2
We plan to rapidly advance combination programs in parallel with monotherapies in Phase 2 Preliminary; pending regulatory feedback CONFIDENTIAL Phase 1 Phase 2 Phase 3 SAD 1 SAD 2 SAD 3 MAD 1 MAD 2 UC SPY001 low dose SPY001 high dose SPY001 low dose + IL-23 SPY001 high dose + IL-23 PBO UC SPY001 (α4
Slide 41: Developing best-in-class combinations to maximize efficacy
Spyre is developing potentially best-in-class combinations to maximize efficacy for patients with IBD Established combination precedent Ideal building blocks Rapid proof-of concept PROGRAM SUMMARY UPCOMING CATALYSTS 2025 Ph2 initiation with SPY001 backbone JNJ VEGA study demonstrated unprecedented e
Slide 42: Precision immunology
Precision immunology We aim to develop companion diagnostics to augment our therapeutic combinations and monotherapies We believe the future of IBD includes combination therapies and precision approaches to break the therapeutic ceiling IL-23 TL1A a4b7 TL1A a4b7 IL-23 IL-23 + a4b7 TL1A + a4b7 IBD pa
Slide 43: Genetic CDx can identify responders to TL1A
Prometheus and Roivant demonstrated POC that a genetic CDx can identify responders to TL1A RVT-3101 TL1A Δ UC clinical remission at 12 weeks Source: Company materials PRA023 TL1A Δ UC clinical remission at 12 weeks CDx partner CDx partner Spyre aims to develop genetic companion diagnostics across a
Slide 44: Spyre Therapeutics Corporate
A SPYRE THERAPEUTICS Corporate
Slide 45: Leadership and BOD
Leadership and BOD Cameron Turtle Chief Operating Officer Justin LaFountaine VP, Corporate Development Peter Harwin Board of Directors Tomas Kiselak Board of Directors Ivana Magovčević-Liebisch Board of Directors Janet Gunzner-Toste SVP, Operations Andy Spencer SVP, Preclinical R&D Russell J. Cox Ch
Slide 46: Cash and anticipated milestones
Cash and anticipated milestones SPY001 (SC, extended half-life a4b7) 2Q – IND/CTN YE – POC PK in HVs Full PK in HVs Phase 2 initiation SPY002 (SC, extended half-life TL1A) 1H – R&D Day 2H – IND/CTN PK in HVs SPY003 (SC, extended half-life IL-23) 1H – R&D Day IND/CTN SPY004 (SC, extended half-life no
Slide 47: I&I companies with compelling science have maintained value
I&I companies with compelling science have maintained value even in market downturns NOTE: “Today” market cap as of April 17, 2023 SOURCE: FactSet. Company S-1s. IPO Raise Market Cap ($M) Min IPO Today Max Stage at IPO Lead program status at fundraising Prometheus Biosciences $219 Lead anti-TL1A pro
Slide 48: Comparable acquisitions illustrate potential exits
Acquirer Target Deal economics (year) Status of lead asset We believe Spyre programs could be at comparable stage by 2025 2026 2027 $1.85B (2021) Proof-of-mechanism in P1a (HVs); potential for UC & autoimmune indications. SPY001 SPY003 SPY002 SPY004 $1.435B total (2021) $1.1B upfront $350M milestone
Slide 49: Thank you
Thank you
Slide 50: Spyre is launching as Paragon's second spin-out
Spyre is launching as Paragon’s second spin-out, focused on developing potentially best-in-class antibodies for IBD Paragon Therapeutics was founded in 2021 by Fairmount. Professionals with deep expertise in antibody engineering and drug development from across the industry. Capabilities augmented b
Aeglea BioTherapeutics — Merger or Acquisition (June 2023) on 6ix