Spyre Therapeutics, Inc. · NASDAQ:SYRE

Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (August 2022)

41 slides from Spyre Therapeutics's investor presentation, Aug 4, 2022

  1. Slide 1: Reimagining The Potential Of Human Enzyme Therapeutics

    Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview – August 2022 Nasdaq: AGLE Exhibit 99.2

  2. Slide 2: Forward Looking Statements

    Forward Looking Statements ©2022 Aeglea BioTherapeutics. External 2 This presentation and the accompanying oral presentation contain “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statement

  3. Slide 3: Addressing Metabolic Imbalances to Improve the Lives of Patients

    Addressing Metabolic Imbalances to Improve the Lives of Patients ©2022 Aeglea BioTherapeutics. External 3 Aeglea BioTherapeutics At Aeglea, we believe that every patient deserves a chance at a better life. We are committed to helping people with rare and devastating metabolic diseases who have limit

  4. Slide 4: Program Highlights and Upcoming Milestones

    ©2022 Aeglea BioTherapeutics. External 4 Program Highlights and Upcoming Milestones Pegzilarginase in ARG1-D: Actively engaged with FDA to identify potential paths to address clinical request in Refusal to File letter and progress the program towards potential U.S. approval On track with EU regulato

  5. Slide 5: Aeglea's Human Enzyme Platform for Rare Metabolic Diseases

    5 Aeglea’s Human Enzyme Platform for Rare Metabolic Diseases 1 Ex-U.S. license and supply agreement with Immedica to commercialize pegzilarginase in Europe and certain countries in the Middle East (European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey

  6. Slide 6: Pegzilarginase for Arginase Deficiency

    Pegzilarginase for Arginase 1 Deficiency

  7. Slide 7: The Progressive Impact of Persistently High Plasma Arginine

    The Progressive Impact of Persistently High Plasma Arginine1-4 Arginase 1 Deficiency (ARG1-D) Disease Overview 7 Infancy2-4,7,8 Initial 6-12 months may be uneventful May present with seizures, episodes of hyperammonemia: irritability, feeding difficulties, poor appetite, nausea/vomiting, decreased a

  8. Slide 8: Pegzilarginase Program Overview

    8 Pegzilarginase Program Overview Commercial Opportunity >2,500 patients in global addressable markets1 >1,150 patients in territories with regulatory and launch plans underway High unmet medical need No approved therapies to address high arginine levels Regulatory Designations U.S. Rare Pediatric D

  9. Slide 9: PEACE Phase 3 Study Design

    Double-blind portion of trial complete – topline data announced December 2021 9 PEACE Phase 3 Study Design *Dosing is weekly and, if needed, dose is modified based on plasma arginine levels with maintenance of blinding. ǂThe first 8 weeks of the open-label extension will be blinded. All study partic

  10. Slide 10: Primary Endpoint Met – Marked and Sustained Reduction in Plasma Arginine

    10 Highly elevated plasma arginine despite standard of care Mean plasma arginine* Pegzilarginase Baseline: 365.4 µM 24-week: 105.5 µM Placebo Baseline: 471.7 µM 24-week: 448.8 µM Primary Endpoint Met – Marked and Sustained Reduction in Plasma Arginine Reduction in Plasma Arginine* *Based on arithmet

  11. Slide 11: Normalization of Plasma Arginine Levels in ARG1-D Patients

    90.5% of pegzilarginase treated patients achieved normal plasma arginine levels (p<0.0001)* No meaningful change in plasma arginine levels in placebo arm Treatment with pegzilarginase surpassed current clinical guideline goals of reducing arginine levels below 200 µM 11 Normalization of Plasma Argin

  12. Slide 12: Mobility Assessed by GMFM-E and 2MWT

    Mobility Assessed by GMFM-E and 2MWT 12 Mean Change from Baseline in 2MWT Mean Change from Baseline in GMFM-E 1 MCID is minimal clinically important difference defined in Cerebral Palsy population. 2Oeffinger D et al 2008; GMFM-E = Gross Motor Function Measure Part E; 2MWT = 2-minute walk test; GMFC

  13. Slide 13: Patient-Level Outcomes Across Efficacy Endpoints

    ©2022 Aeglea BioTherapeutics. External 13 In a patient-level analysis clinically important differences between treatment arms were evident for both arginine normalization and clinical responses 16 of 17 pegzilarginase treated patients normalized arginine levels compared to NO patients receiving plac

  14. Slide 14: Patient-Level Outcomes: Mobility in Select Patients

    ©2022 Aeglea BioTherapeutics. External 14 Patient-Level Outcomes: Mobility in Select Patients Pegzilarginase-Treated Patients Achieving Clinical Response on ≥2 Mobility Outcomes and No Worsening at Week 24 Ages are at the time of enrollment; Normalization defined at ±15% of age/sex-matched mean dist

  15. Slide 15: Pegzilarginase Safety Profile – Results from PEACE

    15 Pegzilarginase Safety Profile – Results from PEACE AE = Adverse Event; *Serious AEs were hyperammonemia/hyperammonemia-related events and vomiting Pegzilarginase was Well-Tolerated with No Discontinuations in Pivotal Study Due to Adverse Events No discontinuations due to treatment-emergent advers

  16. Slide 16: Engaging with U.S. Regulators on Path to Potential Pegzilarginase Approval

    ©2022 Aeglea BioTherapeutics. External 16 Engaging with U.S. Regulators on Path to Potential Pegzilarginase Approval Compelling Clinical Results 48 patients enrolled across 3 clinical studies Primary endpoint of arginine lowering met in Phase 3 study (p<0.0001) – marked and rapid lowering of arginin

  17. Slide 17: AGLE-177 for Homocystinuria

    AGLE-177 for Homocystinuria

  18. Slide 18: Homocystinuria Disease Overview

    Homocystinuria Disease Overview 18 1 >30,000 represents estimated prevalence of Classical Homocystinuria (including B6-responsive and B6-non-responsive) in 38 addressable markets. 2 Mudd et al 1985. 3 Kožich et al, 2020. 4 ~6,000-6,600 represents estimated prevalence of B6-non-responsive Homocystinu

  19. Slide 19: Natural History Study of Untreated Classical Homocystinuria Patients

    Natural History Study of 629 Untreated Classical Homocystinuria Patients 19 Increased Mortality and High Risk of Severe Complications B6-responsive = 231 All patients = 629 B6-non-responsive = 231 MORTALITY NATURAL HISTORY Mudd et al, 1985. Kluijtmans et al, Am. J. Hum. Genet. 65,59-67, 1999 B6-non-

  20. Slide 20: AGLE-177 for Homocystinuria Overview

    AGLE-177 for Homocystinuria Overview 20 Intracellular Metabolism – Normal & Disease State Plasma Metabolism – AGLE-177 Homocysteine (monomer) Homocystine (dimer) AGLE-177 Homocysteine (protein bound) Decrease in plasma homocysteine and homocystine X AGLE-177 Mechanism Engineered Cystathionine -Lyas

  21. Slide 21: Preclinical Data Support Potential Advantages of AGLE-177

    21 Preclinical Data Support Potential Advantages of AGLE-177 Marked survival benefit with total weekly dose as low as 2 mg/kg 1 Daige C. et al. Poster presented at ASHG 2020 Virtual Meeting. 2 Majtan T. et al., Life Sci. 2018; May 1;200:15-25. 3 Mice were maintained on betaine until weaning; tHcy =

  22. Slide 22: Phase 1/2 Clinical Trial to Generate Proof-of-Concept and Path to Pivotal Trial

    ©2022 Aeglea BioTherapeutics. External 22 Phase 1/2 Clinical Trial to Generate Proof-of-Concept and Path to Pivotal Trial Cohort 2 Cohort 3 PART 1 (IV) PART 2 (SC) Dose 0.45 mg/kg n = 4 Currently Enrolling Dose 0.15 mg/kg n = 3 Cohort 1 Cohort 5 (optional) Data Expected in Q4 2022  IV = intravenous

  23. Slide 23: AGLE-177: a Potentially Differentiated Treatment for Homocystinuria

    23 AGLE-177: a Potentially Differentiated Treatment for Homocystinuria Metabolizes both homocysteine (monomer) and homocystine (dimer) Showed total homocysteine reduction, no safety concerns in cohort 1 of Phase 1/2 trial Demonstrated significant survival benefit in CBS -/- mice at low total weekly

  24. Slide 24: Human Enzyme Engineering Platform

    Human Enzyme Engineering Platform

  25. Slide 25: Cystinuria Overview

    Cystinuria Overview 25 Cystinuria: Cystinuria is a metabolic disorder characterized by high levels of amino acid cystine in the urine, leading to the formation of stones in the kidney, ureter and bladder. Persistent stones can result in serious damage to the kidneys, causing an increased risk of hyp

  26. Slide 26: AGLE-325 Preclinical Advancement

    26 AGLE-325 Preclinical Advancement New candidate advanced through lead optimization with preclinical efficacy and PK/PD profile which support attractive clinical dosing schedule µCT Kidney Stone Volume1 Kidney Pathology1 N=16 N=32 INNOVATIVE ENZYME APPROACH Enzymatic reduction of plasma cystine sho

  27. Slide 27: Leveraging Aeglea's Next Generation Human Enzyme Platform

    Leveraging Aeglea’s Next Generation Human Enzyme Platform 27 High activity human pegylated investigational enzyme Degrades key accumulating metabolite Results in restorative phenotypic improvements in genetically engineered mouse model PROOF OF CONCEPT Vehicle Control Therapeutic Enzyme ©2022 Aeglea

  28. Slide 28: Summary

    Summary

  29. Slide 29: Program Highlights and Upcoming Milestones

    ©2022 Aeglea BioTherapeutics. External 29 Program Highlights and Upcoming Milestones Pegzilarginase in ARG1-D: Actively engaged with FDA to identify potential paths to address clinical request in Refusal to File letter and progress the program towards potential U.S. approval On track with EU regulat

  30. Slide 30: Las Cimas Parkway Suite Austin, TX 78746 aeglea.com

    805 Las Cimas Parkway Suite 100 Austin, TX 78746 aeglea.com

  31. Slide 31: Financial Summary

    Financial Summary 31 “Non-GAAP” cash, cash equivalents and marketable securities as of June 30, 2022: $90.41 million (no debt) As of June 30, 2022, 94.2 million2 common shares and pre-funded warrants outstanding Expected funding runway: through second quarter of 2023 1 Includes $1.8mm of restricted

  32. Slide 32: Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels in Phase 1/2 & OLE

    Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels in Phase 1/2 & OLE 32 Plasma Arginine in Response to Pegzilarginase in Phase 1/2 & OLE Studies Baseline: Baseline plasma arginine on standard disease management was markedly elevated 20 Week Analysis1: Median plasma arginine

  33. Slide 33: Mobility Assessments Capture Potential Clinical Benefit of Pegzilarginase in Phase 1/2 Trial & OLE

    Mobility Assessments Capture Potential Clinical Benefit of Pegzilarginase in Phase 1/2 Trial & OLE 33 Continuous Analysis Mean Change from Baseline GMFCS – Level II/III GMFCS – Level I CE = Ceiling Effect 20 Week Analysis: 11/14 (79%) 56 Week Analysis: 11/13 (85%) Categorical Responder Analysis2 1Ad

  34. Slide 34: Improvements in Mobility Measures Sustained Over Time in Phase 1/2 and OLE

    34 Improvements in Mobility Measures Sustained Over Time in Phase 1/2 and OLE 48 1 MCID is minimal clinically important difference defined in Cerebral Palsy population. 2Oeffinger D et al 2008; 3 Analysis weeks are calculated by adding the 8 weeks from Part 2 of the Phase 1/2 study to the weeks of t

  35. Slide 35: PEACE Baseline Demographics

    PEACE Baseline Demographics 35 ©2022 Aeglea BioTherapeutics. External

  36. Slide 36: PEACE Baseline Clinical Characteristics

    PEACE Baseline Clinical Characteristics 36 *Based on arithmetic mean ©2022 Aeglea BioTherapeutics. External

  37. Slide 37: Measuring the Functional Impact of Spasticity in ARG1-D

    Measuring the Functional Impact of Spasticity in ARG1-D 37 Gross Motor Function Classification System (GMFCS) Overall description of current motor function based on: Movements such as sitting, walking Use of mobility devices Gross Motor Function Measure (GMFM) Part E Assesses unaided mobility withou

  38. Slide 38: Attractive Commercial Opportunity and a Targeted Launch Plan

    38 Attractive Commercial Opportunity and a Targeted Launch Plan 1 Catsburg C et al 2022 2 Licensing and supply agreement signed with Immedica Pharma AB in March 2021; countries in agreement include European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey

  39. Slide 39: Continued patient identification momentum across key markets

    Continued patient identification momentum across key markets Gaining valuable insights into disease management and patient characteristics Progress is outpacing relevant benchmarks Driving increased awareness of ARG1-D to facilitate accurate diagnosis THINK ARGININE™: a disease awareness initiative

  40. Slide 40: Laying the Groundwork to Transition Smoothly to Commercial Operations

    Laying the Groundwork to Transition Smoothly to Commercial Operations 40 High-touch patient services model is being developed based on our deep understanding of the needs of the ARG1-D patient community Thoughtful, targeted approach to payer engagement focused on payers most likely to have ARG1-D co

  41. Slide 41: AGLE-177 Improves Pathologies and Correction of Disease Manifestations in a Preclinical Model of Homocystinuria

    AGLE-177 Improves Pathologies and Correction of Disease Manifestations in a Preclinical Model of Homocystinuria 41 Disease Resolution Disease Reversal Dosing Begins Day 10 CBS-/- Macro-steatosis Disease Progression AGLE-177-HIS 25 mg/kg + Betaine Day 23 CBS-/- AGLE-177-HIS 25 mg/kg Day 60 CBS-/- PBS

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