Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (March 2023)
39 slides from Spyre Therapeutics's investor presentation, Mar 2, 2023
Slide 1: Redefining the Possible. Human Enzyme Therapies for People with Rare Diseases
Redefining the Possible. Human Enzyme Therapies for People with Rare Diseases Corporate Overview – March 2023 Nasdaq: AGLE Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements ©2023 Aeglea BioTherapeutics 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 statements include al
Slide 3: Our vision and mission
©2020 Aeglea BioTherapeutics. External Our vision is to redefine the possible, pioneer bold science with human enzymes and deliver groundbreaking medicines that transform lives. We are on a mission to change lives by bringing innovative therapies to underserved rare disease communities.
Slide 4: Redefining the Possible with Human Enzyme Therapies
©2023 Aeglea BioTherapeutics. External Redefining the Possible with Human Enzyme Therapies Strong Scientific Foundation Patient-Focused Approach With engineered human enzymes, we believe we can: Impact underlying key metabolites that drive clinical manifestations Address unmet medical needs with rat
Slide 5: Aeglea's Human Enzyme Therapies for Rare Metabolic Diseases
Program Research Phase 1/2 Phase 3 Regulatory Review Addressable Market Geographic Rights Pegtarviliase Homocystinuria ~25,000 Patients1 Worldwide rights Pegzilarginase Arginase 1 Deficiency >2,500 Patients2 Retain rights outside of Europe and Middle East3 Preclinical Programs Including Cystinuria C
Slide 6: Highlights and Upcoming Milestones
Highlights and Upcoming Milestones Pegtarviliase in Homocystinuria: Fast Track Designation received from FDA Currently dosing in cohort 3 at 1.35 mg/kg once weekly in Phase 1/2 clinical trial Pegzilarginase in Arginase 1 Deficiency: MAA under review with EMA, potential decision on approval in late 2
Slide 7: Pegtarviliase – Potential Best-in-Class Treatment for Homocystinuria
Pegtarviliase – Potential Best-in-Class Treatment for Homocystinuria
Slide 8: Classical Homocystinuria: A Rare Metabolic Disorder With Serious Complications
Classical Homocystinuria (HCU) Classical Homocystinuria: A Rare Metabolic Disorder With Serious and Potentially Deadly Complications Also known as cystathionine beta synthase (CBS) deficiency, Classical Homocystinuria is a serious and progressive metabolic disorder characterized by elevated levels o
Slide 9: Persistently High Homocysteine Levels Put Patients at Risk
With Persistently High Total Homocysteine Levels, Patients Remain at Risk for Serious and Life-Threatening Complications Compliance with severe dietary restrictions and amino acid supplementation is extremely challenging and represents a lifelong burden Vitamin B6 is largely ineffective at lowering
Slide 10: Classical HCU: A Sizeable Patient Population at Serious Risk
Classical HCU: A Sizeable Patient Population at Serious Risk of Severe Complications Over 80% of patients are unable to achieve total homocysteine levels <50 µM with B6 alone, the definition of B6 responsiveness This translates into an estimated ~25,000 treatment candidates in global addressable mar
Slide 11: Pegtarviliase: An Innovative Enzyme Approach to Lowering Homocysteine
Pegtarviliase: An Innovative Enzyme Approach to Lowering Homocysteine Pegtarviliase Mechanism Engineered Cystathionine -Lyase (CGL) enzyme mutated to change its native substrate specificity from cystathionine to both homocysteine and its dimer Concentration gradient drives homocysteine out of tissu
Slide 12: Dose-Dependent Lowering of Homocysteine in Mouse Model
Experimental Design: 10-day old CBS knockout mice were dosed with pegtarviliase twice per week for 5 weeks to ensure they were able to grow to sufficient size for future blood sampling Prior to a single subcutaneous dose of pegtarviliase, there was a two-week wash out To ensure accurate tHcy assessm
Slide 13: Preclinical Data Support Once-Weekly Dosing of Pegtarviliase
©2023 Aeglea BioTherapeutics Preclinical Data Support Once-Weekly Dosing of Pegtarviliase Significant Survival Benefit in Knockout Mouse1,2 1 Daige C. et al. Poster presented at ASHG 2020 Virtual Meeting. 2 Mice were maintained on betaine until weaning; tHcy = total homocysteine Pegtarviliase (10 mg
Slide 14: Phase 1/2 Clinical Trial to Generate Proof-of-Concept
Phase 1/2 Clinical Trial to Generate Proof-of-Concept and Path to Pivotal Trial Cohort 2 Cohort 3 PART 1 (Intravenous) PART 2 (Subcutaneous) Dose 0.45 mg/kg n = 4 Dose 1.35 mg/kg Ongoing Dose 0.15 mg/kg n = 3 Cohort 1 Cohort 5 (optional) Continuing to Dose Patients in Cohort 3 Cohort 4 (optional)
Slide 15: Advancing a Potential Best-in-Class Therapy for Classical HCU
Data from cohorts 1 through 3 may be sufficient for discussions with FDA on pivotal trial design Manufacturing at commercial scale Stable, high-concentration liquid formulation Engagement with the patient and HCP communities to educate and increase awareness Orphan Disease, Fast Track and Rare Pedia
Slide 16: Pegzilarginase for Arginase Deficiency
Pegzilarginase for Arginase 1 Deficiency
Slide 17: The Progressive Impact of Persistently High Plasma Arginine
The Progressive Impact of Persistently High Plasma Arginine1-4 Arginase 1 Deficiency (ARG1-D) Disease Overview 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 ale
Slide 18: Pegzilarginase Program Overview
Pegzilarginase Program Overview Commercial Opportunity >2,500 patients in global addressable markets1 High unmet medical need No approved therapies to address high arginine levels Regulatory Designations U.S. Rare Pediatric Disease (PRV eligible) Breakthrough Therapy U.S. Orphan Drug EU Orphan Drug
Slide 19: PEACE Phase 3: Marked and Sustained Reduction in Plasma Arginine
PEACE Phase 3 Trial: Marked and Sustained Reduction in Plasma Arginine Primary Endpoint: Reduction in Plasma Arginine* Enns G, et al. Poster presented at SIMD 2022 Annual Meeting; *Based on arithmetic mean of values from visit and preceding 3 visits, boxes represent middle 50% with error bars depict
Slide 20: PEACE Phase 3: Mobility Assessed by GMFM-E and 2MWT
PEACE Phase 3 Trial: Mobility Assessed by GMFM-E and 2MWT Pegzilarginase Placebo 12 Weeks 24 Weeks 12 Weeks 24 Weeks MCID1, 2 GMFCS I (4.0 units) GMFCS II (2.8 units) Positive Trend in GMFM-E in Placebo-Controlled Study Suggests Potential Improvement in Mobility Time LS Mean Difference P Value 12 We
Slide 21: Patient-Level Analysis of Arginine Normalization and Clinical Responses
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 placebo Clinical response criteria for ≥1 asse
Slide 22: PEACE Phase 3: Pegzilarginase Safety Profile
PEACE Phase 3: Pegzilarginase Safety Profile Enns G, et al. Poster presented at SIMD 2022 Annual Meeting; 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
Slide 23: Regulatory and Program Status
Regulatory and Program Status MAA Under Review by EMA MAA filing accepted in August 2022 Potential decision on approval in late 2023 Manufacturing in place to support commercialization in Europe and Middle East Continuing to engage with FDA to identify potential path towards BLA resubmission Refusal
Slide 24: Summary
Summary
Slide 25: Highlights and Upcoming Milestones
Highlights and Upcoming Milestones Pegtarviliase in Homocystinuria: Fast Track Designation received from FDA Currently dosing in cohort 3 at 1.35 mg/kg once weekly in Phase 1/2 clinical trial Pegzilarginase in Arginase 1 Deficiency: MAA under review with EMA, potential decision on approval in late 2
Slide 26: Financial Summary
Financial Summary $ Millions Year Ended 12/31/22 Year Ended 12/31/21 Revenue $2.3 $18.7 R&D Expense $58.6 $57.1 G&A Expense $28.5 $27.3 Net Loss $83.8 $65.8 Cash and available funds as of December 31, 2022: $57.31 million (no debt) As of February 21, 2023, 94.3 million2 common shares and pre-funded
Slide 27: Las Cimas Parkway Suite Austin, TX 78746 aeglea.com
805 Las Cimas Parkway Suite 100 Austin, TX 78746 aeglea.com
Slide 28: Homocysteine Metabolism & Pegtarviliase Mechanism of Action
Homocysteine Metabolism & Pegtarviliase Mechanism of Action Methionine Homocysteine Cystathionine Cysteine Cystathionine ß-Synthase (CBS) Homocysteine monomer Homocystine dimer/disulfide ~30% ~1% ~70% Protein-Bound Homocysteine Betaine Pyridoxine (B6) Intracellular Serine Dietary Protein Pegtarvilia
Slide 29: Natural History Study of Untreated Classical Homocystinuria Patients
Natural History Study of 629 Untreated Classical Homocystinuria Patients Elevated levels of homocysteine Mortality by age 30 23% 4% Most common cause of death Thromboembolism Lens dislocation in 50% Age 6 Age 10 Median IQ 56 78 Chance of thrombosis by age 15 27% 12% Increased Mortality and High Risk
Slide 30: Pegtarviliase Improved Pathologies in a Mouse Model of Homocystinuria
Pegtarviliase Treatment Improved Pathologies and Corrected Disease Manifestations in a Mouse Model of Homocystinuria 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-/- P
Slide 31: PEACE Baseline Demographics
PEACE Baseline Demographics Demographic Characteristic Pegzilarginase n=21 Placebo n=11 Overall N=32 Age at Enrollment, y Mean (SD) 9.6 (6.16) 12.9 (6.77) 10.7 (6.47) Range 2-28 5-29 2-29 Age Category, n (%) 2y to less than 6y 5 (23.8) 1 (9.1) 6 (18.8) 6y to less than 12y 8 (38.1) 4 (36.4) 12 (37.5)
Slide 32: PEACE Baseline Clinical Characteristics
PEACE Baseline Clinical Characteristics Clinical Characteristic Pegzilarginase n=21 Placebo n=11 Overall N=32 Plasma Arginine, µM/L Mean* (SD) 365.4 (93.7) 471.7 (79.9) 402.0 (101.8) Median (range) 368.2 (202-572) 483.7 (294-573) 398.2 (202-573) GMFCS level, n (%) 1 9 (42.9) 5 (45.5) 14 (43.8) ≥2 12
Slide 33: Pegzilarginase Reduces Plasma Arginine Levels in Phase 1/2 & OLE
Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels in Phase 1/2 & OLE 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 wa
Slide 34: Mobility Assessments in Phase 1/2 Trial & OLE
Mobility Assessments Capture Potential Clinical Benefit of Pegzilarginase in Phase 1/2 Trial & OLE 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 1Adapt
Slide 35: Improvements in Mobility Measures Sustained Over Time
Improvements in Mobility Measures Sustained Over Time in Phase 1/2 and OLE Endpoint Change from Baseline for Phase 1/2 & OLE Studies3 20-week analysis (N=13) 32-week analysis (N=13) 56-week analysis (N=13) 104-week analysis (N=9)4 GMFM-E 4.2 units 4.1 units 5.8 units 7.1 units 6MWT 32.2 m 21.3 m 44.
Slide 36: Measuring the Functional Impact of Spasticity in ARG1-D
Measuring the Functional Impact of Spasticity in ARG1-D 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 without b
Slide 37: PEACE Phase 3 Study Design
Double-blind portion of trial complete – topline data announced December 2021 Key Endpoints Analysis Primary: Plasma arginine reduction Reduction of plasma arginine compared to placebo Secondary: GMFM-E (walking, running & jumping) 2-Minute Walk Test (distance walked in 2 min) Continuous analysis Im
Slide 38: Patient-Level Outcomes: Mobility in Select Patients
Patient-Level Outcomes: Mobility in Select Patients Pegzilarginase-Treated Patients Achieving Clinical Response on ≥2 Mobility Outcomes and No Worsening at Week 24 Normalization of Mobility in Progressive Disease Supports the Potential Impact of Pegzilarginase Treatment Patient (Age) GMFM-E (Score R
Slide 39: Attractive Commercial Opportunity and a Targeted Launch Plan
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, S
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