Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (January 2022)
40 slides from Spyre Therapeutics's investor presentation, Jan 5, 2022
Slide 1: Reimagining The Potential Of Human Enzyme Therapeutics
Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview – January 2022 Nasdaq: AGLE Exhibit 99.1
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
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
Slide 4: Looking Ahead to 2022
Looking Ahead to 2022 Key 2021 Highlights 4 Pegzilarginase File U.S. BLA (1H 2022) and EU MAA Continue preparations for strong, rapid launch in U.S., Europe and Middle East Presentation of PEACE data at upcoming key metabolic conference; publication of long-term data AGLE-177 Clinical data from Phas
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
Slide 6: Pegzilarginase for Arginase Deficiency
Pegzilarginase for Arginase 1 Deficiency
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
Slide 8: Pegzilarginase Program Overview
8 Pegzilarginase Program Overview Commercial Opportunity >2,500 patients in global addressable markets >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 Di
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
Slide 10: Pegzilarginase Safety Profile – Results from PEACE
10 Pegzilarginase Safety Profile – Results from PEACE * TEAE: Treatment-Emergent Adverse Event; ǂ SAE: Serious Adverse Event; ♢ Adverse Event of Interest Pegzilarginase was Well-tolerated with No Discontinuations in Pivotal Study Due to Adverse Events No discontinuations due to TEAEs Most TEAEs were
Slide 11: Primary Endpoint Met – Marked and Sustained Reduction in Plasma Arginine
11 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 – 24-Week Analysis 80% reduction in mean plasma arginine with pegzilarginase (p<0.0001)ǂ Primary Endpoin
Slide 12: 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 12 Normalization of Plasma Argin
Slide 13: PEACE Mobility Assessed by GMFM-E and 2MWT
PEACE Mobility Assessed by GMFM-E and 2MWT 13 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
Slide 14: Improvements in Mobility Measures Sustained Over Time in Phase 1/2 and OLE
14 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
Slide 15: Clinically Meaningful Results
15 Clinically Meaningful Results Normalized arginine levels which was previously unachievable in this patient population GMFM-E trend highly suggestive of mobility benefit with improvement over time Mean changes in both trials greater than MCID of 4 units and 2.8 units for GMFCS Levels I and II resp
Slide 16: Regulatory Next Steps for BLA Submission
Regulatory Next Steps for BLA Submission Pre-BLA meeting Discussion of data package and additional submission details BLA submission to the FDA Plan to request priority review based on regulatory designations Acceptance of BLA and assignment of PDUFA date Notified of acceptance status expected withi
Slide 17: Attractive Commercial Opportunity and a Targeted Launch Plan
17 Attractive Commercial Opportunity and a Targeted Launch Plan 1 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, Saudi Arabia, United A
Slide 18: 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
Slide 19: Laying the Groundwork to Transition Smoothly to Commercial Operations
Laying the Groundwork to Transition Smoothly to Commercial Operations 19 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
Slide 20: AGLE-177 for Homocystinuria
AGLE-177 for Homocystinuria
Slide 21: Homocystinuria Disease Overview
Homocystinuria Disease Overview 21 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
Slide 22: Natural History Study of Untreated Classical Homocystinuria Patients
Natural History Study of 629 Untreated Classical Homocystinuria Patients 22 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-
Slide 23: AGLE-177 for Homocystinuria Overview
AGLE-177 for Homocystinuria Overview 23 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
Slide 24: Preclinical Data Support Potential Advantages of AGLE-177
24 Preclinical Data Support Potential Advantages of AGLE-177 Marked survival benefit with total weekly dose as low as 2mg/kg 1 Daige C. et al. Poster presented at ASHG 2020 Virtual Meeting. 2 Majtan T. et al., FASEB J. 2017; 31(12):5495-5506. 3 Mice were maintained on betaine until weaning; sc = sub
Slide 25: Phase 1/2 Clinical Trial – Enrollment and Dosing Underway
Phase 1/2 Clinical Trial – Enrollment and Dosing Underway 25 Endpoints Key Inclusion Criteria Enrollment & Dosing Safety and tolerability PK Reduction in plasma total homocysteine levels Classical Homocystinuria diagnosis Plasma homocysteine >80 µM ≥12 years of age Anticipate enrolling 16-20 patient
Slide 26: AGLE-177: a Potentially Differentiated Treatment for Homocystinuria
26 AGLE-177: a Potentially Differentiated Treatment for Homocystinuria Metabolizes both homocysteine (monomer) and homocysteine (dimer) Demonstrated significant survival benefit in CBS -/- mice at low total weekly doses Reduces homocysteine levels in CBS -/- mice with single and twice weekly dosing
Slide 27: Human Enzyme Engineering Platform
Human Enzyme Engineering Platform
Slide 28: Cystinuria Overview
Cystinuria Overview 28 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
Slide 29: AGLE-325 Preclinical Advancement
29 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
Slide 30: Leveraging Aeglea's Next Generation Human Enzyme Platform
Leveraging Aeglea’s Next Generation Human Enzyme Platform 30 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
Slide 31: Summary
Summary
Slide 32: Looking Ahead to 2022
Looking Ahead to 2022 Key 2021 Highlights 32 Pegzilarginase File U.S. BLA (1H 2022) and EU MAA Continue preparations for strong, rapid launch in U.S., Europe and Middle East Presentation of PEACE data at upcoming key metabolic conference; publication of long-term data AGLE-177 Clinical data from Pha
Slide 33: Las Cimas Parkway, Austin, TX – aeglea.com
805 Las Cimas Parkway Suite 100 Austin, TX 78746 aeglea.com
Slide 34: Financial Summary
Financial Summary 34 Cash, cash equivalents and marketable securities as of September 30, 2021: $114.3 million1 (no debt) As of September 30, 2021, 65.9 million2 common shares and pre-funded warrants outstanding Expected funding runway: into 2023 1Includes $1.8mm of restricted. 2Includes 49.3 millio
Slide 35: PEACE Baseline Demographics
PEACE Baseline Demographics 35 ©2022 Aeglea BioTherapeutics. External
Slide 36: PEACE Baseline Clinical Characteristics
PEACE Baseline Clinical Characteristics 36 *Based on arithmetic mean ©2022 Aeglea BioTherapeutics. External
Slide 37: 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 37 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
Slide 38: Mobility Assessments Capture Potential Clinical Benefit of Pegzilarginase
Mobility Assessments Capture Potential Clinical Benefit of Pegzilarginase in Phase 1/2 Trial & OLE 38 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
Slide 39: AGLE-177 Improves Pathologies in a Preclinical Model of Homocystinuria
AGLE-177 Improves Pathologies and Correction of Disease Manifestations in a Preclinical Model of Homocystinuria 39 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
Slide 40: Measuring the Functional Impact of Spasticity in ARG1-D
Measuring the Functional Impact of Spasticity in ARG1-D 40 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
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