Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (March 2022)
40 slides from Spyre Therapeutics's investor presentation, Mar 8, 2022
Slide 1: Reimagining The Potential Of Human Enzyme Therapeutics
Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview – March 2022 Nasdaq: AGLE Exhibit 99.2
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
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 Key Highlights
Looking Ahead Key Highlights 4 Pegzilarginase Submit U.S. BLA (2Q 2022), EU MAA (2022) Continue preparations for strong, rapid launch in U.S., Europe and Middle East Presentation of PEACE data at SIMD; publication of long-term data AGLE-177 Clinical data from Phase 1/2 trial (2H 2022) Plan to open U
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 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
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 and Timeline to Potential U.S. Approval
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: Attractive Commercial Opportunity and a Targeted Launch Plan
16 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
Slide 17: 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 18: Laying the Groundwork to Transition Smoothly to Commercial Operations
Laying the Groundwork to Transition Smoothly to Commercial Operations 18 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 19: AGLE-177 for Homocystinuria
AGLE-177 for Homocystinuria
Slide 20: Homocystinuria Disease Overview
Homocystinuria Disease Overview 20 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 21: Natural History Study of Untreated Classical Homocystinuria Patients
Natural History Study of 629 Untreated Classical Homocystinuria Patients 21 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 22: AGLE-177 for Homocystinuria Overview
AGLE-177 for Homocystinuria Overview 22 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 23: Preclinical Data Support Potential Advantages of AGLE-177
23 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 =
Slide 24: Phase 1/2 Clinical Trial Design
Phase 1/2 Clinical Trial Design 24 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 patients Weekly dosing for 4 week
Slide 25: Phase 1/2 Clinical Trial – Study Acceleration
Phase 1/2 Clinical Trial – Study Acceleration 25 Cohort 2 Cohort 3 PART 1 (IV) PART 2 (SC) Dose 0.45 mg/kg n = 4 Dose 1.0 mg/kg n = 4 Dose 0.15 mg/kg n = 3 Cohort 1 Dose 0.15 mg/kg Cohorts 4 & 5 (optional) Submitted IND to the FDA in February 2022 and Plan to Open U.S. Trial Sites; Clinical Data Exp
Slide 26: AGLE-177: a Potentially Differentiated Treatment for Homocystinuria
26 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
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 Key Highlights
Looking Ahead Key Highlights 32 Pegzilarginase Submit U.S. BLA (2Q 2022), EU MAA (2022) Continue preparations for strong, rapid launch in U.S., Europe and Middle East Presentation of PEACE data at SIMD; publication of long-term data AGLE-177 Clinical data from Phase 1/2 trial (2H 2022) Plan to open
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 December 31, 2021: $95.0 million1 (no debt) As of December 31, 2021, 65.9 million2 common shares and pre-funded warrants outstanding Expected funding runway: into first quarter of 2023 1Includes $1.8mm of restricted. 2Includ
Slide 35: PEACE Baseline Demographics
PEACE Baseline Demographics 35 ©2022 Aeglea BioTherapeutics. External Demographic Characteristic Age at Enrollment, y Mean (SD) Placebo n=11 Overall N=32 9.6 (6.16) 2-28 5-29 2-29 13(61.9) 5(45.5) 18(56.3) Range Pegzilarginase n=21 Age Category, n (%) 2y to less than 6y 6y to less than 12y12y to les
Slide 36: PEACE Baseline Clinical Characteristics
PEACE Baseline Clinical Characteristics 36 *Based on arithmetic mean ©2022 Aeglea BioTherapeutics. External Clinical Characteristic Plasma Arginine, µM/L Mean (SD) Pegzilarginase n=21 Placebo n=11 Overall N=32 median (range) GMFCS level, n(%) 1>2 GMFM-E 2MWT 365.4 (93.7) 368.2 (202-572) 9 (42.9) 12
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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