Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (September 2021)
39 slides from Spyre Therapeutics's investor presentation, Sep 9, 2021
Slide 1: Reimagining The Potential Of Human Enzyme Therapeutics
Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview – September 2021 Exhibit 99.1 Company Logo
Slide 2: Forward Looking Statements
Forward Looking Statements ©2021 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 ©2021 Aeglea BioTherapeutics. External 3 Delivering Metabolic Harmony Aeglea BioTherapeutics (Nasdaq: AGLE) At Aeglea, we believe that every patient deserves a chance at a better life. We are committed to helping people with rare and d
Slide 4: Unlocking the Potential of Human Enzymes to Deliver Life-Changing Solutions
Unlocking the Potential of Human Enzymes to Deliver Life-Changing Solutions for People with Rare Metabolic Diseases ©2021 Aeglea BioTherapeutics. External 4 PEGZILARGINASE IN ARGINASE 1 DEFICIENCY AGLE-177 IN HOMOCYSTINURIA ENZYME THERAPEUTICS PLATFORM Enhanced human arginase that enzymatically lowe
Slide 5: Looking Beyond the Conventional with Next Generation Human Enzyme Therapeutics
Looking Beyond the Conventional with Next Generation Human Enzyme Therapeutics ©2021 Aeglea BioTherapeutics. External 5 Specialized expertise in human enzyme engineering Distinctive disease selection approach Validated metabolite targets Translatable disease models Reduced toxicology risk Establishe
Slide 6: Rethinking the Potential of Human Enzyme Therapeutics
Rethinking the Potential of Human Enzyme Therapeutics ©2021 Aeglea BioTherapeutics. External 6 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
Slide 7: Pegzilarginase for Arginase Deficiency
Pegzilarginase for Arginase 1 Deficiency
Slide 8: Pegzilarginase Program Overview
Pegzilarginase Program Overview ©2021 Aeglea BioTherapeutics. External 8 Arginase 1 Deficiency (ARG1-D) ARG1-D is a serious, progressive disease with early mortality and high unmet medical need due to an autosomal recessive disorder of arginine metabolism. Addressable Market: >2,500 patients Genetic
Slide 9: Arginase Deficiency Patient Needs Not Adequately Addressed
KEY AREAS: Arginase 1 Deficiency Patient Needs Not Adequately Addressed No treatments or approved therapies that effectively reduce arginine levels ©2021 Aeglea BioTherapeutics. External 9 Current standard of care: Severe dietary protein restriction Amino acid supplementation Ammonia scavengers Curr
Slide 10: Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels
Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels ©2021 Aeglea BioTherapeutics. External 10 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: Me
Slide 11: Mobility Assessments Capture Clinical Benefit with Pegzilarginase in Phase 1/2 Trial
Mobility Assessments Capture Clinical Benefit with Pegzilarginase in Phase 1/2 Trial ©2021 Aeglea BioTherapeutics. External 11 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%) Categorica
Slide 12: Safety Summary
Safety Summary ©2021 Aeglea BioTherapeutics. External 12 Clinical data shows pegzilarginase has a favorable safety profile Approximately 1,8501 doses administered Approximately 5001 intravenous doses Most treatment-related adverse events were mild The frequency of treatment-related adverse events de
Slide 13: PEACE Trial Design – Single Global Pivotal Phase Trial
PEACE Trial Design – Single Global Pivotal Phase 3 Trial to Support Registration ©2021 Aeglea BioTherapeutics. External 13 *Dosing is weekly and, if needed, modified based on plasma arginine levels with maintenance of blinding. ǂThe first 8 weeks of the open-label extension will be blinded. All stud
Slide 14: Attractive Commercial Opportunity for Pegzilarginase in ARG1-D
Attractive Commercial Opportunity for Pegzilarginase in ARG1-D ©2021 Aeglea BioTherapeutics. External 14 1 Licensing and supply agreement signed with Immedica PLC in March 2021; agreement covers countries in the European Economic Area and certain countries in the Middle East, United Kingdom, Switzer
Slide 15: Building the Foundation for a Successful Launch
Building the Foundation for a Successful Launch and Enduring Commercial Presence ©2021 Aeglea BioTherapeutics. External 15 Patient Identification Accelerating the diagnosis and identification of patients through ongoing HCP engagement Disease Education and Awareness Driving HCP dialogue about the de
Slide 16: Engaging with HCP and Patient Communities to Accelerate Diagnosis
Engaging with HCP and Patient Communities to Accelerate Diagnosis, Broaden Awareness, and Deepen Understanding of ARG1-D ©2021 Aeglea BioTherapeutics. External 16 Continued patient identification momentum across key markets Results outpacing relevant benchmarks >65% of the estimated U.S. genetic pre
Slide 17: Laying the Groundwork to Transition Smoothly to Commercial Operations
Laying the Groundwork to Transition Smoothly to Commercial Operations ©2021 Aeglea BioTherapeutics. External 17 Preliminary planning around patient services based on our deep understanding of the needs of the ARG1-D patient community Payer profiling to understand likely coverage policies at launch I
Slide 18: Pegzilarginase Program - Key Highlights and Next Steps
Pegzilarginase Program - Key Highlights and Next Steps ©2021 Aeglea BioTherapeutics. External 18 Sustained control of plasma arginine 85% (11/13) of patients at the 56 week analysis were clinical responders Well tolerated and the rates of treatment-related adverse events decreased over time Primary
Slide 19: AGLE-177 in Homocystinuria
AGLE-177 in Homocystinuria
Slide 20: AGLE-177 Program Overview
AGLE-177 Program Overview ©2021 Aeglea BioTherapeutics. External 20 PRV – Priority Review Voucher 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 r
Slide 21: Current Homocystinuria Treatments Have Limited Effectiveness
Current Homocystinuria Treatments Have Limited Effectiveness and Create a Significant Burden for Patients ©2021 Aeglea BioTherapeutics. External 21 Patients intolerant of available adjunctive therapies due to either safety issues or other adverse reactions Therapy-resistant patients on standard dise
Slide 22: Natural History Study of Untreated Classical Homocystinuria Patients
Natural History Study of 629 Untreated Classical Homocystinuria Patients Increased Mortality and Severe Complication Risk in Patients with Homocystinuria ©2021 Aeglea BioTherapeutics. External 22 B6-responsive = 231 All patients = 629 B6-non-responsive = 231 MORTALITY NATURAL HISTORY Mudd et al, 198
Slide 23: Therapeutic Goal is to Improve Control of Total Plasma Homocysteine
Therapeutic Goal is to Improve Control of Total Plasma Homocysteine ©2021 Aeglea BioTherapeutics. External 23 INTRACELLULAR PLASMA Homocysteine Homocystine AGLE-177 Homocysteine (protein bound) Decrease in plasma homocysteine and homocystine X Therapeutic Rationale Elevated levels of plasma tHcy inc
Slide 24: Subcutaneous Dosing Reduces Total Plasma Homocysteine and Improves Survival
Subcutaneous Dosing Reduces Total Plasma Homocysteine and Improves Survival in Preclinical Model ©2021 Aeglea BioTherapeutics. External 24 AGLE-177 (10 mg/kg, BIW) AGLE-177 (3 mg.kg, BIW) AGLE-177 (1.0 mg/kg, BIW) Vehicle (BIW) Single SC Dose in CBS -/- Mouse Model1, 2 In Vivo Efficacy at Multiple S
Slide 25: 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 ©2021 Aeglea BioTherapeutics. External 25 Disease Resolution Disease Reversal Dosing Begins Day 10 CBS-/- Macro-steatosis Disease Progression AGLE-177-HIS 25 mg/kg + Betaine Day 23 CBS-/-
Slide 26: AGLE-177 for Homocystinuria – Enrollment and Dosing Underway
AGLE-177 for Homocystinuria – Enrollment and Dosing Underway ©2021 Aeglea BioTherapeutics. External 26 Endpoints Key Inclusion Criteria Enrollment & Dosing Safety and tolerability PK Reduction in plasma total homocysteine (tHcy) levels Classical Homocystinuria diagnosis Plasma tHcy >80 µM ≥12 years
Slide 27: AGLE-177 Program – Key Highlights
AGLE-177 Program – Key Highlights ©2021 Aeglea BioTherapeutics. External 27 Limited effectiveness of SOC Limited effectiveness of lowering homocysteine, non-compliance and poor tolerability of low methionine diet and Betaine AGLE-177 is an engineered human enzyme designed to address the needs of thi
Slide 28: Human Enzyme Platform
Human Enzyme Platform
Slide 29: Cystinuria Overview
Cystinuria Overview ©2021 Aeglea BioTherapeutics. External 29 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 ki
Slide 30: Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine
Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine in Blood ©2021 Aeglea BioTherapeutics. External 30 INNOVATIVE ENZYME APPROACH Enzymatic reduction of plasma cystine should lower urine cystine and reduce cystine stone formation Creating Novel Cystine Degrading Activity1 - In
Slide 31: Leveraging Aeglea's Next Generation Human Enzyme Platform
Leveraging Aeglea’s Next Generation Human Enzyme Platform ©2021 Aeglea BioTherapeutics. External 31 High activity human pegylated investigational enzyme Degrades key accumulating metabolite Results in restorative phenotypic improvements in genetically engineered mouse model PROOF OF CONCEPT Vehicle
Slide 32: Summary
Summary
Slide 33: Strong Momentum with Near-Term Catalysts
Strong Momentum with Near-Term Catalysts ©2021 Aeglea BioTherapeutics. External 33 ACCOMPLISHMENTS 2021 MILESTONES Pegzilarginase: ARG1-D Enrollment complete Ex-U.S. license and supply agreement with Immedica Topline pivotal Phase 3 data: Q4 2021 Pegzilarginase: ARG1-D PEACE enrollment complete Ex-U
Slide 34: Financial Summary
Financial Summary ©2021 Aeglea BioTherapeutics. External 34 Cash, cash equivalents and marketable securities as of June 30, 2021: $130.4 million1 (no debt) As of July 30, 2021, 65.7 million2 common shares and pre-funded warrants outstanding Expected funding runway: into 2023 1Includes $1.8mm of rest
Slide 35: A Disruptive Platform Producing a New Generation of Human Enzyme Solutions
A Disruptive Platform Producing a New Generation of Human Enzyme Solutions ©2021 Aeglea BioTherapeutics. External 35 Lead assets in three areas of high unmet medical need Looking beyond the conventional, redefining the potential of human enzymes to deliver disruptive solutions Driven by the urgent n
Slide 36: Aeglea contact details
805 Las Cimas Parkway Suite 100 Austin, TX 78746 aeglea.com
Slide 37: Baseline Demographics and Patient Characteristics
Baseline Demographics and Patient Characteristics ©2021 Aeglea BioTherapeutics. External 37 *Values are median (range) unless stated otherwise. Arg, arginine; ARG1, arginase 1; BL, baseline; NH3, ammonia; 6MWT, 6-minute walk test; GMFM-D/E, Gross Motor Function Measure Part D/E; Pt, patient, ** 1 pa
Slide 38: Pegzilarginase Demonstrates Durable Clinical Response at Week Analysis
Pegzilarginase Demonstrates Durable Clinical Response at 56 Week Analysis Overall Combined Response Responder (≥1 MCID increase) No improvement on decline Baseline deficit No baseline deficit ≥-1 MCID decrease Not assessed Patient 1 Patient 2 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient
Slide 39: Designing Enzyme Therapeutics - Pegzilarginase
Designing Enzyme Therapeutics - Pegzilarginase ©2021 Aeglea BioTherapeutics. External 39 Improved Catalytic Activity & Serum Stability Reduced Circulating Arginine levels Substituted Metal Cofactor (Mn2+ replaced with Co2+ ) Pegzilarginase Catalytic activity 1000 800 600 400 200 0 Kact KM (uM) 818 4
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