Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (March 2021)
46 slides from Spyre Therapeutics's investor presentation, Mar 18, 2021
Slide 1: Reimagining The Potential Of Human Enzyme Therapeutics
Reimagining The Potential Of Human Enzyme Therapeutics Corporate Overview – March 2021 Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements ©2020 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 ©2020 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 for People with Rare Metabolic Diseases
Unlocking the Potential of Human Enzymes to Deliver Life-Changing Solutions for People with Rare Metabolic Diseases ©2020 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 ©2020 Aeglea BioTherapeutics. External 5 Distinctive disease selection approach Validated metabolite targets Translatable disease models Reduced toxicology risk Established manufacturing approach Faster, smaller clinical
Slide 6: Rethinking the Potential of Human Enzyme Therapeutics
Rethinking the Potential of Human Enzyme Therapeutics ©2020 Aeglea BioTherapeutics. External 6 *[LINE GRAPH] Program Indication Research Phase 1/2 Phase 3 Approval Pegzilarginase Arginase 1 Deficiency AGLE-177 Homocystinuria Research Programs Cystinuria Undisclosed Rare Diseases
Slide 7: Highly Experienced Leadership Team in Drug Discovery & Development
Highly Experienced Leadership Team in Drug Discovery & Development Anthony G. Quinn, MD PhD Chief Executive Officer Leslie Sloan, PhD Chief Operating Officer Scott Rowlinson, PhD Vice President of Research Michael C. Hanley, MBA Chief Commercial Officer Eric Bradford, MD MBA Chief Development Office
Slide 8: Pegzilarginase in Arginase Deficiency
Pegzilarginase in Arginase 1 Deficiency
Slide 9: Arginase Deficiency Overview
Arginase 1 Deficiency Overview ©2020 Aeglea BioTherapeutics. External 9 Arginase 1 Deficiency (ARG1-D) Arginase 1 Deficiency 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 pa
Slide 10: Arginase Deficiency Patient Needs Not Adequately Addressed
KEY AREAS: Arginase 1 Deficiency Patient Needs Not Adequately Addressed No effective treatments or approved therapies that treat the underlying cause ©2020 Aeglea BioTherapeutics. External 10 Current standard of care: Severe dietary protein restriction Amino acid supplementation Ammonia scavengers C
Slide 11: Global Pivotal Phase 3: PEACE Trial Design
Global Pivotal Phase 3: PEACE Trial Design ©2020 Aeglea BioTherapeutics. External 11 Single, Pivotal Phase 3 Trial Based on Input From FDA and EMA to Support Registration *Dosing is weekly and, if needed, modified based on plasma arginine levels with maintenance of blinding. The first 8 weeks of the
Slide 12: Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels
Pegzilarginase Significantly and Sustainably Reduces Plasma Arginine Levels ©2020 Aeglea BioTherapeutics. External 12 Plasma Arginine in Response to Pegzilarginase Baseline: Baseline plasma arginine on standard disease management was markedly elevated 20 Week Analysis: Median plasma arginine was 112
Slide 13: Pegzilarginase Demonstrates Durable Clinical Response
Clinical Responder defined by achievement of a clinically meaningful response* in one or more of three mobility assessments Pegzilarginase Demonstrates Durable Clinical Response ©2020 Aeglea BioTherapeutics. External 13 20 Week Analysis: 11/14 (79%) 56 Week Analysis: 11/13 (85%) *Clinically meaningf
Slide 14: Key Insights on Timed Walk and GMFM-E in Capturing Clinical Benefit
Key Insights on Effectiveness of Timed Walk and GMFM-E in Capturing Clinical Benefit with Pegzilarginase ©2020 Aeglea BioTherapeutics. Confidential Information 14 GMFM-E (Units) Change from Baseline at 56 Week Analysis Not Assessed Not Assessed GMFCS – Level II/III GMFCS – Level I 6MWT (Meters) CE C
Slide 15: Safety Summary
Safety Summary ©2020 Aeglea BioTherapeutics. External 15 Pegzilarginase was shown to have a favorable safety profile More than 1,3501 doses administered in the Phase 1/2 clinical trial (101A) and Phase 2 OLE study (102A) Approximately 5001 intravenous doses Most treatment-related adverse events were
Slide 16: Arginase Deficiency Market Opportunity
Arginase 1 Deficiency Market Opportunity ©2020 Aeglea BioTherapeutics. External 16 Genetic analysis indicates a prevalence of ~2,500 in global addressable markets Estimates based on ARG1 genetic mutations identified in published literature and in Aeglea clinical development program >300 patients ide
Slide 17: Building a Commercial Organization to Serve the Future
Building a Commercial Organization to Serve the Future Patient Identification Scientific Communications Access & Reimbursement Worldwide commercial rights with ongoing ex-U.S. partnering discussions Strategic, senior commercial leadership team in place with relevant ultra-rare launch experience Plan
Slide 18: Arginase Deficiency Key Highlights and Next Steps
Arginase 1 Deficiency Key Highlights and Next Steps ©2020 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 end
Slide 19: AGLE-177 in Homocystinuria
AGLE-177 in Homocystinuria
Slide 20: Homocystinuria Overview
Homocystinuria Overview ©2020 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 based on results of U.S. ICD-10 claims analysis extrapolated
Slide 21: Current Homocystinuria Treatments Have Limited Effectiveness
Current Homocystinuria Treatments Have Limited Effectiveness and Create a Significant Burden for Patients ©2020 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 CBS Deficient Patients
Natural History Study of 629 Untreated CBS Deficient Patients Increased Mortality and Severe Complication Risk in Patients with Homocystinuria ©2020 Aeglea BioTherapeutics. External 22 B6-responsive = 231 All patients = 629 B6-non-responsive = 231 MORTALITY NATURAL HISTORY Mudd et al, 1985. Kluijtma
Slide 23: Therapeutic Goal is to Improve Control of Total Plasma Homocysteine
Therapeutic Goal is to Improve Control of Total Plasma Homocysteine ©2020 Aeglea BioTherapeutics. External 23 INTRACELLULAR EXTRACELLULAR Homocysteine Homocystine AGLE-177 Homocysteine (protein bound) Decrease in plasma homocysteine and homocystine X Therapeutic Rationale Elevated levels of plasma t
Slide 24: Subcutaneous Dosing Reduces Total Plasma Homocysteine and Improves Survival
Subcutaneous Dosing Reduces Total Plasma Homocysteine and Improves Survival in Preclinical Model ©2020 Aeglea BioTherapeutics. External 24 AGLE-177 (0.81 mg/kg HED, SC BIW, n=11 of 12) AGLE-177 (0.24 mg/kg HED, SC BIW, n=8 of 10) AGLE-177 (0.08 mg/kg HED, SC BIW, n=10 of 11) Vehicle (SC BIW, n=2 of
Slide 25: AGLE-177 Improves Pathologies in Preclinical Model of Homocystinuria
AGLE-177 Improves Pathologies and Correction of Disease Manifestations in a Preclinical Model of Homocystinuria ©2020 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 Proof-of-Concept Phase 1/2 Trial
AGLE-177 for Homocystinuria – Proof-of-Concept Phase 1/2 Trial Development timeline to rapidly progress to Phase 3 trial pending trial results ©2020 Aeglea BioTherapeutics. External 26 Endpoints Key Inclusion Criteria Enrollment & Dosing Safety and tolerability PK Reduction in plasma total homocyste
Slide 27: Homocystinuria Summary
Homocystinuria ©2020 Aeglea BioTherapeutics. External 27 Limited effectiveness of SOC Limited effectiveness of lowering homocysteine, non-compliance and poor tolerability of low methionine diet and Betaine Natural History study illustrates the toxic build up of homocysteine levels leads to a wide ra
Slide 28: Cystinuria Program
Cystinuria Program
Slide 29: Cystinuria Overview
Cystinuria Overview ©2020 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: Cystinuria Patient Needs Not Adequately Addressed
Cystinuria Patient Needs Not Adequately Addressed ©2020 Aeglea BioTherapeutics. External 30 Pearle, Goldfarb et al. 2019 Patient circumstances where ability to maintain high urine volume or comply with high fluid intake is challenging Therapy-resistant patients on optimal standard disease management
Slide 31: Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine
Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine ©2020 Aeglea BioTherapeutics. External 31 HEALTHY Low cystine in urine Healthy Functional Transporter INNOVATIVE ENZYME APPROACH Enzymatic reduction of plasma cystine should lower urine cystine and reduce cystine stone format
Slide 32: Novel Human Enzyme Solution for Cystinuria
Cystinuria Program: Novel Human Enzyme Solution for Cystinuria ©2020 Aeglea BioTherapeutics. External 32 Before Dosing After Dosing Creating Novel Cystine Degrading Activity1 - Increase catalytic activity - Increase serum stability - Improve manufacturability Slc3a1 -/- mouse urine cystine crystals
Slide 33: Prevention of Kidney Stone Formation in Cystinuria Mouse Model
Prevention of Kidney Stone Formation in Cystinuria Mouse Model ©2020 Aeglea BioTherapeutics. External 33 0 1 2 3 4 -1 (Weeks) Reduced Fluid Intake (65% of water) Normal Fluid Intake (age 5-6 wks) Restricted Fluid Intake (age 9-10 wks) Agnello, et al American Society of Nephrology #TH-P0815 [LINE CHA
Slide 34: Human Enzyme Platform
Human Enzyme Platform
Slide 35: Leveraging Aeglea's Next Generation Human Enzyme Platform
Leveraging Aeglea’s Next Generation Human Enzyme Platform ©2020 Aeglea BioTherapeutics. External 35 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 36: Strong Momentum with Near-Term Catalysts
Strong Momentum with Near-Term Catalysts ©2020 Aeglea BioTherapeutics. External 36 ACCOMPLISHMENTS TARGETED MILESTONES Pegzilarginase: ARG1-D Completion of enrollment: March 2021 Topline pivotal Phase 3 data: 4Q2021 Pegzilarginase: ARG1-D Phase 1/2 & OLE efficacy data at 56 week analysis: Statistica
Slide 37: A Disruptive Platform Producing a New Generation of Human Enzyme Solutions
A Disruptive Platform Producing a New Generation of Human Enzyme Solutions ©2020 Aeglea BioTherapeutics. External 37 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 38: Financial Summary
Financial Summary ©2020 Aeglea BioTherapeutics. External 38 Cash, cash equivalents and marketable securities as of December 31, 2020: $148.1 million1 (no debt) As of March 12, 2021, 65.6 million2 common shares and pre-funded warrants outstanding Expected funding runway: into 2023 1Includes $1.8mm of
Slide 39: Las Cimas Parkway Suite Austin, TX 78746 aeglea.com
805 Las Cimas Parkway Suite 100 Austin, TX 78746 aeglea.com
Slide 40: Baseline Demographics and Patient Characteristics
Baseline Demographics and Patient Characteristics ©2020 Aeglea BioTherapeutics. External 40 *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 41: Pegzilarginase Demonstrates Durable Clinical Response
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 42: Pegzilarginase Demonstrates Sustained Improvements in Six Minute Walk Test
Pegzilarginase Demonstrates Sustained Improvements in 6 Minute Walk Test 6MWT – Six Minute Walk Test Mean Change from Baseline (m) 8 Week Analysis 20 Week Analysis 56 Week Analysis 6 32* 45* *p<0.01 Mean Change from Baseline in 6MWT 151 112 86 68 43 35 32 30 29 28 7 -3 -34 6MWT by Patient at 56 Week
Slide 43: Clinically Impactful Improvements at Patient Level with Pegzilarginase
Clinically Impactful Improvements at Patient Level with Pegzilarginase ©2020 Aeglea BioTherapeutics. External 43 Images by kind permission of Dr GA Diaz Patient Background Teenage girl diagnosed at age 1 (presented with hyperammonaemia) Developed severe lower limb spasticity, speech delay, intellect
Slide 44: Arginase Deficiency (ARG1-D)
Arginase 1 Deficiency (ARG1-D) ©2020 Aeglea BioTherapeutics. External 44 Progressive metabolic disease with significant morbidity and early mortality Typically presents in childhood with spasticity, neurocognitive impairment, seizures, growth delay and hyperammonemic episodes Deficiency of Arginase-
Slide 45: Designing Enzyme Therapeutics - Pegzilarginase
Designing Enzyme Therapeutics - Pegzilarginase ©2020 Aeglea BioTherapeutics. External 45 Improved Catalytic Activity & Serum Stability Reduced Circulating Arginine levels Substituted Metal Cofactor (Mn2+ replaced with Co2+ ) Pegzilarginase [PEGZILARGINASE DIAGRAM] [BAR CHART] [BAR CHART] Catalytic a
Slide 46: Pegzilarginase: Clinical Benefit Associated With Extra-Hepatic Enhancement of Arginase 1 Activity
Pegzilarginase: Clinical Benefit Associated With Extra-Hepatic Enhancement of Arginase 1 Enzyme Activity ©2020 Aeglea BioTherapeutics. External 46 Slight improvement in spasticity Transfusion HIGH LOW Blood Exchange HIGH LOW Improved clinical condition Able to sit and roll over on his own Decreased
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