Spyre Therapeutics, Inc. · NASDAQ:SYRE

Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (April 2019)

34 slides from Spyre Therapeutics's investor presentation, Apr 8, 2019

  1. Slide 1: Aeglea BioTherapeutics April 2019

    Aeglea BioTherapeutics © Aeglea BioTherapeuticsAPRIL 2019

  2. Slide 2: Forward Looking Statements

    © AegleaBioTherapeutics1© AegleaBioTherapeutics1Forward Looking StatementsThis presentation and the accompanying oral presentation contain “forward-looking” statements that are based on our management’sbeliefs and assumptions and on information currently available to management. Forward-looking stat

  3. Slide 3: Clinical-Stage Biotechnology Company Engineering Next Generation Human Enzymes

    © AegleaBioTherapeutics2Clinical-Stage Biotechnology Company that Engineers Next Generation Human Enzymes with Enhanced Properties and Novel Activity to Provide Solutions for Diseases with Unmet Medical NeedSpecificityActivityStabilityAegleaBioTherapeutics, Inc. | NASDAQ: AGLE | Austin, TexasEmploye

  4. Slide 4: Pipeline Building Using A Unique Drug Hunting Approach

    © AegleaBioTherapeutics3Rare DiseasesCancerPipeline Building Using A Unique Drug Hunting ApproachPegzilarginaseArginineProduct &TargetIndicationIND EnablingPhase 1Phase 2Status/Expected MilestonesArginase 1 DeficiencyCutaneous Melanoma, Uveal Melanoma, SCLC -Single Agent ExpansionSCLC –Combination w

  5. Slide 5: Strong Momentum With Multiple Anticipated Near-term Catalysts

    © AegleaBioTherapeutics4© AegleaBioTherapeutics4Strong Momentum With Multiple Anticipated Near-term CatalystsRecent Milestones•Consistent, substantial and sustained control of plasma arginine, the key driver of disease manifestations in ARG1-D with pegzilarginaseoSafety profile supports progression

  6. Slide 6: Highly Experienced Leadership Team In Drug Discovery & Development

    © AegleaBioTherapeutics5Highly Experienced Leadership Team In Drug Discovery & DevelopmentAnthony G. Quinn, MD PhDChief Executive OfficerJames Wooldridge, MDChief Medical OfficerLeslie Sloan, PhDChief Operating OfficerCharles N. York II, MBAChief Financial OfficerAaron Schuchart, MBAChief Business O

  7. Slide 7: Arginase Deficiency: Pegzilarginase Lead Program

    © AegleaBioTherapeutics66Arginase 1 DeficiencyAutosomal recessive disorder of the urea cycle that causes toxic levels of arginine to accumulate in the bloodPegzilarginase: Lead Program

  8. Slide 8: Pegzilarginase: An Innovative Approach To Treat Arginase 1 Deficiency

    © AegleaBioTherapeutics7Pegzilarginase: An Innovative Approach To Treat Arginase 1 DeficiencyIndication•Arginase 1 Deficiency (ARG1-D)Patient Population(Addressable Markets)•Greater than600patients•Greater than170 patients identified to dateDiagnosis (Blood Arginine Levels)•Symptomatic cases: spasti

  9. Slide 9: PEACE Pivotal Phase 3: Trial Design

    © AegleaBioTherapeutics8PEACE Pivotal Phase 3: Trial DesignSingle, global pivotal Phase 3 trialbased on input from FDA and the EMA to support registrationEndpoints selected to assess improvements meaningful to patients and physicians-Primary: plasma arginine reduction (97.9% probability of meeting p

  10. Slide 10: Mobility and Adaptive Behavior Assessments Capture Disease Burden

    © AegleaBioTherapeutics9Mobility and Adaptive Behavior Assessments Capture Disease Burden1One patient was wheelchair bound and is not included;. 2Six patients did not receive baseline adaptive behavior assessments. Gross Motor Function Measure Part E6-Minute Walk TestAge/Gender Reference LimitsIndiv

  11. Slide 11: Pegzilarginase Consistently, Substantially, and Sustainably Controlled Plasma Arginine

    © AegleaBioTherapeutics10PegzilarginaseConsistently, Substantially, and Sustainably Controlled Plasma Arginine•Statistically significant reductions in arginine from baseline to dose 1 and dose 8 (p<0.001)•Plasma arginine reduction was sustained with excellent control into the open label extension (m

  12. Slide 12: Capturing Phase 1/2 Clinical Responses with Mobility and Adaptive Behavior Assessments

    © AegleaBioTherapeutics11Capturing Phase 1/2 Clinical Responses with Mobility and Adaptive Behavior Assessments1patients who were within 1 MCID of the maximum score for GMFM are not shown on the graph. Adaptive Behavior includes ABAS andVinelandMCID = minimal clinically important difference; 6MWT =

  13. Slide 13: Safety

    © AegleaBioTherapeutics12Safety•Pegzilarginasewas generally well tolerated-> 300 infusions administered-83% of infusions were = 30 minutes duration•Hypersensitivity reactions were infrequent, managed with standard treatment and did not lead to any patient discontinuations. •Low-titer, emergent ADAs

  14. Slide 14: Key Highlights from New Phase 1/2 Data

    © AegleaBioTherapeutics13Key Highlights from New Phase 1/2 Data•Pegzilarginasewas highly effective in consistently, substantially and sustainablylowering elevated plasma arginine, a key driver of ARG1-D disease manifestations and progression•Plasma arginine reductions were accompanied by improvement

  15. Slide 15: Significant Increase In Patient Identification

    © AegleaBioTherapeutics14Significant Increase In Patient Identification United StatesEuropeRest of World50+Patients100+Patients20+Patients2017April 2018September 201850+Patients100+Patients140+PatientsDecember2018170+Patients

  16. Slide 16: PEACE: Summary and Next Steps

    © AegleaBioTherapeutics15PEACE: Summary and Next StepsPEACE is aligned with collaborative input from FDA and EMAPEACE is a single, global pivotal trialPhase 1/2 data demonstrates clinical impact •30 patients, randomized 2:1 (pegzilarginase: placebo)•24 weeks dosing period•Primary endpoint: arginine

  17. Slide 17: Pipeline: Drug Hunting In Human Enzyme Space

    © AegleaBioTherapeutics16© AegleaBioTherapeutics16PipelineDrug Hunting In Human Enzyme Space

  18. Slide 18: AEB5100: An Innovative Approach To Treat Cystinuria

    © AegleaBioTherapeutics17AEB5100: An Innovative Approach To Treat CystinuriaIndication•CystinuriaPatient Population(Addressable Markets)•Greater than 10,000 patientsUnmet Medical Need •Severe, recurrent flank/abdominal pain and hematuria from an early age•Multiple hospitalizations and invasive proce

  19. Slide 19: Novel Therapeutic Approach For Cystinuria: Enzymatic Reduction Of Cystine

    © AegleaBioTherapeutics18Novel Therapeutic Approach For Cystinuria: Enzymatic Reduction Of Cystine1Biyani and Cartledge EAU-EBU Update Series 4 (2006) 175-183; andLeslie and Nazzal Renal Calculi (Cystinuria, Cystine Stones) (2018)CystinuriaHigh cystine in urine.cystine precipitates .stone formationS

  20. Slide 20: AEB5100: Novel Enzyme With Medical Utility For Cystinuria

    © AegleaBioTherapeutics19•There are no naturally occurring human enzymes that efficiently degrade cystine•Human Cystathionine-Gamma-Lyase (CGL) was engineered to change its native substrate specificityAEB5100: Novel Enzyme With Medical Utility For Cystinuria1Cramer SL et al, 2017 Nature Medicine 23:

  21. Slide 21: Cystinuria Mouse Model Is Highly Translatable To The Human Disease

    © AegleaBioTherapeutics20Cystinuria Mouse Model Is Highly Translatable To The Human DiseaseMouse disease model replicates important aspects of cystinuria stone formation in affected patients •Cystine crystal formation •Kidney stone formation leads to tubular dilatation and hydronephrosis (excess flu

  22. Slide 22: AEB5100: Depletion Of Plasma Cystine Reduces Cystine Crystals In Urine

    © AegleaBioTherapeutics21AEB5100: Depletion Of Plasma Cystine Reduces Cystine Crystals In UrineSlc3a1-/-mouse urinecystine crystals before dosingSlc3a1-/-mouse urinecystine crystals after dosingSingle IP dose of AEB5100 in a preclinical model reduces:-Plasma cystine and cysteine levels-Urine cystine

  23. Slide 23: AEB5100: Effectively Reduces Stones In Cystinuria Mouse Model

    © AegleaBioTherapeutics22AEB5100: Effectively Reduces Stones In Cystinuria Mouse ModelKidneys*Administration of AEB5100 for 6 weeks reduces kidney stone formation in preclinical model Total Stones VolumeNumber of Stones0.0020.140.0021.9153.98.3

  24. Slide 24: AEB4104: An Innovative Approach To Treat Homocystinuria

    © AegleaBioTherapeutics23AEB4104: An Innovative Approach To Treat HomocystinuriaIndication•Cystathionine beta synthase (CBS) deficiency and other formsPatient Population(Addressable Markets)•Approximately 5,000 patientsUnmet Medical Need •Very high -no effective therapy for many patients•Early morta

  25. Slide 25: AEB4104: Therapeutic Approach To Depletion Of Homocysteine And Homocystine

    © AegleaBioTherapeutics24AEB4104: Therapeutic Approach To Depletion Of Homocysteine And HomocystineAEB4104 is an engineered CGL enzyme designed to change its native substrate specificity from cystathionine to both homocysteine and homocystineAEB4104 Reduces Plasma Homocysteine & HomocystineLevels in

  26. Slide 26: AEB4104: Improves Survival & Corrects Disease Manifestations In Preclinical Model

    © AegleaBioTherapeutics25AEB4104: Improves Survival & Corrects Disease Manifestations In A Preclinical Model of HomocystinuriaEstablishes that reductions in the plasma levels of homocysteine and homocystineleads to improvements in disease related abnormalitiesAEB4104 Reverses Severe Liver Abnormalit

  27. Slide 27: Arginine Dependent Cancers: Focus on SCLC and Melanoma

    © AegleaBioTherapeutics2626Arginine Dependent CancersFocus on Small Cell Lung Cancer (SCLC) and MelanomaPegzilarginase: Lead Program

  28. Slide 28: Arginine Depletion In Cancer

    © AegleaBioTherapeutics27Arginine Depletion In Cancer •Extracellular arginine depletion has broad effects on tumor cells1,2,3-Increased autophagy-Inhibition of cell proliferation-Induction of apoptosis•Metabolic pathway remodeling of tumors may increase sensitivity to arginine depletion-Downregulati

  29. Slide 29: Pegzilarginase Oncology Development Program

    © AegleaBioTherapeutics28PegzilarginaseOncology Development Program100B –Solid tumorsdose escalationSCLCUveal melanomaCutaneous melanoma101B –Pegzilarginase+ Pembrolizumab in SCLCDose escalation . Simon 2-Stage Phase 2(Clinical Collaboration with Merck)Phase 2Phase 3: 2L+ SCLCI/O (Pembrolizumab) ±Pe

  30. Slide 30: Pegzilarginase Demonstrates Single Agent Melanoma Clinical Activity In Phase 1

    © AegleaBioTherapeutics29•All TRAEs Grade 3 or less•No infusion reactions were reported following 276 infusions•Three patients experienced treatment-related, serious Grade 3 AEs: 1) Asthenia and failure to thrive, 2) vomiting, and 3) dehydration•Anti-drug antibody (ADA) analysis (N=27 pts):o5 anti-p

  31. Slide 31: Pegzilarginase Demonstrates Single Agent Clinical Activity In Phase 1

    © AegleaBioTherapeutics30-40-20020406080100Cutaneous Melanoma% Change in Target LesionsPatients-30050100150200250-40-20020406080100Study Day of Tumor Measurement% Change in Target LesionsUvealCutaneousCutaneousUvealCutaneousUvealASS1 NegativeASS1 PositiveASS1 UnknownPegzilarginase Demonstrates Singl

  32. Slide 32: Arginine Depletion in Cancers Summary

    © AegleaBioTherapeutics31© AegleaBioTherapeutics31Arginine Depletionin Cancers Summary12Single agent activity in heavily pre-treated Phase 1 melanoma patient populationPegzilarginasesafely and sustainably depletes plasma arginine3Anti-tumor activity appeared greater in tumors lacking ASS1 expression

  33. Slide 33: Financial Summary

    © AegleaBioTherapeutics32FinancialSummary$millionsThree Months Ended 12/31/2018Twelve Months Ended 12/31/2018Grant Revenue$ -$3.9R&D Expense$11.8$36.7G&A Expense$3.5$12.6Net Loss$14.9$44.3Expected funding runway: through 1Q20211.Includes $64.5M net proceeds from equity offering in February 2019 alon

  34. Slide 34: Aeglea BioTherapeutics

    Aeglea BioTherapeutics

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