ASGCT 2020 Fabry & Cystinosis Data Update May 13, 2020 Exhibit 99.1
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Positive trends at six months, including kidney function measures eGFR and serum creatinine measures trending positively at 6 months Pill burden remains significantly lower than at baseline ASGCT 2020 data update – key takeaways plato continues to perform One-month plasma lyso-Gb3 decrease of 43% vs. baseline Three-month leukocyte and plasma enzyme activity levels 3x greater than mean of other three patients at same timepoint in Phase 2 trial Rapid neutrophil and platelet recovery with minimal lymphocyte depletion post Bu90 conditioning First Fabry plato™ patient Sustained long-term positive trends Patient 1 in the Phase 2 trial continues to show stable leukocyte and plasma AGA enzyme activity, now out 22 months Patient 3 in the Phase 2 trial shows increased leukocyte and plasma AGA enzyme activity, decreased plasma lyso-Gb3 level, and stable VCN at new time points All three Phase 1 patients off ERT remain off ERT Long-term Fabry patient data Cystinosis Patient 1 data New data show consistent results across Fabry disease and cystinosis programs
Multiple programs in the clinic Investigational Gene Therapy Proof-of-Concept IND-Enabling Phase 1/2 Commercial Rights Fabry AVR-RD-01 AVROBIO Gaucher AVR-RD-02 AVROBIO Cystinosis AVR-RD-04 AVROBIO Pompe AVR-RD-03 Preclinical AVROBIO Phase 2 Phase 1/2 Phase 1/2 10 patients dosed to date IND: Investigational New Drug
Fabry Disease AVR-RD-01
Goals for gene therapy in Fabry disease UNMET NEEDS: Kidney function Unmet needs: proteinuria, polyuria, kidney failure Cardiac function Unmet needs: left ventricular hypertrophy, fibrosis, heart failure Neuropathic pain Unmet needs: pain and burning sensations in hands and feet, pain crises Everyday burden of illness and life expectancy Unmet needs: fatigue, inability to sweat, joint pain, abdominal pain, diarrhea, vomiting, cloudy vision, hearing loss, tinnitus, rash, angiokeratomas, biweekly infusions, shortened lifespan CNS complications Unmet needs: TIA/stroke, depression, impaired executive function, white matter hyperintensities Sources: Wanner C et al, Med Genetics and Metab, 2018; Burlina A, JIEMS, 2016 CNS: Central Nervous System; TIA: Transient Ischemic Attack
Two AVR-RD-01 Fabry clinical trials 9 patients dosed across Phases 1 and 2 PHASE 1 Investigator-Sponsored Trial* PHASE 2 AVRO – FAB-201 Trial Patients Patients Key Objective Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18-50 year-old males n = 8-12 (4 patients dosed to-date) Treatment-naive 16-50 year-old males Safety and preliminary efficacy Safety and efficacy * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada
Infuse AVR-RD-01 Day 0 Plasma AGA Missing Plasma AGA Analysis Leukocyte AGA Infuse AVR-RD-01 Day 0 *Lab A: Mayo Clinic Laboratories; Lab B: Rupar Laboratory; Lab A Reference Range: >23.1 nmol/hr/mg; Lab B Reference Range: 24–56 nmol/hr/mg †Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A Patient 1: Multiple data trends sustained up to 22 months Leukocyte + Plasma AGA Enzyme Activity Drug Product VCN: 0.7 Vector Copy Number (VCN) VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells KIDNEY FUNCTION remains within normal range at 12 mos. CARDIAC FUNCTION remains within normal range at 12 mos. *Source: https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 EF: Ejection Fraction; LV: Left Ventricular mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 Baseline Month 12 Normal Range mGFR/eGFR Average 116* mL/min/1.73 m2 Male (20–39 years) Reference Range Mean Values ± SD 64.3 ± 4.2% 138.9 ± 24.5 g 67.8 ± 10.7 g/m2 Male (20–39 years) EF (%) LV Mass (Absolute) (g) LV Mass Index (Normalized) (g/m2) Baseline Month 12 Plasma Lyso-Gb3 and Total Gb3 *Reference Value: 2.4 nM; †Reference Value: 4961 nM; 6012 nM before August 2018 (until Day 28 for Patient 1) Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Note: Patient #1 had a skin biopsy score of 3 (severe accumulation) at baseline, a score of 2 (moderate accumulation) at 6 months and a score of 1 (mild accumulation) at 12 months FAB-201 FABRY PHASE 2 Total Gb3 Lyso-Gb3 Infuse AVR-RD-01 Day 0 Note: Visualization of multiple biomarkers adjusted to utilize the same statistical scaling ratio across biomarkers (as compared to prior presentation) New data point
Infuse AVR-RD-01 Day 0 Patient 2: Multiple data trends sustained up to 1 year* Plasma AGA Leukocyte AGA Drug Product VCN: 0.5 VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells *Data from Rupar Laboratory; Reference Range: 24–56 nmol/hr/mg; †Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A KIDNEY FUNCTION remains within normal range mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV Mass Index (Normalized) (g/m2) Baseline Month 12 Source: https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 EF: Ejection Fraction; LV: Left Ventricular Reference Range Mean Values Male 40-49 years 55–65% 58–91 g/m2 Baseline Month 12 Normal Range mGFR/eGFR Average 99 mL/min/1.73 m2 Male (40–49 years) CARDIAC FUNCTION remains within normal range *Reference Value: 2.4 nM; †Reference Value: 4961 nM; Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Note: As patient #2 is a cardiac variant of Fabry disease, this patient had a skin biopsy score of 0 (trace or no accumulation) at baseline and at 6 months Leukocyte + Plasma AGA Enzyme Activity Vector Copy Number (VCN) Plasma Lyso-Gb3 and Total Gb3 FAB-201 FABRY PHASE 2 – Cardiac Variant Total Gb3 Lyso-Gb3 Note: Visualization of multiple biomarkers adjusted to utilize the same statistical scaling ratio across biomarkers (as compared to prior presentation) * Latest data points for this patient are at the 1-year follow-up which = 48 weeks per protocol
FAB-201 FABRY PHASE 2 Infuse AVR-RD-01 Day 0 Drug Product VCN: 1.4 Vector Copy Number (VCN) *Data from Rupar Laboratory; Reference Range: 24–56 nmol/hr/mg; †Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells Plasma Lyso-Gb3 and Total Gb3 Total Gb3 Lyso-Gb3 *Reference Value: 2.4 nM; †Reference Value: 4961 nM; Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Infuse AVR-RD-01 Day 0 Infuse AVR-RD-01 Day 0 Skin Biopsy Score (Patient 3) Baseline 2 6 months 2 Plasma AGA Enzyme Activity Patient 3: Data up to 1 year* suggest trend towards durable engraftment Plasma AGA Leukocyte AGA Infuse AVR-RD-01 Day 0 Leukocyte + Plasma AGA Enzyme Activity Patient 1 Patient 2 Patient 3 Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A New data point Note: Visualization of multiple biomarkers adjusted to utilize the same statistical scaling ratio across biomarkers (as compared to prior presentation) *1-year follow-up = 48 weeks per protocol
Leukocyte AGA (nmol/hr/mg protein) Plasma AGA (nmol/hr/mL protein) Patient 1 Patient 2 Patient 3 Patient 4 AGA: α-Galactosidase A FAB-201 FABRY PHASE 2 Patients 1-4: Plasma and leukocyte enzyme activity sustained up to 22 months Patient #4 dosed using platoTM New data point
New data point Lyso-Gb3: Globotriaosylsphingosine Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype Reduction from Baseline to Last Observation Patient 1 88% Patient 2 NA Patient 3 50% Patient 4 43% Patient 1 Patient 2 Patient 3 Patient 4 FAB-201 FABRY PHASE 2 Patients 1-4: Plasma lyso-Gb3 reduction sustained up to 18 months
Two AVR-RD-01 Fabry clinical trials 9 patients dosed across Phases 1 and 2 PHASE 1 Investigator-Sponsored Trial* Patients Patients Key Objectives Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18-50 year-old males n = 8-12 (4 patients dosed to-date} Treatment-naive 16 - 50 year-old males Safety and preliminary efficacy Safety and efficacy PHASE 2 AVRO – FAB-201 Trial FAB-201 = AVRO-RD-01-201 Study * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ERT: Enzyme Replacement Therapy
Gene Tx + Off ERT Gene Tx + ERT ERT No ERT Gene Tx Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 26% reduction from baseline ERT OFF ERT 18.8 14.0 33.3 10.0 35.7 25.3 26.1 58.5 29.1 15.8 * As of April 27, 2020 (update) Lyso-Gb3: Globotriaosylsphingosine; ERT: Enzyme Replacement Therapy; Tx: Therapy 47% reduction from baseline ERT ON ERT 43% reduction from baseline ERT OFF ERT 23% increase from baseline ERT OFF ERT 37% reduction from baseline ERT ON ERT Patients 1-5: Plasma lyso-Gb3 reduction sustained up to 32 months All patients who have discontinued ERT remain off ERT* FABRY PHASE 1
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Plasma AGA Activity (nmol/hr/mL) Infuse AVR-RD-01 Day 0 = Leukocyte AGA Activity (nmoles/hr/mg protein) 150 100 50 0 300 250 350 = Infuse AVR-RD-01 Day 0 AGA: α-Galactosidase A FABRY PHASE 1 Patients 1-5: Leukocyte and plasma enzyme activity sustained up to 32 months Consistent trends across all patients, 4 patients > 1 year
Drug Product VCN Patient 1 0.7 Patient 2 1.4 Patient 3 0.8 Patient 4 1.4 Patient 5 1.2 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 VCN (per cell) Infuse AVR-RD-01 Day 0 Note: 0.1 VCN is indicative of approx. 5-10% of all nucleated cells having an average of 1-2 copies of the transgene VCN: Vector Copy Number FABRY PHASE 1 VCN stable at 32 months with consistent trend across all other patients 4 patients with 1+ years data
ERT ERT + Gene Therapy Gene Tx Gene Therapy Normal Kidney Function Mild CKD Moderate CKD Severe CKD No ERT eGFR: Estimated Glomerular Filtration Rate; ERT: Enzyme Replacement Therapy; TX: Therapy; CKD: Chronic Kidney Disease FABRY PHASE 1 Patient 1: Kidney function stable at 32 months
Anti-AGA antibodies Pre-existing low titers detected in 4 patients AEs and SAEs reported Phase 1 Fabry (5 patients) and FAB-201 (4 patients) No unexpected safety events or trends identified No SAEs related to AVR-RD-01 drug product Phase 1 AEs (n = 128): Generally consistent with myeloablative conditioning, underlying disease or pre-existing conditions Phase 1SAEs (n = 2): Febrile neutropenia (grade 3) Thrombophlebitis (grade 2) Note: Safety data cut November 26, 2019 AE: Adverse Event; SAE: Serious Adverse Event NOTE: AVR-RD-01 is an investigational gene therapy FAB 201 AEs (n = 98): Generally consistent with myeloablative conditioning, underlying disease or pre-existing conditions Grade 1 or 2 (n = 72) Grade 3 or 4 (n = 30) FAB 201 SAEs: (n = 4) Pre-treatment and prior to conditioning Seizure (grade 2) Post-treatment Dehydration, nausea, vomiting (grade 3) Febrile neutropenia (2 patients, grade 3 & 4)
Cystinosis AVR-RD-04
Goals for gene therapy in cystinosis UNMET NEEDS: Kidney function Unmet needs: renal Fanconi syndrome, proteinuria, chronic kidney disease, kidney failure Vision Unmet needs: corneal cystine accumulation, photophobia, involuntary eyelid closure CNS complications Unmet needs: myopathy, hypotonia, tremors, difficulty swallowing, neurodevelopmental issues (speech and walking delay and cognitive impairment) Endocrine disorders Unmet needs: softening/weakening of bones, bone pain, rickets, long bone deformations, hypophosphatemia, delayed growth, hypothyroidism, pancreatic insulin insufficiency, diabetes, infertility Everyday burden of illness and life expectancy Unmet needs: medications multiple times per day that cause GI discomfort and sulfur body and breath smell, shortened lifespan Sources: Ariceta G et al, Nephrol Dial Transplant, 2015; Elmonem M et al, Orphanet Journal of Rare Diseases, 2016; Gahl et al, NEJM, 2002; Bois et al, J Med Genet, 1976 CNS: Central Nervous System; GI: Gastrointestinal
Patients Key Objectives Up to 6 patients Adults and adolescents Cohorts 1-2 ≥18 years; Cohort 3 ≥14 years Male and Female On oral and ophthalmic cysteamine Safety and efficacy PHASE 1/2 Investigator-Sponsored Trial* * Sponsored by University of California, San Diego Note: AVR-RD-04 aka CTNS-RD-04 Investigator-sponsored* study of AVR-RD-04 in cystinosis patients First patient dosed
PATIENT 1 Age of symptom onset / diagnosis 0 year / 8 months Age dosed with AVR-RD-04 20 years Gender Male Mutation Allele 1: LDM1 Allele 2: Nt1035 (insC) Primary disease signs and SoC treatment related symptoms, including Fanconi syndrome Polyuria Corneal abnormalities Mild photophobia Vomiting Granulocyte Cystine levels at baseline (nmol half cystine per mg protein)* 7.8 Comments NO kidney transplant Cysteamine 1125 mg p.o. every 12 h/day since 2009; discontinued prior to AVR-RD-04 infusion Cysteamine eyedrops 4-5x/day Concomitant medications not listed Cystinosis AVR-RD-04 Phase 1/2 Patient Characteristics Note: AVR-RD-01 aka CTNS-RD-04
New data point Patient 1: Initial data indicate positive trends across multiple measures BIOMARKER ENDPOINTS VCN (vcn/dg) (Drug Product = 2.1) 1 Month 2.9 2 Months 3.0 3 Months 2.0 CLINICAL LAB MEASURES 1.3 1.5 1.5 Asymptomatic Heterozygous Carrier Granulocyte Cystine Range: 0.2 – 1 .9 µmol half cystine/g protein Source: Gertsman I et al., Clinical Chemistry, 2016 VCN: Vector Copy Number; CTNS: Cystinosin, Lysosomal Cystine Transporter; mRNA: Messenger Ribonucleic Acid; eGFR: Estimated Glomerular Filtration Rate; SCr: Serum Creatinine *Data obtained using a novel experimental methodology utilizing in vivo confocal microscopy, to image crystals in the skin behind the ear Urine Volume 24 Hour Urine Volume in L Kidney Function Levels of Cystine in Skin* μm3 Experimental in vivo confocal microscopy Two skin areas, behind the ear and ‘optional’, averaged Analysis and quantification (3D Image-Pro software) Serum Creatinine (mg/dL) normal range: 0.7-1.2 eGFR (mL/min/1.73m2) normal range: >90 2,187 1,493 Average Granulocyte Cystine Level (µmol half cystine/g protein) Baseline 7.8 1 Month 1.3 2 Months 1.5 3 Months 1.5 CYSTINOSIS PHASE 1/2 52 40 38 2.2 2.1 1.6 4.1 2.6
New data point (max per day) OFF Cysteamine ON Cysteamine After Gene Therapy (at 6 months post-gene therapy) Before Gene Therapy 52 20 Number of Medications and Supplements NOTE: Investigational gene therapy CYSTINOSIS PHASE 1/2 Patient 1: Reduced treatment burden at 6 months
No SAEs reported No AEs or SAEs related to AVR-RD-04 drug product AEs reported Consistent with myeloablative conditioning and underlying disease N = 22 (moderate = 9, mild = 13) Phase 1/2 Cystinosis 1 patient dosed No unexpected safety events or trends identified Note: Safety database cut as of January 27, 2020 AE: Adverse Event; SAE: Serious Adverse Event Post-treatment (n = 16, not all events listed) Alopecia, intermittent diarrhea, vomiting Mucositis, intermittent febrile neutropenia, intermittent epistaxis Intermittent blurry vision, intermittent hypokalemia, mucoceles Thrombocytopenia Pre-treatment and prior to conditioning (n = 6, not all events listed) Diarrhea, hypokalemia, dizziness Dehydration, vomiting
plato™ –– AVROBIO’s foundation designed to scale gene therapy worldwide State-of-the-art technologies including automated manufacturing platform Redefines manufacturing best practices Optimized for performance
plato™: Three upgrades designed to optimize potency, safety and durability UPGRADES Increase enzyme activity Increase transduction efficiency Increase VCN Increase marrow space / engraftment Increase consistency and safety 1 | Vector 2 | Conditioning 3 | Automation Upgrades designed to increase Vector Copy Number (VCN), enzyme activity, chimerism and durability * * TDM (therapeutic drug monitoring)
VCN Transduction Efficiency VECTOR UPGRADE: Metrics compared to academic process plato™ UPGRADE 1 (per diploid genome) PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 (%) PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 (nmol/hr/mL) Enzyme Activity PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 Mean = 4.8 2.2x Increase vs. Mean Mean = 0.9 1.8x Increase vs. Mean Mean = 23.3 2.2x Increase vs. Mean FAB-201 FAB-201 FAB-201 VCN: Vector Copy Number; FAB-201: AVR-RD-01 Study NOTE: Data is from drug product FAB-201 patient #4 drug product data with plato™
VECTOR UPGRADE: Metrics compared to academic process plato™ UPGRADE 1 VCN (per diploid genome) PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 1 Transduction Efficiency (%) PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 1 FAB-201 CYS-101 FAB-201 CYS-101 FAB-201 with plato™ 4-plasmid vector (LV2) Bu TDM conditioning Automated manufacturing AVR-RD-04 with “plato-like” 4-plasmid vector Bu TDM conditioning Manual manufacturing 1.8x Increase vs. Mean 2.2x Increase vs. Mean 3.3x Increase vs. Mean* 2.2x Increase vs. Mean* Mean = 0.9 Mean = 23.3 BU TDM: Busulfan Therapeutic Drug Monitoring; VCN: Vector Copy Number; FAB-201: AVR-RD-01 Study; CYS-101: AVR-RD-04 Study; LV: Lentiviral Vector Manufactured at UCLA using UCLA’s assays and methodologies NOTE: Data is from drug product FAB-201 and AVR-RD-04 drug product data
plato™ UPGRADE 2 PRECISION CONDITIONING UPGRADE: Lowest rate of adverse events in the Bu90 range Optimized precision dosing designed to enhance tolerability Targeted busulfan intended to balance optimal engraftment with enhanced safety Adverse Event Probability Optimal Exposure 50 70 90 110 130 Busulfan Cumulative AUC (mg x hr/L) 0.0 0.2 0.4 0.6 0.8 Graft Failure Increased Toxicity Non-Malignant Disorders (n=465 patients) Meta-analysis of 465 patients identified optimal exposure Bu: Busulfan; AUC: Area Under the Curve Sources: Bartelink IH et al, Lancet Haematol, 2016
PRECISION CONDITIONING UPGRADE: Rapid neutrophil and platelet recovery with minimal lymphocyte depletion using Busulfan TDM plato™ UPGRADE 2 Fabry: Patients #1-3 Melphalan 100mg/m2; Patient #4 Busulfan ‘AUC 90’; Cystinosis: Patient #1 Busulfan ‘AUC 90’ Threshold levels for prophylactic supportive care in HSC Tx; ANC <0.5 x 109 per liter (AABB); Platelets <10 X 109 cells/L (AABB) NOTE: Neutrophil counts - G-CSF administration post gene therapy: Pt 1: 7 Doses, Day 7 – 14, Pt 2: 11 Doses, Day 7 – 17, Pt 3: 6 Doses, Day 7 – 12, Pt 4: 5 Doses, Day 8 – 12 NOTE: Platelet counts - Platelet Transfusion: Pt 1: Day 10; Pt 2, 3: Day 11, Pt 4: no transfusion TDM = Therapeutic Drug Monitoring; G-CSF = Granulocyte-colony stimulating factor Cystinosis Patient 1: Busulfan Fabry Patients 1 – 3: Mel Fabry Patient 4: Bu90-TDM Absolute Neutrophil Count (ANC) Platelet Count New data point Absolute Lymphocyte Count
BONE MARROW Potential for widespread microglia engraftment throughout the brain MICROGLIA PERIPHERAL TISSUE Mature Blood Cells Enzyme Neuron Microglia Enzyme Astrocyte Lymphocyte Granulocyte Bloodstream Monocyte Enzyme Macrophage Mature cells area Progenitors area HSC area Bone TRANSDUCED CD34+ CELLS Viscera CNS/PNS IN THE BONE MARROW Busulfan eliminates hematopoietic (CD34+) stem and progenitor cells making space for gene-modified cells BRAIN Busulfan crosses blood-brain barrier and eliminates resident microglia cells making space for gene-modified cells PRECISION CONDITIONING UPGRADE: Designed to access “hard-to-reach” compartments plato™ UPGRADE 2
Drug product production Scalable, global production suites Frozen in aliquots to streamline supply chain CD 34+ hematopoietic stem cells Vector production Large bioreactor 200 liter serum-free suspension culture Automated, closed system Vector with disease-specific transgene INCREASE CONSISTENCY HIGH VOLUME / TITRE 1 2 3 COST-EFFECTIVE SCALE-OUT Cryopreserved to enable convenient dosing Illustrative * AUTOMATION UPGRADE: Designed to deliver large-scale manufacturing 3 plato™ UPGRADE * European manufacturing capabilities planned for 2H 2020; manufacturing capabilities currently in place in U.S. & Australia Differentiated, cost-effective approach
DRUG PRODUCT VECTOR (200 L scale bioreactor runs (109 titre)) 4 production suites ~12 runs per year per suite ~50 patients per run 2,400 PATIENTS ANNUALLY 3 global production suites 8 automated units per suite 100 patients per unit per year 2,400 PATIENTS ANNUALLY Illustrative AUTOMATION UPGRADE: Poised to manufacture at scale plato™ UPGRADE 3 Designed to optimize potency and safety, and overcome historic CMC bottlenecks
3 UPGRADES IN PLACE: plato™ metric compared to academic process plato™ UPGRADE 1, 2, 3 FAB-201: AVR-RD-01 Study FAB-201 THREE MONTH data for patient #4 with plato™ vs. patients #1-3 (nmol/hr/mL) Plasma Enzyme Activity Mean = 1.6 2.9x Increase vs. Mean 2.7 1.4 0.6 4.6 (nmol/hr/mg) Leukocyte Enzyme Activity 3.2x Increase vs. Mean Mean = 18.3 26.0 24.8 4.1 57.9 New data point
Positive trends at six months, including kidney function measures eGFR and serum creatinine measures trending positively at 6 months Pill burden remains significantly lower than at baseline ASGCT 2020 data update – key takeaways plato continues to perform One-month plasma lyso-Gb3 decrease of 43% vs. baseline Three-month leukocyte and plasma enzyme activity levels 3x greater than mean of other three patients at same timepoint in Phase 2 trial Rapid neutrophil and platelet recovery with minimal lymphocyte depletion post Bu90 conditioning First Fabry plato™ patient Sustained long-term positive trends Patient 1 in the Phase 2 trial continues to show stable leukocyte and plasma AGA enzyme activity, now out 22 months Patient 3 in the Phase 2 trial shows increased leukocyte and plasma AGA enzyme activity, decreased plasma lyso-Gb3 level, and stable VCN at new time points All three Phase 1 patients off ERT remain off ERT Long-term Fabry patient data Cystinosis Patient 1 data New data show consistent results across Fabry disease and cystinosis programs
Appendix
Patient 1: 87% substrate reduction in kidney biopsy at 1 year Average number of Gb3 inclusions per peritubular capillary (PTC) Baseline 1 Year (48 weeks) 3.55 0.47 Unpaired t-test for difference between n=55 PTCs at baseline vs. n=101 PTCs at 1 year; p < 0.0001 Error bar represents the standard deviation 3.55 Mean Number of Gb3 Inclusions per PTC Baseline: The last available, non-missing observation prior to AVR-RD-01 infusion Note: With respect to Fabry disease, Gb3 inclusions per PTC is interchangeable with GL-3 inclusions per KIC FAB-201-1: First patient in FAB-201 clinical trial PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary FAB-201 FABRY PHASE 2
Fully Automated Bu-TDM Immunoassay AVROBIO and Saladax announced agreement to develop and validate Saladax’s fully automated nanoparticle immunoassay kit Designed to work on most automated hospital analyzers Regular technician, 24/7 analysis possible with results anticipated in minutes using only microLs of blood Designed to analyze 10-100s samples per machine/hour Expected to eliminate Bu degradation errors as assay conducted in real-time at the point of care Scalable New collaborations advancing leadership in lentiviral gene therapy Antibody-Drug Conjugate AVROBIO and Magenta announced research & clinical collaboration agreement to evaluate Magenta’s preclinical CD117-targeted antibody conjugate to amanitin (MGTA-117) in conjunction with AVROBIO investigational gene therapies Designed to deplete only hematopoietic stem and progenitor cells Has shown promising data in non-human primates MGTA-117 currently in IND-enabling studies Each party retains commercial rights to its own programs
Hematopoietic reconstitution occurs in two distinct phases A few thousand long-term engrafting cells stably sustain levels of transgene product First wave of short-term progenitor cells start to exhaust with progressive takeover by a smaller population of long-term engrafting cells Source: Biasco L et al, Cell Stem Cell, 2016 Clonal Population Time after GT (months) 6 - 12 24 - 48 0 - 3 Long-term engrafting cells Short-term progenitor cells