ASGCT 2022 Cystinosis data update MAY 17, 2022 Exhibit 99.2
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These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our current and prospective product candidates, including AVR-RD-04 for the treatment of cystinosis; the design, commencement, enrollment and timing of ongoing or planned clinical trials and regulatory pathways; our plans and expectations with respect to the development of our clinical and preclinical product candidates, including timing, design and initiation of our potential clinical and registration trials and anticipated interactions with regulatory agencies; the timing of anticipated clinical and regulatory updates; the timing of patient recruitment and enrollment activities, clinical trial results, and product approvals; the timing and results of our ongoing preclinical studies; the anticipated benefits of our gene therapy platform including the potential impact on our commercialization activities, timing and likelihood of success; the expected benefits and results of our manufacturing technology, including the implementation of our plato® platform in our clinical trials and gene therapy programs; and the expected safety profile of our investigational gene therapies. 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These risks and uncertainties include, but are not limited to, the risk that any one or more of our product candidates, including AVR-RD-04 for the treatment of cystinosis, will not be successfully developed or commercialized; the risk that regulatory agencies may disagree with our anticipated development approach for any one or more of our product candidates; the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators; the risk that we may not successfully recruit or enroll a sufficient number of patients for our clinical trials; the risk that we may not realize the intended benefits of our gene therapy platform, including the features of our plato® platform; the risk that our product candidates or procedures in connection with the administration thereof, including our use of busulfan as a conditioning agent or potential use of monoclonal antibody conditioning agents, will not have the safety or efficacy profile that we anticipate; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving our product candidates; the risk that we will be unable to obtain and maintain regulatory approval for our product candidates; the risk that the size and growth potential of the market for our product candidates will not materialize as expected; risks associated with our dependence on third-party suppliers and manufacturers; risks regarding the accuracy of our estimates of expenses and future revenue; risks relating to our capital requirements and needs for additional financing; risks relating to clinical trial and business interruptions resulting from the ongoing COVID-19 pandemic or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises; and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. 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Expanding Phase 1/2 data set shows systemic gene therapy impact AVR-RD-04 is first and only investigational gene therapy for cystinosis Improvements in neurocognitive assessments Stable muscle/grip strength Reduction in cystine crystals in skin and gastrointestinal mucosa Improved or stable eye measures Reduction in leukocyte cystine to target levels Quantified increase in hair strand pigmentation * Data as of May 6, 2022 Proof-of-concept demonstrated in adult population Plan to meet with regulators in 2H 2022 to discuss company-sponsored trial Safety and tolerability profile remains strong* All five patients dosed remain off oral cysteamine
Cystinosis is an attractive commercial market * SOC: standard of care; WAC pricing from Redbook using standard dosing assumptions. Horizon’s Procysbi oral therapy (delayed release cysteamine bitartrate), midpoint between avg. adult and pediatric 5-year cystinosis SOC treatment cost ~$4.3 million* in U.S. ~1,600 patients in U.S., Europe and Japan alone Most severe form, infantile nephropathic cystinosis, affects ~95% of cystinosis population Billion-dollar revenue opportunity SOC does not stop disease progression Vision Corneal cystine accumulation, photophobia Endocrine disorders Softening & deformation of bones, hypothyroidism, diabetes, infertility CNS and muscular complications Myopathy, hypotonia, neurodevelopmental issues Kidney function Frequently require multiple kidney transplants Shortcomings of cysteamine pills often lead to poor patient compliance: Cause sulfur odor on body and breath High daily pill burden can lead to GI discomfort and vomiting SOC is burdensome Disease symptoms persist despite SOC:
NORMAL LYSOSOME CYSTINOSIS LYSOSOME Cystinosis caused by defective gene that encodes cystinosin, an exporter protein Cysteine (monomer of cystine) Functional exporter protein (Cystinosin) Defective exporter protein (Cystinosin) Cystine crystals Cystine crystals build up in lysosomes causing tissue and organ damage Source: Cherqui et al, Nat Rev Nephrol. 2017 Cystine (dimer)
PATIENT MONTHS OFF CYSTEAMINE PILLS AND EYE DROPS POST AVR-RD-04 INFUSION CURRENT STATUS cysteamine pills PATIENT 1 OFF PATIENT 2 OFF PATIENT 3 OFF PATIENT 4 OFF PATIENT 5 OFF cysteamine eye drops PATIENT 1 OFF PATIENT 2 ON (patient restarted July 2021) PATIENT 3 OFF PATIENT 4 Was not on cysteamine eye drops prior to infusion OFF PATIENT 5 OFF CYSTINOSIS PHASE 1/2 Note: Patients 2, 3 and 5 stopped cysteamine eye drops 1-month post-transplant (per protocol); Patient 1 stopped cysteamine eye drops prior to baseline; Patient 4 was not on cysteamine drops prior to infusion. Data as of May 6, 2022 CYSTINOSIS PHASE 1/2: PATIENTS 1-5 All patients continue to be oral cysteamine-independent Patient #1 out 2 ½ years NEW DATA
BEERY TEST OF VISUAL MOTOR INTEGRATION (VMI) Improvement in motor coordination and visual perception observed post gene therapy CYSTINOSIS PHASE 1/2: PATIENTS 1, 3 MOTOR COORDINATION SUBSCORE VISUAL PERCEPTION SUBSCORE NEW DATA Patient 1 Patient 3 Data for Patient 2 are not available; The Beery – Buktenica Developmental Test of Visual Motor Integration (Beery VMI) is a standardized test evaluating the ability of the brain to interpret and translate visual information into an exact motor response
Average Grip Strength (kg) is defined as the average of the largest reading from each hand Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 CYSTINOSIS PHASE 1/2: PATIENTS 1-5 Average grip strength stable up to 27 months Disease progression typically leads to loss of muscle strength over time NEW DATA
Reduction in number of skin cystine crystals below patients’ own SOC baseline at 12+ months CYSTINOSIS PHASE 1/2: PATIENT 1-5 SKIN BIOPSY: AVERAGE INTRACYTOPLASMIC CRYSTALS PER CELL NEW DATA POINT Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 35% reduction 8% reduction 64% reduction 81% reduction For Patient 4 and 5, only their Baseline data is currently available
Reduction in number of cystine crystals in gastrointestinal mucosa below patients’ own SOC baseline at 12+ months CYSTINOSIS PHASE 1/2: PATIENT 1-5 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 76% reduction 73% reduction 53% reduction 28% reduction 86% reduction 85% reduction 83% reduction For Patient 4 and 5, only their Baseline data is currently available RECTAL BIOPSY: AVERAGE INTRACYTOPLASMIC CRYSTALS PER CELL NEW DATA POINT
Crystal buildup in eye clearly visible before gene therapy Treatment goal is to prevent or halt further accumulation of corneal crystals; complete clearance not expected CYSTINOSIS PHASE 1/2: PATIENT 1 Patient 1 at baseline
Decline in corneal crystals and improved photophobia grade CYSTINOSIS PHASE 1/2: PATIENT 1 IVCM: In Vivo Confocal Microscopy; exploratory method; These results are for a single patient only and may vary in the study population; OD: Oculus Dexter (right eye); HRT3: Heidelberg Retina Tomograph 3; Scoring instructions: for each layer, assign a score of 0-4, where 0=no crystal; 1 <25%; 2=25-50%; 3=50-75%; 4>75%; Liang et al., IOVS 2015; * Score range: 1-5 where 1 is no photophobia and 5 is severe; Images obtained for Patient 1 at baseline using Nidek Confoscan and used Heidelberg HRT3 w/ Rostock Corneal Module for all other images BASELINE 18 MONTHS IMAGES/24 MONTHS PHOTOPHOBIA GRADE IVCM Images Photophobia Grade* (patient reported) IVCM Images Photophobia Grade* (patient reported) PATIENT 1 3 1 CORNEAL CRYSTALS 174 µm, OD 331 µm, OD Front of Cornea Back of Cornea 176 µm, OD 331 µm, OD Front of Cornea Back of Cornea Eye layers Right eye Left eye Baseline 12 months Baseline 12 months Anterior Stroma 4 3 4 1.9 Middle Stroma 4 3 4 1.7 Posterior Stroma 4 2.1 4 2 Preliminary scoring performed by Dr. Hong Liang CNRS, Paris, France NEW DATA POINT
Stable corneal crystals and photophobia grade CYSTINOSIS PHASE 1/2: PATIENTS 2 & 3 IVCM: In Vivo Confocal Microscopy; exploratory method; These results are for a single patient only and may vary in the study population; OD: Oculus Dexter (right eye); HRT3: Heidelberg Retina Tomograph 3; Scoring instructions: for each layer, assign a score of 0-4, where 0=no crystal; 1 <25%; 2=25-50%; 3=50-75%; 4>75%; Liang et al., IOVS 2015; * Score range: 1-5 where 1 is no photophobia and 5 is severe; BASELINE 12 MONTHS IVCM Images Photophobia Grade (patient reported) IVCM Images Photophobia Grade (patient reported) PATIENT 2 2 or 3 2 PATIENT 3 2 2 Front of Cornea Back of Cornea Front of Cornea Back of Cornea 43 µm, OD 66 µm, OD 43 µm, OD 66 µm, OD 178 µm, OD 331 µm, OD 178 µm, OD 331 µm, OD NEW DATA
Early cystinosis treatment is essential to prevent kidney complications Frequency1 Characteristics of phenotype1 Disease phenotype Nephropathic cystinosis ~95% of patients Clinical symptoms related to renal Fanconi syndrome during first year of life Fanconi syndrome: Defect of kidney tubules resulting in malabsorption of electrolytes / substances in kidneys2 Frequently require multiple renal transplants with lifetime of immunosuppression Most severe form of cystinosis Infantile Juvenile (“late-onset”) <5% of patients Usually diagnosed later in childhood or during adolescence (after age 10) Typically experience renal Fanconi syndrome and proteinuria Frequently require multiple renal transplants with lifetime of immunosuppression Source: Simon-Kucher & Partners 2020. 1. Emma et al. (2014). Nephropathic Cystinosis: an international consensus document. Nephrology Dialysis Transplantation, 29(4), iv87-iv94; 2. Keefe et al. (2020). Fanconi Syndrome. StatPearls.
eGFR data reinforce need for early intervention Entered trial with progressive kidney disease (eGFR of 48), decline accelerates in line with natural history CYSTINOSIS PHASE 1/2: PATIENT 1 NEW DATA POINT eGFR: Estimated Glomerular Filtration Rate; eGFR calculated using CKD-EPI formula Normal Kidney Function Mild CKD Moderate CKD Severe CKD
12 Month CYSTINOSIS PHASE 1/2: PATIENT 2-3 15 Transplanted kidney not impacted by treatment, as expected Serum creatinine remains stable post infusion NEW DATA POINT NEW DATA Patient 2 – Serum Creatinine (mg/dL) Normal Range: 0.7 – 1.2 Patient 3 – Serum Creatinine (mg/dL) Normal Range: 0.7 – 1.2
Note: Data from Patient 1 up to 12 months have been previously disclosed. Therapeutic range is <1.0 Half Cystine (nmol/mg protein). Measure of 1 is level of healthy heterozygote.; For Patient 1, Leukocyte Cystine Quantification was initiated at approximately week 20 ; *Patient 1: Hemolyzed sample which may potentially lead to lower results; **Patient 1: Sample processed outside of the range of the stability; †Patient 2: Sample was not collected and shipped according to study protocol CYSTINOSIS PHASE 1/2: PATIENTS 1-5 NEW DATA Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 † * * * Leukocyte cystine levels in blood suppressed out to 28 months
CYSTINOSIS PHASE 1/2: PATIENT 1 Cystinosin is located in melanosomes and regulates melanin synthesis Note: GT: gene therapy; Source: Chiaverini et al., FESEB, 2012 Pre-Infusion PATIENT 1 Post-Infusion 24 months 12 Months post GT 24 Months post GT Patient 1 Hair color – RGB intensity NEW DATA Hair strand Darker pigmentation may be a sign of multi- functional cystinosin activity post gene therapy Further enforces systemic reach of gene therapy 25% reduction
CYSTINOSIS PHASE 1/2: PATIENT 3 Cystinosin is located in melanosomes and regulates melanin synthesis Source:* Do not have permission to show patient image; Chiaverini et al., FESEB, 2012 12 Months PT Baseline Patient 3 Hair color – RGB intensity NEW DATA Darker pigmentation may be a sign of multi-functional cystinosin activity post gene therapy Further enforces systemic reach of gene therapy Hair strand PATIENT 3* 37% reduction
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 * From second apheresis; VCN: Vector Copy Number; PBCs: Peripheral Blood Cells; dg: Diploid Genome Drug Product VCN/dg Patient 1 2.1 Patient 2 1.3* Patient 3 1.6 Patient 4 0.6 Patient 5 2.5 CYSTINOSIS PHASE 1/2: PATIENTS 1-5 Sustained engraftment to date demonstrated by VCN plateau for patients beyond 12 months NEW DATA: 9 &12 Months NEW DATA POINT
Phase 1/2 Cystinosis trial (5 patients) No unexpected safety events or trends related to AVR-RD-04 identified No SAEs or AEs related to AVR-RD-04 drug product No SAEs reported Preliminary AEs reported N=40 for subject 1; N=22 for subject 2; N=8 for subject 3; N=25 for subject 4; N=13 for subject 5 Majority of AEs are mild or moderate 1 severe -- Appendicitis unrelated to study treatment or procedures AEs generally consistent with myeloablative conditioning or underlying disease: Pre-treatment and prior to conditioning (not all events listed) Diarrhea, hypokalemia, dizziness Dehydration, vomiting Post-treatment (not all events listed) Alopecia, intermittent diarrhea, vomiting, loss of appetite Mucositis, intermittent febrile neutropenia, intermittent epistaxis Intermittent blurry vision, intermittent hypokalemia, mucoceles Thrombocytopenia AE: Adverse Event; SAE: Serious Adverse Event; safety data cut-off date is May 6, 2022 CYSTINOSIS PHASE 1/2 CYSTINOSIS PHASE 1/2: PATIENTS 1-5
AVROBIO IND FDA approved July 2021 Building regulatory momentum Active IND with US/EU Orphan Designation and US Fast Track Designation Preclinically focused FDA Type C meeting Dec. 2021 Clinical/CMC FDA Type C meeting planned 2022 Plan to initiate AVROBIO-sponsored trial 2023 Two-stage clinical strategy planned: Pre-renal transplant population for initiation in 2023 Post-renal transplant population as second stage Several endpoints across renal/ocular/neuromuscular systems under evaluation US, UK and EU trial sites Trial enabling interaction Actionable feedback incorporated Long-term follow-up study
Expanding Phase 1/2 data set shows systemic gene therapy impact AVR-RD-04 is first and only investigational gene therapy for cystinosis Improvements in neurocognitive assessments Stable muscle/grip strength Reduction in cystine crystals in skin and gastrointestinal mucosa Improved or stable eye measures Reduction in leukocyte cystine to target levels Quantified increase in hair strand pigmentation * Data as of May 6, 2022 Proof-of-concept demonstrated in adult population Plan to meet with regulators in 2H 2022 to discuss company-sponsored trial Safety and tolerability profile remains strong* All five patients dosed remain off oral cysteamine
Appendix
PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 5 Patient baseline characteristics Age of symptom onset/diagnosis 0 year / 8 months 0 year / 6 months 4 years 6 years 8 months Age dosed with CTNS-RD-04 20 years Infused October 2019 46 years Infused June 2020 22 years Infused November 2020 33 years Infused November 2021 31 years Infused March 2022 Gender Male Male Male Male Female Mutation 57-kb deletion c.696dupC, p.Val233Argfs*63 57-kb deletion c.473T>C, p.Leu158Pro c.18_21del, p.Thr7Phefs*7 c.295_298del, p.Val99Ilefs*18 57-kb deletion c.473T>C, p.Leu158Pro 57-kb deletion c.414G>A, p.Trp138* Kidney transplant status and cysteamine dosing prior to CTNS-RD-04 dosing No kidney transplant; stage 3 (moderate CKD) renal failure On oral Cysteamine On Cysteamine drops 2 renal transplants (1987 and 1999) On oral Cysteamine On Cysteamine drops 1 renal transplant (2010) On oral Cysteamine On Cysteamine drops 2 renal transplants (2008 and 2017) On oral Cysteamine Off Cysteamine drops No renal transplant; stage 3 (moderate CKD) renal failure On oral Cysteamine On Cysteamine drops Manufactured CTNS-RD-04 product and busulfan dose 7.88 x 10e6 CD34+ cells/kg VCN: 2.07 94% viability AUC Bu: 81.8 mg.h/L 5.07 x 10e6 CD34+ cells/kg VCN: 1.27 91% viability AUC Bu: 86.7 mg.h/L 9.59 x 10e6 CD34+ cells/kg VCN: 1.59 95% viability AUC Bu: 90 mg.h/L 3.63 x 10e6 CD34+ cells/kg VCN: 0.59 90% viability AUC Bu: 88.5 mg.h/L 9.12 x 10e6 CD34+ cells/kg VCN: 2.5 95% viability AUC Bu: 88.2 mg.h/L CYSTINOSIS PHASE 1/2