Full Press Release Details
MAY 2022 Corporate Presentation Exhibit
Disclaimer This presentation has been
prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on
studies, publications, surveys and other data obtained from third-party sources and AVROBIO's own internal estimates and research. While AVROBIO believes these third-party sources to be reliable as of the date of this presentation, it has not
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"intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words and phrases or similar expressions that are intended to identify
forward-looking statements. 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; 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; the expected safety profile of our investigational gene therapies; and our
financial position and cash runway expectations. Any such statements in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Any forward-looking statements in this presentation are based on our
current expectations, estimates and projections about our industry as well as management's current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of our product candidates 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. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO's actual results to differ from those contained in the forward-looking statements, see the section
entitled "Risk Factors" in AVROBIO's most recent Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO's subsequent filings with the Securities and Exchange
Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Note regarding trademarks: plato is a registered trademark of AVROBIO. Other trademarks referenced in this
Vision Bring personalized gene therapy
to the world. Purpose Freedom from a lifetime of genetic disease.
Leading hematopoietic stem cell (HSC)
gene therapy company Targeting lysosomal disorders representing a multi-billion revenue opportunity Strong efficacy and safety profile to date across two clinical-stage programs Regulatory discussions planned for 2H 2022 to frame approval pathways
for multiple indications Strong balance sheet with cash runway into Q1 2024 Investment highlights 4
Leading lysosomal disorder gene therapy
pipeline Gaucher type 1 AVR-RD-02 Cystinosis AVR-RD-04 Hunter AVR-RD-05 Gaucher type 3 AVR-RD-06 Pompe AVR-RD-03 IND-Enabling Phase 1/2 Indication WHOLLY-OWNED/LICENSED Planned regulatory milestones subject to regulatory agency clearance;
*Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to UCSD from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).
Disease Approx. 2020 Global Net
Sales Five-Year SOC Cost per U.S. Patient* Selected Companies w/ Marketed Therapies Cystinosis $0.2B $4.3M Gaucher $1.5B $2.3M Hunter $0.6B $2.4M Pompe $1.1B $3.2M Multi-billion dollar market opportunity Cost of standard of care in target
indications is extremely high Sources: Rombach S et al., Orphanet J Rare Dis, 2013; van Dussen L et al., Orphanet J Rare Dis, 2014 ; * WAC pricing from Redbook using standard dosing assumptions 2020 Net Sales from company annual and
other reports; Horizon's Procysbi oral therapy (delayed release cysteamine bitartrate), mid point between avg. adult and pediatric Note: Shire acquired by Takeda in 2019; SOC: Standard of Care Total: $3.4B
Significant advantages over standard of
care Lifelong treatments vs. potential single-dose therapy Treatment burden Enzyme or protein level DISEASE PROGRESSION CONTINUES COULD HALT, PREVENT OR REVERSE DISEASE Enzyme Replacement Therapy (ERT) Temporary bolus of enzyme, not curative
Bi-Weekly ERT Plasma Pharmacokinetics of ERT Life-long infusions Transient, intermittent elevation Bi-weekly IV infusions AVROBIO Gene Therapy Designed for 24/7 expression of protein, curative potential Functional Protein Expression in Transduced
HSCs and Their Progeny 24/7 expression One-Time Gene Therapy Long-term, continuous elevation Single IV infusion ERT: Enzyme Replacement Therapy; IV: Intravenous; HSC: Hematopoietic Stem Cells Ability to impact CNS No Yes
Unrivaled commercial-scale platform in
plato MOBILIZATION & APHERESIS Patient Consent & Screening Patient Monitoring CONDITIONING & GENE THERAPY ADMINISTRATION CELL SEPARATION & CULTURE TRANSDUCTION CLOSED, AUTOMATED SYSTEM HARVESTING & CRYOPRESERVATION DRUG
Cystinosis opportunity Not curative,
relentless progression of disease continues; significantly shortened lifespan; kidney transplant often required Substantial side effects (e.g., halitosis and GI disturbances), resulting in low compliance and poor quality of life Burdensome and
expensive - high pill burden and frequent eye drops throughout the day; 5-year treatment cost in the U.S. with SOC ~$4.3 million* WAC pricing from Redbook using standard dosing assumptions. Horizon's Procysbi oral therapy (delayed
release cysteamine bitartrate), midpoint between avg. adult and pediatric Unmet needs with SOC: Vision Corneal cystine accumulation, photophobia, involuntary eyelid closure Endocrine disorders Softening & deformation of bones, hypothyroidism,
diabetes, infertility Everyday burden of illness, reduced life expectancy High pill burden causes GI discomfort; sulfur body odor and breath CNS complications Myopathy, hypotonia, tremors, swallowing, neurodevelopmental issues Kidney function Renal
Fanconi syndrome, proteinuria, CKD, kidney failure Jaxon, living with cystinosis Affects ~ 1:170,000 people Standard of care (SOC): Cysteamine pills & eye drops
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)
AVR-RD-04 collaborator-sponsored
trial AVR-RD-04 trial sponsored by University of California, San Diego; does not use plato platform; AVR-RD-04 aka CTNS-RD-04 Clinical trial funded in part by grants to UCSD from the California Institute for Regenerative Medicine
(CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH) All clinical data in this presentation have been provided by the sponsor and are preliminary and subject to change. For open-label studies in which interim reports
are provided, the data are regularly reviewed and validated. As a result, certain data may change over time, including reductions or increases in the number of reported safety events, until the database is locked at end of study. OBJECTIVES PATIENTS
Safety and tolerability Hypothesis generation of endpoints 6 patients (5 patients dosed to date) Adults and adolescents Cohorts 1-2 >18 years; Cohort 3 >14 years Male and female Oral and ophthalmic cysteamine FULLY ENROLLED: PHASE 1/2
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
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 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
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 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 POIN
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 m, OD 331 m, OD Front of Cornea Back of Cornea 176 m, OD 331 m, 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 m, OD 66 m, OD 43
m, OD 66 m, OD 178 m, OD 331 m, OD 178 m, OD 331 m, OD
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
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 22 Sustained
engraftment to date demonstrated by VCN plateau for patients beyond 12 months
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