Full Press Release Details
Corporate Presentation JANUARY 2021
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
independently verified, and AVROBIO makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. While AVROBIO believes its internal research is reliable, such research 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; 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 anticipated benefits and safety profile of busulfan as a
conditioning agent; 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; the potential impact of the COVID-19 outbreak on our clinical trial programs and business generally, as well as our plans and expectations with respect to the timing and resumption of any development activities that may be temporarily
paused as a result of the COVID-19 outbreak; and the market opportunity for and anticipated commercial activities relating to our investigational gene therapies. 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 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, 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 COVID-19 outbreak 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 on Form 10-Q, 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 presentation are the property of their respective owners. Note regarding future updates: The
statements contained in this presentation reflect our current views with respect to future events, which may change significantly as the global consequences of the COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically
Vision Bring personalized gene therapy
to the world. Purpose Freedom from a lifetime of genetic disease.
Ex vivo lentiviral gene therapy has
emerged as a leading modality across multiple genetic diseases Industry-wide data demonstrate proven record, broad utility TOLERABILITY DURABILITY EFFICACY WIDE REACH BROAD UTILITY Approved ALD Beta thalassemia MLD Investigational Fanconi anemia
Hurler syndrome Sanfilippo A Sanfilippo B SCID-ADA SCID-X Sickle cell disease Wiskott-Aldrich syndrome X-CGD >350 patients >1,000 patient years Pediatrics and adults All mutations No exclusions due to pre-existing antibodies >12 years
post-infusion Head-to-toe, including: Brain Muscle Bone ALD: Adrenoleukodystrophy; SCID-ADA: Severe Combined Immunodeficiency-Adenosine Deaminase Deficiency; SCID-X: X-Linked Severe Combined Immunodeficiency; MLD: Metachromatic Leukodystrophy;
X-CGD: X-Linked Chronic Granulomatous Disease
Leading lysosomal disorder gene therapy
pipeline 13 patients dosed to date IND: Investigational New Drug Fabry AVR-RD-01 Gaucher type 1 AVR-RD-02 Cystinosis AVR-RD-04 Hunter AVR-RD-05 Gaucher type 3 AVR-RD-06 Pompe AVR-RD-03 Proof-of-Concept IND-Enabling Phase 1/2
Fabry Gaucher type 1 Cystinosis Hunter
Gaucher type 3 Pompe COMMERCIAL CALL POINTS REGULATORY PATHWAYS CLINICAL EXECUTION TECHNICAL & MANUFACTURING Halo effect' driven by strong pipeline synergies Replicable path to market
Disease Approx. 2019 Global Net
Sales Five-Year SOC Cost per U.S. Patient* Selected Companies w/ Marketed Therapies Fabry $1.4B $1.7M Cystinosis $0.2B $4.3M Gaucher $1.4B $2.3M Hunter $0.6B $2.4M Pompe $1.0B $3.2M Multi-billion dollar market opportunity Targeting rare
lysosomal disorders with annual sales of ~$4.6 billion 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 2019 Net Sales from
company annual and other reports Horizon's Procysbi oral therapy (delayed release cysteamine bitartrate); midpoint between avg. adult and pediatric Note: Shire acquired by Takeda in 2019 SOC: Standard of Care Total: $4.6B
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
PRODUCT TESTING 1 2 3 4 5
Blood GI System Leukopenia
Lymphopenia Neutropenia Febrile neutropenia Thrombocytopenia Anemia Abdominal pain Diarrhea Mucositis Nausea Vomiting Days Post Gene Therapy Emerging tolerability profile has been predictable and manageable Conditioning-related grade 3-4 AEs were
transient in first 2 plato patients Bu90 TCI Mean Toxicity Grade Bu90-TCI: Busulfan 90-Target Concentration Intervention; AE: Adverse Event; GI: Gastrointestinal Bu90- TCI Busulfan 90 Target Concentration Intervention (TCI) Observations
to-date show short-term side effects start ~1 week after infusion, peak over the next 3-5 days and subside Day 0
PROGRAM PATIENT MONTHS POST-INFUSION
Fabry Phase 1 PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 5 Fabry Phase 2 PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 Gaucher Phase 1/2 PATIENT 1 Cystinosis Phase 1/2 PATIENT 1 PATIENT 2 PATIENT 3 Note: Based on data cut-off date of Nov. 12, 2020
Durability across programs 9 patients out 1 year or more; first patient out 3.5 years
"First Wave" Programs
Fabry, Gaucher Type 1, cystinosis
Fabry disease opportunity Standard
of care (SOC): ERT Not curative, relentless progression of disease continues Burdensome and expensive - bi-weekly ERT infusions required; 5-year treatment cost of ERT = ~$1.7 million* Caused by mutation in gene encoding for alpha-galactosidase
A enzyme Kidney function Proteinuria, polyuria, kidney failure Cardiac function Left ventricular hypertrophy, fibrosis, heart failure Neuropathic pain Pain and burning sensations in hands and feet, pain crises Everyday burden of illness, and life
expectancy Not curative, relentless progression of disease, shortened lifespan CNS complications TIA/stroke, depression, mild cognitive deficiency, white matter hyperintensities Unmet needs with SOC: Fabry Disease Target Product Profile: Prevents,
halts or reverses disease; normalizes lifespan Addresses all patient segments - all genetic mutations, male and female, all ages Lifelong durability - single infusion; off ERT Impacts hard-to-reach organs - e.g., brain, heart,
kidney Well tolerated - no ERT/chaperone therapy-related side effects Travis, living with Fabry disease * WAC pricing from Redbook using standard dosing assumptions Affects ~ 1:40,000 males and 1:118,000 females in U.S.
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 FAB-201 = AVRO-RD-01-201 Study * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ERT:
Enzyme Replacement Therapy
Substantial reduction of substrate
in kidney biopsy at 1 year 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 Average number of Gb3 inclusions per peritubular capillary (PTC) Baseline 1 Year (48 weeks) 3.55 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 0.47 FABRY PHASE 2: PATIENT 1 87% substrate reduction
"The U.S. Food and Drug
Administration today approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease." "In this trial, patients treated with Galafold over six months had a greater reduction in
globotriaosylceramide (GL-3) in blood vessels of the kidneys (as measured in kidney biopsy samples) as compared to patients on placebo." "Galafold was approved using the Accelerated Approval pathway, under which the FDA may approve drugs
for serious conditions where there is an unmet medical need and where a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients." Precedent for use of kidney biopsy data for FDA approval of
drug candidate for Fabry disease
Precedent for use of kidney biopsy
data for FDA approval of drug candidate for Fabry disease Sources: Galafold (Migalastat), Multi-Discipline FDA Review; Germain 2019, Genet Med 21, 1987-1997 (2019) 12.1% -54.1% -42.6% -64.1% -36.3% -45.6% -27.3%
Leukocyte AGA Activity (nmol/hr/mg
protein) Leukocyte AGA Enzyme Activity Lyso-Gb3 Plasma Reference Value: 2.4 nM; Lyso-Gb3: Globotriaosylsphingosine Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype Plasma Lyso-Gb3 Sustained trends over
multiple measures up to 2.5 years Patient 4 dosed using plato FABRY PHASE 2 Plasma AGA Enzyme Activity Plasma AGA Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A Plasma AGA Activity (nmol/hr/mL) VCN: Vector Copy
Number; PBL: Peripheral Blood Leukocytes; dg: Diploid Genome Leukocyte AGA Activity Reference Range: 24-56 nmol/hr/mg protein; AGA: -galactosidase A Drug Product VCN/dg Patient 1: 0.7 Patient 2: 0.5 Patient 3: 1.4 Patient 4: 1.6 Vector
Copy Number Patient 1 Patient 2 Patient 3 Patient 4
29% average lyso-Gb3 reduction below
baseline ERT All patients who have discontinued ERT remain off ERT* FABRY PHASE 1 * As of October 26, 2020 Lyso-Gb3: Globotriaosylsphingosine; ERT: Enzyme Replacement Therapy; Tx: Therapy Gene Tx + Off ERT Gene Tx + ERT Patient 1 Patient 2 Patient 3
Patient 4 Patient 5 25% reduction from baseline ERT OFF ERT 19.0 14.0 33.4 8.2 34.9 25.3 26.1 58.5 29.1 15.8 47% reduction from baseline ERT ON ERT 43% reduction from baseline ERT OFF ERT 20% increase from baseline ERT OFF ERT 48% reduction from
baseline ERT ON ERT ERT No ERT Gene Tx Day 0
Day 0 Kidney function (eGFR) stable
up to 3.5 years* Normal Kidney Function Severe CKD Moderate CKD Mild CKD FABRY PHASE 1 & 2 * Eight of nine patients stable; other patient entered trial with more advanced kidney disease and a baseline eGFR level <50 mL/min/1.73m2. As
expected, this patient has not stabilized, and the patient remains on ERT Note: eGFR was calculated using the CKD-EPI formula eGFR: Estimated Glomerular Filtration Rate; CKD: Chronic Kidney Disease; CKD-EPI: Chronic Kidney Disease Epidemiology
Collaboration Fabry Phase 2 Fabry Phase 1
No unexpected safety events or
trends identified Anti-AGA antibody titers observed in 4 patients in the Phase 1 trial and 2 patients in FAB-201. We believe none of these are of clinical significance Phase 1 SAEs (n=2) Febrile neutropenia (grade 3) Thrombophlebitis (grade 2)
Note: Safety data cut off October 8, 2020; AVR-RD-01 is an investigational gene therapy AE: Adverse Event; SAE: Serious Adverse Event; AGA: Aspartylglucosaminidase FAB 201 SAEs (n=6) Pre-AVR-RD-01 treatment and prior to conditioning Seizure (grade
2) Post-AVR-RD-01 treatment Dehydration, nausea, vomiting (grade 3) Febrile neutropenia (2 patients, grade 3 & 4) Culture negative fevers (grade 2) Mucositis (grade 2) Phase 1 AEs (n=101) Generally consistent with myeloablative conditioning,
underlying disease or pre-existing conditions Grade 3 or 4 (n=17) FAB 201 AEs (n=111) Generally consistent with myeloablative conditioning, underlying disease or pre-existing conditions Grade 3 or 4 (n=22) FABRY PHASE 1 & 2 Anti-AGA antibodies
No SAEs or AEs related to AVR-RD-01 drug product AEs and SAEs reported
Planned global regulatory strategy