UNITED STATES
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CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure. |
On October 19, 2021, AVROBIO, Inc. (the “Company”) issued a press release titled “AVROBIO Reports New Interim Safety Data Across Investigational Gene Therapies for Fabry and Gaucher Disease Type 1.” A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01 | Other Events. |
On October 19, 2021, the Company updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the slide presentation is filed as Exhibit 99.2 to this Current Report on Form 8-K and incorporated into this Item 8.01 by reference.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| 99.1 | AVROBIO, Inc. press release, dated October 19, 2021. | |
| 99.2 | AVROBIO, Inc. slide presentation, dated October 19, 2021. | |
| 104 | The cover page from this Current Report on Form 8-K, formatted in Inline XBR | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| AVROBIO, INC. | ||||||
| Date: October 19, 2021 | By: | /s/ Geoff MacKay | ||||
| Geoff MacKay | ||||||
| President and Chief Executive Officer | ||||||
Exhibit 99.1
AVROBIO Reports New Interim Safety Data Across Investigational Gene Therapies for
Fabry and Gaucher Disease Type 1
No adverse events or serious adverse events related to drug product in 14 patients treated in
Phase 1 and 2 Fabry disease trials and Phase 1/2 Gaucher disease trial
Post-gene therapy administration safety data out 41⁄2 years for first patient dosed
AVROBIO leads way with new industry-leading techniques designed to better elucidate the
safety profile of investigational gene therapies at cellular level
CAMBRIDGE, Mass.—(BUSINESS WIRE)—Oct. 19, 2021—AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today reported new safety data from the first lentiviral gene therapy clinical trials for Fabry disease and Gaucher disease, as well as new high-resolution cellular data providing insights into the mechanisms of action of its gene therapies. The data are being presented at the virtual 28th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), Oct. 19-22, 2021.
“We have worked from the very beginning and at every turn to incorporate a strong safety focus in our proprietary plato® gene therapy platform, by having carefully selected clinical indications; an optimized, state-of-the-art vector; closed and automated manufacturing; use of innovative analytics; and a personalized conditioning regimen, to bring lentiviral gene therapies to patients with lysosomal disorders,” said AVROBIO President and CEO Geoff MacKay. “We believe the data shared this week continue to support the predictable safety profile of our investigational gene therapies targeting lysosomal disorders. Additionally, we’re particularly proud to unveil new industry-leading techniques that are designed to provide additional insight throughout the process, including safety monitoring at the DNA level within different bone marrow and blood cell types.”
Fabry disease clinical trial safety data reinforce predictable and generally consistent safety profile
New safety data from the first eight adult patients dosed in the Phase 2 FAB-GT trial and the five adult patients dosed in the investigator-sponsored Phase 1 trial show no adverse events (AEs) or serious adverse events (SAEs) related to drug product AVR-RD-01. The AEs and SAEs experienced by trial participants to date in the two trials have been generally consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease or pre-existing conditions. Of all safety events reported to date, 4% were classified as SAEs (n=11), consisting of nausea, vomiting, dehydration, fever, febrile neutropenia and mucosal inflammation, all of which resolved without clinical sequelae.
These safety data are from patients in the FAB-GT study with a mean post gene-therapy follow up of 16 months (range: 2-38 months) and the Phase 1 study with a mean post-gene therapy follow-up of 39 months (range: 29-54 months). Safety data from the ninth patient recently dosed in the FAB-GT study are still being analyzed, but preliminary data are consistent with the overall safety profile.
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“Overall, we believe that these data further support the risk-benefit profile of AVROBIO’s investigational gene therapy for Fabry disease. With previously reported durability data out more than three and a half years for the first patient, these new data strengthen the safety profile of this gene therapy,” said Mark Thomas, M.D., principal investigator of the AVROBIO-sponsored FAB-GT Phase 2 trial of AVR-RD-01, an investigational gene therapy for Fabry disease, nephrologist at the Department of Nephrology, Royal Perth Hospital and clinical professor at the University of Western Australia Medical School. “In my team’s experience, target concentration intervention delivers an individualized busulfan dose to patients, which results in anticipated reduced blood cell counts and other common adverse events associated with the routine practice of stem cell transplantation and minimizes risk of out-of-range toxicity.”
With AVROBIO’s Bu90-Target Concentration Intervention (TCI) conditioning regimen, patients receive four daily doses of the conditioning agent busulfan, each adjusted to target a cumulative area under the curve of 90 mg x hr/L. This targeted dosing is intended to maximize busulfan’s ability to make space in the bone marrow for the genetically modified stem cells to engraft, while minimizing the risk of out-of-range toxicity. AVROBIO is also working with clinicians to develop comprehensive care guidelines designed to help gene therapy care teams further proactively mitigate or prevent potential side effects.
Six of the 14 Fabry disease patients in the trials have been treated using AVROBIO’s proprietary plato® gene therapy platform, which includes a state-of-the-art optimized lentiviral vector, proprietary tag technologies, proprietary analytical techniques and Bu90-TCI. The platform’s industry-leading closed, automated manufacturing platform is designed to bring gene therapy to patients worldwide.
The safety data cut-off date for the Phase 1 trial was July 26, 2021, and for the FAB-GT trial was Aug. 20, 2021.
Previously reported efficacy data from the two trials have documented stable and sustained enzyme activity and reductions of 87% and 100% in kidney Gb3 inclusions for the evaluable kidney biopsies of two Fabry disease patients. AVROBIO is planning to share updated efficacy data from both trials during the first quarter of 2022. Enrollment in the FAB-GT trial (NCT03454893) is ongoing, and further details are available on clinicaltrials.gov.
Gaucher disease type 1 clinical data at 12+ months show no unexpected safety events
New safety data from the first patient dosed in the Phase 1/2 Guard1 trial of AVR-RD-02 show no SAEs and no AEs to date related to drug product more than 14 months post-treatment. Reported AEs for this patient, who was treated with investigational AVR-RD-02 incorporating key elements of AVROBIO’s proprietary plato® gene therapy platform, have been consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease and pre-existing conditions. The safety data cut-off date was Aug. 31, 2021.
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A second patient has now been dosed in the trial.
Previously reported efficacy data from the Guard1 clinical trial has shown improvement across biomarkers for the first-treated Gaucher disease patient, as well as platelet and hemoglobin levels maintained in the normal range. Enrollment in the Guard1 trial (NCT04145037) is ongoing, and further details are available on clinicaltrials.gov.
Novel techniques provide insight on safety at DNA level of bone marrow and blood cell types
Standard safety follow-up for ex vivo lentiviral gene therapy patients includes looking at the number and location of transgene insertions broadly across nucleated blood cell populations. AVROBIO has developed a new approach involving high-resolution molecular biology follow-up that enables the collection and monitoring of integration sites for individual cell types and at different stages of cell maturation. Additionally, using single-cell transcriptional profiling, AVROBIO has traced stem/progenitor cell states from their initial source, through transduction, to multiple years after infusion in patients.
All samples analyzed to date show a stable composition of genetically engineered cell populations in the blood starting six months after gene therapy. The company has seen no evidence of persistent dominant clonal expansion across all patients studied. In addition, when combining this information with data derived from the patients’ own bone marrow, the company detected identical insertion sites between blood cell progenitors and their mature cell progeny.
“Patient safety is at the core of our plato® gene therapy platform and we have developed industry-leading techniques, including being able to monitor at the cellular level the integration site and transcription profiles of our investigational therapies. We believe these data provide a valuable and unique tool to monitor at the DNA level the safety of our investigational therapies within the different bone marrow and blood cell types,” adds MacKay.
About AVROBIO Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene therapy designed to drive durable expression of therapeutic protein, even in hard-to-reach tissues and organs including brain, muscle and bone. Our ex vivo lentiviral gene therapy pipeline includes clinical programs in Fabry disease, Gaucher disease type 1 and cystinosis, as well as preclinical programs in Hunter syndrome, Gaucher disease type 3 and Pompe disease. AVROBIO is powered by our industry-leading plato® gene therapy platform, our foundation designed to deliver gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.
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Forward-Looking Statement
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “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 prospective product candidates, the anticipated overall safety profile of our product candidates, the implementation and anticipated benefits of our high-resolution molecular biology monitoring techniques, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, the timing of patient recruitment and enrollment activities, and product approvals, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, and the expected benefits and results of our implementation of the plato® platform in our clinical trials and gene therapy programs, including the use of a personalized busulfan conditioning regimen (Bu90-TCI). Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.
Any forward-looking statements in this press release are based on AVROBIO’s 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 AVROBIO’s 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 AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO 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 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 AVROBIO’s 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 enrollment and development timelines 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 materially and adversely 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.
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Investor Contact:
Christopher F. Brinzey
Westwicke, an ICR Company
339-970-2843
chris.brinzey@westwicke.com
Media Contact:
Kit Rodophele
Ten Bridge Communications
617-999-9620
krodophele@tenbridgecommunications.com
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OCTOBER 2021 Corporate Presentation Exhibit 99.2
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 been verified by any independent source. This presentation may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “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 anticipated benefits and safety profile of busulfan as a conditioning agent; the implementation and anticipated benefits of our high-resolution molecular biology monitoring techniques; 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; 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 that regulatory agencies may disagree with our anticipated development approach for any one or more of our product candidates, including that we may not be able to utilize our planned registration trial of AVR-RD-01 or other product candidates for full approval but instead be required to conduct additional testing, that we may be required to conduct our planned testing in a more time-consuming, expensive, challenging or otherwise different manner than we envision or have conducted for our existing trials, and the risk that regulatory agencies may require additional testing and/or clinical trials for our product candidates prior to initiating registration trials for such 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, 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, 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. Copyright© 2021 AVROBIO, Inc. All rights reserved.
Vision Bring personalized gene therapy to the world. Purpose Freedom from a lifetime of genetic disease.
Leadership in ex vivo lentiviral gene therapy Patients dosed across 3 indications of patients out >6 months show durability; Longest out 3.5 years SOC: Standard of Care 19 100% Leading pipeline for 6 lysosomal disorders First-in-class gene therapies Multi-billion dollar market potential >50,000 target patient population ~$4.8 billion annual net sales SOC Industry-leading platform: plato® Foundation for worldwide commercialization and pipeline expansion Planning for multiple registration trials in 2022; Pivoting to commercial readiness
Leading lysosomal disorder gene therapy pipeline Multiple milestones across pipeline expected over the next 12 months 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 IND-Enabling Phase 1/2 Planned Upcoming Milestones 1Q22 – Clinical and regulatory update at WORLDSymposium™ Mid22 – Initiate registration trial 1H22 – Clinical trial update 1Q22 – Clinical trial and regulatory update 2H22 – Initiate company-sponsored clinical trial 2H22 – Initiate Phase 1/2 clinical trial 2H22 – Initiate registration trial 2H22 – Initiate Phase 1/2 clinical trial Indication WHOLLY-OWNED/LICENSED Planned regulatory milestones subject to regulatory agency clearance
Disease Approx. 2020 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 $1.5B $2.3M Hunter $0.6B $2.4M Pompe $1.1B $3.2M Multi-billion dollar market opportunity Pipeline of first-in-class indications targeting > 50,000 patients 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); midpoint between avg. adult and pediatric Note: Shire acquired by Takeda in 2019 SOC: Standard of Care Total: $4.8B ‡
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
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 PATIENT 5 PATIENT 6 PATIENT 7 PATIENT 8 PATIENT 9 Gaucher Type 1 Phase 1/2 PATIENT 1 PATIENT 2 Cystinosis Phase 1/2 PATIENT 1 PATIENT 2 PATIENT 3 Durability demonstrated across clinical programs First patient out 3.5 years; 10 patients out 1 year or more * Data not yet available
Analysis of 465 non-malignant patients identified optimum exposure to busulfan Bu90-TCI designed with objectives of providing precise target concentration, further improving outcomes, and reducing risk of out of-range toxicity Bu: Busulfan; AUC: Area Under the Curve; TCI: Target Concentration Intervention Sources: Bartelink IH et al, Lancet Haematol, 2016 Adverse Event Probability 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 TCI Dose Bu90 90 mg.m/L Historical data behind Bu90-TCI Optimal Exposure Range
n=0 n=1 n=0 n=0 n=2 n=0 n=0 n=1 n=1 n=1 n=0 Notes: Fabry Phase 2 safety data cut-off August 20, 2021; Gaucher Phase 1/2 safety data cut-off August 31, 2021; AE: Adverse events; For purposes of this presentation, ‘subacute’ is defined as AEs occurring and resolving within 5 to 28 days from the time of dosing; * Resolved with treatment; ** One patient had unresolved and ongoing anemia as of the Fabry Phase 2 safety data cut-off of August 20, 2021, which is generally considered chronic; *** Excludes AEs that are not subacute Grade 3-4 Grade 1 - mild Grade 2 - moderate Grade 3 - severe Grade 4 - life-threatening Other common AEs*** Bu90 TCI Anticipated AEs n=4 n=4 n=4 n=3 Subacute grade 3-4 AEs observed to date after Bu90-TCI conditioning have been predictable and have typically peaked over ~1 week Based on available data from five Fabry Phase 2 patients and one Gaucher Phase 1/2 patient who received Bu90-TCI * **
Developing proactive care approaches for HCPs designed to improve the patient experience Elevated focus intended to prevent or mitigate side effects Source: Matthews, RH et al, Bone Marrow Transplantation, 2007 Proactive management of common side effects Mucositis = magic mouthwash, drugs that accelerate mucosal healing, pain relievers as necessary Nausea = anti-nausea drugs, hydration Risk of infection = improved preventative antimicrobials and rapid neutrophil recovery (can be further enhanced by G-CSF) Risk of bleeding = rapid platelet recovery (can be further enhanced by platelet transfusion) AVROBIO developing proactive care guidelines and facilitating real-time support to clinicians To further improve patient experience for all types of conditioning Side-effect profile addressability
Fabry disease
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, executive function deficit, white matter lesions Unmet needs with SOC: Fabry Disease Target Product Profile**: Prevents, halts or reverses disease; extends/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 * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy Affects ~ 1:40,000 males and 1:118,000 females in U.S. Tom, living with Fabry disease
OBJECTIVES PATIENTS Safety and tolerability Preliminary efficacy n = 5 patients 18 – 59 year-old males On ERT >6 months prior to enrollment FULLY ENROLLED PHASE 1 * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ** FAB-GT f/k/a FAB-201 *** Protocol amendment submitted to FDA increasing enrollment to up to 14 patients, including females. Plan to submit same protocol amendment in other jurisdictions. Two AVR-RD-01 Fabry clinical trials 14 patients dosed across Phase 1 and 2 OBJECTIVES PATIENTS Safety and tolerability Efficacy n = 8-12 patients*** (9 dosed to-date) 16 – 50 year-old males *** Treatment naïve ACTIVELY RECRUITING PHASE 2 Investigator-Sponsored Trial* AVROBIO FAB-GT Trial **
100% substrate reduction 1 Year (48 weeks) Scored by 2 independent, blinded pathologists Patient 4 Clinically meaningful and statistically significant reduction in substrate in first two evaluable kidney biopsies FABRY PHASE 2 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 PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary 87% substrate reduction 1 Year (48 weeks) Scored by 2 independent, blinded pathologists NEW DATA
Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity (nmol/hr/mg protein) Leukocyte AGA Enzyme Activity Plasma AGA Enzyme Activity Plasma AGA Activity Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A Leukocyte AGA Activity Reference Range: 24–56 nmol/hr/mg protein; AGA: α-galactosidase A Durability demonstrated over multiple measures up to 2.5 years Patient 4 dosed using plato® FABRY PHASE 2 Patient 1 Patient 2 Patient 3 Patient 4 VCN: Vector Copy Number; PBL: Peripheral Blood Leukocytes; dg: Diploid Genome Drug Product VCN/dg Patient 1: 0.7 Patient 2: 0.5 Patient 3: 1.4 Patient 4: 1.6 Vector Copy Number
Day 0 70% average plasma lyso-Gb3 reduction FABRY PHASE 2 Patient 1 Patient 2 Patient 3 Patient 4 Reduction from Baseline to Last Observation Patient 1 86% Patient 2 N/A Patient 3 55% Patient 4 69% Lyso-Gb3 Plasma Reference Value: 2.4 nM; Lyso-Gb3: Globotriaosylsphingosine Note: Patient 2 has normal substrate, consistent with late-onset cardiac variant phenotype
ERT No ERT Gene Rx 25.3 26.1 58.5 29.1 15.8 Day 0 25% average plasma lyso-Gb3 reduction below baseline ERT All patients who have discontinued ERT remain off ERT* FABRY PHASE 1 * As of January 11, 2021 Lyso-Gb3: Globotriaosylsphingosine; ERT: Enzyme Replacement Therapy; Rx: Therapy Gene Rx + Off ERT Gene Rx + ERT Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 25% reduction from baseline ERT OFF ERT 19.0 14.7 33.4 8.2 39.2 43% reduction from baseline ERT OFF ERT 48% reduction from baseline ERT ON ERT 44% reduction from baseline ERT ON ERT 35% increase from baseline ERT OFF ERT
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
SAEs & AEs reported CYSTINOSIS PHASE 1/2 No unexpected safety events or trends identified Phase 1 SAEs (n=2) Post gene therapy treatment Febrile neutropenia (1 patient, Grade 3) Thrombophlebitis (1 patient, Grade 2) Phase 2 SAEs (n=9) Pre gene therapy treatment and prior to conditioning Seizure (1 patient, Grade 2) Post gene therapy treatment Dehydration, nausea, vomiting (1 patient, Grade 3) Odynophagia (1 patient, Grade 3) Thrombocytopenia (1 patient, Grade 3) Febrile neutropenia (2 patients, Grade 3) Culture negative fevers (1 patient, Grade 2) Mucositis (1 patient, Grade 2) Dysphagia (1 patient, Grade 1) Phase 1 AEs (n=92) Generally consistent with myeloablative conditioning, protocol mandated-drugs, underlying disease or pre-existing conditions Grade 3 or 4 (n=13) Phase 2 AEs (n=193) Generally consistent with myeloablative conditioning, protocol mandated-drugs, underlying disease or pre-existing conditions Grade 3 or 4 (n=31) AE: Adverse Event; SAE: Serious Adverse Event Based on data from 13 patients treated with AVR-RD-01 in phase 1/2 studies FABRY PHASE 1 & 2 No SAEs or AEs related to drug product AVR-RD-01 Phase 1 safety data cut-off July 26, 2021; Phase 2 safety data cut-off August 20, 2021
Cystinosis
Cystinosis opportunity Standard of care (SOC): Cysteamine pills & eye drops Not curative, relentless progression of disease continues; significantly shortened lifespan; kidney transplant often required Burdensome and expensive – high pill burden and hourly eye drops; 5-year treatment cost with SOC ~$4.3 million* Caused by CTNS gene defect, resulting in cystine buildup in lysosomes Cystinosis Target Product Profile**: Prevents, halts or reverses disease; extends/normalizes lifespan Addresses all patient segments – male & female; kidney transplant independent; all ages Lifelong durability – single infusion; off cysteamine pills and eye drops Impacts hard-to-reach organs – e.g., eye, endocrine organs, brain Well tolerated 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 * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy
Steady enrollment in AVR-RD-04 IST trial in cystinosis AVR-RD-04 trial sponsored by University of California, San Diego; IST does not use plato® platform Note: AVR-RD-04 a/k/a CTNS-RD-04 IST: Investigator Sponsored Trial 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) OBJECTIVES PATIENTS Safety and tolerability Hypothesis generation of endpoints Up to 6 patients (3 patients dosed to date) Adults and adolescents Cohorts 1-2 >18 years; Cohort 3 >14 years Male and female Oral and ophthalmic cysteamine ACTIVELY RECRUITING: PHASE 1/2 AVR-RD-04
4.0 2.6 Sharp drop in the number and size of cystine crystals in skin and rectal biopsies CYSTINOSIS PHASE 1/2: PATIENT 1 Rectal Biopsy Skin Biopsy 35% reduction* Average intracytoplasmic crystals per cell Occupancy of cytoplasmic volume Average intracytoplasmic crystals per cell Occupancy of cytoplasmic volume Baseline 12 months 76% reduction Baseline 12 months 90% 25% 75% 10% 11.3 2.7 Note: These results are for a single patient only and may vary in the study population * Calculation of reduction in average intracytoplasmic crystals per cell in skin biopsy revised based on baseline value of 4.0 (vs. 4.6 as shown in previous presentations)
Substantial decline in corneal crystals observed at 1 year CYSTINOSIS PHASE 1/2: PATIENT 1 Note: These results are for a single patient only and may vary in the study population; IVCM: In Vivo Confocal Microscopy; OD: Oculus Dexter (right eye); HRT3: Heidelberg Retina Tomograph 3 111 µm, OD 174 µm, OD 330 µm, OD 515 µm, OD 724 µm, OD Baseline IVCM images from Nidek Confoscan 12 months post-gene therapy IVCM images from Heidelberg HRT3 w/ Rostock Corneal Module 51 µm, OD 331 µm, OD 513 µm, OD 176 µm, OD Back of cornea CORNEAL CRYSTALS Front of cornea
Photophobia improved meaningfully at 1 year Photophobia, or extreme sensitivity to light, is a hallmark of cystinosis CYSTINOSIS PHASE 1/2: PATIENT 1 Liang, H. IONS May 2015 Cystinosis photophobia intensity associated with: Crystal density (light scattering) Inflammatory cell infiltration Corneal nerve damage Self-Assessed Photophobia Grade (Patient 1) No photophobia, no discomfort Moderate difficulty with light requiring wearing sunglasses Slight difficulty with light causing regular eye blinking Slight difficulty with light causing occasional eye blinking Extreme difficulty with light requiring the patient to remain inside, cannot bear natural light even with sunglasses Severe difficulty with light requiring wearing sunglasses in a quasi-permanent manner
Blond hair and pale skin typical for cystinosis patients 4 months 6 months 9 months Post-Infusion Patient 1 appears to exhibit progressively darkening skin, eyebrows and hair color post-infusion, suggesting a possible impact of cystinosin protein on melanin Note: These results are for a single patient only and may vary in the study population; Background removed for clarity Source: Chiaverini et al., FESEB, 2012 Darker pigmentation may be a sign of multi-functional cystinosin activity post-gene therapy CYSTINOSIS PHASE 1/2: PATIENT 1 Cystinosin is located in melanosomes and regulates melanin synthesis Pre-Infusion
Day 0 VCN trending as expected across patients Patient 1 reached VCN therapeutic plateau DRUG PRODUCT VCN/dg Patient 1 2.1 Patient 2 1.3* Patient 3 1.6 * From second apheresis VCN: Vector Copy Number; PBCs: Peripheral Blood Cells; dg: Diploid Genome CYSTINOSIS PHASE 1/2 Patient 1 Patient 2 Patient 3
AEs are generally consistent with myeloablative conditioning or underlying disease: Pre-AVR-RD-04 treatment and prior to conditioning (not all events listed) Diarrhea, hypokalemia, dizziness Dehydration, vomiting Post-AVR-RD-04 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 AEs & SAEs reported CYSTINOSIS PHASE 1/2 AEs (n=53) Majority of AEs are mild or moderate and resolved SAE (n=1) Post AVR-RD-04 treatment: appendicitis unrelated to study treatment or procedures No unexpected safety events Conditioning-related side effects have been manageable and transient No SAEs or AEs related to AVR-RD-04 drug product Note: Safety database cut as of May 17, 2021 AE: Adverse Event; SAE: Serious Adverse Event
Gaucher type 1
Gaucher disease type 1 opportunity Standard of care (SOC): ERT Not curative, relentless progression of disease continues, including bone crisis and fatigue Burdensome and expensive – bi-weekly infusions required; 5-year treatment cost with ERT = ~$2.3 million* Caused by mutation in the gene encoding for glucocerebrosidase (GCase) enzyme Gaucher disease Type 1 Target Product Profile**: Prevents, halts or reverses disease; extends/normalizes lifespan Addresses all patient segments – all GD1 genetic mutations, all ages, male & female Lifelong durability – single infusion; off ERT/chaperone therapy Impacts hard-to-reach organs – e.g., brain, bone and bone marrow Well tolerated Unmet needs with SOC: Bone-related manifestations Skeletal abnormalities, avascular necrosis, osteoporosis Hemoglobin levels and platelet counts Anemia, thrombocytopenia, easy bruising, bleeding Hepatosplenomegaly Enlarged liver, enlarged spleen Everyday burden of illness, and life expectancy Fatigue, pain, lung disease, biweekly infusions, shortened lifespan CNS complications Increased risk of GBA-Parkinson’s disease Adrianna, living with Gaucher disease type 1 Affects ~ 1:44,000 people worldwide * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy
Guard1: Phase 1/2 study in Gaucher disease type 1 OBJECTIVES PATIENTS Safety Efficacy Engraftment Enrollment goal 8-16 patients 2 patients dosed to date 18-45-year-old males and females Have a confirmed diagnosis of GD1 based on: Deficient glucocerebrosidase enzyme activity Clinical features consistent with GD1 An adaptive, open-label, multinational phase 1/2 study of the safety and efficacy of ex vivo, lentiviral vector-mediated gene therapy AVR-RD-02 for patients with Gaucher disease type 1 ACTIVELY RECRUITING: PHASE 1/2 AVR-RD-02 Gaucher disease type 1 patients who are: ERT-stable for >24 months or Treatment-naïve or Have not received ERT or SRT in the last 12 months GD1: Gaucher Disease Type 1; ERT: Enzyme Replacement Therapy; SRT: Substrate Reduction Therapy
First patient’s plasma chitotriosidase levels spike off ERT Personal history documents response to intermittent and halted ERT use GUARD1: PATIENT 1 Chitotriosidase Plasma Activity Normal Range: 0.0–44.2 μmoL/L/h ERT: Enzyme Replacement Therapy Chitotriosidase is a marker of inappropriately activated macrophages (Gaucher cells) Chitotriosidase Plasma Activity (µmol/L/h) Years Prior to Gene Therapy Infusion
Plasma Chitotriosidase Activity (μmol/L/h) Baseline (ON ERT) 3 months (OFF ERT) 6 months (OFF ERT) 151 125 GUARD1: PATIENT 1 Baseline taken one month prior to gene therapy which is when ERT is discontinued Lyso-Gb1 Plasma Normal Range: 0.5 – 1.2 ng/mL Plasma chitotriosidase activity normal range: 0.0 – 44.2 μmoL/L/h ERT: Enzyme Replacement Therapy Key biomarkers below ERT baseline at 6 months 77 Chitotriosidase is a marker of inappropriately activated macrophages (Gaucher cells) 49% reduction NEW DATA 18 25 32 Plasma Lyso-Gb1 (ng/mL) Baseline (ON ERT) 3 months (OFF ERT) 6 months (OFF ERT) 44% reduction Lyso-Gb1 is a sensitive and specific marker of toxic metabolite accumulation in Gaucher disease
Platelet counts and hemoglobin in normal range at 6 months, despite being off ERT GUARD1: PATIENT 1 Platelet Count Reference Value Adult: 130-400x109/L; Hemoglobin Reference Value: Males: 13.5-17.5 g/dL; Females: 11.5-16.0 g/dL; grey line: local (safety) lab values; pink dots: central (efficacy) lab values; ERT: Enzyme Replacement Therapy Platelet Count (x109 /L) Platelet Count Normal range Hemoglobin Concentration Normal range
GUARD1: PATIENT 1 VCN trending as expected at 6 months VCN, vector copy number; PBL, peripheral blood leukocytes; dg, diploid genome Drug Product VCN/dg Patient 1 3.7 Day 0
No unexpected safety events 12+ months post dosing AVR-RD-02 has not been approved by the FDA or by any other regulatory body and its safety and efficacy has not been established Note: Safety database cut as of August 31, 2021 AE, adverse event; SAE, serious adverse event; G-CSF, granulocyte colony stimulating factor * Unresolved and ongoing as of the safety database cut of August 31, 2021 **Two of the AEs, dehydration and decreased appetite, are noted as related to both G-CSF and busulfan administrations AEs are consistent with myeloablative conditioning, drugs mandated by protocol or study procedures, underlying disease and pre-existing conditions No SAEs reported No SAEs or AEs related to drug product AEs reported, n= 37 GUARD1: PATIENT 1 Event severity assessment 26 AEs were Grade 1 or Grade 2 11 AEs were Grade 3 or 4 Anemia, leukopenia, neutropenia, thrombocytopenia, eye pain, decreased appetite, dehydration, headache, hypophosphatemia, amenorrhea* Event causality assessment 21 AEs definitely, probably or possibly related to busulfan (N= 1 patient dosed) 8 AEs definitely, probably or possibly related to G-CSF** (N= 2 patients enrolled) 1 AE definitely, probably or possibly related to Plerixafor (N= 2 patients enrolled)
Gaucher type 3
Gaucher disease type 3 opportunity Subacute neurological form of Gaucher disease characterized by progressive encephalopathy and associated with the systemic manifestations of Gaucher type 1 Unmet needs with SOC: Bone-related manifestations Bone crises, bone pain, avascular necrosis Hemoglobin levels and platelet counts Anemia, thrombocytopenia, easy bruising, bleeding Hepatosplenomegaly Enlarged liver, enlarged spleen Everyday burden of illness, and life expectancy Fatigue, pain, shortened lifespan Standard of care (SOC): ERT Not curative, relentless progression of disease continues; utility of ERT minimized by its inability to impact the CNS Burdensome and expensive – bi-weekly infusions required; 5-year treatment cost with ERT = ~$2.3 million* Gaucher disease Type 3 Target Product Profile**: Prevents, halts or reverses disease; normalizes lifespan Addresses all patient segments – all genetic mutations, all ages, male & female Lifelong durability – single infusion; off ERT/SRT Impacts hard-to-reach organs – e.g., brain, bone and bone marrow Well tolerated – no ERT-related side effects Maddie, living with Gaucher disease Type 3 CNS complications Seizures, cognitive problems, poor coordination * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy
Lentiviral gene therapy enables global distribution of functional enzyme to brain and bone in preclinical studies Widespread distribution of GFP+ cells in the mouse brain Colocalization with microglia marker Striatum Cortex Hippocampus Cerebellum Midbrain Olfactory Bulb IV-dosed animal DAPI GFP+ Engrafted Cells Iba1 GFP: Green Fluorescent Protein; DAPI: 4′,6-diamidino-2-phenylindole; Iba1: Ionized Calcium-Binding Adapter Molecule 1; IV: Intravenous PRECLINICAL DATA PRECLINICAL DATA PRECLINICAL DATA
plato® –– AVROBIO’s platform for global gene therapy commercialization Solves key industry challenges Redefines manufacturing best practices
Designed to be fully scalable Common components and automation leveraged across manufacturing DRUG PRODUCT Closed system automated platform Scale out of manufacturing suites and automation units to meet patient demand PLASMID 3 of 4 component plasmids used in every vector Each plasmid can be mass produced and stored for use VECTOR State of the art, largest scale, 200L vector production Expansion through simple installation of additional units, mass produced, frozen, and stored for use Note: This diagram is for illustrative purposes only
Proprietary tags deliver therapeutic protein into hard-to-reach organs Figure adapted from Gleitz H et al., EMBO Mol Med, 2018 Fig 3A; *P<0.05, ***P<0.001, ****P<0.0001; LV GT: Lentiviral Gene Therapy Tag normalizes heparan sulfate in brain Tag normalizes glycogen substrate in brain * * * * * * * * * * * * 0 5 10 Normal Mouse Hunter Mouse LV GT LV GT w/ Tag Fold Total Heparan Sulfate over Normal Mouse Hunter syndrome Pompe disease PRECLINICAL DATA LV GT w/ Tag LV GT Pompe Mouse Normal Mouse * * * *
Thank you
Appendix
Patient sample analysis 1-year post-gene therapy FAB-GT Trial* High resolution molecular follow up of gene therapy patients *AVR-RD-01 has not been approved by the FDA or any regulatory agency and its safety and efficacy have not been established. Peripheral blood Bone marrow BM= Bone Marrow PB= Peripheral Blood HSC= Hematopoietic Stem Cells MPP= Multipotent Progenitors MLP= Myelo-Lymphoid Progenitors ETP= Early T Progenitors MEP= Megakaryo-Erythroid Progenitors CMP= Common Myeloid Progenitors GMP= Granulo-Monocyte Progenitors
FABRY PHASE 2 Patient #4 is first Fabry patient dosed with plato® FAB-GT 12 month data for patient #4 with plato® vs. patients #1-3 4.2x Increase vs. Mean (nmol/hr/mL) Plasma Enzyme Activity Mean = 1.4 1.8 1.0 1.4 5.9 6.3x Increase vs. Mean (nmol/hr/mg protein) Leukocyte Enzyme Activity Mean = 14.6 17.9 11.4 14.6 92.0
100% clearance of substrate in kidney biopsy at 1 year Patient dosed using plato® FABRY PHASE 2 Two-sample t-test for difference between average PTCs at Baseline vs. 48 weeks; p < 0.0001; Error bar represents the standard error at Baseline (n=103 PTCs) and 48 weeks (n=99 PTCs); scored by 2 independent, blinded pathologists 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 PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary 100% substrate reduction 1 Year (48 weeks) Patient 4 Average number of Gb3 inclusions per peritubular capillary (PTC)
Durability demonstrated over multiple measures up to 3.5 years FABRY PHASE 1 VCN: Vector Copy Number; PBL: Peripheral Blood Leukocytes; dg: Diploid Genome Vector Copy Number Leukocyte AGA Activity (nmol/hr/mg protein) Leukocyte AGA Enzyme Activity Plasma AGA Activity Reference Range: 5.1–9.2 nmol/hr/mL; AGA: α-galactosidase A Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity Reference Range: 24–56 nmol/hr/mg protein; AGA: α-galactosidase A Drug Product VCN/dg Patient 1: 0.7 Patient 2: 1.4 Patient 3: 0.8 Patient 4: 1.4 Patient 5: 1.2 Plasma AGA Enzyme Activity Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Cardiac function and mass stable across multiple measures up to 1 year FABRY PHASE 2 Source: *Alfakih K et al, J Magn Reson Imaging, 2003 ; **Maceira AM et al, J of Cardiovascular Magnetic Resonance, 2006 *Reference Range Mean Values Male 20-39 yrs; EF: 64.3 ± 4.2%; EDV: 178.6 ± 30.1 mL; CO: 4-8 L/min; LV Mass Index: 67.8 ± 10.7 g/m2 **Reference Range Mean Values Male 40-49 yrs; EF: 58-75 %; EDV: 117-200 mL; CO: 4-8 L/min; LV Mass Index: 58-91 g/m2
Reduction of pre-existing anti-ERT drug IgG antibodies Suggests potential as a therapeutic option independent of pre-existing antibodies San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) Change in pre-existing antibodies reported for Hurler disease (MPS-1) Ex vivo LV gene therapy with conditioning n=6 Evaluable patients (5/6) demonstrated sustained, supraphysiologic blood IDUA activity 4/5 prior ERT (rhIDUA) exposure (5-28 months) 4/5 pre-existing ERT-induced IgG antibodies 6/6 anti-rhIDUA IgGs undetectable 2 months post-gene therapy Fabry Disease Phase 1 IgG Antibody Titer Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 IgG Antibody Titer Negative Control Positive Control ~ ~ FABRY PHASE 1 Source: Gentner B et al., Blood, 2019 ERT: Enzyme Replacement Therapy; IgG: Immunoglobulin G; MPS-1: Mucopolysaccharidosis Type 1; IDUA: Iduronidase: SR-TIGET: San Raffaele Telethon Institute for Gene Therapy; LV: Lentiviral; rhIDUA: Recombinant Human alpha-L-Iduronidase Day 0 Similar results observed in other studies
Updated FDA table of surrogate endpoints (as of 3/31/21) Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure | FDA FDA: Food and Drug Administration Note: FDA guidance provides that the acceptability of a surrogate endpoint in a particular clinical development program should not be assumed to be appropriate for use in a different program.
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
DRUG PRODUCT Poised to manufacture at scale Global infrastructure already in place VECTOR (200L scale bioreactor runs (109 titer)) 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 Note: This diagram is for illustrative purposes only Scale
CMC achievements have defined the plato® story X Strategic investment in technology laid the foundation for our manufacturing leadership Robust production platform Best-in-class LV manufacturing Scalable from plasmid to drug product Global footprint In the clinic in multiple jurisdictions Cost effective Intended to address key COGs issues Manufacturing Analytics Robust platform analytics Best-in-class VCN assay First-in-class transduction assay Deep product characterization First-in-class single cell analytics Potency assay matrix Intended to accelerate regulatory approvals CMC: Chemistry, Manufacturing, and Controls; VCN: Vector Copy Number; LV: Lentiviral; COGs: Cost Of Goods