SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): May 14, 2020
(Exact name of registrant as specified in its charter)
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|Common Stock, $0.0001 par value per share||AVRO||Nasdaq Global Select Market|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
|Item 7.01|| |
Regulation FD Disclosure.
On May 14, 2020, AVROBIO, Inc. (the Company) presented a scientific presentation titled Hematopoietic Stem Cell Gene Therapy Corrects Neuromuscular Manifestations in Preclinical Study of Pompe Mice at the 23rd Annual Meeting of the American Society of Gene & Cell Therapy. A copy of the slide presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 and 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|| |
On May 14, 2020, the Company issued a press release titled AVROBIO Presents New Preclinical Data on Lentiviral Gene Therapy Program for Pompe Disease at ASGCT 2020. A copy of the press release 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.
|99.1||AVROBIO, Inc. slide presentation, dated May 14, 2020.|
|99.2||Press release issued by AVROBIO, Inc., dated May 14, 2020.|
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.
|Date: May 14, 2020||By:|
|President and Chief Executive Officer|
Session: Musculo-skeletal Diseases II Hematopoietic Stem Cell Gene Therapy Corrects Neuromuscular Manifestations in Preclinical Study of Pompe Mice Niek van Til, PhD AVROBIO, Cambridge, MA USA May 14, 2020 Exhibit 99.1
Pompe Program Team 3/25/2020 NSG Study What’s Important Now Monthly Report Niek van Til is an employee of AVROBIO.
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, prospective products and goals, the therapeutic potential of our investigational gene therapies, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, potential regulatory approvals and the timing thereof, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, the expected benefits and results of our implementation of the plato™ platform in our clinical trials and gene therapy programs, the expected safety profile of our investigational gene therapies, timing and likelihood of success, plans and objectives of management for future operations, and future results of anticipated products. 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 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 investigational gene therapies 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 or of encountering challenges in the enrollment or dosing in such 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 investigational gene therapies 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 investigational gene therapies, the risk that we will be unable to obtain and maintain regulatory approvals for our investigational gene therapies, the risk that the size and growth potential of the market for our investigational gene therapies 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 investigational gene therapies. 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 trademark of AVROBIO. Other trademarks referenced in this presentation are the property of their respective owners.
Pompe is a lysosomal and glycogen storage disease Rare, progressive, often fatal neuromuscular disorder POMPE DISEASE Mutations in the acid alpha-glucosidase (GAA) gene resulting in deficient enzyme activity Leads to accumulation of glycogen in tissues and organs, predominantly in muscles Manifests as a spectrum of symptoms and rates of progression across patients of different ages Infantile form (<1% GAA activity) Extreme muscle weakness, “floppy” appearance, enlarged heart, typically die before 1 year Late / delayed onset form (2-40% GAA activity) Weakness of leg and hip muscles, become wheelchair-bound and ventilator-dependent, premature death The standard of care is enzyme replacement therapy Lysosome Normal muscle cell Pompe disease (GAA mutation) Affected lysosomes Affected muscle cells Over time Low acid α-glucosidase function Glycogen storage disorder Lysosome & organelle dysfunction Broad inflammation, muscle atrophy Cytoplasmic glycogen Sources: van der Ploeg, Lancet, 2008 Muscle cell Muscle fiber Patient images courtesy of the patients/their families.
Pompe lentiviral gene therapy program advancing Integrated three-part approach GILT: Glycosylation-Independent Lysosomal Targeting Sources: Burton B et al, J Pediatr, 2017; Ausems M et al, Eur J Hum Genet, 1999; Gungor D et al, Orphanet J Rare Dis, 2011; Maga JA et al, J of Bio Chem, 2013; Bartelink, Lancet Haematol, 2016. THE CHALLENGE Pompe requires 20x more ERT than Fabry or Gaucher Requires GAA activity restored to muscle and CNS AVROBIO’s APPROACH Potent transgene promoter GILT uptake tag Bu90-TDM for CNS impact mg Glycogen / g wet tissue 2 4 6 8 10 12 Dose mg/kg 0 5 10 15 20 HEART GILT-rhGAA rhGAA mg Glycogen / g wet tissue 2 4 6 8 10 12 Dose mg/kg 0 5 10 15 20 DIAPHRAGM GILT-rhGAA rhGAA GILT-tagged Recombinant Human (rh)GAA impacts levels of stored glycogen compared to non GILT-tagged Recombinant Human (rh)GAA in a Pompe mouse model
Intravenous injection Lentiviral Vector Containing Gene of Interest Transduced Lin-hematopoietic stem cells HSC gene therapy in Pompe mice Enrichment of Lin- hematopoietic stem cells DONOR MOUSE Femur/Tibia RECIPIENT MOUSE Irradiation or Busulfan conditioning Isolation of bone marrow cells Transduction of hematopoietic stem cells Lin- cell 4 months follow-up Sources: Douillard-Guilloux G et al, J Gene Med, 2009; van Til et al, Blood, 2010; Stok M et al, Mol. Ther. Meth. Clin. Dev, 2020 in press.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. GAA GILT mutant v1 GILT mutant v2 GILT mutant v3 GILT + tag v1 GILT + tag v2 GILT mutant v4 GFP GILT mutant v1a GILT + tag v1a GILT + tag v2a GILT LTR LTR pr Transgene 2984 2985 2986 2987 2988 3007 2977R 2989 3005 3006 2983 Group number: 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy 7.5Gy Conditioning: 9Gy Busulfan Array of lentiviral vectors tested in vitro and in vivo
High GAA enzyme activity in vitro In vitro Intracellular Secreted HAP1 GAA KO
Urine Hex4: Week 16 Peripheral blood WBCs: Week 16 WT KO 2984 Bu NT NT Bu NS * * 7.5 9Gy * P<0.05 *** P<0.0001 2984 Bu *** * * High GAA enzyme activity and therapeutic response in vivo Therapeutically relevant urine Hex4 biomarker response in treated Pompe mice ** ** ** ***
Vector copy number (<5) optimized for clinical use KO Bu Bu WT GFP groups 2984 7.5 9 Gy Bone marrow cells GAA
GAA enzyme activity Wild type Glycogen KO Bu NT WT NT 2984 Bu 7.5 P<0.0001 9 Gy GAA 2983 2984 Diseased GILT and GILT mutant v1 reduce glycogen by >99% in heart GAA * P<0.01 ** P<0.001
Diaphragm Gastrocnemius ** P<0.01 *** P<0.001 GILT and GILT mutant v1 significantly reduce glycogen in clinically relevant skeletal muscles * ***
11% WT KO 2984 Bu NT NT Bu 7.5 9 Gy NS *** *** Glycogen and GILT and GILT mutant v1 similar to wildtype mice GILT tag is essential for glycogen clearance in CNS and PNS GAA enzyme activity: Cerebrum WT GAA KO 2984 2983 Cerebrum *** P<0.001 Spinal cord <1% GAA 2983 2985 2986 2987 2988 3007 3006 2989 Glycogen
Plasma samples KO Bu NT WT NT 2984 Bu 7.5 9 Gy Blood Glucose (mg/dL) R2 = 0.8409 P <0.0001 GAA Activity (nmols/mL/hr) GILT and GILT mutant v1 do not impact plasma glucose levels GAA protein concentration approximately 300-fold lower than ERT GAA Protein (µg/1.5 mL) GAA protein/mL mouse plasma
Conclusions Clinical development plan is underway 1 2 3 4 Glycogen was significantly cleared in clinically relevant tissues including heart, CNS and skeletal muscles of Pompe mice GILT tag is essential for efficient clearance of glycogen in CNS IND-enabling studies are advancing
Acknowledgements Preclinical Program Team Hannover Medical School Other Collaborators Yildirim Dogan Cecilia Barese Zeenath Unnisa Swaroopa Guda Rena Schindler John Yoon Abhishek Chiyyeadu Bianling Liu Mary Jacobs Claudia Fiorini Vicky Chen Daniel Ivanov Mark DeAndrade Robert Plasschaert Maurine Braun Christine Oborski Daniella Pizzurro Richard Pfeifer Claudia Harper Chris Mason Julie Kerner Betsy Bogard Diana Clarke Cristin O’Rourke Lisamarie Fahy Gabe Cohn Josie Yang Dani Sweeney Jose Gomez Ramesh Arjunji Alayna Tress Fernanda Copeland Mirjam Trame Leslie Jacobsen Manufacturing Robert Kutner Mike Kelly Axel Schambach National Institutes of Health (NIH) Nina Raben BioMarin Jon LeBowitz AVROBIO Pompe Team The research team gratefully acknowledges the contributions and support of the Canadian Pompe community.
AVROBIO Presents New Preclinical Data on Lentiviral Gene Therapy Program for
Pompe Disease at ASGCT 2020
AVROBIOs optimized lentiviral vectors demonstrate significant glycogen reduction in the muscle
and central nervous system of Pompe disease mouse model
Investigational New Drug (IND)-enabling proof-of-concept study for AVR-RD-03 for Pompe
disease currently underway
CAMBRIDGE, Mass., May 14, 2020 AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced new preclinical data for AVR-RD-03 for Pompe disease showcasing how its lentiviral gene therapy approach may potentially correct Pompe disease manifestations in the muscle and central nervous system (CNS). The data will be presented today at the American Society of Gene & Cell Therapy (ASGCT) 23rd Annual Meeting.
AVROBIOs optimized lentiviral vectors for Pompe disease include a proprietary Glycosylation-Independent Lysosomal Targeting (GILT)-tag technology, which consists of a short peptide sequence linked to the therapeutic protein and is designed to enhance uptake in key tissues, and a potent transgene promoter to boost protein production. Data to be presented today demonstrate that AVROBIO-designed lentiviral vectors for Pompe disease incorporating GILT-tag technology significantly reduce toxic accumulation of glycogen in a mouse model of Pompe disease, including in cardiac and skeletal muscle, and the CNS. The toxic buildup of glycogen is caused by a mutation in the GAA gene and leads to a broad range of symptoms for people with Pompe disease, including progressive weakness, loss of motor function and trouble breathing. GAA encodes acid alpha-glucosidase, the enzyme that is functionally deficient in people living with Pompe disease.
Our preclinical data strongly support the potential of our optimized lentiviral vector for Pompe disease with proprietary GILT-tag technology as a novel mechanism in the head-to-toe treatment of Pompe disease, including symptoms that originate in the CNS, said Chris Mason, M.D., Ph.D. AVROBIOs chief scientific officer. We feel a tremendous urgency to advance this therapy for people living with Pompe disease and look forward to completing the IND-enabling studies that could pave our path to the clinic.
The study assessed 10 different lentiviral vectors with therapeutic transgenes in a mouse model of Pompe disease. Each vector was capable of producing expression of the GAA gene and included different versions of the GILT tag. Control vectors without a GILT tag were also tested. The presence of GILT tags substantially improved clearance of glycogen in the brain and spinal cord. The leading vector reduced glycogen in the cardiac muscle, the cerebrum and the spinal cord to levels that closely resembled those seen in wild-type mice. Glycogen content was also significantly reduced in heart, diaphragm and skeletal muscle tissue. Average vector copy number (VCN) in bone marrow was below five and there were no adverse effects seen on the hematopoietic compartment in treated mice. The mice were followed for four months after transplantation.
Based on these data, AVROBIO selected a candidate vector for progression into an Investigational New Drug-enabling proof-of-concept study, which is expected to conclude in 2020.
About Pompe disease
Pompe disease is a lysosomal disorder caused by a mutation in the GAA gene. The lack of the enzyme encoded by GAA results in a toxic buildup of glycogen throughout the body and central nervous system, causing a wide range of symptoms including progressive weakness and loss of motor function. Pompe disease affects about 1 in 58,000 Americans and is treated with enzyme replacement therapy, or ERT, which is typically given as a biweekly infusion for life. ERT slows but does not halt the overall progression of disease and does not cross the blood-brain barrier to address neurological pathologies. Even with ERT treatment, people with Pompe disease experience debilitating symptoms that reduce their quality of life.
About lentiviral gene therapy
Lentiviral vectors are differentiated from other delivery mechanisms because of their large cargo capacity and their ability to integrate the therapeutic gene directly into the patients chromosomes. This integration is designed to maintain the therapeutic genes presence as the patients cells divide, which potentially enables dosing of pediatric patients, whose cells divide rapidly as they grow. Because the therapeutic gene is integrated using the vector into patients stem cells ex vivo, patients are not excluded from receiving the investigational therapy due to pre-existing antibodies to the viral vector.
Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale 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.
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, preclinical trial results and the potential therapeutic benefits of our optimized lentiviral vector with proprietary GILT-tag technology for the treatment of Pompe disease, including the potential for treatment of symptoms originating in the brain and CNS, the design, commencement and timing of ongoing or planned preclinical trials and regulatory pathways, including the timing of completion of our IND-enabling preclinical study for the treatment of Pompe disease, and the anticipated benefits of our lentiviral gene therapy approach. 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 AVROBIOs current expectations, estimates and projections about our industry as well as managements 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 AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned preclinical or 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 our GILT-tag technology and 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 AVROBIOs 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 AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs 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.
Christopher F. Brinzey
Westwicke, an ICR Company
Ten Bridge Communications