Gene Transfer Study in Patients With Late Onset Pompe Disease

Inclusion Criteria:

• Participant is aged ≥ 18 years.

• Participant has a documented clinical diagnosis of Pompe disease by genetic testing.

• Participant has received enzyme replacement therapy (ERT) with rhGAA for theprevious ≥ 2 years.

• Participant has been on a stable standard dose (at least 20 mg/kg every 2 weeks) ofERT with rhGAA for at least the previous 6 months.

• Participant or legally authorized representative(s) (LAR) (if applicable) provideswritten informed consent.

• Participant and LAR(s) are willing and able to comply with study visits and studyprocedures.

• Participant must agree to refrain from blood or blood products donation and sperm oregg donation from the time of AT845 administration until the later of 90 days or 3consecutive negative viral shedding samples

• Participants enrolled in previous protocol versions 1 through 9: Participant hasupright FVC ≥ 30% of predicted normal value. Participants enrolled starting withprotocol version 10 and subsequent amendments: Participant has upright FVC ≥ 30% and ≤ 85% of predicted normal value.

• Participants enrolled starting with protocol version 10 and subsequent amendments:Participant who is able to ambulate ≥ 40 m without stopping and without the use ofan assistive device. The use of an assistive device for community ambulation isacceptable. (Participants enrolled under previous protocol versions 1 through 9 willnot be excluded if they do not meet this criterion during Rescreening visit).

Exclusion Criteria:

• Participant is currently participating in an interventional study or has receivedgene or cell therapy.

• Participant tests positive for AAV8 antibodies with titers >1:20 neutralizing.

• Participant has received immune-modulating agents within 90 days before dosing (useof inhaled corticosteroids is allowed); use of other concomitant medications tomanage chronic conditions must have been stable for at least 30 days before dosing.Concomitant medications that may predispose the participant to peripheral neuropathywill be evaluated.

• Participant has any clinically significant laboratory values (other than thosedirectly associated with LOPD [e.g., GAA, serum creatine kinase (CK)]) that wouldpreclude participation in the study.

• Participant has serological or viral load evidence of HIV-1 or HIV-2.

• Participant has received drugs for treatment of myopathy or neuropathy withimmunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus,methotrexate, cyclophosphamide, IV immunoglobulin, rituximab) within 3 months priorto starting the study

• Participant has a high risk for a severe allergic reaction to rhGAA (ie, previousmoderate to severe anaphylactic reaction to alglucosidase alfa or and/or a historyof sustained high immunoglobulin G [IgG] antibody titers to alglucosidase alfa thatsuggests a high risk for an allergic reaction to ERT).

• Participant has a history of hypersensitivity to β2 agonist drugs such as albuterol,levalbuterol, bitolterol, pirbuterol, terbutaline, salmeterol, which contraindicatespulmonary function testing.

• Participant has an active viral infection based on clinical observation.

• Participant has a history of or concurrent medical condition other than Pompedisease that could jeopardize safety of the participant or impact study results.

• Participant has a history of, or currently has, a clinically important cardiaccondition, such as an echocardiogram (ECHO) with ejection fraction below 40% or hassymptoms or signs of cardiomyopathy that precludes enrollment.

• Participant has a contraindication to study drug or to corticosteroids, or hasdemonstrated hypersensitivity to any of the components of the study drug.

• Participant tests positive for GAA antibodies with titers > 1:50,000 total

• Participant has a history of hypersensitivity to MRI contrast agents includinggadolinium.

• Participant has a known hypersensitivity to local anesthetics such as lidocaine.

• Participant has a bleeding diathesis, e.g., due to anti-coagulation or anti-platelettreatments.

• Participant has a concurrent medical condition (including uncontrolled diabetes,alcohol use disorder, certain autoimmune conditions, Lyme disease, active malignancyrequiring chemotherapy and/or radiation, uremic nephropathy, known exposure to heavymetals) commonly associated with peripheral neuropathy. Other concurrent medicalconditions that may predispose to peripheral neuropathy will be evaluated and actiontaken on a case-by-case basis, following discussion between the Investigator andMedical Monitor.

• Participant who is unwilling to withdraw from ERT.

• Participant has an active symptomatic large fiber peripheral neuropathy diagnosed bya neurologist at a screening visit.

• Age-related sensory changes on NCS without symptoms or mononeuropathy (refers tofocal involvement of a single nerve, usually due to a local cause such as trauma,compression or entrapment) will not be excluded.

• Participant has clinically significant underlying liver disease at Screening, or hasany of the following:

• Alanine Aminotransferase (ALT) > 2 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) > 2 × ULN

• Total bilirubin > 1.5 × ULN

• Alkaline phosphatase (ALP) > 2 × ULN

• ALT and AST are often higher than the normal range in Pompe disease patients.Participants whose liver laboratory tests fall outside the above ranges may beretested and, if the eligibility criteria are met on retesting, may be enrolledafter confirmation by the Medical Monitor.

• In addition, participants with abnormal laboratory results related to confirmedbenign liver conditions including Gilbert's syndrome (defined by asymptomaticunconjugated hyperbilirubinemia [17 to 70 µmol/L or 1 to 4 mg/dL]) and asymptomaticgallstones, will be considered eligible for the study notwithstanding their abnormallaboratory results and may be enrolled.

• Participant is currently on antiviral therapy for hepatitis B or C, orchronic/active hepatitis B or active hepatitis C evidenced by hepatitis B surfaceantigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV)-DNApositivity or hepatitis C virus (HCV)-RNA viral load positivity, respectively.

• Negative viral load assays in 2 samples, collected at least 6 months apart, will berequired to be considered negative. Both natural clearers and those who have clearedHCV on antiviral therapy are eligible. Participant has an active viral infectionbased on clinical observation.