A Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia

Inclusion Criteria:

• Subject was previously enrolled in the BNTC-OPMD-NH-001 natural history (NH) studyand completed at least 6 months of follow-up in the NH study.

• Signed written informed consent prior to the initiation of any study-specificprocedures.

• Males or females, aged ≥50 to ≤65 years at the time of NH study enrollment, withgenetically diagnosed heterozygous OPMD disease (as indicated by 1 of the followingallelic classifications: GCN10/GCN12, GCN10/GCN13, GCN10/GCN14, GCN10/GCN15,GCN10/GCN16) OR

• Males or females, aged ≤65 years at the time of NH study enrollment, withgenetically diagnosed homozygous OPMD disease (as indicated by 1 of the followingallelic classifications: GCN12/GCN12, GCN13/GCN13, GCN14/GCN14, GCN15/GCN15,GCN16/GCN16).

• Subject is eligible and willing to undergo a surgical dissection of the pharyngealregion with intubation under general anesthesia to administer the study drug.

• Subject has moderate dysphagia, defined as pharyngeal area at maximum constriction (PhAMPC) >2.7%(C2-4)^2 with natural sips of thin liquid barium or PhAMPC >2.1%(C2-4)^2 with teaspoon delivery of moderately thick liquid barium.

• Subject is not of childbearing potential, i.e., is postmenopausal (absence ofmenstrual bleeding for ≥1 year before Baseline, without any other medical reason),or has documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomyOR

• Subject or their partner is of childbearing potential and agrees to use 2 highlyeffective forms of contraception during the study and continuing through 52 weeksafter the study drug administration. The 2 authorized forms of contraception arecondom used with 1 of the following methods of contraception:

• bilateral tubal ligation

• combined oral contraceptives (estrogens and progesterone), vaginal ring, orimplanted or injectable hormonal contraceptives with a stable dose for at least 1 month prior to the day of dosing; hormonal contraceptives must inhibitovulation

• intrauterine device inserted at least 1 month prior to the day of dosing OR

• Subject agrees to abstain from heterosexual intercourse during study participationand to use a highly effective form of contraception (as described above) as backupif they become sexually active during the study. Abstinence is only acceptable ifthis is the subject's usual lifestyle. Periodic abstinence (calendar, symptothermal,postovulation methods), withdrawal (coitus interruptus), spermicides only, andlactational amenorrhea method are not acceptable methods of contraception.

• Subjects capable of donating sperm must agree not to donate sperm beginning atScreening and continuing through 52 weeks after the study drug administration.

Exclusion Criteria:

• Subject has received prior treatment with an adeno-associated virus (AAV) vector (e.g., AAV-based therapy for the treatment of hemophilia B [including HEMGENIX®],AAV-based therapy for the treatment of RPE65 mutation-associated retinal dystrophy [including LUXTURNA®]).

• Subject with presence of anti-AAV9 antibody titers >1:50.

• Subject is pregnant or breastfeeding.

• In the investigator's opinion, the subject's pharyngeal muscle is not amenable tointramuscular (IM) injection due to clinically significant atrophy as assessed bymaximum pharyngeal dilation for OPMD subjects (determined by normalized post-swallowhyoid rest pharyngeal area [HRAN] using videofluoroscopy) compared to relative HRANmeasurements of pharyngeal dilation from a database comprising healthy controlsubjects as determined during the Screening Visit of the NH study.

• Subject with contraindication to the videofluoroscopy procedures (e.g., allergy toany of the radiopaque contrast agents planned for use in the study).

• Subject has received gene therapy (e.g., chimeric antigen receptor-positive T celltherapy for the treatment of leukemia, lymphoma, or multiple myeloma [includingABECMA®, BREYANZI®, CARVYKTI™, KYMRIAH®, YESCARTA®, and TECARTUS™], IMLYGIC® for thetreatment of melanoma, SKYSONA® for the treatment of cerebral adrenoleukodystrophy,and ZYNTEGLO® for the treatment of β-thalassemia) within the 6 months prior toScreening.

• Subject for whom any of the proposed study procedures or medications (e.g.,corticosteroids) would be contraindicated.

• Subject has had prior cricopharyngeal myotomy or cricopharyngeal botulinum toxininjection.

• Subject has had cricopharyngeal dilation within the 12 months prior to Screening.

• Subject with pre-existing clinically diagnosed and/or self-reported dysphagia hasbeen hospitalized within the 12 months prior to Screening for treatment of pneumoniaof nonpathogenic origin (e.g., aspiration pneumonitis secondary to aspiration ofsterile gastric contents) or pneumonia secondary to bacterial pathogens. A subjectis eligible for enrollment if diagnosed with pneumonia secondary to documentedpathogenic organism(s)including: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, i.e., coronavirus disease 2019), non-SARS-CoV-2-related viralpathogens, and fungal pathogens.

• Subject has been intubated within the 30 days prior to Screening.

• Subject consumes a very restricted range of diet textures, defined as a score of ≤3on the IDDSI Functional Diet Scale as determined during the Screening Visit of theNH study.

• Subject presents with muscular dystrophy and/or other neuromuscular diseasesdistinct from OPMD, or any other disease that may significantly interfere with thecharacterization of dysphagia in OPMD.

• Subject presents with other disorders associated with dysphagia, e.g., severegastroesophageal reflux, esophageal stricture due to mechanical or chemical trauma,infection (e.g., esophageal moniliasis), drug-induced dysphagia (e.g.,bisphosphonates), esophageal rings and webs, or spastic motility disorders of theesophagus.

• Subject with any concomitant illness likely to significantly decrease lifeexpectancy or any malignancy other than curatively treated skin cancer or in situcarcinoma of the cervix, unless adequately treated or in complete remission for ≥5years.

• Subject has received a diagnosis of head and neck cancer at any time.

• Subject has any history of neck irradiation.

• Subject has undergone a major surgical procedure to the mouth or neck. Subject iseligible for enrollment with a past medical history of routine dental procedures,tonsillectomy, or adenoidectomy.

• Subject has abnormal liver function (serum alanine aminotransferase or aspartateaminotransferase >2.5 × upper limit of normal).

• Subject is immunocompromised or is receiving immunosuppressant therapy.

• Subject has evidence of clinically significant hematological, renal, endocrine,pulmonary, gastrointestinal, cardiovascular, psychiatric, neurologic, or allergicdiseases (including drug allergies but excluding untreated, not clinicallysignificant, seasonal allergies).

• Subject has NCI CTCAE grade 3 hypertension defined as systolic blood pressureconsistently ≥160 mmHg or diastolic blood pressure consistently ≥100 mmHg.

• Subject has malnutrition defined as unintended weight loss of >5-10% during the 1 to 6 months prior to Screening and a body mass index (BMI) of <18.5 to 20 kg/m², orsubject has cachexia defined as weight loss of >5% over the past 6 months or a BMIof <20 kg/m² and ongoing weight loss of >2%.

• Subject has received treatment with an investigational drug, investigational device,or approved therapy for investigational use within the 3 months or 5 half-livesprior to Screening.

• Subject has any kind of disorder that, in the investigator's opinion, compromisesthe ability of the subject to give written informed consent and/or to comply withstudy procedures.

• Subject is unwilling or unable to comply with study procedures and scheduledfollow-up visits.

• Subject has any other medical or social condition that, in the investigator'sopinion, would not permit the subject to complete the study or sign informedconsent.