Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)

VNX-101 is an investigational adeno-associated virus (AAV) gene therapy developed to

express a secreted anti-CD19/anti-CD3 scFv diabody (termed GP101). GP101 binds both

cluster of differentiation (CD)19 and CD3, inducing T-cells to kill both benign and

malignant B-cells. Following a single intravenous (IV) infusion, the vector induces the

liver and key tissues to continuously secrete GP101 into the bloodstream, resulting in

long-term, consistent serum levels of GP101. Potential advantages of VNX-101 over

autologous CAR-T therapy include it is off-the-shelf, provides a gentle onset of action,

does not require lymphodepletion chemotherapy, engages all T-cells continuously

(including those freshly produced from the bone marrow), and utilizes highly efficient

signaling through the native T-cell receptor.

In this 2-part study, dose-finding data from Part 1 of the study (n=~12 patients) will be

used determine the dose for Part 2 in patients. Part 1 is a dose-finding PK study in

adults ≥18 years old designed to determine the minimal dose that achieves target PK serum

levels of GP101 at steady state (8-week timepoint) without dose-limited toxicities,

defined as the recommended Part 2 dose (RP2D). Prior to VNX-101 dosing, subjects may

undergo standard of care chemotherapy to meet dosing criteria. Part 2 (n=~20) will be

opened following data safety monitoring board review of Part 1 data and is designed to

determine the safety and pharmacokinetics (PK) of VNX-101 at the RP2D in a broader array

of subjects. The age range for Part 2 will be expanded to include subjects ≥13 years old.

Patients will be followed for safety and efficacy up to 5 years post VNX-101 dosing.

Long-term follow-up assessments for safety will be conducted for 6 to 15 years post

VNX-101 dosing.