MB-106

Following lymphodepletion (cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day for 3 days), MB-106 is administered to patients with indolent B-cell NHL at one of two dose levels (DL): DL1, 3.3×106; and DL2, 1.0×107 cells/kg. Treatment with MB-106, a third generation CD20 targeting CAR-T, resulted in responses, including CRs, and CAR-T persistence in patients with R/R indolent NHL and was associated with favorable safety profile with no occurrence of Grade 3 or Grade 4 cytokine release syndrome and no ICANS of any grade. CRs have been observed in patients previously treated with CD19-targeted CAR-T in both this multicenter trial and the original single institution trial. Dosing is ongoing in the final dosing level (1.0×107 cells/kg) to establish the recommended Phase 2 dose for a planned pivotal trial in WM.

Lymphodepletion (LD) consists of cyclophosphamide + fludarabine...All 4 pts had BTKi refractory disease (2 ibrutinib, 1 acalabrutinib, 1 zanubrutinib)...One pt received bridging therapy with bendamustine after leukapheresis and before CAR-T infusion (3 DL3 and 1 DL2)... Early results of CD20 CAR-T therapy with MB-106 for BTKi-refractory WM/LPL suggest high efficacy and favorablesafety profile with no grade 3/4 CRS and no grade 2/3/4 ICANS. MB-106 has received orphan drug designation by the US FDA for WM, and a multicenter study is currently active in the US for WM and other B-NHLs. Enrollment also continues in this single institution study, and the results will be updated during the presentation.

Treatment with MB-106, a 3rd-generation CD20 targeting CAR-T, resulted in high ORR and CR rates and CAR-T persistence in FL pts and was associated with a favorable safety profile with no occurrence of Gr 3 or Gr 4 CRS and no ICANS of any grade. A multicenter trial for treatment of B-cell malignancies including FL is ongoing in the US.

P1/2, N=50, Recruiting, Fred Hutchinson Cancer Center | N=35 --> 50

P1/2, N=287, Recruiting, Mustang Bio | Not yet recruiting --> Recruiting

Chimeric antigen receptor T-cells (CAR-T) targeting CD19 are effective, and axicabtagene ciloleucel is currently approved by FDA for treatment of patients (pts) with relapsed FL, but toxicities like cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may limit its use...Lymphodepletion (LD) consists of cyclophosphamide (Cy) ± fludarabine (Flu)...Median time between leukapheresis and LD was 15 days (range: 9-21) and 2 pts received bridging therapy with lenalidomide (1) and high-dose corticosteroids (1)...Conclusion Treatment with MB-106, a third generation CD20 targeting CAR-T, resulted in high ORR and CR rates and CAR-T persistence in FL pts and was associated with favorable safety profile with no occurrence of Gr 3 or Gr 4 CRS and no ICANS event of any grade. A multicenter trial for treatment of B-cell malignancies including FL will start enrollment in 2022.

P1/2, N=287, Not yet recruiting, Mustang Bio

Lymphodepletion (LD) consists of cyclophosphamide (Cy) ± fludarabine (Flu)...Only 1 pt required tocilizumab and dexamethasone...Treatment with MB-106 has also resulted in high ORR and CR rates with ongoing remissions in all patients who achieved a CR. Enrollment is currently ongoing and the data will be updated at the time of presentation.

Lymphodepletion (LD) consists of cyclophosphamide (Cy) ± fludarabine (Flu)... Early results of our ongoing study of CD20 CAR-T for high-risk NHLs suggests an extremely favorable safety profile (no CRS or ICANS of any grades) with the modified manufacturing process. There is also evidence of clinical activity even at low dose levels with observed CRs at DLs 1 and 2. Enrollment at higher DLs is currently ongoing and the data will be updated at the time of presentation.

Background: Chimeric antigen receptor T-cells (CAR-T) targeting CD19 have shown clinical efficacy in high-risk B-cell lymphomas, which has led to approval of 2 such therapies (axicabtagene ciloleucel and tisagenlecleucel) for large B-cell lymphoma after 2 lines of treatment... MB-106 is a fully human third-generation CD20 targeted CAR-T with both 4-1BB and CD28 costimulatory domains...Lymphodepletion (LD) chemotherapy consists of fludarabine and cyclophosphamide...Patients need to meet standard organ function criteria and have adequate blood counts (ANC >750, Hb >8.5, Plts >50,000). Patients with significant neurologic conditions, active CNS lymphoma, or need for systemic immunosuppressive therapy are excluded from the study.