MB-105

P1, N=21, Recruiting, City of Hope Medical Center | Trial completion date: Jul 2028 --> Nov 2026 | Trial primary completion date: Aug 2027 --> Nov 2026

These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 .

P1, N=14, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Dec 2024

We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer.

P1, N=14, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Mar 2024

P1, N=21, Recruiting, City of Hope Medical Center | Trial completion date: Nov 2025 --> Jul 2028 | Trial primary completion date: Nov 2025 --> Aug 2027

P1, N=21, Recruiting, City of Hope Medical Center | Phase classification: P1b --> P1 | Trial completion date: Feb 2026 --> Nov 2025 | Trial primary completion date: Feb 2026 --> Nov 2025

P1b, N=21, Recruiting, City of Hope Medical Center | Initiation date: Jul 2023 --> Oct 2023

P1, N=15, Active, not recruiting, City of Hope Medical Center | Trial primary completion date: Nov 2023 --> Aug 2022

P1, N=15, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=30 --> 15

P1b, N=21, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Initiation date: Sep 2023 --> May 2023

12(86%) had previously been treated with chemotherapy; 9 received two taxanes and 3 docetaxel only...The protocol was amended to reduce the LD dose to 300 mg/m2 cyclophosphamide D1-3... PSCA-CAR T cells have anti-cancer activity in mCRPC with DLT of cystitis. LD was required for greater expansion and activity; lower dose LD improved toxicity without clear negative impact on expansion. Clinical trial information: NCT03873805.

P1b, N=21, Not yet recruiting, City of Hope Medical Center

Additionally, we are actively developing combinations of PSCA-CAR T-cells with secretable T-cell bispecific antibodies to target NEPC antigens. Our studies encompass the in vitro and in vivo safety and efficacy of CAR T-cells engineered to co-target PrAd and NEPC for the treatment of heterogeneous mCRPC.

P1, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

PSCA CAR_s15 NK cells showed therapeutic efficacy in human metastatic PC models without signs of systematic toxicity, providing a strong rationale to support clinical development.

The plan was to begin at a dose of 100 million (M) without lymphodepletion (LD) chemotherapy consisting of fludarabine and cyclophosphamide, then add LD to 100M prior to dose escalation to maximum 600M. PSCA-CAR T cell therapy is feasible in pts with mCRPC with DLT of cystitis, and shows preliminary anti-tumor effect at a dose of 100M plus LD. Dose escalation to 300M may proceed.

Results We observed significant hampering of PSCA-CAR T cell activity in vitro with the presence of M2 macrophages, but not M1 macrophages, coinciding with a robust induction of PD-L1 in both tumor cells and macrophages...Conclusions Recently, immune checkpoint (IC) blockade (ICB) has been utilized in combination with chimeric antigen receptor (CAR) T cell therapy, with the notion that induction of immune responses with CAR T cells may instigate checkpoint pathways in immunologically cold tumors that would otherwise not respond to ICB. This study gives insights to a mechanism by which CAR T cells and ICB work in synergy to modulate immune landscape of immunologically cold tumors, and our ongoing studies will continue to elucidate the TME-mediated immunosuppression of CAR T cell therapy.

P1, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2021 --> Dec 2022 | Trial primary completion date: Feb 2021 --> Dec 2022