P1, N=67, Recruiting, Novelty Nobility, Inc. | Not yet recruiting --> Recruiting

P1, N=67, Not yet recruiting, Novelty Nobility, Inc.

Importantly, the exposure of AML marrow specimens to bispecific aptamer-MMAF conjugates resulted in the selective elimination of primary AML cells in vitro and had no effect on healthy lymphocytes within the same specimens. Thus, these results provide a proof of concept for the generation of bispecific aptamer-drug conjugates directed against human AML cells, which hold the promise of advancing treatment strategies and improving AML patient outcomes.

In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer.

To investigate the activity of CD117-ADC in non-human primates, we administered a single injection of ADC without HSC infusion, resulting in a >99% depletion of CD34+CD90+ bone marrow cells in cynomolgus macaques (n=2 of 3 in 0.1 mg/kg and n=3 in 0.3 mg/kg); similar to the ablation observed with 4 doses of myeloablative busulfan (Bu) (n=3). The transplanted animals with ADC maintained their fertility. Overall, these data indicate that an ADC-based targeted approach offers safer conditioning and could improve the risk-benefit profile in HSC gene therapy.

Objective: To reduce acute and long-term treatment-related toxicities, we have developed a first of its kind treatment intended to improve the safety of allo-HSCT through: 1) a TBI- and busulfan-free conditioning regimen consisting of briquilimab, rabbit ATG (rATG - Thymoglobulin), fludarabine, cyclophosphamide and rituximab - briquilimab (formerly called JSP191) is a monoclonal antibody (mAb) that targets human CD117 to deplete host HSCs enabling blood and immune reconstitution with minimal toxicity with the other agents being used for transient immune suppression to prevent immunologic rejection; 2) transplantation of TCRαβ+ T-cell/CD19+ B-cell hematopoietic grafts - a stem cell therapy that enhances donor hematopoietic and immune reconstitution while decreasing GvHD; and 3) a pre- and post-transplant monitoring protocol to maximize engraftment. All three patients in the Phase 1b portion of the study show early safety and efficacy of this approach. Briquilimab was well tolerated and all patients have shown prompt and durable donor engraftment. This data indicates that it might be possible to remove irradiation or alkylator chemotherapy from the conditioning regimen in patients with FA without matched sibling donors thus decreasing the chances for cancer predisposition in these patients that have inherited DNA repair defects.

P1/2, N=22, Terminated, Magenta Therapeutics, Inc. | N=55 --> 22 | Trial completion date: Oct 2023 --> Feb 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Feb 2023; Sponsor Decision

Acute leukemia in Yemen was equally prevalent between adults and children with slightly more prevalent among males. Flow cytometry, even with a 3-colour strategy, is able to give useful diagnostic information about cell lineage of acute leukaemias. This has proven beneficial for patient management.

MGTA-117 has been well tolerated with no unexpected safety concerns. It has shown proof-of-mechanism (robust receptor binding, selective target cell depletion) and rapid clearance with in vivo stability. Further dose escalation continues, and progress is being made toward development of MGTA-117 to enable HSCT in AML/MDS and gene therapy indications.

MGTA-117 has been well tolerated with no unexpected safety concerns. Preliminary data show in vivo stability of the ADC with rapid clearance from blood, robust binding of MGTA-117 on CD117+ cells, and early evidence of single-agent biological activity. The observed PK/PD profile in humans is highly consistent with predictions based on data from studies in preclinical species.