vixtimotamab (AMV564)

In addition to the anti-tumor effects of AMV564 on the clearance of MOLM13CG cells in vivo, similar effects were seen when primary CD33+ human AML cells were engrafted in NSG mice even when the human T cells made up only 2% of the peripheral blood cells and AML cells made up 98%. These studies suggest that AMV564 is a novel and effective bispecific diabody for the targeting of CD33+ AML that may provide long-term survival advantages in the clinic.

AMV564 was active in vivo in a leukemia xenograft model when co-administered with healthy donor PBMC. Our findings provide a strong rationale for clinical investigation of AMV564 as both a single agent or in combination with anti-PD1 antibody, and in particular, for the treatment of cancers resistant to checkpoint inhibitors.

Jain, et al; Blood 2019; 134 (Supplement_1): 2885. doi: https://doi.org/10.1182/blood-2019-131041

The cytokine profiles of patients treated with AMV564 as monotherapy or in combination with pembrolizumab were assessed using multiplex immunoassays, and the peripheral T cell repertoire was assessed by deep sequencing of the TCRβ locus. Repertoire expansion correlated with increases in effector memory CD8 T cells. These findings in patients treated with AMV564 support the role of MDSC in both limiting the priming and activation of anti-tumor T cells as well as contributing to an immune suppressive and pathologic cytokine response to T cell activation.

Furthermore, significant differences in potency across AML blasts were observed, which could be further impacted by the available T cells. While AMV564 has demonstrated anti-leukemic activity across an unselected relapsed/refractory AML population, this novel assay could be used to select patients in whom blasts are expressing CD33 in a predominantly clustered configuration, and thus identify patients most likely to experience deeper and more durable responses with AMV564 monotherapy.

Gemtuzumab ozogamicin was the first and only CD33-directed antibody-drug conjugate to be US Food and Drug Administration approved for AML...Promising new strategies include cellular therapy mechanisms and linker molecules. This is an exciting target that requires a considerable amount of precision to yield clinical benefit.

Inv. (2013) 123: 4595-4611

AMV564 is safe and tolerable when administered SC at doses of 15 mcg/d alone and 5 mcg/d in combination with pembrolizumab. AMV564 depleted MDSC populations and altered T cell profiles consistent with activation of cytotoxic T cells and a Th1 response. Research Funding: Amphivena Therapeutics

Fourteen patients (39%) had received at least 1 prior salvage regimen and 23 (64%) had received prior intensive chemotherapy, including 13 patients (36%) who had received a high-dose (≥ 1 g/m2) cytarabine-based regimen and 1 patient (3%) with prior allogeneic stem cell transplant. AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement.