vixtimotamab (AMV564) / Affimed - LARVOL DELTA

Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 x CD3 T cell engager. (PubMed, PLoS One) - "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."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CD4 • CD8

ReSTORE T cell engager platform depletes MDSC in parallel with antigen-specific solid tumor cytotoxicity (SITC 2021) - P1 | "The core function of this platform utilizes AMV564, a clinically active molecule that has been shown in a phase 1 study to selectively deplete myeloid-derived suppressor cells (MDSC) and produce clinical responses in cancer patients (NCT04128423).1 Increased levels of MDSC in cancer patients correlate with reduced overall survival, as MDSC suppressive factors impair T cell activation and anti-tumor immunity...Conclusions The clinically validated MDSC-depleting core of the ReSTORE platform molecules allow targeting of specific antigens associated with a variety of solid and hematologic tumor indications. This antigen-specific cytotoxicity of cancer cells occurs in parallel with control of the immunosuppressive MDSC."

Myeloid-derived suppressor cells • Hematological Malignancies • Oncology • Solid Tumor • CD33

[VIRTUAL] AMV564, a clinically active T cell engager, induces a target-dependent adaptive immune response (SITC 2020) - P1 | "Conclusions AMV564 is a potent conditional T cell agonist which is clinically active. We demonstrate that the combination of T cell activation, increased T cell diversity, and target specificity allow AMV564 to deplete MDSCs and restore a native immune response to cancer."

Clinical • Oncology • Ovarian Cancer • Solid Tumor • CD33 • CD8

[VIRTUAL] AMV564, a clinically active T cell engager, induces a target-dependent adaptive immune response (SITC 2020) - P1 | "Conclusions AMV564 is a potent conditional T cell agonist which is clinically active. We demonstrate that the combination of T cell activation, increased T cell diversity, and target specificity allow AMV564 to deplete MDSCs and restore a native immune response to cancer."

Clinical • Oncology • Ovarian Cancer • Solid Tumor • CD33 • CD8

[VIRTUAL] Single-agent anti-tumor activity in relapsed/refractory solid tumors: interim data from the Phase 1 solid tumor trial of AMV564, a novel T-cell engager (SITC 2020) - P1 | "Conclusions AMV564 has been well tolerated across multiple dose levels, with good plasma exposure and evidence of anti-tumor activity when administered subcutaneously. Single-agent anti-tumor activity was observed in an ovarian cancer patient."

P1 data • Acute Myelogenous Leukemia • Endometrial Cancer • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CD33

AMV564, a Bivalent Bispecific (2×2) CD33/CD3 T-Cell Engager, Is Active and Improves Survival in a Mouse Model of Acute Myeloid Leukemia (ASH 2018) - P1; "AMV564 very effectively prolonged survival and dramatically reduced tumor in the bone marrow and peripheral blood. These results are consistent with our previous preclinical data with primary AML and support the testing of this reagent in patients with relapsed and refractory AML in the clinic."

Acute Myelogenous Leukemia • Biosimilar • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Immunodepletion of MDSC By AMV564, a Novel Tetravalent Bispecific CD33/CD3 T Cell Engager Restores Immune Homeostasis in MDS in Vitro (ASH 2017) - P1; "Our findings demonstrate that AMV564 treatment selectively depletes MDSCs to reactivate T lymphocytes by improving both quantity and quality of immune responses leading to the improvement of hematopoiesis. These preclinical data provide a strong rationale for clinical investigation of this innovative approach in patients with MDS."

Bispecific • Checkpoint inhibition • Myeloid-derived suppressor cells • Acute Myelogenous Leukemia • Biosimilar • Inflammation • Myelodysplastic Syndrome

[VIRTUAL] A phase I study to evaluate the T-cell engager AMV564 alone and in combination with pembrolizumab in subjects with advanced solid tumors. (ASCO 2020) - P1 | "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"

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • CD8

Repolarization of T cells by AMV564 in patients progressing on checkpoint blockade (SITC 2021) - P1 | "Extremely elevated levels of regulatory T cells were often observed: after treatment with AMV564, a Th-1-like repolarization of these cells was apparent, often associated with reduction in CD25 (figure 3). Conclusions Treatment with AMV564 yielded substantial reductions in MDSC and favorable polarization of CD8 and CD4 T cells, including Th1-like polarization of Treg. This signature was apparent in patients previously treated with checkpoint inhibitors, despite strong induction of MDSC in response to T cell activation, and high baseline levels (>20%) of Treg. Trial Registration NCT04128423"

Checkpoint inhibition • Clinical • Oncology • CD4 • CD8 • IFNG • IL2RA • IL6 • TMB

Immunodepletion of MDSC by AMV564, a Novel Bivalent Bispecific CD33/CD3 T-Cell Engager ex vivo in MDS and melanoma. (PubMed, Mol Ther) - P1 | "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."

Journal • Myeloid-derived suppressor cells • Preclinical • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Melanoma • Oncology • Solid Tumor • CD33 • PD-L1

AMV564 Depletes Myeloid-Derived Suppressor Cells and Expands T Cells: Potential to Address Key Limitations of Cellular Therapies (ASH 2021) - "Jain, et al; Blood 2019; 134 (Supplement_1): 2885. doi: https://doi.org/10.1182/blood-2019-131041"

Myeloid-derived suppressor cells • Acute Myelogenous Leukemia • Hematological Malignancies • Inflammation • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD8 • GZMB • IL6

Study of AMV564 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=65; Active, not recruiting; Sponsor: Amphivena Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; N=116 ➔ 65; Trial completion date: Sep 2022 ➔ Dec 2021; Trial primary completion date: Sep 2021 ➔ Dec 2021

Clinical • Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Study of AMV564 in Patients With AML (clinicaltrials.gov) - P1; N=53; Completed; Sponsor: Amphivena Therapeutics, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Nov 2020

Clinical • Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase 1 Study of AMV564 in Patients With Intermediate or High-Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1; N=14; Completed; Sponsor: Amphivena Therapeutics, Inc.; Active, not recruiting ➔ Completed; N=80 ➔ 14

Clinical • Enrollment change • Trial completion • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A phase 1 dose escalation with expansion study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AMV564 in subjects with advanced solid tumors (SITC 2019) - "N/A"

Clinical • P1 data • PK/PD data

PHASE 1 FIRST-IN-HUMAN TRIAL OF AMV564, A BIVALENT BISPECIFIC (2×2) CD33/CD3 T-CELL ENGAGER, IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (AML) (EHA 2018) - P1; "AMV564 is well-tolerated and can be administered without the need for incremental dosing and/or pre-medication. AMV564 has a unique PK profile compared to monovalent T-cell engagers, demonstrating a gradual increase in drug concentration and thus the potential for controlled T-cell activation. In a limited number of patients at the lowest dose levels, AMV564 demonstrated anti-leukemic activity."

Clinical • IO Biomarker • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

[VIRTUAL] Single-agent anti-tumor activity in relapsed/refractory solid tumors: interim data from the Phase 1 solid tumor trial of AMV564, a novel T-cell engager (SITC 2020) - P1 | "Conclusions AMV564 has been well tolerated across multiple dose levels, with good plasma exposure and evidence of anti-tumor activity when administered subcutaneously. Single-agent anti-tumor activity was observed in an ovarian cancer patient."

P1 data • Acute Myelogenous Leukemia • Endometrial Cancer • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CD33

Phase 1 First-in-Human Trial of AMV564, a Bivalent Bispecific (2x2) CD33/CD3 T-Cell Engager, in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) (ASH 2018) - P1; "...Fifteen patients (79%) had received at least 1 prior salvage regimen and 11 (58%) had received prior intensive chemotherapy, including 6 patients (32%) who had received a high-dose (≥ 1 gm/m2) cytarabine-based regimen...Grade 2 CRS was observed in 1 patient (treated at 50 mcg/day) without a lead-in dose and was managed with drug interruption and 1 dose of tocilizumab...Conclusion s: AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement. AMV564 has a unique PK profile with a gradual increase in drug concentration and thus the potential for controlled T-cell activation."

Clinical • P1 data • Acute Myelogenous Leukemia • Biosimilar • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology

Phase 1 First-in-Human Trial of AMV564, a Bivalent Bispecific (2:2) CD33/CD3 T-Cell Engager, in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) (ASH 2019) - P1; "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."

Clinical • IO Biomarker • P1 data • CD38 • CXCL8 • IFNG • IL10 • IL2 • IL2RA • IL4 • IL6 • TP53

[VIRTUAL] Results of a phase 1 dose-escalation study of AMV564, a novel T-cell engager, alone and in combination with pembrolizumab in patients with relapsed/refractory solid tumors. (ASCO 2021) - P1 | "AMV564 was well tolerated across multiple dose levels as monotherapy and in combination with pembrolizumab . Subcutaneous injection resulted in clinically relevant plasma exposures . Single-agent and combination therapy anti-tumor activity was observed ."

Clinical • Combination therapy • P1 data • Anemia • Fatigue • Hematological Disorders • Hypotension • Inflammation • Oncology • Ovarian Cancer • Pruritus • Solid Tumor • CD33

A Phase I study of AMV564 in patients with intermediate or high-risk myelodysplastic syndromes. (ASCO 2019) - P1; "Patients will receive up to 4 cycles of AMV564 treatment at the assigned dose level. Clinical trial information: NCT03516591"

Clinical • P1 data

SAFETY AND CLINICAL ACTIVITY OF AMV564, A CD33/CD3 T-CELL ENGAGER, IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (AML): UPDATED RESULTS FROM THE PHASE 1 FIRST-IN-HUMAN TRIAL (EHA 2019) - P1; "Nineteen patients (63%) had received at least 1 prior salvage regimen and 18 (60%) had received prior intensive chemotherapy, including 9 patients (30%) who had received a high-dose (≥ 1 g/m2) cytarabine-based regimen. Marked increases in serum IL6, IL8, and IL10 were observed with evidence of T-cell activation in both blood and bone marrow.Conclusion AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement using a 14-day administration schedule. AMV564 has a unique PK profile with a gradual increase in drug concentrations and thus the potential for better controlled T-cell activation. "

Clinical • IO Biomarker • P1 data

Amphivena Presents New Monotherapy and First Combination Therapy Clinical Data in Solid Tumor Patients (Businesswire) - P1, N=116; NCT04128423; Sponsor: Amphivena Therapeutics, Inc; "Investigational Drug Candidate AMV564 Demonstrates Safety with Evidence of Anti-tumor T cell Expansion and One Complete Response, Multiple Mixed Responses and Durable Disease Stabilization in Solid Tumor Patients. No Cytokine Release Syndrome (CRS) reported in patients treated with subcutaneously administered AMV564 alone and in combination with Pembrolizumab at doses selected for expansion cohorts. Monotherapy dose escalation demonstrates safety and efficacy of subcutaneously (sc) administered AMV564, including a RECIST complete response (CR). AMV564 shown to deplete immunosuppressive MDSC, significantly activate effector CD8+ cells and Th1 T cells, and promote expansion of anti-tumor T cells."

Cytokine release syndrome • P1 data • Oncology • Solid Tumor

[VIRTUAL] MDSC suppress the T cell repertoire and contribute to a pathologic cytokine milieu in cancer patients (AACR 2021) - "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."

Clinical • Myeloid-derived suppressor cells • Oncology • Solid Tumor • CD33 • CD4 • CD8 • IFNG • IL1B • IL6 • TNFA

"ICYMI $AFMD T-cell engager AMV564 highlighted via Amphivena ahead of IPO #AACR21" (@dhovekamp42)

Oncology