BYON4228 / Byondis - LARVOL DELTA

First-in-Human Dose-Escalation and -Expansion Trial with Sirpα Antibody BYON4228 in R/R B-Cell NHL (ASH 2023) - P1 | "Phase 1 clinical trial design: BYON4228.001 (NCT05737628) is the first-in-human clinical trial of BYON4228, in combination with rituximab, in relapsed or refractory (R/R) B-cell Non-Hodgkin's lymphoma (NHL). Tumor response is determined according to Lugano and LYRIC criteria. An extensive biomarker program in the peripheral blood and bone marrow is included in the trial."

First-in-human • IO biomarker • P1 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD20 • SIRPA

A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: Byondis B.V. | Not yet recruiting ➔ Recruiting

Enrollment open • Solid Tumor

Byondis Announces First Patient Dosed in Phase 1 Clinical Trial of Novel SIRPα-Directed Monoclonal Antibody BYON4228 in Patients With Advanced or Metastatic Solid Tumors (Businesswire) - "Byondis B.V...announces the first patient dosed in its Phase 1 dose escalation and expansion BYON4228.002 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of novel SIRPα-directed monoclonal antibody (mAb) BYON4228 alone and in combination with pembrolizumab in patients with advanced or metastatic solid tumors....Part 1 of the BYON4228.002 trial will evaluate the safety of BYON4228 alone and in combination to determine the maximum tolerated dose (MTD), or optimal biological dose (OBD) if the MTD is not reached, and recommended combination dose regimen(s) for expansion (RDE(s))."

Trial status • Solid Tumor

A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=85 | Not yet recruiting | Sponsor: Byondis B.V.

New P1 trial • Solid Tumor

BYON4228.001: First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Byondis B.V. | Trial primary completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Byondis B.V.

Trial initiation date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Byondis B.V. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells. (PubMed, J Immunother Cancer) - "Collectively, this defines BYON4228 as a preclinically highly differentiating pan-allelic SIRPα antibody without T-cell SIRPγ recognition that promotes the destruction of antibody-opsonized cancer cells. Clinical studies are planned to start in 2023."

Journal • Tumor cell • Hematological Disorders • Immune Modulation • Oncology • Solid Tumor • CD47 • SIRPA

BYON4228, an antagonistic SIRPα mAb with a unique and favorable preclinical profile compared to three comparator SIRPα mAbs (AACR 2023) - "Functional studies demonstrate that BYON4228 potentiates both macrophage- and neutrophil-mediated elimination of hematologic and solid cancer cells in vitro in the presence of a variety of tumor targeting antibodies, including rituximab, daratumumab, trastuzumab and cetuximab. Finally, with its impaired Fc-region BYON4228 does not deplete SIRPα+ myeloid cells, in contrast to SIRPAB-11.Thus, BYON4228 differentiates from all three comparator SIRPα mAbs based on at least one fundamental characteristic, thereby underlining its potential to become a best-in-class drug. We therefore endorse its further development for which clinical studies are planned to start in 2023."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD47 • SIRPA

Preclinical Characterization of Anti-SIRPα mAb BYON4228 Published in Journal for ImmunoTherapy of Cancer (PRNewswire) - "Byondis...announced that the Journal for ImmunoTherapy of Cancer (the official journal of the Society for Immunotherapy of Cancer) has published encouraging preclinical data on its investigational monoclonal antibody (mAb) BYON4228....The therapy is scheduled to enter First-in-Human (Phase I) study later this year. The Phase I clinical study (NCT05737628) is designed to evaluate BYON4228 alone and in combination with rituximab in patients with relapsed/refractory CD20-positive B-cell non-Hodgkin's lymphoma....According to the published data, BYON4228 potentiates macrophage- and neutrophil-mediated killing of both hematologic and solid cancer cells in vitro in the presence of a variety of tumor-targeting antibodies... In vivo, BYON4228 promotes the anti-tumor activity of such antibodies."

Preclinical • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Byondis Plans First-in-human Dose Escalation/Expansion Study With the SIRPα-directed BYON4228 (Onco'Zine) - "The Netherlands-based Byondis has planned a first-in-human study with BYON4228, a humanized monoclonal antibody directed against the immune checkpoint signal regulatory protein α (SIRPα). the study is expected to start later this year."

New P1 trial • Hematological Malignancies • Lymphoma • Oncology

First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Byondis B.V.

Combination therapy • New P1 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

BYON4228, a pan-allelic SIRPα blocking antibody with a favorable pre-clinical safety profile, enhances anti-tumor immunity in vitro and in vivo (SITC 2022) - "Functional studies show that BYON4228 potentiates both macrophage- and neutrophil-mediated elimination of hematologic and solid cancer cells in vitro in the presence of several different tumor targeting antibodies like trastuzumab, rituximab, daratumumab and cetuximab, illustrating the broad potential clinical benefit and application of BYON4228. Clinical studies are planned to start in 2022. Ethics Approval Appropriate ethics approvals were present before commencing studies in vivo."

Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD47 • SIRPA

OSE Immunotherapeutics Announces Corporate Update and H1 2022 Results (Businesswire) - "A newly formed SAB combining the expertise of renowned scientific and international key-opinion leaders in the fields of immunology, immuno-oncology, inflammation and immunotherapy...The SAB includes...Dr. Jennifer Wargo...."

BYON4228 is a pan-allelic SIRPα antibody that potentiates killing of antibody-opsonized tumor cells and lacks binding to T cells (AACR 2022) - "Functional studies show that BYON4228 potentiates both macrophage- and neutrophil-mediated elimination of hematologic and solid cancer cells in vitro in the presence of several different tumor targeting antibodies like trastuzumab, rituximab, daratumumab and cetuximab, illustrating the broad potential clinical benefit and application of BYON4228. Collectively, this defines BYON4228 as a pan-allelic anti-SIRPα antibody without T cell SIRPγ recognition that promotes the destruction of antibody-opsonized cancer cells. Clinical studies are planned to start in 2022."

Oncology • Solid Tumor • CD47 • SIRPA

BYON4228 is a pan-allelic SIRP_ antibody that potentiates killing of antibody-opsonized tumor cells and lacks binding to T cells. (ESMO-IO 2021) - "Functional studies show that BYON4228 potentiates both macrophage- and neutrophil-mediated elimination of hematologic and solid cancer cells in vitro in the presence of several different tumor targeting antibodies like trastuzumab, rituximab, daratumumab and cetuximab, illustrating the broad potential clinical benefit and application of BYON4228. Legal entity responsible for the study The authors. Funding Byondis BV."

Oncology • Solid Tumor • CD47 • SIRPA