Publications & Presentations

This presentation focuses on the exploration of virus filter process performance at different positions in the downstream process, finding new virus filters that enable the filtration of higher concentrated samples and placement further downstream in the purification process. The successful flexibility of the filters’ position demonstrated an effective removal of viruses irrespective of low or high flux viral clearance. 

Abstract 3129: BYON4413, an in vivo active CD123-targeting antibody-drug conjugate, combines effectively with azacitidine and venetoclax in acute myeloid leukemia cell lines | Cancer Research | American Association for Cancer Research (aacrjournals.org)

BYON3521 is a proprietary novel c-MET targeting antibody-drug conjugate (ADC) with a cleavable linker-duocarmycin (vc-seco-DUBA) payload that causes irreversible alkylation of DNA in tumor cells. BYON3521 has demonstrated potent and selective killing of c-MET expressing tumor cells in preclinical models, even at low c-MET expression levels. In addition, in vitro studies showed that the active toxin can passively permeate the cell membrane and kill neighboring, c-MET negative cells as a bystander effect. In the ongoing FiH trial, to date, the c-MET-directed ADC BYON3521 is well-tolerated with no DLTs at the investigated dose levels. Patient enrollment is ongoing.

In preclinical models, the CD47-SIRPα axis has been firmly established as an immune checkpoint that inhibits myeloid-derived antibody dependent cellular cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP) mediated by tumor-targeting antibodies, thereby limiting the efficacy of these antibodies. We have generated and characterized preclinically the antagonistic SIRPα-targeting mAb BYON4228 and performed head-to-head comparison studies with three mAbs, that in all probability represent three clinical stage SIRPα-targeting mAbs. These studies focused on: 1) recognition and functionality of both common allelic forms of SIRPα (SIRPαBIT and SIRPα1); 2) recognition and blocking of SIRPγ on T lymphocytes which is reported to affect T cell extravasation and activation; 3) functionality of the antibody Fc-region which can mediate depletion of SIRPα-positive host myeloid immune effector cells thereby compromising a host defense and undermining the effect of immunotherapy.

The efficacy of biopharmaceuticals, such as monoclonal antibody-drug conjugates (ADC), is strongly dependent on maintaining structural integrity throughout industrial process manufacturing, and this is traditionally monitored using spectroscopic techniques. Such methods monitor important aspects of protein structure but offer limited resolution regarding the exact sites of structural change. At the same time, mass spectrometry (MS)-based methods are gaining ground in the pharmaceutical industry because they allow peptides indicative of structural integrity to be detected with shotgun or bottom-up proteomics workflows in a single chromatographic run, and thus localize structural changes with increased accuracy. In this work, we set out to evaluate the complementarity of limited proteolysis-MS (LiP) and hydrogen-deuterium exchange-MS(HDX) for the analysis of protein higher-order structure (HOS) in a biopharmaceutical setup.