BI-1 / Boehringer Ingelheim, Novartis - LARVOL DELTA

Therapeutic Antibodies Against Prion Diseases From PRNP Mutation Carriers (clinicaltrials.gov) - P=N/A | N=213 | Completed | Sponsor: University of Zurich | Unknown status ➔ Completed

Trial completion • CNS Disorders

Non-human primates in the PKPD evaluation of biologics: Needs and options to reduce, refine, and replace. A BioSafe White Paper. (PubMed, MAbs) - "As a result of this specificity, non-human primates (NHP) are often the only preclinical species in which therapeutic antibodies cross-react with the target...In the case of prediction of ocular PK, the body of evidence gathered over the last two decades renders the use of NHPs obsolete. Expert perspectives, advantages, and pitfalls with these alternative approaches are shared in this review."

Journal • Review

Multiscale modeling method for therapeutic antibodies in ion exchange chromatography. (PubMed, Biotechnol Bioeng) - "The consideration of two discrete conformational states of IgG4 mAbs enabled prediction of split-peak elution profiles. Starting from the sequence, the presented multiscale model allows in silico development of chromatography processes before protein material is available for experimental studies."

Journal

Distinct immune stimulatory effects of anti-human VISTA antibodies are determined by Fc-receptor interaction. (PubMed, Front Immunol) - "Importantly, for therapeutic antibodies, the isotype backbone can have a strong impact on antibody function...Similarly, in AML patient samples, anti-VISTA-antibody on IgG4-Pro backbone, but not on IgG1-KO backbone, increased interactions, as a novel readout of activity, between immune cells and CD34+ AML cancer cells. In conclusion, the immune stimulatory effects of antagonistic anti-VISTA antibodies are defined by the antibody isotype and interaction with different Fc-gamma-receptors, highlighting the importance of understanding these interactions when designing immune stimulatory antibody therapeutics for immuno-oncology applications."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Oncology • CD34 • VSIR

Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses. (PubMed, Oncoimmunology) - P1 | "Upregulation of inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3), may limit the antitumor activity of therapeutic antibodies targeting the programmed cell death protein-1 (PD-1) pathway. Overall, ezabenlimab and BI 754111 bound to their respective targets with high affinity and prevented ligand binding. Combining ezabenlimab with BI 754111 enhanced in vitro activity versus monotherapy, supporting clinical investigation of this combination (NCT03156114; NCT03433898)."

Journal • Oncology • HLA-DRB1 • IFNG • LAG3 • PD-L2

An adapted consensus protein design strategy for identifying globally optimal biotherapeutics. (PubMed, MAbs) - "In this first application to therapeutic antibodies, adapted Consensus Protein Design was found to be highly beneficial within lead optimization, conserving resources and minimizing iterations. Future implementations of this general strategy may help accelerate drug discovery and improve success rates in bringing novel biotherapeutics to market."

Journal

An optimally designed anti-human CD40 antibody with potent B cell suppression for the treatment of autoimmune diseases. (PubMed, Int J Pharm) - "Previously described therapeutic antibodies targeting this pathway have various shortcomings, and the full therapeutic potential of this axis has yet to be realized. This uniquely optimized antibody targeting a highly challenging pathway was obtained by applying stringent functional and biophysical criteria during the lead selection process. BI 655064 has favorable target-mediated drug disposition (TMDD)-saturation pharmacokinetics, consistent with that of a high-quality therapeutic monoclonal antibody."

Journal • Gastroenterology • Gastrointestinal Disorder • Glomerulonephritis • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Lupus • Lupus Nephritis • Nephrology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • CD40 • CD40LG

Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody (clinicaltrials.gov) - P=N/A; N=76; Completed; Sponsor: St. Jude Children's Research Hospital; Active, not recruiting ➔ Completed; Trial completion date: Oct 2020 ➔ Apr 2020

Clinical • Trial completion • Trial completion date • Melanoma • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] From sequence to process - in silico DSP development based on quantitative structure-property relationships (ACS-Fall 2020) - "Feature selection revealed which subdomains of the mAb contribute to the adsorption process. Our work demonstrates a bottom-up approach for building mechanistic chromatography models for therapeutic antibodies."

Stress Tolerance of Antibody-Poly(Amino Acid) Complexes for Improving the Stability of High Concentration Antibody Formulations. (PubMed) - "© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci."

Journal • Biosimilar

Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody (clinicaltrials.gov) - P=N/A; N=76; Active, not recruiting; Sponsor: St. Jude Children's Research Hospital; Trial completion date: Feb 2020 ➔ Oct 2020

Clinical • Trial completion date

From sequence to process: In silico DSP development based on quantitative structure-property relationships (ACS-Sp 2020) - "Feature selection revealed which subdomains of the mAb contribute to the adsorption process. Our work demonstrates a bottom-up approach for building mechanistic chromatography models for therapeutic antibodies."

Physical and chemical determinants of drug-like monoclonal antibodies (ACS-Sp 2020) - "Nevertheless, therapeutic antibodies display difficult-to-predict levels of non-specific (heterotypic) and self- (homotypic) interactions that lead to various drug development challenges, including antibody aggregation, abnormally high viscosity and fast antibody clearance...We have validated these predictions using independent sets of antibodies and mutants of antibodies with known specificity problems, and we are expanding our predictive methods using deep sequencing and machine learning. We expect that our findings can be readily used to improve the selection and engineering of antibodies with drug-like specificity."

Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody (clinicaltrials.gov) - P=N/A; N=76; Active, not recruiting; Sponsor: St. Jude Children's Research Hospital; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed