Zymeworks Inc.

Zymeworks Bc Inc.

Pfizer Corporation

Amgen Fremont Inc.

Grant Raymond Wickman

Vahe Bedian

Gordon Yiu Kon Ng

Nina E Weisser

Mario Sanches

Eric Escobar-Cabrera

Surjit Bhimarao Dixit

Sirid-Aimee Kellermann

Michael Aidan North

Xin Jiang

Dana Dan Hu-Lowe

Jianying Wang

Shelley Sims Belouski

Jingchuan Zhang

Karin Kristina Amundson

Shannon Marie Karlicek

Peter Wing Yiu Chan

James Arthur Thomson

Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

Bispecific antigen binding constructs targeting HER2

Described herein methods of using antigen-binding constructs to treat HER2+ tumors in a subject such as breast, lung, or head and neck tumors. In some aspects, the tumor volume in the subject after receiving at least seven doses of the antigen binding construct is less than the tumor volume of a control subject receiving an equivalent amount of trastuzumab. In some aspects, the survival of the subject receiving the antigen binding construct is increased as compared to a control subject receiving an equivalent amount of a non-specific control antibody or as compared to a control subject not receiving treatment.

Methods of using bispecific antigen-binding constructs targeting HER2

Bispecific antigen-binding constructs targeting HER2

Bispecific antigen-binding constructs targeting Her2

Provided herein are monovalent antigen-binding constructs targeting EGFR and/or HER2. The monovalent antigen-binding constructs can include at least one antigen-binding polypeptide comprising a heavy chain variable domain, wherein the antigen-bind polypeptide specifically binds EGFR and/or HER2; and a heterodimeric Fc domain, the Fc domain comprising at least two CH3 domains, wherein the Fc domain is coupled, with or without a linker, to the antigen-binding polypeptide. Also provided are methods of making the constructs and methods of using the constructs.

Monovalent antigen binding constructs targeting EGFR and/or HER2 and uses thereof

Described herein are isolated bi-specific antigen binding constructs, e.g., antibodies. The bi-specific antigen binding constructs include two antigen binding polypeptide constructs, e.g., a Fab and an scFv. The first antigen-binding polypeptide construct monovalently and specifically binds to extracellular domain 4 (ECD4) of HER2 (human epidermal growth factor receptor 2); the second antigen-binding polypeptide construct monovalently and specifically binds to an extracellular domain (ECD) of HER3 (human epidermal growth factor receptor 3). One antigen binding polypeptide construct is a Fab format and the other antigen binding polypeptide construct is an scFv format. The bi-specific antigen binding constructs includes an Fc having two Fc polypeptides each having a CH3 domain for dimerization. Each Fc polypeptide is linked to the C-terminus of one of the antigen binding polypeptide constructs with or without a linker.

Bispecific HER2 and HER3 antigen binding constructs

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Vancouver, Canada

Grant Raymond Wickman