ZYMEWORKS BC INC.

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.

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

Bis-intercalating peptide compounds having Formula I, which are capable of binding DNA and exerting a cytotoxic effect on cells, such as microbial, viral or tumour cells, and conjugates comprising the compounds linked to a targeting moiety, such as an antibody. The compounds and conjugates may be used in the treatment of cancer or a microbial or viral infection, or as diagnostic agents or labelling agents.

Disclosed herein are isolated multi-specific heteromultimer constructs that bind to CD3 expressed on T-cells and to an antigen expressed on B-cells. The multi-specific heteromultimer constructs are capable of bridging T- and B-cells and mediating killing of B-cells. The multi-specific heteromultimer constructs are based on a heterodimeric Fc scaffold or on a segmented albumin scaffold. Also disclosed herein are multi-specific heteromultimer constructs that bind to HER2 and HER3.

The present disclosure describes multivalent (e.g., decavalent or dodecavalent) polypeptide constructs capable of binding to one or more viral spike protein(s) and capable of intercepting the interaction of a spike protein of a viral particle with a surface-bound ACE2 protein of a cell, pharmaceutical compositions comprising such constructs, and methods of producing and using the constructs for the treatment of, e.g., viral infections in a subject in need thereof.

The present disclosure relates to multivalent, e.g., trivalent, and bispecific antibody constructs capable of binding an antigen on a cytotoxic effector cell and a tumor-associated antigen (TAA) on a tumor cell. Pharmaceutical compositions comprising such antibody constructs and methods of preparing and using such constructs and compositions, e.g., for the treatment of cancer, are also disclosed.

Heterodimeric IgA Fc (IgA HetFc) constructs comprising one or more amino acid mutations in the CH3 domain that allow for formation of a heterodimeric Fc having high purity and thermostability. The IgA HetFc constructs may comprise one or more target binding domains. Higher order IgA HetFc multimers comprising multiple IgA HetFc constructs may be prepared in which two of the IgA HetFc constructs are joined by a J chain.

Heterodimeric Fc variants comprising one or more asymmetric amino acid mutations in the CH2 domain and having increased selectivity of binding to FcγRIIb as compared to a parental Fc region, polypeptides comprising the heterodimeric Fc variants and polynucleotides encoding the heterodimeric Fc variants. The one or more asymmetric mutations comprise replacement of a loop in the CH2 domain, a mutation at position 236 in the CH2 domain, or a combination of replacement of a loop in the CH2 domain and a mutation at position 236 in the CH2 domain.

Described herein is a method of treating breast cancer comprising administering a bispecific antigen-binding construct targeting HER2 or a bispecific antigen-binding construct targeting HER2 linked to an auristatin analogue (ADC) in combination with a CDK4/6 inhibitor to a subject.

Provided are heterodimer pairs comprising a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain. At least one of the heterodimers comprises amino acid modifications in the C H1 and/or C L domains, amino acid modifications in the V H and/or V L domains or a combination thereof. The modified amino acid residues are part of the interface between the light chain and heavy chain and are modified in order to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a mammalian cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer preferentially pairs with the second light chain rather than first.