ZYMEWORKS BC INC.

Antibody-drug conjugates (ADCs) comprising an antibody construct that specifically binds c-Met conjugated to one or more drugs, such as the auristatin analogue, compound 1, via a linker. Also described are anti-cMet antibody constructs that have been engineered to include one or more cysteine insertion mutations with each inserted cysteine residue providing a conjugation “handle” allowing for conjugation of a drug-linker to provide an ADC. Further described are multivalent drug-linkers comprising a plurality of the auristatin analogues suitable for use in the ADCs described herein.

The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the C H1 and/or C L domains, one or more amino acid modifications in the V H and/or V L domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified 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 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 typically preferentially pairs with the second light chain rather than first.

The provided scaffolds have heavy chains that are asymmetric in the various domains (e.g. ch2 and ch3) to accomplish selectivity between the various fc receptors involved in modulating effector function, beyond those achievable with a natural homodimeric (symmetric) fc molecule, and increased stability and purity of the resulting variant fc heterodimers. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.

Disclosed herein are compounds having Formula I, or a pharmaceutically acceptable salt thereof, wherein R, R 1 , R 2 , R 3 , and Spacer are described herein. Also disclosed are methods of making and using such compounds, as well as pharmaceutical compositions comprising the compounds, for the treatment of a disease such as cancer.

Purine-derived compounds of Formulae (I)-(IV), immunostimulatory antibody conjugates (ISACs) comprising such compounds, as well as methods for producing and using such compounds, e.g., for the treatment of diseases such as cancer, are disclosed.

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.

The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the C H1 and/or C L domains, one or more amino acid modifications in the V H and/or V L domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified 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 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 typically preferentially pairs with the second light chain rather than first.

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.

Methods of treating subjects having a HER2-expressing cancer with an anti-HER2 biparatopic antibody using a 2-tiered fixed dosing regimen based on the weight of subjects being treated are described. Combination therapy with chemotherapeutic agents and/or a PD-1 inhibitor, for example an anti-PD-1 antibody, are also described.

The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the C H1 and/or C L domains, one or more amino acid modifications in the V H and/or V L domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified 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 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 typically preferentially pairs with the second light chain rather than first.