Antibody Technology Platforms

Engineering fit-for-purpose biotherapeutics

Our technologies leverage Zymeworks’ industry leading expertise in the fields of protein engineering and drug chemistry to discover the next generation of antibody-based therapeutics to combat unmet medical need in hard-to-treat cancers and other serious diseases.

The integration of complementary and antibody-based technologies, embedded in our proprietary multispecific and antibody-drug conjugate (ADC) therapeutic modalities, interfaced with disease biology, enables the development of differentiated and fit-for-purpose therapeutics.

Multispecific Antibody Therapeutics Technology

Zymeworks is an industry leader in multispecific antibody research and the use of this technology in developing therapeutics targeting areas of high unmet medical need.

Our clinically validated technologies harness the flexibility of our proprietary Azymetric™ platform as a foundation to solve biological challenges

The foundation to how we build and design unique multi-functional and multispecific antibodies.

Azymetric™ is a heterodimeric antibody technology that gives us the ability to engineer, screen, and effectively choose the optimal geometry and valency for our targeted treatments. These customized therapeutic antibodies are engineered to simultaneously bind to multiple distinct locations on a target or to multiple targets, resulting in unique mechanisms of action not accessible through typical monospecific antibodies.

Azymetric™ antibodies can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering and internalization, and increase tumor-specific targeting. Our other technologies can all combine with Azymetric™ to engineer the antibody backbone of a bispecific antibody-drug conjugate or the base of a multispecific therapeutic, to overcome known therapeutic barriers resulting in best-in-class bi-specifics and trispecifics.

The core of the Azymetric™ therapeutic platform consists of proprietary amino acid modifications in the heavy and light chains of an IgG-like antibody that enable the transformation of monospecific (single target) antibodies into multispecific antibodies that have alternative target binding formats (e.g. Fabs, scFvs, and VHHs). Engineering the optimal geometry allows for the antibody to simultaneously bind to multiple distinct locations on one or more targets.

Azymetric™ antibodies can be customized to enhance therapeutic activity through our proprietary complementary technologies. This foundational antibody is compatible with glyco-engineering, other Fc fusions and modifications, including our EFECT™ technology, as well as with our T cell engager (TCE) technology, including 2+1 TCE, TriTCE Co-stim and TriTCE checkpoint technology (TriTCE CPI), as well as antibody-drug conjugate technologies.

The Azymetric platform is a differentiated antibody platform that allows for precise control over geometry and valency, essential features for engineering next generation biologics with superior selectivity and function. Clinical validation of this platform has come through zanidatamab, the first regulatory approved therapy using the Azymetric platform, the Phase 3 advancement of a KLK2 targeting T cell engager, pasritamig, through license to J&J, and the advancement of other azymetric molecules with other industry leading pharmaceutical companies.

Customize and optimize the immune response to any antibody

Effector Function Enhancement and Control Technology (EFECT™) allows our scientists to modify an area of the antibody to trigger our immune system to respond in a beneficial way.

The EFECT™ library includes proprietary mutations to the CH2 domain of the antibody’s Fc region to selectively modulate an antibody’s interactions with the Fc-gamma receptors (FcγR) expressed on the surface of immune cells and with a component of the complement pathway (i.e. C1q).

How It Works

Reiterative computer modelling of the Fc domain and functional validation identified a suite of proprietary point mutations that when introduced into the Fc domain can selectively modify its binding profile to either activating or inhibitory Fcγ receptors to enhance or negate binding and subsequent biological responses. As biological challenge dictates, these mutations can be incorporated into antibodies, multispecifics or drug conjugate-based therapeutics.

Harnessing our Azymetric™ technology to screen multiple trispecific formats, geometries and paratope affinities for optimization of T cell activation and antitumor activity, we developed novel platform approache to engineering differentiated next generation Trispecific T Cell Engagers with integrated costimulation.

Providing T cells with signal 1 and signal 2 for enhanced T cell activity and fitness for therapeutic applications in difficult to treat tumors.

Our approach of differentiated next generation Trispecific T Cell Engagers with costimulation (TriTCE Co-stim) includes:

  • Azymetric™ advantage paired with optimized CD3 and CD28 paratopes affinities allows screening of multiple trispecific formats to select those with enhanced antitumor activity and safety
  • Trispecifics that enhance T cell activation via coordinated Signal 1 (CD3) and signal 2 (CD28) engagement in one molecule
  • Conditional CD28 engagement, requiring CD3 binding, and obligate cis T cell binding to enhance safety and antitumor activity
  • Tumor-dependent T cell activation, no T cell activity in the absence of target antigen to enhance safety
  • Increased tumor-dependent T cell fitness, activation, and proliferation leading to enhanced antitumor activity compared to bispecific antibodies

TriTCE Co-stim is a plug and play platform that is transferable to diverse targeting strategies including 2+1+1, pMHC target or logic-gated approaches (Verstrate et al. SITC 2025).

Harnessing our Azymetric™ technology to screen multiple trispecific formats, geometries and paratope affinities for optimization of T cell activation and antitumor activity, we developed novel approaches to engineering differentiated next generation Trispecific T Cell Engagers.

Combining redirected T cell killing with immune checkpoint modulation to enhance activity and therapeutic applications for T cell engagers in solid tumors

Our approach of differentiated next generation Trispecific T Cell Engagers with Checkpoint Inhibition (TriTCE CPI) includes:

  • Azymetric™ advantage paired with optimized PD-1 domain affinities allows screening of multiple trispecific formats to optimize dual MOA of CPI and avidity
  • Enhanced activity of trispecific driven by:
    • Avidity-driven binding to tumor and T cells
    • Dual MOA combining redirected T cell cytotoxicity combined with PD-1/PD-L1 checkpoint blockade at the immunological synapse
  • Dual MOA has potential for enhanced activity of trispecific compared to bispecific and combination therapy

 

Antibody–Drug Conjugate Technology

We are dedicated to the development of best in class or first in class ADC therapeutics that will make a real difference for people impacted by difficult to treat cancers and other diseases.

Our unique approach to the design and development of ADCs paired with our toolbox of protein engineering technologies and proprietary payloads provides us with the flexibility to precisely engineer and develop highly differentiated ADC therapeutics.

Explore our technologies

Our camptothecin payload is specifically designed for antibody-drug conjugate (ADC) use and is paired with established linker and conjugation technologies that provide a good balance of stability, safety, and anti-tumor activity (Petersen et al. Molecular Cancer Therapies).

Zymeworks Topoisomerase 1 inhibitor technology uses a novel fit-for-purpose camptothecin payload with moderate potency and strong bystander activity in conjunction with a traceless, plasma-stable, cleavable peptide linker. The properties of the drug-linker enable conjugation at a drug to antibody ratio up to 8. Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the topoisomerase inhibitor payload ZD06519.

ZymeLink™ Auristatin

ZymeLink™ Auristatin, is an auristatin-based drug-linker that employs an N-acylsulfonamide spacer to link the cytotoxic auristatin core to a protease sensitive linker and was designed to be highly stable and hydrophilic to closely resemble natural antibodies to possess favorable pharmacokinetics and drug exposure. Auristatins are clinically validated antibody-drug conjugate (ADC) payloads that elicit cell death by binding to microtubules and inhibiting their assembly.

ZymeLink™ Auristatin uses traceless cleavable dipeptide linkers with limited hydrophobicity and the option for either cysteine or lysine conjugation. Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the potent microtubule inhibitor ZD02044.

ZymeLink™ Hemiasterlin

ZymeLink™ Hemiasterlin payload employs an N-acylsulfonamide spacer to enable linker cleavage, is specifically designed for antibody-drug conjugate (ADC) application, and is compatible with both cysteine and lysine conjugation. The limited hydrophobicity of Zymelink Hemiasterlin drug linkers provides ADCs with improved pharmacokinetics, stability, and cytotoxin exposure over alternative ADC technologies. Hemiasterlins elicit cell death by binding to microtubules and inhibiting their assembly.

ZymeLink™ Hemiasterlin uses traceless cleavable dipeptide linkers for antibody conjugation and is sufficiently hydrophilic to enable a DAR up to 8. Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the potent bystander active microtubule inhibitor ZD01886.

Site-Specific Conjugation

We used a structure guided approach to find IgG1 conjugation sites that impact the properties of antibody-drug conjugates (ADCs) in different ways. Having a large panel of engineered conjugation sites enables us to tailor ADC properties to our needs, depending on the payload, antibody, target, indication and intended mode of action.

We have identified different sites that are amenable to cysteine insertion without perturbation of IgG structure and function. The inserted cysteine residues can be selectively conjugated with any thiol-reactive drug-linker using a simple chemical process to generate homogeneous ADCs. The desired drug to antibody ratio determines the number of cysteine insertions that are simultaneously employed. Specific insertions can be used to reduce FcgR binding.

Partner with us

Partnership is in Zymeworks’ corporate DNA. Our first FDA-approved therapeutic is in partnership with Jazz Pharmaceuticals and Beigene. And we are actively paired with a number of other entities.

Learn More