T Cell Engagers
Utilizing Azymetric™ to build differentiated and next generation T Cell Engagers
Differentiated 2+1 Bispecific T cell Engager Engineering
Harnessing our Azymetric™ technology to screen multiple bispecific 2+1 formats, geometries and paratope affinities for optimization of tumor selective T cell activation and antitumor activity with minimal cytokine release and on-target, off-tumor toxicities.
Differentiated Trispecific Engineering
Harnessing our Azymetric™ technology to screen multiple trispecific formats, geometries and paratope affinities for optimization of T cell activation and antitumor activity, we developed two novel approaches to engineering differentiated next generation Trispecific T Cell Engagers.
- Trispecific T Cell Engagers with costimulation (TriTCE Co-stim): Providing T cells with signal 1 and signal 2 for enhanced T cell activity and fitness for therapeutic applications in solid tumors
- Trispecific T Cell Engagers with Checkpoint Inhibition (TriTCE CPI): combining redirected T cell killing with immune checkpoint modulation to enhance activity and therapeutic applications for T cell engagers in solid tumors
How It Works
2+1 Bispecific T cell Engager Engineering
Our approach of differentiated next generation 2+1 bispecific T cell engagers includes:
- 2+1 Azymetric™ technology uses bivalent, avidity optimized tumor cell engagement and monovalent CD3 binding
- Novel anti-CD3 paratope with reduced T cell affinity to limit cytokine release syndrome
- Screening of multiple different 2+1 formats, geometries and paratope affinities allows for simultaneous optimization of:
- Tumor selectivity and reduced on-target off-tumor toxicities, and
- Enhanced T cell activation and tumor cell cytotoxicity while limiting cytokine release
- Improved therapeutic window by enhancing both safety and antitumor activity profiles
Trispecific Engineering
Our approach of differentiated next generation Trispecific T Cell Engagers with costimulation (TriTCE Co-stim) includes:
- Trispecifics that enhance T cell activation via Signal 1 (CD3) and signal 2 (CD28) in one molecule
- 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
- 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
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
How We Differ
We bring solutions to the biological problems faced by bispecific T Cell Engagers in the solid tumor microenvironment
Problem #1: Narrow therapeutic window and toxicities due to cytokine release syndrome and on-target off-tumor binding.
Our approach: To mitigate cytokine release and on-target off-tumor binding, we engineer different antibody formats that have low affinity T cell binding but leverage enhanced anti-tumor activity and tumor selectivity through avidity-driven tumor antigen binding.
Problem #2: Limited intratumoral T cell availability and T cell anergy in solid tumors
Our approach: We combine our antibodies with our TriTCE Co-stim technology to increase T cell fitness, survival, durability and proliferation via tumor-dependent T cell co-stimulation.
Problem #3: Immunosuppressive tumor microenvironment limiting T cell responses in solid tumors
Our approach: By customizing our antibodies with TriTCE CPI technology to increase T cell responses through simultaneous checkpoint blockade and avidity-driven binding we have an improved ability to navigate the tumor mircoenvironment.
