Our science
Clinical landscape
Immune checkpoint inhibitors, cell therapies, and ADCs are treatment options available for solid tumors, but each of these modalities brings its own challenges. In an adaptive immune response, T-cell activation is initiated when the T-cell receptor (CD3) is engaged. This immune response is then sustained by the engagement of co-stimulatory receptors like CD28 and CD137. Activation of T-cells through CD3 is often referred to as Signal 1 and co-stimulation as Signal 2. CD3 T-cell engagers, delivering Signal 1 alone, show efficacy as monotherapies in liquid tumors. However, treating solid tumors requires Signals 1 and 2 to overcome the immunosuppressive microenvironment.
Targeted Modalities
Efficacy
Safety
Challenge
Checkpoint Inhibitors
30% response rate,
heme & Solid
Autoimmune & inflammatory toxicity
Low Response Rate
CAR-T Cell Therapy
80% Response Rate,
Heme only
CRS & On-target, off-tumor Toxicity
Limited Patient Access
ADCs
30-40% Response Rate, Heme & Solid
Toxicity related to payload toxin
Sub-Optimal Efficacy at Low Tumor antigen Densities, Dose limiting Toxicities
CD3 T-Cell Engagers
60-80% Response Rate,
Heme only
CRS & on-target, off-tumor toxicity
low Response Rate
in Solid tumors
Swipe to Explore
T-cells in immune-primed tumors
have activated signal 1
Strategy - Boost signal 2 with
CD28 bispecific antibody (+/- SoC)
T-cells in immune-cold tumors
lack signals 1 & 2
Strategy - Deliver both signals 1 and 2 with
CD28 and CD3 bispecific combinations
Our approach
T-cell engagers harness the immune system to combat cancer by targeting tumor associated antigens (TAAs) on cancer cells then recruiting and activating T-cells to unleash potent anti-tumor responses.
While CD3 T-cell engagers are effective treatments for blood cancers, solid tumors present additional obstacles due to the immune-suppressive tumor microenvironment.
Enter CD28, a key co-stimulatory receptor essential for robust and sustained T-cell-mediated tumor clearance. First-generation, super-agonist monoclonal antibodies targeting CD28 stimulated systemic T-cell activation leading to severe dose-limiting toxicities in the clinic.
Stimulating CD28 with tumor-targeted bispecific antibodies delivers a boost of signal 2 boost to T-cells at the site of the tumor while avoiding super-agonist activity.
CD28 has many features of an ideal co-stimulatory target for bispecific therapies because CD28 is constitutively expressed on active and resting T-cells and requires lower tumor antigen density for robust bispecific-induced tumor clearance.
Our Strategic advantage
Maintaining efficacy while reducing toxicity is Rondo Therapeutics’ strategy, providing clinicians flexibility with dosing strategies and combination regimens.
Immune-cell engaging mechanism of action
Sustained T-cell mediated tumor cell killing
Maximum therapeutic window
Development
NGS-based discovery enables rapid characterization and development of highly-diverse binding arm collections which are critical for high-throughput lead optimization.
Using a common-light chain format enables flexible pairing of immune effector and tumor targeting arms.
Our proprietary high-throughput functional and biophysical assays optimize for desired properties and rapidly identify the best bispecific antibody development candidates.
