CT-202 Program
CT-202: Nectin-4 x CD3 Bispecific Antibody
A novel therapeutic target
Nectin-4 is a predictive marker for cancer diagnosis and a validated therapeutic target. Nectin-4 expression has a significant correlation with tumor grade and stages associated to tumor progression. The next generation of anti-cancer therapies targeting Nectin-4 offer the potential to improve patient survival, while reducing harmful side effects.
Overcoming Nectin-4 expression in skin
Many therapies targeting Nectin-4 are being developed due to its ubiquitous expression in several types of cancers. These therapies, however, display a high rate of drug related toxicities due to binding in healthy skin tissue, accentuating the need for alternative approaches of anti-cancer therapeutics targeting Nectin-4.
CT-202 incorporates BioAtla’s Conditionally Active Biologic (CAB) technology that uses pH dependency to drive localized activity of CT-202 to the tumor microenvironment. CT-202 has little to no binding to CD3 or the target antigen in healthy tissue (normal alkaline microenvironment). However, in acid conditions that mirror the tumor microenvironment (high glycolysis), the binding of the antibodies to their target molecules is strong.
CT-202: Nectin-4 x CD3 clinical candidate
CT-202 is a Nectin-4 x CD3 bispecific antibody that incorporates twoNectin-4 binding arms and two CD3 binding single-chain Fv domains in an IgG format with a silenced Fc that is designed to be functionally monovalent to avoid aberrant T-cell activation and to enhance the safety profile. Because of its expression in healthy epidermal keratinocytes, sweat glands, and hair follicles, Nectin-4 targeted treatments are associated with dermatological side effects. CT-202 uses pH dependent binding to both Nectin-4 and CD3 to minimize binding to healthy tissues and maximize binding and T cell activation within the tumor microenvironment. Additionally, cooperative binding through the two Nectin-4 binding arms makes for high affinity and thermodynamically stable binding of CT-202 to tumor. Research has demonstrated that CT-202 is potent with specific lysis of Nectin-4-positive cancer cells over normal cells and can activate cytotoxic T cells without concomitant activation of free cytokines – critical determinants of immunotherapy safety and activity. Preclinical research suggests the potential for convenient dosing with low immunogenicity risk and manufacturing can be scalable to address the significant number of patients who are potentially eligible for CT-202 therapy.
Additionally, preclinical studies illustrate the potential of CT-202 to treat Nectin-4-positive tumors including:
CT-202 was shown to have high potency and target selectivity in both binding and cytotoxicity assays.
In in vivo xenograft experiments, CT-202 induced dose-proportional tumor regressions and was well tolerated.
CT-202 was well tolerated in an exploratory human primate toxicity study, with no clinical signs of toxicity.
Clones of competitor clinical-stage Nectin-4-targeted molecules were generated for benchmarking purposes. Compared to benchmark antibodies, CT-202 was equipotent in xenograft studies and exhibited 30-fold lower IL-6 induction compared to benchmark controls.