By providing T cells with a tumor recognition element, TCEs redirect a patient’s existing T Cells to kill tumor cells. T cells are the most potent killers of tumor cells within the immune system. As a result, TCEs are highly potent with efficacious doses >10,000 fold lower than a typical antibody.
However, TCEs have limitations, such as dose-limiting toxicities, poor pharmacokinetic profiles, and attenuated efficacy.
Janux’s proprietary Tumor Activated T Cell Engager (TRACTr) technology overcomes these limitations by integrating tumor-specific activation with crossover pharmacokinetics to produce best-in-class TCE therapeutics.
TRACTrs exhibit efficacy comparable to TCEs in established preclinical tumor models.
Tumor-specific activation of the TRACTr regresses established tumors in a mouse model that is equivalent to the parental TCE.
Janux’s TRACTr platform prevents risk of liver toxicity and cytokine release syndrome (CRS) typically reported in TCE-treated cynomolgus monkeys. Like humans, cynomolgus monkeys express high levels of the tumor target in multiple healthy tissues and organs representing a stringent test of TRACTr safety.
TRACTr inhibits cytokine release at >200-fold higher doses and >2,000-fold higher plasma levels than the TCE, well above projected human efficacious dose levels.
In cynomolgus monkey pharmacokinetic studies TRACTrs demonstrate significantly improved drug levels compared to a TCE. In the figure below the TRACTr maintains high drug levels for more than 2-weeks, while the TCE is cleared in a few hours.
TRACTr projects to once-weekly dosing in humans.
No activated TCE accumulation was identified at any time point through 2 weeks in cynomolgus studies at multiple dose levels. Based upon these studies, activated TCE levels are more than 100-fold lower than TRACTr.
High protein expression, straightforward purification, and improved stability compared to other TCE and bispecific formats.
- High transient expression levels in CHO cells (>100 mg/L)
- Single step purification using Protein A (>95% purity with <3% aggregates); IEX polishing step results in 99% purity
- Stable at 40°C >8 weeks