Janux Therapeutics has raised $56 million to fund development of T-cell engagers (TCEs). The series A will fund preclinical work on TROP-2 and PSMA candidates, positioning Janux to enter the clinic next year.
Driven by work at companies including Amgen, TCEs have emerged as a promising cancer modality. Yet, in the view of Janux CEO David Campbell, Ph.D., existing platforms suffer from shortcomings that limit the utility of TCEs.
“The development of TCEs has been hindered by poor pharmacokinetics, healthy tissue toxicity and cytokine release syndrome (CRS),” Campbell said. “Previous generation TCEs have not addressed all three of these hurdles in an integrated fashion.”
Campbell sees Janux’s TRACTr technology as a way to address those hurdles. The technology pairs tumor-specific activation with crossover pharmacokinetics to create more targeted, safe and potent TCEs.
“Tumor-specific activation is designed to limit the drug's activity to the tumor, and crossover pharmacokinetics ensures that any activated TCE that escapes the tumor will be rapidly cleared. The goal is to limit healthy tissue accumulation of the activated TCE and further reduce healthy tissue toxicities,” Campbell said.
The result is a pipeline of TCEs that Campbell expects to be suitable for once-weekly dosing and less likely to cause CRS. Janux has persuaded Merck—which signed up to work on two targets last year—and investors of the potential of the platform, positioning it to start validating its approach in the clinic.
Avalon Ventures led the $56 million series A. New investors OrbiMed and RA Capital Management provided assists, as did existing backers Bregua and Correlation Ventures. The syndicate has provided the money to get Janux into the clinic in the first half of next year.
Janux has two lead candidates that target TROP-2 and PSMA. Overexpression of TROP-2 in cancers and evidence that the transmembrane glycoprotein drives disease progression have attracted other researchers, including groups that have explored hitting it with TCEs. To date, TROP-2 antibody-drug conjugates developed by Immunomedics and Daiichi Sankyo have made the biggest impact.
PSMA, a prostate cancer target, is also the focus of development programs based on a wide range of modalities. Amgen posted phase 1 data on a PSMA-targeted TCE last year. The data drop revealed signs of efficacy in heavily pretreated prostate cancer patients, encouraging Amgen to forge ahead with development. However, the fact more than 90% of patients suffered CRS points to a way that Janux could differentiate its candidate, assuming the platform works as Campbell expects.
In preclinical tests, TRACTr TCEs have shown comparable efficacy to standard T-cell engagers without causing the same levels of cytokines release or toxicity to healthy tissues. With $56 million in the bank, Janux is now positioned to start learning whether that promise holds up in subsequent tests.