First Patient Dosed in JANX014 Trial in Metastatic CRPC

The first patient has been dosed in a phase 1 trial evaluating JANX014, a double-masked, prostate-specific membrane antigen (PSMA)–directed T-cell engager (TCE) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to Janux Therapeutics.¹ The first-in-human, open-label, multicenter study will assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.

“We are pleased to have initiated clinical evaluation of JANX014,” said David Campbell, PhD, president and chief executive officer of Janux Therapeutics, in a news release. He noted that the company’s lead prostate program, JANX007, has helped establish a clinical foundation for PSMA-directed TRACTr (Tumor Activated T Cell Engager) therapies, with insights from JANX007 and JANX008 informing ongoing platform development. The company is advancing a broader prostate cancer portfolio across disease stages, including both monotherapy and combination strategies.

Early clinical data with JANX007 demonstrated a favorable safety profile, with no grade 3 cytokine release syndrome (CRS) observed at clinically relevant dose levels using current mitigation strategies. These findings have informed the development approach for subsequent prostate cancer candidates.

“Janux’s tumor-activated technology allows us to evaluate multiple molecular designs against the same validated target,” said William Go, MD, PhD, chief medical officer. “As we advance JANX007, we are also developing complementary approaches, including JANX013, a CD28 co-stimulatory PSMA-TRACTr program, and exploratory candidates such as JANX014. This work is intended to clarify how different mechanisms and masking strategies may translate into clinical benefit across patient populations.”

JANX014 represents an exploratory extension of this strategy, based on research initiated in early 2024 evaluating multiple PSMA-directed approaches. The trial may also help define settings where improved safety profiles and more convenient administration are priorities in mCRPC treatment.

JANX011 and the ARM Platform

Separately, the first patient has also been dosed in a phase 1 trial (NCT07291323) of JANX011, a CD19-targeted bispecific candidate. The study will evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics, and represents the first clinical program from the company’s adaptive immune response (ARM) platform.²

The ARM platform is designed to achieve sustained B-cell depletion by eliciting an adaptive-like immune response while improving the safety and convenience of immune-engaging therapies. Unlike conventional T-cell engagers, which often require repeated dosing, ARM molecules promote controlled T-cell expansion in the presence of target cells, followed by contraction once those cells are eliminated. This approach is intended to enable deep tissue-level clearance without the need for lymphodepletion or preconditioning.

In preclinical studies, a single subcutaneous dose of JANX011 produced deep and durable B-cell depletion in both blood and tissue compartments, along with a prolonged memory B-cell reset. Across a greater than 100-fold dose range, cytokine levels remained low, suggesting a potentially wide therapeutic window and reduced risk of CRS while maintaining target cell depletion.

REFERENCES

1. Janux Therapeutics Announces First Participant Dosed in Phase 1 Study of JANX014. April 16, 2026. Accessed April 20, 2026. https://tinyurl.com/2sx6z5pz

2. Janux Therapeutics Announces First Patient Dosed in Phase 1 Study of JANX011. February 17, 2026. Accessed April 20, 2026. https://tinyurl.com/3zy4pjpw