Janux’s JANX011 T-Cell Engager Shows Deep B-Cell Depletion in Phase 1 Healthy Volunteer Study

Janux Therapeutics’ JANX011, a CD19-targeted bispecific T-cell engager designed for autoimmune disease, produced deep B-cell depletion after a single subcutaneous dose in a phase 1 study in healthy volunteers, with cytokine release syndrome (CRS) limited to Grade 1.¹ At the highest dose tested, 3 mg, three of five participants had greater than 90% depletion of peripheral B cells, including two whose B-cell counts fell below the limit of detection, and reductions persisted through Day 42.¹ The company plans to begin patient studies in immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) in 2027.¹

“This marks an important step forward for Janux,” said David Campbell, PhD, president and chief executive officer of Janux.¹

How is JANX011 different from other T-cell engagers?

JANX011 is the first clinical candidate from Janux’s Adaptive Immune Response Modulator (ARM) platform.² Conventional T-cell engagers activate T cells by binding CD3, a component of the T-cell receptor complex found on nearly all T cells. JANX011 instead engages T cells through TRBV6, a conserved variable domain of the T-cell receptor beta chain.¹ The ARM platform is designed to selectively recruit a defined subset of T cells, with the goal of driving deep, sustained depletion of target cells while limiting broad T-cell activation.¹ In the study, TRBV6-expressing T cells made up about 10% of circulating T cells.¹

Janux has said ARM molecules are designed to drive controlled T-cell expansion while target cells are present, followed by contraction once those cells are eliminated, supporting tissue-level B-cell clearance without lymphodepletion or preconditioning.² In preclinical studies, a single subcutaneous dose produced deep, durable B-cell depletion in blood and tissue.²

Why target B cells in autoimmune disease?

Depleting CD19-expressing B cells to “reset” the immune system has become a major strategy in autoimmune disease, first with CAR-T cell therapies and more recently with T-cell engagers. In a 2024 study in Nature Medicine, investigators treated six patients with multidrug-resistant RA with blinatumomab, an approved CD19×CD3 T-cell engager, under compassionate use.³ Low doses depleted B cells, and treatment was described as safe, with transient increases in body temperature and acute-phase proteins during the first infusion and no clinically relevant CRS.³

Several companies are now developing T-cell engagers specifically for autoimmunity. BioPharm International® has reported on Novartis licensing Abogen’s mRNA-encoded CD19×CD3 T-cell engager ABO2203 and on Oblenio Bio dosing the first patients with its BCMA×CD19×CD3 trispecific LBL-051.

The move into autoimmunity represents a significant expansion for the modality. In a BioPharm International Q&A, Johanna K. Kaufmann, PhD, chief scientific officer of Deck Bio, said that “T cell engagers have so far been restricted to niche indications,” pointing to the challenges of finding suitable targets in solid tumors.

What did the phase 1 study show?

The study enrolled 25 healthy volunteers across five single-ascending-dose cohorts ranging from 30 µg to 3 mg, all given subcutaneously without step-up dosing.¹ B-cell depletion was dose dependent at 1 mg and 3 mg.¹

No CRS occurred at doses from 30 µg to 300 µg among 16 participants.¹ Grade 1 CRS occurred in one of four participants at 1 mg and four of five participants at 3 mg, and all events resolved with acetaminophen.¹ Increases in the cytokines IL-6, TNFα, IFNγ, and IL-2 were limited.¹ There were no serious adverse events or dose-limiting toxicities.¹ At 3 mg, one participant had a transient, asymptomatic Grade 3 elevation in the liver enzyme ALT, and Grade 2 ALT and AST elevations were also observed; none required treatment.¹

Because the trial enrolled healthy volunteers, it was designed to assess safety, pharmacokinetics, and pharmacodynamics rather than clinical efficacy, with early data intended to guide dose selection and the choice of autoimmune indications.²

What happens next?

Janux plans to begin a study in patients with ITP in the first half of 2027 and a study in patients with RA in the second half of 2027.¹ “The results give us a strong foundation to advance JANX011 in autoimmune disease,” Campbell said.¹

Janux is also developing T-cell engager programs in oncology, including its lead candidate JANX007, a PSMA-targeted TRACTr in a phase 1 trial in metastatic castration-resistant prostate cancer.¹

References

1. Janux Therapeutics announces positive initial Phase 1 data for JANX011 in healthy volunteers, supporting planned development in patients with autoimmune disease. News release. Janux Therapeutics; November 9, 2026. Accessed November 9, 2026.
2. Janux Therapeutics announces first patient dosed in Phase 1 study of JANX011. News release. Janux Therapeutics; February 17, 2026. Accessed November 9, 2026.
3. Bucci L, Hagen M, Rothe T, et al. Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat Med. 2024;30(6):1593-1601. doi:10.1038/s41591-024-02964-1