Janux Therapeutics, Inc. announced positive updated clinical data for both of its clinical programs. Janux will host a virtual event February 26, 2024 at 4:30 PM ET. Updated interim clinical data for PSMA-TRACTr JANX007 in mCRPC as of February 12, 2024. JANX007 is in a Phase 1a clinical trial in subjects with advanced or metastatic prostate cancer (mCRPC).

The subjects enrolled in the trial were heavily pre-treated with a median of 4+ lines of therapy. As of February 12, 2024, 23 subjects were treated with JANX007 in the dose escalation portion of the Phase 1a clinical trial. An increasing depth of PSA declines and RECIST responses at higher doses were observed, while a favorable safety profile was maintained.

At a starting dose = 0.1 mg, 14 of 18 (78%) subjects achieved PSA30 declines and 10 of 18 (56%) subjects achieved PSA50 declines. At a starting step dose of = 0.2 mg, 6 of 6 (100%) subjects achieved PSA30 declines and 5 of 6 (83%) subjects achieved PSA50 declines. Initial step doses of JANX007 = 0.2 mg drove deeper and more durable PSA responses, including one subject that achieved a PSA90 decline.

Cytokine Release Syndrome (CRS) was observed to be temporary and mild, presenting only as low-grade 1 or 2 events, and was quickly managed with treatment. These incidents of CRS were mainly reported during the first treatment cycle, with no subsequent occurrences in later cycles. Similarly, the majority of treatment-related adverse events (TRAEs) not associated with CRS were of low severity (Grade 1 or 2) and also primarily occurred in the initial cycle.

There was a low incidence of Grade 3 TRAEs, and no Grade 4 or 5 events were observed. JANX007 has been administered at doses up to 3mg, significantly exceeding the anticipated maximum tolerable dose for the parental T cell engager, while the maximum tolerable dose for the TRACTr has not yet been established. Based on this safety profile, we are continuing dose optimization for JANX007 with the goal of further deepening PSA responses, while maintaining a favorable safety profile.

Janux anticipates providing an update on doses for expansion in the second half of 2024. Interim clinical data for EGFR-TRACTr JANX008 in solid tumors as of February 12, 2024. JANX008 is in a Phase 1a clinical trial in subjects with advanced or metastatic solid tumors known to express high levels of the EGFR target, including colorectal cancer (CRC), squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC).

As of February 12, 2024, 11 heavily pre-treated, late-stage subjects across all four tumor types have been enrolled. Encouraging signs of clinical activity were observed, while a favorable safety profile was maintained. In one subject with NSCLC treated with JANX008 at 0.15mg once-weekly, a confirmed partial response (PR) by RECIST criteria with 100% reduction of the target lung lesion and elimination of liver metastasis with no CRS or TRAEs has been observed.

This subject remains on treatment and their PR has been maintained through their week-18 scan. One subject with RCC experienced a 12% reduction in the size of a large RCC mass and significant clinical benefit with Grade 1 CRS. The early safety profile for JANX008 is consistent with the TRACTr design principles of tumor-specific activation while avoiding healthy tissue toxicity with a broadly expressed target.

In the 11 subjects enrolled at doses up to 1.25mg, which is significantly above the projected maximum tolerable dose of the parental T cell engager, Grade 1 CRS was observed in only two subjects and no Grade 2 or higher CRS was seen. The majority of non-CRS TRAEs were also low-Grade 1 or 2 and occurred predominantly in cycle one. No treatment related serious adverse events or dose-limiting toxicities have been observed.

Based on this safety profile, we are continuing in the dose escalation and optimization portion of the trial for JANX008.