Janux Therapeutics (JANX) Investor Update summary

Clinical program focus and patient population

• Development targets early-line, taxane-naive metastatic castration-resistant prostate cancer (mCRPC) patients, a rapidly growing segment with over 38,000 taxane-naive mCRPC patients in the US.

• JANX007 is a tumor-activated T-cell engager (TCE) targeting PSMA, designed to overcome safety and efficacy limitations of prior PSMA-TCEs.

• The TRACTr platform uses cleavable linkers and masking to reduce toxicity and enhance tumor-specific activation.

• Subjects in clinical studies are heavily pretreated, with a median of 4 prior therapies and high rates of bone and lymph node metastases.

• Early data in taxane-naive patients show rapid, deep PSA reductions and predominantly grade 1 CRS.

Efficacy and safety data

• Over 100 patients have been dosed, with durable PSA reductions and radiographic PFS (rPFS) of 7.9–8.9 months in expanded cohorts.

• Deep PSA reductions (PSA50 in 73%, PSA90 in 26% at ≥2mg) and RECIST response rate of 30% at >2mg achieved.

• Safety profile is manageable, with most adverse events related to CRS, primarily grade 1 or 2, and largely limited to early cycles.

• Optimized CRS mitigation procedures further reduced severity and duration of CRS events.

• Grade 3 adverse events increase at the 12 mg dose, leading to prioritization of 3, 6, and 9 mg doses for further study.

Dosing regimen optimization

• 6mg and 9mg target doses, both QW and Q2W, demonstrated the best balance of efficacy and safety.

• Q2W dosing is supported by comparable efficacy, reduced grade 3 adverse events, and patient convenience compared to weekly dosing.

• CRS mitigation protocol P2 maintains a favorable safety and efficacy profile, with rapid CRS resolution and strong PSA reductions.

• Q2W dosing is preferred for future cohorts, especially in taxane-naive patients, and may facilitate outpatient administration.

• No difference in CRS rates between QW and Q2W regimens; CRS primarily occurs in early cycles.