Halda Therapeutics announced promising first-in-human clinical results for HLD-0915, a novel oral therapeutic that demonstrated significant anti-tumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC) who had exhausted multiple treatment options. The data, presented at the 2025 AACR-NCI-EORTC International Conference, showed encouraging efficacy signals combined with a favorable safety profile.
Clinical Trial Results Show Strong Response Rates
The Phase 1/2 clinical trial (NCT06800313) enrolled 40 patients with mCRPC who had progressed on prior therapies, including at least one androgen receptor pathway inhibitor and up to two prior taxanes. Among 22 patients who completed at least two cycles of therapy, 59% achieved a PSA50 response and 32% achieved a PSA90 response.
"These preliminary results suggest that HLD-0915, an oral, once daily therapy, can achieve meaningful anti-tumor activity with a clean safety profile in mCRPC patients who had failed up to 8 prior mCRPC therapies," said Dr. Andrew Hahn, Assistant Professor at The University of Texas MD Anderson Cancer Center, who presented the data.
The median time to PSA50 response across all doses was 37 days, occurring between one to two treatment cycles. Among patients treated at the 50 mg dose level for at least two cycles, 70% achieved a PSA50 response and 40% achieved a PSA90 response.
RECIST Responses and Biomarker Activity
All five patients with RECIST-measurable disease at baseline achieved partial responses at their first response assessment, with an additional patient showing resolution of soft tissue disease in mixed lesions. Among 16 patients evaluated, 13 showed reductions in circulating tumor DNA (ctDNA) tumor fraction ranging from -70.4% to -99.9%.
Novel Mechanism Overcomes Resistance
HLD-0915 represents a first-in-class oral RIPTAC (Regulated Induced Proximity Targeting Chimeras) therapeutic that works through a novel "hold and kill" mechanism. The bifunctional small molecule holds together androgen receptor and BRD4 proteins with defined orientation, creating new protein-protein interactions that abrogate BRD4 function within cancer cells.
"HLD-0915 demonstrated clinical activity regardless of genomic heterogeneity – including androgen receptor (AR) mutations, splice variants or amplifications," Dr. Hahn noted. This activity across diverse molecular characteristics suggests the mechanism may overcome common resistance pathways that limit current precision oncology approaches.
Safety Profile and Dosing
The treatment showed a favorable safety profile across all dose levels tested (12.5 mg, 25 mg, 50 mg, and 100 mg once daily). Treatment-related adverse events were infrequent and generally low grade, with nausea occurring in 20% of patients and anemia and fatigue each occurring in 10% of patients.
Grade 3 or higher treatment-related adverse events were not observed at the 12.5 mg and 50 mg doses. At higher doses, isolated cases included decreased lymphocytes at 50 mg and liver-related toxicities at 100 mg that were subsequently attributed to bile duct obstruction. All grade 3 or higher events were reversible and resolved, with no grade 5 events reported.
The 25 mg and 50 mg doses have been identified as recommended doses for Phase 2 expansion, which is expected to begin in late 2025. HLD-0915 has received Fast Track designation from the FDA.
Platform Technology Implications
Halda's RIPTAC platform represents a novel approach to precision oncology designed to address cancer's ability to evolve bypass mechanisms of resistance. The company's lead programs are in clinical and preclinical development for major solid tumor types, with additional RIPTAC therapeutic programs in development for serious diseases.
