Halda Therapeutics Announces First-in-Human Results for HLD-0915, an Oral RIPTAC™ Therapeutic Demonstrating Encouraging Safety and Anti-Tumor Activity in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Anti-tumor activity was observed in heavily pretreated mCRPC patients across all dose cohorts; in 22 patients who completed at least 2 cycles of therapy, 59% achieved PSA50 response and 32% achieved PSA90 response
All 5 patients (5/5) with measurable disease according to RECIST criteria achieved a partial response (PR), all by the first response assessment
Results to date exhibit a favorable safety profile with low rates of treatment-related adverse events
BOSTON, Oct. 24, 2025 (GLOBE NEWSWIRE) -- Halda Therapeutics announced today new data from a Phase 1/2 study evaluating HLD-0915, a first-in-class, oral RIPTAC™ therapeutic, in patients with metastatic castration-resistant prostate cancer (mCRPC). The first-in-human findings demonstrate that HLD-0915 was well-tolerated and showed encouraging preliminary signs of anti-tumor activity, including reductions in prostate-specific antigen (PSA) and circulating tumor DNA (ctDNA), and responses by RECIST, in patients with advanced mCRPC who had progressed on multiple prior therapies. Anti-tumor activity was observed at all doses and occurred in patients with heterogeneous, adverse molecular characteristics. These data were presented today as an oral presentation in a plenary session at the 2025 AACR-NCI-EORTC International Conference in Boston, Massachusetts.
“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, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, who presented the HLD-0915 data in the oral plenary session. “Furthermore, HLD-0915 demonstrated clinical activity regardless of genomic heterogeneity – including androgen receptor (AR) mutations, splice variants or amplifications. Given the limited treatment options for mCRPC patients, these clinical findings support the differentiated approach to drive a precision cell-killing effect through a novel mechanism that does not rely on cancer drivers that can cause drug resistance.”
The Phase 1/2 clinical trial (NCT06800313) has enrolled 40 patients. Eligible patients had mCRPC with PSA progression on the prior regimen and must have received at least one androgen receptor pathway inhibitor (ARPI) and may have received up to two prior taxanes and up to one prior radioligand. Objectives of this study include defining the maximally tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), anti-tumor activity, and changes in ctDNA. The patients received a once daily oral dose (6 at 12.5 mg, 7 at 25 mg, 14 at 50 mg, and 4 at 100 mg) in 21-day cycles.
The presentation contains data from all 31 patients dosed as of the data cutoff. A total of 4 patients have discontinued study treatment to date, and there are 8 patients who received less than 2 cycles of therapy and are ongoing.
- At the data cut-off, among all 31 patients who received at least one dose of HLD-0915, 13 (31%) achieved a PSA50 response and 7 (23%) achieved a PSA90 response.
- The median time to PSA50 across doses was 37 days (between 1-2 cycles).
- Among the 22 patients who completed at least 2 cycles of therapy, 59% achieved a PSA50 response and 32% achieved a PSA90 response.
- The 25 mg and 50 mg doses have been identified as recommended doses for Phase 2 expansion.
- Among the 10 patients treated at 50 mg for at least 2 cycles, 70% achieved a PSA50 response and 40% achieved a PSA90 response.
- Among all 5 patients with RECIST-measurable disease at baseline and an on-treatment scan, all achieved a partial response (PR) at the first response assessment, and a 6th patient with a mixed soft tissue and bone lesion had resolution of soft tissue disease. The partial responses were measured by Response Evaluation Criteria in Solid Tumors (RECIST), a standard measure of the effectiveness of cancer treatments.
- 13/16 patients had reductions in ctDNA tumor fraction (-70.4% to -99.9%).
- Treatment-related adverse events (TRAEs) across all doses were infrequent and generally low grade. Across all doses, TRAEs observed in ≥10% of patients were nausea in 6 (20%), anemia and fatigue, each in 3 (10%). Grade ≥3 TRAEs were not observed at 12.5mg and 50mg doses; one patient at 50 mg had decreased lymphocytes and, at 100 mg, one patient had hypertriglyceridemia and one patient had elevations in liver transaminases and bilirubin comprising a dose-limiting toxicity but was subsequently found to have evidence of common bile duct obstruction. All ≥3 TRAEs were reversible and resolved and there was no grade 5 event. There were no AEs of thrombocytopenia.
- The Phase 2 expansion is expected to begin in late 2025. HLD-0915 has been granted Fast Track designation by the FDA.
The abstract is available on the AACR website, and the full presentation is available on Halda’s website here.
About HLD-0915
HLD-0915 is an innovative bifunctional small molecule therapy designed to selectively target prostate cancer tumors cells by holding together, with defined orientation and purpose, androgen receptor (a tumor-specific intracellular targeting protein) and a protein with essential function (effector protein), BRD4. The ternary complex drives the formation of new protein-protein interactions, abrogating BRD4 function selectively within cancer cells which results in an anti-tumor effect. In preclinical prostate cancer models, orally delivered HLD-0915 treatment resulted in tumor shrinkage and declines in prostate-specific antigen (PSA), while delivering a favorable therapeutic index including in models of drug resistance. Halda has presented initial Phase 1 clinical data of HLD-0915 in mCRPC patients demonstrating safety, pharmacokinetics, and efficacy. The first-in-human findings demonstrate that HLD-0915 was well-tolerated and showed encouraging preliminary signs of anti-tumor activity, including reductions in PSA, ctDNA and partial responses by RECIST, in patients with advanced prostate cancer who had progressed on multiple prior therapies. Anti-tumor activity was observed at all doses and occurred in patients with adverse molecular characteristics.
About Halda Therapeutics
Halda Therapeutics is a clinical-stage biotechnology company that has developed a proprietary RIPTAC™ (Regulated Induced Proximity Targeting Chimeras) modality that works by a novel “hold and kill” mechanism for the precision treatment of cancer and other diseases. The novel mechanism of action of RIPTAC therapeutics is uniquely designed to address cancer’s ability to evolve bypass mechanisms of resistance, a common limitation of today’s precision oncology medicines. Our lead RIPTAC programs are in clinical and pre-clinical development for major solid tumor types with additional RIPTAC therapeutic programs in our pipeline to treat serious disease. Halda is led by a leadership team with deep expertise in biotechnology, drug discovery, platform innovation, and clinical development, and is located in New Haven, CT. For more information, please visit www.haldatx.com and follow us on LinkedIn.
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