Johnson & Johnson (J&J) has announced promising phase 1 results for JNJ-6143 (formerly HLD-0915), an investigational once-daily oral Regulated Induced Proximity Targeting Chimera (RIPTAC) small molecule, in patients with advanced prostate cancer who had received multiple prior treatments.

Among patients with measurable disease, 75 percent (12 out of 16) had a confirmed complete or partial response assessed by Response Evaluation Criteria in Solid Tumors (RECIST).

At the 50 mg dose, 77 percent of patients achieved a confirmed reduction in Prostate-Specific Antigen (PSA) levels of at least 50 percent, and 48 percent had reductions of at least 90 percent.

Most Treatment-Related Adverse Events (TRAEs) were mild to moderate.

JNJ-6143 is the first investigational molecule from the company’s RIPTAC platform to advance into clinical studies. The novel mechanism disrupts cancer cell function and triggers cancer cell death using a targeted dual-protein lock between an essential cell survival protein, BRD4, and Androgen Receptor (AR), a tumor-selective protein, which is highly expressed in prostate cancer cells.

Despite advances in treatment, including therapies that target the AR pathway, chemotherapy and radioligand therapy targeting Prostate-Specific Membrane Antigen (PSMA), many patients with advanced prostate cancer experience disease progression, and are left with fewer options.

Median Overall Survival (OS) is approximately 2 to 3 years for patients with metastatic Androgen Pathway Modulation-Resistant (mAPMR) prostate cancer, also known as metastatic Castration-Resistant Prostate Cancer (mCRPC), highlighting the need for new treatment approaches with different mechanisms of action.

Professor Johann de Bono, MD, Head of Division—Cancer Biomarkers, Prostate Cancer Targeted Therapy Group, The Adult Drug Development Unit, ICR Cancer Research Institute, London, UK, said, “Patients with advanced prostate cancer often go through several treatments as their disease becomes increasingly difficult to control, signaling a significant need for treatments that work differently. These early results with JNJ-6143 are encouraging because we are seeing meaningful anti-tumor activity in patients who have already received multiple therapies. The findings give us confidence to further evaluate this new approach for those with difficult-to-treat disease.”

The ongoing phase 1 study is evaluating the safety and anti-tumor activity of JNJ-6143 and was designed to identify the optimal dose for further study in patients with advanced prostate cancer whose disease progressed after prior treatment. Patients received a median of 4 prior therapies, including chemotherapy and PSMA-targeted radioligand therapy.

Among 38 patients receiving the 50-mg once-daily dose, 77 percent had a confirmed reduction of at least 50 percent in PSA, a protein measured in the blood to help monitor prostate cancer, including 48 percent whose PSA levels fell by at least 90 percent.

Reductions in PSA were also observed in patients with high-risk molecular features associated with difficult-to-treat disease. Among patients whose tumors could be measured using imaging, 75 percent had a confirmed complete or partial response.

At the time of the analysis, 71 percent of patients receiving the 50-mg dose remained on treatment, with a median follow-up of 5.6 months. The most common TRAEs were elevated cholesterol levels (18 percent), nausea (16 percent), and elevated triglyceride levels (16 percent). Four patients (11 percent) interrupted their dose, 1 patient (3 percent) reduced their dose, and 1 patient (3 percent) discontinued treatment due to AEs.

The 50-mg once-daily dose will advance into further clinical development, including the phase 2 study (NCT07832292) of JNJ-6143 in metastatic prostate cancer.

Yusri Elsayed, MD, MHSc, PhD, Global Therapeutic Area Head, Oncology, J&J, said, “For nearly 2 decades, we have driven progress in prostate cancer care by repeatedly pursuing new scientific approaches with the potential to change the course of the disease. JNJ-6143 builds on that approach, bringing a fundamentally different oral mechanism to our prostate cancer pipeline. These early results provide an encouraging foundation for its continued development and our broader exploration of the RIPTAC platform across multiple cancer types.”

The phase 1 study (NCT06800313) is a multicenter dose-escalation and dose-expansion study of JNJ-6143 in patients with metastatic androgen pathway modulation-resistant prostate cancer (mAPMR) whose disease progressed after one or more androgen receptor pathway inhibitors.

The study is evaluating the safety, pharmacokinetics and anti-tumor activity of JNJ-6143 and is designed to determine the maximum tolerated dose and optimal dose for further development. Patients had received a median of 4 prior therapies, including chemotherapy and PSMA-targeted radioligand therapy.

The dose-escalation portion evaluated once-daily doses of JNJ-6143 ranging from 12.5 mg to 150 mg, followed by dose expansion randomising patients 1:1 to receive 25 mg or 50 mg once daily. The 50-mg once-daily dose was identified as the preliminary optimal dose for further development based on the clinical activity, safety and pharmacokinetic data observed in the study.

JNJ-6143 is an investigational, once-daily molecule that uses the novel RIPTAC platform. Its targeted dual-protein lock brings together BRD4, an essential protein for cell survival, and the tumor-selective protein, AR, which is highly expressed in prostate cancer cells, and is designed to disrupt cancer cell function and trigger cancer cell death.

JNJ-6143 is being evaluated in phase 1 (NCT06800313) and phase 2 (NCT07832292) studies in patients with metastatic prostate cancer. It is the first investigational compound from the RIPTAC platform to advance into clinical studies.

In December 2025, J&J completed its acquisition of Halda Therapeutics, adding JNJ-6143 and the RIPTAC platform to its oncology portfolio.

The investigational proprietary RIPTAC platform is being explored for the development of oral targeted therapies across multiple tumor types. RIPTAC molecules use a targeted dual-protein lock between an essential protein for cell survival and a tumor-selective protein, designed to disrupt cancer cell function and trigger cancer cell death.

J&J is advancing investigational candidates based on the RIPTAC platform, including JNJ-6143 in advanced prostate cancer.