Regulated Induced Proximity Targeting Chimeras (RIPTACs) represent a novel class of heterobifunctional small molecules designed to selectively target cancer cells by inducing proximity between a tumor-specific protein (TP) and an essential effector protein (EP). This interaction forms a stable ternary complex that disrupts the function of the EP, leading to selective cancer cell death. Unlike traditional therapies, RIPTACs do not require the TP to be a disease driver, thereby expanding the range of potential targets in oncology.

HLD-0915, is an orally bioavailable RIPTAC designed to treat metastatic castration-resistant prostate cancer (mCRPC). Preclinical studies have demonstrated that HLD-0915 effectively induces the formation of a trimeric complex with the androgen receptor (AR) and an essential transcriptional regulator, leading to selective killing of AR-expressing prostate cancer cells. Notably, HLD-0915 has shown superior anti-tumor activity compared to enzalutamide, a current standard-of-care treatment for prostate cancer.

The RIPTAC modality offers a new oral, selective, and widely applicable cancer cell-killing mechanism that can overcome drug resistance and can be used in advanced cancer where resistance has emerged, as well as in early-stage disease where the tumor-specific protein is expressed.

Phase 1 trial is recruiting!

UPDATE: February 25, 2025
The first patient was dosed yesterday

Source.

Clinical trial.