Halda Therapeutics Publishes RIPTAC™ Cancer Treatment Proof in Cell Chemical Biology

Halda Therapeutics, a biotechnology firm based in New Haven, Connecticut, has made significant strides in cancer treatment research with the development of a new class of therapies known as RIPTAC™ (Regulated Induced Proximity Targeting Chimeras). The company recently published compelling data in the peer-reviewed journal "Cell Chemical Biology" that highlights the proof-of-mechanism and pharmacology of these innovative therapeutics. The publication is titled "Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Heterobifunctional Small Molecule Strategy for Cancer Selective Therapies."

RIPTAC therapeutics are engineered as heterobifunctional small molecules with a unique "hold and kill" mechanism. These molecules function by bringing together two specific proteins: one that is tumor-specific and another that is essential for cell function. This interaction inhibits the essential protein’s function, leading to the death of cancer cells. Unlike traditional precision oncology drugs that target the oncogene driving the cancer, RIPTAC therapeutics do not require the target protein to be the cancer driver. This novel mechanism also aims to negate the common issue of resistance that often develops with current cancer treatments, making RIPTACs suitable for both early and late-stage cancer therapies.

Dr. Kanak Raina, the lead author of the study and Head of Biology at Halda Therapeutics, expressed enthusiasm over the data showcasing RIPTAC molecules' mechanism of action. According to Raina, the insights gained from their chemical biology model have laid a solid foundation for Halda's pipeline of RIPTAC therapeutics aimed at treating major cancers.

The publication showcases several chemical biology techniques using a model with a HaloTag‑FKBP target protein to unravel the mechanism and pharmacology of RIPTAC molecules. Key findings from their study include:

- RIPTAC therapeutics exhibited selective anti-proliferative activity in cells expressing the target protein.
- The formation of a ternary complex by the target protein, the RIPTAC molecule, and a pan-essential protein led to the selective abrogation of the essential protein’s function in target-expressing cells, resulting in cell death.
- Various pan-essential cellular proteins were found to be amenable for selective cancer cell killing when included in RIPTAC ternary complexes.

Craig Crews, PhD, a Professor of Molecular, Cellular, and Developmental Biology at Yale University and a scientific founder of Halda Therapeutics, contributed to the paper. Crews is a pioneer in induced proximity biology, which has been instrumental in the vision and invention of heterobifunctional drugs. He emphasized that RIPTAC therapeutics address a critical shortcoming of many current precision cancer medicines, which often depend on oncogenic driver proteins and can lead to drug resistance. The RIPTAC modality introduces a new, oral, selective mechanism for killing cancer cells that can overcome resistance, making it useful in both advanced and early-stage cancers where tumor-specific proteins are present.

Halda Therapeutics is committed to advancing the precision treatment of cancer with its proprietary RIPTAC™ modality. This innovative approach seeks to address the evolving resistance mechanisms in cancer, a common drawback of existing precision oncology medicines. The company is building a robust pipeline of new therapeutics focused on treating difficult-to-address patient populations, particularly those with major solid tumors. Halda's leadership team boasts extensive expertise in bifunctional drug discovery, platform innovation, and company building.