Halda Therapeutics announces publication of data demonstrating proof-of-mechanism of RIPTAC™ therapeutics, a novel drug modality for treatment of cancer

Results from chemical biology study show ‘hold and kill’ mechanism for selective cell killing enabled by RIPTAC therapeutics, a new class of heterobifunctional small molecules


NEW HAVEN, CT, January 2, 2023 – Halda Therapeutics, a biotechnology company developing a novel class of cancer therapies called RIPTACTM (Regulated Induced Proximity TArgeting Chimeras) therapeutics, today announced the publication of data demonstrating proof-of-mechanism and selective cell killing for a RIPTAC therapeutic, published in preprint in bioRxiv and available here. The manuscript entitled, “Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively,” describes the creation of a chemical biology model of RIPTAC therapeutics and illustrate the mechanism of action of this novel drug modality to enable selective killing of cancer cells.

The proof-of-concept study elaborates how RIPTAC therapeutics are heterobifunctional small molecules that work by a novel “hold and kill” mechanism, bringing together two proteins, a cancer-specific protein and a protein with essential function, resulting in abrogation of the essential cell function, and subsequently, cancer cell death. The novel mode of action of RIPTAC therapeutics is designed to overcome the known bypass mechanisms of resistance that evolve during a course of therapy, a common limitation of today’s precision oncology medicines, thereby opening the potential for their use in late and early stages of cancer treatment.

“We are working towards generating new treatment options for cancer patients. This work shows that a novel concept like RIPTAC therapeutics could have significant clinical applications, which is very exciting,” said Kanak Raina, Ph.D., lead author and Senior Director of Biology at Halda. “The chemical biology model that we have built is quite powerful, allowing us to interrogate each step of the mechanism, providing insights into the creation of RIPTAC therapeutics that are advancing in Halda’s pipeline.”

Several chemical biology approaches were explored in the study to exemplify mechanistic principles that are currently being applied by Halda to develop RIPTAC therapeutics in the company’s pipeline. Key findings from the study include:

  • RIPTAC therapeutics demonstrated enhanced anti-proliferative activity in cells expressing the target protein.
  • A ternary complex formed by the target protein, essential protein and the RIPTAC molecule abrogated the function of the essential protein selectively in target-expressing cells, causing cell death.
  • The ternary complex allowed for selective accumulation inside of the cell expressing the target protein.

“Precision medicines for cancer continue to make strides, but there are challenges with durability stemming from the conventional mechanisms of targeting oncogenic driver proteins, which cause tumors to become drug resistant in a large percentage of patients. Findings in this study demonstrate the potential of RIPTAC therapeutics to overcome these challenges by deploying a new heterobifunctional mechanism that does not rely on oncogenic driver proteins and is able to achieve a selecting cell-killing effect on cancer cells in a powerful, new way,” said Kat Kayser-Bricker, PhD, Chief Scientific Officer of Halda Therapeutics. “From this model system, we are now rapidly building a pipeline of RIPTAC therapeutic candidates, moving two lead drug programs toward the clinic.”


About Halda Therapeutics

Halda Therapeutics is a biotechnology company developing a proprietary RIPTAC™ (Regulated Induced Proximity TArgeting Chimeras) modality that works by a novel “hold and kill” mechanism for the precision treatment of cancer. 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. The company has built a robust pipeline of novel mechanism of action therapeutics, with an initial focus on bringing new drugs to address these difficult to treat patient populations. Our leading programs are in major solid tumor types, with additional RIPTAC therapeutic programs in development to treat medical unmet needs in oncology. Halda is led by a leadership team with deep expertise in bifunctional drug discovery, platform innovation, and company building, and is located in New Haven, CT. For more information, please visit www.haldatx.com and follow us on Twitter and LinkedIn.


Media Contact:

Kathryn Morris
The Yates Network LLC



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