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Halda emerges from stealth with bifunctional molecules to treat cancer

The start-up’s compounds ‘hold and kill’ proteins needed for cancer cell survival

by Gina Vitale
February 14, 2023

An illustration of a RIPTAC molecule bringing two proteins together.
Credit: Courtesy of Halda Therapeutics
A regulated induced proximity targeting chimera (RIPTAC) molecule connects a protein with an essential cell function (gray) to a tumor-specific protein (purple), preventing the essential protein from functioning within the cancer cell, killing the cancer cell.

Halda Therapeutics, based in New Haven, Connecticut, is developing a new class of therapies called regulated induced proximity targeting chimeras (RIPTACs) to treat cancer. The company, with $76 million in financing to date, announced today that it will present its RIPTAC data for the first time publicly at the 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco Feb. 16-18. The scientific founder is protein degradation expert and Yale professor Craig Crews.

RIPTACs are bifunctional molecules that draw two different proteins together. On one end of each molecule is a ligand that grabs a tumor-specific protein; on the other end is a ligand that binds a protein that is necessary for the cancer cell to survive. The RIPTAC and the two proteins form a complex within cancer cells that inhibits the protein with the essential function. The company calls the mechanism “hold and kill”—the ternary complexes holds the proteins in a nonfunctioning state until the cancer cells die. “Halda” is an old Scandinavian word for “hold,” Crews says.

At ASCO GU, Halda will present preclinical data of a RIPTAC to treat prostate cancer. The RIPTAC was tested in prostate cell lines and a rodent model of prostate cancer that is insensitive to the current standard of care agent, according to the company.

“We think that this will be less sensitive to resistance,” Kat Kayser-Bricker, Halda’s chief scientific officer, says about RIPTACs. By targeting an essential cellular protein, “it’s actually very difficult for a cell to evolve around that protein,” she says. “It’s always going to be reliant on it.”

RIPTACs are similar in some ways to proteolysis targeting chimeras (PROTACs), a technology for which Crews was an early leader. PROTACs are also double-ended molecules that bring two proteins together; one end binds a disease-causing protein, and another end binds an enzyme called an E3 ligase, which tags the bad protein for destruction. PROTACs are the central technology of Arvinas, a company Crews founded in 2013 and which has several molecules in the clinic for treating cancers.

A number of companies have launched to pursue bifunctional molecules for protein modification in the past year. In July 2022, Vicinitas Therapeutics launched with $65 million to pursue deubiquitinase-targeting chimeras (DUBTACs) for protein stabilization. In December 2022, Entact Bio launched with $81 million to enhance protein function, calling its molecules enhancement-targeting chimeric molecules (ENTACs).



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