Halda Therapeutics has struck a deal with VantAI, entering into a pact that could be worth more than $1 billion to secure a source of targets for its novel approach to oncology and immunology.
Yale University professor Craig Crews, Ph.D., whose work underpinned PROTAC pioneer Arvinas, founded Halda to advance his next big idea. While PROTACs tag proteins for degradation, Halda’s regulated induced proximity targeting chimeras (RIPTACs) create a complex out of a tumor-specific protein and a separate protein essential to healthy cells. By inhibiting the essential protein in cancerous cells, the idea is that RIPTACs could drive the targeted elimination of tumors.
The small molecule modality relies on Halda having tumor-specific proteins and essential proteins. That is where VantAI comes in. The company will use its AI and structural proteomics discovery platform to find and validate target-effector pairs for Halda across oncology and immunology.
VantAI’s application of the platform to RIPTACs follows work on similar modalities. Blueprint Medicines, Bristol Myers Squibb and Johnson & Johnson are partnered with VantAI on molecular glues, another modality that creates a new protein-protein interaction. VantAI’s work with Blueprint and J&J also includes protein degraders.
Halda’s RIPTAC platform is designed to address some of the limitations of older modalities. Typically, drugs hit a protein that a cancer needs to grow and proliferate. RIPTACs, like antibody-drug conjugates, can kill cells regardless of the function of the targeted tumor-specific protein. The protein is only used as a targeting mechanism to spare healthy cells, opening up more of the cancer proteome to Halda.
The efficacy of RIPTACs comes from disrupting proteins that are essential to healthy cells, rather than by inhibiting oncogenic pathways. Inactivating essential proteins kills the cell and, because RIPTACs require the presence of a tumor-specific protein, the cytotoxic effect should be selective to cancerous cells.
Halda, which raised $126 million one year ago, is seeking to validate the concept of its so-called “hold-and-kill” mechanism in a phase 1/2 trial of its lead drug candidate, HLD-0915. The biotech is developing the RIPTAC as a treatment for metastatic castration-resistant prostate cancer. Prostate tumors often develop resistance by boosting expression of the androgen receptor. HLD-0915 turns the defense mechanism against tumors by targeting the androgen receptor.
Partnering with VantAI could give Halda a source of target-effector pairs for its next wave of prospects. The deal could be worth more than $1 billion, including upfront and milestone payments across multiple targets—although the companies didn't offer a breakdown of the financials.