Halda secures $126M in B round for next-gen oral TACs

Approximately a year and a half after stepping out of stealth mode, Halda Therapeutics is poised to begin clinical trials for two cancer treatments known as Regulated Induced Proximity Targeting Chimeras (RIPTACs). With the necessary funding now secured, these trials can commence. Halda was founded by Craig Crews, a Yale School of Medicine professor who also created Arvinas to develop his earlier invention, PROTACs. Halda’s innovative molecules deploy a “hold and kill” strategy to target and eliminate cancer cells, avoiding the protein degradation pathway.

The biotech firm recently concluded a $126-million series B extension, which will be allocated to initiate a study on metastatic castration-resistant prostate cancer in the upcoming half-year. Following this, Halda aims to start clinical trials for its second candidate focused on breast cancer. Kat Kayser-Bricker, Halda's Chief Scientific Officer, emphasized that these developments hold significant value and potential for patient impact, which resonated well with investors. This successful financing round brings Halda’s total funding to $202 million, following its initial $76 million investment in 2023. The round saw participation from new investors such as Deep Track Capital, Frazier Life Sciences, RA Capital Management, Vida Ventures, Boxer Capital, and Taiho Ventures, along with existing investors like Canaan Partners, Access Biotechnology, Elm Street Ventures, and Connecticut Innovations.

RIPTACs represent a sophisticated and unique approach to targeted cancer therapy, according to Arjun Goyal, Vida Ventures’ managing director. These heterobifunctional molecules consist of two halves: one targets a protein expressed in tumor cells, while the other connects with an essential protein necessary for cell survival. By drawing high levels of the essential protein into a ternary complex, the RIPTAC effectively triggers cell death in cancer cells. This method is distinct from other oncology strategies that often face efficacy challenges due to dose-limiting toxicities. RIPTACs, however, only interact in cells with the tumor-specific protein, enabling a very selective cell-killing mechanism.

Unlike traditional targeted oncology therapies, RIPTACs do not require oncogenic drivers as their targeting protein. This could help overcome resistance mechanisms that typically develop as patients advance through standard therapies. The key is identifying target proteins that are more abundant in cancer cells than in normal cells. This setup allows RIPTACs to elicit cell death independently of resistance mutations, making them a promising option in targeted oncology.

Halda’s lead candidate, HLD-0915, targets the androgen receptor (AR), prevalent in prostate cancer cells but minimally present in healthy cells. The requirement for high expression levels of the target protein to induce cell death spares normal tissues, providing an advantageous therapeutic index. Although the specific essential protein involved in HLD-0915 is not disclosed, it is known to play a role in transcriptional regulation.

Another advantage of RIPTACs lies in their oral bioavailability. For prostate cancer, typically managed initially with oral therapies, offering RIPTACs as a subsequent treatment could appeal to patients who prefer oral medication over injected or infused therapies like antibody-drug conjugates or radioligand treatments. Few oral options in development exhibit broad efficacy in a mutation-agnostic manner, making RIPTACs a valuable differentiator. Additionally, oral therapies can be more accessible to rural cancer patients, as they don’t necessitate administration at academic medical centers. This fits well with the current treatment paradigm for these cancers, offering a promising future for RIPTACs in oncology.