Achilles Therapeutics and Arcturus Therapeutics Collaborate on Next-Gen Personalized mRNA Cancer Vaccines

Achilles Therapeutics, a clinical-stage biopharmaceutical firm known for its AI-powered precision T cell therapies for solid tumors, has entered into a research collaboration with Arcturus Therapeutics Holdings, a company specializing in mRNA medicines. This partnership will focus on the development of personalized cancer vaccines (PCVs) using self-amplifying mRNA (sa-mRNA) to target clonal neoantigens.

The collaboration aims to amalgamate Achilles' advanced AI-driven, tumor-targeting technology with Arcturus’ renowned sa-mRNA platform. Dr. Iraj Ali, CEO of Achilles Therapeutics, stated that the collaboration leverages the unique capabilities of their PELEUS platform, which selects targets with high immunogenic potential expressed by all tumor cells, alongside Arcturus' proven STARR vaccine platform. The goal is to produce more potent and durable T cell responses that could positively impact patient outcomes. This joint effort aims to apply Achilles' neoantigen expertise to a new modality beneficial for earlier-stage cancer patients.

The collaboration is expected to yield data demonstrating the efficacy of the PELEUS platform in selecting highly immunogenic clonal neoantigens. These neoantigens will be expressed using the Arcturus STARR® platform to generate robust and lasting T cell responses. Any future clinical development will be a mutual decision between the two companies.

Cancer vaccines work by enhancing the activity of T cells capable of recognizing rare neoantigens on tumor cells. Tumor cells typically carry hundreds of mutations called neoantigens, but only a few can induce T cell responses that effectively control the tumor. Vaccine platforms are generally limited by the number of neoantigens they can target, hence the importance of selecting the most potent neoantigens is vital to maximize clinical efficacy. Achilles’ PELEUS™ platform uses proprietary AI technology to select the most immunogenic clonal neoantigens that have the least immune evasion potential and are present on all cancer cells of a patient.

Achilles Therapeutics is at the forefront of developing precision T cell therapies that target clonal neoantigens—protein markers unique to each individual, expressed on the surface of every cancer cell. The company is conducting two ongoing Phase I/IIa trials: the CHIRON trial in advanced non-small cell lung cancer (NSCLC) and the THETIS trial in recurrent or metastatic melanoma. Achilles utilizes DNA sequencing data from each patient, combined with its proprietary PELEUS™ bioinformatics platform, to identify specific clonal neoantigens and develop T cell-based product candidates targeting those neoantigens.

The PELEUS platform employs advanced Bayesian statistical algorithms to determine which mutations in a patient’s tumor are clonal or subclonal by analyzing DNA sequencing data from multiple tumor regions. Clonal neoantigens are protein markers present on all cancer cells but absent from healthy tissue, making them ideal targets for cancer therapy. PELEUS underpins Achilles’ VELOS manufacturing process, which produces clonal neoantigen-reactive T cells (cNeT).

Arcturus Therapeutics, founded in 2013 and based in San Diego, California, is a global leader in mRNA medicines and vaccines. The company’s key technologies include LUNAR® lipid-mediated delivery, STARR® mRNA Technology (sa-mRNA), and expertise in mRNA drug substance and product manufacturing. Arcturus developed the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine, Kostaive®, approved globally. The company collaborates with CSL Seqirus for mRNA vaccines and operates a joint venture in Japan, ARCALIS, focusing on manufacturing mRNA vaccines and therapeutics. Arcturus’ pipeline includes RNA therapeutic candidates for conditions like ornithine transcarbamylase deficiency and cystic fibrosis, along with partnered mRNA vaccine programs for diseases such as COVID-19 and influenza. The company's platforms extend to various nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics, protected by an extensive patent portfolio.