Achilles Therapeutics plc announced that an abstract highlighting updated interim results from the ongoing Phase I/IIa CHIRON and THETIS clinical trials evaluating clonal neoantigen-reactive T cells (cNeT) has been accepted for a poster presentation at the ESMO Immuno-Oncology Annual Congress (ESMO IO) taking place in Geneva, Switzerland from December 7-9, 2022. cNeT are the active component of the final, precision T cell product which target tumors through recognition of a patient's clonal neoantigens present on all tumor cells. Data on 14 heavily pre-treated patients (eight patients from CHIRON with advanced NSCLC and six patients from THETIS with recurrent melanoma) that received cNeT as monotherapy and had completed at least one post-treatment scan six weeks following dosing by the abstract cut-off date will be presented.

Safety and tolerability observations of cNeT compare favorably to standard tumor infiltrating lymphocytes (TIL) due to less IL-2 related toxicity. Lymphopenia and neutropenia were the most common adverse events, which are principally associated with the conditioning regimen, and no dose limiting high-grade toxicities associated with IL-2 were reported. The best clinical response was a partial response (ongoing at week 33) in a NSCLC patient that showed an investigator-reported 57% total tumor reduction at week 24.

Translational science analysis shows that peak expansion of cytokine-secreting cNeT at day 21 was coincident with signs of systemic immune activation including increased serum IL-6. Stable disease was observed in five NSCLC patients through week 12, with two patients remaining stable beyond weeks 15 and 26. Further characterization of cNeT using single cell RNA and TCR-seq suggests that cNeT products are polyclonal, with reactive T cell clusters bearing signatures of T cell proliferation, cytokine secretion, and tissue migration.