Achilles Therapeutics plc announced interim Phase I/IIa data on the use of clonal neoantigen reactive T cells (cNeT) from the CHIRON study in advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and the THETIS study in recurrent or metastatic malignant melanoma. The update includes data from 18 patients across CHIRON (n=12) and THETIS (n=6) dosed since the previous interim update in December 2022, with two CHIRON patients and one THETIS patient having received enhanced chemo-conditioning and IL-2 dosing aligned to standard tumor infiltrating lymphocyte (TIL) therapy (enhanced host conditioning) in a new Cohort C. This new Cohort C will allow the impact of enhanced host conditioning on cNeT engraftment and persistence beyond 28 days to be evaluated. All trial participants were late-stage, checkpoint refractory patients with progressive disease at the time of lymphodepletion.

The observed tolerability profiles remain favorable and similar to standard TIL therapy. The VELOS? manufacturing process continued to improve with a median 172 million cNeT dosed across the eighteen patients in the update compared to 18 million cNeT in the December 2022 update, with 10 products over 100 million cNeT and five over one billion cNeT.

Summary of new patients treated since the previous update: 18 new patients treated since the last update (12 NSCLC in CHIRON, 6 melanoma in THETIS) with a median of two prior lines of therapy; Data update includes two CHIRON Cohort C (enhanced host conditioning), one THETIS Cohort C and two THETIS Cohort B patients (checkpoint combination); Median cNeT dose of 172 million in the 18 patients reported since the last update with 10 of 18 patients dosed with over 100 million cNeT, including five products over one billion cNeT. Continued favorable tolerability profile for cNeT: Tolerability observations for cNeT compare well with standard TIL therapy; Lymphopenia and neutropenia were the most common adverse events, which are principally associated with the conditioning regimen, and no dose limiting high-grade toxicities were observed. 25% of higher dose (>100M cNeT) patients in CHIRON and THETIS (3 of 12) demonstrated stable disease with some reduction in tumor volume: No new objective responses were observed, which is believed to relate to a lack of cNeT persistence with the previous host-conditioning regimen using lower lymphodepletion and IL-2 compared to standard TIL therapy; Early and significant peaks of cNeT, similar to standard TIL therapy, were observed in the blood of patients receiving reduced intensity conditioning, though with a lack of consistent cNeT persistence beyond 28 days.

Enhanced host conditioning cohort opened in CHIRON and THETIS: Enhanced host conditioning protocol Cohort C has been added to CHIRON and THETIS to evaluate an enhanced regimen of increased lymphodepletion intensity and increased IL-2 dosing on cNeT persistence and hence potentially clinical activity; All three patients dosed using the enhanced host conditioning regimen have shown improvement in cNeT engraftment and some tumor reduction in one case; TCR tracking shows more durable cNeT engraftment beyond week six in the first patient treated with enhanced host-conditioning regimen; A further eight patients are currently under observation with products ready for dosing with a cNeT product. VELOS Manufacturing process further enhanced: 172 million median cNeT dose for the last 18 patients in this update compared to a median of 18 million cNeT in the December 2022 update; The last 10 products manufactured have delivered a median cNeT dose of 611 million.