Iovance Biotherapeutics Inc (IOVA)

[jondoeuk]

Achilles Therapeutics is running two trials in melanoma (NCT03997474) and NSCLC (NCT04032847). In H2 they will have interim-efficacy read-outs, in Q4 2021 full clinical read-outs and in the same quarter will open PhI/II trials for follow-on indications (H&N, TNBC, bladder and/or RCC). In H1 2022 they should open registration directed trials in both melanoma and NSCLC.

After sequencing tumour and blood they use the PELEUS bioinformatics platform* to identify clonal neoantigens (generated early in a cancers' evolution and therefore expressed across many, if not all, subclones). Clonal neoantigen peptides are made and get co-cultured with the patients own APCs (monocyte derived dendritic cells) and then T-cells. After this, neoantigen-specific responses are detected by looking at different data, such as cytokine production. Once found they selectively expand this population. The product contains both CD4+/CD8+ [1,2] subtypes and are likely of the ''younger'' stem central memory and/or central memory phenotype [3,4].

* (This has been trained on data obtained from TRACERx. TRACERx has been the largest ever longitudinal study of tumour evolution in NSCLC and started back in '14. A network of 15 NHS clinical sites will deliver over 840 patients (30,000 biological samples collected to date) with harmonised therapeutic protocols (deep whole-exome sequencing across multi-regions and multi-times). It is more than 3X larger than the TCGA.)

Refs:
1 https://www.jimmunol.org/content/174/5/2591
2 https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201343718
3 https://www.nature.com/articles/nm.4241
4 https://www.pnas.org/content/102/27/9571.long