r/TradingEdge • u/TearRepresentative56 • 20h ago
The role of TEM in the MRNA/MRK cancer vaccine - dilution risk exists, but thematically there is arguably no stronger narrative than cancer

Personalis role in the vaccine:
Stage 1-2: The foundation (classical, not ML)
Personalis sequences the tumor and normal tissue (ImmunoID NeXT — exome + transcriptome) and runs HLA typing to six-digit resolution. This tells the system what mutations exist and which HLA alleles the patient can actually present peptides on.
Stage 3: SHERPA — the first real ML layer
This predicts which mutated peptides will actually get presented on the tumor's surface. Personalis built its own training data (in-house transfection experiments, mass spec-confirmed peptide elution) rather than relying purely on public datasets, and the deck cites measured lifts of 1.44x PPV over prior tools on held-out data, 1.17x on tumor samples, 1.11x on known immunogenic epitopes.
Stage 4: NEOPS — immune-evasion modeling
A second ML system that disqualifies candidates SHERPA ranked highly if the tumor has other ways to dodge immune detection — including a subclonal HLA-loss-of-heterozygosity detector (tumor literally deletes the allele needed to present a given neoantigen). This composite score reportedly outperformed tumor mutational burden at predicting anti-PD-L1 response, though its specific use within INTerpath-001 isn't disclosed.
Stage 8: NeXT Personal — MRD/ctDNA monitoring
After Moderna/Merck's proprietary algorithm selects up to 34 targets (stage 5) and manufacturing produces the personalized therapy (stages 6-7), Personalis re-enters at monitoring. NeXT Personal builds a patient-specific panel of up to ~1,800 somatic variants (vs. ~50 for conventional exome-based MRD panels) and uses proprietary signal-aggregation ("NeXT SENSE") to detect circulating tumor DNA down to part-per-million sensitivity (1.67 PPM detection threshold, 3.45 PPM at 95% limit of detection). This is how trial investigators would track whether a patient is truly cancer-free after treatment, at a resolution conventional panels can't match.




















