Max Goulazian

Target to a designed binder in one week. The full immuno-oncology discovery arc — target ID, a genome-scale counter-screen, a 1.65M-edge network, a whole-body QSP model, and de novo protein design — that normally takes a multidisciplinary team 1–4.5 years, run by one scientist directing Claude. ≈60–270× faster. CD3 T-cell engagers deliver signal 1 but no costimulation, so responses exhaust and fade. Adding a CD28 or 4-1BB arm fixes that — but because the engager grips CD3 on every T cell, it amplifies the CD4 programs that drive cytokine-release syndrome and expand suppressive Tregs. Which costim arm boosts killing without feeding toxicity? We answer it mechanistically. We turned the Marson/Pritchard genome-scale CD4⁺ CRISPRi Perturb-seq screen into a three-axis scoring instrument — effector benefit (from a matched CD8 screen), Treg/IL-10 suppression liability, and CRS-cytokine liability — then fed all three into a whole-body single-cell spatial PBPK/QSP model: 21 tissues gridded at real single-cell resolution (~1.9M cells), every cell an agent running Rhoden bivalent binding kinetics, mechanistic per-myeloid IL-6 with zero fitted scale, validated against 20+ clinical engagers. The verdict: 4-1BB and CD27 co-lead; CD28 is gated out on CRS and Treg liability. We then in-silico-designed binders (RFdiffusion→ProteinMPNN→AlphaFold3) against the winners — a bench-ready next step.

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