The GENESIS Framework R20.4–R23.x extends the validated drift-modulated bistable ODE system (S,R,D) for chronic disease modeling with three major advances: (1) R21.1 demonstrates that therapeutic topology modulation is sequence-invariant — drug order and inter-drug gaps up to 120 days produce identical D_func shifts, separatrix positions, and healthy basin volumes, establishing a "Delta Paradox Analog" for sequential protocols; (2) R21.2 derives the system's analytical curl structure (curl = b·S − d·R) and quasi-potential landscape, characterizing GENESIS as a dominant-gradient bistable system suitable for energy-based world model interpretation; and (3) R22.0–R23.x map the β×η parameter landscape, confirming bistability across β∈[0,4], η∈[0,1.2] while revealing strong D_func compression (down to 0.203 at β=3, η=1) and analytically deriving S-nullcline curvature d²R/dS² = −2·e_eff(D)/b, which increases geometrically with damage accumulation. Key findings include: no hidden bifurcations in realistic parameter ranges; damage D as slow separatrix modulator rather than acute attractor switch (Altfall phenomenon); sub-additive topology modulation in Tier-1 combinations due to geometric saturation; and physiological safety of canonical η=0.5 (r0_eff negativity only at D=2.0, 4.8×D_func). The framework positions GENESIS as a mechanistic world model bridging nonlinear dynamics, systems biology, and LeCun's JEPA/energy-based architectures, with demonstrated parameter identifiability (r0 error 0.40%, k error 0.80%) enabling future data assimilation. Complete development documentation R20.4→R23.x, parameter tables, validation protocols, and analysis notebooks provided as open-access materials. **GENESIS R20.4–R23.x: Complete Development Documentation** This Zenodo record contains the full technical documentation and analysis notebooks for the GENESIS Framework evolution from Reference Architecture 1.1 (R20.4, Feb 2026) through R21.1 (Sequential Intervention Dynamics), R21.2 (Structural Analysis & Disease Landscape), and R22.0–R23.x (β×η Bifurcation Landscapes & Nullcline Curvature). **Core Scientific Contributions:** 1. **Sequence-Invariant Topology Modulation** (R21.1): ΔD_func identical across all 6 drug permutations and T_GAP∈[0,120] days — "GENESIS has no topological memory" 2. **Gradient-Dominant Bistable System** (R21.2): Analytical curl derivation enables quasi-potential disease landscape V(S,R); positions GENESIS as LeCun-class mechanistic world model with dX/dt ≈ −∇V(X) + small rotational term 3. **β×η Window Compression** (R22.0): D_func∈[0.203,0.66] across realistic ranges; no hidden bifurcations; separatrix drift accelerates at high damage-sensitization 4. **Geometric Sharpening** (R23.x): S-nullcline curvature d²R/dS² = −2·e_eff(D)/b explains clinically observed "abrupt" state transitions with disease progression **Files included:**- Complete R20.4–R23.x development documentation (PDF)- Colab-ready analysis notebooks (R21.1–R23.x)- Canonical parameter tables and validation protocols- Reviewer risk checklist (5+1 risks confirmed/characterized) **Keywords:** bistable dynamical systems, chronic disease topology, pharmacological compiler, ME/CFS, Long COVID, D_func threshold, separatrix dynamics, energy-based world models, LeCun JEPA, nonlinear systems biology **License:** Creative Commons Attribution 4.0 International**Publication Date:** March 2026**DOI:** 10.5281/zenodo.[your-number]