Methodology

Probability of Success — the full framework reference

The end-to-end documentation of how Asclepius computes cumulative likelihood of approval. Every multiplier in the chain is cited; every magnitude is grounded in either a peer-reviewed paper or a primary industry source; deviations from the published literature are explicit.

Reflexivity-adjusted Probability of Success

Sponsor capital position structurally adjusts a clinical asset's probability of success. This is the headline methodology choice in Asclepius and the differentiator versus textbook rNPV.

Risk-adjusted NPV — phase-gated cash flows, Monte Carlo priors, and discount conventions

The full mechanics of how Asclepius computes risk-adjusted NPV. Documents the phase-gated cash-flow structure, the four Monte Carlo prior distributions, the mid-year discount convention, and the closed-form-vs-simulation relationship. Every methodology choice is cited or labeled as analytical convention.

8-pillar diligence scorecard — the qualitative overlay on the quantitative core

Documents the 8 pillars Asclepius uses to convert qualitative diligence judgments into a single weighted score and a recommendation tier. Seven pillars are practitioner-standard biotech BD scorecard items; the 8th (computational infrastructure) is the framework's novel contribution. Documents the red-flag auto-cap and green-flag boost mechanics, and consolidates the methodology's Known Limitations.

Worked example — Adagrasib retrospective backtest

Applies the Asclepius framework to adagrasib (Mirati Therapeutics) using only public information available before the KRYSTAL-12 Phase 3 readout (June 2022 cutoff). Framework outputs reconstruct the BMS $4.8B acquisition price (October 2022) within ~5%.

Signaling equilibrium — the formal foundation of the reflexivity adjustment

Derives the reflexivity-adjusted PoS framework from Spence (1973) signaling theory. Maps the costly-signal mechanism onto clinical trial design and cites the modern empirical evidence that strategic-disclosure behavior is operative in the pharmaceutical industry.

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Memo synthesis — what makes a recommendation defensible

A number is not a recommendation. This writeup states the discipline the memo agent enforces: a defensible call carries an explicit conviction level, a verdict on how the structural path-dependencies moved it, a priced close, and a falsifiable kill criterion. The schema forces all four — a memo cannot come back without them.

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Supply constraint as a valuation path-dependency

Manufacturing and raw-material supply constraints are a structural value-and-risk driver adjacent to reflexivity. They add trial-execution risk (a PoS effect) and, distinctively, cap achievable peak sales (an rNPV ceiling). Most rNPV tools price only the demand side of peak sales; Asclepius prices the supply side too.