Curated AI beats frontier LLMs at pharma asset discovery

Historical medical archives and traditional medicines hold immense potential for drug discovery and remain a primary source for current drug development. However, pre-ontological prose and idiosyncratic taxonomies prevent the standardization and medical modernization of the data for use in current biomedical pipelines. Furthermore, no existing LLM agent system, whether tool-calling, retrieval-augmented, or agentic deep-research, can convert such text into verifiable drug-discovery leads at scale. We close this gap with DeepRoot, a multi-agent LLM system that jointly builds and utilizes a verified knowledge graph, showing that grounding and reasoning -- often conflated -- are separable axes the system can compose for therapeutic reasoning. Applied to the Shen Nong Ben Cao Jing, DeepRoot recovers $10$ of $21$ held-out compound-disease treatment pairs at R@$20$ ($47.6\%$ vs $4.8\%$ for a raw corpus LLM and $\sim\!2.4\%$ random) and dominates an LLM-as-judge audit for reasoning quality over baseline LLMs and LLMs with direct tool-call access to the same APIs DeepRoot itself queries. Tool-using LLMs hallucinate evidence on $87\%$ of claims, versus 7-10% for DeepRoot. Graph-only inference hallucinates $0\%$ but ranks lowest on reasoning coherence; DeepRoot KG+LLM is the only condition to win on both axes, pointing toward a route for systematic mining and repurposing of historical medical knowledge.

Artificial intelligence (AI) agents promise to accelerate drug discovery by compressing interpretation and decision-making loops, but practical deployment requires trusted evaluation on realistic program decisions. We introduce TherapeuticsBench Preclinical Pharmacology (TxBench-PP), a verifiable benchmark for small-molecule preclinical pharmacology and the first focused slice of a broader TherapeuticsBench effort across drug-discovery stages and therapeutic modalities. TxBench-PP tests whether agents can recover accurate conclusions from real-world assay data rather than memorized facts from literature. The benchmark contains 100 evaluations indexed by program stage, assay type, and task structure, spanning mechanism-of-action (MoA) and pharmacodynamic (PD) reasoning, compound-target engagement, causal target validation, developability and safety, and translational efficacy. Agents receive realistic workflow snapshots, inspect files in a coding environment, and return structured answers graded deterministically. Across 16 model-harness configurations, comprising 11 models and 4,800 trajectories, no system reliably recovered preclinical pharmacology decisions. The strongest configuration, Claude Opus 4.8 / Pi, passed 59.3% of endpoint attempts (178/300; 95% CI, 51.1-67.6), followed by GPT-5.5 / Pi at 55.3% (166/300; 47.0-63.6).

Agentic large language model (LLM) systems are reshaping scientific workflows in chemistry and drug discovery, but evaluating their open-ended, tool-augmented outputs remains a fundamental bottleneck. The LLM-as-a-Judge paradigm has emerged as a scalable alternative, but existing drug discovery benchmarks deploy LLM judges without validating their alignment with human experts. In this work, we present an LLM-as-a-Judge evaluation framework for ChatInvent, an agentic drug discovery assistant deployed at AstraZeneca, with five contributions. First, we define four output-quality evaluation dimensions---Completeness, Relevancy, Structural Clarity, and Scope Adherence---alongside deterministic Tool Call Correctness checks. Second, we validate the judge through a human alignment study with five expert annotators, comparing Gemini 3.1 Pro, Claude Opus 4.7, GPT-5, and Llama 3.1 70B as candidate judges. Third, we optimize the best-performing judge using few-shot demonstrations of human-annotated examples, improving alignment with the human majority vote from 0.80 to 0.86. Fourth, applying the optimized judge to 70 held-out questions, we surface concrete limitations and find no strong evidence that informal phrasing degrades output quality; it may, however, still be helpful to have the LLM rewrite the original question before querying the agent. Finally, we extend the framework to 38 adversarial questions that are ambiguous, invalid, out-of-scope or ethically sensitive, and show that the agent's refusal behavior is guided by the stated intent of a request. Our framework provides a reusable template for human-aligned evaluation of agentic systems in scientific domains.