{"data":{"event":{"id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","slug":"rentosertib-ipf-phase-2a","title":"Rentosertib, an AI-designed TNIK inhibitor, posts Phase 2a IPF results","short_summary":"Insilico Medicine’s rentosertib (ISM001-055), discovered with generative models, met a Phase 2a safety endpoint in 71 IPF patients; the 60 mg daily arm showed a mean FVC gain of 98.4 ml versus a 20.3 ml decline on placebo.","full_description":"Nature Medicine published the randomized Phase 2a trial on 3 June 2025 after November 2024 topline results. The 12-week China multicenter study reported similar treatment-emergent adverse-event rates across arms, with discontinuations mainly for liver toxicity or diarrhea. FVC improvement at the highest dose is a secondary signal in a small sample and does not establish an approved therapy. Earlier Nature Biotechnology (2024) described AI-based target and molecule design on Insilico’s Pharma.AI stack.","ledger_type":"benefit","primary_domain_id":"c09546b6-10f8-48df-8347-0c1979416464","event_status":"verified","event_date":"2025-06-03T00:00:00.000Z","discovery_date":"2025-06-03T00:00:00.000Z","first_published_date":"2025-06-03T00:00:00.000Z","last_reviewed_date":"2026-10-28T00:00:00.000Z","geographic_scope":"China trial sites; global IPF research","affected_population":"71 trial participants; IPF research community","base_impact_tier":2,"base_score":"3.00","attribution_multiplier":"0.5000","evidence_multiplier":"0.7000","realization_multiplier":"0.5500","durability_multiplier":"0.5000","current_event_score":"0.173300","confidence_level":"high","score_explanation":"A peer-reviewed Phase 2a of an AI-designed first-in-class small molecule is Notable (tier 2) until Phase 3, approval, or a documented patient-outcome effect. Attribution is shared with human chemistry and clinical work (0.50). Peer review raises evidence, not the base tier. Realization is Phase 2a, not approval. Durability uncertain pending larger trials.","methodology_version_id":"8745541b-0f8e-4d5a-9b47-5291d3813a8d","original_methodology_version_id":"d7881163-fb23-4e71-8625-bac1a8662c0f","published_at":"2025-06-03T00:00:00.000Z","created_at":"2026-09-13T20:47:20.075Z","updated_at":"2026-10-28T20:22:47.621Z","flags":[],"domain_name":"Medicine & Health","domain_slug":"medicine-health","methodology_version":"0.2"},"contributions":[{"id":"b1657be7-cc6f-4472-b001-d22ef520fd4d","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":"e2ddaacb-78bf-4ce5-b724-62ed364ff597","role_description":"Used for TNIK target nomination and generative chemistry leading to rentosertib.","attribution_multiplier":"0.5000","credit_share":"0.6000","contribution_score":"0.173300","attribution_rationale":"Company and papers attribute design to generative AI plus substantial medicinal chemistry and clinical execution.","attribution_confidence":"medium","first_used_date":"2021-01-01T00:00:00.000Z","model_version_if_known":null,"review_status":"approved","created_at":"2026-09-13T20:47:20.075Z","model_slug":"pharma-ai-internal-research-model","model_name":"Pharma.AI Internal Research Model","identity_class":"internal_unreleased","is_internal":true,"family_name":"Pharma.AI","family_slug":"insilico-medicine-pharma-ai","organization_name":"Insilico Medicine","organization_slug":"insilico-medicine"}],"sources":[{"id":"c4f038b2-3add-443e-8df8-dee103e06589","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","url":"https://www.nature.com/articles/s41587-024-02143-0","canonical_url":"https://www.nature.com/articles/s41587-024-02143-0","source_type":"peer_reviewed","publisher":"Nature Biotechnology","author":null,"publication_date":"2024-03-12T00:00:00.000Z","retrieved_at":"2026-09-13T20:47:20.075Z","title":"A small-molecule TNIK inhibitor targets fibrosis in preclinical and Phase I studies","excerpt":null,"content_hash":null,"source_reliability_class":"high","is_primary_source":true,"is_independent":true,"is_peer_reviewed":true,"archived_url":null,"created_at":"2026-09-13T20:47:20.075Z"},{"id":"f1005a0f-e2a2-4394-8198-6e94d32e64cd","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","url":"https://www.nature.com/articles/s41591-025-03743-2","canonical_url":"https://www.nature.com/articles/s41591-025-03743-2","source_type":"peer_reviewed","publisher":"Nature Medicine","author":null,"publication_date":"2025-06-03T00:00:00.000Z","retrieved_at":"2026-09-13T20:47:20.075Z","title":"A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial","excerpt":null,"content_hash":null,"source_reliability_class":"high","is_primary_source":true,"is_independent":true,"is_peer_reviewed":true,"archived_url":null,"created_at":"2026-09-13T20:47:20.075Z"},{"id":"c2d8db90-8ec6-4c62-a8fe-db4bcffebb3c","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","url":"https://news.google.com/rss/articles/CBMiowFBVV95cUxPWmlQcE1ZOWNkVDRWQVA1OWpKWDlWN090LUJhQjd4emtWdDRTMGlnSjBOTWVqMDdKUG5DSzFTSjVfeUVJa0kwemNpQXVvcXA3WDVlaC03OGxaU1habXJialZrY1lDRTNzcEp6d0ZfSnZuWmpZeUdYN0RqQTktTmxOdFVhOFFtakJxRWtXdUt2QXNZUTlrNW9lbU5TZ21BV0pBWm9F?oc=5","canonical_url":"https://news.google.com/rss/articles/CBMiowFBVV95cUxPWmlQcE1ZOWNkVDRWQVA1OWpKWDlWN090LUJhQjd4emtWdDRTMGlnSjBOTWVqMDdKUG5DSzFTSjVfeUVJa0kwemNpQXVvcXA3WDVlaC03OGxaU1habXJialZrY1lDRTNzcEp6d0ZfSnZuWmpZeUdYN0RqQTktTmxOdFVhOFFtakJxRWtXdUt2QXNZUTlrNW9lbU5TZ21BV0pBWm9F?oc=5","source_type":"journalism","publisher":"Frontier lab incident news","author":null,"publication_date":"2026-09-18T00:00:00.000Z","retrieved_at":"2026-09-18T16:00:51.890Z","title":"Anthropic's Claude used to breach OpenAI's internal systems - Daily Sabah","excerpt":"Anthropic's Claude used to breach OpenAI's internal systems  Daily Sabah","content_hash":null,"source_reliability_class":"medium","is_primary_source":false,"is_independent":true,"is_peer_reviewed":false,"archived_url":null,"created_at":"2026-09-18T16:00:51.890Z"}],"claims":[{"id":"62ea9b69-091f-4b3f-b332-a0e4dbb2b516","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","claim_text":"Rentosertib was discovered using Insilico’s generative AI platform and completed a randomized Phase 2a IPF trial.","claim_type":"attribution","claim_status":"supported","confidence_score":null,"created_at":"2026-10-28T20:22:47.621Z","updated_at":"2026-10-28T20:22:47.621Z"},{"id":"e1e83d32-608a-4c28-93ea-3e57f3c17003","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","claim_text":"The 60 mg QD arm showed a mean FVC increase of 98.4 ml versus placebo decline of 20.3 ml over 12 weeks.","claim_type":"outcome","claim_status":"supported","confidence_score":null,"created_at":"2026-10-28T20:22:47.621Z","updated_at":"2026-10-28T20:22:47.621Z"},{"id":"8b64a43b-3758-43ba-ba00-6aa38175ab36","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","claim_text":"Rentosertib is an approved IPF therapy.","claim_type":"outcome","claim_status":"disputed","confidence_score":null,"created_at":"2026-10-28T20:22:47.621Z","updated_at":"2026-10-28T20:22:47.621Z"}],"revisions":[{"id":"b9ae8d66-908d-4565-977b-dc3b3540eafd","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.000000","new_score":"0.577500","previous_factors":{},"new_factors":{"evidence":0.7,"base_score":10,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Initial adjudicated seed score under methodology 0.1.","trigger_type":"seed","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-13T20:47:20.075Z"},{"id":"60e0e5c8-81a7-45aa-9474-2a28f5930373","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.577500","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-14T02:35:26.290Z"},{"id":"d005c876-4e5e-4da1-9a69-5acaa8d5e08c","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-17T00:37:09.904Z"},{"id":"631465a1-cdae-4bae-8460-596c549b0f4a","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{"tier":2,"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"new_factors":{"tier":2,"models":["e2ddaacb-78bf-4ce5-b724-62ed364ff597"],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Ingest update: added a follow-up source.","trigger_type":"ingest_update","trigger_source_ids":["c2d8db90-8ec6-4c62-a8fe-db4bcffebb3c"],"reviewer_id":null,"review_status":"published","created_at":"2026-09-18T16:00:51.957Z"},{"id":"00652918-5fea-462c-86c9-d6512885a477","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-18T19:11:40.608Z"},{"id":"6553d3c4-161b-4786-a5a6-2c2d40362beb","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-19T00:53:33.692Z"},{"id":"0206e955-ce77-49b3-8217-cbbc6029e92e","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-21T01:54:16.553Z"},{"id":"992e2fe4-815c-4d84-8d94-4614ad4809fa","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-06T23:04:40.642Z"},{"id":"a81cc583-63c2-44b8-95c8-b5214137c525","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-07T16:12:13.690Z"},{"id":"e0085670-ddaa-4f5e-abce-e0657f8ddcaa","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-11T00:50:27.558Z"},{"id":"b16f573a-3f20-43cc-bcc0-434dedc3ca08","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-11T00:51:25.860Z"},{"id":"565916e4-d797-45bf-a407-6384fb0c3dbb","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-21T19:26:46.597Z"},{"id":"c46e9a1d-5013-4b71-ab57-1b6a68860d63","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-24T18:59:49.597Z"},{"id":"4dd07633-270b-4939-915e-54f75ff4d626","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-27T20:16:14.720Z"},{"id":"dddc41c1-1690-43ad-9dc0-8c677fa3e5dd","event_id":"097115b6-7e20-4a63-a9ea-fb9f5e4944de","model_id":null,"previous_score":"0.173300","new_score":"0.173300","previous_factors":{},"new_factors":{"flags":[],"evidence":0.7,"base_score":3,"durability":0.5,"attribution":0.5,"realization":0.55},"change_reason":"Methodology 0.2: Phase 2a is Notable until Phase 3, approval, or a documented patient-outcome effect.","trigger_type":"editorial_import","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-10-28T20:22:47.621Z"}],"secondary":[{"name":"Biology","slug":"biology"},{"name":"Chemistry","slug":"chemistry"}]},"methodology_version":"0.1"}