{ "docId": "019dd923-622c-750b-8b9a-21918ac10c17", "docSlug": "f3db2294dcf9", "documentTitle": "Harmony Biosciences (HRMY)", "authorId": "58_Scorpion_Capital", "authorName": "Scorpion Capital", "documentKindSlug": "research-note", "documentKindLabel": "Research note", "sourceTypeSlug": "short_seller", "sourceTypeLabel": "Short seller", "presentationDate": "2023-03-28 00:00:00", "orientation": "landscape", "aspectRatio": 1.3333334, "pageNumber": 79, "pageCount": 366, "prevPage": 78, "nextPage": 80, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 0, "notes": "The slide uses a forensic literature review approach to highlight historical concerns about the drug's safety profile (cardiotoxicity, bioavailability, etc.) that were allegedly ignored or suppressed.", "elementsJson": [ "paragraph", "screenshot" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/79", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-79", "components": [ { "bbox": { "h": 0.05, "w": 0.86, "x": 0.07, "y": 0.58 }, "kind": "callout", "text": "2010 review paper on H3 receptor compound programs indicated threw cold water on pitolisant", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "a9d63257-1b91-420d-91f4-bfdf0686b8d4", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "callout", "text": "The development and druggability of tiprolisant (BF2.649 5), reportedly in Phase II clinical trials for a number of potential indications, including cognitive enhancement, have been questioned, since it had limited oral bioavailability, was a potent inhibitor of CYP2D6 and hERG, and also had the potential for inducing phospholipidosis, possibly due to the high clogP (4.8) [76].", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9ccf-50dc124a6c94", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.45, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "paragraph", "text": "Although Harmony and Bioprojet claim pitolisant is effective and safe, our research uncovered devastating, long-buried evidence that other large pharma companies synthesized pitolisant and concluded that it is plagued by severe problems including cardiotoxicity - and that the claims in Bioprojet’s seminal paper could not be replicated in their labs or others. Although pitolisant was approved in the US in 2019, it is a quarter-century old compound - Bioprojet’s key papers were published in the mid-2000’s, and the trials upon which it received FDA approval are circa-2010. Most of the research in the space dates to the 1990’s and 2000’s, after which it fell off a cliff as pharma companies fled after widespread failures. As past of our forensic literature review, we first noted a few lines in a 2010 paper that indicated that “the development and druggability of tiprolisant (BF2.649)” has “been questioned, since it had limited oral bioavailability, was a potent inhibitor of CYP2D6 and hERG, and also had a high potential for inducing phospholipidosis....” – tiprolisant was an earlier name for pitolisant.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "6ff8bac9-8547-48d3-b2c5-dfd8a7696445", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.18, "w": 0.86, "x": 0.07, "y": 0.71 }, "kind": "paragraph", "text": "shorter brain residence time [44]. The development and druggability of tiprolisant (BF2.649 5), reportedly in Phase II clinical trials for a number of potential indications, including cognitive enhancement, have been questioned, since it had limited oral bioavailability, was a potent inhibitor of CYP2D6 and hERG, and also had the potential for inducing phospholipidosis, possibly due to the high clogP (4.8) [76].", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "78165a7b-3481-45a5-956f-147f057286a2", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“the development and druggability of tiprolisant (BF2.649) has been questioned, since it had limited oral bioavailability, was a potent inhibitor of CYP2D6 and hERG, and also had a high potential for inducing phospholipidosis….” — 2010 review paper on H3 receptor compound programs", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9ccf-5414cd395893", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.25, "x": 0.07, "y": 0.92 }, "kind": "source-note", "text": "Source: https://pubmed.ncbi.nlm.nih.gov/20166960/", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "29a6ada6-ecda-463f-87e2-39024f85ecac", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.06, "w": 0.86, "x": 0.07, "y": 0.63 }, "kind": "title", "text": "Histamine H3 Antagonists for Treatment of Cognitive Deficits in CNS Diseases", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "2bfcb779-4315-4b50-a98b-410c3e6bd5d3", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [ { "name": "fraud-exposure", "slug": null, "matchId": "0b2c8c1e-df42-4f15-9096-d31aaabf41fb", "evidence": "The slide explicitly contrasts corporate claims with historical scientific literature to expose potential deception.", "confidence": 0.9 } ], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }