{ "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": 80, "pageCount": 366, "prevPage": 79, "nextPage": 81, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 6, "notes": "The slide uses a primary text block to summarize the contradiction, followed by a direct excerpt from a 2008 paper as evidence.", "elementsJson": [ "paragraph", "callout_box" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/80", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-80", "components": [ { "bbox": { "h": 0.03, "w": 0.86, "x": 0.07, "y": 0.59 }, "kind": "callout", "text": "2008 paper by Abbott researchers indicates they tested pitolisant and that it was a disaster", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "c52bcc00-5bd3-4d48-9d78-95efc3f45d63", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "callout", "text": "Their comments are remarkable and indicated that pitolisant is a total failure on all dimensions: pharmacokinetics, efficacy, and safety.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cce-f5f1ef561cf5", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.45, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "paragraph", "text": "The paper cited a 2008 publication by scientists at Abbott, which we located and is one of the most cited in the field – and we further spoke to a scientist who was closely involved in Abbott’s efforts, which we shall detail. The authors make it clear that they synthesized pitolisant in their lab, as the structure had already been published. Their comments are remarkable and indicated that pitolisant is a total failure on all dimensions: pharmacokinetics, efficacy, and safety. They state that the 84% oral bioavailability claims in Bioprojet’s key 2007 paper – absurdly, only based on an animal study – “were not replicated in our lab (with 30, 5, and 2% bioavailability in mice, rat, and dog).” They add that “this limited oral bioavailability questions the data related to the ability of BF2.639 to increased [sic] histamine brain levels after oral administration” as well as their claims in another key paper. They further indicate severe toxicity: “our laboratory findings suggest that CYP2D6 inhibition, potent hERG binding and the potential for phospholipidosis would likely be important hurdles.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "538c4443-f61a-45b8-8b09-e02247964c50", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.28, "w": 0.86, "x": 0.07, "y": 0.63 }, "kind": "paragraph", "text": "Pharmacokinetic parameters measured by a radioreceptor assay indicated that BF2.649 exhibits 84% oral bioavailability in mice. However, these data were not replicated in our lab (with 30, 5 and 2% bioavailability in mice, rat and dog). One recent report indicated a 2-h half-life and good brain penetration in mice using a superior analytical assay but no detailed pharmacokinetic parameters were provided (Ligneau et al., 2007a). This limited oral bioavailability questions the data related to the ability of BF2.649 to increased histamine brain levels after oral administration in mice and the EEG studies conducted in cats. Further studies these species. BF2.649 is presently under clinical investigation in several Phase II trials for the treatment of schizophrenia, ADHD, dementia and Parkinson’s disease. (www.stanleyresearch.org/programs/trialgrants.htm). From the development point of view, our laboratory findings suggest that CYP2D6 inhibition, potent hERG binding and the potential for phospholipidosis would likely be important hurdles for this novel compound.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "e1efe999-48b7-4926-9486-7e2abb320ea5", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“were not replicated in our lab (with 30, 5, and 2% bioavailability in mice, rat, and dog).” — Abbott Researchers; “this limited oral bioavailability questions the data related to the ability of BF2.639 to increased [sic] histamine brain levels after oral administration” — Abbott Researchers; “our laboratory findings suggest that CYP2D6 inhibition, potent hERG binding and the potential for phospholipidosis would likely be important hurdles.” — Abbott Researchers", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cce-fa3160a6d1c1", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.4, "x": 0.07, "y": 0.94 }, "kind": "source-note", "text": "Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483387/pdf/bjp2008147a.pdf", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "f281a056-dbba-4b01-9b55-3344fa6d3833", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [ { "name": "fraud-exposure", "slug": null, "matchId": "d8d568c4-8cab-44b8-87fa-b91fea09921f", "evidence": "The slide explicitly contrasts published claims with internal lab findings to suggest data manipulation or failure.", "confidence": 0.9 } ], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }