{
  "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": 51,
  "pageCount": 366,
  "prevPage": 50,
  "nextPage": 52,
  "slideType": "villain_critique",
  "function": "name_villain",
  "density": "dense",
  "nDataPoints": 9,
  "notes": "The slide uses a quote from a 2004 NEJM paper to establish a precedent of drug withdrawal, then links the molecular structure (piperidine ring) and receptor activity of pitolisant to these withdrawn drugs.",
  "elementsJson": [
    "paragraph",
    "quote_block",
    "footnote"
  ],
  "metadataConfidence": 0.95,
  "imagePath": null,
  "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/51",
  "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17",
  "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json",
  "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-51",
  "components": [
    {
      "bbox": null,
      "kind": "callout",
      "text": "Drugs withdrawn from market due to QT prolongation share similarities with pitolisant",
      "attrs": null,
      "subkind": null,
      "toolName": "Visual emphasis",
      "toolSlug": "visual-emphasis",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9ccc-c9354d31f582",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.42,
        "w": 0.86,
        "x": 0.07,
        "y": 0.07
      },
      "kind": "paragraph",
      "text": "The NEJM paper is a seminal one but published in 2004, and listed nine drugs withdrawn as of then due to cardiotoxicity and QT prolongation. Two of the nine were histamine receptor antagonists, as is pitolisant, and the molecular structure of all three is defined by a piperidine ring, the significance of which we shall explain. Most of the others that were recalled also have other troubling similarities to Harmony’s drug. Another four of the nine either involved histamine antagonist activity or targeted adjacent neurotransmitters: droperidol was a dopamine receptor antagonist but had histamine antagonist activity; sertindole was a dopamine and serotonin antagonist; cisapride was a serotonin receptor antagonist; and lidoflazine, which contained a piperazine ring in its molecular structure - closely related to the piperidine ring in pitolisant and which has similar binding behavior.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "2c16aa33-b535-4908-a504-dc1ef8648ee4",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.32,
        "w": 0.86,
        "x": 0.07,
        "y": 0.58
      },
      "kind": "quote",
      "text": "IN THE PAST DECADE, THE SINGLE MOST COMMON CAUSE OF THE WITHDRAWAL OR RESTRICTION OF THE USE OF DRUGS THAT HAVE ALREADY BEEN MARKETED HAS BEEN THE PROLONGATION OF THE QT INTERVAL ASSOCIATED WITH POLYMORPHIC VENTRICULAR TACHYCARDIA, OR TORSADE DE POINTES (FIG. 1), WHICH CAN BE FATAL.1 NINE STRUCTURALLY UNRELATED DRUGS THAT WERE MARKETED IN THE UNITED STATES OR ELSEWHERE FOR A RANGE OF NONCARDIOVASCULAR INDICATIONS HAVE BEEN REMOVED FROM THE MARKET OR HAD THEIR AVAILABILITY SEVERELY RESTRICTED BECAUSE OF THIS RARE FORM OF TOXICITY. THESE DRUGS ARE TERFENADINE, ASTEMIZOLE, GREPAFLOXIN, TERODILINE, DROPERIDOL, LIDOFLAZINE, SERTINDOLE, LEVOMETHADYL, AND CISAPRIDE.",
      "attrs": null,
      "subkind": "pull-quote",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "cb49e844-725f-45f3-bf37-f60070922e42",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": null,
      "kind": "quote",
      "text": "IN THE PAST DECADE, THE SINGLE MOST COMMON CAUSE OF THE WITHDRAWAL OR RESTRICTION OF THE USE OF DRUGS THAT HAVE ALREADY BEEN MARKETED HAS BEEN THE PROLONGATION OF THE QT INTERVAL ASSOCIATED WITH POLYMORPHIC VENTRICULAR TACHYCARDIA, OR TORSADE DE POINTES (FIG. 1), WHICH CAN BE FATAL. — NEJM (2004)",
      "attrs": null,
      "subkind": null,
      "toolName": "Authority citation",
      "toolSlug": "authority-citation",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9ccc-cca7a8c3d2c6",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.04,
        "w": 0.5,
        "x": 0.07,
        "y": 0.94
      },
      "kind": "source-note",
      "text": "Source: https://www.washingtonpost.com/archive/politics/1997/12/30/seldane-to-be-taken-off-us-market-by-maker/69d37826-3c40-49b1-8167-06c9c8b191b0/",
      "attrs": null,
      "subkind": null,
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "7f714a98-badf-46f1-bc5c-884b9fd45147",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.03,
        "w": 0.75,
        "x": 0.07,
        "y": 0.52
      },
      "kind": "title",
      "text": "Drugs withdrawn from market due to QT prolongation share similarities with pitolisant",
      "attrs": null,
      "subkind": "headline",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "9976f2d0-f991-4b65-bfb9-af0e79a91667",
      "frameworkName": null,
      "frameworkSlug": null
    }
  ],
  "metrics": [],
  "tools": [],
  "frameworks": [
    {
      "name": "antagonist-introduction",
      "slug": null,
      "matchId": "c196adcc-f05c-48a1-a94a-d6fe4eaff721",
      "evidence": "The slide explicitly links the target drug (pitolisant) to a list of withdrawn drugs (villains) based on shared structural and pharmacological traits.",
      "confidence": 0.9
    }
  ],
  "arcBeats": [
    {
      "to": 70,
      "from": 51,
      "beatId": "f412f440-0381-4eb7-b9f4-292dcebd62be",
      "arcName": "Overcoming the Monster",
      "arcSlug": "overcoming-monster",
      "beatName": "The Victory",
      "beatSlug": null,
      "evidence": "The document presents the conclusion that the company is a house of cards",
      "position": 3,
      "confidence": 0.8,
      "parentBeatName": null,
      "parentBeatSlug": null
    }
  ],
  "loops": [
    {
      "to": 60,
      "from": 50,
      "name": "The Reveal",
      "slug": "05-the-reveal",
      "bestFor": "Product launches, strategic pivots, unexpected findings",
      "matchId": "38dece92-a555-4683-9dd1-5ac3416bf9fd",
      "evidence": "The document presents a detailed analysis of the company's problems",
      "position": 1,
      "objective": "To reveal the extent of the company's problems",
      "structure": "Setup the Question -> Build Suspense -> The Big Reveal",
      "confidence": 0.8,
      "description": "Build mystery and anticipation, then deliver a surprising or powerful conclusion"
    }
  ],
  "imagePathAlt": null,
  "thumbSrc": null,
  "thumbSrcAlt": null,
  "locked": true
}