{
  "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": 150,
  "pageCount": 366,
  "prevPage": 149,
  "nextPage": 151,
  "slideType": "preempt_rebuttal",
  "function": "preempt_rebuttal",
  "density": "dense",
  "nDataPoints": 3,
  "notes": "The slide uses a specific calculation (153 ng/mL * 4 * 2 = 1224 ng/mL) to quantify risk.",
  "elementsJson": [
    "paragraph",
    "bullet_list",
    "footnote"
  ],
  "metadataConfidence": 1,
  "imagePath": null,
  "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/150",
  "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17",
  "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json",
  "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-150",
  "components": [
    {
      "bbox": {
        "h": 0.06,
        "w": 0.45,
        "x": 0.07,
        "y": 0.44
      },
      "kind": "callout",
      "text": "Common antihistamines and antidepressants are CYP2D6 inhibitors e.g, Benadryl, Claritin, Prozac",
      "attrs": null,
      "subkind": "primary",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "dc4772f0-bd9e-4896-9fb0-47b52139851e",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.06,
        "w": 0.38,
        "x": 0.55,
        "y": 0.44
      },
      "kind": "callout",
      "text": "Paper indicates all five common antihistamines are strong CYP2D6 inhibitors",
      "attrs": null,
      "subkind": "primary",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "ddafff0a-fbc4-4020-acf9-8054cf8ef34e",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": null,
      "kind": "callout",
      "text": "At a potential 4X increase, patients would be hit 153 ng/mL times 4 (fold change at 90% CI per the label for poor metabolizers) times 2 (Harmony’s claimed fold change in the presence of CYP2D6-inhibiting drugs), which equals 1224 ng/mL – a red-alert level for cardiotoxicity.",
      "attrs": null,
      "subkind": null,
      "toolName": "Visual emphasis",
      "toolSlug": "visual-emphasis",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9cd5-ae67e5f417ee",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.35,
        "w": 0.45,
        "x": 0.07,
        "y": 0.51
      },
      "kind": "list",
      "text": "Amiodarone, Bupropion, Chlorpheniramine, Chloroquine, Chlorpromazine, Cinacalcet, Diphenhydramine, Duloxetine, Fluoxetine, Halofantrine, Haloperidol, Imatinib, Paroxetine, Perphenazine, Propafenone, Propoxyphene, Quinidine, Quinine, Terbinafine",
      "attrs": null,
      "subkind": "bullet",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "7e40b0e2-c046-444c-93bf-d1571fe5ac79",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.35,
        "w": 0.86,
        "x": 0.07,
        "y": 0.07
      },
      "kind": "paragraph",
      "text": "We further note an inevitable combination which further escalates the danger: patients that are already poor CYP2D6 metabolizers who are concurrently taking a CYP2D6 inhibiting drug like an SSRI or common OTC antihistamines.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "48923c9d-89c0-4a97-b7e1-8823fcba3d0d",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.15,
        "w": 0.38,
        "x": 0.55,
        "y": 0.51
      },
      "kind": "paragraph",
      "text": "Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes. Conclusion: All five H1-antihistamines studied inhibited CYP2D6 markedly...",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "e7a8c34f-685f-4908-8fa4-a8c46cae2f1f",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": null,
      "kind": "quote",
      "text": "Conclusion: All five H1-antihistamines studied inhibited CYP2D6 markedly... — Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes",
      "attrs": null,
      "subkind": null,
      "toolName": "Authority citation",
      "toolSlug": "authority-citation",
      "confidence": null,
      "componentId": "019dd953-64d0-7099-9cd5-b05aa5ac7082",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.03,
        "w": 0.5,
        "x": 0.07,
        "y": 0.94
      },
      "kind": "source-note",
      "text": "Source: https://www.pharmacytimes.com/view/2009-03-10041; https://pubmed.ncbi.nlm.nih.gov/11936702/",
      "attrs": null,
      "subkind": null,
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "d2bb9f94-5142-42e4-9e35-dea84a4c3e51",
      "frameworkName": null,
      "frameworkSlug": null
    }
  ],
  "metrics": [],
  "tools": [],
  "frameworks": [],
  "arcBeats": [],
  "loops": [],
  "imagePathAlt": null,
  "thumbSrc": null,
  "thumbSrcAlt": null,
  "locked": true
}