{ "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": 88, "pageCount": 366, "prevPage": 87, "nextPage": 89, "slideType": "villain_critique", "function": "name_villain", "density": "dense", "nDataPoints": 1, "notes": "Uses expert quotes to establish a 'villain' (the drug class/mechanism) and preemptively rebut its efficacy.", "elementsJson": [ "paragraph", "quote_block", "footnote" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/88", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-88", "components": [ { "bbox": null, "kind": "callout", "text": "H3 receptor drugs as a class are doomed by “huge patient-to-patient variability,” lack of bioavailability, and blood-brain barrier issues", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-43e7b1904a69", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "paragraph", "text": "He emphasized the severity of the drug development obstacles unique to H3 receptor compounds, which means that “you’ll never be able to take that product into a clinical program to bring a reasonable effect to the patient,” except by giving them an over-the-top toxic dose in the range of 30X the max dose on the pitolisant label, given the volume needed to overcome the “very, very low bioavailability.” He underscored the “huge patient-to-patient variability in terms of how it’s absorbed: “the biggest problem here is what we call DMPK, Drug Metabolism and Pharmacokinetics, the mechanism of action.” He added pitolisant is also doomed as “having the same problem” and that therefore “you will never see a significant effect, a reasonable and reproducible one.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "a55b6662-3c12-4268-8b88-e72511f0d668", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.12, "w": 0.86, "x": 0.07, "y": 0.8 }, "kind": "quote", "text": "Theirs is also having the same problem, all belonging to the H3-R inverse agonist kind of drug. And they are very simple, actually molecules, and they can have multiple indications. But the problem, if you don't solve it, it's basically that the bioavailability is extremely low. You will never see a significant effect, a reasonable and reproducible one.", "attrs": null, "subkind": "testimonial", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "4684ef30-2176-4fdf-8ae3-fa95fe9db937", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.25, "w": 0.86, "x": 0.07, "y": 0.48 }, "kind": "quote", "text": "The biggest problem of that molecule, the receptor, is interesting. The class is interesting. Narcolepsy is a huge need. Here is the problem. This product has a huge patient-to-patient variability in terms of how it's absorbed and how it actually passes the blood-brain barrier or moves past the blood-brain barrier. So, the biggest problem here is what we call the DDMPK, Drug Distribution and Metabolism, the mechanism of action. In a lab, it works wonderfully. In cells, it works, even in rat models, and we've even done models in dogs, and it works. The problem is in humans, the metabolism of such drug classes allows very high variability and very, very low bio-availability to reach even a 1% maximum. And that's why you'll never be able to take that product into clinical program to bring a reasonable effect to the patient, except that you have to give patients something like 900 grams of the drug because the bio-availability is too low, and the variability is very high.", "attrs": null, "subkind": "testimonial", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "5fce490a-c31f-4966-9cf2-551916124f6c", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "The biggest problem of that molecule, the receptor, is interesting. The class is interesting. Narcolepsy is a huge need. Here is the problem. This product has a huge patient-to-patient variability in terms of how it's absorbed and how it actually passes the blood-brain barrier or moves past the blood-brain barrier. So, the biggest problem here is what we call the DDMPK, Drug Distribution and Metabolism, the mechanism of action. In a lab, it works wonderfully. In cells, it works, even in rat models, and we've even done models in dogs, and it works. The problem is in humans, the metabolism of such drug classes allows very high variability and very, very low bio-availability to reach even a 1% maximum. And that's why you'll never be able to take that product into clinical program to bring a reasonable effect to the patient, except by having to give patients something like 900 grams of the drug because the bio-availability is too low, and the variability is very high. — Senior pharmaceutical executive/scientist, previously at Abbott and now at another major pharma company", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-44c5830a36fc", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.3, "x": 0.07, "y": 0.95 }, "kind": "source-note", "text": "Source: Scorpion Capital consultation calls with experts", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "38947532-8c20-4d20-bf1a-bad2f6c39ea9", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [ { "name": "antagonist-introduction", "slug": null, "matchId": "3ef00a86-d7f0-431e-b06d-f39d37092232", "evidence": "Frames the H3 receptor drug class as the 'villain' or doomed entity.", "confidence": 0.9 } ], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }