{ "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": 94, "pageCount": 366, "prevPage": 93, "nextPage": 95, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "overcrowded", "nDataPoints": 0, "notes": "The slide uses a Q&A transcript format to corroborate previous claims about drug instability and poor blood-brain barrier penetration.", "elementsJson": [ "paragraph", "quote_block", "footnote" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/94", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-94", "components": [ { "bbox": null, "kind": "callout", "text": "The bioavailability was fluctuating in both animals and humans.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-84f7c32f6438", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.09, "w": 0.86, "x": 0.07, "y": 0.75 }, "kind": "paragraph", "text": "Q: “Did you guys in the PK studies measure distribution in the brain, whether it crossed the blood-brain barrier? Any radiography?” A: “Radio labeling - some people do get the drug and we did that and that’s what the bioavailability—it’s kind of addressing the bioavailability point. And yeah, it was not that freely passing the blood-brain barrier just like with Abbott. So, that’s why the bioavailability data was fluctuating.” –Longtime scientific leader at GSK", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "24b1c9ab-f535-4361-b850-cafee839cece", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.86, "x": 0.07, "y": 0.71 }, "kind": "paragraph", "text": "Q: “And so, that’s why you guys had to escalate the dose, and then you’ve got a toxicity problem.” A: “Yeah, exactly.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "760bb59a-6ccd-424a-b172-a56c25bccbba", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.46 }, "kind": "paragraph", "text": "Q: “When you say fluctuating - some people had it, some people didn’t? Or you just never knew if it was going to get in there or not?” A: “Some people had more concentration, more bioavailability than others. And the same for the animal. Some subjects more than others, so that’s what I mean by fluctuating among subjects. And also, within the same subject, when you take it at a different time period or when you measure it at a different time period, it’s not sustaining the same bioavailability for a good time. You need some time for the drug to stay there in order to bind. So, sometimes, you measure, and you find a good concentration, and then all of a sudden, it’s gone. There is some mechanism of clearance for this drug.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "84cdaa4d-6568-419d-af86-a91cf24c2470", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.08, "w": 0.86, "x": 0.07, "y": 0.62 }, "kind": "paragraph", "text": "Q: “So, you mentioned variability but do you remember what the actual level of bioavailability was? It was just not enough to be therapeutic, so you said you had to increase the dose, what was it? Like 1%, 3%? “ A: “Yeah-yeah, that’s exactly what I mean. And we needed it to reach to a certain concentration. It never reached it, or if it reached it, it was not reaching it and sustaining it for a long time.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "c5cda5fb-db17-48f8-ab84-a517aa76fda9", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.3 }, "kind": "paragraph", "text": "Q: “And what was the bioavailability problem that you observed?” A: “The bioavailability, I mean, the concentration in the brain was less than, around 3 [Inaudible 0:16:23] or less. And sometimes, when you take samples, and even in animals where unfortunately we take their brains and we measure the drug there. We realized that there are some low concentration in some samples and some of the samples, good concentration, and bioavailability in the brain tissue. So, we don’t know how the blood-brain barrier is actually interacting with the molecule. The bioavailability was fluctuating in both animals and humans.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "cb1a5e9a-9e26-4667-918e-5802418a4976", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.06, "w": 0.86, "x": 0.07, "y": 0.23 }, "kind": "paragraph", "text": "Bioavailability was highly variable and unpredictable, even within the same patient at different times due to “mechanism of clearance for this drug”; never reached therapeutic concentration and/or sustained it; blood-brain barrier issues", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "e7137173-3eb6-4559-936d-259c5985b7e9", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“The bioavailability, I mean, the concentration in the brain was less than, around 3 [Inaudible 0:16:23] or less. And sometimes, when you take samples, and even in animals where unfortunately we take their brains and we measure the drug there. We realized that there are some low concentration in some samples and some of the samples, good concentration, and bioavailability in the brain tissue. So, we don't know how the blood-brain barrier is actually interacting with the molecule. The bioavailability was fluctuating in both animals and humans.” — Longtime scientific leader at GSK", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-8b61d6767619", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.25, "x": 0.07, "y": 0.91 }, "kind": "source-note", "text": "Source: Scorpion Capital consultation calls with experts", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "1c364a3b-e302-42c3-8a2d-e05fd171f236", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.15, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "In addition to toxicity, the GSK scientist shared pharmacokinetic and bioavailability problems identical to the ex-Abbott scientist’s color, stating it never reached therapeutic concentrations in the blood and couldn’t sustain them even if it did.", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "db2bc88c-7035-4506-a3ae-22be5ea1437f", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }