{ "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": 92, "pageCount": 366, "prevPage": 91, "nextPage": 93, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 2, "notes": "The slide uses a Q&A transcript format to highlight a specific failure case study.", "elementsJson": [ "paragraph", "quote_block", "footnote" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/92", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-92", "components": [ { "bbox": null, "kind": "callout", "text": "He indicated that the toxicity was alarming enough that GSK’s governance committee quickly and prematurely terminated the trial after an interim reading, even though it had only enrolled 30-35 patients out of 100 planned.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-13e02d0e4654", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.55, "w": 0.86, "x": 0.07, "y": 0.34 }, "kind": "paragraph", "text": "Q: “And what happened -when did it fail and why?”\nA: “It failed later, actually, at later stages. There are many why's. It's a kind of weird case but unfortunately, there was no good efficacy. And that was puzzling. When we attempted to increase the dose, there was some issues with the toxicity part.”\nQ: “What were the toxicity issues? And these are all animal studies? Are these are healthy volunteer studies?”\nA: “I'm talking to you about the animal studies and first time in humans and also phase 2 as well.\nQ: “So, there was toxicity—where did you guys observe the toxicity in the animal and volunteers in the phase 2 studies?”\nA: “Normally, we start with animals, as you probably know. And we do dose escalation in animals, so we did that, and it was fine up to the dose that we tried with animals. The first time in a human, as you probably know, they try a lower dose, which was fine. In the second study, phase 2, which again, this is toxicity but it's a larger population you do what's called dose escalation to try to see what's the tolerability of the subject in terms of dosing, and what dose they can tolerate. And yeah, there were some serious side effects when we tried to increase the dose.”\nQ: “Do you remember at what dose that happened?\nA: “We started from 25 mg, we tried 50 mg, 250 mg, 100 mg, something like that. That was one of the problems because it's working with cellular signaling.”\nQ: “This was the Alzheimer's trial, GSK239512?”\nA: “Yes, I think you are right.”\nQ: “I'm just looking it up online while we're talking. A 16-week, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Started November 2009. It was supposed to end a year later, in November 2010. Do you remember how many patients were enrolled?”\nA: “Yes, that was actually phase 2 was less than 100, I think there were 30. I think we did around 30-35 patients for phase 2.” – Longtime scientific leader at GSK", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "7dd4f71a-e147-4e28-acba-a25bc668c1ef", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.45, "x": 0.07, "y": 0.3 }, "kind": "paragraph", "text": "Failure due to toxicity and lack of efficacy; phase 2 prematurely halted", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "e299a009-5cb5-4a85-9e3f-c11e4f8655e2", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“no good” on efficacy and “issues with the toxicity”: “there were some serious side effects when we tried to increase the dose.” — Longtime scientific leader at GSK", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd0-1591e7f61735", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.25, "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": "9a4f1286-3eec-4360-9169-e63ef6dc4346", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.22, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "The scientist walked us through one phase 2 study in particular, at similar doses to the pitolisant trials. He stated it was “no good” on efficacy and “issues with the toxicity”: “there were some serious side effects when we tried to increase the dose.” He indicated that the toxicity was alarming enough that GSK’s governance committee quickly and prematurely terminated the trial after an interim reading, even though it had only enrolled 30-35 patients out of 100 planned.", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "f88dfbc5-69c8-4a77-a9ec-67e845fe5d73", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }