{ "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": 99, "pageCount": 366, "prevPage": 98, "nextPage": 100, "slideType": "villain_critique", "function": "name_villain", "density": "dense", "nDataPoints": 0, "notes": "The slide uses a combination of summary bullet points and direct quotes from a consultation call to discredit the competitor's scientific rigor.", "elementsJson": [ "paragraph", "quote_block", "footnote" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/99", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-99", "components": [ { "bbox": null, "kind": "callout", "text": "Doesn't bind b/c of speciation issues; never tested it against the proper receptor; amateur hour; Schwartz used “old-school pharmacology” with rodents and lacked ability to test properly against the human H3 receptor", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-64d0-7099-9cd1-153547846c2b", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.06, "w": 0.86, "x": 0.07, "y": 0.33 }, "kind": "paragraph", "text": "Doesn’t bind b/c of speciation issues; never tested it against the proper receptor; amateur hour; Schwartz used “old-school pharmacology” with rodents and lacked ability to test properly against the human H3 receptor", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "26ca1166-5c83-4027-8a29-60d73a6ae049", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.03, "w": 0.86, "x": 0.07, "y": 0.64 }, "kind": "paragraph", "text": "Bioprojet compounds were for rats and lacking “data against the human receptor”; also off-target H4 receptor binding", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "65b79f8f-ba67-4471-9756-dd65f9db580e", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.25, "w": 0.86, "x": 0.07, "y": 0.68 }, "kind": "quote", "text": "“The point I’m making is they had great compounds for rats. I’d never seen data against the human receptor. They must have it somewhere. The other thing is some of those compounds, a year after [redacted] cloned the H3 receptor, he cloned the H4 receptor, so there’s a fourth histamine receptor. We characterized the histamine H4 receptor. And one of the first things we did was take all the H3 compounds that we had access to, to determine if they had an affinity for the H4 receptor. I’ve never seen that data for pitolisant. I think that’s less likely but for them to have H4 affinity, but I don’t know [..] The other thing is I’ve never seen data with respect to speciation. So, how does it perform against, say, a mouse, rat, dog, or human? And we wanted to show our compounds were super-specific, and we knew they had an affinity for H3 in the mouse, so what we did is we made a knockout mouse that had no H3 receptors, and we showed that our compounds didn’t bind anywhere in these animals where there were no H3 receptors. So, we knew that our compounds were highly specific for the H3 receptors. All of this stuff is published. I don’t want to bad-mouth another scientist, but I would say there were limitations on what Schwartz could do in terms of characterizing the compound.” – Longtime senior scientist at Johnson & Johnson, with global leadership roles in neuroscience", "attrs": null, "subkind": "testimonial", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "93d81a8c-4d6d-4c77-9cea-4426eb0f8806", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.22, "w": 0.86, "x": 0.07, "y": 0.4 }, "kind": "quote", "text": "“The other thing I’ve never seen for that molecule is, well, is speciation. The reason we could move very, very fast is that we had the human cloned receptor. So, we could screen our compounds against the human receptor, whereas all the work done prior to that—and Abbott was quick to do this as well because they had actually cloned a receptor that mistakenly characterized it as a cholinergic receptor, not a histamine receptor [...] But when Jean-Charles Schwartz did this, it was old-school pharmacology with, I guess, it was rodent tissue strips or something. Or it was in some sort of tissue. So, they used rats. So, all their compounds that they found initially were good for rats. And then they kept advancing the compound, but, of course, they hadn’t got access to the human clone, so they didn’t know how good it was against the human receptor. There was a Wakix screen against the human receptor, but it was really, really complex. And I remember talking to Sir James Black, who had found the H2 antagonist years ago, about what tissue do you use in humans. And I don’t know if anybody ever did, but I think it was a saphenous vein, which is the big vein in your leg. So, there are at least three receptors there, and you could do the tissue-type screening.”", "attrs": null, "subkind": "testimonial", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "e6cb7eb9-9989-43ac-9958-382fe28e8ca0", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“The other thing I've never seen for that molecule is, well, is speciation. The reason we could move very, very fast is that we had the human cloned receptor. So, we could screen our compounds against the human receptor, whereas all the work done prior to that—and Abbott was quick to do this as well because they had actually cloned a receptor that mistakenly characterized it as a cholinergic receptor, not a histamine receptor [...] But when Jean-Charles Schwartz did this, it was old-school pharmacology with, I guess, it was rodent tissue strips or something. Or it was in some sort of tissue. So, they used rats. So, all their compounds that they found initially were good for rats. And then they kept advancing the compound, but, of course, they hadn't got access to the human clone, so they didn't know how good it was against the human receptor.” — Longtime senior scientist at Johnson & Johnson, with global leadership roles in neuroscience", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-64d0-7099-9cd1-1afd0e6922a9", "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": "a4a25478-94db-414a-bea0-c3af45366ae6", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.22, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "title", "text": "He outlined red flags that undermine Bioprojet’s scientific claims: that they lacked the ability to test pitolisant properly against a human H3 receptor and were dependent on rodents; used “old-school pharmacology” and had no idea “how good it was against the human receptor”; “I don’t want to bad-mouth another scientist...but there were limitations on what Schwartz could do...in characterizing the compound”; “I’ve never seen data with respect to speciation...how does it perform against...mouse, rat, dog, or human?”", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "5fb2ffc7-8b5d-492f-8da5-90bc3e704037", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }