{ "docId": "019dd923-622c-750b-8b9a-8c03a48e7d6f", "docSlug": "86e21d9d1e23", "documentTitle": "PMV Pharmaceuticals (PMVP)", "authorId": "60_Wolfpack_Research", "authorName": "Wolfpack Research", "documentKindSlug": "research-note", "documentKindLabel": "Research note", "sourceTypeSlug": "short_seller", "sourceTypeLabel": "Short seller", "presentationDate": "2022-05-19 00:00:00", "orientation": "portrait", "aspectRatio": 0.77272725, "pageNumber": 2, "pageCount": 19, "prevPage": 1, "nextPage": 3, "slideType": "executive_summary", "function": "frame_problem", "density": "overcrowded", "nDataPoints": 3, "notes": "The slide highlights the high prevalence of p53 mutations (50-60%) and the specific Y220C mutation (1%) targeted by PMV, while noting the historical failure of similar approaches.", "elementsJson": [ "paragraph", "footnote" ], "metadataConfidence": 0.95, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-8c03a48e7d6f/2", "deckHref": "/decks/019dd923-622c-750b-8b9a-8c03a48e7d6f", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-8c03a48e7d6f.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-8c03a48e7d6f#slide-2", "components": [ { "bbox": null, "kind": "callout", "text": "The bull-case for the drugs and company is that this is a tumor-agnostic therapeutic approach with wide potential therapeutic applications. However, PMV's proposed therapeutic strategy has been tried before, and it never worked.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-70f9-71ae-a677-d4277132de93", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.04, "w": 0.76, "x": 0.117, "y": 0.143 }, "kind": "paragraph", "text": "Mutations in the p53 Protein Are a Focus of Cancer Research Because Mutations in the Protein Allow for Cancer Cells to Survive and Spread", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "2dc20339-43f6-4944-9564-7608d7a23c0b", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.09, "w": 0.76, "x": 0.117, "y": 0.31 }, "kind": "paragraph", "text": "Decades of research have identified specific hotspots or point mutations in the gene. These point mutations occur when a single DNA base change from the wild-type (normal) p53 gene can inactivate the p53 protein and result in the survival and unchecked progression of cancer cells. Many human genes require multiple mutations to fail, but unfortunately p53 is susceptible to a single mutation. This makes it the most widely mutated gene in human cancer.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "303fea32-ea6f-4374-af63-ec3cc7f47926", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.11, "w": 0.76, "x": 0.117, "y": 0.19 }, "kind": "paragraph", "text": "Known as the “guardian of the genome,” the p53 protein detects cell mutations and initiates a process to repair damage at a molecular level or activates apoptosis (programmed cell death) if the repair is unsuccessful. Mutations in the p53 protein limit its ability and result in the survival and progression of cancer cells it would otherwise target.2 P53 mutations are present in approximately 50-60% of all cancers and p53 has been a focus for cancer researchers since its discovery in 1979.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "34435bb3-d93c-49a5-858f-8c8b4337c5c9", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.11, "w": 0.76, "x": 0.117, "y": 0.48 }, "kind": "paragraph", "text": "PMV Pharmaceuticals, Inc. (PMVP) is an oncology company developing a suite of small molecule, tumor-agnostic, therapies targeting the tumor suppressor protein p53. The company's lead drug candidate and only clinical-stage asset is PC14586, an oral, small molecule stabilizer and reactivator of a specific p53 point-mutation, Y220C. This point mutation is present in ~1% of all cancers, or about 75,000 newly diagnosed cases each year. There are currently no FDA approved drugs that specifically target the Y220C p53 mutation.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "44d5d5ea-0424-4b01-a2e3-9a1500adcafe", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.04, "w": 0.76, "x": 0.117, "y": 0.43 }, "kind": "paragraph", "text": "PMV Developed a Drug Designed to Target Hotspot Mutations to p53 Proteins Present in 1% of All Cancers, Potentially a Lucrative Product, if Successful", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "b1a1795a-4dfa-4b5c-8a14-c24fb6eb26e7", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.11, "w": 0.76, "x": 0.117, "y": 0.75 }, "kind": "paragraph", "text": "The p53 mutation is prolific in human cancer, so this area has been the subject of numerous academic studies. The PubMed database shows research programs targeting Y220C have been attempted since 2006. Several academic papers3 have suggested that targeting the Y220C mutation could be a viable approach, although the lack of interest by large well-funded pharma companies speaks volumes about the results of these studies. Clinicaltrials.gov shows that none of the candidates mentioned in these academic papers have progressed into clinical development.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "c8f2266d-710f-4e22-9032-02e1b0b75c25", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.07, "w": 0.76, "x": 0.117, "y": 0.61 }, "kind": "paragraph", "text": "PMV’s clinical and preclinical pipeline includes small molecule assets that target three of the top ten p53 hotspot mutations. The bull-case for the drugs and company is that this is a tumor-agnostic therapeutic approach with wide potential therapeutic applications. However, PMV’s proposed therapeutic strategy has been tried before, and it never worked.", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "edeb2510-50e6-4660-bb26-8faa395b6ee1", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.04, "w": 0.15, "x": 0.117, "y": 0.88 }, "kind": "source-note", "text": "2 See Appendix 1\n3 See Appendix 2", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "40268fb4-5453-4a3b-91ce-89b6e5300c11", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.45, "x": 0.117, "y": 0.095 }, "kind": "title", "text": "Introduction: Understanding the p53 Protein", "attrs": null, "subkind": "headline", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "4d8faf3e-ca2f-416f-bd44-5b65d1d885b9", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [ { "to": 2, "from": 1, "name": "Cost Of Inaction", "slug": "27-cost-of-inaction", "bestFor": "Urgent budget requests, compliance, risk mitigation", "matchId": "95bed1b6-baf6-4d2e-b967-e557c4e83292", "evidence": "The executive summary warns investors about the potential failure of PMV Pharma's drug candidate.", "position": 1, "objective": "Warns investors about the potential consequences of inaction", "structure": "The Status Quo -> The Hidden Costs Accumulating -> The Future State of Inaction -> The Tipping Point", "confidence": 0.6, "description": "Quantify what happens if the audience does nothing" } ], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }