{"id":6468,"date":"2024-10-28T08:03:31","date_gmt":"2024-10-28T12:03:31","guid":{"rendered":"https:\/\/dewpointx.com\/?p=6468"},"modified":"2024-10-28T08:03:35","modified_gmt":"2024-10-28T12:03:35","slug":"dewpoint-therapeutics-announces-nomination-of-first-c-mod-development-candidate-dptx3186-for-treatment-of-wnt-driven-cancers","status":"publish","type":"post","link":"https:\/\/dewpointx.com\/dewpoint-therapeutics-announces-nomination-of-first-c-mod-development-candidate-dptx3186-for-treatment-of-wnt-driven-cancers\/","title":{"rendered":"Dewpoint Therapeutics Announces Nomination of First C-Mod Development Candidate DPTX3186 for Treatment of Wnt-Driven Cancers\u00a0\u00a0"},"content":{"rendered":"\n<ul class=\"wp-block-list\">\n<li><em>Orally administered small molecule condensate modulators (c-mods) are a novel class of therapeutic agents designed to target condensates to modify disease<\/em>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><em>DPTX3186 is Dewpoint\u2019s first development candidate inhibiting beta catenin activity through a novel condensate mechanism for the treatment of Wnt-driven cancers<\/em>.&nbsp;<br>&nbsp;<\/li>\n\n\n\n<li><em>DPTX3186 shows significant tumor growth inhibition, stasis, and regression in preclinical models of Wnt-driven cancers<\/em>.&nbsp;<br>&nbsp;<\/li>\n\n\n\n<li><em>&nbsp;IND anticipated in mid-2025 followed by Phase 1 initiation in 2H 2025<\/em>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<p><strong>BOSTON, Massachusetts,\u202fOctober 28, 2024<\/strong>\u202f\u2013\u202f<a href=\"https:\/\/dewpointx.com\/\" target=\"_blank\" rel=\"noreferrer noopener\">Dewpoint Therapeutics Inc.<\/a>, the leading biotechnology company that develops therapeutics by targeting biomolecular condensates, announced today the nomination of its first development candidate, DPTX3186, an orally administered small molecule condensate modulator (c-mod) inhibiting the oncogenic function of beta catenin, as a potential therapeutic agent for treatment of Wnt-driven cancers. The development candidate was discovered using Dewpoint\u2019s fully automated, AI\/ML-enabled state-of-the-art platform and proprietary chemical library.&nbsp;<\/p>\n\n\n\n<p>Beta catenin is a key transcription factor in the Wnt signaling pathway, which plays a crucial role in various physiological processes in healthy cells<sup>1,2<\/sup>. Aberrant activation of beta catenin, as part of constitutively active transcriptional condensates<sup>3,4,5<\/sup>, is associated with carcinogenesis and tumor progression in colorectal cancer, gastrointestinal cancer, non-small cell lung cancer, breast cancer, liver cancer, and other types of cancers<sup>1,2<\/sup>. Beta catenin is often considered an\u202f\u2018undruggable\u2019 target, due to the presence of disordered regions and structural features lacking suitable drug binding pockets. Historically, the development of beta catenin therapies has been frequently hindered by toxicity and off-target effects<sup>1<\/sup>.\u00a0\u00a0<\/p>\n\n\n\n<p>DPTX3186 is a small molecule c-mod that acts through a\u202f<a href=\"https:\/\/nam02.safelinks.protection.outlook.com\/?url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DWJ4Hykdop2M&amp;data=05%7C02%7Cmfenn%40dewpointx.com%7Cf2adcecdb2e341e3477808dcee2fb9bc%7C90e40691582b44bb8124772d391e157d%7C0%7C0%7C638647135950310887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&amp;sdata=02ydKoTNYw4epwd4wXggsIDyD2fJJNtZniiecixeHyA%3D&amp;reserved=0\" target=\"_blank\" rel=\"noreferrer noopener\">novel mechanism of action<\/a> to sequester beta catenin into nuclear depot condensates. This sequestration leads to downregulation of beta catenin related genes, resulting in significant tumor cell killing. DPTX3186 demonstrates activity across various beta catenin\/Wnt-driven tumor cell types, while exhibiting minimal toxicity in healthy cells. In patient-derived and cell-derived xenograft models it displays significant tumor growth inhibition including regression and tumor stasis.&nbsp;&nbsp;<\/p>\n\n\n\n<p>\u201cNominating this development candidate marks a significant milestone in our journey to deliver the\u202ffirst condensate modulating drug to the clinic,\u201d said Ameet Nathwani, CEO of Dewpoint Therapeutics. \u201cThe discovery and selection of DPTX3186 for a target considered \u2018undruggable\u2019 underscores the transformative potential of our state-of-the-art platform combined with a fresh perspective on the underlying biology, through the lens of condensate science. This approach enabled us to identify and advance a novel class of therapeutic agents to address diseases of high unmet need. To date, DPTX3186 has demonstrated significant activity in preclinical models across multiple types of cancer, high selectivity for tumor cells, and a mechanism of action on the beta catenin\/Wnt pathway. To accelerate the development of DPTX3186, we partnered with Evotec. Together, we will leverage Evotec\u2019s INDiGO platform for the rapid and efficient generation of a high-quality IND-enabling package. We anticipate filling the IND in mid-2025, followed by the commencement of Phase 1 clinical trial in the\u202fsecond half of\u202f2025.\u201d\u00a0<\/p>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li>Yu F, Yu C, Li F,\u202fet al.,\u202f<em>Sig Transduct Target Ther.<\/em>\u202f6, 307 (2021). <a href=\"https:\/\/doi.org\/10.1038\/s41392-021-00701-5\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1038\/s41392-021-00701-5<\/a>&nbsp;&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"2\" class=\"wp-block-list\">\n<li>Shang S, Hua F, Hu ZW.&nbsp;<em>Oncotarget.<\/em> 8(20):33972-33989 (2017). <a href=\"https:\/\/doi.org\/10.18632\/oncotarget.15687\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.18632\/oncotarget.15687<\/a><\/li>\n<\/ol>\n\n\n\n<ol start=\"3\" class=\"wp-block-list\">\n<li>Gui T, et al., Targeted perturbation of signaling-driven condensates. <em>Mol. Cell.<\/em> 83(22):4141-4157 (2023). <a href=\"https:\/\/doi.org\/10.1016\/j.molcel.2023.10.023\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1016\/j.molcel.2023.10.023<\/a>&nbsp;&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"4\" class=\"wp-block-list\">\n<li>Zamudio A, et al., <em>Mol. Cell<\/em>. 76(5):753-766 (2019). <a href=\"https:\/\/doi.org\/10.1016\/j.molcel.2019.08.016\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1016\/j.molcel.2019.08.016<\/a>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"5\" class=\"wp-block-list\">\n<li>Boija, A, et al., <em>Cell.<\/em> 2018 Dec 13;175(7):1842-1855.e16 <a href=\"https:\/\/doi.org\/10.1016\/j.cell.2018.10.042\" target=\"_blank\" rel=\"noreferrer noopener\">10.1016\/j.cell.2018.10.042<\/a>&nbsp;<\/li>\n<\/ol>\n\n\n\n<p><strong>About Condensates&nbsp;<\/strong>&nbsp;<br>Condensates are membraneless organelles that form dynamically throughout the cell via a process called phase separation. These subcellular compartments organize and concentrate molecules within cells to enable a diversity of key biochemical processes. The dysregulation of biomolecular condensates has been observed in many diseases, including cancer, diabetes, and neurological disorders. Condensate-modulating drugs (c-mods) potentially provide novel therapeutic options for complex diseases and historically undruggable targets. Learn more about condensate science at <a href=\"https:\/\/condensates.com\/\" target=\"_blank\" rel=\"noreferrer noopener\">Condensates.com<\/a>.&nbsp;<\/p>\n\n\n\n<p><strong>About Dewpoint Therapeutics&nbsp;<\/strong>&nbsp;<br>Dewpoint is the leading biotech company in the application of biomolecular condensate biology towards the development of a new generation of therapeutics to address diseases of high unmet need. The realization that a vast range of conditions are regulated by or arise from the dysfunction of condensates has provided new possibilities for modulating the function of high-value targets previously deemed \u2018undruggable,\u2019 opening unexplored avenues to identify hundreds of novel therapeutic targets. Dewpoint\u2019s proprietary AI\/ML-powered state-of-the-art platform underlies a drug discovery pipeline that spans multiple therapeutic areas, including oncology, neurodegenerative, cardiopulmonary, and metabolic diseases. Through collaborations with Bayer, Novo Nordisk, and Evotec, Dewpoint pushes the boundaries to accelerate the translation of condensate biology into medicine for patients suffering from difficult-to-treat diseases. Learn more at\u202f<a href=\"https:\/\/dewpointx.com\/\" target=\"_blank\" rel=\"noreferrer noopener\"><strong>Dewpointx.com<\/strong><\/a>\u202fand follow us on\u202f<a href=\"https:\/\/twitter.com\/dewpoint_tx\" target=\"_blank\" rel=\"noreferrer noopener\"><strong>X<\/strong><\/a>\u202fand\u202f<a href=\"https:\/\/www.linkedin.com\/company\/dewpointtherapeutics\/\" target=\"_blank\" rel=\"noreferrer noopener\"><strong>LinkedIn<\/strong><\/a>.&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>BOSTON, Massachusetts,\u202fOctober 28, 2024\u202f\u2013\u202fDewpoint Therapeutics Inc., the leading biotechnology company that develops therapeutics by targeting biomolecular condensates, announced today the [&hellip;]<\/p>\n","protected":false},"author":10,"featured_media":3339,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[5],"tags":[48],"class_list":["post-6468","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-releases","tag-add-to-home-page"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Dewpoint Therapeutics Announces Nomination of First C-Mod Development Candidate DPTX3186 for Treatment of Wnt-Driven Cancers\u00a0\u00a0 | Dewpoint Therapeutics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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