Tango Therapeutics Shifts Focus from TNG908 to More Promising Cancer Drug Candidates, TNG462 and TNG456

<!DOCTYPE html> <html lang="en"> <head> <meta charset="UTF-8"> <title> Tango Therapeutics Shifts Focus from TNG908 to More Promising Cancer Drug Candidates, TNG462 and TNG456 </title> <meta name="viewport" content="width=device-width, initial-scale=1.0"> <link rel="canonical" href="https://www.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/" />  <script async src="https://www.googletagmanager.com/gtag/js?id=G-YK7FCK71TD"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-YK7FCK71TD'); </script> <meta name="description" content="Tango Therapeutics halts enrollment in its TNG908 glioblastoma trial due to limited efficacy and shifts focus to advancing TNG462 and TNG456, two promising PRMT5 inhibitors targeting MTAP-deleted cancers. This pivot comes as TNG908 struggles with CNS penetration, while TNG462 shows durable responses in non-CNS tumors. 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This pivot comes as TNG908 struggles with CNS penetration, while TNG462 shows durable responses in non-CNS tumors. Tango aims to move TNG456 into clinical trials next year, positioning it for potential success in treating brain tumors."> <meta name="twitter:image" content="https://www.biopharmatrend.com/files/blog/social/iStock-1423600542_S7eRjdV.jpg">  <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/" /> <meta property="og:title" content="Tango Therapeutics Shifts Focus from TNG908 to More Promising Cancer Drug Candidates, TNG462 and TNG456" /> <meta property="og:description" content="Tango Therapeutics halts enrollment in its TNG908 glioblastoma trial due to limited efficacy and shifts focus to advancing TNG462 and TNG456, two promising PRMT5 inhibitors targeting MTAP-deleted cancers. This pivot comes as TNG908 struggles with CNS penetration, while TNG462 shows durable responses in non-CNS tumors. Tango aims to move TNG456 into clinical trials next year, positioning it for potential success in treating brain tumors." /> <meta property="article:published_time" content="2024-11-07T14:54:43+00:00"> <meta property="article:modified_time" content="2024-11-07T14:54:43+00:00"> <meta name="author" content="Roman Kasianov"> <meta property="og:image" content="https://www.biopharmatrend.com/files/blog/social/iStock-1423600542_S7eRjdV.jpg"> <script type="application/ld+json">{ "@context": "https://schema.org", "@type": "NewsArticle", "headline": "Tango Therapeutics Shifts Focus from TNG908 to More Promising Cancer Drug Candidates, TNG462 and TNG456", "datePublished": "2024-11-07T14:54:43+00:00", "dateModified": "2024-11-07T14:54:43+00:00", "description": "Tango Therapeutics\n(NASDAQ: TNGX)\nannounced that it is stopping enrollment in its TNG908 clinical trial\nfollowing disappointing results for glioblastoma, a highly aggressive brain cancer. Instead, Tango will concentrate on advancing two other small molecule PRMT5 inhibitors, TNG462 and TNG456, which target similar pathways but hold promise for more favorable outcomes.", "image": "https://www.biopharmatrend.com/files/blog/social/iStock-1423600542_S7eRjdV.jpg", "url": "https://www.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://www.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/" }, "publisher": { "@type": "Organization", "name": "BiopharmaTrend", "url": "https://www.biopharmatrend.com", "logo": { "@type": "ImageObject", "url": "https://www.biopharmatrend.com/static/img/bpt_logo.png" } }, "author": [ { "@type": "Person", "name": "Roman Kasianov", "url": "https://www.biopharmatrend.com/contributor/743/" } ] }</script> <style type="text/css"> 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TNG456</h1> </header> <footer class="post-meta"> <div class="tooltip"> <span class="glyphicon glyphicon-pencil"></span> by <a href="/contributor/743/">Roman Kasianov</a> </span>    <span style="white-space: nowrap;"> <span class="glyphicon glyphicon-folder-open"></span>   News </span> <div class="tooltip-text"> <div class="tooltip-close" onclick="this.parentElement.parentElement.classList.toggle('tooltip-show');"></div> <p><b>Disclaimer</b>: All opinions expressed by Contributors are their own and do not represent those of their employers, or BiopharmaTrend.com. <br> Contributors are fully responsible for assuring they own any required copyright for any content they submit to BiopharmaTrend.com. This website and its owners shall not be liable for neither information and content submitted for publication by Contributors, nor its accuracy.</p> </div> </div> <div> <span class="glyphicon glyphicon-calendar" title="Published on"></span> <time datetime="2024-11-07">Nov. 7, 2024</time>    </em> </div> <div class="tags"> <b>Topics: </b> <a href="/topic/clinical-trials/">Clinical Trials</a>    </div> <div> <strong>Share: </strong>   <a target="_blank" rel="nofollow" href="https://www.linkedin.com/sharing/share-offsite/?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in LinkedIn" src="/static/img/soc-in.7bc286fd757e.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://www.reddit.com/submit?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in Reddit" src="/static/img/soc-reddit.342e87a07115.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://twitter.com/intent/tweet?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in X" src="/static/img/soc-x.3c80e8291cba.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://news.ycombinator.com/submitlink?u=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in Hacker News" src="/static/img/soc-y.587f16a5f3f3.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://www.facebook.com/sharer/sharer.php?u=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/&display=page"> <img alt="Share in Facebook" src="/static/img/soc-fb.3031a5a810f0.png" width="28" height="28" /></a>  <a target="_blank" rel="nofollow" href="mailto:?subject=Biopharmatrend.com&body=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Send by email" src="/static/img/soc-mail.41ce3608f438.png" width="28" height="28"></a>   |  <a href="/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/pdf/" target="_blank" rel="nofollow"> <span style="vertical-align: text-top; color: deepskyblue; font-size: 1.5em;" class="glyphicon glyphicon-print"></span></a> </div> </footer> <section> <p><a href="http://www.tangotx.com/">Tango Therapeutics</a> (NASDAQ: TNGX) <a href="http://www.businesswire.com/news/home/20241106825271/en/Tango-Therapeutics-Reports-Positive-TNG462-Clinical-Data-and-Provides-Update-on-PRMT5-Development-Program">announced that it is stopping enrollment in its TNG908 clinical trial</a> following disappointing results for glioblastoma, a highly aggressive brain cancer. Instead, Tango will concentrate on advancing two other small molecule PRMT5 inhibitors, TNG462 and TNG456, which target similar pathways but hold promise for more favorable outcomes.</p> <h4><strong>TNG908’s Glioblastoma Setback</strong></h4> <p>TNG908, designed as a brain-penetrant MTA-cooperative PRMT5 inhibitor, was initially developed to leverage synthetic lethality by selectively targeting MTAP-deleted tumors—a mutation found in about 10-15% of solid tumors. While <strong>TNG908 showed efficacy in non-CNS tumors</strong> like non-small cell lung cancer (NSCLC) and pancreatic cancer, its performance in glioblastoma patients was underwhelming. <strong>No partial responses were observed among 23 glioblastoma patients</strong> treated at active doses, with the median time on study lasting less than eight weeks.</p> <p>In assessing the lack of CNS efficacy, Tango noted that cerebrospinal fluid (CSF) exposure was significantly lower than expected, reaching only 30% of plasma levels in patients, well below the threshold required for therapeutic effect in the brain.</p> <p><strong>Dr. Adam Crystal</strong>, President of Research and Development at Tango, said:</p> <blockquote> <p>“We're disappointed that TNG908 hasn’t met our expectations for glioblastoma treatment... but we’re optimistic about TNG456, which we believe offers the potency, selectivity, and brain penetrance needed to meaningfully impact CNS cancers.”</p> </blockquote> <h4><strong>The Shift to TNG462 and TNG456</strong></h4> <p>Tango is now pivoting to its other pipeline assets, TNG462 and TNG456, <strong>both of which also target PRMT5</strong> but demonstrate greater potential in trials to date.</p> <blockquote> <p>See also: <a href="https://www.biopharmatrend.com/post/402-the-explosion-of-therapeutic-modalities-small-molecules-biologics-and-everything-in-between/">The Explosion of Therapeutic Modalities: Small Molecules, Biologics, and Everything in Between</a></p> </blockquote> <p><strong>TNG462</strong>, a selective PRMT5 inhibitor, <strong>has shown durable responses across multiple tumor types</strong> in an ongoing phase 1/2 trial, with particular promise in patients with cholangiocarcinoma, where 3 out of 7 showed confirmed partial responses. Tango plans to expand the trial and initiate several combination studies in early 2025, testing TNG462 with both standard therapies and innovative agents such as RAS(ON) inhibitors from Revolution Medicines.</p> <p>Meanwhile, <strong>TNG456</strong>, a next-generation brain-penetrant PRMT5 inhibitor, <strong>is</strong> <strong>scheduled to enter clinical trials in early 2025.</strong> This candidate is <strong>designed to overcome the CNS exposure limitations seen in TNG908</strong>, with preclinical primate studies showing CSF exposure reaching up to 110% of plasma levels. Tango plans to study TNG456 as both a monotherapy and in combination with Eli Lilly’s CDK4/6 inhibitor Verzenio, focusing on glioblastoma, NSCLC, and other solid tumors.</p> <blockquote> <p>“We’re confident that TNG456’s enhanced profile will enable us to pursue treatment for glioblastoma more effectively,” <strong>said Crystal.</strong> “We’ve seen promising preclinical synergy with Verzenio, and this approach aligns with our broader mission to explore novel synthetic lethal targets in cancer.”</p> </blockquote> <p>Following the announcement, Tango’s shares dropped 26% to $3.81 in premarket trading, reflecting investor concerns about the challenges facing TNG908 and the need for stronger clinical data in the PRMT5 inhibitor space. Tango is among a growing group of companies pursuing this novel target, with Amgen, Bristol Myers Squibb, and AstraZeneca also making progress in PRMT5 therapies. Amgen recently set a high bar with first-in-human data from its PRMT5 inhibitor AMG 193, and Bristol Myers Squibb bolstered its efforts by acquiring Mirati Therapeutics.</p> <p>With the discontinuation of TNG908, Tango Therapeutics is doubling down on TNG462 and TNG456, two candidates it hopes will push the boundaries of precision oncology. As the company repositions itself in a challenging market, these drugs represent Tango’s latest effort to harness synthetic lethality for a targeted attack on cancer, capitalizing on MTAP-deleted mutations while preserving healthy cells.</p> <blockquote> <p>“We remain focused on delivering innovative treatments for patients with MTAP-deleted cancers, even as we navigate the inherent challenges of this field,”<strong> said Dr. Barbara Weber, President and CEO of Tango.</strong> "Our commitment is to advance TNG462 and TNG456 as viable therapeutic options, especially for those with limited options in aggressive cancers."</p> </blockquote> <div class="product-list"> </div> <p> <b>Topics: </b> <a href="/topic/clinical-trials/">Clinical Trials</a>    </p> </section> </article> <div style="margin: 1em 0 2em; padding: 0.5em 0;"> <strong>Share: </strong>   <a target="_blank" rel="nofollow" href="https://www.linkedin.com/sharing/share-offsite/?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in LinkedIn" src="/static/img/soc-in.7bc286fd757e.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://www.reddit.com/submit?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in Reddit" src="/static/img/soc-reddit.342e87a07115.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://twitter.com/intent/tweet?url=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in X" src="/static/img/soc-x.3c80e8291cba.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://news.ycombinator.com/submitlink?u=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Share in Hacker News" src="/static/img/soc-y.587f16a5f3f3.png" width="28" height="28"></a>  <a target="_blank" rel="nofollow" href="https://www.facebook.com/sharer/sharer.php?u=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/&display=page"> <img alt="Share in Facebook" src="/static/img/soc-fb.3031a5a810f0.png" width="28" height="28" /></a>  <a target="_blank" rel="nofollow" href="mailto:?subject=Biopharmatrend.com&body=https%3A%2F%2Fwww.biopharmatrend.com/post/1014-tango-therapeutics-shifts-focus-from-tng908-to-more-promising-cancer-drug-candidates-tng462-and-tng456/"> <img alt="Send by email" src="/static/img/soc-mail.41ce3608f438.png" width="28" height="28"></a> </div> <div class="subscribe-block"> <div class="subscribe-inner"> <h3 style="line-height:1.5; 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Tango Therapeutics Shifts Focus from TNG908 to More Promising Cancer Drug Candidates, TNG462 and TNG456