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- KbbabyKbbaby
  ·2023-12-11
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- KbbabyKbbaby
  ·2023-09-09
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  Enliven Therapeutics: Preclinical Company With Interesting Value Proposition
  Enliven Therapeutics, Inc. is a recently merged biopharma company focused on developing oncology candidates for leukemia and lymphoma.The company has raised $165 million in a private placement to fund
  Enliven Therapeutics: Preclinical Company With Interesting Value Proposition
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- KbbabyKbbaby
  ·2023-06-29
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news…","images":[],"top":1,"highlighted":1,"essential":1,"paper":1,"likeSize":0,"commentSize":0,"repostSize":0,"link":"https://ttm.financial/post/217762843463848","repostId":"2360058157","repostType":2,"repost":{"id":"2360058157","kind":"highlight","pubTimestamp":1692377822,"share":"https://ttm.financial/m/news/2360058157?lang=&edition=fundamental","pubTime":"2023-08-19 00:57","market":"us","language":"en","title":"Enliven Therapeutics: Preclinical Company With Interesting Value Proposition","url":"https://stock-news.laohu8.com/highlight/detail?id=2360058157","media":"seekingalpha","summary":"Enliven Therapeutics, Inc. is a recently merged biopharma company focused on developing oncology candidates for leukemia and lymphoma.The company has raised $165 million in a private placement to fund","content":"<html><body><ul><li>Enliven Therapeutics, Inc. is a recently merged biopharma company focused on developing oncology candidates for leukemia and lymphoma.</li><li>The company has raised $165 million in a private placement to fund its pipeline, which includes two phase 1 candidates.</li><li>ELVN-001 targets chronic myeloid leukemia and shows promise in preclinical tests, while ELVN-002 is a selective HER2 inhibitor with potential in HER2-driven cancers.</li></ul><p><figure><picture> <img height=\"1024px\" loading=\"lazy\" sizes=\"(max-width: 768px) calc(100vw - 36px), (max-width: 1024px) calc(100vw - 132px), (max-width: 1200px) calc(66.6vw - 72px), 600px\" src=\"https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w750\" srcset=\"https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w1536 1536w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w1280 1280w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w1080 1080w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w750 750w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w640 640w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w480 480w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w320 320w, https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg?io=getty-c-w240 240w\" width=\"1536px\"/> </picture><figcaption> <p>andreswd/E+ via Getty Images</p></figcaption></figure></p> <p>Largely speaking, every other early stage biopharma I cover starts out with a candidate targeting some form of leukemia/lymphoma. Here’s one more to add to that list - <strong>Enliven Therapeutics, Inc.</strong> (<span>NASDAQ:ELVN</span>) - a<span> phase 1 stage recently launched company with a ~$600mn valuation.</span></p> <p>Although I said “recently launched,” Enliven is actually the result of a merger between privately-held Enliven and publicly traded Imara Therapeutics. The merger closed in February this year, and the new entity began life, progressing two oncology candidates from Enliven. This reverse merger benefitted IMRA shareholders, which was otherwise a dead stock. IMRA, with its “dying breath,” also managed to sell one of its assets for a considerable sum.</p> <p>Meanwhile, Enliven, too, did its bit to strengthen the newly-formed company. Besides completing a successful merger, it raised $165mn in a private placement led by Fairmount (co-lead), Venrock Healthcare Capital<span> Partners (co-lead), Fidelity Management &amp; Research Company, RA Capital Management, Frazier Life Sciences and Commodore Capital. All its existing institutional investors also participated in the private placement. The cash balance enables it to fund its pipeline through multiple near-term </span>catalysts<span>. These are:</span></p> <blockquote> <p>ELVN-001</p> <p>Ph1a data expected in 2024 for highly selective active site BCR-ABL inhibitor including T315I for Chronic Myeloid Leukemia</p> <p>ELVN-002</p> <p>Ph1a data expected in 2024 for CNS penetrant, selective and irreversible HER2/pan-HER2 mutant inhibitor for HER2-driven cancers</p> </blockquote> <p>Both assets, the company says, are “ supported by preclinical evidence of an improved therapeutic index.” They are both in phase 1 trials. Here’s the pipeline:</p> <p><figure contenteditable=\"false\"><picture> <span><img loading=\"lazy\" src=\"https://static.seekingalpha.com/uploads/2023/8/18/saupload_h8IqU0el1eQeNuhbqlNoPpoaFeVou6CcL3kGbSkThDARHMm79Ejn30JKMmoMS8PN_hXZMc3dCz6JOfAHKOslSGdKhuXjecheNhOMFdqcyM0xZfQ5pfqgO1-9MIePRRk_XevAygJalNtu_mHVWidYj5o_thumb1.png\"/></span> </picture><figcaption><p>ELVN PIPELINE <span>(ELVN WEBSITE)</span></p></figcaption></figure></p> <p>Lead candidate ELVN-001 is targeting CML as an initial indication. There are many approved drugs in the space, including generics, and they drive over $6bn in annual sales. However, the company says that barring asciminib, all other approved TKIs have “poor kinase selectivity, resulting in tolerability issues that impact efficacy.” A large number of patients switch therapies because of this, and because of lack of molecular response. Some of these drugs also come with comorbidities, drug-drug interaction related restrictions, and difficult dosing regimen, which restrict adoption. Increasing number of patients in the 3L setting also creates an unmet need.</p> <p>Looking at this from another angle, six small-molecule inhibitors have been approved by the FDA to treat a specific type of leukemia called BCR-ABL1-driven Chronic Myeloid Leukemia (CML). These inhibitors, known as TKIs or tyrosine kinase inhibitors, include Imatinib, Nilotinib, Dasatinib, Ponatinib, and Bosutinib. They work by targeting a specific part of a protein called ABL1 tyrosine kinase.</p> <p>Although these TKIs are helpful in treating CML, they have a specificity problem. They can accidentally affect other proteins in the body, causing unwanted side effects. As a result, they might not work as effectively as they could to treat CML.</p> <p>Another challenge with these TKIs is that they can stop working overtime. This is because the cancer cells can change in a way that makes the TKIs less effective. One specific change is called the T315I mutation. It makes the TKIs less able to do their job.</p> <p>However, a new TKI called Asciminib has been approved in 2021. This one works differently. It interacts with a special part of the ABL1 protein, which makes it more specific and causes fewer side effects.</p> <p>But there's a catch with Asciminib. To work against a specific change in the ABL1 protein (the T315I mutation), patients need to take a higher dose – five times higher – compared to what's normally approved. This higher dose can make it harder for some patients to tolerate the treatment.</p> <p>Also, the problem of cancer cells becoming resistant to treatment is still there with Asciminib. Some changes in the ABL1 protein can still make the treatment less effective. This is a challenge, especially when these changes happen in the same special part of the protein that Asciminib targets.</p> <p>ELVN-001 also targets ABL1, but it is much more specific. Unlike other TKIs, it does not cause problems like low blood cell counts, swelling, and heart issues. In preclinical tests, ELVN-001 worked well against BCR-ABL1-driven CML. Indeed, preclinical data for ELVN-001 was better than these approved peers, and it worked well even in TKI-resistant tumors.</p> <p>ELVN-001 was also safe, with good PK/PD data - it was absorbed, spread around the body, and removed from the body easily and quickly. Animal studies showed strong therapeutic effects in tumor cells.</p> <p>The second asset, ELVN-002, is a CNS penetrant, selective, and irreversible pan-mutant HER2 TKI. That means it can get through the blood brain barrier, is specific to HER2 and its mutations, and its effects are long-lasting. Selectivity is important to differentiate between HER2 and EGFR, which are structurally similar. Thus, approved drugs that are dual EGFR/HER2 inhibitors - which is most of them - are dose-limited by EGFR-driven toxicity. Tucatinib is the only approved HER2-selective TKI, but its problem is that it is not pan-mutant like ELVN-002, and does not have potency against key mutants like HER2 YVMA, the most common Exon 20 insertion mutation (E20IM) in NSCLC, and L755, the most common HER2 breast cancer mutation. Moreover, these TKIs are not sufficiently brain penetrating, and do not adequately address brain metastases.</p> <p>Contrast that with what the company claims for ELVN-002:</p> <ul> <li><p>Designed to irreversibly inhibit HER2 and multiple key HER2 mutations, including HER2 YVMA and L755</p></li> <li><p>Selectively inhibit HER2 while sparing EGFR to prevent EGFR-related toxicities, with the potential for improved efficacy in NSCLC and other cancers</p></li> <li><p>Demonstrated superior pre-clinical activity in HER2- amplified subcutaneous and intracranial models, and an improved safety margin in NHPs compared to tucatinib.</p></li> </ul> <p>So far so good, but like I always warn my readers, preclinical data has nearly nothing to offer investors. Their import is for clinical investigators who need to take them through human trials and prove their claims; so if you are buying a preclinical stage company, you didn’t get that idea from me. Although, to be honest, some preclinical data are more promising than others, and this one is somewhere in between. Its logic is promising, but its claims need more vigorous proving.</p> <h2>Financials</h2> <p>ELVN has a market cap of $631mn and a cash balance of $277mn. R&amp;D expenses were $15.2 million for the second quarter of 2023, while G&amp;A expenses were $5.0 million. At that rate, the company has a cash runway of 12 quarters, but, of course, expenses will increase over time.</p> <p>The stock is almost entirely held by PE/VC firms, institutions and hedge fund managers. keyholders are 5AM Ventures, Orbimed and FMR LLC. IMRA was heavily transacted by insiders, but ELVN is yet to begin that much.</p> <h2>Risks</h2> <p>Enliven Therapeutics is a preclinical company with no human data, and I do not suggest investing in such companies. These are not for regular investors.</p> <p>The company is newly-launched, therefore, their current cash position may not adequately reflect their future expenses.</p> <h2>Bottom Line</h2> <div></div> <p>Enliven Therapeutics, Inc. does provide a strong logic for its programs, and there is supporting preclinical data. I will revisit this company probably next year, when they have human data to show.</p></body></html>","source":"seekingalpha","collect":0,"html":"<!DOCTYPE html>\n<html>\n<head>\n<meta http-equiv=\"Content-Type\" content=\"text/html; charset=utf-8\" />\n<meta name=\"viewport\" content=\"width=device-width,initial-scale=1.0,minimum-scale=1.0,maximum-scale=1.0,user-scalable=no\"/>\n<meta name=\"format-detection\" content=\"telephone=no,email=no,address=no\" />\n<title>Enliven Therapeutics: Preclinical Company With Interesting Value Proposition</title>\n<style type=\"text/css\">\na,abbr,acronym,address,applet,article,aside,audio,b,big,blockquote,body,canvas,caption,center,cite,code,dd,del,details,dfn,div,dl,dt,\nem,embed,fieldset,figcaption,figure,footer,form,h1,h2,h3,h4,h5,h6,header,hgroup,html,i,iframe,img,ins,kbd,label,legend,li,mark,menu,nav,\nobject,ol,output,p,pre,q,ruby,s,samp,section,small,span,strike,strong,sub,summary,sup,table,tbody,td,tfoot,th,thead,time,tr,tt,u,ul,var,video{ font:inherit;margin:0;padding:0;vertical-align:baseline;border:0 }\nbody{ font-size:16px; line-height:1.5; color:#999; background:transparent; }\n.wrapper{ overflow:hidden;word-break:break-all;padding:10px; }\nh1,h2{ font-weight:normal; line-height:1.35; margin-bottom:.6em; }\nh3,h4,h5,h6{ line-height:1.35; margin-bottom:1em; }\nh1{ font-size:24px; }\nh2{ font-size:20px; }\nh3{ font-size:18px; }\nh4{ font-size:16px; }\nh5{ font-size:14px; }\nh6{ font-size:12px; }\np,ul,ol,blockquote,dl,table{ margin:1.2em 0; }\nul,ol{ margin-left:2em; }\nul{ list-style:disc; }\nol{ list-style:decimal; }\nli,li p{ margin:10px 0;}\nimg{ max-width:100%;display:block;margin:0 auto 1em; }\nblockquote{ color:#B5B2B1; border-left:3px solid #aaa; padding:1em; }\nstrong,b{font-weight:bold;}\nem,i{font-style:italic;}\ntable{ width:100%;border-collapse:collapse;border-spacing:1px;margin:1em 0;font-size:.9em; }\nth,td{ padding:5px;text-align:left;border:1px solid #aaa; }\nth{ font-weight:bold;background:#5d5d5d; }\n.symbol-link{font-weight:bold;}\n/* header{ border-bottom:1px solid #494756; } */\n.title{ margin:0 0 8px;line-height:1.3;color:#ddd; }\n.meta {color:#5e5c6d;font-size:13px;margin:0 0 .5em; }\na{text-decoration:none; color:#2a4b87;}\n.meta .head { display: inline-block; overflow: hidden}\n.head .h-thumb { width: 30px; height: 30px; margin: 0; padding: 0; border-radius: 50%; float: left;}\n.head .h-content { margin: 0; padding: 0 0 0 9px; float: left;}\n.head .h-name {font-size: 13px; color: #eee; margin: 0;}\n.head .h-time {font-size: 11px; color: #7E829C; margin: 0;line-height: 11px;}\n.small {font-size: 12.5px; display: inline-block; transform: scale(0.9); -webkit-transform: scale(0.9); transform-origin: left; -webkit-transform-origin: left;}\n.smaller {font-size: 12.5px; display: inline-block; transform: scale(0.8); -webkit-transform: scale(0.8); transform-origin: left; -webkit-transform-origin: left;}\n.bt-text {font-size: 12px;margin: 1.5em 0 0 0}\n.bt-text p {margin: 0}\n</style>\n</head>\n<body>\n<div class=\"wrapper\">\n<header>\n<h2 class=\"title\">\nEnliven Therapeutics: Preclinical Company With Interesting Value Proposition\n</h2>\n\n<h4 class=\"meta\">\n\n\n2023-08-19 00:57 GMT+8&nbsp;&nbsp;&nbsp;<a href=https://seekingalpha.com/article/4629610-enliven-therapeutics-preclinical-company-with-interesting-value-proposition><strong>seekingalpha</strong></a>\n\n\n</h4>\n\n</header>\n<article>\n<div>\n<p>Enliven Therapeutics, Inc. is a recently merged biopharma company focused on developing oncology candidates for leukemia and lymphoma.The company has raised $165 million in a private placement to fund...</p>\n\n<a href=\"https://seekingalpha.com/article/4629610-enliven-therapeutics-preclinical-company-with-interesting-value-proposition\">Web Link</a>\n\n</div>\n\n\n</article>\n</div>\n</body>\n</html>\n","type":0,"thumbnail":"https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1462151150/image_1462151150.jpg","relate_stocks":{"ELVN":"Enliven Treateutics","BK4007":"制药"},"source_url":"https://seekingalpha.com/article/4629610-enliven-therapeutics-preclinical-company-with-interesting-value-proposition","is_english":true,"share_image_url":"https://static.laohu8.com/5a36db9d73b4222bc376d24ccc48c8a4","article_id":"2360058157","content_text":"Enliven Therapeutics, Inc. is a recently merged biopharma company focused on developing oncology candidates for leukemia and lymphoma.The company has raised $165 million in a private placement to fund its pipeline, which includes two phase 1 candidates.ELVN-001 targets chronic myeloid leukemia and shows promise in preclinical tests, while ELVN-002 is a selective HER2 inhibitor with potential in HER2-driven cancers.   andreswd/E+ via Getty Images Largely speaking, every other early stage biopharma I cover starts out with a candidate targeting some form of leukemia/lymphoma. Here’s one more to add to that list - Enliven Therapeutics, Inc. (NASDAQ:ELVN) - a phase 1 stage recently launched company with a ~$600mn valuation. Although I said “recently launched,” Enliven is actually the result of a merger between privately-held Enliven and publicly traded Imara Therapeutics. The merger closed in February this year, and the new entity began life, progressing two oncology candidates from Enliven. This reverse merger benefitted IMRA shareholders, which was otherwise a dead stock. IMRA, with its “dying breath,” also managed to sell one of its assets for a considerable sum. Meanwhile, Enliven, too, did its bit to strengthen the newly-formed company. Besides completing a successful merger, it raised $165mn in a private placement led by Fairmount (co-lead), Venrock Healthcare Capital Partners (co-lead), Fidelity Management & Research Company, RA Capital Management, Frazier Life Sciences and Commodore Capital. All its existing institutional investors also participated in the private placement. The cash balance enables it to fund its pipeline through multiple near-term catalysts. These are:  ELVN-001 Ph1a data expected in 2024 for highly selective active site BCR-ABL inhibitor including T315I for Chronic Myeloid Leukemia ELVN-002 Ph1a data expected in 2024 for CNS penetrant, selective and irreversible HER2/pan-HER2 mutant inhibitor for HER2-driven cancers  Both assets, the company says, are “ supported by preclinical evidence of an improved therapeutic index.” They are both in phase 1 trials. Here’s the pipeline:   ELVN PIPELINE (ELVN WEBSITE) Lead candidate ELVN-001 is targeting CML as an initial indication. There are many approved drugs in the space, including generics, and they drive over $6bn in annual sales. However, the company says that barring asciminib, all other approved TKIs have “poor kinase selectivity, resulting in tolerability issues that impact efficacy.” A large number of patients switch therapies because of this, and because of lack of molecular response. Some of these drugs also come with comorbidities, drug-drug interaction related restrictions, and difficult dosing regimen, which restrict adoption. Increasing number of patients in the 3L setting also creates an unmet need. Looking at this from another angle, six small-molecule inhibitors have been approved by the FDA to treat a specific type of leukemia called BCR-ABL1-driven Chronic Myeloid Leukemia (CML). These inhibitors, known as TKIs or tyrosine kinase inhibitors, include Imatinib, Nilotinib, Dasatinib, Ponatinib, and Bosutinib. They work by targeting a specific part of a protein called ABL1 tyrosine kinase. Although these TKIs are helpful in treating CML, they have a specificity problem. They can accidentally affect other proteins in the body, causing unwanted side effects. As a result, they might not work as effectively as they could to treat CML. Another challenge with these TKIs is that they can stop working overtime. This is because the cancer cells can change in a way that makes the TKIs less effective. One specific change is called the T315I mutation. It makes the TKIs less able to do their job. However, a new TKI called Asciminib has been approved in 2021. This one works differently. It interacts with a special part of the ABL1 protein, which makes it more specific and causes fewer side effects. But there's a catch with Asciminib. To work against a specific change in the ABL1 protein (the T315I mutation), patients need to take a higher dose – five times higher – compared to what's normally approved. This higher dose can make it harder for some patients to tolerate the treatment. Also, the problem of cancer cells becoming resistant to treatment is still there with Asciminib. Some changes in the ABL1 protein can still make the treatment less effective. This is a challenge, especially when these changes happen in the same special part of the protein that Asciminib targets. ELVN-001 also targets ABL1, but it is much more specific. Unlike other TKIs, it does not cause problems like low blood cell counts, swelling, and heart issues. In preclinical tests, ELVN-001 worked well against BCR-ABL1-driven CML. Indeed, preclinical data for ELVN-001 was better than these approved peers, and it worked well even in TKI-resistant tumors. ELVN-001 was also safe, with good PK/PD data - it was absorbed, spread around the body, and removed from the body easily and quickly. Animal studies showed strong therapeutic effects in tumor cells. The second asset, ELVN-002, is a CNS penetrant, selective, and irreversible pan-mutant HER2 TKI. That means it can get through the blood brain barrier, is specific to HER2 and its mutations, and its effects are long-lasting. Selectivity is important to differentiate between HER2 and EGFR, which are structurally similar. Thus, approved drugs that are dual EGFR/HER2 inhibitors - which is most of them - are dose-limited by EGFR-driven toxicity. Tucatinib is the only approved HER2-selective TKI, but its problem is that it is not pan-mutant like ELVN-002, and does not have potency against key mutants like HER2 YVMA, the most common Exon 20 insertion mutation (E20IM) in NSCLC, and L755, the most common HER2 breast cancer mutation. Moreover, these TKIs are not sufficiently brain penetrating, and do not adequately address brain metastases. Contrast that with what the company claims for ELVN-002:  Designed to irreversibly inhibit HER2 and multiple key HER2 mutations, including HER2 YVMA and L755 Selectively inhibit HER2 while sparing EGFR to prevent EGFR-related toxicities, with the potential for improved efficacy in NSCLC and other cancers Demonstrated superior pre-clinical activity in HER2- amplified subcutaneous and intracranial models, and an improved safety margin in NHPs compared to tucatinib.  So far so good, but like I always warn my readers, preclinical data has nearly nothing to offer investors. Their import is for clinical investigators who need to take them through human trials and prove their claims; so if you are buying a preclinical stage company, you didn’t get that idea from me. Although, to be honest, some preclinical data are more promising than others, and this one is somewhere in between. Its logic is promising, but its claims need more vigorous proving. Financials ELVN has a market cap of $631mn and a cash balance of $277mn. R&D expenses were $15.2 million for the second quarter of 2023, while G&A expenses were $5.0 million. At that rate, the company has a cash runway of 12 quarters, but, of course, expenses will increase over time. The stock is almost entirely held by PE/VC firms, institutions and hedge fund managers. keyholders are 5AM Ventures, Orbimed and FMR LLC. IMRA was heavily transacted by insiders, but ELVN is yet to begin that much. Risks Enliven Therapeutics is a preclinical company with no human data, and I do not suggest investing in such companies. These are not for regular investors. The company is newly-launched, therefore, their current cash position may not adequately reflect their future expenses. Bottom Line  Enliven Therapeutics, Inc. does provide a strong logic for its programs, and there is supporting preclinical data. I will revisit this company probably next year, when they have human data to show.","news_type":1},"isVote":1,"tweetType":1,"viewCount":376,"authorTweetTopStatus":1,"verified":2,"comments":[],"imageCount":0,"langContent":"EN","totalScore":0},{"id":192407978303744,"gmtCreate":1688005080295,"gmtModify":1688005575120,"author":{"id":"4139683026970702","authorId":"4139683026970702","name":"Kbbaby","avatar":"https://community-static.tradeup.com/news/03a42197953698ebfdcac2cf8bdaa6f5","crmLevel":1,"crmLevelSwitch":0,"followedFlag":false,"authorIdStr":"4139683026970702","idStr":"4139683026970702"},"themes":[],"htmlText":"Share your opinion about this news…","listText":"Share your opinion about this news…","text":"Share your opinion about this news…","images":[],"top":1,"highlighted":1,"essential":1,"paper":1,"likeSize":3,"commentSize":0,"repostSize":0,"link":"https://ttm.financial/post/192407978303744","repostId":"2346816478","repostType":2,"isVote":1,"tweetType":1,"viewCount":375,"authorTweetTopStatus":1,"verified":2,"comments":[],"imageCount":0,"langContent":"EN","totalScore":0}],"defaultTab":"posts","isTTM":true}