Annovis Bio: Funding May Be An Issue For Announced Phase 3 Trials

seekingalpha10-18

Annovis plans to initiate two Phase 3 trials for Alzheimer's and file for Parkinson’s approval despite failing primary endpoints in the overall population.The company lacks sufficient funds, with only...

Source Link

Disclaimer: Investing carries risk. This is not financial advice. The above content should not be regarded as an offer, recommendation, or solicitation on acquiring or disposing of any financial products, any associated discussions, comments, or posts by author or other users should not be considered as such either. It is solely for general information purpose only, which does not consider your own investment objectives, financial situations or needs. TTM assumes no responsibility or warranty for the accuracy and completeness of the information, investors should do their own research and may seek professional advice before investing.

Comments

We need your insight to fill this gap

Leave a comment

{"i18n":{"language":"en_US"},"isChannel":false,"data":{"share":"https://ttm.financial/m/news/2476456925?lang=en_US&edition=fundamental","thumbnail":"https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1818667823/image_1818667823.jpg","is_english":true,"pubTime":"2024-10-18 04:29","share_image_url":"https://static.laohu8.com/5a36db9d73b4222bc376d24ccc48c8a4","id":"2476456925","market":"sg","top_or_hot":-1,"title":"Annovis Bio: Funding May Be An Issue For Announced Phase 3 Trials","media":"seekingalpha","content":"<div>\n<p>Annovis plans to initiate two Phase 3 trials for Alzheimer's and file for Parkinson’s approval despite failing primary endpoints in the overall population.The company lacks sufficient funds, with only...</p>\n\n<a href=\"https://seekingalpha.com/article/4727476-annovis-bio-funding-may-be-an-issue-for-announced-phase-3-trials\">Source Link</a>\n\n</div>\n","source":"seekingalpha","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>Annovis Bio: Funding May Be An Issue For Announced Phase 3 Trials</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\">\nAnnovis Bio: Funding May Be An Issue For Announced Phase 3 Trials\n</h2>\n\n<h4 class=\"meta\">\n\n\n2024-10-18 04:29 GMT+8&nbsp;&nbsp;&nbsp;<a href=https://seekingalpha.com/article/4727476-annovis-bio-funding-may-be-an-issue-for-announced-phase-3-trials><strong>seekingalpha</strong></a>\n\n\n</h4>\n\n</header>\n<article>\n<div>\n<p>Annovis plans to initiate two Phase 3 trials for Alzheimer's and file for Parkinson’s approval despite failing primary endpoints in the overall population.The company lacks sufficient funds, with only...</p>\n\n<a href=\"https://seekingalpha.com/article/4727476-annovis-bio-funding-may-be-an-issue-for-announced-phase-3-trials\">Source Link</a>\n\n</div>\n\n\n</article>\n</div>\n</body>\n</html>\n","isBrief":false,"type":0,"news_type":1,"symbol":"ANVS","symbol_name":"Annovis Bio, Inc.","start_time":0,"source_url":"https://seekingalpha.com/article/4727476-annovis-bio-funding-may-be-an-issue-for-announced-phase-3-trials","article_id":"2476456925","we_media_id":null,"thumbnails":["https://static.seekingalpha.com/cdn/s3/uploads/getty_images/1818667823/image_1818667823.jpg"],"rights":null,"url":"https://stock-news.laohu8.com/highlight/detail?id=2476456925","pubTimestamp":1729196952,"sourceInfo":{"source_id":"seekingalpha","name":"Seeking Alpha"},"weMediaInfo":null,"summary":"Annovis plans to initiate two Phase 3 trials for Alzheimer's and file for Parkinson’s approval despite failing primary endpoints in the overall population.The company lacks sufficient funds, with only","collect":0,"end_time":0,"defaultTopTitle":"seekingalpha.com","property":[],"viewcount":null,"language":"en","relate_stocks":{"ANVS":"Annovis Bio, Inc.","BK4139":"生物科技"},"translate_title":"Annovis Bio：资金可能是已宣布的3期试验的一个问题","themeId":null,"isJumpTheme":false,"ttsUrl":null,"symbols_score_info":{"ANVS":0.9},"content_text":"Annovis plans to initiate two Phase 3 trials for Alzheimer's and file for Parkinson’s approval despite failing primary endpoints in the overall population.The company lacks sufficient funds, with only $12.1 million in cash, probably requiring dilution to finance expensive Phase 3 trials.Annovis relies on subgroup analyses to claim efficacy, but these results lack statistical significance and may not meet FDA approval standards.The stock is at risk of performing poorly due to financial constraints and questionable efficacy.wildpixel/iStock via Getty Images Thesis On October 15, 2024, Annovis Bio, Inc. (NYSE:ANVS) announced that the FDA had cleared the path to launch two Phase 3 studies in Alzheimer's disease [AD]. I fail to see how the completion of a well-designed and well-executed 6-month trial may be sufficient to support an NDA filing, as the FDA typically requires two successful well-controlled trials, and Annovis currently has none. Annovis would also like to file a request for drug approval based on Phase 3 data on Parkinson's disease. However, the trial did not meet the UPDRS II and UPDRS III endpoints in the intent-to-treat population. The related press release focused on cognition and minor subgroups. I wonder how Annovis will find the cash to run these trials, file for approval in PD, and then subsequently do a commercial launch. The company had $4 million in cash at the end of June 2024. Running Phase 3 trials is costly, and $200 million may not even cut it. At a $110 million market cap, the dilution would need to be enormous for Annovis to run these trials. Seeking Alpha's Quant model has a Strong Sell rating on the stock. Company Introduction Annovis is a biotech company focused on treatments for Alzheimer's disease and Parkinson's disease. Its drug candidate, Buntanetap, is the furthest advanced for Parkinson's disease, having been tested in a Phase 3 trial for this indication. As for Alzheimer's disease, the company has done a Phase 2/3 trial. Both trials had topline data readouts over the past months. Buntanetap for Parkinson's disease The Phase 3 data for Parkinson's disease Annovis reported repeated delays in the announcement of its Phase 3 data in Parkinson's, due to alleged data cleaning. The trial had already ended in December 2023. On July 2, 2024, Annovis reported that Buntanetap showed dose-dependent and statistically significant improvements in cognition in the overall enrolled PD population. PD patients with substantial cognitive decline exhibited a very pronounced improvement. The company reported a statistical improvement in the MDS-UPDRS Part II, Part III, Part II+III, and Total scores in PD patients with a >3-year diagnosis. A similar improvement was reported in PD patients with Postural Instability and Gait Difficulties (PIGD). No p-values have, at any time, been communicated by Annovis to corroborate the presence of statistical significance. In an accompanying webinar, the company laid out its plans to file for FDA approval in October 2024 based on this data, while at the same time planning an 18-month long larger Phase 3 trial. Of note, Annovis seems to focus on early PD patients, although the improvements were alleged to occur in patients with a diagnosis > 3 years. Buntanetap did not show an effect on the whole ITT population in MDS-UPDRS II and III During the accompanying webinar, Annovis stated [min. 5.50 and min. 6.20] that in the entire ITT population, UPDRS 2 pretty much does not move. The total ITT population does not change at all in UPDRS 2. On the UPDRS 3 scale, both the placebo and the patients on the drug improved by -3 points. ITT population, MDS-UPDRS II and III (Webinar presentation) The trial has therefore failed to reach its most important endpoints. Annovis then sub-selected small subgroup populations to detect efficacy, without discussing overlap between these subgroups. Subgroups were: - patients with a diagnosis >3 years, accounting for 34% of the ITT population; - patients with PIGD, accounting for only 21% of the ITT population; - patients with impaired cognition, accounting for 12% of the ITT population. Subgroup analyses (Webinar presentation) Though the press release claimed it was, the effect was only statistically significant on all four measurements in the 20 mg group, and therefore not statistically significant in the 10 mg group. The * indicates significance from placebo. Results of patients with a >3-year diagnosis and (left) and PGID (right) (Webinar) A complicated path to approval Annovis mentioned during its webinar that it would like to ask for a meeting in October 2024 and file for approval [min. 15]. At the same time, the company laid out its plan for an additional 18-month long Phase 3 trial. Development path for approval in PD (Webinar presentation) I do not think the FDA will accept such an NDA request, as Buntanetap did not show efficacy compared to placebo on the primary and secondary endpoints in the ITT population, and because post hoc subgroup analyses cannot provide substantial evidence of effectiveness. Filing for approval in PD additionally comes with a fee above $3 million. In my opinion, realistically, that plan probably needs to be aborted. Buntanetap for Alzheimer's disease Introduction I have covered the results of a Phase 2/3 trial for Alzheimer's before. The Phase 2/3 trial failed to meet primary and secondary endpoints in the entire population. The MMSE rating scale was a secondary endpoint of that trial, which the company never reported on. As shown in the table below, the MMSE scores were only used to differentiate patients at the start of their respective trials. The company also excluded 37% of patients, claiming they did not have Alzheimer's disease. The full trial results were shown in a shareholders' letter released a few days after initial topline data, lacking the concrete outcome of patients on placebo. The shareholders' letter only mentions divergence. That is important, as the placebo had apparently performed so well on the trial. Full trial results (Shareholders letter) In a subsequent webinar, the company showed that placebo patients had improved in the overall population, similar to what Buntanetap did. Placebo response in AD trial (Webinar presentation) The company also confirmed in that webinar that the trial did fail the primary endpoint, and that it was not a pivotal study [min. 27]. Another complicated path to approval On October 15, 2024, Annovis Bio, Inc. (ANVS) announced that the FDA had cleared the path to launch two Phase 3 studies in Alzheimer's disease [AD]. These two studies should lead to two New Drug Applications [NDAs], one for symptomatic treatment, and one for disease-modifying treatment. The company claims that the completion of a well-designed and well-executed 6-month trial may be sufficient to support an NDA filing, potentially within one year of the study's initiation. I fail to see how such would be the case, as the FDA typically requires two successful well-controlled trials, and Annovis currently has none. Moreover, for an NDA to be filed within one year of study initiation, the 6-month study would need to enroll at an absolute record pace. I do not think that timeline is realistic. Buntanetap's short-term efficacy is scrutinized by Seeking Alpha analysts AR Capital Management and C.C. Abbott, as the Phase 2/3 trial had failed to bring statistically significant results. Buntanetap's long-term efficacy has never been tested before. It feels to me that Annovis is yet again too optimistic about Buntanetap's efficacy, and how the company would plan to execute all these Phase 3 trials it has planned. It results from the financing section below that the company has about $4 million in cash, with an ELOC financing facility that allows it to continue to survive in the short term. However, running two or even three Phase 3 trials would mean a huge cost to the company. The average Phase 3 trial in Alzheimer's disease costs $340 million. Even if Annovis would somehow be able to cut that in half, running two such trials would still have the company end up needing cash of more than $300 million. Add to that, running another long Phase 3 trial in Parkinson's, which, I assume, will not be cheaper than $100 million either. All of this would mean that Annovis would probably need to find $300-$400 million in financing to run all of its planned projects, all while having a $110 million market cap. The only solution to that seems to be a massive dilution of shareholders. Finances As of June 30, 2024, Annovis had cash and cash equivalents of $4.0 million. Warrant exercises and ELOC financing allowed it to raise $7.1 and $7.0 million respectively, leaving the company with $12.1 million as of August 14, 2024. The company considers that that is enough to support operations through the planned AD and PD FDA meetings and continue until the initiation of the two pivotal studies planned, i.e., early 2025. The company's most recent negative cash flow is -$3.4 million, and that of a quarter before was -$7 million, and it was -$29.2 million for the past year. The pivotal studies would require ample cash, which Annovis needs to secure at least in part before initiation of trials if it were prudent. Annovis does have a mixed shelf outstanding allowing it to pick up further financing of up to $250 million. Risks In line with the above, SA's Quant rating currently has a Strong Sell rating on the stock. The company has seen a tremendous reduction in working capital and has a very low return on total assets. The year-on-year reduction of working capital is -95.23% while the median in the healthcare sector median is -7.82%, and the return on total assets is -852.43% while the median in the healthcare sector is -27.43%. Seeking Alpha Quant rating, October 16, 2024 (Seeking Alpha) As for the risks to my thesis, as mentioned in earlier coverage, the Company has an investor base that continues to support the company's results and appears to believe the drug works. Some investors seem to consider the Phase 3 results in PD a success. Conclusion The Phase 3 trial in Parkinson's, which Annovis has run, appears to have failed to meet the primary endpoint and all secondary endpoints in the intent-to-treat population. The alleged success was based on small subgroups with a diagnosis of >3 years or PIGD, representing respectively only 34% and 21% of the entire ITT population. In both cases, the 10 mg subgroup did not produce statistically significant results, only the 20 mg subgroup did. Finally, no p-values have been communicated. On that basis, Annovis would like to file for approval and would like to run an additional 18-month long Phase 3 trial. I think the path toward approval is difficult, and the company lacks the finances to run another Phase 3 trial. The company would also like to run two additional Phase 3 trials in Alzheimer's disease, considering that the completion of a well-designed and well-executed 6-month trial may be sufficient to support an NDA filing, potentially within one year of the study's initiation. I think that timeline is overly optimistic. I also fail to see how, with no statistically significant results to date in the overall treated population with Parkinson's disease, the company can file for approval with only one six-month Phase 3 trial.  Finances seem to be the biggest problem for Annovis. Annovis will need to tap into further financing, with an expected cost of over $300 million to run its additional trials. At a market cap of about $110 million and a Strong Sell Quant rating, I believe the company's stock is at risk of performing badly in the foreseeable future.","kind":null,"is_publish_news":true,"is_publish_highlight":false,"is_publish_live":false,"is_publish_wemedia":null,"editions":null,"column":"","sentiment":"0","news_tag":"analysis","news_rank":0,"symbols":[],"gpt_button":1},"commentList":[],"isCommentEnd":true,"newsSizeData":{"likeSize":0,"commentSize":0,"repostSize":0,"favoriteSize":0,"likeStatus":false,"favoriteStatus":false},"APP":{"userAgent":"Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)","isDev":false,"isTTM":true,"deviceId":"web-server-community-laohu8-v3","version":"4.29.2","shortVersion":"4.29.2","platform":"web","vendor":"web","appName":"ttm","isIOS":false,"isAndroid":false,"isTiger":false,"isTHS":false,"isWeiXin":false,"isWeiXinMini":false,"isWeiBo":false,"isQQ":false,"isBaiduSwan":false,"isBaiduBox":false,"isDingTalk":false,"isToutiao":false,"isOnePlus":false,"isHuaWei":false,"isXiaomi":false,"isXiaomiWebView":false,"isOppo":false,"isVivo":false,"isSamsung":false,"isMobile":false},"href":"/m/news/2476456925"}