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Where are the Trillion Dollar Biotechs?
Sep. 7th, 2025 04:28 am![[syndicated profile]](https://www.dreamwidth.org/img/silk/identity/feed.png){kind=small}
metafilter_feedThe Dismal Economics of Bio-Tech Research. A long, detailed analysis of why biotech research is still hard. "Human genetics, drug repurposing, and AI are the most common levers [cited to improve things], and each promises to cut costs or derisk pipelines. But the more you look into specific companies and their stories, the more you notice that these strategies rarely work. This is especially true once you turn to age-related diseases, the only market large enough to rescue pharma's economics, yet the one where our best heuristics work the least."
"There are also plenty of examples of selecting a genetically validated target, often outside of oncology or CNS, and failing over and over again to deliver on the promise. CETP variant was enriched in centenarian cohorts and showed coronary heart disease reduction in people with the variant, yet 4 different drugs failed in early-stage trials (likely asset-specific failure). MSTN inhibition leads to obvious muscle mass gains, yet there were 4 failed MSTN antibodies before Scholar Rock got apitegromab approved earlier this year (indication/trial design failure). The list goes on and on. " --- "One number that is worth appreciating is that 80% of all costs associated with bringing a drug to market come from clinical-stage work. That is, if we ever get to molecules designed and preclinically validated in under 1 year, we'll be impacting only a small fraction of what makes drug discovery hard. This productivity gain cap is especially striking given that the majority of the data we can use to train models today is still preclinical, and, in most cases, even pre-animal. A perfect model predictive of in vitro tox saves you time on running in vitro tox (which is less than a few weeks anyway!), doesn't bridge the in vitro to animal translation gap, and especially does not affect the dreaded animal-to-human jump. As such, perfecting predictive validity for preclinical work is the current best-case scenario for the industry. Though we don't have a sufficient amount and types of data to solve even that. " --- Probability of Success by Clinical Trial Phase and Therapeutic Area. (P1 = Phase 1) Therapeutic AreaP1 to P2P2 to P3P3 to ApprovalOverall Oncology57.632.735.53.4 Metabolic/Endocrinology76.259.751.619.6 Cardiovascular73.365.762.225.5 Central Nervous System73.251.951.115.0 Autoimmune/Inflammation69.845.763.715.1 Genitourinary68.757.166.521.6 Infectious Disease70.158.375.325.2 Ophthalmology87.160.774.932.6 Vaccines (Infectious Disease)76.858.285.433.4 Overall66.448.659.013.8 Overall (Excluding Oncology)73.055.763.620.9
"There are also plenty of examples of selecting a genetically validated target, often outside of oncology or CNS, and failing over and over again to deliver on the promise. CETP variant was enriched in centenarian cohorts and showed coronary heart disease reduction in people with the variant, yet 4 different drugs failed in early-stage trials (likely asset-specific failure). MSTN inhibition leads to obvious muscle mass gains, yet there were 4 failed MSTN antibodies before Scholar Rock got apitegromab approved earlier this year (indication/trial design failure). The list goes on and on. " --- "One number that is worth appreciating is that 80% of all costs associated with bringing a drug to market come from clinical-stage work. That is, if we ever get to molecules designed and preclinically validated in under 1 year, we'll be impacting only a small fraction of what makes drug discovery hard. This productivity gain cap is especially striking given that the majority of the data we can use to train models today is still preclinical, and, in most cases, even pre-animal. A perfect model predictive of in vitro tox saves you time on running in vitro tox (which is less than a few weeks anyway!), doesn't bridge the in vitro to animal translation gap, and especially does not affect the dreaded animal-to-human jump. As such, perfecting predictive validity for preclinical work is the current best-case scenario for the industry. Though we don't have a sufficient amount and types of data to solve even that. " --- Probability of Success by Clinical Trial Phase and Therapeutic Area. (P1 = Phase 1) Therapeutic AreaP1 to P2P2 to P3P3 to ApprovalOverall Oncology57.632.735.53.4 Metabolic/Endocrinology76.259.751.619.6 Cardiovascular73.365.762.225.5 Central Nervous System73.251.951.115.0 Autoimmune/Inflammation69.845.763.715.1 Genitourinary68.757.166.521.6 Infectious Disease70.158.375.325.2 Ophthalmology87.160.774.932.6 Vaccines (Infectious Disease)76.858.285.433.4 Overall66.448.659.013.8 Overall (Excluding Oncology)73.055.763.620.9
Sand Battery Heating a Small Finnish town
Sep. 7th, 2025 04:01 ammetafilter_feedA small Finnish town (Pomainen, Finland) is now being heated by a sand battery from Polar Night Energy. This is a giant sand silo encased 100 by 40 feet container. This method is used seasonally to offset wind power. I am posting this because sand batteries were mentioned before in comments and people were debating whether this could work or not. It is out there now - seasonal - but still, out there and functioning. Link is from LiveScience.
"The absolute perfect test of being a 'free speech machine'"
Sep. 6th, 2025 07:21 pmmetafilter_feedA recent episode of The Rest is Entertainment discusses the ethics of performing at the Riyadh Comedy Festival, part of Saudi Arabia's Vision 2030 PR campaign.
More details including how much people are getting paid at the Humorism newsletter. Tickets to see the headliners are available on the official site, including Louis C.K., Kevin Hart, Pete Davidson, Jimmy Carr, Hannibal Buress, and Zarna Garg.
More details including how much people are getting paid at the Humorism newsletter. Tickets to see the headliners are available on the official site, including Louis C.K., Kevin Hart, Pete Davidson, Jimmy Carr, Hannibal Buress, and Zarna Garg.
Music, the occult / religion & geometry / math were all connected for Co
Sep. 6th, 2025 06:10 pmmetafilter_feedThelonious Monk once said "All musicians are subconsciously mathematicians". Musicians like John Coltrane though have been very much aware of the mathematics of music and consciously applied it to their works. The "Coltrane Circle" is (to me) proof of it in Coltrane's case ... from John Coltrane's Tone Circle [Roel's World]
Maru (2007-2025)
Sep. 6th, 2025 10:51 ammetafilter_feedMaru (まる) - the beloved Scottish Fold boy with a penchant for (among other things) boxes, fish bowls and swings - has passed over The Rainbow Bridge after a short illness.
My thoughts go out to his friends Hana and Miri and, of course, his remarkable human. Maru previously.
My thoughts go out to his friends Hana and Miri and, of course, his remarkable human. Maru previously.
いつも応援してくださる皆さまへ。To everyone who always supports Maru.
Sep. 6th, 2025 10:00 ammaru_feedいつも応援してくださる皆さまへ まるさんは本日9月6日（土）、午前7：15分に天国へ行ってしまいました。 実は、まるさんはこの1週間で、とても体調が悪くなっていました。 2週間前までは食欲も旺盛で、毎食完食、そして体重も […]
A song about David Attenborough
Sep. 6th, 2025 08:22 ammetafilter_feedDavid Attenborough by Biscuithead & the Biscuit Badgers. Found on Threads.
Scientists uncover the secret lives of dugongs in Moreton Bay
Sep. 6th, 2025 07:14 ammetafilter_feedScientists uncover the secret lives of dugongs in Moreton Bay. The world's largest health study of dugongs in Moreton Bay provides critical clues for helping conserve the enigmatic marine mammal, especially in other locations where numbers are falling.
The Ski Club of International Journalists is as real as you or me
Sep. 6th, 2025 07:01 ammetafilter_feedThey walked back to the hotel, out of the cold, into the warm bosom of Nations Night, and were whopped by a musky, dark, magnificent smell ... the many cured meats of Europe and Eurasia ... fermented milks and fermented grains ... raw mollusks and salted cod ... goat cheese and anchovies and sausage and wine ... a thrilling blend of sounds and deep stenches ... the French cracking oysters ... the Swiss melting raclette...the Kazakhstanis slicing some kind of dried animal leg ... the Canadians pouring maple syrup on snow... an Italian DJ playing Linkin Park's "Numb" ... from Intrigue on the Slopes of Bardonecchia by Noah Rawlings [The Paris Review; ungated]
Wikipedia is resilient because it is boring
Sep. 6th, 2025 06:40 ammetafilter_feedThe world's largest encyclopedia became the factual foundation of the web, but now it's under attack.
Excellent article on Wikipedia and the challenges it faces as it approaches its 25th birthday.
Excellent article on Wikipedia and the challenges it faces as it approaches its 25th birthday.
an inverted kill file, reconstructed virtually
Sep. 6th, 2025 12:57 ammetafilter_feedSluda Builds built the Kowloon Walled City in Minecraft.
More about the place in Flashbak, and the excerpt from 'Bloodsport' filmed there.
More about the place in Flashbak, and the excerpt from 'Bloodsport' filmed there.
weekend open thread – September 6-7, 2025
Sep. 5th, 2025 11:07 pmaskamanager_feed
This comment section is open for any non-work-related discussion you’d like to have with other readers, by popular demand.
Here are the rules for the weekend posts.
Book recommendation of the week: Morningside Heights, by Cheryl Mendelson. The woman who wrote the amazing Home Comforts: the Art and Science of Keeping House also wrote a novel! Two married musicians grapple with the their careers, the troubled love lives of their friends, the aftermath of a neighbor’s death, and the way rapid gentrification may soon push them out of their beloved home. (Amazon, Bookshop)
* I earn a commission if you use those links.
The post weekend open thread – September 6-7, 2025 appeared first on Ask a Manager.
Researching the Far Plane
Sep. 5th, 2025 08:34 pmmetafilter_feed(Sigma, the narrator): "Hello esteemed researcher! We at the Zooliminology Project are glad to have you here.
You have been selected for your aptitude in your field of [INSERT FIELD HERE].
We are the only organization in the world researching phenomena in the plane of reality just next door."
Videos: Orientation (8m) - Ghost (4m) - Water 2 (3m) - Prince (5½m) - Longlegs (5m) - Golbo (3½) Please, do not the Longlegs.
"Every day, someone or something disappears from our world with no trace, only to reappear a few minutes or hours later. Though this often gets mistaken with someone just being forgetful. Remember the time you lost your remote? You didn't lose it, it simply fell between the cracks of reality only to return moments later. Or it didn't. It's hard to tell. Less commonly, anomalies will leak into unpopulated urban areas, manifesting as strange creatures or bent space, only to later disappear without warning. Only a quarter of these reports come from drunk homeless people. With us, you'll get to dive into the heart of these strange occurrences. You'll do this by delving into the place where missing objects go and whence reality-bending phenomena come: The Far Plane.
Videos: Orientation (8m) - Ghost (4m) - Water 2 (3m) - Prince (5½m) - Longlegs (5m) - Golbo (3½) Please, do not the Longlegs.
"Every day, someone or something disappears from our world with no trace, only to reappear a few minutes or hours later. Though this often gets mistaken with someone just being forgetful. Remember the time you lost your remote? You didn't lose it, it simply fell between the cracks of reality only to return moments later. Or it didn't. It's hard to tell. Less commonly, anomalies will leak into unpopulated urban areas, manifesting as strange creatures or bent space, only to later disappear without warning. Only a quarter of these reports come from drunk homeless people. With us, you'll get to dive into the heart of these strange occurrences. You'll do this by delving into the place where missing objects go and whence reality-bending phenomena come: The Far Plane.
the anthropic principle
Sep. 5th, 2025 07:39 pmmetafilter_feed"In a landmark settlement, Anthropic, a leading artificial intelligence company, has agreed to pay $1.5 billion to a group of authors and publishers after a judge ruled it had illegally downloaded and stored millions of copyrighted books. The settlement is largest payout in the history of U.S. copyright cases. Anthropic will pay $3,000 per work to 500,000 authors." Anthropic Agrees to Pay $1.5 Billion to Settle Lawsuit With Book Authors, NYT (archive)
The Author's Guild has a page on what to do if you believe you may be impacted.
The Author's Guild has a page on what to do if you believe you may be impacted.
open thread – September 5, 2025
Sep. 5th, 2025 03:00 pmaskamanager_feedIt’s the Friday open thread!
The comment section on this post is open for discussion with other readers on any work-related questions that you want to talk about (that includes school). If you want an answer from me, emailing me is still your best bet*, but this is a chance to take your questions to other readers.
* If you submitted a question to me recently, please do not repost it here, as it may be in my queue to answer.
The post open thread – September 5, 2025 appeared first on Ask a Manager.
An engineer restores pay phones for free public use
Sep. 5th, 2025 12:09 pmmetafilter_feedAn engineer restores pay phones for free public use. (Orange County, Vermont)
"I was twelve when the das started killing themselves all around me"
Sep. 5th, 2025 11:51 ammetafilter_feedAnd that, believe it or not, was the end of Bertie's chances. By making the financial crash a culturally live issue again, she channelled 1.21Gws of raw artistic power directly into Bertie's campaign and sent it like a DeLorean, back into all those futures lost.
Irish country pop singer CMAT's new single Euro-Country, has just scuppered any chances ex-Taoiseach Bertie Ahern had of entering the upcoming presidential elections, as he was in charge during the 2008 crisis and its aftermath in which the male suicide rate in Ireland spiked.