This is great news! I think people forget how anti-skin cancer protocols even as simple as applying suntan lotion weren't as popular as recent as 50-60 years ago. Lots of "sun children" of the 50s and 60s are now feeling the repercussions of only applying baby oil and are getting hit with lots of melanoma.
What’s funny is before the 50s and 60s everyone knew you should cover up and women wore bonnets. That too much sun was bad for you.
Laura Ingalls Wilder of Little House fame (I mention this a lot as I read these to my children as an adult, and they’re a fascinating look at 1880s America) has lots of places where her mother says “put on your bonnet! Don’t get too much sun!”. We act like people in the past were ignorant but people in the 50s and 60s were just a very special type of arrogant, all of Chesterton’s fences were torn down during that time period.
I don't think that was because of UV exposure or anything related. Look at Bedouin tribes even today. They wrap up head to toe, man and woman and child alike, not to avoid tanning but because prolonged exposure to direct infrared will fry you like an egg.
I grew up in the same general region as Wilder, and we sought shade not to avoid sunburn. We were all chestnut brown by the end of summer anyway. It's because the direct sunlight on an August afternoon was brutally hot, and you wanted as little of it to hit your skin as possible.
They thought too much sun was bad for you because back then tanned skin was considering a mark of being poor and pale skin was a mark of being wealthy since rich people didn’t have to work outside.
They also had puritanical Victorian notions of modesty and covering up.
There was no knowledge linking sun exposure to cancer or negative health effects. People in the past indeed were ignorant on many things.
Or rather, linked to completely wrong negative health effects that were just “common knowledge” thus requiring no actual evidence like:
People with light skin should always wear a hat that fully covers the head/face in tropical/equatorial climates (okay, good so far) or else the powerful sun rays will penetrate the skull (?) causing brain damage that will make you go insane (!?!?)
Victorians may have inadvertently protected themselves against excess mortality due to melanomas with their pith helmets, but it’s pretty hard to argue they were actually “correct” with modern hindsight considering the entire chain of reasoning was wrong.
(For example, you see this in Kipling’s writing where he’ll randomly include an ominous case of some guy who forgot/lost his hat and promptly had to be committed to an insane asylum, as one does).
Unless you are albino (which is a large set of other problems) being in the sun all day will develop enough of a tan that you won't sunburn. There might be a problem in spring, but by summer time most people will have spent enough time outdoors that they wouldn't sunburn. I've always been the lightest person in town (a tie in Stockholm) and I can spend all day outside without any sunscreen and I won't burn on the parts of my body normally not covered (my arms), but other parts would burn in a few minutes (If I took off my hat or shirt...)
Black people who spend all their time indoors or covered up will get sunburned if they go outside. If that black person gradually increases their sun exposure they can (in a few weeks) reach the point where they can be outside without sunscreen and they will not get sun burned.
Note that I'm making no claims on how natural sunburn resistant affects skin cancer.
This is silly.... most of the world didn't live in england.
All cultures (including mine), have a way to warn kids, or adults for not to stay too long in the sun.
From normal sunburn, to feeling light-headenes/fainting due to heat excaustion, etc.
In the winter was the opposite. (stay in the sun to get some sunlight and not get sick).
So, they knew, and had nothing to do with 'class'. Also, they knew some sun was good/beneficial, especially during the winter.
> before the 50s and 60s everyone knew you should cover up and women wore bonnets. That too much sun was bad for you.
I'd say partly true, mostly false. As sibling comment mentions, much of this was driven by fashion and class etc. and not from some fundamental understanding of damaging UV exposure.
Furthermore there was research that was trendy at the time called "heliotherapy" [0] where all sorts of diseases were believed curable by sun exposure, including smallpox, TB, etc.
We developed creams that stopped sunburn, but were still great at getting you cancer. A lot of the ads from 70s and 80s talked about how they stopped UVB but let the tanning UVA through! So yes, they didn't burn, but the long term cancer rates exploded, along with all the skin aging.
So it's not that they ignored the all knowledge. I blame most of it on the rather detrimental tech advancement. Like cigarettes with filters: now safer (except you can smoke more now, and the cancer risk is still a disaster)
> We act like people in the past were ignorant but people in the 50s and 60s were just a very special type of arrogant,
I’d be curious to know if tetraethyllead in gasoline has anything to do with people from that time being cavalier about exposure to the sun, or if the science was just not there to make the connection between sun exposure and skin cancer.
+1. Also, just to call out, it doesn't need to be _warm_ for you to need sunblock. Even when it's cooler / cloudier out there you can still get skin damage. Look for UV rating rather than temperature. Conversely, it being hot doesn't imply high-UV either.
I didn't know about the UV index or what it meant until like three years ago. It blows my mind I went that long without understanding. It was actually wonderful to learn that I could just see if I needed sunblock based on a 0-10 scale.
We never wore sunscreen as kids because we didn't burn. I probably have had three sunburns in my life. Learned once I became an adult that that wasn't sound logic...
I think the Apple Watch or the Weather app or something finally taught me UV index about the same time. Has this information always been readily available? Similarly mind blown about it.
I’ve always wondered about this. I have fair skin, and I tend to burn somewhat easily in very sunny environments like the beach.
However, I’ve never gotten so much as a whisper of sunburn / suntan / anything on an actually cloudy day where sun wasn’t hitting me directly. Is the damage a different type that’s imperceptible? Or is this a public health comms strategy where they assume people will see a single cloud in the sky and decide it’s fine to skip sunscreen, so they talk about how you should slather yourself with sunscreen 24/7, even if the sun is obscured?
I think the point is just about temperature. I've experienced this out on lakes in the northern US for example. It's sunny but not like a tropical beach, and maybe even a little chilly. But you'll definitely get burnt without sunscreen
People who are new to skiing/snowboarding are often surprised that their faces get sunburned, because of course it's cold and so how could they get burned
> Cutaneous melanoma (CM) accounted for around 331,700 cancer cases globally in 2022
> An estimated 267,353 (95% uncertainty intervals [UI]: 242,818, 278,638) CM cases were UVR attributable globally in 2022
UVR = Ultraviolet radiation
Cutaneous melanoma (CM) is the vast majority of melanoma cases in the US at least:
> The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, from https://pubmed.ncbi.nlm.nih.gov/9781962/
tl;dr ~80% of Cutaneous melanoma cases are attributable to UV exposure.
Please be careful and charitable in reading others' words, especially as they relate to scientific topics.
OP did not say that melanoma has no sun exposure risk but that it is lower than the risks associated with other cutaneous cancers (e.g., SCC and BCC) and it would seem that's true based on the very short search I performed.
Yes, but OP said that in response to a comment attributing melanoma to sun exposure, in a conversation where nobody had brought up SCC or BCC. It's still a misleading comment, in my opinion.
Yes, however the trial succeeded. But by "how much", is not yet released. This trial was not against placebo, but the already existing, and effective Keytruda treatment.
Huge, uplifting, news, hope the study will bear further fruit. Considering that 90% of all clinical trials fail, it's good to read about a truly promising one for once.
Yes, mRNA vaccines are promising for many but not all cancer types, and there are many ongoing clinical trials. There's also a lot we yet don't know about how to design them.
One of the leading problems is that we don't know how to pick the right neoantigens (mutant cancer proteins) which can trigger the optimal immune response.
Moderna used a simple heuristic, "how likely is this antigen to show up on the cell surface?" which makes sense, since an antigen has to show up on the cell surface for the immune system to see it. But there's so much missing from this model, and we just don't have enough data. Failures in clinical trials of mRNA vaccines may well be caused by this problem. (Yes, this is a good problem for AI, if we can get enough data).
Individualized immune cancer therapy has been touted as the next big thing for half a century. It's nothing new, and with few exceptions, such as skin cancer, has failed to yield much. scientists, for decades, have tired to harness the immune system to attackcancer and it almost never works.
Those few exceptions have been monumental in how they've changed cancer treatment. Skin cancer has been particularly well treated with immunotherapy, but other cancers have also benefited from the exact same research and drugs (as it turns out, the specific mutations the immunotherapies like Keytruda target express in other cancers). The reason skin cancer gets so much attention is because it's one of the most commonly diagnosed and treated cancers. (Colon is more common, I believe, but it often doesn't get detected. Get your colonoscopies folks).
It has moved fast enough that I've heard from multiple oncologists that the all 5 year survivability numbers are dated because the treatments are newer than the studies.
We've come a LONG way in a very short period in terms of cancer treatment. It still sucks, but not as much as it once did.
> Individualized immune cancer therapy has been touted as the next big thing for half a century. It's nothing new, and with few exceptions, such as skin cancer, has failed to yield much. scientists, for decades, have tired to harness the immune system to attackcancer and it almost never works.
"Almost never" is doing a lot of work. You may be aware that most drugs fail over the course of development and human trials?
Anyway, checkpoint inhibitor therapy is a massive boon to oncology and was only brought into widespread use over the past 15 years.
Personalized mRNA vaccines are in fact, extremely new, and only made possible by recent advances across multiple fields. This comment reveals a total lack of basic understanding on this topic.
I believe the comment was talking specifically about immunotherapy rather than personalized mRNA. But I'd agree it's still misinformed as immunotherapy has been a game changer across multiple cancers.
u/danjl was originally asking about "this class of drugs", which is more reasonably interpreted as referring to personalized mRNA vaccines rather than the much broader concept of (personalized or not) immunotherapy.
The comment is wrong because it's stupid. Just because we've known that personalized immunotherapy was a promising idea for a long time, and have been trying it with the limited tools we had (CAR T being the poster child, and while an incredible advancement for blood cancers and many other diseases, it is notoriously dangerous and expensive), does not mean we had the technology to accomplish it. Today's results are only possible because of recent advancements in multiple fields, and to respond with "they've tried immunotherapy for decades" is profoundly ignorant. You may as well say, "scientists have been trying to cure cancer for years."
I think the "expected value" was priced in, but regardless of the result, this trial would move the stock price towards that direction.
Biotech is one of the very very very few areas of the stockmarket where specialist knowledge generates alpha.
Trolling through random biotechs, learning about their tech, and investing in the most promising applications of that tech in the most impactful areas is something that happens somewhat on publicly traded markets. With tech, most of that happens pre-IPO.
Even if you were to optimally price in all available information you still have uncertainty of what will actually happen. i.e. A 1 dollar coin flip has an expected value of 50c before it’s thrown and it will collapse either to zero or to one after the uncertainty is resolved.
It was priced in, the share price prior to the news being released was taking into account a probability measurement of the trial succeeding or failing. You can’t price in both options of a binary outcome simultaneously, so part of the equity price was functionally equivalent to a call option on the outcome of the drug trial that only resolved after the trial results are announced.
It’s similar to the situation where a company puts out a public offer to buy another company at say, $50 a share on a day that the acquisition target is trading at $40/share.
If the stock of the target company is trading at $46/share, the market is pricing in the probability of the acquisition not happening. If the market knew the acquisition would happen with 100% certainty, the price of the target company shares would be equal to the buyout share price offer. You can assume the risk of the acquisition not happening by purchasing shares at $46, and if it does end up going through, you earn $4 a share from assuming that risk.
My father has gastric melonama and pretty much last few days left — does someone with knowledge know if this vaccine can be of any help? Or any registry available?
Deepest sympathies, and I'm no oncologist - but I think that'd be like trying to patch hull of the Titanic after her stern has lifted out of the water. So many cascading failures are in motion by then that saving him really isn't possible.
Ever since I first heard of them a decade ago, it seemed that mRNA therapeutic vaccines were going to be the next wave of massive improvements in care. It's taken a bit longer than I had expected, and it's not that mRNA is the only way to make these sorts of vaccines, it's just so much better than the alternatives.
I don't know if that counts as the same "trick" or not as it's another antiviral vaccine. Not that I disagree with you.
I read that this mRNA flu vaccine can be more effective then the regular annual flu shot, simply because the time to create it is shorter, therefor the guess at what strains will circulate that year is more accurate.
I mean, the question is almost always about whether it's economical or not, right? Whether you can find diseases it's efficacious to treat with this mechanism, and prove it (trials are expensive).
not really a huge win. It's going to cost taxpayers significancy and may not improve survival much or total life expectancy . The stock is way overextended, assuming it even works well enough to be a commercial success. History has shown this is seldom the case. I would short it if wasn't so expensive and risky to do so. They would not even specify how much it improved the 5 year survival rate.
> not really a huge win. It's going to cost taxpayers significancy and may not improve survival much or total life expectancy . The stock is way overextended. It's a long way from anything that can be used on patients, assuming it even works well enough to be a commercial success. History has shown this is seldom the case. I would short it if wasn't so expensive and risky to do so.
Buddy, this is a phase 3 trial. This is about as close as you can get to "anything that can be used on patients" without already being approved.
It is clear that you don't have experience in this area.
According to Gemini, Moderna uses machine learning to speed up sequence selection and mRNA optimization. After all, this is not a mass-produced vaccine, but a personalized one.
I for one would like to see the data rather than a press release. Is this even serious? A press release with no link to outside twitter?
I feel like everything companies, and presidents, say now is directly geared to triggering AI trades.
The only thing they are looking at with this drug is people living one more month over existing drugs.
THIS IS NOTHING.
"The median PFS (progression-free survival) for KEYTRUDA was 5.5 months (2-week group) and 4.1 months (3-week group) compared to 2.8 months for ipilimumab (HR 0.58, P<0.00001 for the KEYTRUDA groups vs. ipilimumab,"
The median PFS (progression-free survival) for KEYTRUDA was 5.5 months (2-week group) and 4.1 months (3-week group) compared to 2.8 months for ipilimumab (HR 0.58, P<0.00001 for the KEYTRUDA groups vs. ipilimumab, 95% CI, 0.46-0.72 for 2-week group and 0.47-0.72 for 3-week group, respectively). The estimated 6-month PFS rates for the KEYTRUDA and ipilimumab arms were 47.3 percent, 46.4 percent and 26.5 percent, respectively. One-year OS for KEYTRUDA was 74.1 percent (2-week group) and 68.4 percent (3-week group) compared to 58.2 percent for ipilimumab (HR 0.63 [95% CI, 0.47-0.83, P=0.00052] for the 2-week group and HR 0.69 [95% CI, 0.52-0.90, P=0.00358] for the 3-week group). At the time of analysis, median overall survival was not reached in any treatment group.
1. That's not what progression-free survival means.
2. I don't think AI was mentioned once in this press release.
3. This drug was approved for trial in 2014, so if it had something to do with deep learning, that would actually be a massive announcement.
4. The paragraph immediately following the one you clipped talks about Overall Response Rate (ORR) and throughout the release they discuss Overall Survival (OS).
5. This is not "NOTHING" in statistical terms, but even more so to people with melanoma.
Interjecting with a fact. Moderna described the neoantigen immunogenicity prediction algorithm they used to design the vaccines as “a deterministic machine learning (ML) algorithm,” so it may be a small neural network or more traditional algorithm, probably not deep learning.
No it isn’t. They did a test with great specificity and got undeniable P values. Now they can refine the action and start saving people. This is a huge, huge win.
you're also looking at a different, older study. Keytruda is a little strange in that it has a very long tail in survivorship, works best in certain cases, and median PFS isn't a really great metric.
In other news, your barber thinks you need a haircut.
Until there is a proven net overall health benefit to this therapy, I wouldn't waste much ink on it. Also, can someone please tell me how one controls the dose for an mRNA therapy ?
If you actually had melanoma (a very aggressive type of skin cancer) you would be glad for one more chance of maybe still being alive a few years from now.
This is great news! I think people forget how anti-skin cancer protocols even as simple as applying suntan lotion weren't as popular as recent as 50-60 years ago. Lots of "sun children" of the 50s and 60s are now feeling the repercussions of only applying baby oil and are getting hit with lots of melanoma.
What’s funny is before the 50s and 60s everyone knew you should cover up and women wore bonnets. That too much sun was bad for you.
Laura Ingalls Wilder of Little House fame (I mention this a lot as I read these to my children as an adult, and they’re a fascinating look at 1880s America) has lots of places where her mother says “put on your bonnet! Don’t get too much sun!”. We act like people in the past were ignorant but people in the 50s and 60s were just a very special type of arrogant, all of Chesterton’s fences were torn down during that time period.
I don't think that was because of UV exposure or anything related. Look at Bedouin tribes even today. They wrap up head to toe, man and woman and child alike, not to avoid tanning but because prolonged exposure to direct infrared will fry you like an egg.
I grew up in the same general region as Wilder, and we sought shade not to avoid sunburn. We were all chestnut brown by the end of summer anyway. It's because the direct sunlight on an August afternoon was brutally hot, and you wanted as little of it to hit your skin as possible.
No I think you’re looking at this wrong.
They thought too much sun was bad for you because back then tanned skin was considering a mark of being poor and pale skin was a mark of being wealthy since rich people didn’t have to work outside.
They also had puritanical Victorian notions of modesty and covering up.
There was no knowledge linking sun exposure to cancer or negative health effects. People in the past indeed were ignorant on many things.
Or rather, linked to completely wrong negative health effects that were just “common knowledge” thus requiring no actual evidence like:
People with light skin should always wear a hat that fully covers the head/face in tropical/equatorial climates (okay, good so far) or else the powerful sun rays will penetrate the skull (?) causing brain damage that will make you go insane (!?!?)
Victorians may have inadvertently protected themselves against excess mortality due to melanomas with their pith helmets, but it’s pretty hard to argue they were actually “correct” with modern hindsight considering the entire chain of reasoning was wrong.
(For example, you see this in Kipling’s writing where he’ll randomly include an ominous case of some guy who forgot/lost his hat and promptly had to be committed to an insane asylum, as one does).
That's the thing about traditions and Chesterton's fences, you don't need to know why they work for them to work.
Pretty sure a bad sunburn sucked back then as much as now, and was something one tried to avoid.
Unless you are albino (which is a large set of other problems) being in the sun all day will develop enough of a tan that you won't sunburn. There might be a problem in spring, but by summer time most people will have spent enough time outdoors that they wouldn't sunburn. I've always been the lightest person in town (a tie in Stockholm) and I can spend all day outside without any sunscreen and I won't burn on the parts of my body normally not covered (my arms), but other parts would burn in a few minutes (If I took off my hat or shirt...)
It's bizarre that you cite being outside at 60 degrees latitude as evidence related to high UV exposure.
That's like a resident of Porto saying most people don't get frostbite walking around outside in winter...
I've been outside at lots of different latitudes. I don't live in Stockholm, but I've been there.
I don’t think this is correct, Black people still get sunburns
Black people who spend all their time indoors or covered up will get sunburned if they go outside. If that black person gradually increases their sun exposure they can (in a few weeks) reach the point where they can be outside without sunscreen and they will not get sun burned.
Note that I'm making no claims on how natural sunburn resistant affects skin cancer.
This is silly.... most of the world didn't live in england.
All cultures (including mine), have a way to warn kids, or adults for not to stay too long in the sun. From normal sunburn, to feeling light-headenes/fainting due to heat excaustion, etc.
In the winter was the opposite. (stay in the sun to get some sunlight and not get sick).
So, they knew, and had nothing to do with 'class'. Also, they knew some sun was good/beneficial, especially during the winter.
> before the 50s and 60s everyone knew you should cover up and women wore bonnets. That too much sun was bad for you.
I'd say partly true, mostly false. As sibling comment mentions, much of this was driven by fashion and class etc. and not from some fundamental understanding of damaging UV exposure.
Furthermore there was research that was trendy at the time called "heliotherapy" [0] where all sorts of diseases were believed curable by sun exposure, including smallpox, TB, etc.
0: https://en.wikipedia.org/wiki/Light_therapy#History
We developed creams that stopped sunburn, but were still great at getting you cancer. A lot of the ads from 70s and 80s talked about how they stopped UVB but let the tanning UVA through! So yes, they didn't burn, but the long term cancer rates exploded, along with all the skin aging.
So it's not that they ignored the all knowledge. I blame most of it on the rather detrimental tech advancement. Like cigarettes with filters: now safer (except you can smoke more now, and the cancer risk is still a disaster)
> We act like people in the past were ignorant but people in the 50s and 60s were just a very special type of arrogant,
I’d be curious to know if tetraethyllead in gasoline has anything to do with people from that time being cavalier about exposure to the sun, or if the science was just not there to make the connection between sun exposure and skin cancer.
My parents were nudists. So I spent a bunch of 60s % 70s getting sunburn. I bet that even baby oil would have cut some of that down.
+1. Also, just to call out, it doesn't need to be _warm_ for you to need sunblock. Even when it's cooler / cloudier out there you can still get skin damage. Look for UV rating rather than temperature. Conversely, it being hot doesn't imply high-UV either.
I didn't know about the UV index or what it meant until like three years ago. It blows my mind I went that long without understanding. It was actually wonderful to learn that I could just see if I needed sunblock based on a 0-10 scale.
We never wore sunscreen as kids because we didn't burn. I probably have had three sunburns in my life. Learned once I became an adult that that wasn't sound logic...
I think the Apple Watch or the Weather app or something finally taught me UV index about the same time. Has this information always been readily available? Similarly mind blown about it.
I’ve always wondered about this. I have fair skin, and I tend to burn somewhat easily in very sunny environments like the beach.
However, I’ve never gotten so much as a whisper of sunburn / suntan / anything on an actually cloudy day where sun wasn’t hitting me directly. Is the damage a different type that’s imperceptible? Or is this a public health comms strategy where they assume people will see a single cloud in the sky and decide it’s fine to skip sunscreen, so they talk about how you should slather yourself with sunscreen 24/7, even if the sun is obscured?
I think the point is just about temperature. I've experienced this out on lakes in the northern US for example. It's sunny but not like a tropical beach, and maybe even a little chilly. But you'll definitely get burnt without sunscreen
People who are new to skiing/snowboarding are often surprised that their faces get sunburned, because of course it's cold and so how could they get burned
Geography has a lot to do with it as well. Proximity to the equator, altitude, etc.
I knew HN was geriatric, but damn
melanoma , unlike the others, has a much weaker link to sun exposure. its why melanoma often appear in areas with no sun exposure
Misleading comment.
From https://onlinelibrary.wiley.com/doi/10.1002/ijc.35463
> Cutaneous melanoma (CM) accounted for around 331,700 cancer cases globally in 2022
> An estimated 267,353 (95% uncertainty intervals [UI]: 242,818, 278,638) CM cases were UVR attributable globally in 2022
UVR = Ultraviolet radiation
Cutaneous melanoma (CM) is the vast majority of melanoma cases in the US at least:
> The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, from https://pubmed.ncbi.nlm.nih.gov/9781962/
tl;dr ~80% of Cutaneous melanoma cases are attributable to UV exposure.
Please be careful and charitable in reading others' words, especially as they relate to scientific topics.
OP did not say that melanoma has no sun exposure risk but that it is lower than the risks associated with other cutaneous cancers (e.g., SCC and BCC) and it would seem that's true based on the very short search I performed.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5742376/
Yes, but OP said that in response to a comment attributing melanoma to sun exposure, in a conversation where nobody had brought up SCC or BCC. It's still a misleading comment, in my opinion.
The criticism and correction were polite, helpful, and appropriate.
The original comment is misleading. Your reply is bizarre, and seems to deliberately misread the original comment, the reply, and the context.
Substantially better link:
https://www.merck.com/news/merck-and-moderna-announce-phase-...
Still no actual Phase 3 data presented.
Yes, however the trial succeeded. But by "how much", is not yet released. This trial was not against placebo, but the already existing, and effective Keytruda treatment.
I believe both were done with Keytruda. Control was Keytruda without the mRNA treatment.
So this should answer the question of "how much better is this with the best we currently have".
This content is geo/IP fenced
Hope this helps:
https://archive.ph/SQQ97
My father is currently dying of malignant melanoma with brain metastasis...
I wish this treatment was available a few years ago.
That is devastating. How are you doing?
Huge, uplifting, news, hope the study will bear further fruit. Considering that 90% of all clinical trials fail, it's good to read about a truly promising one for once.
Will this targeted approach be beneficial to other cancer types? Is there any data or theory about this class of drugs as a more general therapy?
Yes, mRNA vaccines are promising for many but not all cancer types, and there are many ongoing clinical trials. There's also a lot we yet don't know about how to design them.
Here's a great blog post on this, "How to build a cancer vaccine, and whether they will work this time": https://www.owlposting.com/p/how-to-build-a-cancer-vaccine-a...
Here's the blog post I wrote on personalized mRNA vaccines: https://hedonicescalator.substack.com/p/did-paul-conyngham-r...
One of the leading problems is that we don't know how to pick the right neoantigens (mutant cancer proteins) which can trigger the optimal immune response.
Moderna used a simple heuristic, "how likely is this antigen to show up on the cell surface?" which makes sense, since an antigen has to show up on the cell surface for the immune system to see it. But there's so much missing from this model, and we just don't have enough data. Failures in clinical trials of mRNA vaccines may well be caused by this problem. (Yes, this is a good problem for AI, if we can get enough data).
Individualized immune cancer therapy has been touted as the next big thing for half a century. It's nothing new, and with few exceptions, such as skin cancer, has failed to yield much. scientists, for decades, have tired to harness the immune system to attackcancer and it almost never works.
> and with few exceptions
Those few exceptions have been monumental in how they've changed cancer treatment. Skin cancer has been particularly well treated with immunotherapy, but other cancers have also benefited from the exact same research and drugs (as it turns out, the specific mutations the immunotherapies like Keytruda target express in other cancers). The reason skin cancer gets so much attention is because it's one of the most commonly diagnosed and treated cancers. (Colon is more common, I believe, but it often doesn't get detected. Get your colonoscopies folks).
It has moved fast enough that I've heard from multiple oncologists that the all 5 year survivability numbers are dated because the treatments are newer than the studies.
We've come a LONG way in a very short period in terms of cancer treatment. It still sucks, but not as much as it once did.
> Individualized immune cancer therapy has been touted as the next big thing for half a century. It's nothing new, and with few exceptions, such as skin cancer, has failed to yield much. scientists, for decades, have tired to harness the immune system to attackcancer and it almost never works.
"Almost never" is doing a lot of work. You may be aware that most drugs fail over the course of development and human trials?
Anyway, checkpoint inhibitor therapy is a massive boon to oncology and was only brought into widespread use over the past 15 years.
Personalized mRNA vaccines are in fact, extremely new, and only made possible by recent advances across multiple fields. This comment reveals a total lack of basic understanding on this topic.
I believe the comment was talking specifically about immunotherapy rather than personalized mRNA. But I'd agree it's still misinformed as immunotherapy has been a game changer across multiple cancers.
u/danjl was originally asking about "this class of drugs", which is more reasonably interpreted as referring to personalized mRNA vaccines rather than the much broader concept of (personalized or not) immunotherapy.
The comment is wrong because it's stupid. Just because we've known that personalized immunotherapy was a promising idea for a long time, and have been trying it with the limited tools we had (CAR T being the poster child, and while an incredible advancement for blood cancers and many other diseases, it is notoriously dangerous and expensive), does not mean we had the technology to accomplish it. Today's results are only possible because of recent advancements in multiple fields, and to respond with "they've tried immunotherapy for decades" is profoundly ignorant. You may as well say, "scientists have been trying to cure cancer for years."
I listened to a great podcast on this just a month ago - too bad that I thought all of this would obviously be priced in already… https://virological.podigee.io/51-21-cancer-vaccines-how-the...
I think the "expected value" was priced in, but regardless of the result, this trial would move the stock price towards that direction.
Biotech is one of the very very very few areas of the stockmarket where specialist knowledge generates alpha.
Trolling through random biotechs, learning about their tech, and investing in the most promising applications of that tech in the most impactful areas is something that happens somewhat on publicly traded markets. With tech, most of that happens pre-IPO.
Even if you were to optimally price in all available information you still have uncertainty of what will actually happen. i.e. A 1 dollar coin flip has an expected value of 50c before it’s thrown and it will collapse either to zero or to one after the uncertainty is resolved.
I don't believe the efficient market hypothesis. However even if you do, new information has arrived and that will affect the price.
Hard to price in the political factors now involved in Moderna's success or lack of success.
It was priced in, the share price prior to the news being released was taking into account a probability measurement of the trial succeeding or failing. You can’t price in both options of a binary outcome simultaneously, so part of the equity price was functionally equivalent to a call option on the outcome of the drug trial that only resolved after the trial results are announced.
It’s similar to the situation where a company puts out a public offer to buy another company at say, $50 a share on a day that the acquisition target is trading at $40/share.
If the stock of the target company is trading at $46/share, the market is pricing in the probability of the acquisition not happening. If the market knew the acquisition would happen with 100% certainty, the price of the target company shares would be equal to the buyout share price offer. You can assume the risk of the acquisition not happening by purchasing shares at $46, and if it does end up going through, you earn $4 a share from assuming that risk.
My father has gastric melonama and pretty much last few days left — does someone with knowledge know if this vaccine can be of any help? Or any registry available?
Deepest sympathies, and I'm no oncologist - but I think that'd be like trying to patch hull of the Titanic after her stern has lifted out of the water. So many cascading failures are in motion by then that saving him really isn't possible.
Ever since I first heard of them a decade ago, it seemed that mRNA therapeutic vaccines were going to be the next wave of massive improvements in care. It's taken a bit longer than I had expected, and it's not that mRNA is the only way to make these sorts of vaccines, it's just so much better than the alternatives.
I'm very very excited to see what comes next.
This appears to be a potentially huge win for health. The market has Moderna up 153% at time of writing, which is some sort of validation I suppose.
Related stories:
https://www.fiercebiotech.com/biotech/merck-and-modernas-per...
https://www.reuters.com/legal/litigation/merck-moderna-say-m...
https://www.wsj.com/health/pharma/moderna-merck-vaccine-succ...
oh nice. If it goes up another 100% I may not lose money on this stock anymore.
And if it doubles after that, I may even beat a passive S&P 500 investment.
You know many stocks have done better than the SP500, right?
invest only in the ones that are going to go up - why didn't i think of that?!
I am in fact aware that some of my stock investments have beaten the market while others have underperformed the market.
MRNA, as it happens, is the latter.
I mean, this appears to be validation of mRNA in general, right?
Saving a couple million people in the pandemic wasn’t validation enough?
100%. What I meant to say was that this proves that it wasn't somehow a one trick pony.
There is also a mRNU flu vaccine now: https://www.modernatx.com/ir-insights-mflusiva
I don't know if that counts as the same "trick" or not as it's another antiviral vaccine. Not that I disagree with you.
I read that this mRNA flu vaccine can be more effective then the regular annual flu shot, simply because the time to create it is shorter, therefor the guess at what strains will circulate that year is more accurate.
https://pubmed.ncbi.nlm.nih.gov/41701031/
But it is yet more validation. mRNA technology is here, get used to it.
I mean, the question is almost always about whether it's economical or not, right? Whether you can find diseases it's efficacious to treat with this mechanism, and prove it (trials are expensive).
not really a huge win. It's going to cost taxpayers significancy and may not improve survival much or total life expectancy . The stock is way overextended, assuming it even works well enough to be a commercial success. History has shown this is seldom the case. I would short it if wasn't so expensive and risky to do so. They would not even specify how much it improved the 5 year survival rate.
> not really a huge win. It's going to cost taxpayers significancy and may not improve survival much or total life expectancy . The stock is way overextended. It's a long way from anything that can be used on patients, assuming it even works well enough to be a commercial success. History has shown this is seldom the case. I would short it if wasn't so expensive and risky to do so.
Buddy, this is a phase 3 trial. This is about as close as you can get to "anything that can be used on patients" without already being approved.
It is clear that you don't have experience in this area.
According to Gemini, Moderna uses machine learning to speed up sequence selection and mRNA optimization. After all, this is not a mass-produced vaccine, but a personalized one.
I for one would like to see the data rather than a press release. Is this even serious? A press release with no link to outside twitter?
I feel like everything companies, and presidents, say now is directly geared to triggering AI trades.
The only thing they are looking at with this drug is people living one more month over existing drugs.
THIS IS NOTHING.
"The median PFS (progression-free survival) for KEYTRUDA was 5.5 months (2-week group) and 4.1 months (3-week group) compared to 2.8 months for ipilimumab (HR 0.58, P<0.00001 for the KEYTRUDA groups vs. ipilimumab,"
https://www.merck.com/news/keytruda-pembrolizumab-mercks-ant...
The median PFS (progression-free survival) for KEYTRUDA was 5.5 months (2-week group) and 4.1 months (3-week group) compared to 2.8 months for ipilimumab (HR 0.58, P<0.00001 for the KEYTRUDA groups vs. ipilimumab, 95% CI, 0.46-0.72 for 2-week group and 0.47-0.72 for 3-week group, respectively). The estimated 6-month PFS rates for the KEYTRUDA and ipilimumab arms were 47.3 percent, 46.4 percent and 26.5 percent, respectively. One-year OS for KEYTRUDA was 74.1 percent (2-week group) and 68.4 percent (3-week group) compared to 58.2 percent for ipilimumab (HR 0.63 [95% CI, 0.47-0.83, P=0.00052] for the 2-week group and HR 0.69 [95% CI, 0.52-0.90, P=0.00358] for the 3-week group). At the time of analysis, median overall survival was not reached in any treatment group.
1. That's not what progression-free survival means.
2. I don't think AI was mentioned once in this press release.
3. This drug was approved for trial in 2014, so if it had something to do with deep learning, that would actually be a massive announcement.
4. The paragraph immediately following the one you clipped talks about Overall Response Rate (ORR) and throughout the release they discuss Overall Survival (OS).
5. This is not "NOTHING" in statistical terms, but even more so to people with melanoma.
Interjecting with a fact. Moderna described the neoantigen immunogenicity prediction algorithm they used to design the vaccines as “a deterministic machine learning (ML) algorithm,” so it may be a small neural network or more traditional algorithm, probably not deep learning.
No it isn’t. They did a test with great specificity and got undeniable P values. Now they can refine the action and start saving people. This is a huge, huge win.
you're also looking at a different, older study. Keytruda is a little strange in that it has a very long tail in survivorship, works best in certain cases, and median PFS isn't a really great metric.
/me shakes head in disbelief and closes the tab
There are a zillion news sources for this: OP what would possess you to pick the (largely dead) right wing Musk-owned Twitter ("X" )?
Has more posts than HN, yet would you describe this platform as 'dead'?
In other news, your barber thinks you need a haircut. Until there is a proven net overall health benefit to this therapy, I wouldn't waste much ink on it. Also, can someone please tell me how one controls the dose for an mRNA therapy ?
If you actually had melanoma (a very aggressive type of skin cancer) you would be glad for one more chance of maybe still being alive a few years from now.
not if you dropped dead from a heart attack after your therapy. Are you familiar with vioxx ? https://www.npr.org/2007/11/10/5470430/timeline-the-rise-and...
Yeah while a positive step, I do not understand a 90% stock increase.
Oh yeah? Show me your discounted cash flow analysis.