Kithani
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Investing General Discussion
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Furry
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Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting - Merck.com
At a median 5-year (60.3 months) planned follow-up of the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, intismeran autogene in combination with KEYTRUDA demonstrated a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death compared to...
www.merck.com
Data points with links to the clinical trials. Looks promising on a skim.
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Arden
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Haus
I am Big Balls!
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Hearing a summary of how this thing works essentially it is this :
- You get diagnosed with Melanoma
- They take a sample of the cancer from you
- Since it's based on your genetic they have to gene sequence it.
- Look at that compared to your regular genetics and look for markers that differentiate the cancer
- Build a custom mRNA vaccine based on those specific markers to target your specific cancer
- Deliver it, and couple it with a known immuno-booster to amp up it's behavior
- Effectively attacks the melanoma
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Sheriff Cad
scientia potentia est
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It's not too different than how CAR-T therapy is working now.
With CAR-T, they remove T-cells from the cancer patient, get them to divide in the lab and then use a viral vector to reprogram the DNA of the T-cells to attack your specific cancer. Then they put those reprogrammed T-cells back into you and your immune system goes wild attacking the cancer.
Sounds like two approaches to getting your immune system to attack the cancer.
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Sheriff Cad
scientia potentia est
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Everything is expensive at first and gets cheaper over time, like your mom.
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Arden
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Haus
I am Big Balls!
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So once again I come for an opinion from those who are deeper on these stock strategy topics than I am..
I have been working with an actual professional financial planner and they brought up one tool they wanted to talk about that made my "something seems fucky here" sense go off.
A managed fund they run to essentially operate like an index fund with similar returns while also maximizing a tax loss farming strategy to bring down overall tax obligation for other moves I make which will generate large capital gains hits. Is this a real thing? It's being recommended by a large, well known, name in financial planning, but just seems like some slightly dodgy fuckery going on. I'm probably going to be moving a large amount of capital out of an over-concentrated position over the next 2-4 years, so the idea here was to play a strategy of generating and harvesting tax losses to offset as much of the gains as possible. But in my head that means losing a ton of money??
I have been working with an actual professional financial planner and they brought up one tool they wanted to talk about that made my "something seems fucky here" sense go off.
A managed fund they run to essentially operate like an index fund with similar returns while also maximizing a tax loss farming strategy to bring down overall tax obligation for other moves I make which will generate large capital gains hits. Is this a real thing? It's being recommended by a large, well known, name in financial planning, but just seems like some slightly dodgy fuckery going on. I'm probably going to be moving a large amount of capital out of an over-concentrated position over the next 2-4 years, so the idea here was to play a strategy of generating and harvesting tax losses to offset as much of the gains as possible. But in my head that means losing a ton of money??
Sheriff Cad
scientia potentia est
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Without seeing the numbers my knee-jerk reaction is it sounds like they get you on the management fee in their managed fund in order to get some perceived tax gains later - but the tax gains won't offset the management fee. But you'd have to run the numbers on that for your particular situation.
One of the reasons unmanaged index funds are so good is the like 0.01% management fee.
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Haus
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I agree, which is why I'm digging through their stuff right now. Just didn't know if anybody else was leveraging this strategy... Seems it's called "tax-loss harvesting via direct indexing". They manage an account and inside it they individually invest in a mix of stocks approximating an index. Then their people actively sell loss positions to harvest losses from them while keeping profitable positions. Usually performs similarly to an index, but with additional "tax harvesting" and yeah it boil down to which is greater, the overall portfolio performance + tax losses harvested versus the fee for the managers. I'm going over those numbers this coming week, they're sending those over.
All indicators are that this is a known and legal process, used by people (apparently like me) who need to find a way to lessen taxes from divestitures of large holdings. Right now it's considered one of those "It's legal, but not really the intent of the statutes" scenarios, but until they close the loophole... well.. As they say in MMOs, "Exploit early, exploit often".
I do suspect it will come down to if they save me more in taxes than I get charged in fees.
Gravel
Mr. Poopybutthole
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You can do tax loss harvesting on your own with a brokerage account. You don't need to pay someone a percentage of AUM to do it for you.
That said, in my opinion, it's a complete waste of time. It's something the super rich do, and for some reason people with portfolios in the millions decided was worthwhile.
That said, in my opinion, it's a complete waste of time. It's something the super rich do, and for some reason people with portfolios in the millions decided was worthwhile.
Sheriff Cad
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I don't think this even works in an index fund. People ask, "why don't you just buy a weighted basket of the index yourself rather than pay the index management fee of 0.01%". And you could. But when prices change, the weighted basket of stocks the index carries also changes, and they rebalance all the time.
The reason this is great is because you do NOT get taxable events for intra-ETF trades; i.e. if the manager buys and sells stuff, you don't pay capital gains taxes (and I'm pretty sure selling at a loss doesn't get you any deductible losses either).
I'd be very interested to see the actual paperwork on this because what they're describing doesn't sound logical at all. It might save THE FUND tax money, I'm not even sure on that, but I don't see how it can be a taxable event for you to harvest losses when you didn't sell anything.
Haus
I am Big Balls!
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That's part of the structure. I'm not buying a "fund". I am funding an account, then within that account their people buy all the individual stocks , buying and selling actual individual shares, and weaving around wash sale rules. So I don't own $100k of <fund>, I own $100k of individual stocks, but managed by someone else like it was a fund.
Sheriff Cad
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You'd get totally killed every time they rebalance the index though, when they buy and sell in the fund, you'd be getting taxable events on the gains and losses. I don't see any way that they can harvest the losses while the gains aren't taxable events. And since they can't rebalance with the index the way normal index funds do (at least not often), it seems like this would really come down to whether the management percentage swamps the tax savings, which I'm not sure how you could know.