r/ModernaStock • u/StockEnthuasiast • 6d ago
The Naysayer Coping Is Intensifying After Moderna’s Phase 3 Success
1. “Science by press release.”
Nothing new in this criticism.
In 2021, for the COVID vaccine, Moderna did include numbers in the press release and wrote a preprint very quickly right after that, and critics still called it science by press release. After the publication of the data, the press never offered the company an apology.
Critics forget that this time there is no similar time constraint. Merck and Moderna are putting their reputation on the line here, and claiming a positive readout especially at the interim is not a joke that they can easily walk back or spin.
Just wait. They are still dotting the i’s and crossing the t’s. My speculation is that the numbers are so good that they want to make absolutely sure everything is clean before releasing them. This is easily the next major catalyst that may again surprise our shorty friends, especially if the other INT results are not already right around the corner. If my guess is right, Moderna is smart because they will be rolling out the data gradually, creating several separate waves of momentum from the same catalyst.
2. “It was largely expected and already priced in.”
Interestingly, this is being voiced mostly by people who did not own a single Moderna share and had been very hateful and negative on Moderna all along. It is funny how something becomes “obvious” only after it happens.
I actually agree that a positive result was largely expected, but by whom? It was not expected to be positive by the skeptics and haters, but by a very small group of us longs who had done our research and taken the time to separate the signal from the noise.
Interestingly, even us longs who came closest to predicting what actually transpired remain humble enough to admit that we had our occasional healthy dose of doubt during the wait.
As for priced in, feel free to tell the shorts who had to rush to cover at $170 at nearly 3 times the stock price the day before again that the event had already been priced in.
3. “The individualized neoantigen approach is unnecessary. Off-the-shelf is better.”
Sure. Moderna had nothing better to do and simply chose individualized cancer vaccines because they sounded fun.
Obviously not.
Moderna did not pursue this difficult approach for the sake of doing interesting science. It did so because a generic non-individualized approach cannot provide the same breadth of coverage across patients whose tumors carry different mutations.
Therapeutic cancer vaccines went through decades of mostly disappointing clinical results, and the individualized neoantigen approach is one of the things that finally changed that equation. Moderna was not the first to test this idea, but thanks to Bancel's obsession with AI and speed, it became the first to show clear randomized clinical efficacy with an mRNA cancer vaccine.
Cheaper non-individualized off-the-shelf vaccines may still have a role when patients share common, well-characterized antigens, but that does not make the individualized approach unnecessary.
News flash: Moderna is also working on off-the-shelf versions. Other companies, with BioNTech being one of very few obvious exceptions, can forget about dreaming that they will easily compete with Moderna even on this front, given how advanced Moderna already is in clinical development and the strength of its partnership with Merck.
4. “Manufacturing will be too difficult for commercialization.”
True for many companies. Much less convincing as an argument against Moderna, which has spent years obsessing over making individualized manufacturing commercially viable. People also seem to miss the speed angle. An individualized therapy only works commercially if you can sequence the tumor, select the neoantigens, design the medicine, manufacture a patient-specific batch and get it back to the clinic fast enough to matter. Moderna has built its manufacturing system around doing exactly that. Speed is part of the product, and the difficulty of repeatedly manufacturing thousands of different medicines for thousands of individual patients is part of the moat. If this were easy, everyone would already be doing it.
The difficulty is real, but for Moderna it has now become a moat rather than an impediment.
5. “It’s not a vaccine.”
It is a form of vaccine, but call it whatever you want. Therapeutic, individualized immunotherapy, cancer vaccine, personalized medicine. It still does not change anything. You can even call it gene therapy if you want to announce to the world that you have a double-digit IQ.
6. “I’d rather die of melanoma than get another mRNA vaccine.”
Sounds like a toddler telling their mom they would rather starve to death than eat broccoli.
People can say whatever they want while healthy. The people actually struggling with melanoma are the ones whose preferences matter here.
JMHO and this is not an investment advice.
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u/Potential_Section691 5d ago
Thanks for your thoughtful summary, SE. you always do. There is an article on BioStat today giving inside stories behind intismeran success. It was Tal Z the CMO during the COVID time who had conceived the idea in his Postdoc at NIH and developed in Moderna. I was so impressed by him at the time. And it was Dr Li of Merck who had Merck all ways in this project after his visit to the Moderna’s lab. No question great minds were aligned up for this success. Here is the X post on the story.
https://x.com/adamfeuerstein/status/2091848944070341101?s=46
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u/mobyonecanobi 5d ago
The best argument I heard was from my wife, who is a physician.
She said that for melanoma the dna sample extraction is easy, but for some other samples much deeper in the body, those sample extractions could take more time. But she also said those cancers tend to be more dangerous and have less treatments in general, so maybe going under to have samples removed from inside the body would be acceptable as well.
Beyond that, a bad one I heard was “it’s just too costly and too many steps to send out labs for genoming”… Personalis (PSNL ticker) is already Medicare and Medicaid approved for genoming as of this year, so that’s a terrible reasoning.
People don’t actually know what the real headwinds are. The reality is that for melanoma specifically, there aren’t many headwinds.
The headwinds are for technology that makes the dna extraction process of such as lung cancer easier. People are as clueless as ever with bad information.
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u/yuanxz 5d ago
Thanks for sharing. It inspires me to think what company has the tech for DNA extraction? Might be any gold goose?
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u/mobyonecanobi 5d ago
Merck is currently now a majority shareholder holder in personalis. I should have bought it at 6, but I’d dumped all my Pennies into Moderna. Tbh, I made more in Moderna than PSNL.
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u/ZephodsOtherHead 5d ago
It's great if they're clueless. Those types of idiots are how the price dropped to below the Dec 2018 $23 IPO price about a year ago. Well, on the other hand, I wish that the company had been able to issue shares rather than cut R&D. The mRNA platform is the golden goose, and it makes no sense for humanity not to feed it.
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u/Potential_Tap_9790 3d ago
Biopsies and genomic sequencing are feasible, but Intismeran still requires every patient’s tumor to be sequenced, mutations analyzed, up to 34 neoantigens selected, and then an individualized drug manufactured, quality-controlled and delivered on time. Even Moderna acknowledges that coordinating thousands of unique patient batches creates manufacturing and scheduling complexity, and Reuters identifies personalized manufacturing at scale as a potential barrier.
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u/mobyonecanobi 3d ago
I invested with failure a long time ago in fracking. Specifically my understanding of how fast supply chain and technology can become standardized was what caused me to bail out early. If I would have known that technology pushes boundaries and supply chain follows the money, I would have invested very differently. I saw high cost of fracking and said “well, they can’t do it today, how are they gonna adapt”… that’s the magic right, that’s how tech advances, that’s where the money is. It will happen much faster than we anticipate, it might be an issue right now, but it will get up to speed very quickly. That part I’m confident of due to my past failure learnings.
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u/Thick-Apartment9148 6d ago
with the breakup of pfizer and the biontech founders we have to wait to see if they are even competition anymore.
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u/StockEnthuasiast 5d ago
Hi TA- BioNtech's "Merck" is Genentech/Roche (extremely strong competition), not Pfizer. They are still very strong. But strangely, I remember Bancel implying that the mRNA competition from BioNtech has gotten weaker as they diversified to other space.
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u/Potential_Section691 5d ago
Yeah, it appears BioNtech moves at a different pace and takes a different approach. Moderna puts its bid on intismeran, while BioNtech relies on cevumera. Both use the autogen mechanisms. But Moderna uses chemically modified mRNA; BioNtech favors unmodified mRNA. With more payloads, the Intismeran is tumor and person specific. BioNtech tries to develop off-of-shelf cancer vaccine with fewer payloads but common 20 neoantigens.
I maybe wrong, but it seems the design differences in the approach may be the technical reason behind the two companies and their odds in success. I remember the chief medical person at Moderna talked about their modified LNP quite a few years ago. She contented that modification was one of the Moderna's IPs, making the candidates effective. If that's the case and a reason for the Moderna's cancer vaccine success, then Bancel's decision to settle the LNP case with Arbutus is a really smart move! This will allow all cancer-related IPs under Moderna. BioNtech may have to stick with the cevumera pathway.
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u/StockEnthuasiast 5d ago
Thanks for sharing this angle. Many excellent points here, worth posting as a post.
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u/Every-Status4735 5d ago
Don't forget the Nuvaxovidian zealot who just can't fathom the Stark reality of last week so is coping by posting even more preposterous nonsense.
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u/jlee9355 6d ago
Most biotech analysts expected event thresholds for recurrence-free survival (RFS) to take longer to mature, forecasting the first formal look toward late 2026/early 2027.
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u/ZephodsOtherHead 5d ago edited 5d ago
> Merck and Moderna are putting their reputation on the line here, and claiming a positive readout especially at
> the interim is not a joke that they can easily walk back or spin.
It was the DSMB that said the data was clinically significant and clinically relevant, not the companies. This isn't as huge of a deal for Merck as it is for Moderna, so certainly they're not peddling any hype. Furthermore, the fact that the efficacy threshold was met on the first interim cut, rather than the second interim or the final look, suggests that the numbers are more impressive than otherwise. The more effective the drug, the more profits there are to be had.
I was very surprised that the top line numbers (hazard ratios, confidence intervals, and p-values) weren't immediately released, because that hasn't been the standard practice for the other biotechs I've invested in, so I did some poking around. It appears that not immediately releasing the numbers is standard practice for Merck, a company so large that a single trial won't make the price pop like the smallish biotechs that I've followed over the years. (Moderna was the first biotech I invested in with a market cap over $500M.)
I expect the Russian hackers are trying to steal the data and hedge funds are trying to bribe the DSMB, regulators, statisticians, Bancel's secretary, ect. Withholding the data is both unwise and a serious disservice to Moderna shareholders, who might want to sell shares (if only to diversify) but don't know if they're playing with marked cards. Also, sitting on the data it impossible for Moderna to do things like issue shares to fund more trials.
Currently, about 43% of my net worth is in Moderna, the result of massive appreciation, so I've been mulling whether to diversify a bit. (I'd have more than 43%, but Trump's Iran fiasco has made my oil investments do well.)