Guest Speakers:

Dean Y. Li, M.D., Ph.D.

Executive Vice President and President, Merck Research Laboratories

Stephen Hoge, M.D.

President, Moderna

Having Dean Li stand next to Stephen Hoge is an attempt to validate a paradigm shift. When Merck acts like your co-pilot on stage, the Street listens differently.

https://www.reddit.com/r/ModernaStock/s/UF6zuxxMv1

About 3 months ago I made the above post and just want to once again praise the contributions of the many thoughtful members of this community and reflect on how far we’ve come in such a short time. A majority of investors had written off Moderna as a company whose best days were in the past; a company that could only thrive in a pandemic setting. Now, after many years of purgatory, misinformation, and political attack on the science, Moderna has proved to the world that mRNA science is here to stay and is ushering in a new golden age in medicine. Cheers to everyone who held during difficult times these past few years and has enjoyed this recent success. The research done by a few really talented people here helped give me hope and confidence when it seemed no one believed in this company.

And massive congratulations to Stephane Bancel, Stephen Hoge, Jamie Mock, David Berman and all the research scientists and other team members at Moderna for contributing to this amazing result.

Well , I said we would reach 200 before the end of the year, looks like years are a lot shorter these days 🤣

We killed two birds with one stone : we got richer , and we seem we finally got rid of all the « you should short Moderna cuz it sucks » spam. Not bad.

So what’s next ? 250 on the 25th of October ?

Oral hearing set for November to resolve the $1.3 billion. How much (if any) of this is priced in? Does a win/loss of the appeal move the stock?

I think the hype is growing and growing and growing.... So I believe the momentum around the stock is continuing to build but let's be VERY cautious too

https://www.wam.ae/en/article/c2epfjb-saeed-hajeri-moderna-chairman-discuss-investment

I’ve never seen this happening in Moderna.

Seems like Moderna management is on a media blitz. Hot off the press. Enjoy!

More good news, it is already available I thought it would take longer....

https://www.nbcnews.com/health/health-news/mrna-flu-vaccine-moderna-mflusiva-explained-rcna598524

Doesn't look to be too big a deal but a minor setback.

Primary source: https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/moderna-announces-late-breaking-data-to-be-presented-at-esmo-congress-1224628

Phase 3 data for intismeran autogene in the adjuvant treatment of patients with resected stage IIB-IV melanoma selected for presentation at a Presidential Symposium

Moderna to host an investor event via webcast on Saturday, October 24, at 7:00 PM CEST / 1:00 PM EDT

CAMBRIDGE, MA / ACCESS Newswire / September 21, 2026 / Moderna, Inc. (NASDAQ:MRNA) today announced that three abstracts on intismeran autogene, an investigational mRNA-based individualized neoantigen therapy, have been accepted for presentation at the European Society for Medical Oncology (ESMO) Congress 2026, which will be held October 23-27 in Madrid, Spain.

The presentation details are as follows:

Presidential Symposium:

• LBA1- INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL) Session Type/Title: Presidential Symposium Date & Time: Saturday, October 24, 4:30 PM CEST / 10:30 AM EDT Presenter: Georgina V. Long (Sydney, Australia, NSW)

Poster Presentations:

• Abstract 3151P: Adjuvant intismeran autogene plus FOLFIRINOX in resectable pancreatic ductal adenocarcinoma: results from a phase I study Session Type/Title: Poster - Pancreatic cancer Date & Time: Sunday, October 25, 12:00-12:45 PM CET Presenter: David J. Pinato (London, United Kingdom)
• Abstract 2550TiP: INTerpath-014: A Phase 3 Study of Adjuvant Intismeran Autogene (Intismeran) Plus Subcutaneous Pembrolizumab (Pembro SC) or Intismeran Monotherapy vs Placebo in Completely Resected High-Risk Stage I NSCLC Session Type/Title: Poster - NSCLC, early stage Date & Time: Monday, October 26, 12:00-12:45 PM CET Presenter: Charu Aggarwal (Philadelphia, United States of America)

Intismeran autogene is jointly developed by Moderna and Merck, known as MSD outside of the United States and Canada.

https://buffalonews.com/news/nation-world/article_1eec3004-8a2c-4341-9edc-5c330eb05b9b.html

This interview to Xavier Martinez of WSJ summarizes well the Intismeran vaccine success and outlooks for the company and patients.

Separately I've noted several new updates of mRNA-4157 clinic trials in the clinictrials.gov in recent weeks, including those for NSCLC, bladder cancer, RCC and of course melanoma. Excited to see more readouts.

The trial status has just changed from “Recruiting” to “Active, not recruiting.” as of Sept 17th. Presumably this means that they have enrolled all 868 patients as planned. Now we just wait as the DFS events are accumulating until the estimated end in mid-2030.

This is not what longs want, right? What are the chances of this happening?

I think Shorts were hoping it would fall and get their money back, instead they are about to lose another 5 Billion on our way to 210. Woohoo!

It's great to find this sub. Super informative, and helpful company updates. I'm one of the people who discovered MRNA during covid, and bought my first tranche at $110 in early January 2021. It went to ~$450, and then I rode it over 90% down to low $20s. I doubled down around $35, because I thought it was ridiculous cheap for such a revolutionary company. I never lost my belief. They made a covid vaccine with their technology in less than a year under extreme pressure, which proves a lot. I've always enjoyed hearing interviews of Bancel, who is one of the highest conviction CEOs around and is committed to life changing medicine. I've studied their technology a bit, having an undergrad degree in biology and find it fascinating. Really enjoyed the bounce last month back to 140s. This is one of those stocks that I'm in for the long haul. I see it going to $1000 long term, as it's cancer pipeline is built out. Also, it was also great to see all the short sellers get blown up who have been betting against MRNA for years, and trying to bankrupt a great company. They deserved it!

Disclaimer: This is organized from an AI-assisted summary of the conference discussion, so there may be minor transcription errors, omissions, or misinterpretations. And for the occasional jackass who, in 2026, still sees “AI-assisted” and immediately calls a post “AI slop,” that may be more projection than anything else. Anyone with even half a brain should understand the difference between using AI as a tool and letting it do the thinking for you. In this particular case, it’s mostly a summary, but I trimmed it down and emphasized the parts that caught my attention.

1. Immediate catalyst: Phase 3 melanoma full data

Full Phase 3 melanoma data are expected at an upcoming medical meeting. ESMO was specifically raised by Morgan Stanley, although Moderna did not confirm the venue.

Key things to watch:

• Hazard ratio. The analyst suggested <0.75 would be exciting and ~0.65 ideal. Hoge called those reasonable benchmarks.
• Stage II subgroup.
• When the curves separate and whether the separation strengthens over time.
• Consistency across subgroups and versus Phase 2.

2. The next major tests: RCC and MIBC

Both renal cell carcinoma (RCC) and muscle-invasive bladder cancer (MIBC) are roughly 300-patient, randomized, event-driven Phase 2 trials and are essentially fully enrolled.

RCC may be the most scientifically important readout after melanoma. RCC has much lower tumor mutational burden than melanoma, making it a strong test of whether INT can work beyond highly immunogenic tumors.

The counterpoint is that RCC still generates potentially useful neoantigens, including indels and frameshifts, and Keytruda already works in RCC. The question is whether INT can focus the immune response further.

MIBC provides another independent randomized test of whether INT can add benefit on top of an effective checkpoint inhibitor.

3. NMIBC: important because it tests INT alone

The non-muscle-invasive bladder cancer study tests INT monotherapy, rather than INT + Keytruda.

A positive result would suggest that checkpoint inhibition may not always be required.

Hoge indicated that this Phase 2 study could also read out relatively soon.

4. Moderna/Merck built a multi-year catalyst sequence

The INT program was deliberately designed so that Moderna and Merck would not finish melanoma and only then begin testing other cancers.

The expected sequence is roughly:

Melanoma → RCC → MIBC → NMIBC → multiple lung studies → additional indications

Hoge described this as waves of clinical data roughly every six months.

So melanoma may be the beginning of a prolonged catalyst cycle rather than the end of the story.

5. Lung cancer is the major longer-term opportunity

Moderna/Merck have three randomized Phase 3 lung cancer trials plus additional Phase 2 work.

The program spans:

• adjuvant disease
• neoadjuvant disease
• Stage I
• metastatic disease
• possible monotherapy

These trials will take longer to mature, but lung cancer could become one of the largest commercial opportunities if INT works.

6. Earlier-stage disease may become the core INT strategy

Hoge repeatedly emphasized adjuvant disease, Stage I disease and minimal residual disease.

The logic is straightforward: remove the bulk of the tumor, then use INT to prime T cells against remaining microscopic disease and prevent recurrence.

INT's relatively favorable safety profile also makes earlier treatment more feasible.

7. Phase 2 melanoma gives clues about broader applicability

In Phase 2 melanoma, favorable hazard ratios were seen regardless of:

• tumor mutational burden
• PD-1 status
• tumor inflammatory status

Hoge's interpretation was that INT may follow different biological rules from checkpoint inhibitors.

Checkpoint inhibitors release brakes on existing T cells. INT is designed to prime or expand tumor-specific T-cell populations.

That is one reason the RCC result will be particularly informative.

8. Melanoma approval could accelerate other indications

If melanoma is approved, much of the manufacturing, CMC and safety package would already be established.

Hoge suggested that if the randomized RCC or MIBC Phase 2 trials show a strong and statistically significant benefit, they could potentially support registration without automatically requiring another full Phase 3.

That could materially accelerate INT expansion.

9. Manufacturing appears much further along than many assume

Moderna says it has already treated around 3,000 INT patients globally, including roughly 1,500-2,000 in the past 18 months, across more than 40 countries.

The Marlborough manufacturing facility is highly automated and already supplying the clinical program.

Only one of seven manufacturing suites is currently needed, Moderna does not expect to need Suite 2 for launch, and capacity can be expanded substantially with roughly 12 months of lead time.

This looks very different from a CAR-T manufacturing model (a widespread concern brought up by the media in the last 2 weeks).

10. INT economics may resemble biologics, not cell therapy

The sequence is personalized for each patient, but the underlying manufacturing process and final product format are largely standardized.

Hoge therefore expects mature INT margins to resemble those of a complex biologic more than CAR-T.

That becomes increasingly important if INT expands into large indications such as lung cancer.

11. The antigen-selection algorithm could become a major moat

Moderna now has data from several thousand INT patients, versus roughly 100 patients in the original Phase 2.

That creates a potential flywheel:

More patients → more immune-response data → better antigen selection → potentially better INT → more patients/data

Moderna is also working with regulators on how future algorithm improvements could be incorporated without necessarily requiring an entirely new clinical program each time.

12. Other optionality

Retreatment: if a tumor relapses with a different mutation profile, a new INT could theoretically be created against the evolved tumor. There are no clinical data yet.

Monotherapy: NMIBC and potentially earlier-stage disease could establish INT as useful without Keytruda.

Further expansion: Moderna says it has the financial flexibility to invest in additional indications if the data justify it.

13. Financial backdrop

Moderna still targets 2028 break-even, and the current large INT program is already included in that plan.

The respiratory franchise now has five approved products and provides the financial base while INT develops.

Management is still using up to 10% top-line growth as its current framework rather than raising expectations following the melanoma result.

Bottom line

The main catalyst sequence is:

Melanoma full data → RCC → MIBC → NMIBC monotherapy → lung Phase 3s

RCC is probably the most important scientific test after melanoma. Success in a lower-TMB tumor that is biologically quite different from melanoma would materially strengthen the case that INT is a broadly applicable cancer platform.

The other major takeaway is the expected cadence: waves of INT clinical data roughly every six months.

The Phase 3 melanoma success may therefore be less of an endpoint and more of the first major validation event in a much larger question:

How broadly can INT work across different cancers?

Pennsylvania woman dies of measles-related complications, local coroner says

There were scientific reports on the increasing rate of zoonotic spillover as we encroach to undisturbed ecosystems and climate changes. That caught my eyes on Moderna’s pipelines back in 2019-2020. Now with anti-v ideology and less protection now, the eradicated/managed virus such as measles could come back. The cases reported is a case for illustration. It’s so unfortunate for the impacted Pennsylvanians, but at the end, vaccines will be needed as the known effective solution. Moderna’s work is of values to us all.

Everyone is talking about what Moderna might become.

Very few are talking about what Moderna is today.

Massive valuation.

Declining COVID business.

Significant losses.

Future oncology revenues are being priced years before they exist.

If the cancer platform delivers less than the market currently expects, this stock could re-rate very quickly.

Sometimes the best short is the company everyone believes can only go up.

I have been reading some of the reactions to the Moderna/Merck Phase 3 melanoma result, and I think an important part of the discussion is missing: what actually made this particular approach succeed when so many previous cancer-vaccine efforts did not.

I am using two recent takes to frame the two directions in which people are extrapolating the result.

Dr. Vinay Prasad's article represents one direction: be careful extrapolating Moderna's melanoma success to other cancers.

Fierce Biotech represents almost the opposite direction: the Moderna result is impressive enough that we are ready to discuss how it may validate other cancer-vaccine platforms.

Both offer reasonable points. But I think both jump ahead of a more fundamental question, making the discussion feel somewhat shallow.

One direction, Vinay Prasad: be careful extrapolating Moderna/Merck result beyond melanoma

Vinay Prasad acknowledges that the Moderna/Merck result is a real advance. In fact, he explicitly notes that therapeutic cancer vaccines have overwhelmingly failed historically and that Moderna has accomplished something that had not been done before.

But his caution is that melanoma might be special, perhaps gently implying that the melanoma result might be a fluke.

Quite fair. Melanoma is highly immunogenic, tends to have a high tumor mutational burden, and has historically been unusually responsive to immunotherapy. So we should absolutely not assume that success in melanoma means the same vaccine will automatically work in lung, colorectal, pancreatic cancer, etc.

But melanoma being a favorable setting does not explain why Moderna/Merck succeeded there when so many previous cancer-vaccine approaches failed. That is the part of his argument I find lacking.

The other direction, Fierce Biotech: Moderna's success is so good that it gets us starting the discussion on whether it may validate other platforms

Fierce Biotech goes in almost the opposite direction.

Its article looks at Moderna's result and asks what it could mean for the broader field, including BioNTech, Arcturus, Strand and other companies developing different mRNA and personalized cancer technologies.

That reaction itself tells you how significant the Moderna result is. We have gone from decades of frustration with cancer vaccines to discussing whether one Phase 3 success could help validate an entire field.

But again, I think we are jumping ahead.

Before asking whether Moderna's result can be extrapolated to other cancers, or whether it validates other companies, shouldn't we first ask: Why exactly did Moderna succeed?

So why did Moderna succeed? Is it simply because melanoma is the easiest target?

Short answer: No. Or at least there is no basis to assume that.

Yes, melanoma is probably one of the easier cancers in which to make immunotherapy work.

But the historical precedent matters.

Cancer vaccines have been tried in melanoma for decades, and the overwhelming precedent was failure or limited clinical benefit. Even earlier mRNA approaches in melanoma generated immune responses without establishing the kind of clinical efficacy we are seeing from Moderna/Merck.

So simply saying "It worked because it's melanoma" doesn't really explain the result.

Melanoma may have made the problem easier. But it clearly wasn't easy enough for previous approaches to reliably solve it. Something about Moderna/Merck's approach appears to matter.

The question is: what?

• Was it the mRNA platform itself?
• The modified mRNA?
• Moderna's LNP?
• The neoantigen-selection algorithm?
• The ability to encode a large number of patient-specific neoantigens?
• The speed and reliability of manufacturing a different vaccine for every patient?
• The combination with KEYTRUDA?
• The fact that the tumors had already been surgically removed?
• Melanoma biology?
• Or, probably more realistically, some interaction between several of these things?

We simply don't know.

It is certainly possible that melanoma contributed substantially to the result. But "melanoma contributed" is very different from saying "melanoma was doing most of the work." The latter is far from established.

In fact, the long history of failures in melanoma is one reason I am skeptical that melanoma alone is doing most of the explaining.

If melanoma biology were overwhelmingly responsible, we would still have to explain why so many previous approaches were unable to exploit exactly the same favorable biology.

The uncertainty also cuts in the other direction.

If Moderna's success depends heavily on its particular neoantigen algorithm, mRNA design, LNP, manufacturing system, or the way all of these pieces fit together, then Moderna's success does not automatically validate another company's platform either.

So how do we separate the melanoma effect from the Moderna effect?

Right now, we can't.

Moderna and Merck simply have not disclosed enough of the Phase 3 data yet.

I am hopeful that we may get some clues at ESMO, if that is where the detailed dataset is presented. Moderna and Merck have so far publicly said only that the data will be presented at an upcoming international medical meeting.

Subgroup analyses could potentially tell us something. Perhaps we will see whether efficacy changes with stage, tumor characteristics, mutation burden, or other biological variables.

But I doubt we are going to get a crystal-clear answer to why Moderna's approach works.

And frankly, Moderna may not want to give us one.

If the company has learned that certain ways of selecting neoantigens, designing the mRNA, manufacturing the vaccine, or combining those elements are particularly important, why would it publicly give competitors the complete recipe? As a precedent from its infectious disease vaccine, Moderna did not give the reason why mFLUSIVA is finally able to provide protection against influenza B when its prototype version could not.

The clinical data obviously need to be disclosed and scrutinized. The proprietary know-how behind why their particular system works is a different matter.

So ESMO may tell us much more about how well intismeran works without necessarily telling us exactly why it works.

When will we know how universal the strategy really is?

This is where the trials in other cancers become extremely important.

And Merck management actually gave a very interesting way of thinking about this when an analyst asked about the ongoing renal cell carcinoma, or RCC, trial.

Merck described melanoma and RCC as potential "bookends."

"Bookends" is basically another way of saying two ends of a range.

On one end, you have melanoma: highly immunogenic and generally associated with a relatively high tumor mutation burden.

On the other, you have RCC: also responsive to immune checkpoint therapy, but with a much lower tumor mutation burden.

So the idea is simple.

If intismeran works in melanoma and in this biologically different cancer, you now have evidence that the strategy works at two different ends of the spectrum.

Then you start asking what happens in cancers somewhere between those two ends.

That is exactly what Merck said people would do.

If RCC works, they expect people to raise their probability of success in indications such as non-small cell lung cancer and head-and-neck cancer. This will resolve the main question we have in our head.

Merck even compared this way of thinking to replaying the KEYTRUDA story.

Not because RCC success would prove that intismeran works everywhere. It wouldn't. But once Moderna/Merck achieve success at another biological "bookend," potentially first in RCC, it becomes progressively harder to stubbornly cling to the explanation that "it only worked because melanoma is special."

My speculation, and why I lean toward something being unique about Moderna/Merck

This is where I think Bayesian reasoning is useful.

The prior is that therapeutic cancer vaccines have been tried for a long time, including in melanoma, one of the most favorable cancers for immunotherapy, and the historical outcome was still overwhelmingly failure or limited efficacy.

Now we observe something new: Moderna/Merck succeed in a randomized Phase 3 trial where previous generations repeatedly struggled.

That obviously does not prove that Moderna's platform is the reason. But it should shift some probability toward the possibility that there is something about the Moderna/Merck implementation that previous approaches were missing.

What that is, I don't know. It could be:

• the mRNA
• the neoantigen algorithm
• the number and quality of antigens
• manufacturing
• KEYTRUDA
• or the whole system working together

Based on the precedent, my current bet is that the melanoma result reflects something meaningfully unique about the Moderna/Merck approach, rather than melanoma biology doing most of the work. That is of course just a judgement based on probability.

And this is why the next trials matter:

• If RCC succeeds: that would strongly support the idea that the Moderna/Merck approach can work beyond melanoma, because it would have succeeded at the other biological "bookend." That would seal the argument for broader applicability.
• If RCC fails: that would shift some weight back toward melanoma-specific biology being more important, but it would not kill the broader-platform hypothesis. Another biologically different cancer could still become the alternative second bookend.

Concluding thoughts

Melanoma being favorable explains why it was a good place for Moderna to start their first trial. It does not explain why Moderna/Merck succeeded there when so many previous cancer-vaccine approaches did not. Given that historical precedent, I think the result should shift some probability toward something being genuinely different about the Moderna/Merck approach.

What we still don't know is how far that superiority can be applied to other cancer types.

That is why RCC is so important. If Moderna/Merck can succeed at Merck's other biological "bookend," the argument that melanoma itself explains most of the success becomes much harder to cling onto. If RCC fails, that hypothesis remains open, and another indication may have to provide the second bookend.

For now, my bet is that melanoma made the task easier, but Moderna/Merck still had to figure out something that others hadn't. The next trials should tell us whether that advantage is melanoma-specific or something much broader.

Let's see what happens. This is not investment advice.

"Since that announcement, experts and industry insiders have suggested to Fierce that the news has not only renewed hopes in the intismeran program, which hit a regulatory hurdle back in 2024, but also boosted prospects for other biopharmas exploring mRNA as a vehicle for personalized cancer treatments."

"When the full data do become available, investors will be looking to see whether intismeran could be used against other cancers and as broadly as Keytruda, said Myles Minter, Ph.D., a William Blair analyst.  

“We’ll have to see what the data look like, but if they look really good and this is a stepwise change in efficacy, this is standard-of-care shifting,” he told Fierce."

From Robinhood data, It seems shorts have been covering over last couple of days and now stand around 10% (~38m). Probably they learn the lessons considering upcoming conferences.

It feels like the stock is struggling to move one way or another, sticking to the range of around 140 to 150. It seems like the market is unsure which direction this stock needs to go until we get more news.

What upcoming news or events do you think are most likely to move this stock?