Last month Moderna reported the first individualized cancer vaccine to pass a Phase 3. Moderna CEO Stéphane Bancel and a16z's Jorge Conde on what that actually means: The treatment works by sequencing a patient’s tumor and healthy cells, identifying the mutations relevant to their cancer, and encoding up to 34 of them into an mRNA specific to the individual. Rather than simply unleashing the immune system, the goal is to teach it what to recognize and attack. In this conversation, they unpack the engineering challenge of manufacturing a different medicine for every patient, how Moderna has brought the process down to roughly 42 days from biopsy to treatment, and what it would take to manufacture personalized medicines at scale. 00:00 Intro 02:35 A Phase 3 that beat the standard of care 06:00 Why today's immunotherapy fails 40% of patients 09:35 A vaccine for cancer you already have 11:20 Why mRNA worked where 1,000 trials failed 13:15 90% of cancer antigens are unique to you 16:35 Why this vaccine only gets better from here 21:00 The only thing Moderna needs is your DNA sequence 22:20 Why the first robot was intentionally inefficient 27:10 How the FDA approves a drug that's different every time 33:05 A cancer treatment with the side effects of a flu shot 33:30 Why pancreatic cancer is worth a risk 36:30 Rare liver disease next, then autoimmune YouTube: @moderna_tx @JorgeCondeBio

Hear me out. On paper COMMIT is a "Positive" trial. It is also a spectacular demonstration that Atezolizumab monotherapy should never be used for metastatic MSI-H CRC (we can talk about adjuvant). COMMIT was a randomized first-line study in metastatic MSI-H/dMMR CRC. It began as a 3-arm trial of: • mFOLFOX6/bevacizumab (this sucks) • atezolizumab alone • mFOLFOX6/bevacizumab/atezolizumab After KEYNOTE-177 changed the standard of care, the chemotherapy-only arm closed after 20 patients. The trial continued with 82 patients randomized between atezo alone and the four-drug combination. The headline is that adding FOLFOX/bevacizumab to atezo improved PFS: HR 0.42 Median PFS: 24.5 vs 5.3 months ORR: 86% vs 46% Primary progression: 2.8% vs 32.4% The truth is Atezolizumab PALES in comparison to its contemporary PD1/PDL1 agents in this setting. Single-agent atezo: 12-month PFS 35% 24-month PFS 32% For comparison: Pembrolizumab in KEYNOTE-177: 12-month PFS 55% 24-month PFS 48% Nivolumab in CheckMate 8HW: 12-month PFS 63% 24-month PFS 56% This is not evidence that every patient with metastatic MSI-H CRC needs chemotherapy, bevacizumab, and immunotherapy. It is evidence that NO ONE SHOULD BE USING ATEZOLIZUMAB IN METASTATIC MSI-H CRC. And now, drumroll please… The only positive randomized adjuvant immunotherapy strategy in stage III dMMR colon cancer is ATOMIC: FOLFOX + atezolizumab. That makes COMMIT more than a roast. It raises a important question about ATOMIC. Should we be using Atezolizumab in the adjuvant setting? Do we need to be giving chemotherapy here? Looking forward to what others make of this but this is the real question. @TheGutOncLab @OncoAlert @oncodaily

How often does a company stop an actively enrolling global phase III trial and open an entirely new registration study? Well, it happened last week. Agenus is moving from BATTMAN to ROBBIN (which certainly has some ethical implications for starting/stopping a study I won't comment on). BATTMAN was testing BOT/BAL against best supportive care in refractory MSS metastatic colorectal cancer. An important question, but a best supportive care control was never likely to gain traction in the United States. ROBBIN moves BOT/BAL where it may have its best chance to work: previously untreated, high-risk stage II/III MSS colon cancer, before surgery and while the primary tumor remains intact. The rationale borrows from FOxTROT and builds on early neoadjuvant immunotherapy work from MSK and others like @pashtoonkasi . The early BOT/BAL data are compelling: • Pathologic response in approximately 60–70% • Major pathologic response in ~35–40% • pCR in ~30% Those are extraordinary numbers for MSS colon cancer and outperform the chemotherapy experience from FOxTROT. ROBBIN will randomize 850 patients to short-course neoadjuvant BOT/BAL followed by standard care versus standard care alone, with event-free survival as the primary endpoint. Will the pathologic responses translate into fewer recurrences? I think there is a real chance they will. The tradeoff will be toxicity. Grade 3 colitis/diarrhea occurred in 13% in one of the early cohorts, although there were no grade 4 events and almost no impact on surgical timing. So yes, you can still smell the colitis. But it may be worth it. @TheGutOncLab @Onco_Nexus @oncodaily @OncoAlert

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Check out the recap from John Roy, Ph.D.'s latest podcast with Oren Hershkovitz, CEO of Enlivex Ltd. (NASDAQ: $ENLV). Those interested can listen to the podcast on all platforms or on our website. Links are accessible in our full report! $ENLV #Enlivex# #Biotech# #Immunotherapy# #DigitalAssets# #Crypto# #Blockchain# #PredictionMarkets# #HealthcareInnovation# #ClinicalTrials# #DrugDevelopment# #Web3# #Tokenization# #SmallCapStocks# #InvestorInsights# #WaterTowerResearch# @Enlivex

SITUATION ANALYSIS: White Pill Wednesday Yesterday, Moderna and Merck announced an incredible result in cancer treatment. Their personalized mRNA cancer vaccine, intismeran autogene, substantially slowed recurrence of melanoma, the most serious type of skin cancer, in a Phase 3 clinical trial. The trial also showed a reduction in the risk of the cancer spreading to distant parts of the body. Moderna stock nearly tripled, surging 177% on the news. Merck rose 12.6%. Oncologists often say “cancer is like a snowflake” — there are hundreds of different types, and even patients with the same type of cancer have a unique set of mutations in their particular tumor. Historically, this has made cancer very difficult to treat. Now, doctors can sequence the DNA of a removed tumor and identify “neoantigens”, or mutated proteins that appear in the patient’s cancer cells but not their healthy cells. They then manufacture a custom messenger RNA (mRNA) vaccine that tells the patient’s cells to produce these neoantigens. This helps the patient’s T cells, a type of immune system cell, to hunt down and destroy cancer. In combination with Merck’s cancer immunotherapy drug Keytruda (pembrolizumab), it works better than Keytruda alone. This is a big deal. The first clinical trial testing a neoantigen vaccine was initiated in 1997, and billions of dollars have been spent over decades with little success. This trial is the first Phase 3 success for any individualized neoantigen therapy. It remains to be seen whether intismeran will work for other types of cancer beyond melanoma and how easily it can be scaled. Moderna and Merck have also not published effect sizes, survival times, or full statistical results, which will likely be presented at the European Society for Medical Oncology (ESMO) Congress in Madrid on October 23-27. But for now, it looks like another battle has been won in humanity’s millennia-long war against cancer. Written by @theojaffee. Read more at our link in bio.

Scientists figured out how to strip away the 'sugar shield' that protects cancer cells from immune attacks. Cancer cells are notorious masters of disguise, often coating themselves in a thick layer of sugar-derived molecules known as glycans to remain invisible to the body's natural defenses. This sugary camouflage acts as a physical shield and a molecular 'off switch,' suppressing immune cells and rendering many modern immunotherapies, like checkpoint inhibitors, ineffective. However, researchers from MIT and Stanford University have engineered a breakthrough therapeutic class called 'AbLecs' (antibody-lectin chimeras) specifically designed to strip away this protective barrier and expose hidden tumors. Developed by MIT's Dr. Jessica Stark and Stanford Nobel laureate Dr. Carolyn Bertozzi, AbLecs work by anchoring a glycan-binding lectin protein directly to cancer cells using a tumor-targeting antibody. This molecular pairing prevents the cancer’s sugars from shutting down neighboring immune cells, giving macrophages and natural killer cells the green light to attack. In pre-clinical trials, this plug-and-play platform dramatically reduced lung metastases and outperformed existing antibody drugs, paving the way for adaptable, next-generation immunotherapies that could soon help the estimated 80% of cancer patients who do not respond to current treatments. source: Stark, J. C., & Bertozzi, C. R. (2025). Antibody-lectin chimeras for glyco-immune checkpoint blockade. Nature Biotechnology.

Stripe's @RuxandraTeslo on why today's Moderna Phase 3 melanoma win probably won't hold in lung cancer or other solid tumors: "People are betting on Moderna's platform, so they expect these results won't just hold in skin cancer. They will also repeat themselves in other types of solid cancer, for example lung cancer. That might happen or it might not happen." "Skin cancer is the ideal cancer for cancer vaccines because it has this very high mutational burden, which allows the immune system to recognize the tumor very well. It's the cancer that responds so well to all immunotherapies." "Here we have seen the most bullish cancer, the best cancer for this type of vaccine. I'm excited about results in the future, but that is a big caveat, that we've seen the most favorable terrain in which these vaccines could be tested." @WorksInProgMag @stripe