Alex Cheng @Syde_Walker

Towards mRNA therapeutics 2.0 nature.com/articles/s4157… This new Review discusses progress and insights from clinical studies on mRNA-based drugs, including enzyme replacement therapies, cancer immunotherapies, genome-modifying therapies and immune cell reprogramming therapies

ASCO 2026 HIGHLIGHTS #ASCO26 delivered a striking mix of practice-changing late-stage data, long-term follow-up, molecularly guided treatment strategies and rare-tumor studies that would once have struggled to attract this level of attention. I used @Larvol CLIN data to identify the ten most exciting trial results. Here they are: RASolute 302: daraxonrasib in metastatic pancreatic cancer RASolute 302 was arguably the most important single therapeutic readout at ASCO 2026. Daraxonrasib, a multi-selective RAS(ON) inhibitor, was tested in previously treated metastatic pancreatic ductal adenocarcinoma. The trial showed median overall survival of 13.2 months with daraxonrasib versus 6.7 months with chemotherapy, corresponding to a 60% reduction in the risk of death. Reuters also reported tumor shrinkage or disappearance in more than 30% of treated patients, compared with about 10% on chemotherapy. This is strategically important because pancreatic cancer has long been one of the most difficult tumors to treat, and RAS has historically been considered hard to drug. If approved, daraxonrasib could become a major new treatment option and a platform asset for earlier-line and combination strategies. CROWN: LORBRENA in first-line ALK-positive advanced NSCLC The seven-year CROWN update is one of the strongest long-term targeted therapy datasets in advanced solid tumors. In previously untreated ALK-positive advanced or metastatic NSCLC, LORBRENA showed a 55% probability of remaining alive without disease progression at seven years, compared with 3% for crizotinib. Median progression-free survival was still not reached, with a hazard ratio of 0.19, representing an 81% reduction in the risk of progression or death. Pfizer also reported a 94% reduction in the risk of intracranial progression. The strategic meaning is clear: for some molecularly defined lung cancers, long-term disease control is now a realistic expectation. The CROWN data also reinforce the commercial value of CNS penetration and durable intracranial control in ALK-positive NSCLC. HARMONi-6: ivonescimab plus CT in first-line squamous NSCLC HARMONi-6 is important because it was not simply another chemo-immunotherapy trial. Ivonescimab, a PD-1/VEGF bispecific antibody, plus chemotherapy was compared directly with tislelizumab plus chemotherapy in previously untreated advanced squamous NSCLC. The study showed median overall survival of 27.89 months versus 23.69 months, with a hazard ratio of 0.66. The 24-month overall survival rates were 64.7% versus 48.6%. This matters because the comparator was an active PD-1 plus chemotherapy regimen, not chemotherapy alone. If confirmed in global studies, HARMONi-6 could challenge the current PD-1/chemotherapy paradigm and accelerate interest in PD-1/VEGF bispecific antibodies. PROTEUS: ERLEADA before/after surgery in high-risk localized PC PROTEUS tested perioperative ERLEADA plus androgen deprivation therapy in newly diagnosed high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy. The trial met both primary endpoints. Pathological complete response or minimal residual disease was 8.9% versus 1.0%, and metastasis-free survival improved with a hazard ratio of 0.80. Five-year metastasis-free survival was 78.2% versus 73.5%. Time to subsequent therapy was also extended to 74.2 months versus 41.5 months. This trial is important because it brings systemic intensification into the curative-intent surgical setting. The effect size is not spectacular, but the paradigm shift is meaningful: high-risk localized prostate cancer may need earlier systemic control, not only salvage treatment after recurrence. KEYNOTE-A39: PADCEV plus KEYTRUDA in 1L advanced urothelial cancer KEYNOTE-A39 / EV-302 confirmed the durability of PADCEV plus KEYTRUDA in previously untreated locally advanced or metastatic urothelial carcinoma. With 42.8 months median follow-up, median overall survival was 33.6 months with PADCEV plus KEYTRUDA versus 15.9 months with chemotherapy, with a hazard ratio of 0.53. The 3.5-year overall survival rate was 44.0% versus 24.6%. Objective response rate was 67.5% versus 44.2%, and complete response rate was 30.4% versus 14.5%. This is now one of the clearest examples of an antibody-drug conjugate plus immunotherapy combination replacing platinum chemotherapy as the central first-line standard. The long-term data strengthen confidence in durability, although neuropathy and treatment management remain important in real-world practice. LIBRETTO-432: RETEVMO in RET fusion-positive early-stage NSCLC LIBRETTO-432 extends precision oncology into curative-intent lung cancer. The study enrolled patients with resected stage IB-IIIA RET fusion-positive NSCLC and randomized them to adjuvant RETEVMO or placebo. The trial reported a statistically significant event-free survival benefit and is positioned alongside ADAURA in EGFR-mutant disease and ALINA in ALK-positive disease. The key strategic point is testing. If RET-targeted adjuvant therapy becomes standard, molecular profiling at diagnosis and resection becomes even more important. This is another example of the metastatic precision oncology model moving into early-stage disease. NATALEE: KISQALI plus endocrine therapy in HR+, HER2- early BC NATALEE continued to support adjuvant KISQALI plus a nonsteroidal aromatase inhibitor in HR-positive, HER2-negative early breast cancer. At a median follow-up of 55.4 months, the 36-month invasive disease-free survival rate was 90.8% with KISQALI versus 88.0% with aromatase inhibitor alone. The 60-month invasive disease-free survival rate was 85.5% versus 81.0%. The broader eligibility criteria included high-risk node-negative patients, where KISQALI showed a hazard ratio of 0.606. The commercial and clinical question is not whether CDK4/6 inhibition works in early breast cancer, but which patients should receive it. NATALEE broadens the addressable population, but also raises familiar questions around access, toxicity, treatment duration and patient selection. IMvigor011: TECENTRIQ guided by ctDNA in bladder cancer IMvigor011 is one of the most conceptually important trials on the list. In muscle-invasive bladder cancer after surgery, serial ctDNA testing was used to identify molecular residual disease. ctDNA-positive patients randomized to TECENTRIQ had median disease-free survival of 9.9 months versus 4.8 months with placebo, and median overall survival of 32.8 months versus 21.1 months. Persistently ctDNA-negative patients had excellent outcomes, with 88% disease-free survival at two years. This trial may prove influential beyond bladder cancer. It supports a future in which adjuvant therapy is not given simply because clinical risk is high, but because molecular residual disease is detected. That is a major shift in how oncology treatment could be personalized after curative-intent surgery. SARC041: VERZENIO in dedifferentiated liposarcoma SARC041 is notable because it is the first positive phase 3 trial ever reported in dedifferentiated liposarcoma. VERZENIO improved median progression-free survival to 9.7 months versus 1.5 months with placebo, with a hazard ratio of 0.38. Six-month progression-free survival was 60% versus 22%, and 12-month progression-free survival was 39% versus 13%. Median overall survival was not reached versus 25.5 months, with an overall survival hazard ratio of 0.55, despite high crossover from placebo to VERZENIO. The response rate was modest, but that is not the main point. In this disease, durable disease control is clinically meaningful. SARC041 may establish CDK4/6 inhibition as a real treatment option in a rare sarcoma subtype where systemic standards have been weak. KEYNOTE-564: KEYTRUDA in adjuvant clear-cell RCC KEYNOTE-564 remains one of the most important adjuvant immunotherapy datasets in kidney cancer. The trial evaluated KEYTRUDA after nephrectomy in patients with clear-cell renal cell carcinoma at increased risk of recurrence. Earlier analyses established KEYTRUDA as the first adjuvant regimen to significantly improve both disease-free survival and overall survival versus placebo after surgery. Reported outcomes include disease-free survival hazard ratio of 0.71 and overall survival hazard ratio of 0.66. At ASCO 2026, the focus shifted toward ctDNA analysis in KEYNOTE-564, exploring whether molecular residual disease could help identify patients at highest risk of recurrence and potentially refine adjuvant treatment decisions. This is strategically important because KEYNOTE-564 is no longer only a positive adjuvant immunotherapy trial. It is now part of the broader question of how to personalize adjuvant treatment in renal cell carcinoma. If ctDNA can help distinguish patients who truly need treatment from those who may be safely observed, it could reshape future trial design, treatment selection and health-economic modelling in kidney cancer. See attached Summary Table of Key Trial Results from ASCO 2026 Strategic interpretation Several patterns stand out. First, ASCO 2026 strongly reinforced the move into earlier disease. PROTEUS, LIBRETTO-432, NATALEE, IMvigor011 and KEYNOTE-564 all address treatment before overt metastatic relapse. The future oncology battleground is increasingly the prevention of recurrence, not only treatment after recurrence. Second, molecular selection is becoming embedded across the disease continuum. RET fusions in early NSCLC, ALK in metastatic NSCLC, ctDNA in bladder cancer and renal cell carcinoma, RAS in pancreatic cancer and CDK4 biology in liposarcoma all show the same direction of travel: treatment value depends on identifying the right patients at the right time. Third, ADCs and bispecific antibodies are now challenging major standards. PADCEV plus KEYTRUDA has transformed first-line urothelial cancer. Ivonescimab may challenge PD-1 plus chemotherapy in squamous NSCLC if global data confirm the China results. Fourth, rare tumors are no longer peripheral. SARC041 shows that prospective data in rare cancers can still change practice, even when the commercial story is smaller than in lung, breast, prostate or kidney cancer. © Robert F. Siegmund, PhD MBA | Life Code GmbH I deliver strategic insights and product forecasting models to biopharma companies across the product lifecycle. Reach out to me!

Another major advance vs cancer! @ASCO #ASCO26 Personalized neoantigen mRNA vaccine 5 year follow-up vs metastatic melanoma reduced recurrence and death by 49% (on top of Keytruda) ascopubs.org/doi/10.1200/JC…

Check this out! accessnewswire.com/newsroom/en/he…

📢Introducing BiomniBench — the first benchmark focused on evaluating the process, not just the final answer, of AI agents on long-horizon biology research tasks. We evaluate whether each analysis step is statistically sound and scientifically defensible — just like peer review, where the validity of the process matters, not matching a single ground-truth answer. Built with first authors from Nature, Cell, and Science papers, BiomniBench captures 100 most ambitious research tasks across disease areas. Huge headroom for performance, jagged frontiers across tasks, and many more interesting results:

Yuanhao Qu @YuanhaoQ

a month ago

𝗖𝗮𝗻 𝗔𝗜 𝗮𝗴𝗲𝗻𝘁𝘀 𝗽𝗲𝗿𝗳𝗼𝗿𝗺 𝗯𝗶𝗼𝗺𝗲𝗱𝗶𝗰𝗮𝗹 𝗱𝗮𝘁𝗮 𝗮𝗻𝗮𝗹𝘆𝘀𝗶𝘀 𝘁𝗮𝘀𝗸𝘀 𝗯𝗲𝗵𝗶𝗻𝗱 𝗽𝗮𝗽𝗲𝗿𝘀 𝗶𝗻 𝗡𝗮𝘁𝘂𝗿𝗲, 𝗖𝗲𝗹𝗹, 𝗮𝗻𝗱 𝗦𝗰𝗶𝗲𝗻𝗰𝗲? To find out, we built 𝗕𝗶𝗼𝗺𝗻𝗶𝗕𝗲𝗻𝗰𝗵, a benchmark we co-developed with the original paper

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FDA leaders say one pivotal trial, not two, should be ‘default’ for drug approvals biopharmadive.com/news/fda-makar… via @BioPharmaDive

If you are a beginner researcher, this paper will help you.

1/🚨More bad news for the Gene Therapy field. Last Wednesday, the FDA raised concerns about life-threatening cases of Cancer - including Leukaemia, in patients that were treated with Bluebird bio’s Skysona - a gene therapy treatment for cerebral adrenoleukodystrophy (CALD). $XBI

Genetix Biotherapeutics @genetix_biotx

4 years ago

#NewsfromtheNest: We are thrilled to announce that the @US_FDA has approved our first gene therapy for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions! Read more in our press release: investor.bluebirdbio.com/news-releases/… [1/2]

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“My advice would be to spend less time on finance, spend less time in the conference rooms, less time on PowerPoint, and more time on just trying to make your product as amazing as possible.” — Elon Musk 🎥 @elon_docs

In less than a minute, Washington hit these 3 points: Point 1: If you don't fail, you're not even trying. Point 2: To get something you've never had, you have to do something you've never done. Point 3: Imagine the ghosts of your unfulfilled potential.

youtube.com/live/yH0mGVt1f… ODAC on CODEBREAK 200 is a great watch. Polished pharma presentation. I liked the “they feel it and I see it” line. The @FDAOncology critique was a masterclass in analysing bias in open label studies and limitations of BICR. @BTOGORG

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Discussant…. There 56 antiPDL1/PD1 assets in development. Nuts #ASCO23 #LCSM

KEYNOTE789: beautifully presented by James Yang. 492 randomised. 35%X over. A positive but negative trial? #ASCO23 #LCSM

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#ASCO23 will take us to the agnostic ADC era. In the just released #HERALD phase 2 trial, 62 patients with 16 different advanced cancer types and detectable HER2 amp on ctDNA received T-DXd. ORR 56.6% DCR 90% Responses in 13 cancer types. meetings.asco.org/abstracts-pres…

GSK announces positive headlines for checkpoint inhibitors in the NSCLC setting clinicaltrialsarena.com/comment/gsk-ch… 来自 @TrialsArena

The best way to ensure good code is to have a good organization. This paper from Microsoft looking at 50M lines of code found that organizational factors were far more powerful in explaining the number of bugs than any technical aspect of the project. microsoft.com/en-us/research…

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Nirsevimab vs Palivizumab from Sanofis R&D day.

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Here’s the Atlas Venture 2022 Year In Review. This year, given the 2+ year rollercoaster in the mkts, we start with a deep dive into both the public and private #biotech capital markets, then to the industry overall, closing with an update on ⁦Atlas youtu.be/LONM9ekseJ4

The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans science.org/doi/10.1126/sc…

New #GBDStudy suggests alcohol consumption carries significant health risks and no benefits for young people; some older adults may benefit from drinking a small amount. Find out more: hubs.li/Q01gVGGb0 @IHME_UW

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