Moderna bets on mRNA’s second act with cancer, autoimmune programs and AI research platform

At its recent annual Science Day, Moderna signalled a strategic expansion beyond its established vaccine and rare disease franchises, unveiling new programs in in vivo CAR-T and solid tumor oncology. The firm also revealed an AI-driven research platform it says will accelerate the pace of drug discovery across its pipeline.

The company publicly revealed two pipeline programs: mRNA-6007, an in vivo CAR-T candidate for autoimmune disease, and mRNA-2151, a multiplexed T-cell engager for ovarian cancer. The company revealed Lucy, an internal machine learning platform designed to run closed-loop experimental cycles.

Moderna built its commercial foundation on a single modality, lipid nanoparticle-delivered mRNA for infectious disease vaccines. These announcements indicate that the company is now attempting to replicate that infrastructure logic across oncology and autoimmune disease, using the same manufacturing base and the same LNP chemistry.

The company is arguing that the properties that made mRNA vaccines work at scale can translate to different disease categories. The company’s decade-plus of human clinical data gives it a learning advantage that later entrants cannot easily close.

Moderna’s pipeline is expansive, encompassing some three dozen programs spanning respiratory vaccines, latent-virus vaccines, oncology and rare disease, plus new forays into in vivo CAR-T and multiplexed T-cell engagers.

Stocks surge as analysts weigh the pipeline

Moderna’s stock had already climbed roughly 48% in the weeks leading into Science Day, lifted in part by the FDA advisory committee’s unanimous vote a week earlier in favor of mRNA-1010, its investigational flu vaccine. The rally continued after the event. Shares closed at $59.75 on Science Day, June 25, then jumped nearly 15% the following day as investors weighed the pipeline disclosures, including the plan to move mRNA-6007 into the clinic in 2027. The stock kept climbing into early July, touching a 52-week high of $85.60. As of midday July 7 it traded near $80, down about 2.6% on the day but roughly 75% above its early-June low.

William Blair analyst Myles Minter wrote in a note that FDA briefing documents revealed “no major deficiencies,” which he said boosted confidence in mRNA-1010’s approval prospects. Leerink Partners’ Mani Foroohar, in a separate note, described the FDA analysis as indicative of a “less-harsh regulatory stance.”

The Science Day pipeline disclosures added further momentum, with Piper Sandler raising its price target to $77 from $69 while maintaining an Overweight rating, citing the company’s cancer antigen therapy and in vivo CAR-T programs.

Even after the run, Wall Street stays cautious. The majority of firms rate Moderna a Hold or Sell, and the average 12-month price target sits in the mid-$40s, with Piper Sandler’s $77 the most bullish. At roughly $80, the stock now trades above every published analyst target.

Lucy aims to learn faster than any rival

Moderna revealed its machine learning platform called “Lucy”, which the company said is designed to connect data across lab notebooks and files into a continuously improving learning system. Lucy sits at the center of a closed-loop automation platform running in Moderna’s labs, linking experimental cycles with AI-driven hypothesis generation, with no human intervention between cycles.

The company says it can test hundreds of thousands of iterations per learning cycle, including multiplexed in vivo screening in mice and primates. Lucy uses barcoding systems to simultaneously place up to one thousand candidates into a single mouse or primate, then deconvolutes the results on the back end to assess each candidate’s performance.

Lucy has access to all of Moderna’s human mRNA clinical trials and data from ongoing trials. The company also partnered with OpenAI for Lucy as part of a broader strategy to incorporate public-domain datasets alongside proprietary clinical data.

Lucy can vary the mRNA design, LNP formulation or run combinatorial approaches to access both simultaneously at a scale that was previously impossible, said David Huss, Chief Technology Officer for Research at Moderna.

mRNA-6007 takes CAR-T into the body

Moderna announced its first in vivo CAR-T program, called mRNA-6007, at its June 25 Science Day event. The therapy targets B-cell-mediated autoimmune diseases, with an initial focus on systemic lupus erythematosus, and is scheduled to enter the clinic in 2027.

mRNA-6007 uses a dual-CAR approach, encoding two CARs to target both the full B-cell lineage and plasma cells, which Moderna said could achieve broader immune reset than single-CAR approaches targeting B cells alone.

Rather than extracting a patient’s cells, engineering them in a lab and reinfusing them, mRNA-6007 reprograms immune cells directly inside the body using targeted LNPs. It uses a multiplexed mRNA approach, aiming for deep B-cell depletion with transient CAR expression and potential immune reset.

With its mRNA expertise, Moderna is aiming to create treatments that are similarly efficacious to ex vivo CAR-T therapies, but free from lymphodepletion and complex manufacturing. Conventional ex vivo CAR-T for autoimmune disease requires weeks of manufacturing, is patient-specific and typically requires chemotherapy lymphodepletion. Moderna aims to create an off-the-shelf, injectable mRNA product.

mRNA-6007 therapies will enter human trials by the end of 2027, Moderna said. Moderna is completing IND-enabling studies and conducting a series of pre-submission health authority engagements. Preclinical studies in mice and non-human primates showed safety, tolerability and evidence of response, though this data has not yet been published.

The in vivo CAR-T space is nascent, but fast-moving. Capstan Therapeutics, now part of AbbVie, is running a Phase 1 study of CPTX2309, an anti-CD19 in vivo CAR-T candidate that transiently programs CD8+ T cells. CREATE Medicines, a clinical-stage company, has dosed more than 50 patients across its in vivo CAR clinical programs, pursuing both autoimmune and oncology indications.

Cartesian Therapeutics announced a strategic licensing agreement with WestGene Biopharma in June to develop in vivo CAR-T for autoimmune diseases, with a clinical trial expected to begin this year. Kernal is also targeting this space, currently in the preclinical stage with plans to advance its lead candidate towards development for multiple sclerosis.

Several academic groups have also published in vivo CD19 Car-T data in lupus patients using LNP-mRNA approaches. mRNA-6007’s multiplexed design, encoding two CARs, could be a differentiating factor for the therapy.

mRNA-2151 targets solid tumors

Moderna also spoke about its mRNA-2151 therapeutic, the first time the program has been named and detailed publicly. mRNA-2151 is a multiplexed T-cell engager produced encoding two kill T-cell engagers against two clinically validated tumor-associated antigens for ovarian cancer and a co-stimulatory molecule. The specific antigen targets are currently undisclosed.

As ovarian cancer’s tumor microenvironment is particularly immunosuppressive, T cells tend to become exhausted and lose killing ability. The co-stimulatory addition differentiates this therapy from mRNA-2808 and helped T cells retain killing ability under repeat stimulation. In a mouse xenograft model, T-cell engagers alone controlled tumor growth, but adding the co-stimulator molecule produced complete responses and more durable tumor control.

T-cell engagers have mostly struggled in solid tumors compared to blood cancers. Only two FDA-approved T-cell engagers, tarlatamab and tebentafusp, target solid tumors. Moderna is betting that encoding a co-stimulatory molecule alongside the kill signal in a single mRNA product could make the difference in solid tumors.

mRNA-2151 is moving toward early development in ovarian cancer, Moderna said, with its advancement supported by encouraging early clinical results from mRNA-2808.

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Filed Under: Biotech, clinical trials, Immunology, Oncology

 

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