U.S. drugmaker Moderna is expanding its cancer drug development efforts on the back of the phase 3 success of its personalized messenger RNA (mRNA) cancer vaccine.
Beyond combination use with immuno-oncology drugs, the company is assessing the possibility of a vaccine monotherapy, and it is expected to broaden research to "in vivo chimeric antigen receptor T cells (CAR-T)," which kill cancer cells directly in the body with a single injection.
On the 7th, according to the pharmaceutical and biotech industry, Moderna is developing a range of mRNA-based cancer vaccines and therapeutics. Its personalized cancer vaccine "intismeran autogene," which recently delivered phase 3 results in combination with Merck's (MSD) immunotherapy Keytruda, is also undergoing additional studies, including as a monotherapy.
Kim Hee-su, a vice president at Moderna Korea, said, "In addition to the combination regimen co-developed with MSD, we are looking at the monotherapy potential of intismeran autogene," and noted, "Preclinical studies are underway, and we expect to enter full-fledged clinical trials around the end of next year."
The intismeran autogene and Keytruda combination regimen, whose clinical results were released in May, met its primary goals of suppressing cancer recurrence and metastasis in a phase 3 trial in high-risk melanoma patients. This is the first time an mRNA-based cancer vaccine has met primary endpoints in a phase 3 trial.
Intismeran autogene is manufactured as a personalized therapy by analyzing tumor tissue to identify cancer-specific mutations, selecting neoantigens likely to elicit an immune response, and tailoring them to each patient.
Currently, MSD is leading development of the combination regimen, including late-stage trials. In Korea, MSD has completed enrollment of melanoma patients for a late-stage trial and is conducting the study.
Leveraging the trial results, Moderna plans to expand the use of mRNA in cancer therapy beyond personalized cancer vaccines.
A representative field is "in vivo CAR-T," a next-generation CAR-T technology that kills cancer cells directly in the body with a single injection. The approach delivers RNA to specific immune cells to generate CAR-T cells inside the patient, and is considered a next-generation technology that could significantly change the manufacturing process for conventional cell therapies.
Kim said, "If mRNA is applied to in vivo CAR-T, there could be changes to the complex manufacturing process of current cell therapies," adding, "If we can reduce the steps of harvesting a patient's cells, manipulating and culturing them externally, and reinfusing them, and instead directly induce immune cell functions in the body, it could evolve into a new treatment approach."
The company is also developing mRNA therapeutics that target antigens commonly found in specific cancer patient groups. The lead candidate, "mRNA-4359," is in phase 2 as both a Keytruda combination and a monotherapy for melanoma and Non-small cell lung cancer (NSCLC). In phase 1/2 results released in Apr., it showed a meaningful antitumor response as first-line therapy for advanced or metastatic melanoma.
While broadening the scope of the mRNA platform in oncology, Moderna is also seeking new growth drivers in infectious disease vaccines. Norovirus vaccine development is cited as the next key program.
Norovirus is a major infectious disease that causes vomiting and diarrhea mainly in winter, but vaccine development is considered difficult due to the virus's diversity and frequent mutations. In the past, multiple corporations attempted to develop vaccines but failed to achieve sufficient results in clinical trials. Moderna is currently conducting late-stage clinical trials of a norovirus vaccine.
Moderna stresses that, for its core existing business of the COVID-19 vaccine, a stable vaccination base should be maintained with a focus on older adults and high-risk groups.
Recently, as COVID-19 is increasingly perceived as similar to a cold, vaccination rates have remained lower than for influenza. According to the Korea Disease Control and Prevention Agency, the budget for procuring next year's COVID-19 vaccines is down about 10% from this year, and the procurement volume has decreased by about 500,000 doses.
Kim said, "Because COVID-19 remains a significant respiratory infectious disease that can lead to hospitalization and death among older adults, regular vaccination is needed for high-risk groups such as older adults and the immunocompromised," adding, "In line with the rise in the older population, we need to ensure sufficient vaccination opportunities for high-risk groups at the times they need them."