Messenger ribonucleic acid (mRNA), which drew global attention for COVID-19 vaccines, is charging into the realm of cancer treatment.
On the 19th (local time), Moderna and Merck (MSD) said that their personalized mRNA cancer vaccine "intismeran autogene" met primary goals of preventing cancer recurrence and metastasis in a phase 3 clinical trial in high-risk melanoma patients.
This is the first time a personalized mRNA cancer vaccine has achieved primary goals in a phase 3 trial. On the news, Moderna shares on the New York Stock Exchange closed at $174.38, up 176.97% from the previous day. MSD shares also rose 12.6% to $152.20, a record high.
◇"Carriers" emerge as the key to mRNA commercialization
In the pharma-bio industry, there was an assessment that Moderna, which had suffered weak results due to waning COVID-19 vaccine demand, proved new growth potential for mRNA.
Moderna and MSD's "intismeran autogene" is different from a typical preventive vaccine.
RNA makes proteins or regulates gene activity based on the genetic information contained in DNA. Of these, mRNA delivers the "blueprint" that tells cells to make specific proteins.
An mRNA-based cancer vaccine analyzes a patient's tumor to find neoantigens from unique mutations in cancer cells, then manufactures, for each patient, mRNA targeting up to 34 neoantigens. After surgery, it is administered together with MSD's immunotherapy Keytruda so that the immune system attacks remaining cancer cells.
For such personalized therapies to be commercialized, there are significant hurdles. After analyzing a patient's tumor and selecting targets, one must make the mRNA and deliver it in a form that can function inside the body.
In the end, just as important as which RNA is made is how accurately and quickly it can be sent to the desired cells. In particular, RNA therapeutics such as mRNA and siRNA can be easily degraded in the body, so they need carriers that protect the RNA and transport it into the target cells.
◇The make-or-break for RNA therapies is "delivery"… technology race among domestic corporations
Accordingly, beyond developing RNA therapeutics themselves, the technology race to protect nucleic acids such as mRNA and siRNA and deliver them to desired cells is also intensifying.
Samyang Biopharm(0120G0) is developing a delivery technology that can be applied to personalized mRNA cancer vaccines. It is "NanoReady," based on the proprietary gene delivery platform "SENS."
By simple analogy, NanoReady is a carrier like a "courier" that transports mRNA to desired immune cells. When mRNA encoding characteristics of cancer cells is delivered to splenic dendritic cells, these cells inform T cells of the cancer's features and induce an attack.
According to the company, after confirming selective delivery to splenic dendritic cells and a strong T-cell immune response in mice, it also confirmed antigen-specific T-cell immune responses in nonhuman primates. The study results were published in the international journal Journal of Controlled Release.
NanoReady's differentiator is that its carriers can be prepared in advance. The carrier is manufactured and stored without RNA, and then combined when patient-specific mRNA is ready. This can be advantageous for shortening the manufacturing time of personalized cancer vaccines. The company said it estimates NanoReady's mRNA loading per particle is about 20 times higher than that of conventional LNP.
A Samyang Biopharm official said, "We have secured preclinical evidence showing that NanoReady is a platform applicable to diverse mRNA candidates," and added, "We will push to expand the platform business, including our own follow-up development of mRNA cancer vaccines, global technology transfers, and joint new drug development."
ST Pharm(237690) is expanding its business scope by securing both mRNA-stabilizing technology and carriers. While expanding its mRNA contract development and manufacturing (CDMO) business using proprietary technology, it has also embarked on joint research into AI-powered mRNA design and optimization.
◇RNA beyond the liver… aiming for the brain
Unlike existing RNA therapeutics, which have mainly been developed to target the liver, the industry views technologies that send RNA to tissues outside the liver—such as the brain, muscle, and heart—as the next battleground. In particular, the brain, where drug delivery is difficult because of the blood-brain barrier (BBB), is cited as a representative untapped market.
OliX Pharmaceuticals(226950) recently developed a second-generation OASIS-CNS platform that combines a shuttle crossing the BBB and confirmed that subcutaneously or intravenously administered siRNA suppresses target genes in deep brain regions of mice, such as the striatum and hippocampus. In some regions, inhibition exceeded 70% to 80%.
ABL Bio(298380) is also expanding the application of its BBB shuttle platform "Grabody-B" to siRNA. In joint research this year, it confirmed the potential to deliver not only to the brain but also to peripheral tissues such as muscle, heart, and lung when combining Grabody-B with siRNA. How far a drug can be sent is becoming a competitive platform advantage in itself.
Beyond delivery, technology to precisely modify RNA itself has also emerged as a competitive axis. Rznomics(476830) is developing "trans-splicing" technology that uses RNA replacement enzymes to cut out disease-causing RNA and change it to desired RNA sequences. Last year, it signed a deal worth up to $1.3 billion with Eli Lilly and Company for joint development of a genetic hearing loss therapy, gaining recognition for its technology.
Moderna's clinical success can be seen not only as the opening of the mRNA cancer vaccine market but also as a signal that the competitive stage for RNA drugs is expanding. Beyond precisely designing RNA, the capability to deliver it accurately to desired cells and tissues and to produce it reliably is emerging as the competitive key for domestic corporations.