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Stephane Bancel, CEO of Moderna, was at a Lebanese restaurant celebrating a friend\u2019s birthday late on August 13 when he got the call.<\/span><\/p>\n An mRNA cancer vaccine the company had been developing with Merck had hit its mark \u2014 the first success of a therapeutic cancer vaccine in late-stage testing after more than 100 years of failed attempts.<\/span><\/p>\n Cancer experts hailed it as the beginning of an era of custom-made vaccines that train the immune system to \u200bfight an individual patient\u2019s cancer. In a trial of more than 1,000 patients with localized melanoma, the vaccine kept tumors from coming back or spreading.<\/span><\/p>\n With full trial details pending, Wall Street is already estimating \u200cbillions of dollars in sales.<\/span><\/p>\n Bancel likened news from that call to the day in late 2020 that Moderna announced its COVID-19 vaccine trial results.<\/span><\/p>\n \u201cIt was a moment that we\u2019d worked really hard toward. We knew what was at stake for the planet with COVID,\u201d Bancel said in an interview. It\u2019s the same with cancer, he said, adding that the disease touches nearly everybody at some point.<\/span><\/p>\n That moment of joy was brief. \u201cI went right away into, \u2018OK, what are all the things we have to do?’\u201d<\/span><\/p>\n For Dean Li, president of Merck Research Laboratories, it was largely the \u200bsame. When Eliav Barr, Merck\u2019s head of global clinical development, called Li, he already had a list of urgent tasks: ready the data for presentation at an international cancer meeting, turn to the U.S. FDA review, \u200band apply the study\u2019s strengths to other ongoing trials.<\/span><\/p>\n \u201cIt isn\u2019t hallelujah,\u201d Li recalls. \u201cIt\u2019s boom.\u201d<\/span><\/p>\n HOW THEY GOT THERE<\/span><\/p>\n For Merck and Moderna, it was a moment built over 10 years, according to \u2060eight current and former company executives.<\/span><\/p>\n When they announced a partnership in 2016 to develop a cancer vaccine, the companies had been working for over a year on a separate vaccine venture.<\/span><\/p>\n For the cancer collaboration, Merck paid $200 million upfront in 2016 \u200band another $250 million in 2022. The companies share costs and profits.<\/span><\/p>\n At that time, Merck\u2019s Keytruda was emerging as a powerhouse in a new class of drugs called checkpoint inhibitors that could unleash the immune system to fight cancers by removing a natural \u200bbrake.<\/span><\/p>\n \u201cWhat Keytruda taught the world was that, yes, there is an immune recognition of cancer, but cancer is clever in putting up barriers, and Keytruda removes those barriers,\u201d Merck\u2019s Barr said during an interview in late May.<\/span><\/p>\n Next, he said, companies, including Merck, looked for ways to further rev up the immune system, testing Keytruda with next-generation immunotherapy drugs such as TIGIT inhibitors. \u201cIt didn\u2019t work,\u201d Barr said.<\/span><\/p>\n Tal Zaks, who served as Moderna\u2019s chief medical officer from 2015-2021, immigrated to the U.S. from Israel in 1996 to work on cancer vaccines at the National Cancer Institute.<\/span><\/p>\n \u201cWe \u200bfailed back then, and we failed for many years,\u201d Zaks said.<\/span><\/p>\n But he thought new technologies based on mRNA plus checkpoint inhibitors, as well as cheaper genetic sequencing, might open a path toward success.<\/span><\/p>\n Moderna had the mRNA technology, but as a \u200byoung company, expensive cancer trials were out of reach.<\/span><\/p>\n Bancel said Moderna spoke with companies that had checkpoint inhibitors, but knew Merck well and was swayed by its experience mounting Keytruda trials.<\/span><\/p>\n Keytruda, which Merck\u2019s Li calls a \u201cmiracle drug,\u201d is used against 20 different kinds of \u200ccancerous tumors and \u206045 types and stages of cancer. But exactly what aspects of the tumor the drug targets, and why some patients respond better than others, remains a mystery.<\/span><\/p>\n Messenger ribonucleic acid, or mRNA, is present in every cell of the body. Its job is to carry genetic instructions from the cell nucleus to parts that make specific proteins.<\/span><\/p>\n The vaccine, known as intismeran autogene, trains the immune system to attack cancer cells by targeting mutations unique to each patient\u2019s tumors.<\/span><\/p>\n Prior cancer vaccines that attempted to train the immune system to target one or two specific tumor mutations failed.<\/span><\/p>\n The companies decided to test the vaccine in melanoma, which has among the highest number of mutations of any cancer and against which checkpoint inhibitors had a record of success.<\/span><\/p>\n They also \u200bdecided to test it in patients with early-stage melanoma following \u200bsurgical removal of their tumors. That gave the companies \u2060critical time to create a customized vaccine based on a patient\u2019s tumor and additional time for their immune systems to respond.<\/span><\/p>\n With mRNA technology, the companies were able to target dozens of mutations.<\/span><\/p>\n \u201cYou have many, many more shots on goal and therefore a much greater chance to succeed,\u201d Moderna co-founder and MIT scientist Robert Langer said via email.<\/span><\/p>\n The companies paired the vaccine \u200bwith Keytruda\u2019s ability to activate the body\u2019s immune system T-cells that hunt down abnormal cells.<\/span><\/p>\n \u201cThe whole special thing about Keytruda was that it would unlock the dogs of war,\u201d \u200bLi said.<\/span><\/p>\n The vaccine provides 34 patient-specific \u2060cancer targets for those dogs to recognize, he said, and only one needs to work. \u201cWith the personalized cancer treatment, the dog has your scent.\u201d<\/span><\/p>\n Both companies stand to benefit significantly if the vaccine is approved. U.S. approval could come as soon as next year.<\/span><\/p>\n Merck later this decade faces the patent expiration of Keytruda, until recently the world\u2019s top-selling drug. For Moderna, it offers a lifeline amid sagging COVID shot demand, and a reputational boost.<\/span><\/p>\n U.S. Health Secretary Robert F. Kennedy Jr. has criticized the safety and efficacy of \u2060mRNA vaccines for \u200binfectious disease, without evidence, and cut $500 million in related projects.<\/span><\/p>\n Moderna\u2019s shares, which had fallen around 90% from their COVID peak, are up more than 130% \u200bsince the vaccine results were announced. Wall Street analysts see sales topping $1 billion by 2030 and $3 billion by 2035, according to LSEG data.<\/span><\/p>\n The next test is finding whether the approach can work in cancers with fewer mutations, including lung, kidney and pancreatic cancers.<\/span><\/p>\nFINDING A PARTNER<\/span><\/h2>\n
WHAT\u2019S NEXT<\/span><\/h2>\n