Success after a century of failures: Inside Moderna and Merck’s cancer vaccine breakthrough — The Straits Times

RESOLVING THE LEDGER

Cancer experts hailed it as the beginning of an era of custom-made vaccines that train the immune system to fight an individual patient’s cancer.

Moderna and Merck developed the first successful mRNA therapeutic cancer vaccine after over 100 years of failures, showing promise in preventing melanoma recurrence in a large trial. The vaccine targets dozens of patient-specific tumour mutations and works with Merck’s Keytruda to enhance the immune system’s ability to fight cancer. Approval could come by 2027, with potential sales in billions; companies plan to improve the vaccine and test it on other cancers with fewer mutations. AI generated

Stephane Bancel, chief executive of Moderna, was at a Lebanese restaurant celebrating a friend’s birthday late on Aug 13 when he got the call.

An mRNA cancer vaccine the company had been developing with Merck had hit its mark – the first success of a therapeutic cancer vaccine in late-stage testing after more than 100 years of failed attempts.

Cancer experts hailed it as the beginning of an era of custom-made vaccines that train the immune system to fight an individual patient’s cancer. In a trial of more than 1,000 patients with localised melanoma, the vaccine kept tumours from coming back or spreading.

With full trial details pending, Wall Street is already estimating billions of dollars in sales.

Bancel likened news from that call to the day in late 2020 that Moderna announced its Covid-19 vaccine trial results.

“It was a moment that we’d worked really hard towards. We knew what was at stake for the planet with Covid,” Bancel said in an interview. It is the same with cancer, he said, adding that the disease touches nearly everybody at some point.

“I went right away into, ‘OK, what are all the things we have to do?’”

For Dean Li, president of Merck Research Laboratories, it was largely the same. When Eliav Barr, Merck’s 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 US FDA review, and apply the study’s strengths to other ongoing trials.

“It isn’t hallelujah,” Li recalls. “It’s boom.”

For Merck and Moderna, it was a moment built over 10 years, according to eight current and former company executives.

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.

For the cancer collaboration, Merck paid US$200 million (S$255 million) upfront in 2016 and another US$250 million in 2022. The companies share costs and profits.

At that time, Merck’s 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 brake.

“What 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,” Merck’s Barr said during an interview in late May.

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.

Tal Zaks, who served as Moderna’s chief medical officer from 2015-2021, immigrated to the US from Israel in 1996 to work on cancer vaccines at the National Cancer Institute.

“We failed back then, and we failed for many years,” Zaks said.

But he thought new technologies based on mRNA plus checkpoint inhibitors, as well as cheaper genetic sequencing, might open a path towards success.

Moderna had the mRNA technology, but as a young company, expensive cancer trials were out of reach.

Bancel said Moderna spoke with companies that had checkpoint inhibitors, but knew Merck well and was swayed by its experience mounting Keytruda trials.

Keytruda, which Merck’s Li calls a “miracle drug”, is used against 20 different kinds of cancerous tumours and 45 types and stages of cancer. But exactly what aspects of the tumour the drug targets, and why some patients respond better than others, remains a mystery.

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.

The vaccine, known as intismeran autogene, trains the immune system to attack cancer cells by targeting mutations unique to each patient’s tumours.

Prior cancer vaccines that attempted to train the immune system to target one or two specific tumour mutations failed.

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.

They also decided to test it in patients with early-stage melanoma following surgical removal of their tumours. That gave the companies critical time to create a customised vaccine based on a patient’s tumour and additional time for their immune systems to respond.

With mRNA technology, the companies were able to target dozens of mutations.

“You have many, many more shots on goal and therefore a much greater chance to succeed,” Moderna co-founder and MIT scientist Robert Langer said via e-mail.

The companies paired the vaccine with Keytruda’s ability to activate the body’s immune system T-cells that hunt down abnormal cells.

“The whole special thing about Keytruda was that it would unlock the dogs of war,” Li said.

The vaccine provides 34 patient-specific cancer targets for those dogs to recognise, he said, and only one needs to work. “With the personalised cancer treatment, the dog has your scent.”

Both companies stand to benefit significantly if the vaccine is approved. US approval could come as soon as 2027.

Merck later this decade faces the patent expiration of Keytruda, until recently the world’s top-selling drug. For Moderna, it offers a lifeline amid sagging Covid shot demand, and a reputational boost...

Success after a century of failures: Inside Moderna and Merck’s cancer vaccine breakthrough — The Straits Times | AIPROPX