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Pandemic winners face hurdles as they seek to bring their groundbreaking technology to oncology

Steve Haycock had most of his colon removed last year but doctors have told the 43-year-old that his bowel cancer is highly likely to come back — unless a personalised vaccine trial pays off.

The product is made by German Covid-19 jab maker BioNTech, which has identified proteins specific to mutations in his cancer cells and designed a vaccine that will prime his immune system to attack new tumours containing them.

“It’s given me a lot of confidence to be on this trial,” he said. “I’m only in this position because things are going badly for me but I do feel privileged.”

BioNTech and US coronavirus jab rival Moderna, both of whose shares have slid about 80 per cent since their 2021 pandemic peaks, are betting on cancer vaccines to revive their fortunes. Using the mRNA technology behind their Covid products, they hope to drastically improve outcomes and lead a new field of cancer care.

But it is early days for personalised vaccine technology and many hurdles remain. Making a personalised vaccine for each patient will be costly and come with supply chain challenges, while pharma groups are constantly advancing other drug types in the ever competitive cancer field.

While “it’s very attractive and very exciting”, said Miranda Payne, a melanoma specialist leading a Moderna trial at Oxford’s Churchill Hospital, “it’s a little bit hard to see how you’ll scale it up for everybody who might need it”.

Several companies have tried to develop cancer vaccine-style products in recent years but the products have struggled to induce an effective response to tumours, especially in late-stage cancer when the immune system is already weak.

“Vaccines have historically been an abysmal investment,” said Marek Poszepczynski, an oncology expert at life sciences investor the International Biotechnology Trust. “Cancers are very, very good at escaping the immune system.”

BioNTech and Moderna are hoping to succeed where others have failed as they seek to develop broad portfolios of cancer treatments. Bolstered by Covid-19 revenues, both spent record sums on research and development last year.

BioNTech’s product, available to Haycock through an NHS trial, is years from commercialisation. Moderna’s jab for melanoma, a type of skin cancer that can spread to other areas of the body, was developed with Merck and is in more advanced trials.

As mRNA taught the immune system to recognise and fight Covid-19, it can instruct immune cells to recognise proteins known as neoantigens that are particular to mutations in an individual’s cancer.

Every Moderna jab is tailor-made, with each patient’s tumour genomically sequenced to select the best-suited 34 neoantigens. The vaccine then directs the immune system to recognise these neoantigens and attack future cancer cells that contain them.

The BioNTech product used to treat Haycock is being co-developed with Roche subsidiary Genentech and works similarly, with up to 20 neoantigens selected.

Although it rose to global prominence through Covid, BioNTech’s main focus since it was founded in 2008 has been cancer. “Personalisation of our mRNA vaccines is our most important innovation,” Uğur Şahin, chief executive, told the Financial Times.

Moderna chief executive Stéphane Bancel recalled how he told staff late in the pandemic that “10 years from now, people would have forgotten what we did for the world during the pandemic because we’ll be known as one of the most impactful cancer product companies”.

Positive data in June from a mid-stage trial of the company’s skin cancer jab showed that a personalised vaccine could be closer than ever. “Some investors are sceptical but this is a science business,” Bancel added.

Among a group of 157 late-stage melanoma patients treated with Merck’s blockbuster cancer immunotherapy Keytruda, the risk of death or disease recurrence fell 49 per cent among those who also received Moderna’s vaccine. Moderna is now pushing ahead with late-stage trials.

Combining products with treatments such as Keytruda could prove key to realising vaccines’ potential.

Merck’s drug is the most successful of a wave of immunotherapies known as checkpoint inhibitors. First approved by the US Food and Drug Administration in 2014 for advanced melanoma patients, Keytruda is now used against 17 cancer types, including breast, lung, blood and skin cancers. It was the world’s highest-selling drug last year with $25bn in sales.

Checkpoint inhibitors “remove the brakes” on immune system cells that stop them from attacking tumours, said Lawrence Young, an oncology professor at the University of Warwick, while vaccines then direct the immune cells to target the cancer.

While only 20-40 per cent of patients respond to the drugs, experts say the dual action of the vaccines could increase this number.

“Scientifically, it makes a lot of sense to combine them,” said Peter Kiener, an investor with ICG Life Sciences who is an oncology expert. “If you can add on a vaccine that’s tolerable, you could change that response rate from 20-30 to 50-60 per cent of patients. Then you really can have a tremendous impact on the disease.”

BioNTech is also trialling a personalised melanoma vaccine to be delivered alongside Keytruda but is developing another melanoma jab to be used with a checkpoint inhibitor developed by Regeneron. The company said last month that tumours had shrunk more in patients receiving the vaccine than in those on standard treatment, although it has not disclosed detailed results.

The personalised approach does have drawbacks. “It’s very expensive if you have to sample the tumour, sequence it and make a bespoke vaccine,” said Young. “While the individualised approach is exciting and will be proof of principle, I suspect there will be a more generalised approach.”

BioNTech is trying both strategies: its melanoma product with Regeneron is an “off-the-shelf” jab that uses just four melanoma antigens, at least one of which is present in 90 per cent of melanomas. This could be cheaper to produce but less targeted than the Moderna product.

It is one of eight ongoing trials for mRNA cancer vaccines that BioNTech is conducting, including personalised vaccines for lung, pancreatic and colorectal cancer.

But Moderna is likely to be first to market. Having shown the potential of its jab in melanoma, the company is launching phase-three trials testing the jab on the most common type of lung cancer and another form of skin cancer, as well as earlier-stage trials in kidney and bladder cancer, among others.

It also plans to study its cancer vaccine as a standalone treatment on patients with early-stage cancer, without administering Keytruda as a dual therapy.

“The ambition we have with Merck is to take [the cancer vaccine] to all the places and make it just as big as the checkpoint inhibitors have become,” said Stephen Hoge, Moderna’s president who runs its research and development efforts.

In Oxford, Payne has been helping patients who have had melanoma surgery participate in the Moderna phase-three trial.

“There’s been huge interest in it”, she said, adding that Moderna reached its recruitment goal for participants in June, well ahead of an original mid-2025 target.

But Payne’s experience also points to other challenges for the vaccine makers. She said one in four patients suggested by her had been turned away because of issues with the tumour samples and identifying enough neoantigens to make the vaccines.

To bolster its supply chain, Moderna has invested $322mn in a vaccine manufacturing facility in its home state of Massachusetts. BioNTech is also investing in new facilities near its headquarters in Mainz, Germany, that it hopes to open by the end of the year.

But Kyle Holen, Moderna’s oncology head, admitted that the process of sequencing the tumours could still be smoother. Moderna cannot currently use sequencing data from a patient’s biopsy to diagnose their cancer, meaning a second set of tests has to be carried out.

Şahin said he expected the drugs to be more expensive than existing immunotherapies and that the price tags would have to be justified by preventing future strains on healthcare systems.

“It can only be expensive if it really addresses a high medical need and if it reduces downstream costs associated, for example, by preventing metastatic cancer,” he said.

But several experts added that there were alternatives that could also prevent cancers returning, potentially at a lower cost.

A 2023 study found that giving advanced melanoma patients Keytruda both before and after surgery, instead of only after, could also delay cancers from recurring. Three-quarters of patients who received it before and after had no cancer within two years, against half who received the drug only after surgery.

Merck also recognises there are limitations to the vaccines. “The Achilles heel of this particular therapy is that it requires that the immune system remains intact so they can create an immune response,” said Eliav Barr, Merck’s chief medical officer, meaning younger patients would be most likely to benefit from the drug.

And despite the impressive melanoma data, experts remain doubtful about how helpful vaccines will be against other cancers or as a standalone treatment.

Melanoma is among the cancers with the highest frequency of genetic mutations, lending itself to be targeted by immunotherapy, according to Elizabeth Jaffee, a professor of oncology at Johns Hopkins University. Vaccines may not fare as well against less immune-responsive cancers, she said.

Meanwhile, rival pharma players are also advancing alternative treatments such as CAR-T therapies, another highly costly, personalised product where patients’ immune cells, or T cells, are extracted and genetically modified to better kill cancer cells before being reinjected.

“The cancer vaccines are going to have to show they can compete against [a] raising bar,” said Susan Galbraith, head of research and development at AstraZeneca, which is backing CAR-T and cell therapies.

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Still, both BioNTech and Moderna have made significant progress in recent years. Once Moderna’s phase 3 trial is fully enrolled, the company will apply to the US FDA for an accelerated approval, Bancel said, which could come as early as next year.

BioNTech’s products will take longer to advance but Şahin said he expected to be able to launch new cancer treatments by 2026, with a personalised vaccine coming before 2030. The products, he believes, will be similarly impactful as checkpoint inhibitors such as Keytruda.

“We shouldn’t forget this is not only a new product but a new concept, a new technology,” he said. “Vaccines are one of the [treatments] with the greatest scepticism but I see more and more people being enthusiastic about them.”

One of the enthusiasts is Haycock, who is eight rounds into almost 20 appointments at which he receives the vaccine.

“I’ve gone from leading my life thinking it’s only a matter of time before my cancer is going to come back to thinking, if this works, I won’t necessarily have to worry too much,” he said.