From Naomi Kresge
When the founders of BioNTech AG started their first company in 2001, their European colleagues who attended a gathering to discuss fighting cancer with the immune system could fit in a small university hospital conference room.
This year, some 2,000 immunologists will crowd into the annual meeting on the banks of the Rhine in Mainz to talk about advances in cancer immunotherapy. One offshoot — immune oncology drugs like Merck & Co.’s Keytruda — has already revamped cancer treatment, with sales expected to reach $19 billion this year. Those successes are fueling hope for biotechs like Oezlem Tuereci and Ugur Sahin’s BioNTech that are developing therapies once seen as a long shot: personalized vaccines that train the body’s T-cells to attack tumors.
The concept has gained traction over the past 18 months, and money is flowing in. After U.S. rival Moderna Inc. pulled off one of the biggest public listings in biotech history, BioNTech is weighing a share sale that could value it at $5 billion.
Still, the risks are great. Cancer vaccines are unproven and similar approaches have failed repeatedly in the past, even in the hands of big drugmakers like GlaxoSmithKline Plc. Moderna will burn through $500 million in cash this year, Oddo analysts led by Pierre Corby said in a note.
“Even though they have a totally different, powerful new technology, they’re doing something that’s had a trail of failure for decades and decades,” said Brad Loncar, chief executive of Loncar Investments, which owns Moderna’s stock through an exchange-traded fund. Getting it to work “will be easier said than done.”
Moderna and BioNTech both work with mRNA, molecular couriers that tell cells what proteins to make. The idea depends on finding uniquely mutated proteins on an individual’s tumor — not found elsewhere in the body. Then scientists can code mRNA to tell immune cells how to attack those tumor cells, effectively sharpening their tools to find and attack specific features.
Both born to Turkish immigrant families — Tuereci’s father would take her to his job as a surgeon, while Sahin’s parents worked at a Ford factory in Cologne — the science power couple met at the beginning of their medical careers in Germany. They started down the road toward cancer vaccines in the early 1990s at Johannes Gutenberg University in Mainz.
Observing that no two patients’ cancers had exactly the same genetic mutations, they began working with the head of their department on the question of whether any of the body’s systems was equally as adaptable, and could be used as a defense. The answer was the immune system.
But at the time, cancer vaccines were “considered as a crazy idea,” Tuereci recalled. “Pharma companies would not even deal with immune therapy concepts.”
The group turned its focus to what was then another new technology, monoclonal antibodies. In 2001, they founded Ganymed Pharmaceuticals AG, a name inspired by a Turkish word for “prize,” with Tuereci as CEO. Three years ago, Japanese drugmaker Astellas Pharma Inc. bought the company for as much as 1.2 billion euros ($1.4 billion).
Their most important backers for Ganymed were the German billionaires Andreas and Thomas Struengmann. The twin brothers began investing in biotech after selling generic-drug maker Hexal to Novartis AG for about $7.4 billion in 2005 and bankrolled the founding of BioNTech in 2008. The company’s name rhymes with Genentech, one of the first giant biotech companies and arguably the U.S.’s most successful.
Such success has eluded cancer vaccines for years. Doctors began experimenting with the idea in the 1890s, when a New York physician found that injecting patients with bacteria spurred a cancer-fighting response. How and why the injections were occasionally successful or often didn’t work was never explained, and the field moved on.
Doctors returned to the idea decades later and in 2010, Dendreon’s Provenge was approved in the U.S. It was such a commercial flop that the company filed for bankruptcy four years after its debut. Cancer vaccines backed by Glaxo, Merck KGaA and Bristol-Myers Squibb Co. bombed in patient trials.
Today, faster computing and gene sequencing technology allow scientists to find unique mutations and quickly put them in cancer vaccines. Two years ago, the scientific journal Nature published a pair of small studies that renewed interest in the field. One from BioNTech showed that tumors spread less frequently in melanoma patients who got their vaccine. Two of five people whose skin cancer had spread saw their tumors shrink, and in a third person, who got the vaccine with another immune therapy, the disease disappeared completely.
Alongside a similar small study from rival Neon Therapeutics Inc., it was the first evidence that doctors could use mutations unique to a tumor cell to train the immune system to attack specific cancers, said Patrick Ott, clinical director of the melanoma center at Harvard University’s Dana-Farber Cancer Institute. BioNTech finally had results that hinted its mRNA approach might work.
“Vaccines have been used for decades,” said Ott, who helped lead Neon’s trial. “But with the technology we have, we can go another route.”
A lot more study is needed to expand on those trials, said Cornelis Melief, a Dutch immunologist who helped pioneer the cancer vaccine field. BioNTech is working with Swiss oncology giant Roche Holding AG to compare cancer vaccines with a solo immune treatment in more than 100 people with melanoma. Results are expected in September 2022.
“The jury is out,” said Dan Menichella, CEO of a German rival, CureVac GmbH, that is working on another cancer vaccine with U.S. drugmaker Eli Lilly & Co. “That’s why people are trying lots of different approaches, to see which one is going to work.” .