Expanding the frontiers of science

Starting in 2012, the pharmaceutical industry got an unexpected kick, imbuing the sector with a sense of hope and excitement not seen since the rise of biotech in the 1970s and unleashing an innovation frenzy that only accelerated with the advent of new technologies, including artificial intelligence. The first signs that the pharmaceutical industry was bound for a major transformation were visible around the millennium, when researchers were able to decipher the human genome – accompanied by much political fanfare and science fiction scenarios. But, as always during periods of hype, the basic research insights would not easily be translated into workable therapies – at least at first. Only a few treatments made it over the finishing line in the 2000s, with most companies not even trying to enter the field after the sector was hit by major regulatory scrutiny following the much-publicized death of a patient. Novartis, which in the 1990s and early 2000s worked on a brain cancer project, had given up on gene therapy and remained focused on the development of small-molecule drugs and biotech therapies, citing too many hurdles. But with the advent of Nobel Prize–winning gene scissor technology CRISPR in 2012, which allowed precise DNA manipulation, gene technology once again moved to the limelight. It not only made gene therapies look like an achievable goal. It gave researchers a highly efficient tool to better understand genetics and shed light on biological mechanisms that were out of reach with existing genetic tools such as zinc finger nucleases and others. Novartis was among the first companies in the industry to move ahead during this phase. Its appetite to reenter the field proved that the failure of its early foray into gene therapy was not a lost cause. The experience gathered during the project taught the company the pros and cons of such research, made it aware of potential pitfalls, and gave Novartis enough courage to reclaim the field as it understood the knowledge gaps that led to the demise of its previous venture. By 2014, Novartis opened a dedicated gene therapy unit to follow through on a CAR-T treatment developed by the University of Pennsylvania amid which T cells are genetically reprogrammed to recognize and attack cancer cells. The results were not only convincing from a research point of view but changed the outlook for the entire industry as many competitors followed in the footsteps of Novartis and created dedicated gene therapy units themselves. A few years later, Novartis not only won the first approval for a CAR-T therapy, but once again led the sector into a new era as it did 15 years earlier when it had developed the first personalized cancer therapy and with it ushered a new era for an industry which for decades had limited means to beat cancer.

Gaining momentum With the appointment of Vas Narasimhan to the CEO position in 2018, the momentum toward breakthrough science accelerated even more. While boosting research in the gene and cell therapy space and adding clout to the company’s production capabilities, Novartis further expanded its reach through acquisitions. This helped Novartis extend its lead in the field. Next to cancer therapies, the company also worked in other therapeutic areas such as neuromuscular diseases and eyecare. But gene and cell therapy was not the only focus area. Novartis also carved out novel spaces, including radioligand therapy – adding fresh dynamic to an industry arena that previously was reserved to highly specialized hospitals that treated each patient individually, making access and reliability a key challenge. Novartis aimed at industrializing the approach, which had emerged from the idea that if cancer cells can be identified through specific molecular markers on their surface, they can also be targeted with extraordinary precision. By attaching a radioactive isotope to a molecule that selectively binds to tumor cells, researchers created a treatment capable of delivering radiation directly to cancer while largely sparing surrounding healthy tissue.

The approach combines diagnostics and therapeutics in a single platform, allowing physicians first to visualize tumors and then use the same biological pathway to attack them. What began as a highly specialized form of nuclear medicine already in the 1950s gradually evolved into a new pillar of precision oncology. Next to several acquisitions, Novartis also pushed ahead to build a state-of-the-art research facility in Basel. “This was really a very heavy lift,” recalled Markus Reschke, who helped establish the operation. Working with radioactive material meant creating heavily shielded laboratories, installing specialized safety systems and bringing together expertise that had rarely existed under one roof. The challenge was not only technical but also cultural. Nuclear medicine was a comparatively small field, and many of the scientists joining the effort were stepping outside traditional pharmaceutical disciplines. What attracted them was the opportunity to build something from the ground up. “We are trying to do something really new here,” said researcher Josefine Reber, who joined the radioligand team after working in academia. The ambition was not simply to improve existing therapies, but to develop an entirely new class of medicines capable of reaching diseases that had proven difficult to tackle with conventional drugs or biologics.

That ambition reflected a broader shift taking place across the industry. As researchers gained a deeper understanding of disease biology, medicine increasingly moved beyond the boundaries of classical chemistry and biotechnology. Radioligands became one of several new platforms through which Novartis sought to rethink how diseases could be treated. What began as a niche scientific field gradually evolved into one of the most promising avenues in oncology, combining biology, imaging, and nuclear physics in ways that would have seemed almost unimaginable only a generation earlier. On top of two approved treatments, Novartis has a new radioligand candidate in the pipeline and is investing some 40 percent of its oncology R&D in this promising arena, which has – of course – attracted a series of followers in pharma space. Real progress with artificial intelligence At around the same time that Novartis spread its wings into gene, cell, and nuclear medicine, it also moved ahead with its efforts in the realm of artificial intelligence, which got a massive boost around 2015, when the first AI-driven system was able to beat a human player at a highly complex board game. Google-owned artificial intelligence firm DeepMind under its CEO Demis Hassabis, who has since been awarded with the Nobel Prize in chemistry for his efforts in protein structure prediction, was able to pull the feat after the AI industry for years was stuck in a sort of hibernation mode, where progress was minimal and big breakthroughs were rare. Before 2015, AI was, at best, a topic that would come up at specialized conferences or in science fiction novels or movies. But with AlphaGo’s win over South Korean Go champion Lee So-dol, AI was rapidly becoming ubiquitous. Terms like machine learning would be discussed in newspapers and TV shows, with science fiction all of a sudden becoming eerily real. Novartis was quick to realize that AI held massive potential for an industry that was rich in data and equipped with deep scientific knowledge. Within a short time span, the company set up a dedicated unit and started work on several large projects, including a monitoring system for clinical trials and a data lake that would make use of the millions of patient years in data that the company had amassed over decades of clinical trials.

Besides aiming to hit upon nuggets of data that could help Novartis speed up research and development, Novartis created the platform data42 to find insights that lay buried in files across the company, which no one had the resources to sift through before the system was set up. Today, data42 not only provides researchers access to a massive database. The AI-driven system, which has been structured and cleaned over an extended period of time, was also one of the key reasons Fiona Marshall was excited join Novartis as President of Novartis Biomedical Research. “I had heard about this initiative even before my arrival, and upon joining, I immediately sought to learn more about it,” she had told live magazine, adding that she and her team started to increase investment in the platform, which now is an integral part of the company’s research and development efforts and instrumental in leveraging its efforts as AI is gaining momentum across all industries.

In the past, pathology samples were screened under the microscope. Today, researcher can analyze samples digitally – and in high numbers.

Reconnecting to the roots While artificial intelligence is now a vital part in all of its daily activities, Novartis also pushed into the RNA field, which received a major boost during the pandemic. The foray into RNA-based therapies allowed the company – in some sense – to also reconnect to its roots as it built its first siRNA production platform in Schweizerhalle, the cradle of Basel’s chemical industry, which was built on the salt deposits discovered here in the 19th century. Novartis engineers and manufacturing specialists built an entirely new production capability inside an existing factory, fitting kilometers of piping, specialized synthesizers, and large-scale purification equipment into a complex three-floor facility while ongoing operations continued around them. For Michael Wessels, a chemist by training, the project represented more than an engineering challenge. It was evidence that chemistry was entering a new era. The clean-room environment, the sophisticated manufacturing processes, and the combination of chemical and biological principles looked very different from the traditional production lines that had defined the industry for generations. The new facility produces small interfering RNA, or siRNA, a technology that silences disease-causing proteins before they are even made. The science emerged in the 1990s but required decades of innovation before it became clinically viable. Today, researchers see RNA medicines as a new class of therapeutics positioned between traditional small molecules and biologics.

For Schweizerhalle, the technology offers more than a new product line. After years in which manufacturing volumes declined as the industry shifted toward biotechnology, RNA production has given the site a renewed sense of purpose. What was once regarded as a relic of Basel’s industrial past is increasingly viewed as a blueprint for the future of pharmaceutical manufacturing. The renaissance in Schweizerhalle is in some sense a symbolic movement that has affected the entire company, which within the span of a decade has pioneered new technological platforms and entered new therapeutic domains, living up to its vision to reimagine medicine and create new treatments for millions of people worldwide. The pioneering spirit is in many ways like the one exhibited a century ago, when the Novartis predecessor companies ventured into the pharmaceutical sector. Their courage created a new dawn back then as the courage of Novartis does today, raising the prospects to redefine what is possible and putting technology in the service of patients everywhere.