Precision medicine

Driven by curiosity

Going all in

Building a team

Reimagining medicine

Science

Opening a new research avenue

Bringing together top-notch biology and particle physics, radioligand therapy offers a new avenue for medicine to broaden its arsenal for difficult-to-treat diseases such as cancer. The fledgling field, which has seen several new therapies reach the market in the past few years, could get another boost as Novartis opens its first fully dedicated nuclear medicine lab in Basel.

Text by Goran Mijuk, photos by Laurids Jensen and Bjoern Myhre

Before and after entering the research facility, scientists check their personal radiation levels.

Table of contents

Precision medicine

Driven by curiosity

Going all in

Building a team

Reimagining medicine

Published on 12/12/2022

The atmosphere in the newly built radiopharmaceutical lab on the Novartis Campus in Basel was bursting with excitement in late spring of 2022. The more than dozen team members were buzzing busily over the extended facility floor, preparing the last steps before the state-of-the-art lab finally goes online.

The team – under the leadership of Markus Reschke – was only a few days from activating the research facility. The eagerly awaited moment would bring more than two years of meticulous preparation to a close and serve as the starting point for a new chapter in the long innovation quest of the Novartis Institutes for BioMedical Research.

“This has been quite a journey,” recalled Reschke, when I met him shortly before the lab opening. The biologist by training had been with the project since its first days, when Novartis decided to invest in a radioligand lab in Basel and “go all in” on one of the most advanced medical therapeutic domains. “To see it finally go live is like a dream come true.”

The venture of Novartis into nuclear medicine goes back to 2018. This is when the company completed its bid to take over Advanced Accelerator Applications, or AAA, a pioneer in radioligand therapy, which combines disease-binding vectors – special molecules – with radioactive agents. In 2018, the company upped the ante by acquiring US-based Endocyte, which operates in the same field.

The takeovers came only a few months after Vas Narasimhan rose to the Chief Executive position at Novartis and moved the company to embrace new cutting-edge technologies that go beyond traditional small-molecule and biotech drugs.

Besides extending activities in cell, gene and radioligand therapy, Narasimhan also broadened the company’s scope in areas such as short interfering RNA – or siRNA – technology, which can be used to silence disease-triggering pathways. At the time, Narasimhan said his aim was to “make the game board bigger to find breakthrough therapies.”

Protective clothing is of paramount importance when working in the facility.

Precision medicine

Since Narasimhan’s initial push, Novartis has launched several cutting-edge therapies and ramped up efforts to deepen its research and production footprint in highly innovative areas. This entails new cell and gene research labs and production facilities as well as scaled-up production capacity for siRNA therapies, among other things.

Setting up such research and production sites in emerging areas, however, is far from easy. This is especially true in the radioligand sphere. Although nuclear medicine can trace its origins back to the 1930s, it has until recently been a niche area.

This changed, however, around a decade ago when AAA ventured outside its home turf. Initially, the company produced isotopes for cancer diagnostics, but it pivoted to drug development to work on a therapeutic approach which aimed to combine a disease-binding biologic with a radioactive particle. The idea: The biologic vector finds cancer cells in the body, which are then destroyed by nuclear particles in a very precise fashion.

Such nuclear medicine approaches were previously executed manually in specialized hospitals. But AAA aimed to industrialize the process. The goal was to develop a drug that could be delivered globally, instead of forcing patients to visit specialized clinics.

It took the small AAA team several years to develop a therapy. But when the company eventually succeeded in getting a ready-to-use radioligand therapy onto the market, the moment was more than just another drug launch. It was the dawn of a new form of personalized medicine.

The therapy not only offered the possibility to treat some forms of cancer in a very targeted way, but also provided the opportunity for precise diagnostics. It was an epoch-making feat.

Researchers combine targeting vectors with radioligands in heavily lead-shielded containers...

Driven by curiosity

The huge success came with one drawback, though. The emerging field of ready-to-use nuclear therapies was so new that Novartis needed to plough the field for some time before it could establish a research route forward after taking over AAA. The dearth of experts and the fact that setting up a radioligand lab is a massive endeavor was further complicating things.

Curiosity did the trick, as a small team of scientists started to comb through potential options. One of them was Markus Reschke. “I’m a biologist by training and really an outsider to nuclear medicine,” Reschke said, when I asked him about his decision to join the nuclear medicine group in the early stages. “When I saw the first readouts of what radioligand therapy can do for patients, I was really intrigued. I didn’t hesitate when I was asked to join the small team and start the discussion as to how we wanted to structure research.”

While the team worked on potential strategies, it also connected extensively with AAA’s lead scientist Maurizio Mariani to learn more about the technology and look at all possible research options. “This was a fascinating period, as I was able to learn more about the technology and connect this new knowledge with my expertise in biology,” Reschke remembered.

...so-called hot cells.

Going all in

After considering all possible options, it became clear that the best way forward was to build a specialized radiopharmaceutical lab. “This is when the decision was taken to create a facility in Basel which would include end-to-end capabilities to really give us a cutting edge in this emerging field,” Reschke explained.

The idea was to have a fully integrated research facility with in vitro and in vivo labs as well as a specialized lab in which researchers combine targeting vectors with nuclides in heavily lead-shielded containers, so-called hot cells.

To set up the facility in Switzerland was no accident either. With the Paul Scherrer Institute in the small town of Wuerenlingen, located an hour’s ride from Basel, one of the world’s radiotherapy hotspots was just around the corner. The proximity was not just helpful to enable a know-how transfer. It also served as a learning and validation center for the Novartis lab, where prospective associates also received training to handle radioactive material.

The Paul Scherrer Institute was also instrumental in supporting Novartis with the installation of the lab on Campus. “This was really a very heavy lift as this is the first such lab we built here on Campus,” Reschke said. “As we use radioactive particles, we had to install a series of protective measures throughout. The support from the Paul Scherrer Institute was vital in this respect.”

The lab, which is located on the eighth floor of an older lab building in the northern part of the Campus, had to be shielded from the rest of the building by extensive lead protection. In addition to many other structural extras, the lab’s piping system had to be designed to operate independently from the rest of the building in order to avoid any potential contamination.

Additional safety measures also needed to be installed at each junction of the facility, including radioactive measurement tools and a special shower cabin, where researchers can decontaminate. On top of that, doors and closets were protected by heavy lead shielding to limit radiation.

“It took us more than two and a half years to get from the first drawings of how to structure the lab to going online,” Reschke said. “But it was worth the time, even if it meant that we had to get through a very steep learning phase.”

Scientists check the properties of the radioligands...

Building a team

Reschke said that building the team was equally challenging, given that nuclear medicine is still a comparatively small medical field. But when looking for new talent, a guiding principle was to tap into the natural curiosity of scientists. This, Reschke said, helped attract a slew of researchers who joined the team and were ready to get training to gain the necessary expertise.

However, Novartis was able to attract highly trained specialists. One of them was Josefine Reber, who joined the company in 2020. Reber has extensive experience in the radioligand sphere. She completed her doctorate at the Paul Scherrer Institute / ETH Zurich and worked at the Helmholtz Zentrum, a leading research center in Munich (Germany), among others.

“For me, the key reason to join Novartis and help set up a brand-new radioligand research arm was really about taking responsibility for patients,” Reber said, when I asked her why she made the transition from academia to industry. “What we have built here is a true discovery site that allows us to develop novel molecules that could make a difference for patients.”

Reber acknowledged too that the field was still small compared to more established arenas. She stressed, however, that recent breakthroughs in oncology made the technology very attractive and viable to target diseases which are difficult to treat with classic biologics or chemical drugs.

“Also, given that we have been able to create a vertically integrated facility, which includes in vitro and in vivo labs, we can really drive the science forward,” Reber said. “On top of that, working with all the colleagues on a single floor will also speed up communication and mutual learning, which I believe is a further strong asset.”

...before these are transported to the in vivo labs.

Reimagining medicine

Reber, like many of her colleagues who have joined the team over the past two years, such as lab leaders Sravanth Hindupur and Philipp Holzer, among many others, is full of ambition for the things to come.

“We are trying to do something really new here,” she explained. “We are working with cutting-edge tools that hold the potential to bring a completely new class of medicines to patients who up to now have had limited treatment options,” Reber said.

Like her colleagues, Reber feels pride that Novartis has taken this route. “This is not only inspiring in a scientific sense, as we can do deep science in a novel way. It reflects the company’s strong and lasting commitment to medicine and society.”

While Reber and her colleagues are taking the first steps to familiarize themselves with the new work environment, their enthusiasm and ambition will be needed in the months and years ahead, as the team works with novel compounds that have never been tested before. But hopes are high.

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