Reshaping research at Novartis

How Fiona Marshall is building the pharma’s science programs to meet its development and commercial priorities 

The unifying theme for Novartis’ pipeline ambitions is creating durable treatments, according to the pharma’s head of research, Fiona Marshall. And as she carries the thread into the earliest stages of research, Marshall is reshaping the department to ensure the scientific problems they address align with the company’s stated goals.

Marshall became president of Biomedical Research at  Novartis AG (SIX:NOVN; NYSE:NVS) on Nov. 1, 2022. On The BioCentury Show, Marshall discussed the structural changes she has introduced in her first year, and delved into some of the scientific projects her team is working on, including CAR T, siRNA and radioligand therapy programs. 

Novartis changed the name of its research arm from NIBR (Novartis Institutes for BioMedical Research) — essentially dropping the Institutes — to align with the focus that aims to represent multidisciplinary teams rather than discrete stand-alone institutes. Along with that, there’s greater coordination with the development arm, led by President of Development and CMO Shreeram Aradhye, as well as the commercial team. “Rather than going off and working on multiple different diseases where we think there’s very exciting science,” she said, the group gains alignment ahead of time, so “it’s not just us, pushing to them — look at this cool new thing.” 

The dialogue is two-way, and even though there’s not always perfect alignment at the start, there’s both adherence to the core therapeutic areas, and flexibility for a broader aperture. “Then we have a pull as well as a push for the portfolio,” said Marshall.

Marshall said that the idea of durable treatments plays out through Novartis’ CAR T, siRNA and radioligand therapy programs, in some cases through sustained efficacy, and in others through better tolerability or reduced frequency of administration. She sees the opportunity for medicine to “change people’s lives, because you basically forget that you’re ill, or maybe you’re not ill any more.”

Though Novartis is aggressively taking its CAR T cell technology into B-cell driven autoimmune diseases, it’s also working on creating CAR T products for solid tumors, which means identifying tumor specific antigens to deliver the therapy to the right place. The same targeting issue is relevant to its radioligand therapy programs and to siRNA. 

“We have a lot of work focused on what we call the ‘surfaceome’ — mapping the surface of cells,” said Marshall, which the company is doing both via internal research using biochemistry and in silico work on some “favorite cell types,” as well as via external alliances.

One of Novartis’ major focus areas is radioligand therapies, which Marshall notes is a technology that has been around for many years. “What’s new is how we can scale up,” she said. Like antibody-drug conjugates, radioligand therapies are modular, needing to match a ligand, vector — such as an antibody — and a radioisotope, but ADCs and RLTs have different challenges. 

The short half-life of the radioisotope means its timing has to be closely managed. “So the patient is ready for the therapy, then you make it, and you have to deliver it to the patient in a small timescale, five days,” which precludes stocking up on drug substance.

While the technology is gaining attention and popularity among biotechs, manufacturing is a high barrier to entry, said Marshall, and an area where she believes Novartis’ investment in global manufacturing sites and capabilities gives it an advantage. “We’re building the numbers of hospitals that are now able to deliver RLT, and many hospitals are very excited about getting into nuclear medicine,” she said. 

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