Novartis may be launching an array of vehicles to shuttle drugs across the blood-brain barrier, but executives told Fierce that the Swiss pharma is “always looking” for new ways to traverse this final frontier of neuroscience.
The company's most recent play was a $165 million upfront deal with SciNeuro Pharmaceuticals in January for the worldwide license to an amyloid beta-targeting antibody for Alzheimer's disease. One of the appeals of SciNeuro's monoclonal antibody is how it harnesses transferrin receptor (TFR) to drive drugs into the brain, according to Nazem Atassi, M.D., global development head of neurology and gene therapy at Novartis.
“TFR is the most advanced [modality] in the space to get drugs through the blood-brain barrier,” Atassi told Fierce in an interview last week.
Finding ways to bypass this barrier has been a key goal for neurodegenerative-minded companies for years. The barrier protects the inner surfaces of the blood vessels inside the brain and controls how certain chemical molecules go into and out of the brain.
Novartis’ fellow Swiss pharma Roche, which has a brain shuttle bispecific 2+1 amyloid-beta-targeting monoclonal antibody in phase 3 development, penned a shuttle-focused deal with Manifold Bio late last year to work on direct-to-vivo AI-guided brain shuttles.
By that point, Novartis had already placed one neuroscience bet on TFR when it handed $200 million to Arrowhead Pharmaceuticals to develop its preclinical siRNA program targeting alpha-synuclein in order to treat Parkinson’s and other synucleinopathies.
“TFR is very widely expressed, although very highly expressed on the brain endothelium,” Bob Baloh, M.D., Ph.D., global head of neuroscience at Novartis Biomedical Research, told Fierce in the same interview.
“You can tune TFR, and we're seeing those molecules get into the clinic across a variety of companies—including ours,” he said.
The collaborations with Arrowhead and SciNeuro involve attempting to tune TFR to get drugs into the brain and remain in preclinical testing for now. But Novartis’ work to tune TFR to muscle is further ahead thanks to the pharma’s $12 billion buyout of Avidity Biosciences in October 2025.
That deal gave Novartis ownership of Avidity’s pipeline of clinical-stage antibody-oligonucleotide conjugates for muscle dystrophies. They include the Duchenne muscular dystrophy therapy delpacibart zotadirsen (del-zota), which uses an anti-TFR1 antibody to deliver an oligonucleotide to target cells. The therapy was tied to a statistically significant 25% increase in dystrophin production among people amenable to exon 44 skipping and is currently on track to be submitted to regulators in the coming weeks.
Meanwhile, a phase 3 study for delpacibart etedesiran in myotonic dystrophy Type 1 is due to read out in the second half of the year, with a late-stage study of the DUX4-targetting delpacibart braxlosiran for facioscapulohumeral muscular dystrophy currently enrolling, Atassi explained.
“If you look across the three programs in clinic that Avidity has, you will see common themes—they're all muscle diseases, they all use TFR [to] drive the payload to the muscle, and in all of them you see very robust target engagement,” he said.
Not content with riding Avidity’s pipeline of muscle dystrophy drugs to regulators, Novartis is also hoping to turn the company’s tech to neurodegenerative diseases like Alzheimer’s and Parkinson’s.
It’s a “little bit easier” to tune TFR to muscle because correctly-tuned formats can enter these tissues quite effectively, according to Baloh.
“It's a little bit harder to tune for the brain, and that's why I think if you look across the industry, you'll see that the brain programs are just a little behind,” he added.
Whether trying to tackle Alzheimer’s by targeting amyloid beta, tau or neuroinflammation, all companies run headfirst into the blood-brain barrier.
That's why Novartis has another iron in the fire thanks to a deal last year to give Sironax $175 million in upfront and near-term payments in return for the option to license the Massachusetts-based biotech’s blood-brain barrier crossing tech. For now, the pharma is keeping the specific targets of that pact under wraps.
Baloh sees the recent progress made across the space as “exciting” because it means getting drugs to the brain has become “an engineering problem” rather than remaining a pipe dream.
“That's where we obviously see a lot of opportunities, so we're doing a whole series of deals now,” he told Fierce.
Despite having bet on a range of options, the Novartis execs aren’t ruling out splashing more cash in the future.
“We believe there could be other shuttle systems, and simultaneously we're going to investigate if those do perform better or differently from what you can do with TFR, because we really believe that the opportunity space is so large that that's the right way to approach it,” Baloh said.
“We have really strong teams internally working on the blood-brain barrier—they're collaborating actually with externals and academics,” he continued.
“I don't think you will really ever only have one solution to this problem,” Baloh said. “Having a toolbox that you can then use is probably the best way to approach.”
“We're absolutely always looking,” Baloh added when asked whether Novartis is eying up other blood-brain barrier plays.
Atassi agreed that no good solutions are off the table: “Beyond TFR, we're looking at all the options of how to get drugs across the blood-brain barrier.”