Think Roche is out of the Alzheimer’s disease business? Think again.
Just over a week after handing back rights to two failed assets to AC Immune, Roche Pharmaceuticals CEO Teresa Graham turned attention to a “homegrown” molecule, the next in Roche's long-running Alzheimer’s disease portfolio. Trontinemab uses Roche’s “brain shuttle” technology to try and break through the blood-brain barrier to boost efficacy.
Left behind by peers Eisai, Biogen and Eli Lilly, Roche hopes this next asset can finally help break through into the Alzheimer’s market. The company had a runner-up phase 3 candidate in gantenerumab, which sputtered out in the clinic in 2022 and was ultimately dropped after decades of work.
Roche is expecting a key phase 3-enabling readout for trontinemab in 2024. The Swiss pharma will hold a neurology R&D day on March 11 to showcase phase 1/2 data from one cohort in the dose-escalation group. But for now, Graham said the company likes the preliminary data, which has shown the amyloid-beta targeting antibody clears the sticky plaques faster than traditional monoclonal antibodies—which include Eisai and Biogen’s Leqembi and Lilly’s donanemab.
“You can see that it does exactly what we know we need to do with neurological treatments going forward, and that is get across that blood-brain barrier to deliver more antibody where [the] antibody is needed,” Graham said during Roche’s fourth-quarter earnings call Thursday.
The brain shuttle technology helps get the medicine where it needs to be. “You can actually flood the antibody into the brain all at the same time, getting the medicine exactly where it's needed,” Graham noted.
Early results showed that trontinemab “just drops plaque like a stone,” Graham said, leading to “almost complete resolution extremely, extremely quickly.”
“We do know now that the removal of plaque does correlate with increased clinical benefit for these patients and so we truly believe that there is a very unique opportunity for trontinemab,” Graham said.
The med is part of Roche’s R&D Excellence program, she noted.
Elsewhere in neurological disease, Roche has prioritized external partnerships, including a $60 million upfront pact with Ionis Pharmaceuticals that includes two preclinical RNA-targeting programs in Alzheimer's and Huntington’s diseases.
Waiting for TIGIT
While the Alzheimer’s program is a bit of a long shot, given the storied history of clinical failures in the disease, Roche has another high-profile asset that analysts are impatiently waiting for. That’s the TIGIT med tiragolumab, which is being tested in the phase 2 SKYSCRAPER-01 trial. A pivotal readout in non-small cell lung cancer has been pushed back, and is now expected in the second half of this year.
Roche revealed the SKYSCRAPER-01 delay last month during the J.P. Morgan Healthcare Conference in San Francisco. Once again during the earnings call, executives were asked about their level of confidence in the TIGIT target, which has shown mixed data from the company itself and peers in the industry.
CEO Thomas Schinecker said the company has not seen any additional data on tiragolumab than what has been released publicly to this point. But the phase 2 data they have looked at so far show that tiragolumab is an active molecule.
“So overall, our confidence level is such that we are starting more phase 3 trials. So obviously, we believe that this could be a medicine,” Schinecker said.
Roche has stacked the med on top of a very effective standard-of-care in the NSCLC trial, tacking on a novel pathway to go after cancer, Graham said. She pointed to the readouts so far as evidence that Roche should keep going.
“We invested heavily in the TIGIT pathway for very good reason and I think that's because we believe that it very well has the opportunity to be biologically active and to help patients,” Graham said. “So at this point, we're in the uncomfortable position of waiting.”
In January, Roche did get a slight boost to its TIGIT bet when the SKYSCRAPER-08 trial in esophageal cancer showed that patients lived longer on a combination of tiragolumab, the PD-L1 drug Tecentriq and chemotherapy, compared to those on placebo and chemotherapy. Despite the statistically significant results, questions were raised about the choice of comparator. The current first-line standard of care in patients with advanced esophageal squamous cell carcinoma is a checkpoint inhibitor plus platinum-based doublet chemotherapy, not what was used in the SKYSCRAPER-08 study.
Roche also pared down its pipeline by eight candidates in a year-end clearout. Schinecker promised a similar number of candidates will be shelved at the end of the first quarter, too.