Alector is heading into 2022 backed by GlaxoSmithKline, which will allow the immuno-neurology biotech to go after four or five diseases at once—and at a time when neurodegenerative drug development has been catapulted into the spotlight.
Co-founder, CEO and Director Arnon Rosenthal, Ph.D., said Alector’s next steps could change now, after Alzheimer’s drug development was revitalized in 2021 thanks to the approval of Biogen’s Aduhelm.
While Alector has a wider aim in neurodegenerative diseases—with Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis prospects in the works—the FDA’s decision to approve Aduhelm based on biomarker data has read through to the biotech’s entire catalogue of potential therapies. Rosenthal has watched the agency’s assignment of breakthrough therapy tags to Eli Lilly and Biogen-Eisai since the June decision for Aduhelm, and his company is mulling how to respond to the agency’s regulatory interest.
“A lot of large pharmas who went out of Alzheimer's disease and neurodegeneration are coming back to the field,” Rosenthal said in an interview. “Also investors are a lot more willing to invest in the disease because they now see that you could get faster approval. So I think absolutely it's true that there is a significant sort of revival.”
RELATED: GSK, under pressure to perform, pens $2.2B deal with Alector focused on neuro R&D, Alzheimer's
He cited Bristol Myers Squibb, which paid Prothena $80 million to opt in on a license for an anti-tau therapy called PRX005 in June, soon after the controversial FDA decision on Aduhelm.
Alector also saw this interest firsthand in July, when the company signed a $2.2 billion deal with GSK to develop next-generation drugs for neurodegenerative diseases, including Parkinson’s and Alzheimer’s. The deal came with a nice $700 million upfront with $1.5 billion in milestones possible later on.
And Rosenthal hinted that GSK was not the only horse in the race.
“This partnership was very competitive. All the large pharma were interested,” he said.
But Alector ultimately chose GSK because the Big Pharma’s resources would allow the biotech to “do things in parallel rather than sequentially,” according to Rosenthal. That means Alector can tackle four or five diseases at once, rather than having to pick a single candidate at a time. This will cut the drug development timeline significantly, the CEO said.
RELATED: Alector bolsters 'immuno-neurology' approach—and GSK's $700M bet—with early phase 2 data
Alector will tap GSK’s international presence and experience in late-stage drug development, he said. “We are getting a lot of resources from GSK that allow us to do multiple diseases in parallel. We are getting a global reach,” Rosenthal said. “It's really synergizing our labs [and] large pharma capabilities with the small startup mentality of taking risks and moving quickly.”
As for what readouts to expect from Alector this year, Rosenthal said the company will have more data in frontotemporal dementia. The company has three trials listed as active in this indication for AL001, a GSK-partnered med that targets the progranulin gene, which is thought to contribute to degeneration and cause dementia.
But Alector will also be deliberating internally about whether to switch up future trials for their Alzheimer’s therapies to focus more on biomarkers.
Biomarkers are physical measurements that can signal changes to underlying disease but don’t necessarily prove a therapy's clinical efficacy. In Aduhelm's case, Biogen submitted data on the reduction of beta amyloid, a misfolded protein thought to cause the disease.
“We're in the midst of a double-blinded phase 2 that we did not want to sort of break open, but we are now really thinking big,” Rosenthal said. That phase 2 trial, called INVOKE-2, is testing AL002 in 265 patients with early Alzheimer’s disease. The therapy is in development through a partnership with AbbVie.
Alector is also conducting what Rosenthal calls a major effort to discover new biomarkers, because the biotech’s therapies focus on genes thought to trigger dementias and neurodegeneration rather than on beta amyloid or tau.
RELATED: Eisai takes baton from Biogen as next Alzheimer's prospect follows in Aduhelm's footprints
“We are designing our clinical trials to really rely heavily on biomarkers to get biomarker signals early on—again, both to decide whether to advance to larger studies and really to use it as a tool to interact with the regulatory agency to see if we can get faster approvals,” Rosenthal said.
With that said, Rosenthal agrees that biomarkers are not enough, that Alector has to prove its drugs can clear up the devastating symptoms of the diseases they’re targeting. The main goal of Alector’s midstage trial for AL002 is focused on disease progression, while other outcome measures look at changes in certain biomarkers.
“Biomarkers are still not validated enough to really become a complete surrogate for clinical efficacy, it's not like blood pressure that's completely sufficient to get an approval” in other indications, Rosenthal said.