PHILADELPHIA – Preliminary results from a small study have shown that blood tests developed by Sunbird Bio can detect tau aggregation in the brain, researchers reported Tuesday at the Alzheimer's Association International Conference.
Researchers from the Cambridge, Massachusetts-based biotech company and collaborators at the Florey Institute, a brain research center in Parkville, Australia, identified a high correlation between elevated levels of blood-based tau proteins bound to small lipid particles known as extracellular vesicles (EVs) and the presence of tau tangles in the brain, as measured by standard PET imaging.
Tau is a hallmark sign of Alzheimer's and an emerging therapeutic target for the devastating neurodegenerative disease. When tau misfolds and aggregates in the brain, the proteins form clumps within neurons known as tangles. The presence of these tau tangles follow the buildup of beta-amyloid, another Alzheimer's biomarker, and are thought to contribute to dysfunctional neurons, neurodegeneration, and cognitive decline.
For the study presented at the AAIC meeting, Sunbird Bio analyzed blood samples from 10 patients who were known to have tau PET positivity and 22 healthy control subjects from the Australian Imaging, Biomarker, and Lifestyle (AIBL) Flagship Study of Aging. In the observational AIBL study, researchers regularly collect data on a cohort of more than 3,000 seniors to support investigations into Alzheimer's onset and progression.
Investigators were able to distinguish between patients with and without tau pathology using a combination of assays developed by Sunbird Bio that measure EV-bound total tau, phosphorylated-tau (p-tau) 231, and p-tau 396. The assays had a correlation of 92 percent to PET scans and when tested on a separate cohort of healthy samples, demonstrated a negative-predictive value of 93 percent.
By contrast, when using assays that measure the presence of tau and p-tau proteins more broadly — not specifically the tau proteins that bind to EVs — investigators weren't able to discern the patients with tau pathology. Since Sunbird Bio's tests are based on the idea that aggregated tau binds to EVs, the company says it can more precisely detect tau tangles by homing in on EV-bound tau.
"Just detecting the presence of a protein doesn't tell you that you're dealing with an unhealthy patient," said Sunbird Bio CEO John McDonough, noting that some tau proteins also circulate in the brains of healthy patients. That's why he believes it's important to find ways to detect the sticky protein clumps.
Sunbird Bio's tau assays are based on the company's lead diagnostic platform APEX, which is designed to detect and measure low concentrations of EV-bound aggregated protein biomarkers, including the small amounts of EV-bound tau proteins that pass through the blood-brain barrier and into the bloodstream.
The company, which was founded in Singapore in 2020, plans to share additional validation data on its tests at conferences throughout the year, not only for tau but also for other biomarkers of neurodegeneration, said Nicholas Ho, Sunbird Bio's scientific cofounder and director of innovation. "I want to showcase how flexible the platform really is," he said.
The science that underpins the APEX platform and Sunbird Bio's approach to blood-based biomarker testing was developed by company founder Huilin Shao at the National University of Singapore, where she's an associate professor in the department of biomedical engineering. Shao currently sits on Sunbird Bio's board of directors.
Sunbird Bio is initially focusing on developing blood-based diagnostic tests for neurological disorders like Alzheimer's and Parkinson's disease. It also began developing tests for early-stage cancer, after it merged with protein diagnostic company Glympse Bio last year. It maintains Glympse Bio's former office in Cambridge, Massachusetts, as its corporate headquarters, while maintaining operational headquarters in Singapore.
Among neurologists, there's growing interest in blood-based tests for beta-amyloid and tau. In recently released guidelines, an Alzheimer's Association work group expressed support for beta-amyloid testing as a way to diagnose Alzheimer's and said that the presence of certain types of tau can provide insight into patients' disease severity and progression.
These markers are typically measured using PET imaging or cerebrospinal fluid (CSF) analysis, but blood tests, if validated, could be a more convenient and cost-effective option for patients.
That's becoming increasingly important with the emergence of disease-modifying Alzheimer's therapies that target specific proteins underlying the disease. Two such therapies on the market, Eisai and Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab), are both indicated for early Alzheimer's patients with evidence of beta-amyloid pathology. Drugmakers are studying other beta-amyloid- and tau-targeting drugs, too, which may require testing for tau to determine eligibility or to monitor treatment. Lilly, for example, is studying LY3372689, an OGA enzyme-inhibiting anti-tau therapy, in a Phase II trial of patients with early Alzheimer's and tau pathology, as measured by PET imaging.
PET scans are extremely accurate, McDonough said, but they're expensive and require specialized equipment. "Having a blood test that could work either in parallel with or, more ideally, replace a PET scan could be extremely useful in determining who to treat," McDonough said, referring to anti-tau medications that may be coming down the pike.
The results presented at AAIC build on previous findings from Sunbird Bio. In March, at the Tau2024 Global Conference in Washington, D.C., the firm presented another analysis from the AIBL study, in which they dug into the predictive value of EV-bound tau and EV-bound p-tau, separately. Investigators were able to identify patients with tau pathology using assays that measure EV-bound tau with a correlation of 93 percent, and when using assays that measure EV-bound p-tau, they achieved a correlation of 90 percent.
Sunbird Bio will conduct another clinical study next year to validate its tau assays in a larger patient population, McDonough said. For that study, he expects researchers will analyze blood samples from about 50 to 100 patients and, again, compare results against standard PET imaging.
The firm hopes to begin commercializing and making its blood tests for neurological diseases available to biopharma researchers later this year, beginning with the beta-amyloid test, McDonough said. The tau test will likely be available in 2025, as well as a test for gauging alpha-synuclein, which could be used within research studies for Alzheimer's and Parkinson's. Some doctors and researchers have proposed defining and staging Parkinson's based on the presence of alpha-synuclein.
Sunbird Bio's next step after making neurological tests available for research use will be getting them to the clinic as part of patient care, which will require more rigorous clinical validation. The company doesn't have a set timeline for when it expects to make the tests clinically available, but McDonough estimated it could happen in late 2026.
Sunbird Bio is also developing a blood test to detect amyloid-related imaging abnormalities (ARIAs), a common adverse event seen in patients receiving anti-amyloid Alzheimer's drugs. The company wants to make this test available to researchers next year but hasn't disclosed what proteins the test detects. The labels for both Leqembi and Kisunla recommend that patients get MRIs during the first few months of treatment to monitor for ARIAs.
While Sunbird Bio has considered other disease settings, for now, the company largely remains focused on developing tests for the neurodegenerative space, Ho said. He sees opportunities for Sunbird Bio to partner with biopharma companies that could use its tests to support longitudinal monitoring, for stratifying patients in clinical trials, or for identifying patients with protein biomarkers that their therapies are designed to target.
"There's a huge unmet need here," he said. "This is where we can make the most impact."