💊Rudolph Tanzi has long dreamt of a “little white pill” to prevent Alzheimer’s. His company Acta Pharmaceuticals is launching with $24 million in seed financing to test one. The pill is designed to prevent the formation of sticky amyloid plaques, which accumulate in patients with Alzheimer’s and are thought to drive the disease. “Amyloid in the brain is like a kitchen sink filling up with water and overflowing,” Tanzi told Endpoints News’ Ryan Cross. He compared the commercially available Alzheimer’s drugs Leqembi and Kisunla to “Roto-Rooter”: “They unclog the drain,” he said. “But the tap is still leaky, so the sink fills up again.”

Acta’s drug was made to “turn off the tap,” so to speak. “It will be the statin of Alzheimer’s disease,” Tanzi predicted. Acta is gearing up this month to begin testing the candidate, a gamma-secretase modulator called GSM-779690T, in about 70 healthy volunteers in Australia. The initial focus is safety, but Tanzi says the trial will also show whether the drug decreases the long and sticky form of amyloid that causes plaques and raises the short protective amyloid.

The company is preparing for some big challenges. Amyloid begins accumulating in the brain a decade or two before symptoms emerge, and an ideal trial could take just as long. Tanzi thinks such a trial is infeasible and is banking on the FDA warming up to amyloid-based biomarkers as a proxy for a drug’s likely efficacy. Ryan has more details here about the road ahead, potential competitors and Tanzi’s parallel research on supplements.

🧠Outside of amyloid, the tau protein has been the most promising drug target in Alzheimer’s disease. Tau forms toxic buildups in the brain called tangles after amyloid is already present, and some researchers believe these tangles have more to do with dementia than amyloid plaque. Individuals with both amyloid and tau buildup in their brains often go on to develop Alzheimer’s. 

Enter Arrowhead. The biotech is attempting to target tau using a subcutaneous injection, a different approach from other recent tau efforts that are injected directly into the spine. This week, Arrowhead said the highest of three doses of ARO-MAPT tested in healthy volunteers reduced tau in the cerebrospinal fluid. Tau levels fell by an average of 73% and a maximum of 85% about three months after participants got injections two weeks apart. 

Arrowhead credits the success to its drug delivery technology, which shuttles its gene-silencing siRNA therapy across the protective blood-brain barrier. Dozens of companies are racing to develop their own brain-targeting technologies, spurred by data from Roche’s so-called Brainshuttle approach, which ferries antibodies across the barrier. So far, most of the competition has remained preclinical. Now Arrowhead has emerged as one of the hot field’s frontrunners. Read more here. 

🔎The company has blamed a failed study for a genetic bone disease on the trial design. The drug, called efzimfotase alfa, is under FDA priority review with a decision due in the first half of 2027. It’s for a disease called hypophosphatasia that can cause bones to weaken, affecting strength and mobility, Ayisha Sharma wrote. AstraZeneca announced in March that efzimfotase alfa showed an improvement over placebo based on a walking test, but the data missed statistical significance. 

AstraZeneca’s suggesting a subgroup of patients with adult-onset disease threw off the results. In that group, the proportion of patients who had lost mobility at baseline was “imbalanced” between the treatment and placebo arms, said Marc Dunoyer, CEO of AstraZeneca’s rare disease unit Alexion. “Mobility is not the best endpoint” for patients who have already lost it, Dunoyer told Endpoints in an interview. Ayisha has the full story here.