Alzheon plans Alzheimer's approval next year with new $100M

Alzheimer’s disease treatments have faced significant challenges in terms of safety, efficacy, and accessibility, despite recent drug approvals and a high number of patients in need. As Eli Lilly's donanemab, another anti-beta amyloid antibody, is close to FDA approval, Alzheon is exploring a different approach to address the key issues that have hampered drug development in this field.

On Wednesday, Alzheon secured $100 million in a Series E funding round to complete the APOLLOE4 Phase III study of valiltramiprosate (ALZ-801) for early Alzheimer’s patients and prepare it for commercialization. The funding, led by Alerce Medical Technology Partners, raises Alzheon’s total equity financing to $185 million. The pivotal trial results are anticipated in the third quarter, with a regulatory submission to the FDA planned by the end of the year. If successful, CEO Martin Tolar expects the oral small molecule to be available to U.S. patients in 2025. “We truly are at the dawn of a new era,” Tolar stated, highlighting the potential to change the standard of care for Alzheimer’s.

Founded over a decade ago, Alzheon aims to develop an Alzheimer’s treatment by identifying the toxic agents driving the disease and effective biomarkers for tracking progression and treatment efficacy. Their initial clinical program focuses on patients homozygous for APOE4, a significant genetic risk factor for Alzheimer’s. Around two-thirds of Alzheimer’s patients carry one copy of the APOE4 gene, while about 15% are homozygous, meaning they have two copies. For those with two copies, the disease is almost inevitable.

Interestingly, existing anti-beta amyloid antibodies, such as Biogen and Eisai’s Leqembi (lecanemab) and the discontinued Aduhelm (aducanumab), along with Lilly’s donanemab, have shown less effectiveness and more side effects in APOE4-homozygous patients. In contrast, Alzheon’s approach targets small, soluble amyloid aggregates, which are precursors to the plaques targeted by most antibody therapeutics, as the primary culprits in disease pathology.

Tolar explained that beta amyloid, a neurological protein, increases as we age and becomes harder for the brain to clear. This accumulation leads to the formation of toxic, soluble oligomers that harm the brain. The brain then sequesters these oligomers into insoluble amyloid plaques, which have been the focus of many Alzheimer’s treatments. However, Tolar argues that targeting plaques is not effective for cognitive and functional improvement. Instead, preventing the formation of these plaques is crucial, a goal achieved by valiltramiprosate, which blocks beta amyloid from clumping into oligomers.

Clinical data supports Alzheon’s strategy. While Leqembi and donanemab demonstrated 27% and 29% patient improvements, respectively, on the Clinical Dementia Rating scale, Phase II results for valiltramiprosate showed an 81% functional benefit on the same scale. Tolar noted the significant impact of the treatment, stating, “These patients usually are at the edge of a cliff. They are a little forgetful. But in a year and a half they don't recognize their children, their spouses. And we can keep them stable for two years.”

Additionally, valiltramiprosate could be safer since it doesn’t target plaques, which may cause amyloid-related imaging abnormalities (ARIA) leading to brain edema and hemorrhage. “We have shown in over 3000 patients, in a three-year follow-up, that we don't have an increase in brain hemorrhages,” Tolar highlighted.

Another advantage of valiltramiprosate is its oral administration, making it cheaper and easier for patients to take over the long term, unlike antibody IV infusions. This could significantly improve the accessibility and adherence to treatment for Alzheimer’s patients.