Catalyzing Combination Therapies
2025 marked an all-time high of 20 trials focused on combination therapies, several of which are funded by the ADDF. Combination therapies and precision medicine revolutionized cancer care, and we are bringing the same strategy to Alzheimer’s – advancing treatments informed by biology, guided by biomarkers, and tailored to each individual.
Advancing a Diverse Pipeline
Just five years ago, an effective Alzheimer’s treatment still felt like a distant dream. Today, we not only have multiple drugs that can slow the disease, but now – with the FDA approving a subcutaneous formulation of Leqembi for maintenance dosing – we are nearing the day when patients can leave infusions behind altogether and deliver drugs at home. This is a catalyst for the next generation of Alzheimer’s care, reducing the burden on patients and caregivers, which will ultimately make it easier to combine multiple treatments so we can target the full spectrum of aging biology – an approach the ADDF has championed since our inception.
In 2025, we launched a special issue in collaboration with the Journal of Prevention of Alzheimer’s Disease (JPAD), highlighting how combination therapies are redefining what’s possible in Alzheimer’s research and care – providing a clear roadmap to chart this next frontier. The ADDF has been seeding the pipeline with a diverse array of novel drugs from day one, and as the science matures, we are seeing the pace of progress continue to increase.
In November, Novo Nordisk presented topline results from their phase 3 Evoke trials of semaglutide, an oral GLP-1 drug. While the trials did not meet their primary endpoint, they show a fundamental shift in how we approach the development of new Alzheimer’s treatments, expanding beyond amyloid to target the complete pathobiology of the disease. The ADDF invested early in science that laid the groundwork for the Evoke trials, providing nearly $1 million beginning in 2011 to support Dr. Paul Edison’s pioneering phase 2 study of liraglutide, an early generation injectable GLP-1 medication.
Accelerating Innovation Through Venture Philanthropy
The ADDF’s returns in 2025 totaled nearly $4.6 million thanks to our unique venture philanthropy model. At the ADDF, we take on risks that traditional funders often avoid, supporting promising approaches that may otherwise go overlooked or underfunded. A selection of these pioneering projects is highlighted below.
Targeting “Junk” DNA to Slow Alzheimer’s Progression
Transposon Therapeutics is testing a novel drug, TPN‑101, to treat Alzheimer’s disease by targeting inflammation. The drug acts on LINE‑1 DNA elements – segments of “junk” DNA that, when activated by the tau proteins present in Alzheimer’s, produce a response that mimics a viral immune trigger. This activation leads to inflammation, DNA damage, and neuronal cell death. TPN‑101 aims to halt this inflammatory cascade and preserve brain cells, potentially slowing disease progression. The ADDF is supporting Transposon’s phase 2 clinical trial.
Harnessing Microglia for Neuroprotection
Modulo Bio is developing a highly brain-penetrant CSF1R inhibitor designed to treat FTD and ALS. CSF1R is predominantly expressed on microglia cells and is crucial for modulating the brain’s immune response. The novel drug aims to reprogram microglia into a neuroprotective state in genetic forms of FTD and ALS, potentially slowing or stopping disease progression. With ADDF support, Modulo will advance this novel drug toward clinical trials and identify biomarkers to help determine which patients are most likely to benefit. In 2025, Modulo joined Lilly Gateway Labs, which will provide the team with world-class infrastructure and direct access to Lilly's neuroscience expertise – a proof point of how ADDF funding helps spur critical industry investment.
A Novel Strategy to Fight Inflammation
Therini Bio’s drug candidate, THN391, fights inflammation – a key target as we develop the next generation of treatments informed by the biology of aging. In April 2025, Therini announced positive results from the drug’s phase 1a trial, showing THN391 to be well tolerated in healthy subjects. It has been gratifying to see the ADDF’s support of this program attract other key players in the Alzheimer’s field, including the Foundation For a Better World, Eli Lilly, and Apollo Health Ventures. Therini commenced a phase 1b trial this summer.