When Derek Small watched his father’s early-onset dementia worsen nearly a decade ago, he observed symptoms of neuroinflammation and synaptic dysfunction. Although not a scientist by training, Small already had years of experience launching biotech companies focused on drug discovery development and clinical trials for various disorders and diseases.
Motivated by his father’s dementia journey, Small shifted the focus of his Indianapolis-based venture creation firm, Luson Bioventures, to solely invest in neuroscience biotech startups. Small and a team of Indiana University School of Medicine researchers have since co-founded a startup, Monument Biosciences, dedicated to developing the next generation of Alzheimer’s disease treatments.
“If you have dementia, it’s like you’re a completely different person. Not only do you not remember people’s names, but you also can’t even really function,” said Small, whose father, John Small, died in 2017 at the age of 74. “After all I had been working on in drug discovery, neuroinflammation and synaptic dysfunction were the two phenotypes coming through to me that I felt like we had drugs that could help, or we had ways to target with new drugs.”
After launching a different biotech startup focused on synaptic dysfunction in 2018, Small searched for collaborators to study neuroinflammation.
“I was talking with scientists and pharmaceutical companies all over the world about novel neuroinflammation approaches,” Small said. “I wasn’t just looking in the Midwest.”
That global search eventually led Small back to Indianapolis, where he met Alan Palkowitz, research professor of medicine at the IU School of Medicine and the president and CEO of the Indiana Biosciences Research Institute.
“I was extremely excited to learn that a pharmaceutical industry veteran like Alan — someone who has led countless drug-discovery-to-clinical-translation programs in his 25-plus years at Eli Lilly — and the TREAT-AD team were not only working on neuroinflammation,” Small said, “but they were also thinking much bigger than the other research groups I had met with to date around the world and were focusing on a next-generation approach that perfectly aligned with our strategy at Luson Bioventures.”
Monument Biosciences, which is housed within the Indiana Biosciences Research Institute, started to incubate in 2023. Small partnered with Palkowitz and his TREAT-AD co-principal investigators Bruce T. Lamb and Timothy Richardson, along with several other researchers at the IU School of Medicine. The nonprofit research institute is also the home to Luson Bioventures, Syndeio Biosciences and the TREAT-AD laboratories.
“Even in our initial application for TREAT-AD, we envisioned a future scenario where the output of our work would have the potential to reach patients,” Palkowitz said, “We ultimately saw the best way to accomplish this is through a company that could recruit investment and build the right infrastructure to focus on clinical development.
“Derek wanted to start a company focusing on neuroinflammation, which had been the emphasis of our TREAT-AD center. It really was a natural convergence.”
IU School of Medicine researchers leading the way
The IU School of Medicine has several programs dedicated to Alzheimer’s disease research, from basic and translational science to clinical research and innovation. The comprehensive program even drew the attention of Bill Gates, the co-founder of Microsoft.
In addition to Palkowitz, Lamb and Richardson, Monument Biosciences co-founders from the IU School of Medicine include Stephanie Bissell, Adrian Oblak, Brent Clayton, Jeff Dage and Jared Brosch. Cristian Lasagna-Reeves, a former IU School of Medicine faculty member, is also a co-founder. The group includes investigators who study the biology of Alzheimer’s disease, medicinal chemistry, disease biomarkers and clinical research.
Before launching Monument Biosciences, Small had worked closely with Anantha Shekhar, the former executive associate dean for research at the IU School of Medicine. Small and Shekhar has previously co-founded startups Gate Neurosciences, Syndeio Biosciences and Anagin.
“It’s really extraordinary and actually underappreciated how much the IU School of Medicine has contributed to the neuroscience field,” Small said. “They have world-class quality science, great people and full-service patient care for dementia and Alzheimer’s disease. I consider it one of the top research consortiums in the world for Alzheimer’s disease and related dementias.”
Bridging the gap between basic science and clinical trials
Biotech startups have often bridged the gap — sometimes referred to as the “valley of death” — between basic research and drug development.
“If we’re really thinking about accelerating innovation to patients, placing assets into a company and raising money through investors who are motivated in this space is a great formula,” Palkowitz said. “But at the same time, we’re able to continue to advance science and build on the work we’ve done within TREAT-AD.”
Through Luson Bioventures, Small has launched and led several neuroscience and infectious disease companies, including Assembly Biosciences, Naurex and others, guiding companies as the founding CEO through clinical development, IPOs and strategic exits.
“Our goal is to take lead candidates from the TREAT-AD pipeline and move it toward clinical trials,” Small said. “That’s where our team steps in with the next stages of drug development.”
Dolby Family Ventures is also a major investment partner of Monument Biosciences, Small said. The venture firm was created in honor of Dolby Laboratories founder Ray Dolby, who died of Alzheimer’s disease. The firm funds dozens of companies focused on disease-modifying treatments for Alzheimer’s disease and depression.
TREAT-AD, which launched in 2019 and received a five-year grant renewal in December 2024 from the National Institute on Aging, narrowed down a list of hundreds of potential drug targets for Alzheimer’s disease to a portfolio of five that are promising potential new therapies.
Monument Biosciences set up an exclusive licensing arrangement with the IU Innovation and Commercialization Office to develop drug targets discovered through TREAT-AD into potential therapeutics for clinical trials. Richardson said the center’s portfolio of targets focuses on the neuro-inflammatory component of Alzheimer’s disease, a novel way of approaching the disease. potential therapeutics for clinical trials. Richardson said the center’s portfolio of targets focuses on the neuro-inflammatory component of Alzheimer’s disease, a novel way of approaching the disease.
“TREAT-AD hopes to take Alzheimer’s disease treatments to the next level by focusing on microglia, a specialized type of immune cell primarily responsible for clearing amyloid and protecting the brain,” Richardson said.
One of the center’s most advanced projects is targeting a microglial-specific gene associated with Alzheimer’s disease, which the team received a five-year grant from the National Institute on Aging to study. The gene, INPP5D, encodes the protein SHIP1 and is also one of the top targets for Monument Biosciences, Richardson said, along with the gene PLCG2, an immune cell-specific gene that has also been rigorously studied by IU School of Medicine researchers.
“I don’t think we’ve been in a more exciting period for the potential of impacting Alzheimer’s patients with new innovation,” Palkowitz said. “Our hope is that what we’re doing through Monument Biosciences and having our roots in the research community at IU and the Indiana Biosciences Research Institute is going to make a big impact on the disease. We look forward to what the future holds.”