Targeted therapies for Alzheimer's disease, including lecanemab (Leqembi) and donanemab (Kinsula), are designed to reduce the buildup of beta-amyloid plaques in the brain. But not all patients respond well to treatment, and some experience amyloid-related imaging abnormalities (ARIA), a potentially fatal side effect.
With the global dementia treatment market valued at nearly $20 billion in 2025 and projected to double by 2034, companies are racing to find more effective approaches to slow Alzheimer's progression — and ultimately prevent the disease. Manija Kazmi and her team at Aggregate Biosciences are among the innovators leading that charge.
Aggregate Biosciences is developing novel diagnostics and therapeutics to detect and eliminate amyloid aggregates in the blood, aiming to change the way amyloid-related diseases like Alzheimer’s and certain forms of type 2 diabetes are diagnosed and treated.
Kazmi and her colleagues have shown that not all amyloid is created equal, which might explain why patients respond differently to current amyloid-targeted drugs.
"We have shown that depending on the local environment and the concentrations of various components, amyloid can take on different forms called morphotypes," Kazmi discovered.
That finding unearthed an opportunity to create a therapeutic like no other: morphotype-specific monoclonal antibodies that capture amyloid aggregates in their soluble form, before they've had a chance to accumulate into the damaging plaques associated with Alzheimer's.
"In their monomeric state, amyloid molecules are perfectly fine. It's only when the local concentration increases that they start to form longer aggregates that can develop into full-on plaques," Kazmi explained.
In recognition of this work, Kazmi has been named a finalist for the 2025 XSeed Award, which provides grants of up to $250,000 to New York City minority- and women-led life science and healthcare startups working on novel preclinical drug development projects. Winning teams also join the ecosystem of Cure, a healthcare innovation campus headquartered in New York City.
A Serendipitous Finding Halts Amyloids Before They Aggregate
Kazmi has spent nearly 30 years as a member of the laboratory of Thomas Sakmar, MD, at The Rockefeller University, where the team has long explored the role of G protein-coupled receptors in biological processes.
About 15 years ago, they shifted their focus to amyloid biology and made a critical discovery: a protein called nucleobindin-1 (NUCB1) could capture amyloid structures at an early state called a protofibril. This state is the prelude to the formation of disease-causing aggregates.
NUCB1 became the first of the researchers' CLAMPs: chaperone-like amyloid-modulating proteins.
"The protofibrils go through the elongation process very quickly, and we were thrilled to be able to use NUCB1 to capture them, study them and use them to make antibodies," said Kazmi.
The discovery was a serendipitous one, triggered by the research of two students then in the Sakmar laboratory. One was studying NUCB1, and the other was exploring amyloid. Both molecules depend on calcium. When the researchers ran NUCB1 through a fluorescence assay with amyloid, they witnessed a surprising response.
"We spiked it with a little bit of NUCB1, and lo and behold, the curve indicating that amyloid aggregation is taking place flatlined, showing that NUCB1 was able to capture the protofibrils," recalled Kazmi.
Recognizing that more than 30 diseases are related to amyloid aggregation, they knew the findings could have extraordinary implications.
Expanding the Discovery to Alzheimer's and Diabetes
Kazmi and Sakmar then collaborated with scientists at the Karolinska Institute in Sweden to show how NUCB1 binds to brain tissue. They also partnered with Ronald Parchem, PhD, at Baylor College of Medicine, who had developed a mouse model of type 2 diabetes.
While amyloid association with Alzheimer's is well known, its contribution to type 2 diabetes is not widely recognized. One hallmark of type 2 diabetes is the toxic build-up of human islet amyloid polypeptide (hIAPP) aggregates in the pancreas. Individuals with high amyloid levels are sometimes said to have “type 3 diabetes,” and they face a significantly higher risk of developing Alzheimer's.
Kazmi, Parchem and their team showed that two CLAMP-derived monoclonal antibodies designed to detect hIAPP protofibrils in the blood and deposits in the pancreas delayed the progression of type 2 diabetes and lengthened overall survival in the mouse model. They published this provocative discovery in Advanced Science in 2022.
With proof-of-concept studies validating the antibodies in human and mouse models, their next steps include integrating structural and computational modeling data to refine the antibody’s specificity. This modification would expand its precision targeting capabilities across the full diversity of amyloid morphotypes.
Kazmi and her colleagues also created a companion tool called AggMap, a precision diagnostic platform designed to stratify patients based on their dominant amyloid morphotypes. Their innovation is enabling a tailored first-in-class therapeutic strategy for Alzheimer's and other amyloid-related diseases.
Kazmi's Leap from Academia to Entrepreneurship
Kazmi, Parchem and Sakmar were ready to launch Aggregate Biosciences when they discovered that amyloid exists in a range of different morphotypes — distinct types that may correspond to each person's disease.
With the computational biology expertise of Brian Petkov, PhD, and the industry experience of Sharon Blaettler, PhD, and W. Vallen Graham, PhD — a former Rockefeller University researcher who entered the entrepreneurial space by founding (and then exiting) Thelium Therapeutics — Kazmi, Parchem, Graham and Sakmar co-founded Aggregate Biosciences in 2024. The team is currently in intellectual property negotiations with Rockefeller.
For Kazmi, the decision to become an entrepreneur came at the right time.
"My kids were grown and I was at a phase of my life when I thought I could try a few more things. I did not have starting a biotech on my BINGO card, but it felt absolutely right," she said. "Every step of this journey has been fulfilling and rewarding in a way I didn't know existed and couldn't have appreciated until I was in this space."
What XSeed Award Funding Could Do
In early 2025, Kazmi was accepted as a Westchester County Biosciences Accelerator Cohort of Life Sciences Startup, which provides founders with a fundable business plan as well as a professional network.
Aggregate Biosciences was also accepted into the QB3 incubator and won a Golden Ticket from Biolabs at NYU Langone. As part of the Golden Ticket program, Aggregate Biosciences can access wet lab space at BioLabs on Varick Street in lower Manhattan.
An XSeed grant would provide the funding needed to set up this lab, especially because expected federal funding they were awarded has yet to come through.
"We have the personnel, we have the technology and we just need the initial infusion that would allow us to take off," Kazmi contended.
She hopes that five years from now, Aggregate Biosciences will have established strategic partnerships and exited certain assets to pharma. Perhaps there could even be a blood test that someone could have at their annual physical to examine their "amyloidome": their personal panel of amyloid morphotypes, enabling doctors to match patients who have amyloid-related diseases with precision therapies.
"I was drawn to the XSeed Award because it is specifically for women and minorities," Kazmi added. "I was born in Afghanistan so for me, a little girl from Kabul, to be sitting here now as a finalist for XSeed is really tremendous."
Kazmi’s Advice for Would-be Life Science Entrepreneurs
Kazmi offers some guidance to those considering crossing the bridge from academia into the entrepreneurial space.
"Go for it!" she encouraged. Mentorship is key.
"I think finding mentors and not being afraid to ask for input and help are very important. Seek out mentors who can give you guidance, and pursue programs that can help you understand how to make this leap,” she said. “The mentorship we have received allowed us to raise the bar for our company."
Learn more about the XSeed Award and past winners.