According to Todd Haim, chief of the Office of Small Business Research at the National Institute on Aging (NIA), Alzheimer’s disease (AD) is a major issue. In his opening remarks on a BIO Digital panel, titled “Brave Innovations: public and private solutions to advance Alzheimer’s therapeutics and diagnostics in a risk-averse climate,” he provided data showing why new treatments for AD and AD-related dementias (ADRD) are desperately needed. With 5.7 million people currently affected in the U.S., that number is predicted to rise dramatically to 14 million by 2050. Despite the massive investments that have been made in AD drug development over the last decade, there has been poor return, with the field suffering several late-stage clinical setbacks for disease-modifying drug candidates, causing a subsequent pullback in biotech company R&D spending. The panelists discussed how public-private partnerships are helping to accelerate the development of novel innovations once again.
The NIA Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs can help spark innovation in AD/ADRD research, Haim explained. They offer nondilutive, no-strings-attached funding up to $2.5 million (depending on funding opportunity) to commercialize products addressing aging and aging-related diseases and conditions, Alzheimer’s disease and related dementias. The NIA’s budget has been boosted recently to $118 million following Congress increasing funding specifically directed toward AD research.
The advantage of being awarded funding from those programs also provides recognition and validation of an emerging company’s technology that helps attract additional funding, venture capital and a potential strategic partner, Haim added.
The NIA also provides added infrastructure for developing high-quality research tools and technologies needed to validate and advance the next generation of drug targets for Alzheimer’s disease. The Accelerating Medicines Partnership-Alzheimer's Disease (AMP-AD) program’s open-science enterprise has provided more than 500 new candidate targets for AD. The AMP-AD program is a precompetitive partnership among government, industry and nonprofit organizations that focuses on discovering novel, clinically relevant therapeutic targets and on developing biomarkers to help validate existing therapeutic targets.
Alessio Travaglia, scientific program officer at the Alzheimer’s Disease Discovery Foundation (ADDF), described how the venture philanthropy organization is supporting AD by providing funding to global academic centers and biotech companies that are advancing therapeutic and biomarker development for Alzheimer's and related dementias. Several key areas are supported, including translational research to develop new drugs and to build preclinical evidence, along with IND-enabling studies and early stage clinical trials for novel and repurposed drugs. The ADFF is also working with companies that have been awarded SBIR/STTR grants and may need bridge funding to obtain additional data in support of an SBIR/STTR-Phase 2 grant or for other NIH grants.
Previously, AD research converged on a number of single targets and focused on developing treatments for the disease in its late stages. The failures of those approaches and the lack of clinically predictive models have taught us we need to focus on the disease earlier in its cycle, said Michal Preminger, head, Johnson & Johnson Innovation, East North America. “We need to take a step back and develop a deeper understanding of the natural history of the disease.” This is where effective diagnostics and biomarkers will be key to diagnose AD in the predementia stages and predict the rate of decline. Johnson & Johnson is involved in neuroscience and neurodegeneration, with interest in disease-modifying activity, symptomatic treatment of cognitive impairment and neuropsychiatric conditions, and biomarkers and diagnostics.
Preminger noted there are several public-private partnerships focused in that area, including the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery study, the European Prevention of Alzheimer’s Dementia (EPAD) project and the UK Biobank.
The company is working on digital markers to detect Alzheimer’s disease earlier. In its partnership with Medopad (now Huma), a health tech AI company, ReVeRe, developed and clinically validated by Janssen, is a tool allowing for remote and automated assessment and monitoring of verbal memory in individuals at risk of Alzheimer’s.
In January last year, Winterlight Labs Inc., of Toronto, entered a collaboration with Janssen Pharmaceuticals Inc., facilitated by Johnson & Johnson Innovation LLC, to focus on developing a sensitive digital biomarker that can distinguish patients with mild cognitive impairment from healthy elderly subjects. The company has developed technology that extracts 500 features from speech and language and uses artificial intelligence to create disease-specific digital biomarkers.
Panelist Joel Braunstein, CEO of C2n Diagnostics, said his firm is very close to being able to offer its APTUS-Aβ test that will measure various types of amyloid beta in the blood and then factor in additional data, such as age, to develop a probability score for amyloid-related pathology in the brain. It is also pursuing FDA approval and seeks to offer it as an in vitro diagnostic to identify which patients exhibiting potential early symptoms of Alzheimer’s disease might benefit from a PET scan follow-up.
C2n was formed in 2007 by scientific co-founders David Holtzman and Randall Bateman of Washington University School of Medicine in St. Louis and Lifetech Research, a technology research and venture development firm. Braunstein noted that since that time, the firm has been fortunate to access external partnerships that have allowed it to progress and develop the technology. Its most recent award in May was $20 million from the GHR Foundation, which will help position the company’s blood test for entry into the clinic.
PPPs are vital
Panelist Susan Catalano, co-founder and chief scientific officer of Cognition Therapeutics Inc., echoed the sentiment, commenting that “public-private partnerships are absolutely critical to advancing therapeutics in the AD/ADRD field.” The company, she said, has received funding from the NIA and ADDF to support discovery and advancement of its lead compound, CT-1812 (Elayta).
This week, Cognition reported that the NIA had awarded it a grant expected to total $75.8 million over five years to support a 540-patient phase II study of CT-1812 in individuals with early Alzheimer’s disease. The study will be conducted in conjunction with the Alzheimer’s Clinical Trials Consortium (ACTC), an NIH-funded clinical trial network of 35 academic sites with expertise in clinical trials in Alzheimer’s disease. Participants will be randomized to receive CT-1812 or placebo for 18 months. In addition to a battery of cognitive measures, the study will use a variety of biomarkers to measure target engagement and assess changes in neurodegeneration and disease progression.
CT-1812, a brain-penetrant small-molecule drug that has been shown to target the sigma-2 receptor, a key regulator of the cellular damage response, is being advanced in four phase II trials. The compound displaces toxic amyloid beta oligomers from synapses and protects against further oligomer binding, potentially stopping the synapse damage and destruction that is characteristic of neurodegenerative diseases such as AD.