These Biotechs are Using the Same Treatments for Multiple Neurodegenerative Diseases: Here's Why it Works

Neurodegenerative diseases (NDDs) are among the most devastating conditions for patients and caregivers, and they're some of the most difficult to diagnose and treat. Many of the drugs already on the market face difficulties getting into the patient's brain because of the need to cross the blood-brain barrier and the difficulties of one drug candidate to affect multiple disease pathways.

Due to these difficulties, several companies have halted their NDD pipelines. However, several biotech firms continue to push their most promising drug candidates forward, and with increasing success in some cases.

The advantages of treating multiple NDDs with the same drugs

In fact, some of these companies have found that their treatments for one neurodegenerative disease works quite well for other NDDs — an exciting and critical finding due to the difficulties of treating these diseases. Additionally, targeting multiple diseases with one drug candidate increases its total addressable market, making these treatments even more valuable than they would be if they only targeted one disease.

One estimate pegs the global NDD market at around $42.4 billion in 2023 with a compound annual growth rate (CAGR) of around 3%, bringing the market's value to about $52.8 billion by 2030. Of these totals, Alzheimer's alone accounted for about $5.1 billion in 2022 with a CAGR of 8%, while Parkinson's accounted for $5 billion.

Other NDDs of note with potentially overlapping treatment mechanisms include various other forms of dementia and amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease. Companies that can develop treatments for multiple NDDs will be in much better positions for future growth.

Neurodegenerative diseases affect cognitive functions, motor functions, or a combination of both. Many NDDs, including Alzheimer's and Parkinson's, affect primarily seniors, as the risk of developing them rises with age. Unfortunately, while the development and progression of such diseases often result in similar symptoms, a lack of understanding of the mechanisms and causes of these diseases has restricted available treatment options.

However, taking a fresh look at inflammation as a potential cause or trigger rather than a symptom or side effect is opening new avenues for treatment that are being explored by several biotech firms. Here are five publicly traded biotech firms with drug candidates targeting multiple NDDs in their pipelines.

Alector

Targeting a type of cell called microglia, Alector (ALEC) focuses on the role the immune system plays in NDDs and aims to redirect the aberrant immune cell activity in the brain to improve function. Specifically, the company is working on Alzheimer's, ALS, and frontotemporal dementia, also known as FTD.

Alector's AL001 and AL101 target the protein progranulin specifically to treat FTD and Alzheimer's, although progranulin deficiency has been linked to multiple NDDs, including FTD, Alzheimer's, Parkinson's, and ALS, among others. Progranulin is an immune regulatory protein that plays a critical role in regulating inflammation.

In a press release announcing the company's first-quarter earnings results, Alector's chief medical officer, Dr. Gary Romano, said, "We are very encouraged by recent drug development programs in neurological disorders that have successfully leveraged treatment effects on biomarkers to support clinical efficacy. All our clinical studies are designed to deliver robust biomarker and clinical data that will evaluate the therapeutic effects of our antibody candidates on disease pathophysiology and clinical disease progression."

In a Phase 2 trial of its latozinemab, Alector observed normalized cerebrospinal fluid and plasma levels of glial fibrillary acidic protein (GFAP). FTD patients with faster rates of brain atrophy typically have higher GFAP levels. Alector is now conducting a Phase 3 trial for latozinemab.

Athira Pharma

Athira Pharma (ATHA) is working on a treatment for Alzheimer's, Parkinson's, and Lewy body dementia (LBD). Two trials for fosgonimeton in Alzheimer's are in Phases 2 and 3, with enrollment in the open-label extension of the Phase 2/3 trial ongoing. Meanwhile, the fosgonimeton trial in Parkinson's disease dementia and LBD is in an exploratory Phase 2 clinical trial.

Athira's approach also has a neuroinflammatory aspect to it. The company designed its proprietary drug discovery platform to develop drug candidates with the potential to impact a broad range of neurological problems. Athira presented its findings at the 2023 International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD) earlier this year.

“New therapeutic strategies for neurodegenerative diseases are urgently needed," said Athira Chief Scientific Officer Kevin Church, Ph.D. "Our presentations at AD/PD highlight a wide range of preclinical evaluations demonstrating the ability of fosgonimeton, or its active metabolite fosgo-AM… to address multiple aspects of neurodegeneration,” said Kevin Church, Ph.D., Chief Scientific Officer of Athira. "These findings include notable neuroprotective, neurotrophic, and anti-inflammatory effects, as well as reduction of disease-related protein pathologies following multiple and varied challenges in models of Alzheimer’s and Parkinson's."

BioVie 

BioVie (BIVI) (Disclaimer: BioVie is a client of Quantum Media Group, LLC) is working on a treatment for Alzheimer's and Parkinson's. The company has enjoyed positive clinical results in both illnesses for its candidate NE3107. Interestingly, the trials so far have shown that NE3107 improves both cognition in Alzheimer's patients and motor symptoms in Parkinson's patients.

Historically, researchers focused on abnormal accumulations of the protein ß-amyloid in the brains of Alzheimer's patients. In Parkinson's, the focus was generally on the protein α-synuclein, which is believed to reduce dopamine in the brains of patients, resulting in various symptoms, including the tremors that are the hallmark of Parkinson's.

However, BioVie is approaching both NDDs by targeting inflammation. In a recent poster presentation at the 2023 International Association of Parkinsonism and Related Disorders World Congress, BioVie summarized its latest findings.

Parkinson's patients treated with NE3107 plus the usual standard of care, which is levodopa and carbidopa, experienced greater improvements as measured by the Motor Disease Society – Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part III, versus those treated with a placebo plus the standard of care. Five of the 19 patients treated with NE3107 plus the standard of care were in an "on state" in the morning, meaning their motor symptoms were controlled, compared to none of those who received the placebo.

Meanwhile, BioVie found improvements in neurophysiological, neuropsychological, and biomarker status in Alzheimer's patients. The company found reduced levels of TNF-α, indicating reduced inflammation, in 61% of the 18 patients treated with NE3107. BioVie also reported statistically significant improvements in mood and memory in treated patients.

“We believe chronic, low-grade inflammation mediated by TNF-α is the starting point for many things going wrong in the body,” commented Cuong Do, BioVie’s President and CEO. “Inflammation leads to insulin resistance, which is required for Parkinson’s symptoms in patients with low dopamine levels. Inflammation leads to hypermethylation of our DNA, which affects many genes associated with Alzheimer’s as well as drives the phosphorylation of tau and production of AAP, which leads to more ß-amyloid.”

Coya Therapeutics 

Coya Therapeutics (COYA) (Disclaimer: Coya Therapeutics is a client of Quantum Media Group, LLC) focuses on regulatory T cells, also known as Tregs, to treat ALS and Alzheimer’s. Coya has linked dysfunctional Tregs with neuroinflammation, which has been found to be a key issue in multiple neurodegenerative diseases, including ALS, Alzheimer’s, and Parkinson’s. In fact, the company recently announced that its candidate COYA 301 increased Treg function and halted cognitive decline in Alzheimer's patients in an open-label study. Additionally, in a proof-of-concept, open-label study in ALS that was previously reported, the company’s candidate COYA 302 also significantly enhanced Treg function. In fact, patients in that COYA 302 study reported no decline or minimal decline in symptoms as measured by the Revised ALS Functional Rating Scale (ALSFRS-R) scale over 48 weeks.

COYA 301 is a Treg-enhancing biologic that reduces inflammation, while COYA 302 is a biologic combination of COYA 301 with abatacept, which blocks other types of inflammatory cells. The combination may result in a synergistic reduction in inflammation. 

“We believe that targeting regulatory T cells with our biologics is ideal, as this pathway sits upstream of multiple immune mechanisms that contribute to inflammatory processes, including pro-inflammatory cytokines such as IL-1, IL-6, and TNF--α, T effector cells, macrophages, and microglia, and B cells,” explained Howard H. Berman, Ph.D., CEO of Coya Therapeutics. “Moreover, regulatory T cells are dysfunctional in neurodegenerative diseases, and our biologics are intended to enhance these regulatory T cells while suppressing other pro-inflammatory cell types. Our clinical proof-of-concept data in two different neurodegenerative diseases is promising, and we intend to leverage biomarkers in our future trials to make the studies more robust.”

Investing in clinical-stage treatments for NDDs

The biotech sector has been ripe for investment over the last several years, and many stocks in the space have gone on tremendous tears. However, biotech can be a risky sector to invest in although with great risk also comes the possibility of great rewards.

Of course, investors are always advised to do their own due diligence before investing in any stock, no matter what sector it's in.

Ari Zoldan is CEO of Quantum Media Group, LLC. Coya Therapeutics Inc. and BioVie Inc. are clients of Quantum Media Group.

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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