By the time we enter middle age, most of us have begun to realize the effects of the aging process. Osteoarthritis, vision and hearing loss, dementia, and many other conditions are well-known effects of aging, but there is one side effect that's only just starting to capture attention: inflammation.
As a result, a growing number of researchers are using the word "inflammaging" to reflect the effect inflammation has on our bodies as we age. In fact, several biotech companies have picked up on this trend and are working on treatments for aging-related diseases like Parkinson's and Alzheimer's that specifically target inflammation. Investors can gain exposure to this trend through many biotech stocks.
What is inflammaging and what does it have to do with aging diseases?
For all the damage it does to some patients, inflammation actually has positive and negative effects on the body. For those who have no autoimmune or other inflammation-related disorders, the pro-inflammatory and anti-inflammatory responses are balanced.
When all is functioning as it should, inflammation enables healing after an injury and helps fight off infections. However, chronic illness results when inflammation runs out of control. Additionally, researchers have found that as we age, immune dysregulation begins to occur. As part of this process, pro-inflammatory markers start to overrun our anti-inflammatory markers, contributing to increased disease in our senior years.
For this reason, many researchers started to consider whether aging-related diseases could be treated by targeting those pro-inflammatory markers or the related immune dysregulation. Traditionally, Alzheimer's treatments were designed to target the ß-amyloid protein, which accumulates abnormally in the brains of patients with the disease. The result of that accumulation is a growing number of plaques in the brain, which have been linked to the worsening cognitive symptoms that are the hallmark of Alzheimer's disease.
On the other hand, the conventional approach to treating Parkinson's disease targeted the abnormal accumulation of the α-synuclein protein in the brain, which blocks dopamine transmission, leading to Parkinson's characteristic tremors and other symptoms.
However, several studies have demonstrated that non-aspirin, non-steroidal anti-inflammatory (NSAID) use was associated with a sizable reduction in Parkinson's risk. This supports the argument for an inflammatory cause in this aging-related disease and, by implication, many others.
These biotech stocks are among the companies taking this tactic to treat illnesses that have been linked to aging.
Annovis Bio
Annovis Bio (ANVS) is developing its candidate buntanetap to treat Alzheimer's disease (AD) and Parkinson's disease (PD). The company's Parkinson's clinical trial is now in Phase 3, while its Alzheimer's trial is in Phase 2/3. Both trials are expected to end by the end of 2023. Annovis Bio is also testing buntanetap in a Phase 2 clinical trial for Lewy body dementia (LBD).
The drug candidate is designed to block the major neurotoxic proteins responsible for AD and PD even before they are produced. A buildup of those proteins is thought to result in inflammation leading to AD or PD in patients.
So far, the company's Phase 2 clinical trial displayed a statistically significant improvement of 30% in cognition after 25 days on one scale commonly used to measure cognition in AD. Alzheimer's patients who received buntanetap saw a statistically significant 23% improvement from their baseline.
Meanwhile, PD patients displayed statistically significant improvements in their motor symptoms on two different scales commonly used to measure PD severity.
Athira Pharma
Athira Pharma (ATHA) is developing its candidate fosgonimeton for AD and PD. The company has one AD trial in a Phase 2/3 open-label extension clinical trial and another in a Phase 2 open-label extension trial. Its Parkinson's dementia and LBD trials are in the exploratory Phase 2 clinical phase.
Fosgonimeton is designed to enhance signaling in the HGF/MET neurotrophic system, which is believed to reduce inflammation, slow neurodegeneration and provide neuroprotection. Thus far, Athira has presented preclinical data suggesting that fosgonimeton provided neuroprotective effects in models of amyloid-ß-mediated toxicity.
The company also presented data suggesting that improvements in plasma biomarkers of neuroinflammation and neurodegeneration correlate with improved cognition and function in AD patients with mild-to-moderate disease.
BioVie
BioVie (BIVI) is developing its candidate NE3107 for AD and PD. The company's Phase 3 clinical trial in mild-to-moderate AD just completed its last patient treatment visit, and it expects to report topline data in November or December. In May, BioVie presented the rationale for a potentially pivotal trial of NE3107 in PD at the 2023 International Association of Parkinsonism and Related Disorders World Congress
NE3107 is designed to selectively block inflammatory pathways, reducing inflammation while enhancing insulin sensitivity — without blocking the homeostatic functions of those pathways. Thus far, BioVie has enjoyed positive clinical results for its candidate in both AD and PD.
The company reported that as measured on one key Parkinson's scale, PD patients who received NE3107 and the standard of care, which is levodopa and carbidopa, saw greater symptom improvements versus those who received a placebo and the standard of care.
Additionally, six of the 20 patients receiving NE3107 with the standard of care reported being in an "on state" in the morning. In other words, their motor symptoms were well-controlled with NE3107 so that they can get out of bed in the morning. On the other hand, none of the patients taking the placebo were in the "on state" after their usual PD medications wore off overnight.
AD patients receiving NE3107 saw a reversal of their cognitive decline rather than a slowing to their decline as reported by the recently approved drugs. BioVie reports that such improvements were significantly correlated to reductions of TNF-α (i.e., inflammation). Patients also experienced improvements with biomarkers and neuropsychological and neurophysiological status.
Unity Biotechnology
Unity Biotechnology (UBX) is developing UBX1325 to treat age-related eye diseases like diabetic macular edema (DME). Currently, the drug candidate is Phase 2 and 2b trials for DME.
UBX1325 is designed to target senescent cells, which can secrete large numbers of pro-inflammatory proteins, leading to dysfunction and degradation of tissue. Unity reports that senescent cells have been implicated in several age-related diseases.
So far, a Phase 2 trial has found that a single injection of UBX1325 resulted in a statistically significant improvement in best corrected visual acuity through 48 weeks versus sham treatment. Unity is currently enrolling DME patients in a Phase 2b trial to compare UBX1325 with aflibercept, a medication used for DME, neovascular age-related macular degeneration and other eye diseases.
Investing in inflammaging-related biotech stocks
More and more researchers have begun to study the ways inflammation can lead to chronic diseases as we age. As a result, there's now an official definition for inflammaging, which is "aging-associated chronic inflammation that results from combined genetic, epigenetic and metabolic dysfunction in different cell types and organs."
Thus, with the growing amount of evidence indicating that inflammation plays a significant role in the development of age-related diseases, the investment thesis for inflammaging-related biotech stocks seems clear. In fact, the inclusion of names like Unity Biotechnology indicates that there are many more aging-related diseases than most investors may be aware of.
Disclaimer: Ari Zoldan is CEO of Quantum Media Group, LLC. BioVie is a client 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.
Other Topics
Stocks
Ari Zoldan
Ari Zoldan is the CEO of New York-based Quantum Media Group, LLC. The company provides investor relations, public relations and equity research services to publicly traded companies. As an on-air media personality, Ari can be seen regularly on major media outlets and is frequently quoted in mainstream news outlets covering business, innovation and emerging trends.
Read Ari's Bio