None Alzheimer’s disease research and drug development is evolving at a rapid pace. Decades of research has led to the approval of the first disease-modifying drugs and new pathological discoveries. The first blood-based biomarker tests will bring equitable access to screening and diagnosis while accelerating clinical research. These major breakthroughs in the last few years alone represent a pivotal time in the Alzheimer’s disease landscape.“This is an unprecedented time for Alzheimer’s research. Significant advances have been made in understanding pathological factors affecting disease, long-awaited disease-modifying treatments have been approved and more convenient diagnostic tools are becoming available - all major steps in changing the course and impact of this once-elusive disease,” stated Dr. David Morgan, Director of the Alzheimer’s Alliance and Professor of Translational Neuroscience at Michigan State University.A new era of Alzheimer’s disease therapiesThere are now ten treatments approved for Alzheimer’s disease, including two recently-approved disease-modifying drugs – the most recent approved in July 2024. The disease-modifying treatments are a class of monoclonal antibodies that target the removal of amyloid-beta plaque build-up in those with mild cognitive impairment or early Alzheimer’s disease.Researchers convening at the recent Alzheimer’s Association International Conference acknowledged that the community can build upon the latest advances. “We need new therapies, many more targets, better drugs, more convenient drugs, but it is important that we have changed the landscape by having disease-modifying therapies.”Next wave of Alzheimer’s disease testing - plasma-based biomarker testsOne of the major advances in the Alzheimer’s disease landscape is the emerging blood-based biomarkers tests that are expected to improve diagnosis in primary care, reduce wait times for treatment initiation, accelerate clinical trial recruitment and greatly lower the cost of diagnosing Alzheimer’s.Only 10 years ago, Alzheimer’s disease diagnosis relied on symptom observations. Since then, the gold standard has moved to a PET scan or lumbar puncture. These diagnostic options are costly, invasive and inaccessible in many communities.One of the challenges to accessing the new monoclonal antibody treatments is the availability of PET scans to screen for qualified patients. The convenience of blood-based biomarker tests would relieve this bottleneck. A panel has been assigned by the Alzheimer’s Association to conduct a systematic review of the plasma-based biomarker tests and expects to provide a clinical practice guideline in early to mid 2025.Emerging biological pathways as drug development targetsMost of the recent drug development efforts have been focused on mechanisms that aim to remove amyloid plaque build-up or tau tangles, main hallmarks of the disease.Researchers are now turning their attention to the role of inflammation in Alzheimer’s disease development and progression. Most recently, a study of a GLP-1 agonist, part of a class of drugs used for diabetes, weight loss and heart disease, demonstrated neuroprotective effects that may help to protect the brains of people with Alzheimer’s disease. Previous studies have shown how GLP-1 agonists can reduce neuroinflammation. The GLP-1 agonists did not alter amyloid-β and tau biomarkers nor show improvements in cognition, but the anti-inflammatory and neuroprotective effects of GLP-1 agonists warrant further studies and opens new biological pathways in the potential treatment of Alzheimer’s.The study showed the potential of repurposing diabetes drugs in the treatment of Alzheimer’s and exploring drug candidates that target similar biological pathways to diabetes treatments.Identifying a combination of therapies or a multi-factorial ApproachTo treat a complex disease such as Alzheimer’s will likely require a combination of therapies or a multi-factorial approach. The Alzheimer’s Association has identified modifiable risk factors associated with the development and progression of Alzheimer’s disease including untreated visual loss, LDL cholesterol, hearing loss, depression, Type 2 diabetes, exercise and cognitive stimulation. While these preventative lifestyle measures may delay the onset and progression of Alzheimer’s disease, lifestyle habits alone are unlikely to prevent disease development.Clinicians believe that a multi-factorial approach will be required that includes lifestyle habits and a combination of disease-modifying and symptomatic treatments that target multiple biological pathways.InMed’s INM-901 demonstrates a novel, multi-factorial approach to treating Alzheimer’sAmong the drug candidates in preclinical development is InMed’s INM-901, a promising small molecule that has demonstrated disease-modifying effects and appears to target multiple biological pathways, including the peroxisome proliferator-activated receptor (PPAR), which is associated with diabetes development and plays an important role in cell metabolism and immune response.Preclinical studies of INM-901 in well-characterized Alzheimer’s disease models indicate that INM-901 reduces neuroinflammation and cell death and promotes the growth of neurites in the brain – which enables cell-to-cell communication and is essential for brain processing. The growth of neurites, which is diminished in patients with Alzheimer’s, signifies enhanced neuronal function and may indicate the potential to restore the damage caused by Alzheimer’s disease.InMed’s INM-901 is among the several promising treatments in development that may be able to change the course of Alzheimer’s disease.

2024-07-22

·FierceBiotech

InMed’s INM-901 Demonstrates Potential as a Multi-factorial Approach to Treating Alzheimer’s Disease

None InMed Pharmaceuticals (Nasdaq:INM) recently released preclinical data indicating its proprietary, small molecule compound, INM-901, targets multiple biological pathways associated with Alzheimer’s disease. Among the most interesting data from these studies was the ability of its compound to extend the length of neurites, which may indicate enhanced neuronal functioning in the brain and the potential to reverse the damage caused by Alzheimer’s disease. The company was encouraged with these breakthrough preclinical results and will be advancing the development of the INM-901 Alzheimer’s disease program. INM-901 May Address Multiple Pathologies Related to Alzheimer’s Disease InMed’s in vitro and in vivo studies demonstrated encouraging effects in a well-characterized Alzheimer’s disease preclinical model. In this study, InMed’s INM-901 demonstrated neuroprotective effects by reducing cell death in an amyloid-beta-induced cytotoxicity study and demonstrated an ability to promote the growth and extension of neurites (neuritogenesis), an essential component of cell-to-cell communication. INM-901 also demonstrated reduced neuroinflammation and showed improvement in behavior, cognitive function and memory in in vivo studies. These promising early data of INM-901 represent the potential for disease-modifying effects as well as the potential to reverse neuronal damage associated with Alzheimer’s disease. InMed’s Senior VP of Preclinical Research and Development, Dr. Eric Hsu, is encouraged by the results indicating INM-901 may target multiple pathologies. “There continues to be a major unmet medical need for this multi-factorial disease and differentiated therapeutic mechanisms may play an important role. We believe the development of INM-901 may address several pathological factors including neuroinflammation, neuroprotection and neuritogenesis.” Study Reveals InMed’s INM-901 Targets CB1, CB2 and PPAR Pathways Research indicates that activating the endocannabinoid 1 (CB1) and endocannabinoid 2 (CB2) receptors may induce neuroprotective effects that may help protect brain cells from damage and death. Enhancing the natural activity at these receptors may help to slow the progression of Alzheimer’s disease, in which neuronal cell death is a hallmark. CB1 and CB2 receptors are part of the endocannabinoid system which is involved in almost every facet of the body’s functioning and plays a key role in brain function. Activation of these receptors may address factors influencing Alzheimer’s disease progression. Studies of INM-901 demonstrate that this small molecule drug candidate acts as a preferential signaling ligand for CB1/CB2 and impacts the peroxisome poliferator-activated receptor (PPAR) signalling pathway. InMed’s INM-901 May Be Delivered Via Oral Administration InMed’s INM-901 is a small molecule, orally available drug candidate. Importantly, INM-901 appears to safely and effectively cross the blood/brain barrier, which is essential to any compound targeting diseases such as Alzheimer’s. The drug delivery options of small molecules could greatly reduce treatment costs and the compliance challenges associated with large molecule antibody therapies. Alzheimer’s Disease Presents a Major Unmet Medical Need Alzheimer’s is a complex neurodegenerative disease and its progression is caused by several pathological factors. A multifaceted approach is needed to effectively address its diverse causes and symptoms. According to the Alzheimer’s Association, an estimated 6.9 million Americans aged 65 and older are living with Alzheimer’s, about two-thirds of them are women. Alzheimer’s disease is the fifth leading cause of death amongst the elderly and the healthcare cost is substantial at an estimated $360 billion in the U.S. alone with another estimated $350 billion in unpaid care. Until recently, there were few treatment options available for those living with Alzheimer’s disease. Previously, patients could only turn to cholinesterase inhibitors that were intended to improve cognitive and behavioral symptoms. New, recently approved treatments are showing disease-modifying effects that aim to reduce the build-up of amyloid-beta plaques, a hallmark of Alzheimer’s disease. While these long-awaited treatments offer hope to patients, major challenges exist for this class of large-molecule compounds. As large molecules, these antibody therapies are not orally available and must be delivered via intravenous infusion every two to four weeks. In addition, there are safety concerns around brain bleeding, requiring an MRI scan every 6-12 months. INM-901 has shown to be a potentially disease-modifying small molecule drug candidate presenting an attractive therapeutic pathway with encouraging preclinical results. Long-term behavioral, mechanisms of action and receptor interaction studies are underway with data read-out expected early in the second half of calendar 2024. Representatives from InMed will be attending the Alzheimer’s Association International Conference in Philadelphia, PA from July 28 to August 1, 2024. Watch this video presentation by InMed’s CEO, Eric A. Adams as he discusses the potential role of INM-901 in Alzheimer’s treatment.