Anavex’s Blarcamesine Achieves Pre-specified Efficacy in Phase IIb/III Alzheimer’s Trial: Data Presented at CTAD Conference 2024

Data of Blarcamesine confirm upstream SIGMAR1 activation

Presented as Late Breaking Oral Communications at Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2024

Oral, once daily blarcamesine meaningfully slowed clinical decline for early Alzheimer’s disease patients with good comparative safety profile and no associated neuroimaging adverse events

NEW YORK, Oct. 31, 2024 (GLOBE NEWSWIRE) — Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today presented new data from the Phase IIb/III study showing that blarcamesine (ANAVEX®2-73), once daily orally, demonstrates pre-specified clinical efficacy through upstream SIGMAR1 activation.

Clinical data confirmed the mechanism of action (MoA) by pre-specified SIGMAR1 gene analysis in people with early Alzheimer’s disease (AD). The data were presented by Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Anavex Scientific Advisory Board at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, which is taking place October 29 – November 1, 2024, in Madrid, Spain.

SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. In Alzheimer’s disease patients, mutations (variants) of genes have generally been identified as disease risk factors. Likewise, impaired SIGMAR1 function (gene mutation, variants) leads to potential suboptimal function. Hence, patients who carry the non-mutated, common SIGMAR1 wild type (WT)1 gene, are expected to have stronger beneficial response to blarcamesine than patients with a SIGMAR1 mutation (variant), who nevertheless also benefited from treatment.2

This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; P=0.008] in the ITT analysis. This signal was even stronger in the pre-specified common SIGMAR1 wild type (WT) group with slowed clinical progression by 49.8% at 48 weeks in the active group vs. placebo, respectively [LS mean ADAS-Cog13 difference of -2.317; P=0.015]. Equal analysis with CDR-SB led to comparable consistent results.

“These data are very exciting, particularly featuring blarcamesine’s novel upstream mechanism of action, enhancing autophagy through SIGMAR1 activation, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer’s disease continuum,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “The advantage of blarcamesine is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and good comparative safety profile. We are on track for regulatory submission of blarcamesine in Europe (EMA) in the current quarter 2024.”

Overall, blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than 2 points.3 This suggests superior numerical clinical efficacy compared to approved therapies while also slowing neurodegeneration in early AD patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, could represent a novel treatment that could be complementary or an alternative to anti-beta amyloid monoclonal antibody drugs.

“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide. We believe, the clinically meaningful study results provide the potential for patients and their families to have a better and longer quality of life,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer’s disease and provide broader access to a diverse population with early Alzheimer’s disease.”

The presentation is available on the Investors section of the Company’s website at www.anavex.com.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson’s disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

For Further Information:
Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
Email: info@anavex.com

Investors:
Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: andrew@barwicki.com


1 WT = homozygous dominant (TT)
2 Hampel H, Williams C, Etcheto A, et al. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer’s disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (N Y). 2020; 6(1):e12013.
3 Muir RT, Hill MD, Black SE, Smith EE. Minimal clinically important difference in Alzheimer’s disease: Rapid review. Alzheimers Dement. 2024;20(5):3352-3363. doi:10.1002/alz.13770

AriBio Licenses Exclusive Marketing Rights for AR1001 for Alzheimer’s Disease in China for $770 Million USD

SEONGNAM-SI, South Korea–(BUSINESS WIRE)–AriBio Co., Ltd. (AriBio), announces signing of exclusive marketing rights for AR1001, an investigational drug for early Alzheimer’s disease, in China for up to $770 million USD.

The term consists of a non-refundable upfront payment of 120 billion KRW (approximately 90 million USD), with the total deal summing up to 5.59 billion RMB (approximately 770 million USD) inclusive of milestone payments with additional royalties. The upfront payment will be paid starting from mid-2024.

In response to the increasing Alzheimer’s disease population in China, prominent pharmaceutical companies have sought to develop safe and effective oral treatments for Alzheimer’s disease. To date, AriBio has partnered for exclusive marketing rights in South Korea with Samjin Pharmaceutical for 100 billion KRW. And now, the partnership has expanded to China, cumulating to 1.12 trillion KRW (approximately 840 million USD). Considering the market competition for Alzheimer’s drugs in China and the sales strategy, the licensee requested not to be disclosed until an agreed upon time.

The global Phase 3 clinical trial for AR1001 in early Alzheimer’s disease patients (Polaris-AD) is on-going in the United States, United Kingdom, and South Korea. Furthermore, the clinical trial is awaiting regulatory approval in China and the European Union. This study will be conducted across 180 global sites. The first patient enrollment began in the United States in December 2022, and the rest of the regions are actively enrolling.

Matthew (Jai Jun) Choung, CEO and Chairman of AriBio, stated, “This deal demonstrates our unwavering commitment to developing meaningful treatments for Alzheimer’s disease, and our partners will help position AR1001 for success in the major Asian territories. We are building momentum in our AR1001 program, as we continue to discuss with other potential partners in Asian countries, the Middle East, South America, as well as Europe and the United States.”

About AR1001

AR1001 is a PDE5 inhibitor being developed as an investigational oral agent for the treatment of Alzheimer’s disease. Pre-clinical studies have confirmed neuroprotective effects of AR1001 via inhibiting neuron apoptosis and restoring synaptic plasticity. AR1001 has also demonstrated robust reduction of hyperphosphorylated tau proteins in pre-clinical models as well as in a Phase 2 trial.

About AR1001-ADP3-US01

AR1001-ADP3-US01 (NCT05531526) is a Phase 3 double-blind, randomized, placebo-controlled, multi-center trial to evaluate the efficacy and safety of AR1001 over 52 weeks in participants with early Alzheimer’s disease. The study aims to assess the efficacy and safety of AR1001 in slowing the progression of Alzheimer’s disease through various cognitive and functional assessments. The details of the clinical trial are available at ClinicalTrials.gov.

About AriBio

AriBio Co., Ltd. is a biopharmaceutical company based in South Korea with offices in both South Korea and the United States. The company focuses on the development of novel therapies for neurodegenerative diseases. The company continues to expand its partnerships to accelerate the development of meaningful treatment options for neurodegenerative diseases.

Contacts

Fred Kim

fredkim@aribiousa.com

Promising Results: TGR-63 Enhances Memory in Alzheimer’s Mouse Model

IGC Pharma today announced the results of preclinical studies investigating its drug candidate TGR-63 as a treatment for Alzheimer’s disease. The data demonstrated enhanced memory function in an Alzheimer’s mouse model, including improved memory acquisition, consolidation, and retrieval.

TGR-63 is a therapeutic candidate designed to disrupt the structure of the amyloid-β (Aβ) peptide, mitigating symptoms such as memory loss and disrupted learning ability, signs of cognitive impairment. TGR-63 targets a critical neuropathological hallmark of Alzheimer’s Disease by addressing the misfolding and aggregation of Aβ peptides, specifically the toxic Aβ42 aggregation species associated with neuronal toxicity and cognitive decline. The cognitive impact of TGR-63 was assessed using two renowned behavioral tests, the Novel Object Recognition (“NOR”) Test and the Morris Water Maze (“MWM”), conducted on APP/PS1 genetically modified Alzheimer’s mice.

Ram Mukunda, CEO, commented, “These results underscore the efficacy of TGR-63 in enhancing spatial memory function in an Alzheimer’s disease model, offering promising implications for potential therapeutic interventions in Alzheimer’s and related neurodegenerative conditions. The improvements in memory acquisition, consolidation, spatial memory formation, and retrieval highlight its potential in addressing cognitive impairment in Alzheimer’s Disease. We are optimistic about TGR-63’s potential and anticipate advancing it towards a Phase 1 trial, enriching our clinical portfolio.”

The NOR Test, a cornerstone of preclinical research, evaluates recognition memory, a component of declarative memory responsible for recognizing previously encountered stimuli. Widely applicable across neuropharmacology and neurobiology, this test provides crucial insights into memory function and potential interventions for memory-related disorders such as Alzheimer’s. During the NOR Test, Alzheimer’s mice displayed a significantly diminished Discrimination Index (“DI”) compared to normal mice, indicating impaired long-term memory. TGR-63-treated Alzheimer’s mice showed a 51% improvement in DI, signifying promising therapeutic efficacy. After 48 hours, while untreated Alzheimer’s mice experienced a 100% decline in memory, those treated with TGR-63 demonstrated an 86% increase in DI, suggesting robust long-term potentiation (“LTP”) formation and successful memory retrieval.

The Morris Water Maze (“MWM”) is a pivotal tool in cognitive research, offering deep insights into spatial learning and memory processes. In this test, mice are trained to find a hidden platform in a pool over four days. Particularly crucial in neurodegenerative diseases like Alzheimer’s, the MWM allows researchers to explore spatial navigation and memory formation mechanisms. Over four days of training, TGR-63-treated mice exhibited a statistically significant reduction in the time required to locate the hidden platform, reflecting improved spatial memory acquisition. Additionally, when the platform was removed, the untreated AD mice spent 87% of their time away from the target area, while TGR-63-treated mice spent only 66% of their time away. TGR-63-treated mice also spent more time in the target area, showing improved spatial memory retrieval.

IGC Pharma is currently underway with a Phase 2b trial in the United States and Canada evaluating IGC-AD1 for agitation in Alzheimer’s. The trial encompasses 146 patients, with half assigned to the treated group receiving IGC-AD1, while the other half, the control group, receiving a placebo.

About IGC Pharma Inc. (dba IGC):

IGC Pharma is pursuing innovative solutions to fight Alzheimer’s disease and related challenges. IGC Pharma’s portfolio comprises five assets, all with a singular mission – to transform the landscape of Alzheimer’s treatment. IGC-AD1 and LMP target neuroinflammation, Aβ plaques, and neurofibrillary tangles. IGC-AD1 is currently in a Phase 2b clinical trial for agitation in dementia due to Alzheimer’s (clinicaltrials.gov, NCT05543681). TGR-63 targets Aβ plaque to disrupt the progression of Alzheimer’s disease. IGC-M3 targets the inhibition of Aβ plaque aggregation with the potential to create a profound impact on early-stage Alzheimer’s. IGC-1C targets tau and neurofibrillary tangles in a forward-thinking approach to Alzheimer’s therapy. In parallel, IGC Pharma is at the forefront of Generative AI development, with projects including clinical trials, early detection of Alzheimer’s, and drug interactions with cannabinoids.

Forward-Looking Statements:

This press release contains forward-looking statements. These forward-looking statements are based largely on IGC Pharma’s expectations and are subject to several risks and uncertainties, certain of which are beyond IGC Pharma’s control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, the Company’s failure or inability to commercialize one or more of the Company’s products or technologies, including the products or formulations described in this release, or failure to obtain regulatory approval for the products or formulations, where required, or government regulations affecting AI or the AI algorithms not working as intended or producing accurate predictions; general economic conditions that are less favorable than expected; the FDA’s general position regarding cannabis- and hemp-based products; and other factors, many of which are discussed in IGC Pharma’s U.S. Securities and Exchange Commission (“SEC”) filings. IGC Pharma incorporates by reference the human trial disclosures and Risk Factors identified in its Annual Report on Form 10-K filed with the SEC on July 7, 2023, and Quarterly Report on Form 10-Q filed with the SEC on February 14, 2024, as if fully incorporated and restated herein. Considering these risks and uncertainties, there can be no assurance that the forward-looking information contained in this release will occur.

Contacts

Investors
IMS Investor Relations

Rosalyn Christian

igc@imsinvestorrelations.com
(203) 972-9200

Media
JVPRNY

Janet Vasquez

jvasquez@jvprny.com
(212) 645-5498

Alpha Cognition – developing novel treatments for neurodegenerative diseases such as Alzheimer’s Dementia and Amyotrophic Lateral Sclerosis

Alpha Cognition is a clinical stage, biopharmaceutical company dedicated to developing novel treatments for under-served neurodegenerative diseases such as Alzheimer’s Dementia and Amyotrophic Lateral Sclerosis (ALS).

Alpha Cognition - developing novel treatments for neurodegenerative diseases such as Alzheimer’s Dementia and Amyotrophic Lateral Sclerosis

ALPHA-1062, a patented new chemical entity that has demonstrated safety and improved ALPHA-1062, is a patented new chemical entity being developed as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ALPHA-1062’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia and as an intranasal formulation for traumatic brain injury.

ALPHA-0602 (Progranulin) is expressed in several cell types in the central nervous system and in peripheral tissues, promotes cell survival, regulates certain inflammatory processes, and plays a significant role in regulating lysosomal function and microglial responses to disease. Its intended use for the treatment of neurodegenerative diseases has been patented by the Company and Alpha-0602 has been granted an Orphan Drug Designation for the treatment of Amyotrophic Lateral Sclerosis by the FDA.

ALPHA-0702 and ALPHA-0802 are Granulin Epithelin Motifs, or GEMs, derived from full length progranulin which have therapeutic potential across multiple neurodegenerative diseases. Progranulin is comprised of 7½ Granulin Epithelin Motifs (GEMs). GEMs are important in regulating cell growth, survival, repair, and inflammation. Individual granulin domain peptides are approximately 60 amino acids in length (~7kDa). GEMs are metabolically stable and resistant to proteolysis (long half-life). Evidence suggests that not all GEMs are equally potent at promoting cell survival signaling or reducing proteinopathy, and may compete (e.g., binding to effectors) with active GEMs and effectively decrease their potency. Specific GEM combinations have been shown to be more effective than full length progranulin in promoting Cathepsin D maturation. GEMs have been shown to be important in regulating cell growth, survival, repair, and inflammation. Alpha-0702 and ALPHA-0802 are designed to deliver this with potentially lower toxicity, and greater therapeutic effect.

More info : http://www.alphacognition.com/

Keywords : Alpha Cognition , neurodegenerative diseases , dementia , Alzheimer’s Dementia , Alzheimer Disease , Amyotrophic Lateral Sclerosis , acetylcholinesterase inhibitor , orphan drug , CNS , neuroscience , traumatic brain injury , Granulin Epithelin Motifs , Gene Therapy