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Our Butyrylcholinesterase Inhibitor (BChE-I) Portfolio in Neurodegenerative Diseases

Butyrylcholinesterase (BChE) is a promising target for treating advanced stages of Alzheimer's disease (AD). Its prevalence increases in severe AD, making it suitable for mid- to severe AD patients. Additionally, BChE is linked to key AD hallmarks, such as amyloidogenesis. Exploring hybrid drugs that target BChE alongside other therapeutic objectives holds potential for anti-Alzheimer's treatments.

Pharmaeconomica's Breakthrough in Alzheimer's Drug Discovery

 

Global Impact: Dementia affects over 55 million people worldwide, costing $1.3 trillion annually, with Alzheimer's being the most prevalent form. By 2028, approximately 1,000,000 patients in the US, UK, Spain, France, Italy, Germany, and Japan will be in the late stages of Alzheimer's disease.

Unmet Needs: There is currently no cure for Alzheimer's disease (AD). Traditional cholinesterase inhibitors are limited by toxicity and diminishing efficacy, while recent disease-modifying treatments suffer from poor adoption due to limited effectiveness, increased logistical demands, and adverse events.

Our Research: Pharmaeconomica has discovered selective, brain-specific butyrylcholinesterase (BChE) inhibitors, PE01 and PE02, for late-stage AD using in-silico methods and validated in vitro. Additionally, we are screening dual-action compounds targeting MDM2, gamma-secretase, BACE-1, and TAU in neurodegenerative diseases.

Advanced Virtual Screening: We identified optimal analog compounds by screening 35 million compounds using the PE01 and PE02 scaffolds, validated by molecular dynamics simulations. Our structure-based approach refined top ligands from a 5 million molecule library, and our PREDIT framework employed machine learning to successfully pinpoint promising analogs for BChE inhibition.

Potential First-in-Class Therapy: Our new mechanism of action involves highly selective and brain-specific BChE inhibition in Alzheimer's. BChE activity rises significantly in AD, making it a key therapeutic target. Inhibiting BChE can provide symptom relief and potentially slow disease progression through neuroprotection. Selective BChE inhibitors have shown promise in boosting acetylcholine (ACh) levels and improving cognition in animal studies, indicating potential for new Alzheimer's treatments.

Market Opportunity: The global market for dementia drugs was valued at $20.1 billion in 2021 and is projected to grow at a compound annual growth rate (CAGR) of 9.3% from 2022 to 2030, reaching an estimated market size of $36.7 billion by 2030. Pharmaeconomica's innovative approach positions us to capture a significant share of this expanding market, addressing a critical unmet need with our pioneering Alzheimer's therapies.

Whispering to Granddad
Targeting the Beta-Amyloid Pathway with Innovation

At Pharmaeconomica, we are revolutionizing Alzheimer's Disease (AD) drug discovery through relentless innovation and a focus on efficacy, specifically targeting the Beta-Amyloid (Aβ) pathway. Utilizing our proprietary AI-Powered Biophysics Drug Discovery Platform, we harness advanced AI and machine learning to identify and optimize lead compounds with exceptional precision. Our cutting-edge strategies are designed to develop transformative therapies that significantly improve patient outcomes and advance the fight against AD.

Workflow Overview

Integrated Virtual Screening: Utilizing our proprietary datasets of approximately 4 billion small molecules and specialized peptide libraries, we identify promising candidates targeting the Aβ pathway. This extensive collection enables us to discover potential drug candidates, either as small molecules or peptides, with the ability to target AD in both individual and dual-action manners.​

Dual-Action Candidates 

Targeting Key Enzymes: We focus on discovering compounds capable of individually targeting crucial enzymes such as BACE1 and gamma-secretase or offering dual inhibition to block multiple pathological pathways simultaneously. This dual-action approach aims to enhance therapeutic efficacy and address the multifaceted nature of AD.​

 

Enhancement with non-canonical amino acids (NCAAs)

Innovative Peptide Design: For peptide-based hits, we incorporate NCAAs to improve peptide stability, bioavailability, and target affinity. This novel approach sets our peptide therapeutics apart from traditional methods, offering new standards in drug design.​

 

Computational and Machine Learning Edge

Advanced Tools: We leverage state-of-the-art computational resources and machine learning algorithms to refine hit selection, predict efficacy, and optimize lead compounds. This streamlines the drug discovery process, from identifying potential drugs to optimizing their structures for better efficacy, paving the way to preclinical readiness.​

 

Advancing Beyond Existing Aβ Pathway Inhibitors​

 

Pharmaeconomica's Approach

Dual-Action Strategy: Our strategy focuses on dual-action small molecules and peptides. Incorporating NCAAs into peptide leads represents a groundbreaking method to overcome traditional hurdles in peptide drug development, such as stability and efficacy.​

 

Data-Driven Design

Computational Precision: Our computational platform enables the rational design of compounds and peptides, including structure-activity relationship (SAR) studies. This ensures high specificity and potency against Aβ targets, relying on detailed analyses to create highly effective drugs.​

 

Preclinical Promise

Ready for Testing: We are advancing lead compounds with enhanced brain penetration and minimized toxicity, ready for rapid transition into preclinical testing. This approach promises significant advancements in AD treatment efficacy and safety, positioning our leads for preclinical success and beyond.

 

Our innovative methodologies and robust research infrastructure ensure that we are not just discovering theoretical molecules but are advancing viable candidates poised for preclinical success.

Partner with Us

Unlock the Future of Alzheimer's Treatment with PE01 & PE02:

  • Innovative Collaborative R&D: Partner with us in refining and optimizing the potential of these leads. Exploit our expertise and capabilities to achieve shared success.

  • Exclusive Opportunities: Get early access to groundbreaking research and data surrounding our portfolio, and stay at the forefront of neurodegenerative treatment innovations.

  • A Partnership with Purpose: Join our mission to revolutionize treatments for Alzheimer's and other neurodegenerative diseases. Let's combine our strengths to redefine the therapeutic frontier for Alzheimer's and related conditions.

 

Reach out to us today for exclusive collaborative opportunities and be part of the next big leap in neurodegenerative disease treatment.

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