Why Next Gen MPS Technology: Part 1 – Mind the Gap
The biopharmaceutical landscape is undergoing a transformative shift. Precision medicines—such as CRISPR technology, CAR-T cell therapies, antisense oligonucleotides, monoclonal antibodies, and antibody-drug conjugates (ADCs)—are emerging as groundbreaking treatments for diseases once deemed untreatable. These therapies promise to revolutionize how we address a wide range of conditions, from chronic illnesses to rare genetic disorders, all while offering significant improvements in both performance and patient outcomes.
However, these next-generation therapeutics also come with a unique set of challenges. They require sophisticated, human-specific testing environments to fully assess their mechanisms of action, safety, and efficacy. Yet, the current preclinical testing platforms seem to be struggling to keep up with the rapid pace of innovation in the drug development pipeline. In this first installment of our series, we’ll explore the novel therapeutic modalities on the horizon, the technologies currently used to evaluate them, and why they may not be enough to meet the growing demands of modern drug discovery. In Part 2, we will dive into the solution: the Javelin tissue chip platform and how it seeks to bridge this critical gap.
Next-Gen Drug Modalities: The Promise of Precision Medicine
The next generation of therapeutics is defined by innovative treatments that leverage human-specific cells, genetic material, proteins, and antibodies. These therapies are designed to target the root causes of diseases with unprecedented specificity, providing more effective solutions with fewer side effects. Here’s a closer look at some of these novel modalities:
Gene Therapies
Gene therapies aim to correct or replace faulty genes. These treatments include:
Antisense Oligonucleotides (ASOs), an emerging area of drug development targeting disease at its source whereby short nucleotide strands, designed to bind to specific molecules of mRNA, interfere with their downstream functions
mRNA Therapies, like the COVID-19 vaccines, which instruct cells to produce specific proteins to trigger immune responses or treat disease.
siRNA (Small Interfering RNA), which silences specific genes to regulate protein production and potentially reverse disease processes.
Gene Editing, a groundbreaking technology that allows for direct editing of the DNA with unparalleled precision.
Biologics
Biologics are large, complex molecules, often produced by living organisms, that are used to treat a wide range of diseases. These include monoclonal antibodies (mAbs) that target specific antigens or proteins involved in disease progression, and antibody-drug conjugates (ADCs) and bispecifics, which combine the targeting capability of monoclonal antibodies with the cell-killing power of chemotherapy.
While these treatments are promising, they also introduce complexities that must be understood at a deeper, more physiological level. That’s where testing and evaluation come in.
The Translational Gap: A Growing Challenge
The challenge of evaluating the safety and efficacy of these next-gen therapies lies in the inability of current preclinical testing platforms to capture the complexity and physiological relevance of human diseases. While these therapies are designed to work specifically in humans, traditional testing methods often fall short in providing accurate, predictive results.
Animal Models: Falling Behind the Times
Animal models have long been the standard for drug testing, but they’re increasingly viewed as insufficient for evaluating the cutting-edge therapies of today. Key issues include:
Lack of Human-Specificity: Animal models cannot fully replicate the human cellular and molecular dynamics necessary for accurately evaluating human-specific therapies. Essential human-only biomarkers, drug targets, and genetic sequences cannot find translational relevance in animal models.
Time and Cost Intensive: Animal studies often require significant time and financial resources with no guarantee of translational success.
Increased Regulatory Support of Human-Based Discovery: In the face of growing concerns about animal welfare and scientific efficacy, initiatives like the FDA Modernization Act (FDAMA) and the FDA Innovative Science and Technology Approaches for New Drugs (ISTAND) are aiming to phase out animal testing for certain drugs, including monoclonal antibodies. This is a clear signal that animal models are no longer sufficient for modern drug discovery, with an intention toward human-based experimental designs
Static 2D Cell Cultures: A Stagnant Solution
2D cell cultures were once a breakthrough in drug testing, but they’ve shown significant limitations in evaluating the complexity of modern therapies:
Lack of Cytoarchitecture and Microenvironment: 2D cultures fail to replicate the tissue architecture necessary for simulating in vivo-like, organ-organ communication and systemic circulation.
Limited Long-Term Viability: Chronic exposure studies are critical to assess long-term safety, but static 2D cultures often do not maintain viability over extended periods, limiting their usefulness for comprehensive studies.
Inadequate Testing Capabilities: While useful for initial screening, these systems cannot effectively simulate the range of responses to modern therapies, such as cell-based treatments or gene editing.
Current 3D Cultures (e.g. Microfluidics and Organoids): A Step Forward, But Not Sufficient
Microfluidic systems and organoid models were hailed as significant advancements, offering more physiologically relevant platforms for drug testing. However, these systems also exhibit critical constraints:
Limited Quantitative Information: Most systems are not optimized to assess a wide variety of genetic, metabolic, and biomarker activities, which are platform requirements to meet current modality evaluation needs
Short-Term Focus: Many of these platforms are designed for short-term experiments, which makes them ill-suited for chronic studies or longitudinal monitoring of therapies.
Skilled Personnel Needed: These systems often require highly specialized expertise, making it harder for pharmaceutical companies to integrate them into standard workflows.
Closing the Gap: The Need for Human-Relevant Systems
To bring modern therapeutics to the next level, we need innovative and robust technologies that provide deeper insights into human-specific responses. These systems need to be able to:
Simulate Healthy and Disease-State Human Physiology: Recreate the complex interactions that occur in human tissues and organs, whether in a fit and expected state or disordered state, something animal models and traditional cell cultures struggle to achieve.
Ensure Long-Term Viability and Elucidate Chronic Effects: Maintain functional tissues and cells over extended periods to monitor chronic exposure and late-onset side effects.
Generate Translational Data for Clinical Outcomes: Offer insights that are directly translatable to human outcomes, ensuring that therapies move smoothly from the lab to the clinic without unnecessary setbacks.
In the next part of this series, we will explore how the Javelin Tissue Chip Platform is designed to address these critical gaps in drug discovery and development. Stay tuned to learn more about how this innovative technology is poised to help researchers and pharmaceutical companies close the gap between early-stage research and successful therapeutic outcomes.
In Part 2, we'll delve deeper into the specifics of the Javelin tissue chip platform and how it's helping the biopharma industry meet the growing demands of next-generation therapeutics.