VIABLE, REPRODUCTIVE RESULTS

Phase X® is a novel drug development paradigm that generates predictive human data at the preclinical stage. With Phase X®, AnaBios researchers can test potential drug candidates using ex-vivo human tissue-based and in-vitro cell based assays. Combining novel human tissue preservation methods, advanced shipping logistics and innovative tissue interrogation techniques, AnaBios continues to shape the future of translational science and drug discovery.

With access to a vast network of hospitals and transplant centers across the United States, Phase X® is scalable to effectively support preclinical drug discovery programs. Our proprietary technology enables us to ethically recover functional human tissue to ensure consistently viable and reproducible results.

USING HUMAN TISSUE FOR TARGET IDENTIFICATION AND VALIDATION

Access to functionally viable human tissue samples from healthy and diseased donors allows AnaBios to help researchers in their discovery of novel molecular targets. The gold-standard quality of tissue samples recovered utilizing our  unique technology, combined with our proprietary laboratory equipment, enables the creation of reliable data for gene expression profiling[1][2], proteomics[3], metabolomics and system biology parameters[4].

Because our tissue samples are never fixed or frozen during the recovery process, Phase X® allows scientists to perform human ex-vivo pharmacology in preclinical settings and study drug effects in humans before advancing to clinical trials. This approach bypasses the traditional obstacles encountered when relying solely on animal models, where cross-species differences complicate the interpretation of data and extrapolation of findings to clinical settings. In addition, unlike stem cell-derived models, Phase X® offers the advantage of authentic adult human cells and tissues to provide a higher level of correlation with human clinical outcomes.

LEAD OPTIMIZATION AND CLINICAL CANDIDATE SELECTION

Phase X® ensures that lead optimization accurately enhances drug safety and efficacy profiles in humans—not just animal models. Our strategy maximizes the probability that preclinical data will successfully translate during clinical development. Clinical candidate selection based on reliable, predictive human cell and tissue data provides the best opportunity for successful clinical development, thus avoiding the risks posed by species differences between animal models and human patient populations.

PROVEN VALIDATION OF PHASE X®

Phase X® has proven to be successful in assessing drug-related cardiac safety risks of potential drug candidates. The potential for a drug to induce dangerous arrhythmias, or changes in cardiac contractility, can be evaluated with high accuracy in tests run on isolated adult human primary cardiomyocytes.

Validation studies conducted with more than 50 clinical compounds have shown that AnaBios’ human cardiomyocyte-based platform has a predictivity of compound pro-arrhythmic risk of well over 90% [5]. In addition, Phase X® is currently being utilized by numerous pharmaceutical companies across the globe to support their medicinal chemistry efforts and ensure that unwanted cardiac activities are identified early in the drug development process.

Recently, the U.S. Food & Drug Administration (FDA) awarded AnaBios a contract to obtain critical translational data from our ex-vivo human cardiac platform, signed a research collaboration agreement with the company to focus on human primary cardiomyocytes and has awarded AnaBios a grant to develop a biomarker with its cardiomyocyte platform.

ACCESS TO DISEASED TISSUE

With access to diseased human tissue and organs, AnaBios has enabled its clients to conduct ex-vivo pharmacology studies on cells and tissues recovered from consented donors that were affected by heart failure, atrial fibrillation, diabetes and other diseases. The value of this is demonstrated by the high correlation between Phase X® data and human clinical responses. In another example, we performed studies on neurons isolated from consented donors suffering from various forms of chronic pain. These studies not only confirmed a drug’s activity in humans, but also helped identify specific pain indications that may be most effective.

REFERENCES

[1] “Comparative Transcriptome Profiling of the Human and Mouse Dorsal Root Ganglia: An RNA-Seq-Based Resource for Pain and Sensory Neuroscience Research,” Pain (2018), Ray, et al., doi: 10.1097/j.pain.0000000000001217

[2] “Quantitative Differences in Neuronal Subpopulations Between Mouse and Human Dorsal Root Ganglia Demonstrated with RNAscope in Situ Hybridization,” Pain (2020) Shiers, Klein & Price,  doi: 10.1097/j.pain.0000000000001973

[3] “Comparison of the Rat and Human Dorsal Root Ganglion Proteome,” Scientific Reports (2018), Schwaid et al. doi: 10.1038/s41598-018-31189-9

[4] “Utilizing Human Precision-Cut Lung Slices to Study the Impact of Persistent Hypoxia on the Contractile Responses of Small Intrapulmonary Arteriole,” ATS Conference 2020, Bai, Oldham & Ai,  https://doi.org/10.1164/ajrccm-conference.2020.201.1

[5] “Adult Human Primary Cardiomyocyte Model for the Simultaneous Prediction of Drug-induced Inotropic and Pro-arrhythmia Risk,” Frontiers of Physiology (2017), Nguyen et al.,  doi: 10.3389/fphys.2017.01073