There is a growing need to address the high failure rate of drug candidates as they progress through clinical trials. Altis Biosystems aims to bring its technological advances to the forefront. This will enable the drug development process to more effectively translate results from preclinical experiments to late-stage clinical trials. But how does Altis envision the future of the pharma industry as they tackle these challenges? Through innovative approaches, Altis aims to reshape this future.
Breaking the Conformity of Inadequate Testing Platforms
The struggle for companies to successfully transition promising preclinical research to late-stage clinical trials has existed for decades. Altis envisions the future of the pharma industry by addressing these challenges head-on. Roughly 85–90% of drug candidates either display toxic side effects or fail to show efficacy once tested in real-world conditions. Rectifying this issue would lead to a massive growth in efficiency for pharmaceutical companies. It would reduce costs and free resources to invest in other innovations. It is here that Altis Biosystems can enhance the robustness of preclinical research. By doing so, they improve the quality of predictive models. Consequently, researchers can have increased confidence in the viability of drug candidates as they progress into clinical trials.
Typically, preclinical studies are conducted using either tumor tissue cell culture lines or whole-animal studies. They only include limited experiments employing primary human tissues. By underutilizing primary human tissues, it is unsurprising that many of these experiments do not accurately reflect human biology and disease states. They also do not translate well into clinical studies. We believe that, with an improved platform to undertake these initial experiments, developers can move forward with greater conviction concerning early results.
In the past, experts may have balked at the cost and difficulty of using primary human tissue. This tissue has limited viability; it needs multiple donors, resulting in inconsistency; and has a poor proliferative capacity. However, with new stem cell technologies, it is now possible to use primary human stem cells. Induced pluripotent stem cells (iPSCs) can also be used to create cell lines and tissues in the lab.
iPSCs are a cutting-edge technology with a wide range of applications. However, they have drawbacks in achieving a physiologically accurate intestinal model. How Altis envisions the future of the pharma industry includes overcoming such hurdles. Donor cells can be easily obtained. However, they must be genetically modified to create a stem cell bank, which must be differentiated under very strict protocols. This involves complex and time-consuming logistics to create the desired lineage(s) that also possess a fetal gene expression pattern.
Human intestinal stem cells, by contrast, are already epigenetically modified to limit them to a range of differentiated types. Altis envisions a future in the pharma industry where these cells form the appropriate diversity of intestinal epithelial cell types. As such, the Altis system uses primary human stem cells to generate a platform. This platform mimics real human intestinal biology far more accurately than models using iPSCs.
Unpacking the Complexity of In Vitro Intestinal Models
Most human diseases involve a combination of effects from multiple environmental factors and multiple genes. This complexity is more pronounced with gastrointestinal studies, which must also account for the microbiome. Altis envisions the future for the pharma industry by addressing these complexities. The future of increasingly accurate intestinal models is dependent on identifying and replicating several specific features. These include the selection of primary human tissues exhibiting the target disease or disease susceptibility. They also include co-culturing additional relevant tissues and accounting for the microbiome. Additionally, the anaerobic conditions present in the lumen must be included, as well as modeling the physiological mucous layer. As we model each of these factors more accurately, we will move toward an ever-more refined and effective testing platform. This will enable consistent translation of preclinical results to real-world successes.
Our current foci are threefold. Firstly, to expand our possible tissue variety, creating a biobank of donor stem cells from individuals with intestinal related diseases. Secondly, replication of the anaerobic conditions of the intestinal lumen. Finally, to pursue a model that recapitulates the intestinal mucous layer. We appreciate the immense difficulty of the task ahead. Our vision will require uniting experts across multiple disciplines. This challenge may not be simple, but it is certainly worthwhile.