Angela L Huang PhD, Founder and President
Modern drug discovery is a capital-intensive process involving steps before an ordinary compound becomes a therapeutic agent. It consists of identifying screening hits, biologics, and optimization of those hits to increase the affinity, selectivity, efficacy/potency, and metabolic stability. Despite advances in technology and understanding of biological systems, new therapeutic discovery still needs fine-tuning in order to fast track the entire process and enhance the speed-to-market of novel drugs.
To this end, the delineation of etiology and pathophysiology of drug discovery requires a physiologically relevant experimental model of disease that accurately recapitulates the respective pathophysiology and clinical manifestations. Often, researchers employ animal modeling— most frequently transgenic rodent or other animal models —and immortalized cell lines as a preclinical efficacy model for their research and drug discovery & development programs. However, time and again, these programs fail to translate the results from animal models to patients. And, due to different biological responses, animal models often fail to translate the success during patient relevant clinical trials as they do not reflect the same disease phenotype or pathophysiology as humans. On the other hand, the immortalized cells divide indefinitely; they are artificially engineered in the lab and sometimes express unique gene patterns not found in the normal cells. Thus, researchers need a patient relevant model of diseases that effectively recapitulates the pathophysiological mechanisms during research and drug discovery and development programs. This is where California-based biotechnology company, Tempo Bioscience comes into the limelight.
Tempo Bioscience develops human inducible pluripotent stem cells (iPSCs) that facilitate drug discovery and development, biobanking, and biomarker development programs. “We offer more than 22 iPSC-based cell types for different diseases and provide scientists with a variety of combinations to creatively use the cells and model a particular aspect of a disease,” states Angela L Huang PhD, Founder and President at Tempo Bioscience. These cell models enable researchers to evaluate promising drug candidates during preclinical trials and pave the way for clinical development.
Established in 2013, the cornerstone of Tempo Bioscience was laid when Angela discovered a pressing need for cell models that were phenotypically more relevant to human diseases for preclinical scientists in the drug discovery and development industry. Angela mentions, “Traditionally, scientists in the last three to four decades were either using immortalized cancer cells or rodent models for preclinical trials. Nevertheless, in the end, humans are neither big mice and nor immortalized cell lines. So, we wanted to have a patient-relevant set of tools to better understand biology and mechanism of drugs before they eventually get into clinical trials.” Thus, she developed, patented, and commercialized Tempo’s core technologies to help scientists answer questions pertaining to relevant human genetic pathways during drug discovery and development.
Delivering Distinctive Advantages
We offer more than 22 iPSC-based cell types for different diseases and provide scientists with various combinations to creatively use the cells to model a particular aspect of a disease
Tempo Bioscience’s iPSC models can be derived from various donors—healthy donors, patients, and extended family members of patients. These donor-derived iPSCs serve as an indispensable resource for modeling disease phenotypes in-a-dish. They can be further reprogrammed into various lineage-specific cell types such as neurons, melanocytes, hepatocytes, kidney proximal tubules, and microglia. Furthermore, iPSCs and iPSC-derivatives can be cultured as spheroids and organoids (mini-organs). In the lab, cells are typically grown as a 2D monolayer, but many cell types can be adopted into 3D spheroid models to represent their native tissue environments better. Depending on the disease model, 3D spheroids can be further differentiated and engineered into organoids (mini-organs).
The most significant advantage of using iPSC-based cell models is, unlike primary cells and immortalized cell lines, iPSCs from patients are genetically defined and manifest their disease phenotypes appropriately. iPSCs generated from donors, patients, and family members preserve their entire genomic background information. Therefore, their cellular phenotypes are reflective and valuable for drug mechanisms and targeted gene mechanism discoveries. Further, iPSC-derived cell types can also reflect patients’ disease severity, allowing researchers to choose the appropriate cohort to determine the effects of a drug candidate. “Scientists can learn a lot about clinical outcomes in terms of toxicity, safety, and efficacy from cells in vitro using iPSC-based cell models,” says Angela.
Another advantage of using donor and patient-derived iPSCs is its ability to identify novel clinically relevant drug targets. Scientists have yielded several potential drug targets through mutations discovered from patients using genomic sequencing and mapping methods.
Notably, the iPSC-based cell models have been touted as a novel autologous and allogeneic cell source for cell replacement therapy for several degenerative diseases, including Alzheimer’s, ALS, kidney deficiencies, Parkinson’s, and rare cancer, as well as many orphan disorders that have Mendelian inheritance traits.
Along with iPSC-based cell models, the company also offers Phenotypic cell-based and target-based assay systems using Tempo Biosensors, which are intensiometric fluorescent reporters of LIVE-cell imaging and reporting of cell-based activities in real time. They help researchers answer questions concerning pain, inflammation, and cytotoxicity during the drug development processes.
“We offer innovative assay solutions to help scientists evaluate their candidates and prioritize their project pipelines, and move forward in their preclinical development programs,” informs Angela. Further, using iPSC and iPSC derivative cell models, Tempo Bioscience also helps in biomarker identifications and validations – a unique identifier of a patient population’s disease characteristics.
A Peer-to-Peer Approach
Scientists can learn a lot about clinical outcomes in terms of toxicity, safety, and efficacy from cells in vitro using iPSC-based cell models
Unlike other companies that undertake standardized marketing campaigns, Tempo Bioscience takes a different route and engages with scientists using a peer-to-peer strategy to understand their specific requirements before delivering its solutions. Angela illustrates an instance where the company was tasked with developing cell models for drug candidate validation studies associated with neuropathic pain. As researchers struggled to find an appropriate cell model for their drug development program, Tempo Bioscience worked with scientists to design assays using its proprietary Tempo-iSenso™ and Tempo-iSchwann™ products, enabling them to understand the efficiency of their drugs. Additionally, with the company’s assays and iPSC cells, scientists were also able to evaluate additional compounds and their potential clinical impacts on patients. “We have received validations (from clinical data) from the scientists that our assays and iPSC models have been a valuable asset for them in establishing the efficacy of drugs during drug development programs,” extols Angela.
As more and more scientists testify to the efficacy of iPSC-based cell models, Tempo Bioscience is witnessing significant traction for its products + services in the drug discovery and development arena. Along with new clients, the company is also helping several returning clients promptly bring novel therapeutic drugs to the market. Besides, upon clients’ request to deliver cell models from a multitude of patients and donors, the company scales up the production of its iPSC-based cell models.
Moving forward, Tempo Bioscience aims to launch more innovative complex models for the CNS, Oncology, and other complex diseases. “We are developing oncology-relevant cell-based models to look at tumors and we are working on designing new models for evaluating the Blood-Brain-Barrier function for all drug candidates,” mentions Angela. As animal models have become difficult to access with the onset of the Covid 19 pandemic, the company is collaborating with scientists to help them move away from immortalized and animal-based models to more potent iPSC-based cell models during their drug discovery and development programs. “Trust patient-relevant cell models, they are really helpful in validating your drug development processes. And, what we have learned from past experiences is that if you design the right assay using these iPSC derived cells, they will help you with the preclinical and clinical trial, design, or other types of validation studies,” concludes Angela.