Tempo Bioscience: Spearheading Drug Discovery and Development With Ipsc Models

CIO VendorAngela L. Huang PhD, Founder & President Back around May of 2013 (when Tempo Bioscience was founded) Angela Huang, identified a persistent scientific need existing in the drug discovery and development industry. Preclinical scientists in the industry needed human cell models that were phenotypically more relevant to human health than animal models. However, traditional mouse models or immortalized cell line based technologies that existed couldn’t assay drug candidates to answer questions about relevant human genetic pathways during discovery and development. Her penchant for problem-solving and the fervor to provide the industry with a relevant technology drove Angela to conceptualize Tempo Bioscience. Being the Founder and President of the company, she says, “We wanted to combine the different technologies into a system of patient relevant models: biosensor reporters and human adult stem cells.” The following years witnessed Tempo Bioscience delivering iPSCs based biosensors— enabling technologies for preclinical drug discovery and development, biobanking, and biomarker development in an efficient and synchronized manner, and also served as valuable tools for pre-clinical pharmacology, cellular toxicology, novel compound discovery, and validation. Angela developed, patented, and commercialized Tempo’s core technologies and together with Tempo’s team, the enabling technologies became available to scientists globally.

"At Tempo Bioscience We Strongly Believe In The Advantages Of Using Ipsc-Based Models For Target Validation, Preclinical Drug Discovery And Development, And Biomarker Discovery"

Tempo Bioscience’s iPSCs and iPS-derivative cell types can be used by scientists in a pre-clinical setting representing patients’ phenotypes “in a dish” and creating companion-diagnostic biomarkers. “At Tempo Bioscience we strongly believe in the advantages of using iPSC-based models for target validation, preclinical drug discovery and development, and biomarker discovery,” states Angela. Tempo Bioscience’s genetically relevant and multi-donor iPSC models can validate screening, discovery, and preclinical development data. As a whole, the models serve as “pre-clinical trials” to evaluate promising drug candidates. When utilized appropriately, this new process can streamline pharmaceutical development.

Further, iPSCs can also be leveraged to develop a variety of disease models (from cancer models to rare diseases), which makes it easier for the scientists to discover and develop drugs. Tempo Bioscience follows a unique idea to expand on the concept of biosensors and iPSC model to benefit the industry. At its core, Tempo Bioscience focuses on intensiometric biosensors that can report a variety of functionalities such as cationic flux, cytotoxicity or mitochondria activities by providing image-based and kinetic-based analysis tools.
Another highlight of Tempo Bioscience, as Angela mentions, is their capability to reprogram patient blood or skin samples into iPSCs using the non-genetic method without using vector systems or viral carriers, which ensures that the cells will not turn tumorigenic or suffer from chromosomal rearrangements.

An Innovative Drug Discovery and Development Model

Many applications in the biotech and pharmaceutical industry have traditionally relied on human primary cell types and immortalized cell lines. “A major advantage of iPSCs is that they can be derived from a variety of 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,” says Angela. The diversity and limitations of donated primary tissues have often been a time-consuming and rate-limiting factor when scientists try to procure primary samples. Furthermore, donors’ primary cells usually come from only one or two donors at a time during the procurement process, and depending on the number of independent biorepositories needed for a procurement project, variabilities can be found between sample collections and processing.

We Build Models Leveraging The Concept of Ipsc and Combine It With The Biosensors To Provide Scientists With More Assay Options For Validating Drug Targets And Conduct Efficacy Evaluation

Given these challenges to acquire primary tissues and cells, immortalized cell lines are typically used as a primary source for preclinical screenings and non-animal-model studies in the industry. Although the immortalized cell lines present as a cost-effective cell source for the over-expression of targeted genes-of-interest in a study, they are often derived from immortalized tumorigenic cells of human or rodent origin. Furthermore, gene expression networks and profiles found in tumors do not reflect the same gene expressions found in terminally differentiated human cell types such as neurons, osteoblasts, kidney, liver, or esophageal, to name a few. Unlike primary cells and immortalized cell lines, Tempo Bioscience’s iPSCs from patients manifest their disease phenotypes and are genetically defined. This also leads to reflective cellular phenotypes which are useful for drug mechanisms and target gene mechanism discoveries. Variations of the disease manifestations aid in drug candidate validation when a patient’s clinical phenotype and drug candidate responses correlate in-a-dish. iPSC lines from patients’ donated somatic cells (blood or skin) recapture aspects of their phenotype. “This variability may seem daunting to the researcher who is used to immortalized cell lines, where one consistent line is the expected norm,” mentions Angela. “The variability can serve to represent drug candidate responses in a population of individual patients.” This generates a “patients in-a-dish” model in order to determine the effects of drug candidates experimentally.

Another advantage of using Tempo Bioscience’s donor and patient-derived iPSCs is an ability to identify novel drug targets that are clinically relevant. Mutations discovered from patients using genomic sequencing and mapping methods have yielded many potential drug targets.

Covering all Grounds

Aside from engineering iPSC and iPS derivative models for evaluating drug candidates—small molecules, biologics, or gene therapy—Tempo Bioscience’s iPSC models provides other useful functions such as biomarker discovery and streamlined procurement.

iPSC and iPS-derivative models simplify procurement challenges in terms of streamlining standard operating procedures (SOPs). Reprogramming donors’ samples into iPSCs serve as a normalizing step for Tempo Bioscience for guaranteeing better consistency of cryopreserved iPSCs and iPS-derived cell types. “A biomarker is a unique identifier of a patient population’s disease characteristics. It can be defined as a chromosomal marker, a gene expression pattern, a genetic variant, a genomic structural feature (such as rearrangements or translocations), a cellular phenotype, an aberrant tissue pathology, or a bodily excretion product,” says Angela. “Traditionally, biobanks have been sought after for their collected donor samples such as bodily fluids, skin, or tumor biopsies. However, the challenge is to gather appropriate cohorts and their relevant tissue samples and cell types for drug target validation.” This is a critical step in the preclinical drug development process. By obtaining relevant cell types, Tempo Bioscience validates whether traditional in vitro models applied during the discovery process truly reflect the disease state.

Toward an Empowered Future

With customized biosensor assay systems, Tempo Bioscience’s cell models allow scientists to use human cells where an animal model doesn’t exist. Further, the scientists are also enabled by the biosensors to operationalize assay and help them validate their combined drug target in a pre-clinical setting.

The uniqueness of Tempo Bioscience stems from its innovation and customization aspects. The company can build patient-relevant assay and cell models according to the clients’ specific needs— whether they want a mixture of cell types or putting different layers together in a 3D spheroid.

Having established a strong presence in the bioscience industry by delivering iPSC-based solutions, Tempo Bioscience aims to continue the expansion of the biosensor and biomarker reporters. The company announced the launch of its central nervous system (CNS) product line of human cell types for in vitro research and development (R&D) and chemical testing in 2014 (and continue to add new products in non-CNS areas between 2015-2018) and going ahead will be extending and delivering its offerings to help research organizations in different diseases, assay applications, and grinding clinical trial in a dish. They will also be working to transition the state of their technology from a niche provider status to mainstream in the near future.

According to Angela, there are significant scientific and manufacturing challenges ahead in providing iPS-derived cell therapy products as therapies for patients. As a set of discovery and preclinical tools, iPSCs and their derivative cell types provide important resources for all drug discovery scientists. “I anticipate that the international iPSC community will discover new drug candidates and biological insights to further understand the unique mechanisms of different human diseases in the coming years. Research groups look for better drug targets with every passing hour, and we will be there to help them with the iPSC model,” she informs. “By using the right design of patients versus healthy donor in a controlled manner, we have been streamlining the drug target and will continue to improve our solutions in the years to come.”