Founded in 2014 and headquartered in San Diego, CA, iXCells Biotechnologies is a cell biology and cell technology company specializing in pre-clinical drug discovery solutions. iXCells provides primary cells and iPSC derived cells, custom iPSC services, and functional bioassay development and execution, among other products and services.
In this interview with Nianwei Lin, Co-Founder and President of iXCells Biotechnologies, we discuss the company’s product pipeline, innovative drug discovery solutions, CRO services, and its future goals.
Interview with Dr. Nianwei Lin, Co-Founder and President of iXCells Biotechnologies
Cade Hildreth: What was your professional path before you founded iXCells Biotechnologies?
Dr. Nianwei Lin: I received my Ph.D. degree in genetics from the College of Medicine at the University of Florida, where I studied apoptotic cell death using Drosophila as the genetic model. In 2011, I started my postdoctoral training at Sanford-Burnham Medical Research Institute, where I went on to study the self-renewal and differentiation control of embryonic stem cells and focused my research on long noncoding RNAs (lncRNA) mediated regulation.
I joined Drug Safety Research & Development (DSRD) team at Pfizer in August 2014, with my work focused on effects of lysosomal dysfunction on membrane trafficking and signal transduction, as well as the implication in toxicity, efficacy and resistance development. Because of my background in academic and industrial settings, I have an enthusiasm for translational research in the development of disease relevant drug discovery strategies with the evolving new technologies.
Cade Hildreth: When did you found iXCells and why?
Dr. Nianwei Lin: In light of the growing and unmet needs in development of disease relevant cellular models in the drug discovery industry, my partners and I founded iXCells Biotechnologies in December 2014 in San Diego, a hub for biotech and pharmaceutical research and innovation. iXCells is a cell biology and cell technology company specialized in providing innovative pre-clinical drug discovery solutions with the focus on disease relevant cellular models enabling technologies and services to the academic, biotech and pharma communities to accelerate the pace of drug discovery.
Cade Hildreth: Why did you choose to focus the company specifically around iPS cell technologies?
Dr. Nianwei Lin: With the ever-evolving technologies in iPS cell and genome editing, we truly believe that there is an emerging blue ocean associated with these technologies in a variety of research areas including toxicity testing, drug discovery, disease modeling, tissue engineering and cell therapy to treat degenerative diseases within the context of precision medicine, hence mitigating the risk of graft versus host disease.
Cade Hildreth: What unique science and technology platforms has iXCells developed, and what are the advantages of utilizing these cell types in research?
Dr. Nianwei Lin: There are two major Disease-in-a-dish platforms developed here at iXCells: primary cells isolation directly from normal or diseased donors, and functional validated human cells derived from iPSC engineering.
In contrast to cell lines, primary cells which are isolated directly from tissues, have normal cell morphology and maintain many of the important markers and functions seen in vivo. Therefore, the data obtained from using primary cells is more relevant and reflective of the in vivo environment. However, there are disadvantages of primary cells, including the finite lifespan and limited expansion capacity, and highly variable donor phenotypes, making them a major limiting factor for some research.
In addition, some cell types are extremely difficult to obtain from the donors or patients with certain disease conditions which may be a limiting factor in scaling research studies. For example, it is almost impossible to isolate neurons from the patients with neurodegenerative diseases.
On the other hand, iPSC-derived cells are perfectly complementary to primary cells in many aspects. With the infinite expansion capacity, iPS cells provide unlimited resources for various applications such as disease mechanistic studies, phenotypic screening, personalized medicine and cell therapy, hence represent a more reliable source and consistent quality of cells needed for scaling research studies and screening workflows.
Also, by reprogramming the skin or blood cells, we can easily get unlimited patient-derived cells and further convert them into the terminally differentiated cell types, such as cardiomyocytes, motor neurons, GABAergic neurons, astrocytes, microglia, liver cells, etc.. Finally, with the combination of genome editing technology, we can generate isogenic lines with the identical genomic background except for the disease-causing mutations, which are valuable tools for disease mechanism studies and phenotype-based drug screening.
Cade Hildreth: What types of products does iXCells offer?
Dr. Nianwei Lin: We offer our customers access to high quality primary cells, normal and diseased iPS cell lines and iPSC-derived cells. The optimized culture media are also available for most of our cell lines with detailed culturing protocols that enable our customers to establish the success culture. We currently offer more than 70 primary cell types covering several major cell categories, including fibroblasts, endothelial cells, epithelial cells, PBMCs, immune cells, muscle cells, neuronal cells, liver cells, stem cells, etc..
Our iPSC derived cell lines include motor neurons, cortical neurons, GABAergic neurons, skeletal muscle cells, astrocytes, dopaminergic neurons, etc.. In 2016, iXCells launched the first-to-market iPSC-motor neuron products. With a single culture medium, we provide a highly pure, functional validated and ready-to-use neuronal culture to our clients for their applications in neuron science and drug discovery. We are also developing a growing list of disease panel for iPS cell lines and iPSC-derivatives, with the focus on neurodegenerative diseases.
Cade Hildreth: What types of CRO services does iXCells offer?
Dr. Nianwei Lin: iXCells offers a variety of customized CRO services to meet needs in different stages of pre-clinical research. We offer our clients custom isolation of primary cells, such as fresh PBMC isolation which is available to our customers in southern California. We also help our clients develop their disease models with our services in iPSC generation (integration-free), genome editing and directed differentiation. In addition, many of our contracted projects involve further characterization of the developed disease models and bioassays, such as immunoassays, cytotoxicity, neuronal assays, image-based analysis, etc..
Finally, with iXCells’ expertise in personalized cellular models, we have increasing service requests for Antisense Oligonucleotide (ASO) drug screening. Our service offerings cover the patient-specific cell line engineering, large scale cell production and automated screening, providing our customers with a front-to-back solution for their ASO drug discovery.
Cade Hildreth: What trends are you seeing within the iPS cell sector and how is iXCells rising to meet them?
Dr. Nianwei Lin: We have been witnessing a fast-growing interest in the field of in vitro disease modeling using iPSC-derived human cells during the past decade. Many of our clients from big pharma are exploring the applications of innovative cellular models for phenotypic screening. Cells derived from isogenic lines are also widely used to study the mechanisms of some complex diseases, such as ALS, Alzheimer’s disease, Autism, etc. We are seeing more applications with co-culture of multiple cell types, or iPSC-derived organoids as a unique system to examine mechanisms ranging from organ development to homeostasis and disease. In one of the collaborations with our customer, we developed iPSC-motor neurons and skeletal muscle cell co-culture system and explored the potential application in the Neuromuscular disorder (NMD) using high-content imaging analysis.
Another trend in iPSC sector we are seeing is the emerging applications in personalized medicine. With the recent advancement of RNA biology technologies in therapeutics, there is an explosion in the field of Antisense Oligonucleotide (ASO) drug development using patient-specific cells. iXCells is currently working with Timothy Yu’s team at Boston Children’s Hospital to utilize a patient-derived cellular model to develop a treatment for an Orphan Neurogenetic Disease.
It requires a synergy of scientists, entrepreneurs, and regulatory professionals to tackle the rare diseases and help millions of patients and their families. With our strength in iPSC engineering and translational research, we are developing an innovative business model that can contribute to the N-of-1 solution for the rare disease community from discovery through regulatory approval.
Cade Hildreth: While iXCells is serving the preclinical research community, what do you see as the future of iPSC-derived cell therapeutics?
Dr. Nianwei Lin: As mentioned, iXCells is mainly focused on the pre-clinical market at this stage. However, we are developing our strategy map to expand our served markets into iPSC-derived cell therapeutics in the future.
In a joint effort to develop motor neuron replacement therapy for amyotrophic lateral sclerosis (ALS), iXCells was collaborating with the Lu lab at UCSD and the Chen lab at Beijing Institute for Brain Disorders to test the iPSC-motor neurons in ALS animal models (Liu et al., Neural Regen Res. 2022). The highly pure, functionally validated, and ready-to-use hiPSC-MN progenitor cells were generated using iXCells’ proprietary method.
We transplanted hiPSC-MN progenitor cells into the spinal cord ventral horn in immunodeficient rats. Animals survived 3 or 6 months post transplantation. Transplanted hiPSC-derived MN progenitors labeled with GFP survived well in the host spinal cord, and the engrafted cells could differentiate into mature ChAT+ MNs, indicating preservation of MN fate and continuous maturation of MNs in vivo.
Additionally, transplanted MNs extended into a large number of nerve fibers following the motor axon tracts along the white matter of the spinal cord. Furthermore, there was no tumor formation or any detectable expression of classical tumorigenic factors 6 months after transplantation, indicating good safety. In the future, we will transplant hiPSC-MNs into the SODG93A transgenic and WT monkeys to study the potential of MN replacement therapy for ALS.
Aligned with our strategy of entering the cell therapy arena, there are two approaches to enable our cell therapy production capabilities. One is to partner with CDMO(s) that are specialized in cGMP cellular products and services, the other is to establish our own cGMP iPS cell development and production facility, organically, or through M&A. We are investigating both strategies while continuing to rapidly expand our RUO market share.
Cade Hildreth: What are your five-year goals for iXCells?
Dr. Nianwei Lin: We have a 3-step growth plan for iXCells in the next 5 years. The first is to continue steering the company into the scalable growth or hypergrowth phase by restructuring our business and expanding teams, recruiting executive management team members, increasing market visibility and brand building, and implementing a cloud-based ERP solution that will integrate workflows to create operational efficiencies. The second phase includes strategic collaboration with big pharma and biotech companies in drug discovery and maintaining our leading position in iPSC disease modeling.
We are planning to establish the comprehensive solution for ASO drug screening for personalized medicine, covering the ASO design, synthesis, and large scan screening. The company has established relationships with some of the pioneers in the field of rare disease, and we wish to become influencers as a commercial player in the coming years. Finally, as a part of the long-term corporate development plan, iXCells is interested in expanding its capacities in cGMP cellular development and production, and iPSC-derived cell therapy by entering into strategic partnerships or through M&A transactions.
Cade Hildreth: What separates iXCells from other iPSC product and service providers?
Dr. Nianwei Lin: We consider ourselves not only as a product and service provider, but also a highly valued partner in drug discovery and innovation. Firstly, our position as a cell biology company allows us to offer applications experience on our product catalog and often times facilitates our assay service offerings. Having approximately 50% of our employees on our scientific team as Ph.D. level scientists enables us to actively and heavily engage with our customers to provide strategic planning and proof of concept (POC) study design. This flexibility and opportunity to provide collaborative discussions is a significant differentiator.
Besides the fee-for-service terms, we are also open to risk-sharing or co-development opportunities, enabling us and our clients to develop complex assays that advance their drug discovery efforts. In such a scenario, our clients can utilize the newly developed platforms to screen for their candidate drugs, and iXCells is allowed to license the platforms to other drug discovery firms under certain conditions.
Besides the cutting-edge sciences, client-centricity has been embedded in our company culture. Our scientific team are easily reachable and accountable. From standard cell-based assays to much more advanced in vitro drug development of neurodegenerative diseases, we are always ready to collaborate. We stand by our clients’ side from strategic planning and study design to experimental execution and data analysis. iXCells has very good customer retention rate and we have become a preferred service/product provider of many organizations including top ranking pharmaceutical companies.
Cade Hildreth: What types of partnerships or collaborations would iXCells be open to considering?
Dr. Nianwei Lin: We offer multiple partnerships and/or collaborations terms to meet the different needs at different stages of drug discovery. For CRO services with established protocols and predictable deliverables, we have fee-for-service terms for our customers. We also provide full-time equivalent (FTE) services to customers who wish to have more flexibility during their POC studies.
In addition, for more complex assays that requires significant R&D efforts, iXCells will first evaluate the customer’s request internally. If the services can spawn new products or bioassays which align with company’s commercial interest, we will propose the risk-sharing terms for co-development of such iPSC-derived cells or assay platforms.
For our catalog products, we are open to collaboration with OEM or CDMO partners. We already have many channel partners located in several major global markets and we will continue to expand our partner network to reach more end users of our products and services worldwide. We offer flexible terms and conditions with our partners that fit with their business logistics and targeted markets.
Finally, we are interested in exploring potential partnerships, collaborations or licensing arrangements that can help iXCells Biotech expand access to new products and/or services that benefit our customers by providing innovative solutions for their cell-based applications.
Cade Hildreth: How can people get in touch with you or learn more about iXCells?
Dr. Nianwei Lin: If you are interested in our offerings at iXCells, feel free to follow our LinkedIn page. You can also find more information in our website www.ixcellsbiotech.com regarding our products, services, company news and career opportunities. Finally, I am happy to be connected through my LinkedIn account to expand my professional network.