AxoSim is honored to welcome Edward “Ted” Spack, PhD, as its new Executive Director of Research and Development. Ted brings more than 30 years of start-up biotech experience, including co-founding a biotech and mentoring local SF Bay area and international entrepreneurs on innovation and biotech management. He also led a multi-institutional translational science consortium (Stanford, UC Berkeley, UCSF, UCSD, SRI International) and managed an innovative grant program developed by the National Multiple Sclerosis Society. Prior to working in biotech, Ted received his PhD in cellular immunology from The Johns Hopkins University and completed a postdoctoral fellowship at Stanford University. AxoSim’s marketing department had the pleasure of taking time for a Q&A with Ted.
What are you most looking forward to in your new role as Executive Director of Research & Development?
I have already enjoyed working with the management and scientists at AxoSim, and in my expanded role I will have an increased opportunity to support communication and coordination between the business and science sides of the company. The accomplishments to date of the company at this stage in its development are truly impressive, and as AxoSim enters its next phase of growth, building on a solid foundation of success, I look forward to adding my experience in guiding early-stage companies and in building product value. Although there is much we can do on our own, key partnerships with academic experts and pharma partners will expand our impact. Several key relationships are already well established, and I look forward to contributing my experience in project and alliance management, as well as increasing our interactions with the scientific and business communities, to maximize the value created by these partnerships. In the short run, it will be exciting to thoroughly characterize the omics expression of our NerveSim® cells through their stages of outgrowth and activity, prioritizing current targets and potentially identifying new ones. I am also looking forward to working with our BrainSim team to build a solid model of human nerve demyelination and remyelination.
How will your past experience help you in this role and ultimately the company?
I developed a passion for early-stage companies ever since joining my first start-up biotech out of my post-doctoral fellowship at Stanford University. In my initial biotech experience I led a therapeutic for Multiple Sclerosis from discovery to Phase I clinical trial, gaining experience in the stages of early drug development. I have since held senior positions in several start-up biotechs, including one I co-founded as an academic spinout targeting neuroinflammation. These experiences taught me valuable lessons in the importance of team alignment and identifying the critical paths of product and company development. AxoSim has a very strong technical and management team working well in sync, and as the company grows and faces new challenges, I will contribute my experience in managing science and supporting the interactions and growth of its key resource- its people. I have applied this experience in mentoring companies and scientists through several roles in my career. While at SRI International, in addition to helping to build the immunology and biodefense programs and leading business development in the Biosciences Division, I ran a drug discovery and translational development consortium that included Stanford, UC Berkeley, UC San Francisco, and UC San Diego to support the maturation and partnering of early-stage projects. As Managing Director of a National Multiple Sclerosis Society public/private collaborative grant program with EMD Serono, I worked with my pharma counterparts to identify and guide novel programs in MS therapeutics. I have mentored early-stage companies in California and Canada through the California Life Sciences Institute FAST program, and have also taught international start-up companies and academics in Chile, Finland, and Japan through the SRI Innovation workshop. My business development experience includes in-licensing and out-licensing preclinical programs and providing alliance management on a Phase III clinical drug, now approved for peripheral T cell lymphoma. I will draw on this experience to help manage and expand external partnerships with key academic leaders and pharmaceutical companies, especially in areas of peripheral neuropathy and pain. In addition to these external activities, I will also work with our management team and staff to maintain a positive and productive company culture.
What excites you about the work being done at AxoSim in preclinical neuroscience drug discovery?
AxoSim is at the cutting edge of science with two technological platforms, NerveSim® and BrainSim®. These platforms have already proven their worth in identifying neurotoxic compounds, and are at the threshold of becoming indispensable tools for drug discovery. The work that AxoSim has already accomplished with NerveSim demonstrates that human nerve cells can be grown in 3-D culture along with Schwann cells in a nerve fiber which conducts electrical impulses. The two key words of this technology are human and functional. The challenge of past in vivo animal models of pain is that they often fail to translate to clinical success. Recent work at leading academic labs suggest that at least part of the reason for past failures is differences in gene expression between mouse and human peripheral nerves. Testing drug candidates in actual human nerves and measuring their impact on a set of functional parameters holds the promise of providing a more relevant, predictive system.
The other thing that excites me about AxoSim is the team. I know from experience how rare it is to maintain the convergence of technology and talent. The power of young companies, when properly nurtured, is the ability to make quick decisions and to synergize diverse skills in a coordinated team approach. The team at AxoSim is outstanding, and the partnerships they have already established amplifies their skills. I am excited to join this focused team and excited to push the NerveSim and BrainSim technologies to provide new solutions for intractable neuroscience challenges.
Microphysiological systems (MPS) as a field is continuing to grow and expand the capacity of R&D with human data- How do you think this will impact the future of neuroscience drug discovery efforts? What is the future of AxoSim’s platforms in the space?
Microphysiological systems (MPS) will not replace all in vivo studies- we still need to characterize pharmacokinetic (PK) and pharmacodynamic (PD) properties of drug candidates and to assess efficacy and toxicity in complex systems. However, the earlier MPS with relevant human constructs can predict efficacy and safety in the drug development process, the more time and cost will be saved and the more likely the right drugs will enter clinical testing. The AxoSim MPS platforms have the potential to become gold standards of neurological safety testing, akin to the hERG assay for cardiotoxicity, reducing the likelihood that a neurotoxic drug will enter clinical trials by testing functional effects on relevant human nerve cells.
Of equal or greater importance is the potential of AxoSim’s NerveSim and BrainSim MPS systems for improving drug discovery. These platforms are likely to play a critical role in prioritizing drug screening hits and early leads by providing functional readouts of efficacy. Although demonstrations of target engagement by binding measurements are important, the ability to perform structure activity relationship (SAR) assessments and drug optimizations on human cells based on functional readouts should improve the success rate in future neuroscience drug discovery and development efforts.
Biggest obstacles in neuroscience drug development from your viewpoint? How do we tackle them?
Among the biggest obstacles in neuroscience drug development is the lack of predictive models that will support optimization of drug characteristics for clinical applications. Neurological systems are complex and difficult to replicate in 2-D in vitro cultures. Often, the field has relied on animal models of human pathology, but these require overexpression of altered genes or treatments that only produce some of the characteristics of human disease. Pain models in animals have proven notoriously unreliable in predicting successful results in the clinic, and in other neurological models such of Alzheimer’s Disease and Multiple Sclerosis too many drug candidates that provide benefit to mice are ineffective in human patients. Models that involve human cells, expressing human targets, and that provide functional readouts of efficacy are likely to provide more predictive models for relevant drug development.
Another obstacle is sourcing and maintaining human cells comprising peripheral and central nerves. To ensure reliable, reproduceable results these cells must maintain consistent expression patterns. For the NerveSim platform, AxoSim is working with leading biotech and academic sources of Schwann cells and nerve cells derived from induced pluripotent stem cells (iPSCs). Well qualified cell lines are essential for drug discovery, and AxoSim has devoted extensive efforts to secure and thoroughly characterize cells for consistent results. AxoSim can also establish nerve chip culture from human dorsal root ganglia. By sourcing these primary cells, the company can compare the response of nerve cells from healthy vs disease patients, contributing to our understanding of disease mechanisms and variability amongst patient populations.
Establishing an in vitro model of neuroinflammation remains another significant challenge to neuroscience drug development. Incorporating microglia and other immune cells into our 3D models may provide an opportunity to explore the affects of immunomodulation on neurological conditions in the peripheral and central nervous systems.
First 100 days at AxoSim, what do they look like for you? Biggest goal you hope to achieve?
AxoSim has built a strong foundation of technological achievement and partnerships. In my first 100 days I look forward to working with the business and science teams to advance our internal and external goals. On the technological front, there are opportunities to develop transcriptomic and proteomic atlases of our NerveSim and BrainSim systems, including analyzing how expression changes with outgrowth and in response to stimulation or biological insult. On the business front, there are several partnerships with pharma and academic leaders that I hope to accelerate. Just as nerves grow and make new synapses, companies grow and expand their connections, discovering new synergies and new solutions. I look forward to applying my experience with early-stage biotech companies to support the further growth of AxoSim, and to working with its dedicated team to improve internal processes and deliver solutions for important neurological challenges.