Expert Profile
Charles Leach started his career studying Biomedical Sciences at Newcastle University, specializing in Immunology and Autoimmune research. His diverse background in Management Consultancy and Biotechnology Business Development, has helped him channel his passion for enabling partnerships through a technology centric approach. At Ncardia, Charles is one of the first points of contact to understand our client’s pain points and introduce how our scientific solutions will form that winning partnership.
Charles Leach, Business Development Manager
Insights
The knowledge generated over the past four decades is starting to show the benefits
Given the globally aging population, finding treatments for neurodegenerative disorders is paramount to ensure longer and healthier lives. Whilst there has been tremendous progress in understanding disease etiology, there is considerably less to show in terms of therapies making it to patients. Nonetheless, the approval of new therapeutics such as Aducanemab, Lecanemab, and most recently Donanemab, have brought hope in treating Alzheimer’s disease.
“The neurodegenerative field has been a core focus for drug developers over the past four decades. The knowledge generated by those efforts are starting to show real benefit for patients. As an example, many therapeutic developers were focusing on interfering the late stage aggregation of key proteins such as Tau, a-syn or TDP-43, which didn’t result in efficacious therapies. However, we now know that taking a multi-stage approach in targeting protein aggregation (ie, including early stages of the process) holds real promise for disease-modifying therapies.”
A common theme across drug developers is finding the right model for their scientific question
To make this promise a reality for patients, there are still important challenges to overcome. Neurodegenerative disorders are complex diseases with multiple cell types and factors involved, which makes drug discovery even more difficult here than other areas. As Charles supports drug developers in their work, he knows their struggles well.
“Depending on the project and stage, the specific problem will be different, but a common theme is finding the right model for their scientific question. Drug developers need to make accurate predictions about their compounds, and that accuracy must be balance with speed, price, and throughput.
Immortalized cell lines, are commonly used in Parkinson’s research. They are cost- and time-effective but lack accuracy and physiological relevance. A batch of patient derived iPSC-dopaminergic cells is much more relevant and might be more expensive in the short-term, but definitely worthwhile when it mitigates risk from the offset and increases success in later stages and/or reduces the need for animal models.”
The right model can help you reduce – with confidence – the number of candidates entering in vivo studies
The impact of iPSC technology in the field of neurodegenerative disorders is starting to be seen widely, particularly with the increasing recognition that no one condition is cell autonomous, but instead, multiple cell types are involved in disease propagation. As Charles explains, many drug developers are seeking physiologically relevant in vitro models with several cell types represented, including astrocytes, microglia and neurons.
“One of our proudest achievements to date is supporting a key client developing therapeutics against ALS. We reduced the number of candidates entering in vivo studies by ~80%! Can you imagine the amount of cost, time and lives (animal and hopefully human) saved with this process? If you look at the in vivo models available for ALS, the rodent to human correlation is very low. With our expertise in human biology and drug screening, we were able to provide a relevant model based on iPSC-motor neurons and developed custom phenotypic assays to evaluate the efficacy of client’s therapy.”
Maximizing the potential of iPSC-based models with expert partners
Overall, the introduction of iPSC technology is pushing drug development into an exciting time. One of the examples mentioned by Charles is the use of iPSC-derived dopaminergic neurons for cell replacement. This therapy has just recently met its primary endpoint in PhI clinical trial for patients with Parkinson’s disease.
Maximizing the potential of iPSC technology to offer relevant alternative models is needed to develop next-gen therapies. According to Charles, the support shown by the FDA to alternative approaches coupled with the era of expert partners like Ncardia, are key drivers of this change.
“The iPSC-NDD field is moving at a breakneck speed! It’s been refreshing to see big pharma reinvesting into the space through internal research, as well as adopting new technologies through mergers and acquisitions (M&A). However, external expertise is still very much needed to accelerate progress and increase confidence in the process. At Ncardia, our decade’s worth of experience has expanded the field considerably and kept us at its forefront. Combining expert neuroscientists, iPSC specialists and large screening capabilities is key to successfully support the multi-year programs of our partners - all of which you'll find here at Ncardia!”
Are you wondering how iPSC technology could advance your therapeutic development programs? Contact our experts