April 05, 2018

With cell therapies hurtling toward the market, it’s time to prepare for the future

By Dr. Madhusudan Peshwa, PhD, Chief Technology Officer, Cell Therapy

Collaborating on the newest technology solutions for tomorrow’s immunotherapy applications

Peshwa joined Cytiva as Chief Technology Officer for the Cell Therapy division in 2018. In this role, he works with customers and partners to contribute to furthering the clinical development and commercial manufacturing of cell and gene-based drugs on a fully integrated scale. His goal is to provide end-to-end flexible technology solutions that enable companies to launch and deliver new therapies.

It is an exciting time to work in cell therapy, and I get even more excited when I think about what the future holds for the field. There’s no question that cell therapy is going to be an increasingly strong way to manage and treat diseases, and it has the potential to reach thousands more patients with various illnesses. I think cell therapy is an integral part of the industry’s move toward precision health and is the penultimate step toward providing even more precise treatments.

For me, precision health means being able to image a patient, collect real-time information about their disease and use that real-time information to prescribe a customized course of therapy, be it cell therapy or another with small molecules, large molecules or nucleotides. Physicians then give that treatment to a patient, measure the effect of the treatment, and then afterward again use functional imaging studies to figure out how the disease has been impacted. Here are some of the opportunities and promising advancements I see coming to the industry, and why I believe collaboration on scalable solutions will be the key to bringing them to reality:

Dr. Madhusudan Peshwa

Vision to reality: The importance of collaborating on scalable solutions

The cell therapy industry is facing two big challenges. The first challenge is finding a cell therapy product with sufficient clinical or biological activity that leads to a meaningful clinical benefit, such as a remarkably high 83% complete remission rate as we’ve seen recently with CAR-T therapies. The second challenge is effectively manufacturing such a therapy with the least complexity, and a control on cost of goods.

After your product is identified, the concept really comes down to the ability to deliver a commercially viable product. Cell-based therapies differ from small molecule drugs. While you cannot define compositional matter of the cell, you can define compositional matter of a small molecule – the way you manufacture a cell often imparts a certain biological activity, and that defines its therapeutic index. You need to be able to replicate that therapeutic index or attribute of that cell product through the entire course of development.

So, if your research starts with a manufacturing system and process that gives you a certain desired outcome, you need to be able to replicate the same attribute at a bigger scale as you progress through clinical trials and into commercial phases. Rather than working from the ground up and building up more capacity later in your development, I believe that it’s easier to work from the top down by incorporating scalable solutions from the start. Determine the appropriate commercially viable manufacturing system, deconstruct that and use critical elements from that in your early research. This approach will help to assure that there is consistency and comparability in terms of the product attributes. It’s helpful to work with an industry collaborator that has this understanding of what is needed to transition from clinical trials to commercial launch.

Many elements go into defining a commercially viable cell therapy manufacturing process. I’m thrilled to now be part of the cell therapy team at Cytiva because they have been working on flexible solutions that connect equipment and services to support companies along the workflow steps. With an eye towards the future, they have identified the value in integrating equipment into a higher-level strategy supported by digital and data analytics. That digital support can provide a lot more information that is going to be meaningful in understanding product attributes.

New possibilities in cell engineering

With so many advancements on the horizon, our capability to partner with the customer will only continue to grow as cell therapy evolves for new applications.

Very simplistically, a small molecule therapy is a single input/single output system. One molecule binds something and triggers an activity. A cell, however, is a complex bag of many different inputs and outputs, allowing control of many different pathways at the same time. This means the future of regenerative medicine will undoubtedly be in engineering cells -- engineering them using viral vectors and/or non-viral approaches and trying to modulate multiple pathways.

Effective engineering is already being demonstrated in oncology. One of the biggest excitements has been with immuno-oncology drugs -- antibodies and bi-specific T cell engagers -- where various checkpoints are blocked and combined in different therapeutic applications. But cells are much more versatile. You can put a chimeric antigen receptor (CAR) inside of a cell, and you can get the cell to home in on the tumor. You can even use genetic tools to block a favorite checkpoint pathway in the T cell, creating a combination product within that same T cell.

There are more than 900 regenerative medicine trials underway globally, including trials in cell and gene therapy, which is a 19 percent increase since 2016. Many of these early-stage clinical studies are using gene-modified cells, with nonviral approaches. I think we’re going to see a convergence of these multiple modalities.

Road to precision health

Advancements like those in cell engineering are just one of the elements needed to make precision health a reality. The industry also needs highly trained people with the right skill set. These people need exposure to equipment, processes and expertise, and that’s where Cytiva can help partner from start to finish. If we can work backwards, scale and develop versions of product attributes that help people at different temporal stages of their development, then we could have a ready-made scalable solution. If we work together across the industry to increase speed to market to help get effective and safe therapies to patients faster, then together we can bring tremendous value to the field and help pave the way to precision health.

Read more about Peshwa here.