In this podcast, we spoke with Dr. Brad Taylor from Nucleus Biologics and Randy Jacinto from Cytiva about the benefits of using a custom media for cell and gene therapy process development. Topics included current development challenges, increases in the number of cell and gene therapies in clinical trials, and employing custom cell culture media solutions to address these issues.

We started the discussion by talking about the most pressing challenges facing cell and gene therapy development.

Randy began by explaining that the most pressing challenges are the cost of manufacturing, lower than expected adoption rates, and complex logistics around supply chain. At Cytiva, he shared that they are addressing these challenges by automating many parts of the workflow and simplifying the logistics. In addition, the recent partnership with Nucleus Biologics will allow customers easy access to cell culture media solutions that can help accelerate the development of these cell therapies.

Brad added that he also hears from customers that there is difficulty accessing consistent, reliable products and materials in single source situations. Companies are working with suppliers who guard their materials with trade secrets and this hinders the ability for that therapy to progress to the clinic.

He went on to say that the scalability of cell therapies is also an issue, particularly as the industry moves into allogeneic therapies where manufacturing requires larger scale processes. He stressed that at Nucleus and in conjunction with Cytiva, they are committed to making sure that customers have a consistent supply of reagents and cell culture media to help them meet the rigorous quality standards.

Next, I asked about what potential issues will arise with the large increase in cell and gene therapies in clinical trials, and the forecasted further increase over the next five years.

Brad said that the regulatory approvals of cell therapies is really accelerating globally. Scaling processes for allogeneic therapies certainly lends itself to custom development and custom process development. So, it is important to not be locked into one size fits all type models. Nucleus wants to make sure that developers of these complex therapies can derisk their processes. Developers want to be able to accentuate desired attributes of their cell therapies and reduce those that are not desirable and cell culture media can have a profound impact in this area.

He went on to describe a collaboration with the University of Pennsylvania, where Nucleus demonstrated that individual components can help expedite therapies and improve outcomes. In those publications, authors were able to show an increase in in vivo efficacy, cytotoxicity, and transduction efficiency by changing the cell culture media components for CAR T cells.

Randy added that in addition to the scalability challenges, another primary challenge around cell therapies is the labor cost. Cytiva has estimated that labor costs contribute close to 48% of the total manufacturing costs of the drug therapy. To address these labor costs, Cytiva is working through automation as well as digitalization of the workflow and this will help overall improve the scalability and reduce costs. In addition, Cytiva is working with Nucleus Biologics because they truly believe that custom media is a key component in improving the overall efficacy of that drug therapy.

Next, I asked about the focus of the Cytiva and Nucleus Biologics collaboration agreement and what they hoped to achieve together.

Randy explained that it could not be a better partnership because the companies share a common vision of advancing novel therapeutics like cell therapies, which they believe will have a true transformative impact on the healthcare landscape.

He went on to say that the challenge has been with science workflows advancing much faster than the actual process of manufacturing itself. Cytiva believes that partnering with Nucleus Biologics will allow them to provide innovative tools that can help accelerate the development of these cell therapies.

Brad agreed and added that it is about development acceleration. The partnership makes sense because they have synergistic solutions. Nucleus is providing a custom cell culture media to Cytiva clients to help them build their processes around Cytiva bioreactors. This will allow their clients to expedite their therapies. Nucleus clients will also have access to solutions that allow them to build cell culture media into their processes earlier in development. The earlier those can be built, the more expedited downstream pathways are going to be.

He added that customers will own the media that they create and will be able to take this media through their process feeds. They will be able to build out that media process using Nucleus’ proprietary platforms. Cytiva and Nucleus Biologics want to see their customers have success and so they are giving them the tools to do this in an expedited way.

I asked a follow up question about what this means for their cell and gene therapy customers.

Brad said that it is about turning control over to scientists, researchers, and drug developers, earlier in the process so when they can build their media, process, and model, using small quantities of custom media that allow them to quickly iterate and test much faster, generating less waste. They will have the flexibility to build in components that allows them to enhance their desired cellular characteristics early on. All of those steps early in that process will allow them to simplify their downstream scale up as well. Nucleus can scale with customers from the bench top all the way to a GMP grade media. Quantities can also be scaled from small amounts to 2000 liter volume.

Randy added that Cytiva consistently hears from customers about the need for speed and flexibility. The speed to determine what works, what doesn’t work, and the flexibility to scale up the process when the time is right from preclinical all the way to commercial scale. Cytiva and Nucleus both welcome this paradigm shift in the cell culture media market.

He went on to say that Cytiva believes that there’s a one size fits none model where custom media can enable meeting critical quality attributes that can potentially impact the efficacy of the drug therapy. Furthermore, this custom media provides customers the speed and flexibility they’ll need to advance their drug development.

I then asked about the Xuri™ Media AI Guide that was recently launched by Nucleus Biologics and Cytiva. Brad described the Xuri™ Media AI Guide and the Xuri™ Media Designer System.

Brad stated that both are based on Nucleus Biologics’ proprietary platforms. The AI guide creates custom media formulations in just a matter of minutes, replacing the more traditional approach of many hours in front of Pub Med digging through publications. The AI guide extracts the most relevant and most recent data and identifies high value compounds within those publications. It looks at how those compounds affect cell performance, essentially tracing that back to a critical quality attribute of the cell that a user would like to enhance, for instance cytotoxicity or proliferation. The formulations are assembled essentially within that platform for the client. Using a novel neural network, the guide combines the customer input with the published findings to build a formula to accentuate the desired characteristic of the cells.

After the formula is suggested and the customer or researcher signs off, they can take that into the media designer system, which allows them to customize every aspect of that media. Customers can pick the grade of the components, the container, and the scale from 2 liters up to 2000 liters. We have built a system whereby customers can customize media to fit their specifications and at the end, it’s all their intellectual property. In this way, we are democratizing media and turning control and individual ownership over to the client.

I followed up by asking about additional benefits of the guide.

Randy shared that it empowers customers with speed and flexibility to customize their own media. The flexibility to know exactly what raw materials are in those formulations and own that IP. Moreover, they can order it in whatever format they need to meet their current development cycle, whether it be bottles at the early preclinical or the ability to get bags and different tubing port sizes. It is a truly flexible platform that allows customers to save time during their process development phase.

I then asked if they could look forward and share what kinds of changes or advancements are needed to continue to further improve the cell and gene therapy development space and move the industry forward.

Randy said that he thinks the last six years have brought tremendous growth in the cell therapy market, and he believes that the next 10 years will be completely transformative in terms of what additional advancements are seen in this space. Cytiva will continue to seek digital solutions to accelerate the development around these cell and gene therapies. In addition, one the main drivers of widespread adoption is around high manufacturing costs and that these therapies are not able to be provided to all patients. For example, a typical CAR T cell therapy can cost upwards of $500,000 for single dose. At Cytiva, they believe that automation of key areas within the process can reduce overall manufacturing costs and enable these cell therapies to be accessible to a broader community.

Another area that is really critical is around the advancements of allogeneic therapies and being able to take the economies of scale from scale out to scale up. Randy thinks that allogeneic therapies will be a main driver in further adoption.

Brad added that he thinks further automation and developments around artificial intelligence are very exciting. He explained that these are very complex biological systems. It is a cell, but it’s being genetically modified right to perform a specific purpose in a human, so anything that can be built using artificial intelligence and processes will allow expedited development.

Lastly, he said that both Nucleus Biologics and Cytiva share a passion for the environment, and they are committed to bringing sustainability to cell therapy. These therapies create quite a bit of waste, and it is something that we are all willing to accept because of the phenomenal potential. However, if you think about providing these therapies to every patient that needs it, then there could be a high environmental cost. At Nucleus biologics, they have been working product development that brings processes and instrumentation that helps with bringing sustainability to the cell therapy process manufacturing process.

I closed by asking if they had anything that they would like to add for listeners.

Randy said that he was very excited with the partnership with Nucleus Biologics and looking forward to working with customers and addressing these key challenges to provide novel therapies to a greater number of sick patients.

Brad shared that he is excited about their shared vision for the future and about the potential that this collaboration has for their customers. Cytiva customers are going to be able to utilize Nucleus products early in development to help them streamline and accelerate their research. Likewise, Nucleus customers are going to greatly benefit from Cytiva’s phenomenal level of industry experience and knowledge.

For more information, please see Xuri™ AI Media Guide.