New Platform, New Potential

Meet the Jasons

Jason Bock trained in biology at MIT. Despite the appeal of burgeoning computer technology, he became captivated by the molecular nature of biology. Studying Molecular and Cellular Physiology at Stanford, his aim was to discover and clone new genes during the time when the genome was being sequenced. He later joined Human Genome Sciences (a 2012 GSK acquisition) to learn how to use these therapeutically. Over the following 20 years and more, his focus shifted to small, medium, and large sized biotech companies developing complex biologics with the aim of taking new products into the clinic. With more than 25 new products now in the clinic with commercial intent, three have reached global commercialization.  

In 2022 he helped form CTMC as a joint venture between Resilience and MD Anderson Cancer Center to accelerate patient access to cell therapies by bridging cell therapy development and manufacturing with MD Anderson’s clinical trial capabilities. He has coordinated broadened opportunities for biotechs to work alongside academia to help them develop and manufacture new products and run clinical studies. The past two years have seen six new products in clinical testing.

“If we could create something novel with the intention of accelerating the transformation that cell therapies would bring, that would be something worthwhile creating.” 

Jason C. Foster is the CEO of OriBiotech, of which he became the third employee in 2019 after a career in technology and healthcare. With little previous knowledge of cell and gene therapies, he had been “blown away” by the potential of these new modalities and thus set himself the challenge of scaling them out to patients. Founded by two professors at University College London, Ori was founded upon the need to develop new, living, personalized medicines. What gets Foster out of bed each morning is the fact that few patients can be treated with current modalities, using the current technologies and processes. Opening up access for all who need it, everywhere in the world, is his modus operandi.

“The fact that we had effective cures for cancer showed incredible clinical impact for patients, mostly late stage patients, without any other recourse. I was incredibly excited to get involved in this field.”

Cell therapies offer innovative cures. That’s a fact. Complex manufacturing, however, is a limiter. It’s not possible to manufacture enough for everyone. New technologies and approaches are needed – and they are starting to appear in markets. Is this the start of a step change? 

Ori Biotech recently announced the commercial launch of its IRO cell and gene manufacturing platform, presenting scientific data in collaboration with CTMC, a joint venture between Resilience and the MD Anderson Cancer Center. Ori Biotech CEO Jason C. Foster sought the expertise of CTMC CEO – and TMM’s 2024 Power List entrant – Jason Bock to help bring this platform to the market. The two Jasons agreed to speak with us to discuss the history behind the collaboration, as well as the future ahead. 

What have been the major lessons learned in cell therapy manufacturing so far?
 

Jason Bock: The excitement and demand for cell therapies is unprecedented. When previous new modalities were developed, such as antibodies, nobody was cured immediately. The new antibody drugs helped and we could see the potential of antibodies to target specific proteins and have a relatively long half life, but initially there wasn’t any dramatic shift. Over time, everything developed in parallel. We became better at engineering antibodies, increasing the titers, picking targets, and using them in different ways, which increased the therapeutic utility. At the same time, the field’s ability to develop and manufacture antibodies also improved, meaning, they could be produced at the right scale and cost.

With cell therapies, cancer patients with no previous options have been cured. The step change in the therapeutic utility is stark and the demand is enormous, but we need time to figure out how to produce these therapies at scale. We need to be able to characterize them, understand them, and regulate them. You can’t snap your fingers and accomplish all of this instantly.

Right now, only around 5 percent of patients are benefitting from cell therapies and some see that as a failure of a field. However, the patients that do have access are seeing huge benefits – even though we are still only in the early stages of the field. In the next 10 to 15 years, cell therapies are going to completely transform the practice of medicine and how healthcare can be delivered. 

I don't think anything we've experienced so far with cell therapies has been unexpected. There are always growing pains with any new modality reaching the commercial stage. The scale of the demand is more than other modalities have experienced and the solution will need to come from a collaborative approach. We need a better understanding of the products, better analytics, better media and reagent development, and more innovation in manufacturing equipment and systems.

At CTMC, we try to participate in as many of these avenues of success as we can. Partnering with early stage academic or biotech groups developing new treatments, for example, enables us to create a system to accelerate their ability to develop new therapies and get them through regulatory interactions and to the clinic. If they work, we can scale them and move forward. If not, we move onto the next one. Evaluating, adopting, and validating new manufacturing technologies is also an important aspect of how we can contribute, which is how we came to work with Ori. We’ve evaluated a lot of different systems, but have now been working with Ori for over 18 months. We’ve had some really important results in manufacturing. 

Jason C. Foster: Autologous cell therapies present challenges that the industry has never had to face before – both in terms of manufacturing and supply chains. The industry has applied the best learnings from biologics and other modalities in the first iteration of processes, but we now need a second generation of more bespoke technologies to solve the challenges and really make a step change. Repurposing equipment from other modalities can only get us so far. This year and the coming years will be big ones for innovation in the field as we build on the knowledge that has been created to date. Focus areas will be scaling out, real-time monitoring, and automation. 

What are the problems with repurposing equipment from other aspects of biopharma manufacturing?
 

Bock: The steep demand shift for cell therapies has led to a huge scramble over the past 5 years. What do we already have? What do we already know how to do? How can we apply that to cell therapy? There has been a lot of repurposing but it’s like duct taping things together or trying to fit a round peg into a square hole. Some people think that if you push hard enough, it can be okay, but we need fit-for-purpose solutions for cell therapy. 

What we liked about Ori is that they had taken a step back and looked at what the field really needed in the long term. When we talk about repurposing, there are also a lot of companies out there repurposing existing supply chain models. For example, companies are building cell therapy facilities next to their antibody facilities. For most drugs, you manufacture the product and ship it to the pharmacy – that’s it. Cell therapies have very different supply chains, starting materials, and manufacturing cycles – and you are working with very short timelines. Supply chains need to be aligned with the new reality.

What’s the story behind the Ori Biotech platform? 
 

Foster: I started talking with Jason when he was still at MD Anderson Cancer Center. It was a collaboration between MD Anderson and Resilience that led to the creation of the CTMC. We wanted to work together, but it took a while to get the partnership up and running because these things always take paperwork! MD Anderson is the largest cancer center in the world, treating 100,000 patients every year so it’s definitely the place to be to advance cell therapy and manufacturing. CTMC has been able to provide really important feedback on our system. 

To develop the platform, we started with a blank canvas (actually, it was a blank napkin at dinner one evening between Bruce Levine and our founders!). We talked about what is important to enable cell therapies to be manufactured and delivered. We felt that the key was to build a platform that takes as much of the human labor and knowledge requirements out of the boring, monotonous tasks. It's not value-adding for expert scientists to move fluids from one step to the next or be fiddling with a micropipette – these are things that automation and robotics can do. So, we looked at the workflow and asked where humans can be removed from repetitive processes to free them up for more valuable work. Consider the cell culture environment; you need to interact with this to perhaps add growth factors or viral vectors to perform genetic reprogramming. This can be done with automated fluid handling, which can interact with the cell culture, put things in, and take samples out automatically. 

It’s all about creating the most efficient and repeatable path from raw material to therapeutic. The vein-to-vein time is currently long for cell therapies. At the same time, patients are very sick – in some cases passing away before they can receive their treatment. If we can shrink the vein-to-vein times, it will be much better for patients. This can be done by automating key manual tasks, creating an environment that emulates the human body to allow the cells to grow more easily, and using inline sensors that can check in on the process in real time. Are the cells doing well? At what speed are they expanding? Do things need adding or removing? All these things are currently done by very experienced humans – who are very expensive and hard to find.

We also need processes that work at different scales. Right now, it takes a lot of time and brainpower to develop the products at lab scale, but then things need to change to get into the clinic, and then again to get to the commercial scale. What works for 10 patients won’t work for 10,000. We have developed a platform that's flexible enough at the research and development stage, but that can also scale up to the clinic. It’s the same instrument, the same consumables, the same reagents, and the same process, but at clinical and commercial scales in a GMP environment. Users should have the flexibility they need to design the best process early on using the platform, and then it can scale as their program advances. 

Bock: With antibodies, you scale up the volume from a 100 l tank to a 20,000 l tank. You can also realize economies of scale because it doesn't require 100 more people or 20,000 more people to do it. It takes a lot more capital, but you don't have to scale the labor force with the manufacturing quantity. Cell and gene therapy manufacturing still uses manual processes. Automation can decouple the scaling of the labor from the quantity of batches produced and help to speed things up. Even speeding up aspects such as tech transfer, as we have demonstrated with Ori, can also be a massive win for everyone. 

Can you share the challenges faced and overcome during development of the technology?
 

Foster: I could talk all day about the challenges! It's incredibly difficult to create technology of any kind – just the engineering and software work is full of difficulties! When you are dealing with biology, there is also the challenge that biology has a mind of its own when you try to get it to behave itself. 

What we really sought to do was to automate better biology. Historically, therapy developers would have to make a trade off; if you wanted automation, you would have to accept that the biological results may not be as good as using bags and flasks in the lab. We wanted to change this, so we put biological performance first. For the last five years, we've been working with partners like CTMC, therapy developers, and CDMOs, to get their insight and to make sure we could get the biology right. 

From there, it was a case of building the automation around the biology – and I’m proud to say that it works! Jason and I presented data at ISCT to show we could automate better biology, show the biological results, and deliver better results for clinical programs. We tech transferred an existing process onto the platform, which took around six weeks – pretty fast in the tech transfer world! We were able to perform at the same level or even slightly better than the previous process. 

Now, we're in a position where we are demonstrating that we can make the same product in two different places, which hasn't really been shown before. Decentralized manufacturing is a hot topic, but there’s not a lot of data to support it because human processes are extremely hard to do in one location, let alone replicating them in two or three or more!

We tech transferred to another site and we ran the process in parallel. We did three runs at each site using the same donor cells, reagents etc to show that we could deliver the same product in two different places. We sent the output to CTMC for analysis and all six batches (three from each location) met their CQs for their clinical product. This is a powerful proof of concept that the IRO system could do multi-site manufacturing relatively quickly, even though biology doesn't always behave. I would say this is a big first step forward in demonstrating the power of the platform. We don't have to just manufacture at one site, in one place, one country, or on one continent. Cells that don't have to get on a plane are always going to be faster to get back to the patient. 

Bock: What initially attracted us to Ori was the engineering. The design of a bioreactor is so important! You want a system that allows for a very wide, dynamic range of operation based on volume. Being able to adjust volumes of operation is always important in biological processes. When we did the viral transduction, we were able to reduce the volume in the culture and do a very specific programming in terms of mixing because the Ori platform was engineered to allow a degree of freedom to optimize mixing conditions and facilitate high efficiency viral vector transduction.

We added the same amount of virus in cells in different systems, but we saw better transduction with Ori. Everything is easier if you get higher or more efficient transduction. That was the engineering forethought that enabled better biology. We were really surprised by the performance. We had hopes for the automation and the online analytics, but I didn't expect it to be that significant. The speed at which we were able to implement and optimize the process was fantastic. It's not perfect; there’s always room for improvement but that makes it even more exciting.

What are you working on next?
 

Foster: There is an urgent need for technologies that can help companies reach commercial manufacturing for cell therapies. Companies are spending billions of dollars, but something right now isn’t working because we’re not treating enough patients. Several big pharma companies now have approved cell therapy products, but in 2023 the industry collectively treated only around 9000 patients. That’s fantastic for those 9000 and their families, but tens of thousands of other patients do not have access. 

We want to make an impact on patients. When the platform launches, we want to make sure it can be used in clinical trials as soon as possible. CTMC and Ori have a type D meeting coming up with the FDA to discuss that path forward and we're anxious to get the agency's view on comparability and how we could include the platform in a clinical trial – perhaps with CTMC or as part of some other partnerships. 

Bock: The industry needs to get more therapies to patients. We understand the magnitude of the challenge of what lies ahead, but this is what the early part of exponential growth looks like. You start from a very small base, but in time the numbers will increase. As an example, J&J is pouring billions into this space and recently got manufacturing and CMC improvements approved by the FDA, which they expect will double their manufacturing output. They have stated they want to treat 10,000 patients in 2025. Kite also recently announced that they had shortened their manufacturing processes. However, what we really need to start seeing are more step changes rather than incremental improvements. 

How keen are cell therapy developers to try out new technologies?
 

Foster: There are roughly 700 companies operating in this field right now, with around 2,500 clinical trials happening across academia and industry. People often talk about the big pioneers who have been breaking the ice for everyone, but for the hundreds of other companies out there there is an opportunity for them to try something new, such as new distribution models and new types of technologies because they won’t have legacy infrastructure already in place. A lot of companies are looking to the original pioneers and thinking about how they can avoid the challenges they faced and really push towards cell therapy 2.0. 

Bock: That said, it’s almost impossible for early-stage biotechs to jump directly into novel manufacturing technologies because of the risks. 

Our collaboration and study with Ori took an existing product that was being manufactured with a traditional cell therapy process and ran it alongside the Ori process. This is how you generate data that convinces others of the benefits of new approaches. We directly translated the process onto the Ori platform, ran it in parallel, and showed how the two compare in terms of value and output. For the field to evolve, we need to establish comparability and get FDA alignment.

Give us a bold prediction for the future of cell therapy in healthcare…
 

Bock: It’s still early days, but I believe that cell therapy will transform the way almost all aspects of healthcare are delivered. We often see innovations or transformations first in oncology, but you can see, even now, that cell therapies are also having an impact in other areas, including autoimmune diseases and hemophilia – and there’s even talk about what cell therapy can do for diabetes. We will look back on the period before cell therapies and compare it to the stone age and black and white TV. It's a totally different world of therapeutics.

Foster: I agree with this. My bold vision is accessible, curative cell therapies. This idea of having to poison a patient (with chemotherapy) to poison their cancer will be an outdated idea. We often talk about the cost of cell therapies being very high, but if we add up all the costs of treating people in the traditional way, it dwarfs the cost of these therapies. The ability to cure diseases in an affordable way, and making them accessible, is what we need. I envision a new model for healthcare that includes new models of therapeutic delivery and manufacturing to support these new therapeutic modalities with an incredibly curative potential for patients.