Envisioning the (Cost-Effective) Future of Cell and Gene Therapy Manufacturing

In this interview, Jason Foster, CEO and Kevin Gordon, Chief Data Officer of Ori Biotech discuss the opportunity that led to founding the company, the role of digital technologies in cell and gene therapy development and their vision for the future of the industry.

Could you tell us a little about Ori Biotech and the company’s mission?

JF: Ori was founded by Chris Mason and Farlan Veraitch who met at University College London in 2015. At that time, the cell therapy industry was starting to celebrate positive results for patients. As manufacturing experts, Chris and Farlan focused on some of the bigger questions: how are we going to make these treatments widely accessible for patients? That was the genesis moment for Ori.

I met the team in 2018 and got really excited about cell and gene therapy but was also horrified by the fact that there were cures for cancer that patients couldn’t access because they couldn’t be manufactured. That’s our mission – to enable widespread patient access to this new generation of lifesaving cell and gene therapies.

You describe your platform as ‘revolutionary’. What makes this so different from other platforms?

JF: Unlike many platforms that may have been repurposed other areas, our platform has been uniquely developed from the ground up specifically for CGT process development and manufacturing. Ori is also a cloud-native platform with a digital-first perspective.

First, we capture all data and transform it into useful information for operators by analysing trends, reports and benchmarking. Process development teams can then compare their process in depth across runs, across sites and across operators. The second step is to turn that information into actionable insights. We can say to customers that we noticed this part of your process has a lot of variability and recommend how to eliminate that variability based on data driven expertise. The third leg of the stool is engineering: create a repeatable process that works and then automate it to achieve high throughput, high quality so that it can drive cost down substantially.

We bring the biology, the data, the engineering and automation together. That is what makes our approach unique and makes us uniquely able to solve the scalability challenge in cell and gene therapy, giving access to every patient who needs it.

To what extent can you be revolutionary and be taking those strides while remaining within the necessary regulatory frameworks?

JF: There’s a reason why biopharma is often on the lagging side of the adoption curve. I often say that kind of inertia is built into the system on purpose in healthcare so that we don’t change things too fast because people’s lives are potentially at risk.

Our technology is revolutionary but our standards are well aligned with regulatory frameworks. From the regulators’ perspective, they’re approving therapies that very few people may benefit from. The process is inefficient, expensive and logistically challenging, but it may not have to be this way. Ori’s solution actually ensures safety and improves quality, while our digital approach provides transparency and ease for regulatory reviews.

Furthermore, regulatory approval is a time consuming step. Ori’s unique ability to monitor centrally but manufacture locally with a distributed system can cut down vein-to-vein time significantly. Our platform thus supports the regulatory process to bring therapies to patients much faster.

To what extent are digital technologies being integrated into cell and gene therapy manufacturing? What advantages are conferred with increasing adoption of digital technologies?

KG: Data itself can start to move the industry forward. What we’re seeing at the moment is people are layering on top of traditional systems, other pieces to capture some of that in process data in motion, to understand what’s happening and to provide better information about what there is to learn.

What we’re working towards is the ability to stream data directly off of the platforms to a format that can be used by other partners in the ecosystem. There are a lot of advantages to streamlining data in real time, including greater transparency with regulators, which in turn can lead to greater chance of approvals for systems that allow for greater density in manufacturing and better throughputs.

In the areas of QA, QC and release, the ability to do a release by exception is just starting to come in. To be able to do that, you need to better understand your upper and lower boundaries of those parameters. As developers employ the correct instruments and equipment, it’s going to become one of these self-fulfilling and accelerating feedback loops in that the more they get to see and understand, the more they can improve their processes, increase their throughput speed and increase their manufacturing density in those facilities.

JF: Because these are personalised medicines, you have to have zero defect, a 100% control. The regulators are seeing this digital approach as a means to get there. This then creates implications around distributed manufacturing, around the ability to concentrate the amount of throughput through a given facility, bring down cost of goods, etc. And it becomes a foundational element that ties all the other pieces together. I can’t underscore enough the importance of this and how important it is to Ori’s vision of the future.

As you observe the cell and gene therapy landscape, what do you feel are the most pressing challenges that we need to address?

JF: One of the biggest challenges that remains for the industry is making these products widely available.

Look at the recent Abecma approval – multiple myeloma is a very challenging condition to treat and it’s a relatively large patient population. With the label for Abecma, the patient will have had to fail four or five different rounds of treatment before they could have access to this therapy, which is potentially curative. We’re restricting cures for cancer to only the sickest patients. Why? Because they’re very hard to make and are very expensive.

Translating therapeutic development from preclinical and discovery phases to a commercialisation ascension with a CDMO often takes years and millions of dollars; it can be done with small numbers, such as 30–100 patients in a clinical trial. But getting to that point without thinking about manufacturing and scale means you’re often wedded to a process that turns out to be not scalable.

We have to think about manufacturing and scale from the very beginning. A platform like Ori has the flexibility to allow for designing different processes and trialling different tools. If the process works on the platform, there is a level of assurance that the product can scale into the clinic, and then commercially, where many more patients can ultimately be treated.

That’s the promise of Ori – being flexible enough for that early stage development but also being scalable enough that we can create high quality, repeatable processes that can address thousands of patients at greatly reduced cost of goods.

KG: Something that we’re all very passionate about is how can you get a much larger set of doses through a more compressed manufacturing density. It comes down to removing one component from the current state, which is paper in the manufacturing process. If you want to think about being able to run 1,000 doses through 1,000 square feet of space at some point in the future, you’d be standing on currently two and a half feet of paper to be able to do that today. We need to rethink the necessity of those paper batch records. At Ori, we very much have a perspective there and solutions around it, within our instruments as well as our broader platform and ecosystem.

Tell me a little bit more about the sorts of projects or customers that are most of interest to Ori Biotech?

JF: We’re focused on cell therapy and gene-modified cell therapy, and our customers fall into three major types. The first is therapy developers, and we already have several collaborations that are already underway.

The second would be contract manufacturing – CDMOs that are helping those therapy developers translate those processes and run clinical trials.

Finally, there are academic institutions doing early stage research that need those flexible tools because that’s really where most of these new approaches generate. If we get them familiar with the Ori tool set, we can really help amplify their impact and future-proof how those products make it into the clinic and ultimately to scale.

For those academic partners, we will soon be launching our Lightspeed early access program which will provide a few select partners access to technology pre-commercialisation with a goal of getting feedback to ensure that what we create is fit for purpose.

Is there anything else we should be looking out for or looking forward to?

JF: We’re about 14 months or so away from the first commercial launch of the first generation platform. Our hope is that ultimately we’re able to shave years off the drug development timeline for therapy developers to improve the speed of patient delivery and dramatically reduce cost of goods, from 50% to potentially 80–90%. CGT can then be introduced earlier in the treatment pathway, treating more patients and achieving much greater clinical benefits.

It will be very exciting to see the hardware, software and data platform all working together for the first time within the Ori ecosystem, because this doesn’t exist out there in the CGT world today. We’re hoping that we can drive adoption and help move the next generation of cell and gene therapies forward so we can all achieve the benefits for patients that we’re trying to.

For those companies that are bringing innovative solutions to the market, we’d love to chat with them and see how we might be able to work together because no one company is going to solve this on their own. There are just too many challenges. We hope to be a good actor in this industry and bring best of breed, integrated solutions to our customers and our already established ecosystem.

This feature was produced in partnership with Ori Biotech.