A head start can be a real advantage. Early diagnosis has traditionally been the linchpin of successful cancer treatments. Similarly, at IN8bio, data from early-phase clinical trials that are recorded in the company’s production management system and its quality management system (QMS) have produced successful results that are scalable from the small trial phase to commercialization.
By leveraging Honeywell’s Sparta Systems software, which includes TrackWise QMS, and Honeywell’s Manufacturing Excellence Platform (MXP), the clinical-stage biopharmaceutical company has been able to focus its gamma-delta T cell therapies on Phase 1 trials that can then be scaled to commercial production as trial patients become relapse-free over time.
IN8bio believes cancer-zero can become a reality. The company’s story starts 30 years ago with a child who could not be saved. “Our founder was a transplant nurse working with pediatric oncology patients,” explained Kate Rochlin, chief operating officer at IN8bio, who spoke at the 2023 Honeywell Users Group in Orlando, Florida.
The power of gamma-delta T cells
Dr. Lawrence Lamb, co-founder of IN8bio, was doing salvage transplants with six kids who did not have a good donor and had no other cancer-treatment options. He was trying to figure out why two patients survived and four didn’t. “The only thing he could find was gamma-delta T cells,” noted Rochlin. This ultimately prompted him to harness the power of gamma-delta T cells in the next-generation of cell-therapy manufacturing.
Gamma-delta T cells are different from natural-killer (NK) cells because they can also amplify immune signals. “They can go from donor to recipient,” explained Rochlin. “We know its natural function is to differentiate between healthy and sick cells. Patients with high gamma-delta T cells had a higher survival rate of cancer. How do we make this happen on purpose vs accidentally?”
IN8Bio’s INB-100 is an allogeneic product candidate, initially developed for the treatment of patients with acute leukemia undergoing hematopoietic bone marrow transplantation. This was the first clinical trial of an expanded and activated allogeneic gamma-delta T cell immunotherapy.
“Because you can’t fully wipe out the immune system, these patients have a high rate of relapse,” explained Rochlin. “The patients on this trial have no other options.” Remarkably, every patient treated with INB-100 is still in the study relapse-free, some more than three years. “These cells are expanding and proliferating,” she said. “We’re very proud of this patient population.”
Cell therapy to scale
It’s relatively easy to make enough cells to cure in small trials, but it’s much more difficult to release products to treat at a clinical scale. “How do you scale from a small clinical trial into Phase 2 with hundreds of patients and then into a commercial product?” asked Rochlin.
IN8bio’s approach has been to lean into Honeywell management systems to record and manage the process from the beginning rather than the traditional approach of paper-based development logs. IN8bio could then contract good-manufacturing-practice capacity in other people’s facilities and pay them for that space.
“In cell therapy, we don’t scale up,” explained Rochlin. “We scale out. We go from academic manufacturing partnerships to manufacturing collaboration and then to an IN8bio manufacturing facility.”
IN8Bio would expand its capabilities for GMP manufacturing by first establishing a reproducible process for the Food & Drug Administration (FDA) and then access underutilized GMP space for expansion. It would streamline and digitalize using MXP and scale quality systems using the Sparta Systems eQMS to enable multi-center manufacturing while maintaining control.
The IN8bio process can take 14 days to manufacture and then 14 additional days to release due to FDA testing, mainly for sterility, explained Rochlin. “We’re trying to understand why some cells expand more slowly than others,” she said. “How can we accelerate this? We say nine to 14 days, but it’s usually nine. In the leukemia trials, we’re at seven. IN8bio is trying to understand what in the blood is causing that.”
“You want to be in control of your process, so the FDA agrees with you,” explained Rochlin. “Otherwise, they might put guard rails on that you might not be able to meet,” she said. “We wanted to integrate everything, so our document control is in there. You end up in a place where you want to be sure people are trained on your most recent version of the process.”
IN8bio was able to customize to make sure the systems talked to each other. “We had four or five specific use cases to make them work together—whether it was automatically triggered, or we wanted to decide if it should be a quality event,” said Rochlin.
“How do you find systems you can work with and grow with early on?” she said. “You can’t figure out the digitalization later because you have to stop and go back. You don’t have time. You have to start in Phase 1.”
Paper pushers
From a quality and batch-record standpoint, many cell-therapy companies are still on paper, explained Rochlin. “We saw delays in paper batch records,” she said. “Waiting to ‘fill it in later’ creates messes. With this Honeywell system, if you don’t fill it in, you can’t proceed. Batch records are long and complex, so paper can be very cumbersome, some having 80-90 pages per batch.”
It’s very hard to manage multiple products at once,” said Rochlin. “Unlike traditional manufacturing, these products have to be released in two weeks,” she explained. “On paper, that’s hard to do. An electronic system was very important, especially because we’re a small company with just 30-40 people. We can’t manage multiple platforms. Cell therapy is an expensive therapy. How do we keep cost of goods down in the long run? We wanted a system that could be rebuilt in a year. Learning to plan for the future is incredibly helpful because it helps you to understand where you need to go.”
One of the things IN8bio loves about Sparta Systems and other Honeywell software is its ability to communicate. “Everything talks with each other the way it should, so you can extract data in small records,” said Rochlin. “We’ve been able to pull small subsets of data to go back and analyze.”
The systems need to talk with each other because things fall outside the process, she emphasized. “The way Sparta talks to the Honeywell system, it allows everything to go into the system,” explained Rochlin. “We don’t have the luxury of waiting until the end. It allows our quality manager to be able to get into the system and see the quality event that’s being triggered and see the batch record. What are the dynamics of what’s going on in that bioreactor? We’ve built a lot of models to understand that. We’re not looking at it the way you’d look at a drug compound.”
