The manufacturing of cell therapies is highly complex, often depending on skilled manual labor. The Israeli startup Adva Biotechnology aims to use automation, optical sensing and artificial intelligence to remove the manual component from the process.
Cancer cell therapies such as CAR-T immunotherapies have demonstrated enormous potential for treating forms of blood cancer. Currently available therapies involve extracting a cancer patient’s immune T cells, genetically engineering them in the lab, and returning them to the patient to kill cancer cells.
One of the drawbacks of these therapies is that growing cells in a manufacturing setting is highly complex. This means that the therapies are expensive and largely limited to the wealthiest nations.
According to Noam Bercovich, vice president of development at the Israeli firm Adva Biotechnology, CAR-T cell therapies have been something that most cancer patients are unable to receive.
“All the companies manufacturing this therapy use semi-automated solutions, which demand lots of human input in terms of quantity and expertise,” Bercovich added.
To bring more automation into the cell therapy manufacturing process, Adva Biotechnology was founded in 2016 by its CEO Ohad Karnieli in Bar-Lev High-Tech Park in Israel. Adva Biotechnology is working on an automated cell culture kit powered by artificial intelligence and optical sensors.
Prior to founding Adva Biotechnology, Karnieli had served as vice president of technology and manufacturing at the cell therapy firm Pluristem Therapeutics, which is now known as Pluri. He also founded the CDMO Atvio Biotechnology, which was acquired by Orgenesis in 2018.
Bercovich was a process engineering manager at Pluristem and had known Karnieli for almost 12 years before ADVA Biotechnology was founded.
“We worked together and [Karnieli] left the place, called me and told me about his idea. And I said I’d join right away,” recalled Bercovich.
In an online presentation, Adva’s founder and CEO Ohad Karnieli explained that current manufacturers are only able to measure a few parameters in cell cultures on a few occasions.
“We don’t really know what’s happening inside the system or inside our cultures,” he stated. “We put the cells in the incubator and we have no idea what’s happening. We need much more in-process controls.”
The equipment, named ADVA X³, uses sensors and artificial intelligence to handle the fine adjustments that are often required when growing cells, such as monitoring and tweaking levels of nutrients in the cell culture medium. It consists of a single-use kit that slots into an electronic system. According to Adva Biotechnology, the kit can culture from 10 million to 20 billion cells in the same chamber. In addition, the kit has the ability to grow CAR-T cells, natural killer (NK) cells, exosomes, viruses and more.
At present, ADVA X³ is available only to early adopters. After a patent dispute with the CDMO giant Lonza, Adva entered a licensing agreement with Lonza in May 2022 to enable the startup to launch its equipment in the U.S. The device will face its first field test manufacturing an advanced therapy for a clinical trial in 2023.
“Once it’s tested in a clinical trial … that is when we can look at the device and say, ‘We made it. It’s the real thing,’” said Bercovich.
Adva is part of a wave of startups geared towards bringing automation to the world of advanced therapy manufacturing, such as Ori Biotech and Cytera Cellworks. Bercovich said that Adva’s fast adoption of optical sensing technology is what helps the company stand out from the crowd.
Automated cell therapy manufacturing technology such as the ADVA X³ could also enable the advent of decentralized manufacturing. In this scenario, for example, a CAR-T therapy could be produced at the hospital where a cancer patient is staying, rather than being shipped off to a large, expensive central location.
“If I can take my manufacturing and bring it to the patient, a lot of the logistics and the huge footprint are basically eliminated,” stated Karnieli. “We need decentralized manufacturing with centralized control, meaning remote access, alerts and all these different automation properties.”
Adva Biotechnology bankrolled its research with a crowdfunding campaign in 2020, and with a seed round in 2021. The company is now in the middle of raising another funding round.
According to Bercovich, while a lot of attention has been paid to the business potential of automation in cell therapy manufacture, Adva’s also mindful that these advances can lead to more treatments that save lives.
“Behind all this, it’s a potential cancer treatment,” said Bercovich. “This is something that we speak about every now and then to not forget.”