Bayer reported positive data earlier this month demonstrating the safety of its Parkinson’s disease pluripotent stem cell (PSC) candidate bemdaneprocel in a Phase I study.
The allogeneic product was added to Bayer’s pipeline when it bought out BlueRock Therapeutics in 2019, effectively launching the firm into the cell and gene therapy (CGT) space. BlueRock continues to be run as an independent subsidiary within the Big Pharma’s network – “at arm’s length” – but Bayer spoke candidly about how the allogeneic nature of such therapies will be critical to making cell therapies sustainable going forward.
“We all know that in the autologous oncology – especially blood oncology – space, the response rates are very spectacular and it's really curing and changing lives,” Nuno Fontes, head of Global Biologics Development (GBD) at Bayer said during the BPI West plenary session in San Diego, California this week.
“We all know the prohibitive cost of these treatments in the range is over hundreds of thousands of dollars per treatments, and, of course, this is not sustainable.”
All approved chimeric antigen receptor (CAR) T-cell therapies are autologous. They are all made by taking, reengineering, and reintroducing a patient’s own cells and have list prices of around $400,000 to $500,000 per treatment.
The European Union (EU) approved the first allogeneic cell therapy, Atara Biotherapeutics’ Ebvallo (tabelecleucel), in December 2022. Pierre Fabre, which owns the EU licensing rights to Ebvallo, has not publicized its pricing strategy. In April last year, Gamida Cell won US approval for Omisirge (omidubicel), an allogeneic cell therapy for patients with blood cancers who are set to undergo stem cell transplantation.
While Omisirge still has a wholesale acquisition cost (WAC) beyond $300,000, prices for allogeneic cell therapies will rapidly fall as the industry overcomes critical chemistry, manufacturing, and controls (CMC) bottlenecks, said Fontes, opening up treatments to millions of patients.
The CMC challenges are far higher than with biologics, with comparability being the most dominant issue when scaling up, he said. However, “there are other issues related to the complexity of these products; cells are very, very large compared to proteins and small molecules, as we know, and it's very difficult to characterize them fully.”
Furthermore, there are raw material stability problems along with scalability issues due to a cell’s sensitivity to its growth conditions, which can change when increasing production.
“It's a very complex field, we have a lot to focus on when we are working out how should we then overcome [them]?” At BlueRock/Bayer, a ‘Comprehensive Global Cell Therapy Industrialization Program’ began in 2020 has been undertaken to overcome the bottlenecks by looking at lessons learned from the industrialization of large molecules, he explained. This is focused around five elements:
Process – Focused around having centralized Credentials Quality Assurance Systems (cCQAs), process understanding, and media platforms, this “is really fundamentally to understanding cell biology and how things report from the cellular and molecular perspective.”
Equipment – “Most of the cell therapies in the beginning are made with what was already out off the shelf for the biotech industry, but of course, in many cases, those are not the optimal solutions,” he said. BlueRock has been working with vendor Cytiva to design a modular, flexible, closed, and automated platform with the result being capable of covering over 90% of the firm’s cell therapy assets.
CMC ecosystem – Incorporating an integrated CMC strategy, a quality by design (QbD) approach, data/knowledge management, and artificial intelligence, this is “basically the glue between process and all the other parts,” he said.
Manufacturing facilities – These flexible and modular facilities offer capable and ready capacity to supply the markets and the populations in need. Fontes cited the $250 million Berkeley, California plant, which opened its doors last October as key to supporting bemdaneprocel as it scales through the clinic.
Talent – Described as the most important, Fontes said having a high-performance team with strong cell therapy competencies and capabilities as critical. “We have the people and the talent that do everything and put it together,” he said, further encouraged through leveraging experience from industry and academia.
In summary, Fontes said such an end-to-end industrialization platform for allogeneic therapies “will help to bring the promise of cell therapies to thousands of patients on a global scale.” And when looking at the future of such a modality, autologous facilities serving just tens to low-three-figure numbers of patients will pale in significance to allogeneic facilities, which will have the ability to serve patients in their hundreds of thousands.
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