SUZHOU, China – Genome editing startup Edigene Inc. and CAR T developer Immunochina Pharmaceuticals Co. Ltd., both from Beijing, have unveiled joint efforts to develop an allogeneic CAR T therapy for cancer. Terms remain undisclosed.

Edigene CEO Dong Wei remained tight-lipped when BioWorld asked about the specific target of the CAR T therapy. But the aim is to create a potentially best-in-class therapy using allogeneic T cells. Currently approved CAR T therapies, such as Kymriah (tisagenlecleucel, Novartis AG) and Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.) are autologous therapies.

“Allogeneic T cells have the potential to transform the CAR T concept in multiple attributes, including lower costs, better quality control and more importantly, the possibility of an ‘off-the-shelf’ portfolio of CAR T products for a particular type of cancer,” Wei told BioWorld.

“As we know, cancer usually consists of a mixture of mutated cells with uncontrollable growth. A portfolio of allogeneic CAR T products targeting a pool of cancer antigens could be really attractive to manage this devastating disease in the future,” he added.

Under the partnership, Edigene will contribute its expertise in genome editing and allogeneic T-cell process, while Immunochina will share its CAR T technology. “What we can say now is that this is a 50-50 alliance in research and development,” Wei added.

“We have been collaborating for a few months now to work out the feasibility of integrating our science,” he said.

While both companies are advancing the joint project, they are well aware of how different their clinical development could be from that of autologous CAR T therapies.

“Allogeneic T-cell process differs from the autologous T-cell process in multiple ways,” Wei explained. He named a few technical challenges. “First, one has to know how to select the healthy donors, as T cells from each donor may be quite different in suitability for CAR T development,” he said.

The second challenge, Wei pointed out, is that genome editing is complex science, involving issues such as which targets to edit, how to obtain high on-target editing while minimizing off-target editing, and how to integrate optimally with CAR transfection.

“Third, the scale of cell expansion and final processing is much larger and more complex than that of the autologous CAR T manufacturing process,” he said. “How to achieve a large enough scale to be commercially attractive while maintaining the desirable properties of the final product requires expertise.”

Challenging as that sounds, Wei said Edigene’s team has spent years building up the know-how in those areas. However, the company’s R&D capability in CAR T therapies remains limited, so its strategy is to develop allogeneic CAR T products through partnering with a company that has expertise in the field.

As one of the contenders in China’s CAR T race, Immunochina has two IND approvals so far. In April, its self-developed, CD19-targeted IM-19 received trial clearance for the treatment of non-Hodgkin lymphoma and acute B-lymphocytic leukemia in China. Another product candidate that is in clinical stage is CD123-targeted IM-23 for relapsed or refractory acute myeloid leukemia.

“We have accumulated considerable experience in late-stage hematological malignancies, with two IND approvals,” said Immunochina CEO Ting He. “Although a number of breakthroughs have been made by autologous T cells lately, allogeneic T cells could also play an important role in the future.”

He said the partnership with Edigene on allogeneic T cells could lead to exciting discoveries. Speaking to BioWorld, he explained why allogeneic T cells are promising.

“When genomes are precisely and efficiently edited, allogeneic T cells could be safe for any patient,” He said. “Our pilot study demonstrated that with the CAR gene added, allogeneic CAR T-cells are potent against target tumor cells both in vitro and in vivo. We will soon extend the research to clinical settings.”

He said he remains confident that both companies could achieve milestones in the coming months.

As they accumulate more know-how in developing cell therapies, Chinese CAR T therapy developers have started to explore the potential of allogeneic T cells.

In April, Shanghai-based Gracell Biotechnologies Co. Ltd.’s allogeneic CAR T therapy candidate, GC-007G, won IND approval in China for CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). The biotech plans to initiate phase I studies in the second quarter this year.

“We are delighted that this first-of-its-kind CAR T program will soon be evaluated in IND-approved clinical trials,” said Gracell CEO William Cao. “We expect donor-derived CAR T therapy, GC-007g, may become a good alternative solution to the r/r B-ALL patients who may not be eligible for autologous CAR T therapy due to infections and other conditions, to those who do not respond to autologous CAR T therapy, or to those whose CAR T cells fail to be manufactured successfully.”

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