Imugene, the Australian biotech firm seeking to redefine cancer immunotherapy, is making headway with Azer-cel (azercabtagene zapreleucel), its lead allogeneic CAR T-cell therapy. With new data from an ongoing Phase Ib trial in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the company is not only reporting deeper responses than previously disclosed but is also preparing to enter pivotal discussions with U.S. regulators.

Announced this week, the updated trial results show a Complete Response (CR) rate of 55% and a best overall response rate (ORR) of 75% among patients treated with Azer-cel and interleukin-2 (IL-2), a common cytokine used to support CAR T-cell activity. This builds on data shared in February 2025, when four of seven patients achieved a complete response. Since then, two additional CRs and three partial responses have emerged among the treated population. Responses have been durable, with the longest remission now ongoing beyond 450 days.

“We’re extremely encouraged by the data emerging from the Phase Ib study,” Bradley Glover, PhD, COO of Imugene, told Inside Precision Medicine. “The depth and durability of responses we’re observing give us strong confidence in Azer-cel’s potential to be a transformative therapy in the allogeneic CAR T space.”

Going allogeneic

DLBCL is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for approximately 30,000 new cases annually in the United States and 160,000 globally. Though treatable in many patients, those who relapse or fail to respond to first- and second-line regimens face steep odds. Even with autologous CAR T therapies, which have reshaped expectations in this space, approximately 60% of patients eventually relapse. These individuals often have few options left, underscoring the urgent need for new, effective approaches.

“That’s a million-dollar question that I’m sure Kite Pharma, BMS, and Novartis would love to get an answer to: why is their product basically 50–70% effective in the commercial setting?” said Glover. “The effectiveness may range from 50% to 70%, and the observed variability likely reflects differences in the starting material, patient characteristics, the manufacturability of their cells, and their previous lines of therapy. These patients have really had a mix, at least in the autologous CAR T space. Many companies are conducting extensive translational research to understand the reasons behind the failures of autologous CAR T therapies, specifically whether the issues are due to receptor CD19 internalization, loss of the antigen, or insufficient cell delivery at the start to effectively eliminate the cancer. There are likely many factors explaining the failures of autologous CAR T therapies. I think a lot of folks are looking at that.”

Glover stated that closely examining autologous CAR T failures has been crucial in defining their approach. “I’d say that the performance of Azer-cel in areas with CAR T failures primarily depends on the health of the starting material, the patient, and the gene editing; many factors contribute to what I believe makes our product successful,” said Glover. “Additionally, we are using IL-2, and after infusing our allergenic product, we observe an expanding bolus of our T cells, along with kinetics and pharmacokinetics that are similar to those of the autologous CAR T. Our product in vivo is performing as well, certainly as well as kinetics go, as the autologous CAR T. We think that contributes to the durability and the responses we’re seeing, all the while not increasing any concern on the safety profile.”

Imugene acquired Azer-cel through its 2023 acquisition of Precision Biosciences’ allogeneic CAR T platform, a move that now appears strategically prescient. The therapy targets CD19, a well-established surface marker found on malignant B cells. What sets Azer-cel apart, however, is its design: in addition to CD19-directed CARs, the T cells are engineered with proprietary gene edits to reduce immunogenicity and promote longer-lasting cell persistence—an elusive goal in the allogeneic field.

Azer-cel could be a quick and ready-to-use option that doesn’t sacrifice effectiveness like autologous CAR T-cell therapies do, with challenges in production, availability, and speed. Unlike autologous CAR T therapies, which are manufactured from a patient’s own T cells in a multi-week process, Azer-cel is engineered from healthy donor cells—a process that dramatically reduces manufacturing time and allows for on-demand treatment. That matters in DLBCL, where rapid disease progression can leave patients unable to wait.

“Azer-cel is differentiated from all other allogeneic CAR T cell therapies in its novel genetic modifications that reduce the risk of graft-versus-host responses and its combination with IL-2,” Glover explained. “This is a key innovation that underpins the activity we’re seeing.”

CAR T’s pivotal moment?

The Phase Ib trial enrolled patients with relapsed or refractory DLBCL who had received at least two prior therapies, including many who had progressed after previous autologous CAR T treatments. These patients often have limited options and poor prognoses. Among the 12 patients treated, nine achieved an objective response, including six complete responses. Importantly, the responses appeared durable at the time of data cutoff, with multiple patients maintaining remission beyond six months. Glover emphasized the gravity of this achievement: “These are patients with very advanced disease. All have progressed after CAR T therapy. So, to see this level of activity and durability from an allogeneic approach is not only clinically meaningful—it’s unprecedented.”

The safety profile was also favorable. Cytokine release syndrome (CRS), a common complication in CAR T therapy, was mostly low-grade. There were no cases of high-grade neurotoxicity or graft-versus-host disease (GVHD), a concern with any allogeneic cell therapy. “We’ve been very pleased with the tolerability of Azer-cel,” Glover noted. “The absence of severe CRS or neurotoxicity, even in this fragile population, speaks to the careful engineering of the product.”

According to Imugene, none of the patients required bridging therapy during the trial, and the treatment was administered with a median turnaround time of just a few days. This rapid deployment contrasts sharply with the weeks-long manufacturing cycles of autologous CAR T therapies like Yescarta or Kymriah.

In recognition of the therapy’s potential, the FDA granted Fast Track Designation to Azer-cel for DLBCL in March 2025, accelerating its path toward approval. Imugene plans to request an End-of-Phase I (Type B) meeting with the FDA in Q4 2025.

Fast Track status brings the potential for more frequent regulatory meetings, rolling review of submissions, and eligibility for accelerated approval and priority review. These mechanisms could allow Azer-cel to reach patients faster than traditional timelines, should efficacy and safety continue to hold up.

The FDA has yet to approve an allogeneic CAR T therapy for any indication, despite multiple contenders in late-stage development. Persistence, safety, and manufacturing consistency remain key areas of scrutiny. Still, the agency has shown increasing openness to innovative cellular products, particularly those that address urgent unmet needs. “We’re working closely with regulatory agencies to ensure a clear path forward,” Glover said. “There’s growing recognition that we need more scalable, accessible immunotherapies—and Azer-cel is built with those needs in mind.”

Imugene plans to initiate its Phase II trial in 2026, enrolling a larger cohort of patients across the United States, Europe, and Asia. The company is also exploring additional indications, including primary CNS lymphoma, Waldenström Macroglobulinemia, follicular lymphoma, and marginal zone lymphoma, as well as potential combination strategies. “We believe Azer-cel represents a platform—not just a single product,” Glover added. “It’s a foundation for future CAR T innovations that could expand across hematologic and even solid tumors.”

To expand the reach of Azer-cel, Glover said that Imugene is already looking at enrolling autologous CAR T naive patients with CD19+ lymphoma—patients have not had autologous CAR T—for future testing. Should Azer-cel prove successful in larger trials, it has the potential to revolutionize the field of CAR T-cell therapy, realizing the long-standing promise of universal, off-the-shelf cellular immunotherapy. Much will depend on Imugene’s ability to replicate these results, scale manufacturing, and navigate the regulatory pathway. But for now, the early data is undeniably impressive.

Redefining immunotherapy

The company’s goal is to bring Azer-cel to market as the first off-the-shelf CAR T therapy in aggressive lymphomas. This ambition places it in direct competition with other allogeneic players like Allogene Therapeutics and CRISPR-backed partners like Caribou Biosciences. Yet Imugene appears confident that Azer-cel’s data speaks for itself.

“As we progress into Phase II, our primary focus is to validate the efficacy, safety, and persistence we’ve already observed,” Glover stated. “But we’re also laying the groundwork for commercial scalability. That’s the real promise of allogeneic CAR T—broad, equitable access.”

To that end, Imugene is investing in manufacturing optimization, regulatory engagement, and biomarker analysis to better understand the immunologic underpinnings of response and resistance. Early translational studies suggest that Azer-cel may drive robust immune reconstitution in responders, a finding that could have implications beyond lymphoma.

Beyond Azer-cel, Imugene is developing a range of novel immunotherapies aimed at activating the immune systems of cancer patients to treat and eradicate tumors, with programs focused on both hematological and solid tumors. Imugene has two platforms: an allogenic CAR T-cell therapy for blood cancers and an oncolytic virus for solid tumors, which can be used separately or together in clinical programs. One product is called onCARlytics—using an oncolytic virus to target and kill the tumor cell, but also to drive expression of CD19 at the cell surface that can be recognized by CAR Ts.

The virus goes and finds the solid tumor cells and begins killing them like a normal oncolytic virus, but it also forces that virus to express CD19 on the cell surface, which is normally not on solid tumors, and it turns the solid tumors into a blood tumor that you can then go in and use a CD19 targeting agent and kill. It’s a clever application of precision medicine to get around the challenges of personalization, as each tumor possesses a unique set of markers, and each individual possesses a unique set of markers. However, the onCARlytics therapy unifies all tumors by imbuing them with CD19.

Azer-cel and their onCARlytic platform challenge the status quo of autologous CAR T, positioning Imugene as a serious contender in a field already dominated by Big Pharma. “The goal is not just to develop another CAR T,” Glover said. “It’s to redefine what CAR T can be—for patients, providers, and health systems around the world.”