Imugene Achieves Major Milestone: First Australian Patient Dosed in Azer-Cel Phase 1b Trial

Key Highlights

• First Australian Patient Dosed: Imugene (ASX: IMU) begins its Phase 1b trial of azer-cel at Royal Prince Alfred Hospital in Sydney.
• Azer-Cel as a Game-Changer: This allogeneic CAR T-cell therapy offers a faster, off-the-shelf alternative to traditional autologous CAR T therapies.
• Promising US Results: U.S. trial cohorts report multiple complete responses (CR) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Introduction

Imugene Limited (ASX: IMU), a clinical-stage immuno-oncology leader, has taken a significant step forward by dosing its first Australian patient in the Phase 1b clinical trial of azer-cel (azercabtagene zapreleucel).

Conducted at Sydney’s Royal Prince Alfred Hospital, the trial focuses on patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), a challenging and aggressive form of non-Hodgkin’s lymphoma (NHL).

Azer-Cel: Redefining CAR T-Cell Therapy

Azer-cel is part of a new wave of allogeneic CAR T-cell therapies, standing out as a readily available treatment alternative to traditional autologous CAR T therapies.

Key Advantages of Azer-Cel

• Off-the-Shelf Solution: Utilizes pre-manufactured donor T-cells, eliminating the lengthy manufacturing process required for autologous therapies.
• Faster Access: Significantly reduces the time between diagnosis and treatment, making it ideal for patients with aggressive diseases like DLBCL.
• Broader Reach: Expands accessibility for patients who may not qualify for or tolerate autologous CAR T therapies.

DLBCL: Addressing a Critical Unmet Need

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent and aggressive form of NHL, with over 80,500 new cases annually worldwide. Despite recent advancements, a considerable proportion of patients either relapse or do not respond to existing treatments, underscoring the urgency for innovative solutions like azer-cel.

Promising U.S. Cohort Results

Imugene's (ASX: IMU) previous trials in the U.S. demonstrated azer-cel’s potential to deliver meaningful clinical outcomes, including:

• Complete Responses (CR): Three patients achieved CR after failing multiple prior treatments, including autologous CAR T therapies.
• Durable Responses: Patients in Cohort B, treated with lymphodepletion chemotherapy and interleukin-2 (IL-2), showed robust responses lasting beyond 90 and 120 days.

These outcomes highlight the therapy's potential to overcome resistance mechanisms associated with previous treatments.

About the Azer-Cel Phase 1b Trial

The Phase 1b trial is an open-label, multi-center study evaluating the safety, tolerability, and clinical activity of azer-cel in patients with relapsed or refractory DLBCL.

Innovative Trial Design

• Combination Therapy: Incorporates lymphodepletion chemotherapy and IL-2 to enhance azer-cel’s efficacy.
• Patient Criteria: Targets individuals who have previously undergone autologous CAR T-cell therapy.
• Focus on Safety and Efficacy: Establishing the foundational data for potential larger-scale trials.

“Achieving the first patient dosed for azer-cel in Australia is a pivotal moment for Imugene and patients battling DLBCL,” said Leslie Chong, Managing Director and CEO. “This trial underscores our commitment to developing off-the-shelf immunotherapies that can improve outcomes for patients with limited options.”

Chong also emphasized the importance of bringing cutting-edge treatments to Australia, aiming to expand recruitment across multiple sites nationwide.

The Future of CAR T-Cell Therapy in Australia

Imugene’s (ASX: IMU) introduction of allogeneic CAR T-cell therapy in Australia is not just a medical milestone; it represents a profound transformation in the treatment of aggressive lymphomas like diffuse large B-cell lymphoma (DLBCL).

Therapies like azer-cel are poised to address longstanding challenges in the field, including time, cost, and accessibility, redefining the standard of care for non-Hodgkin’s lymphoma (NHL). Traditional autologous CAR T-cell therapies require harvesting and modifying a patient’s own T-cells, a process that can take weeks or even months.

For patients with aggressive diseases like DLBCL, this timeline can be a critical limitation. Allogeneic CAR T-cell therapy, like azer-cel, eliminates this bottleneck by utilizing pre-manufactured donor T-cells, offering an off-the-shelf solution that is ready for immediate use.

Time: Saving Lives in Critical Moments

Time is often the most crucial factor for patients with relapsed or refractory DLBCL.

• Challenge: Traditional CAR T-cell therapies involve lengthy manufacturing timelines, during which disease progression may worsen.
• Solution: Azer-cel drastically reduces this timeline by leveraging pre-prepared T-cells, enabling patients to receive treatment promptly.
• Impact: Faster treatment initiation can improve patient outcomes, particularly for those in critical conditions where every day counts.

Cost: Making Advanced Therapies Affordable

The cost of CAR T-cell therapy has historically been a barrier to widespread adoption.

• Challenge: Autologous CAR T-cell therapies are expensive due to their personalized nature, complex manufacturing processes, and logistics.
• Solution: Allogeneic therapies like azer-cel have the potential to lower production costs through scalable manufacturing, making them more affordable for healthcare systems and patients.
• Impact: Reduced costs could lead to broader adoption across public and private healthcare sectors, ensuring that more patients have access to life-saving treatments.

Accessibility: Bridging the Inclusion Gap

Accessibility remains one of the most pressing challenges in deploying advanced therapies like CAR T-cell treatments.

• Challenge: Even with time and cost improvements, ensuring these therapies reach a majority of patients—especially those in remote or underserved areas—requires innovative strategies.
• Solution: Expanding clinical trial networks, decentralizing treatment centers, and integrating digital technologies for remote monitoring can enhance access to care.
• Impact: Making allogeneic CAR T-cell therapies available across Australia, including in rural and regional areas, ensures inclusivity and better health outcomes for all patients.

The Role of Allogeneic Therapies for NHL Treatment Protocols

By solving for time, cost, and accessibility, azer-cel has the potential to redefine the treatment protocols for NHL:

• Standardization of Care: Allogeneic therapies simplify logistics, enabling more consistent and predictable outcomes.
• Wider Eligibility: Patients who are ineligible for autologous therapies due to health conditions or prior treatments can benefit from off-the-shelf options.
• Scalable Solutions: With global healthcare systems facing increasing demands, scalable solutions like azer-cel ensure sustainability while addressing growing patient needs.

Looking Ahead

Imugene's (ASX: IMU) Phase 1b trial of azer-cel in Australia is a groundbreaking step in immuno-oncology. By combining innovative technology with promising early results, this trial brings new hope to patients with relapsed or refractory DLBCL.

As recruitment expands and data accumulates, we can say for sure that azer-cel will emerge as a transformative therapy. This is especially when we consider the global fight against aggressive lymphomas.