Allogene Therapeutics announced a significant strategic restructuring on Thursday, including a 22% workforce reduction and a reprioritization of its clinical pipeline to extend its financial runway into 2026. The company's stock dropped more than 20% in Friday morning trading following the announcement.
The biotech company is pivoting its development strategy to focus on four key allogeneic CAR-T assets, with particular emphasis on cemacabtagene ansegedleucel (cema-cel, previously known as ALLO-501A) for newly diagnosed large B-cell lymphoma patients.
Strategic Pipeline Shift
Allogene is deprioritizing two of its most advanced clinical trials that were designed to support approval in advanced lymphoma. Instead, the company will redirect resources toward a new study testing cema-cel immediately after standard R-CHOP treatment in recently diagnosed patients.
The new Phase 3 trial, named ALPHA3, will enroll approximately 230 large B-cell lymphoma patients who are at risk of relapse after completing six cycles of R-CHOP therapy. According to Allogene, about 30% of patients initially responding to R-CHOP will eventually relapse, creating a significant unmet need.
"Until now, CAR-T development has been defined by how autologous CAR-Ts are made and used. As a management team with extensive experience in both autologous and allogeneic CAR-Ts and the only company with the breadth of data to demonstrate comparability between the two, we are uniquely positioned to potentially redefine the development and trial design of allogeneic CAR-T products," said Allogene CEO David Chang in a statement.
The ALPHA3 trial will use cema-cel as a "one-time, off-the-shelf" procedure that can be administered once the disease is discovered and initial treatment has been provided. The primary endpoint will be event-free survival. Allogene plans to begin enrolling patients in mid-2024.
Focus on Chronic Lymphocytic Leukemia
While deprioritizing most of the ALPHA2 trial, Allogene will add a new Phase 1 cohort of 12 chronic lymphocytic leukemia (CLL) patients to be treated with cema-cel. This cohort aims to demonstrate that patients with CLL will not be reliant on their own T cells' fitness to benefit from CAR-T treatment—a potential advantage for allogeneic therapy. Enrollment for this cohort is expected to begin in the first quarter of 2024.
Previous data from June 2023 showed promising results in the ALPHA/ALPHA2 trials, with seven out of 12 patients in Phase 1 achieving a complete response, and five patients maintaining that response through the sixth month.
Expanding into Autoimmune Diseases
Looking beyond oncology, Allogene plans to explore cell therapy applications in autoimmune diseases. The company intends to start a study next year testing a medicine that may not require standard chemotherapy preconditioning, though it has not specified which autoimmune condition it will target.
"There's a lot of opportunities we can think about," Chang noted, suggesting that conditions like lupus could be potential targets, following the path of other companies investigating CAR-T therapies for autoimmune disorders.
Market Position and Financial Strategy
Allogene has been a pioneer in developing "off-the-shelf" cell therapies derived from donor cells, positioning them as more convenient alternatives to personalized CAR-T therapies currently used for blood cancers. However, the company has faced challenges in matching the efficacy of personalized treatments and has seen its share value decline by nearly 90% from previous highs.
Zachary Roberts, Allogene's research and development chief, explained the strategic shift: "We were really looking for an opportunity to stand alone." The company believes the ALPHA3 study could demonstrate the potential for off-the-shelf treatments to be used at community cancer practices, not just at major treatment centers that typically administer cell therapies.
The restructuring and pipeline reprioritization are designed to reduce cash burn and extend the company's financial runway into 2026. The workforce reduction is expected to be completed by the end of January 2024.
"This entirely new approach to development creates an advantage for our investigational AlloCAR T products now and in the future while providing a clinical framework to generate far more competitive CAR T products and dramatically expand market opportunity," Chang added.
