Wugen, Inc., a clinical-stage biotechnology company based in St. Louis, has announced the dosing of the first patients in its pivotal Phase 2 study evaluating WU-CART-007, a potential first-in-class, off-the-shelf CAR-T cell therapy. The therapy targets CD7 and is being developed for pediatric and adult patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma (T-ALL/LBL).
The global pivotal trial, named T-RRex, comes after encouraging results from the Phase 1/2 study that demonstrated clinically manageable safety and significant anti-leukemic activity. The earlier study showed an overall response rate of 91% and a composite complete remission rate of 73% in heavily pretreated patients with R/R T-ALL/LBL.
"The data we have previously reported from our Phase 1/2 study on the WU-CART-007 program has paved the way for the initiation of this pivotal study, and suggests it has the potential to set a new standard of care for relapsed or refractory T-ALL/LBL," said Kumar Srinivasan, Ph.D., M.B.A., president and chief executive officer of Wugen.
Addressing a Critical Treatment Gap
T-ALL/LBL represents a significant unmet medical need, with no new treatments approved for these conditions in the past two decades. These hematologic malignancies are particularly challenging to treat in the relapsed or refractory setting, where patients face historically poor outcomes.
"It's been 20 years since a new medicine was approved for patients with relapsed or refractory T-ALL/LBL, which remain challenging hematologic malignancies with limited treatment options in the relapsed or refractory setting," noted Cherry Thomas, M.D., chief medical officer of Wugen. "WU-CART-007 has shown clinical response and manageable safety, making it a promising off-the-shelf cell therapy candidate to fill a longstanding treatment gap."
Dr. Thomas added that enthusiasm for the program has been reflected in faster-than-anticipated study recruitment, highlighting the urgent need for new therapeutic options in this patient population.
Innovative Technology Platform
WU-CART-007 represents a significant technological advancement in CAR-T therapy. It is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy specifically engineered to overcome challenges in treating CD7+ hematological malignancies.
The therapy utilizes CRISPR/Cas9 gene editing technology to delete CD7 and the T cell receptor alpha constant (TRAC), which prevents CAR-T cell fratricide (self-destruction) and mitigates the risk of graft-versus-host-disease (GvHD). Unlike traditional autologous CAR-T therapies that use a patient's own cells, WU-CART-007 is manufactured using healthy donor-derived T cells, eliminating the risk of malignant cell contamination.
Pivotal Study Design
The T-RRex study is designed as a single-arm trial evaluating the efficacy and safety of WU-CART-007 in patients with R/R T-ALL/LBL. The study will include two groups: a relapsed/refractory cohort and an exploratory minimal residual disease (MRD)-positive cohort.
Results from the earlier Phase 1/2 study were presented at both the American Society of Hematology Annual Meeting in December 2024 and the European Hematology Association Hybrid Congress in June 2024.
Regulatory Support and Accelerated Pathways
The therapeutic potential of WU-CART-007 has been recognized by regulatory agencies worldwide. The program has received multiple accelerated approval pathway designations from the U.S. Food and Drug Administration, including:
- Regenerative Medicine Advanced Therapy (RMAT) designation
- Fast Track designation
- Orphan Drug designation
- Rare Pediatric Disease designation
Additionally, the European Union has granted Priority Medicines (PRIME) Scheme designation for the treatment of R/R T-ALL/LBL. These designations provide increased agency support to expedite development and review processes.
"The program has earned multiple U.S. Food and Drug Administration accelerated approval pathway designations, including RMAT, Fast Track, Orphan Drug, and Rare Pediatric Disease, as well as Priority Medicines designation in the EU," Srinivasan explained. "With this pivotal study now underway, we are advancing toward a much-needed off-the-shelf CAR-T option for patients who face historically poor outcomes and limited treatment alternatives."
Broader Implications for Cell Therapy
Wugen's progress with WU-CART-007 represents an important advancement in the field of allogeneic cell therapies. Off-the-shelf CAR-T treatments could potentially address many limitations of current autologous approaches, including manufacturing time, consistency, and availability.
The company is positioning itself as a leader in next-generation cell therapies, developing not only CAR-T treatments but also memory natural killer (NK) cell therapies for various cancers. The success of this pivotal trial could have far-reaching implications for the treatment paradigm of T-cell malignancies and potentially other hematological cancers.
For patients with T-ALL/LBL who have relapsed or become refractory to existing treatments, WU-CART-007 offers a promising new option in a field that has seen little innovation for decades. The T-RRex study is registered on clinicaltrials.gov with the identifier NCT06514794.
